Background Prenatal exposure to fine particulate matter (PM_2.5) is closely associated with cortical damage and neuroinflammation in offspring. The cyclic guanosine monophosphate–adenosine monophosphate synthase (cGAS)–stimulator of interferon genes (STING) signaling pathway is a key regulator of inflammation and may be subject to epigenetic regulation. Objective To investigate the role of cGAS-STING pathway activation in PM_2.5-induced cortical damage in offspring mice during pregnancy and the underlying epigenetic regulatory mechanisms. Methods Open field tests were used to assess depressive-like behavior in offspring mice. Morphological analysis was conducted to evaluate cortical damage and microglial activation in offspring brains. Real-time fluorescent quantitative PCR (RT-qPCR) and Western blot (WB) were performed to detect changes in the expression of key molecules in the cGAS-STING pathway in cortical tissue. A PM_2.5-induced microglial cell injury model was established in BV2 cells. Microglial activation was observed, cell viability was measured using the Cell Counting Kit-8 (CCK-8), and the expression levels of inducible nitric oxide synthase (iNOS) and key molecules in the cGAS-STING pathway were detected by RT-qPCR and WB. Bioinformatics analysis was performed to explore the epigenetic regulatory association between the STING signaling pathway and lysine-specific demethylase 5A (KDM5A). Changes in KDM5A mRNA and protein expression, as well as the protein level of histone H3 lysine 4 trimethylation (H3K4me3), were detected in an in vitro PM_2.5 injury model. Using small interfering RNA (siRNA) technology, the KDM5A gene was silenced in BV2 cells exposed to PM_2.5. The protein expression of H3K4me3 was detected to evaluate improvements in microglial activation, changes in inflammatory markers such as iNOS and mannose receptor (CD206), and alterations in the cGAS-STING pathway. Results Compared with the control group, the total distance of offspring mice in the PM_2.5 group was significantly reduced, and both the distance traveled and the time spent in the central area of the open field were significantly decreased (P<0.01, P<0.001), indicating depressive-like behavior in the offspring mice. Compared with the control group, the offspring mice in the PM_2.5 group exhibited disorganized cortical structure and significantly activated microglia (P<0.01), with significantly increased mRNA and protein levels of cGAS and STING (P<0.05, P<0.01, or P<0.001). The in vitro experiments demonstrated that the PM_2.5 treatment induced BV2 cells to polarize toward the M1 phenotype, exhibiting a distinct amoeboid morphology, with upregulated expression of the pro-inflammatory factor iNOS (P<0.05, P<0.01, or P<0.001) and activation of the cGAS-STING pathway (P<0.05, P<0.01). The analysis of RNA-seq data from KDM5A knockout cells revealed significantly downregulated STING expression, suggesting that KDM5A may activate the STING signaling pathway. The in vitro experiments further confirmed that the PM_2.5-treated BV2 cells exhibited significantly elevated mRNA and protein levels of KDM5A (P<0.01), while the H3K4me3 protein levels were markedly reduced (P<0.05). After silencing KDM5A in BV2 cells exposed to PM_2.5, compared with the PM_2.5+siNC group, the PM_2.5+siKDM5A group showed no obvious microglial activation and polarized toward the M2 phenotype, with significantly decreased expression levels of iNOS, cluster of differentiation 16 (CD16), and interleukin-1β (P<0.05, P<0.01), and significantly increased expression levels of anti-inflammatory factors CD206, YM1, and interleukin-10 (P<0.01, P<0.001). Meanwhile, the expression levels of cGAS and STING were also reduced (P<0.05, P<0.01). Conclusion KDM5A activates microglia through the cGAS-STING pathway, thereby contributing to PM_2.5-induced cortical damage in offspring mice during pregnancy.

Traditional Chinese medicine(TCM)serves as a treasure trove of ancient knowledge,holding a crucial position in the medical field.However,the exploration of TCM's extensive information has been hindered by challenges related to data standardization,completeness,and accuracy,primarily due to the decen-tralized distribution of TCM resources.To address these issues,we developed a platform for TCM knowledge discovery(TCMKD,https://cbcb.cdutcm.edu.cn/TCMKD/).Seven types of data,including syndromes,formulas,Chinese patent drugs(CPDs),Chinese medicinal materials(CMMs),ingredients,targets,and diseases,were manually proofread and consolidated within TCMKD.To strengthen the integration of TCM with modern medicine,TCMKD employs analytical methods such as TCM data mining,enrichment analysis,and network localization and separation.These tools help elucidate the molecular-level commonalities between TCM and contemporary scientific insights.In addition to its analytical capabilities,a quick question and answer(Q&A)system is also embedded within TCMKD to query the database efficiently,thereby improving the interactivity of the platform.The platform also provides a TCM text annotation tool,offering a simple and efficient method for TCM text mining.Overall,TCMKD not only has the potential to become a pivotal repository for TCM,delving into the pharmaco-logical foundations of TCM treatments,but its flexible embedded tools and algorithms can also be applied to the study of other traditional medical systems,extending beyond just TCM.

Traditional Chinese medicine (TCM) serves as a treasure trove of ancient knowledge, holding a crucial position in the medical field. However, the exploration of TCM's extensive information has been hindered by challenges related to data standardization, completeness, and accuracy, primarily due to the decentralized distribution of TCM resources. To address these issues, we developed a platform for TCM knowledge discovery (TCMKD, https://cbcb.cdutcm.edu.cn/TCMKD/). Seven types of data, including syndromes, formulas, Chinese patent drugs (CPDs), Chinese medicinal materials (CMMs), ingredients, targets, and diseases, were manually proofread and consolidated within TCMKD. To strengthen the integration of TCM with modern medicine, TCMKD employs analytical methods such as TCM data mining, enrichment analysis, and network localization and separation. These tools help elucidate the molecular-level commonalities between TCM and contemporary scientific insights. In addition to its analytical capabilities, a quick question and answer (Q&A) system is also embedded within TCMKD to query the database efficiently, thereby improving the interactivity of the platform. The platform also provides a TCM text annotation tool, offering a simple and efficient method for TCM text mining. Overall, TCMKD not only has the potential to become a pivotal repository for TCM, delving into the pharmacological foundations of TCM treatments, but its flexible embedded tools and algorithms can also be applied to the study of other traditional medical systems, extending beyond just TCM.

AIM:To investigate the role and mechanism of histone demethylase lysine-specific demethylase 5A(KDM5A)in regulating the Notch signaling pathway in particulate matter 2.5(PM2.5)-induced cortical damage in off-spring mice.METHODS:A pregnancy PM2.5 exposure model was established using intratracheal nebulization.Pregnant mice were randomly divided into PBS control group and PM2.5 exposure group.The cortices of offspring mice were isolated 14 d after birth.Golgi staining,electron microscopy and other methods were used to detect damage to neurons and chroma-tin in the cortex.Western blot,RT-qPCR and immunofluorescence staining were used to detect the mRNA and protein ex-pression of KDM5A in the cortex,and the distribution of KDM5A co-localized with neural cells.A PM2.5-treated PC12 cell injury model was established to detect changes in cell viability and the expression of proteins related to cell proliferation and apoptosis.Further,Western blot,RT-qPCR and immunofluorescence staining were used to detect the mRNA and pro-tein expression of KDM5A,the distribution of KDM5A co-localized with neurons,and changes in the protein level of his-tone H3K4me3.Bioinformatics methods were used to predict the interaction between KDM5A and Notch1,which was fur-ther validated by transfection experiments.In both in vivo and in vitro PM2.5 exposure models,changes in key molecules of the Notch signaling pathway and the co-expression of Notch1 with neural cells in the cortices of 14-day-old offspring mice and PC12 cells were detected.RESULTS:Prenatal PM2.5 exposure during pregnant led to a reduction in the number of neurons and decreased dentritic complexity in the cerebral cortex of offspring at 14 d after birth.It also caused abnormal chromatin condensation within neuronal nuclei,decreased mRNA and protein expression of KDM5A protein in the cortex,increased H3K4me3 protein levels(P＜0.05),and a significant reduction in KDM5A/NeuN double-positive cells.Expo-sure to PM2.5 also resulted in decreased viability and proliferation,and increased apoptosis of PC12 cells,with reduced ex-pression of KDM5A mRNA and protein,increased H3K4me3 protein expression(P＜0.05),and a reduction in the num-ber of KDM5A/MAP-2 double-positive cells.Bioinformatics analysis and transfection experiments in PC12 cells revealed that Notch1 is a downstream target gene of KDM5A.Further in vivo and in vitro experiments found that PM2.5 exposure lead to decreased mRNA and protein expression of key Notch signaling molecules Notch1,Jagged1 and Hes1,and reduced numbers of Notch1/NeuN and Notch1/MAP-2 double-positive cells.CONCLUSION:Exposure to PM2.5 can lead to abnor-mal expression of KDM5A in the offspring's cerebral cortex,which may cause neuronal damage by down-regulating the Notch signaling pathway,a downstream target.This could be one of the significant factors contributing to the neurodevelop-mental disorders in offspring exposed to PM2.5 during pregnancy.

AIM:To investigate the role and mechanism of histone demethylase lysine-specific demethylase 5A(KDM5A)in regulating the Notch signaling pathway in particulate matter 2.5(PM2.5)-induced cortical damage in off-spring mice.METHODS:A pregnancy PM2.5 exposure model was established using intratracheal nebulization.Pregnant mice were randomly divided into PBS control group and PM2.5 exposure group.The cortices of offspring mice were isolated 14 d after birth.Golgi staining,electron microscopy and other methods were used to detect damage to neurons and chroma-tin in the cortex.Western blot,RT-qPCR and immunofluorescence staining were used to detect the mRNA and protein ex-pression of KDM5A in the cortex,and the distribution of KDM5A co-localized with neural cells.A PM2.5-treated PC12 cell injury model was established to detect changes in cell viability and the expression of proteins related to cell proliferation and apoptosis.Further,Western blot,RT-qPCR and immunofluorescence staining were used to detect the mRNA and pro-tein expression of KDM5A,the distribution of KDM5A co-localized with neurons,and changes in the protein level of his-tone H3K4me3.Bioinformatics methods were used to predict the interaction between KDM5A and Notch1,which was fur-ther validated by transfection experiments.In both in vivo and in vitro PM2.5 exposure models,changes in key molecules of the Notch signaling pathway and the co-expression of Notch1 with neural cells in the cortices of 14-day-old offspring mice and PC12 cells were detected.RESULTS:Prenatal PM2.5 exposure during pregnant led to a reduction in the number of neurons and decreased dentritic complexity in the cerebral cortex of offspring at 14 d after birth.It also caused abnormal chromatin condensation within neuronal nuclei,decreased mRNA and protein expression of KDM5A protein in the cortex,increased H3K4me3 protein levels(P＜0.05),and a significant reduction in KDM5A/NeuN double-positive cells.Expo-sure to PM2.5 also resulted in decreased viability and proliferation,and increased apoptosis of PC12 cells,with reduced ex-pression of KDM5A mRNA and protein,increased H3K4me3 protein expression(P＜0.05),and a reduction in the num-ber of KDM5A/MAP-2 double-positive cells.Bioinformatics analysis and transfection experiments in PC12 cells revealed that Notch1 is a downstream target gene of KDM5A.Further in vivo and in vitro experiments found that PM2.5 exposure lead to decreased mRNA and protein expression of key Notch signaling molecules Notch1,Jagged1 and Hes1,and reduced numbers of Notch1/NeuN and Notch1/MAP-2 double-positive cells.CONCLUSION:Exposure to PM2.5 can lead to abnor-mal expression of KDM5A in the offspring's cerebral cortex,which may cause neuronal damage by down-regulating the Notch signaling pathway,a downstream target.This could be one of the significant factors contributing to the neurodevelop-mental disorders in offspring exposed to PM2.5 during pregnancy.

Pulmonary blast injury has become the main type of trauma in modern warfare, characterized by externally mild injuries but internally severe injuries, rapid disease progression, and a high rate of early death. The injury is complicated in clinical practice, often with multiple and compound injuries. Currently, there is a lack of effective protective materials, accurate injury detection instrument and portable monitoring and transportation equipment, standardized clinical treatment guidelines in various medical centers, and evidence-based guidelines at home and abroad, resulting in a high mortality in clinlcal practice. Therefore, the Trauma Branch of Chinese Medical Association and the Editorial Committee of Chinese Journal of Trauma organized military and civilian experts in related fields such as thoracic surgery and traumatic surgery to jointly develop the Clinical treatment guideline for pulmonary blast injury ( version 2023) by combining evidence for effectiveness and clinical first-line treatment experience. This guideline provided 16 recommended opinions surrounding definition, characteristics, pre-hospital diagnosis and treatment, and in-hospital treatment of pulmonary blast injury, hoping to provide a basis for the clinical treatment in hospitals at different levels.

Adipose Tissue ; Cadaver ; Humans ; Vertebral Artery

Objective To investigate the changes in dietary behavior and physical exercise of people of different ages during the epidemic of Coronavirus Disease 2019 (COVID-19), and to explore the influencing factors of weight gain. Methods A structured electronic questionnaire was used to investigate the basic conditions, weight, eating behavior and physical exercise of 1 125 subjects. The χ² test or non-parametric test was used to compare the changes in the three age groups (<30, 30~65, >65 years), and Logistic regression analysis was used to explore the factors affecting weight gain. Results Among the three age groups, young people under 30 years old changed greatly in the consumption of grains, red meat, and high-calorie snacks, and in the physical exercise, and there was a significant amount of people experiencing such changes, while for those older than 65 years old, the frequency of intake of grains, red meat, and high-calorie snacks before and after the outbreak was basically unchanged. In addition, compared with the population who basically did not change dietary behavior during the epidemic, the increase in the consumption of grains (OR = 2.469), red meat (OR = 1.582), and high-calorie snacks (OR = 1.815), and the decrease in physical exercise (OR = 1.702 ) were independent risk factors for weight gain during the epidemic (P <0.05). Conclusions During the epidemic of COVID-19, the young people (<30 years old) experienced the largest changes in dietary intake (grain, red meat, and high-calorie snacks) and exercise, while the elderly people (>65 years old) maintained basically unchanged. The increased intake of grains, red meat and high-calorie snacks, and lack of physical exercise could lead to weight gain.

Objective:Calcium/calmodulin-dependent kinase kinase (CAMKK2) is activated in prostate cancer (PCa). The aim of our study is to identify the effects of preadipocyte and CAMKK2 on the PCa cell invasion.Methods:The coculture system between PCa cells and preadipocyte cells (3T3L1) was established and then Transwell assay was used to determine the invasive effect after coculture. Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to investigate the CAMKK2 expression in the coculture system.Results:The 3T3L1 cells promoted the invasion of PCa cells (DU145 and 22RV1; P<0.01). Meanwhile, the 3T3L1 cells can increased expression of CAMKK2 in PCa cells ( P<0.01). CAMKK2 reversed the invasive effects of preadipocyte cells on the PCa cells. Conclusions:Our study demonstrates that the preadipocyte may promote the PCa cell invasion possibly by mediating the CAMKK2 expression.

Objective To summarize the characteristics of clinical manifestation of bone flare after the treatment with new endocrine therapy in patients with metastatic castration-resistant prostate cancer (mCRPC) in order to evaluate the curative effect of patients properly and determine the reasonable treatment strategy.Methods We retrospectively analyzed the clinical data of two patients with mCRPC performed "bone flare" defined as PSA decline and bone metastases progression in the initial treatment with new endocrine therapy in Urology Department of Peking University First Hospital,and analyzed the clinical characteristics and treatment methods with the relative literature.Case 1,a 79-year-old man,presented with frequent urination and prostate-specific antigen (PSA) was 115.900 ng/ml,was diagnosed as prostate cancer (cT3N0M1) with bone metastasis.After androgen deprivation therapy of 24 months,PSA elevated and multiple bone metastases progressed.The patient was diagnosed with mCRPC and then began the treatment of enzalutamide.Case 2,a 62-year-old man,complained about emaciation and frequent urination,was diagnosed with prostate cancer(cT4N1M1)with bone and lymph metastases.After androgen deprivation therapy of 22 months,PSA elevated and multiple bone metastases progressed.The patient was diagnosed with mCRPC and then began the treatment of abiraterone.Results Case 1 was treated with enzalutamide and 2 months later PSA decreased from 133.400 ng/ml to 5.530 ng/ml,while bone scan showed multiple bone metastases,part of which was newly metastatic lesions.6 months later,the number of metastatic lesions kept stable,and part of lesions presented metabolism decrease.8 months later,the number of metastatic lesions began to decrease.1 year later,the patient started to receive chemical therapy because of the progression of the disease.After 5 cycles of chemotherapy,PSA progression occurred and chemotherapy was stopped.Liver failure and disseminated intravascular coagulation caused death in June 2016.Case 2 was treated with abiraterone and 2 months later PSA decreased from 54.820 ng/ml to 3.580 ng/ml,while bone scan showed multiple bone metastases,part of which was newly metastatic lesions.6 months later,the number of metastatic lesions began to decline.10 months later,the number of metastatic lesions kept stable.The treatment of abiraterone was continued so far and the patient was in a stable condition.Conclusions Enzalutamide and abiraterone,two new endocrine therapy,are determined as preferred methods for the treatment of mCRPC.The bone scanning is required to evaluate the possibility of "bone flare" which is defined as PSA decline and bone metastases progression in the initial treatment.These patients should be evaluated to make appropriate clinical decision.