Objective To analyze the disease burden of early-onset colorectal cancer (EOCRC) at the global, regional, and national levels from 1990 to 2021, and to predict the disease burden trend from 2022 to 2026. Methods Based on the Global Burden of Disease (GBD) database, the incidence, mortality, and disability-adjusted life year (DALY) rate of EOCRC across 204 countries and regions from 1990 to 2021 were obtained. The time trends of these indicators were assessed by calculating the estimated annual percentage change (EAPC), and the contributions of ten risk factors to the EOCRC burden were analyzed. The autoregressive integrated moving average (ARIMA) model was used to predict the disease burden from 2022 to 2026. Results From 1990 to 2021, the number of new global EOCRC cases increased from 107 310 to 211 890, with the incidence rising from 3.96 to 5.37 per 100 000 people. In 2021, global EOCRC incidence, mortality, and DALY rate increased with age; males had higher rates than females in terms of incidence, mortality, and DALY rate in all age groups. In 2021, East Asia had the highest number of new cases, deaths, and DALY. From 1990 to 2021, the global EAPC for incidence rate was 0.96%, and death rate was –0.38%. ARIMA model indicated that from 2022 to 2026, the global incidence of EOCRC would continue to rise, while mortality and DALY rate would be expected to decline. Conclusions The disease burden of EOCRC has significantly increased globally from 1990 to 2021, with notable regional, age, and sex differences. By 2026, the mortality and DALY rate of EOCRC will decline, while the incidence is expected to further increase, highlighting the urgency of taking active measures to address the growing trend of EOCRC.

ChuanWu (CW), the dried mother root of Aconitum carmichaelii Debx., is a well-known traditional Chinese medicine (TCM) recognized for its potent efficacy but inherent toxicity, primarily due to its alkaloid content. Traditional and modern detoxification methods for CW include proper processing, rational compatibility, and specialized decoction techniques, among which honey-boiled CW is particularly distinctive. However, research on the detoxification mechanism of honey-boiled CW remains limited. This study investigated this mechanism by analyzing alkaloid transformation and supramolecular aggregation. Honey-boiled and water-boiled CW preparations were compared. Ultra-high-performance liquid chromatography-tandem mass spectrometry was used to analyze CW alkaloids, specifically diester alkaloids (DDAs), monoester alkaloids (MDAs), and non-esterified diterpenoid alkaloids (NDAs). Transmission electron microscopy was employed to observe and identify supramolecular aggregates in the honey-boiled CW decoction. In vivo absorption of water-boiled, honey-boiled, and NADES-boiled CW was compared. Median lethal dose (LD₅₀) tests assessed toxicity, including hepatotoxicity and nephrotoxicity. In vitro experiments evaluated the safety, anti-inflammatory, and analgesic effects of CW-medicated serum on RAW264.7 cells, with in vivo validation in mice. Results showed that honey promoted the conversion of highly toxic DDAs to less toxic MDAs and prevented MDAs from hydrolyzing into NDAs. Honey-boiled CW formed approximately 250 nm supramolecular aggregates that encapsulated MDAs, inhibiting their conversion to NDAs. These encapsulated MDAs acted as a stable delivery system with higher bioavailability than free benzoylmesaconine. Subsequent mouse experiments confirmed that honey-boiled CW significantly increased the LD₅₀ of CW while reducing hepatotoxicity and nephrotoxicity. Additionally, honey-boiled CW significantly improved cell safety and enhanced anti-inflammatory and analgesic effects. Our findings reveal that honey-boiled CW exhibits a potent detoxification mechanism by influencing alkaloid transformation and facilitating the formation of supramolecular aggregates. This study lays the groundwork for developing detoxification or synergistic strategies within honey-boiled TCM.

Objective To explore the regulatory mechanism of angiopoietin 1(ANGPT1)on proliferation,invasion and angiogenesis of prostate cancer cells.Methods Mouse prostate cancer cell line(RM-1)was divided into control group,NC-oe group,ANGPT1-oe group,NC-sh group and ANGPT1-sh group.NC-oe,ANGPT1-oe,NC-sh and ANGPT1-sh were transfected into RM-1 cells by Lipofectamine3000 reagent.The transfection efficiency was verified by RT-qPCR and Western blot,cell proliferation was detected by MTT assay and EdU stai-ning and cell invasion was detected by Transwell assay.The cells were divided into the following groups:control group,Tie2-expressing monocytes/macrophages(TEMs)group,NC-oe+TEM group,ANGPT1-oe+TEM group,NC-sh+TEM group and ANGPT1-sh+TEM groups.RM-1 and TEM were co-cultured.RM-1 cells were collected after 72 hours and subjected to MTT proliferation assay,EdU staining assay and Transwell invasion assay.The co-cultured cell supernatant from each group mouse umbilical vein endothelial cells(MUVECs)were co-incubated with cell supernatant collected from each group cells and then to detect the number of tubules formed.The co-cul-tured cell supernatant of each group was collected,and the level of MMP-9,VEGFA and COX-2 were detected by ELISA.Results 1)Compared with control group and NC-oe group,the level of ANGPT1 mRNA and protein in ANGPT1-oe group was increased(P＜0.05).Compared with control group and NC-sh group,the level of ANGPT1 mRNA and protein in ANGPT1-sh group was decreased(P＜0.05).2)Compared with control group,the cell viability,EdU positive rate,counting of invasive cells and of tubules formed in TEM group significantly increased(P＜0.05),the level of MMP-9,VEGFA and COX-2 in the supernatant was increased(P＜0.05).Compared with TEM group and NC-oe+TEM group,the cell viability,EdU positive rate,counting of invasive cells and of tubules formed in ANGPT1-oe+TEM group decreased(P＜0.05).The level of MMP-9,VEGFA and COX-2 in the supernatant was significantly decreased(P＜0.05).Compared with TEM group and NC-sh+TEM group,the cell viability,EdU positive rate,counting of invasive cell and of tubules formed in ANGPT1-sh+TEM group all increased(P＜0.05).The level of MMP-9,VEGFA and COX-2 in the supernatant were increased(P＜0.05).Conclusions The decreased expression of ANGPT1 in prostate cancer significantly enhances the promotion effect of TEMs on the proliferation,invasion and angiogenesis of prostate cancer cells,thus promoting the progression of prostate cancer.

Objective To investigate the prevalence and risk factors of work-related musculoskeletal disorders (WMSDs) among construction workers. Methods A total of 5 783 workers were selected as participants from 12 construction companies in Guangdong Province, Guangxi Zhuang Autonomous Region and Zhejiang Province using a convenient sampling method. The revised Musculoskeletal Disorders Questionnaire was used to investigate the prevalence and influencing factors of WMSDs. Results The prevalence of WMSDs was 27.4% among the construction workers. The prevalence of WMSDs in shoulder, neck, waist/lower back and hand/wrist was 10.6%, 9.5%, 9.5% and 9.4% respectively, which was higher than that in other body parts. Bianry logistic regression analysis showed that the risk of WMSDs in construction workers with junior high school education and below was higher than that of high school/ college and above (P<0.05). The risk of WMSDs was higher in drinkers than that in non-drinkers (P<0.01). The worse the health status of construction workers, the higher the risk of WMSDs (P<0.01). The risk of WMSDs in those who exercised once or twice a month was lower than that in those who did not exercise (P<0.05). The risk of WMSDs was higher in construction workers with longer working hours in uncomfortable postures and greater back bending amplitude at work (all P<0.01). The risk of WMSDs in construction workers with hands holding above the shoulder was higher than that with hands below the shoulder (P<0.05). Construction workers who repeated the same work daily, involved in high-temperature work, often worked overtime, had insufficient rest time, and had a shortage of department personnel had a relatively high risk of WMSDs (all P<0.01). Conclusion The prevalence of WMSDs among the construction workers was relatively high, and the most common WMSDs occurred in shoulder, neck, waist/lower back and hand/wrist. Individual characteristic, work type, work posture and work organization are the influencing factors of WMSDs. Comprehensive measures, especially ergonomic measures based on personal and occupational characteristics should be taken to reduce the risk of WMSDs among construction workers.

Objective To explore the effect of young plasma intraperitoneal injection on the fertility and ovarian function of aging mice and analyze its potential molecular mechanism.Methods Fifty-four-week-old female C57BL/6 mice and 8-week-old male C57BL/6 mice were selected.Among them,the female mice were randomly divided into three groups:the young plasma group,the aging plasma group and the normal saline group.The young plasma group and the aging plasma group received intraperitoneal injection of plasma from young(25-29 years old)and elderly(45-49 years old)female donors,respectively.Each injection was 500 μL,administered every other day for 2 weeks.The saline group received an equal volume of saline.After the last injection,mating experiments were conducted to evaluate fertility.Ovarian histopathological changes were observed by HE staining.Oocytes and fertilized eggs were collected after superovulation and cultured in vitro to assess oocyte quality and embryo developmental potential.Transcriptomic analysis of ovarian tissue was performed,followed by KEGG and GO enrichment analysis.Results Compared with the normal saline group and the aging plasma group,the number of offspring increased in the young plasma group,which reflected higher extrusion rate of first polar body(PB1),decreased fragmentation rate of oocytes and increased conversion rate of two-cell embryos and increased formation rate of blastocysts.There were no significant differences in these indicators between the aging plasma group and the normal saline group.Transcriptomic sequencing revealed that the differentially expressed genes in ovarian tissue of the young plasma group were mainly involved in steroid biosynthesis and metabolic pathways.Among them,the expression level of steroid sulfatase protein was significantly upregulated.Conclusion Systemic infusion of young plasma enhances the reproductive potential of aging ovaries in elderly mice.The sulfated steroid metabolites in plasma may be key substances in restoring ovarian function and delaying the process of ovarian aging.

Cerebral ischemia/reperfusion injury(CIRI)is a pathophysiological process affecting the prognosis of patients with acute ischemic stroke(AIS).Its mechanism is complex and remains unclear.Long non-coding RNA(LncRNA)are a class of non-coding RNA(ncRNA).Early studies of LncRNA focused on their relationship with tumor-related diseases,but recent studies have found that they are also closely related to the pathological process of CIRI.LncRNA participate in the damage and repair processes of CIRI by affecting oxidative stress,autophagy,and apoptosis of the nervous system,as well as the inflammatory response and other mechanisms.They can regulate the progression of CIRI in a positive or negative way,and they play an important role in the related signaling pathways.This review focuses on the mechanisms bv which LncRNA regulate CIRI.

Objective To explore the effect of young plasma intraperitoneal injection on the fertility and ovarian function of aging mice and analyze its potential molecular mechanism.Methods Fifty-four-week-old female C57BL/6 mice and 8-week-old male C57BL/6 mice were selected.Among them,the female mice were randomly divided into three groups:the young plasma group,the aging plasma group and the normal saline group.The young plasma group and the aging plasma group received intraperitoneal injection of plasma from young(25-29 years old)and elderly(45-49 years old)female donors,respectively.Each injection was 500 μL,administered every other day for 2 weeks.The saline group received an equal volume of saline.After the last injection,mating experiments were conducted to evaluate fertility.Ovarian histopathological changes were observed by HE staining.Oocytes and fertilized eggs were collected after superovulation and cultured in vitro to assess oocyte quality and embryo developmental potential.Transcriptomic analysis of ovarian tissue was performed,followed by KEGG and GO enrichment analysis.Results Compared with the normal saline group and the aging plasma group,the number of offspring increased in the young plasma group,which reflected higher extrusion rate of first polar body(PB1),decreased fragmentation rate of oocytes and increased conversion rate of two-cell embryos and increased formation rate of blastocysts.There were no significant differences in these indicators between the aging plasma group and the normal saline group.Transcriptomic sequencing revealed that the differentially expressed genes in ovarian tissue of the young plasma group were mainly involved in steroid biosynthesis and metabolic pathways.Among them,the expression level of steroid sulfatase protein was significantly upregulated.Conclusion Systemic infusion of young plasma enhances the reproductive potential of aging ovaries in elderly mice.The sulfated steroid metabolites in plasma may be key substances in restoring ovarian function and delaying the process of ovarian aging.

Cerebral ischemia/reperfusion injury(CIRI)is a pathophysiological process affecting the prognosis of patients with acute ischemic stroke(AIS).Its mechanism is complex and remains unclear.Long non-coding RNA(LncRNA)are a class of non-coding RNA(ncRNA).Early studies of LncRNA focused on their relationship with tumor-related diseases,but recent studies have found that they are also closely related to the pathological process of CIRI.LncRNA participate in the damage and repair processes of CIRI by affecting oxidative stress,autophagy,and apoptosis of the nervous system,as well as the inflammatory response and other mechanisms.They can regulate the progression of CIRI in a positive or negative way,and they play an important role in the related signaling pathways.This review focuses on the mechanisms bv which LncRNA regulate CIRI.

Objective To explore the regulatory mechanism of angiopoietin 1(ANGPT1)on proliferation,invasion and angiogenesis of prostate cancer cells.Methods Mouse prostate cancer cell line(RM-1)was divided into control group,NC-oe group,ANGPT1-oe group,NC-sh group and ANGPT1-sh group.NC-oe,ANGPT1-oe,NC-sh and ANGPT1-sh were transfected into RM-1 cells by Lipofectamine3000 reagent.The transfection efficiency was verified by RT-qPCR and Western blot,cell proliferation was detected by MTT assay and EdU stai-ning and cell invasion was detected by Transwell assay.The cells were divided into the following groups:control group,Tie2-expressing monocytes/macrophages(TEMs)group,NC-oe+TEM group,ANGPT1-oe+TEM group,NC-sh+TEM group and ANGPT1-sh+TEM groups.RM-1 and TEM were co-cultured.RM-1 cells were collected after 72 hours and subjected to MTT proliferation assay,EdU staining assay and Transwell invasion assay.The co-cultured cell supernatant from each group mouse umbilical vein endothelial cells(MUVECs)were co-incubated with cell supernatant collected from each group cells and then to detect the number of tubules formed.The co-cul-tured cell supernatant of each group was collected,and the level of MMP-9,VEGFA and COX-2 were detected by ELISA.Results 1)Compared with control group and NC-oe group,the level of ANGPT1 mRNA and protein in ANGPT1-oe group was increased(P＜0.05).Compared with control group and NC-sh group,the level of ANGPT1 mRNA and protein in ANGPT1-sh group was decreased(P＜0.05).2)Compared with control group,the cell viability,EdU positive rate,counting of invasive cells and of tubules formed in TEM group significantly increased(P＜0.05),the level of MMP-9,VEGFA and COX-2 in the supernatant was increased(P＜0.05).Compared with TEM group and NC-oe+TEM group,the cell viability,EdU positive rate,counting of invasive cells and of tubules formed in ANGPT1-oe+TEM group decreased(P＜0.05).The level of MMP-9,VEGFA and COX-2 in the supernatant was significantly decreased(P＜0.05).Compared with TEM group and NC-sh+TEM group,the cell viability,EdU positive rate,counting of invasive cell and of tubules formed in ANGPT1-sh+TEM group all increased(P＜0.05).The level of MMP-9,VEGFA and COX-2 in the supernatant were increased(P＜0.05).Conclusions The decreased expression of ANGPT1 in prostate cancer significantly enhances the promotion effect of TEMs on the proliferation,invasion and angiogenesis of prostate cancer cells,thus promoting the progression of prostate cancer.

AIM:To investigate the impact of platycodin D(PD)on the viability,migration,invasion,apop-tosis and cell cycle of osteosarcoma cells in vitro,along with its underlying mechanisms.METHODS:Human osteosarco-ma cells MG63 and U2OS were divided into control group(0 μmol/L)and PD treatment group(6.25,12.5,25,50 and 100 μmol/L,respectively).Human osteosarcoma cells MG63 and U2OS were categorized into control groups(0 μmol/L PD)and PD treatment groups(6.25,12.5,25,50 and 100 μmol/L).The CCK-8 assay determined cell viability and identified effective treatment concentrations.MG63(15 μmol/L PD)and U2OS(25 μmol/L PD)were specifically ana-lyzed.Cell scratch and Transwell assays assessed migration and invasion.Hoechst 33342 staining examined nuclear mor-phological changes.Flow cytometry analyzed cell cycle distribution and apoptosis rate.Western blot measured protein ex-pression levels:cleaved caspase-3,cleaved PARP,c-Jun N-terminal kinase(JNK),p-JNK,B-cell lymphoma-2(Bcl-2),Bcl-2-ssociated X protein(BAX),matrix metalloproteinase 2(MMP-2),MMP-9,cyclin-dependent kinase 4(CDK4),cyclin D1,CDK1,cyclin B1,extracellular signal-regulated kinase(ERK)and p-ERK.Proteome sequencing of MG63 cells was performed.RESULTS:PD treatment significantly decreased cell survival,scratch healing rate,and invasive cell numbers,while increasing apoptosis rates(P<0.05).Morphological changes such as nuclear hyperchroma-tism and fragmentation were observed in PD-treated cells.PD induced G2/M phase arrest in MG63 and G0/G1 phase arrest in U2OS cells.PD treatment upregulated BAX,cleaved caspase-3,cleaved PARP,and p-JNK/JNK,while downregulat-ing Bcl-2,MMP-2,MMP-9,CDK4,cyclin D1,CDK1,cyclin B1,and p-ERK/ERK(P<0.05).Proteome sequencing re-vealed PD's involvement in cell division,cell cycle regulation,focal adhesion,apoptosis,and the MAPK signaling path-way.CONCLUSION:PD inhibits cell viability,migration,and invasion of osteosarcoma cells in vitro,while promoting apoptosis and inducing cell cycle arrest.These effects are likely mediated through modulation of the MAPK signaling path-way.