To analyze the disease burden, temporal trends, and attributable risk factors of early-onset female breast cancer (EOBC) in China and globally from 1990 to 2021.

Objective To investigate the potential active ingredients and the mechanism of Coreopsis tinctoria Nutt. in the prevention and treatment of hyperlipidemia. Methods Ultra-high performance liquid chromatography-Quadrupole-Exactive Orbitrap mass spectrometry (UPLC-Q-Exactive Orbitrap MS) was used to qualitatively analyze the fractions and blood components of flavones in Coreopsis tinctoria Nutt. The intersection targets of flavones in Coreopsis tinctoria Nutt. and hyperlipidemia were screened,and the protein-protein interaction network was constructed and analyzed by the STRING 12.0 database. Finally,the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used for enrichment analysis. Results A total of 25 compounds were detected from the flavones in Coreopsis tinctoria Nutt.,and their structures were identified,including ten chalcones,nine flavanones,four flavonols,one aurone,and one biflavone. The analysis of blood components showed that marein,flavanomarein,okanin,isookanin and 5,7,3',5'-tetrahydroxyflavanone-7-O-β-D-glucopyranoside were the main components of the flavones in Coreopsis tinctoria Nutt. in blood. Network pharmacological GO and KEGG enrichment analysis showed that the flavones in Coreopsis tinctoria Nutt. may regulate phosphatidylinositol 3-kinase/protein kinase B,tumor necrosis factor,hypoxia-inducible factor-1 signaling pathway and other signaling pathways in the regulation and prevention of hyperlipidemia. Conclusion Coreopsis tinctoria Nutt. can prevent and treat hyperlipidemia,and the mechanism may be related to the five blood components of the flavones in Coreopsis tinctoria Nutt.,including marein,flavanomarein,okanin,isookanin and 5,7,3',5'-tetrahydroxyflavanone-7-O-β-D-glucopyranoside.

BACKGROUND:Intervertebral disc degeneration is an important cause of low back pain.At present,there are many modeling methods for disc degeneration in China and abroad,but there is not a model for low back pain due to disc degeneration. OBJECTIVE:To compare the effect of mechanical puncture combined with tumor necrosis factor α and complete Freund's adjuvant with a conventional disc mechanical puncture alone. METHODS:A total of 18 male adult Sprague-Dawley rats were randomly divided into 3 groups,with 6 animals in each group.No treatment was given in the blank group.Animal models of intervertebral disc degeneration were made in the L4-5 segments of rats in the control using conventional mechanical puncture.In the experimental group,on the basis of mechanical puncture,tumor necrosis factor α+complete Freund's adjuvant was injected into the L4-5 intervertebral discs using a microinjector to establish a model of disc degeneration induced by mechanical puncture combined with inflammatory factors.Four weeks after surgery,the pain threshold of rats was measured by the hot plate method for assessing the perception of heat injury in rats with intervertebral disc degeneration.MRI examination was performed to observe the disc degeneration in each group.ELISA was used to detect the levels of serum tumor necrosis factor α,interleukin 1β,interleukin 6 and prostaglandin E2.Hematoxylin-eosin and Safranin O-fast green staining were used to observe the morphological changes of the disc. RESULTS AND CONCLUSION:In terms of pain,the behavioral pain threshold of the experimental group was continuously decreased,and the levels of serum inflammatory factors were significantly higher compared with the control group.In terms of morphology,the MRI results showed that the L4-5 nucleus pulposus signal completely disappeared in the experimental group.Histopathological results showed that in the control group,the nucleus pulposus was intact,more notochord cells were visible,and some fiber rings were ruptured,while in the experimental group,there are fewer notochord cells and the structure of the nucleus pulposus and fibrous ring is disturbed,with the boundary disappearing.To conclude,mechanical puncture combined with tumor necrosis factor alpha and complete Freund's adjuvant can successfully establish a discogenic low back pain model in rats.This operation is simple and economical to achieve obvious disc degeneration and low back pain,with greatly shortened molding cycle.This model can be used as a reference for studying discogenic low back pain models.

Radiotherapy is a first-line treatment for a variety of malignant tumors by inducing DNA damage to kill tumor cells. However, tumor cells have different sensitivities to radiotherapy, ultimately leading to different therapeutic effects. Histone acetylation, regulated by histone acetyltransferase (HAT) and histone deacetylase (HDAC), is involved in the regulation of cell radiation sensitivity by influencing DNA damage repair. The main mechanisms are recruiting DNA repair related proteins and mediating chromatin dynamic changes. In this article, the role of histone acetylation modification in tumor radiotherapy was reviewed, aming to provide the basis for the radiotherapy sensitization strategy based on histone acetylation.

Objective To explore the inhibitory effect of Sidaxue, a traditional Miao herbal medicine formula, on articular bone and cartilage destruction and synovial neovascularization in rats with collagen-induced arthritis (CIA). Methods In a SD rat model of CIA, we tested the effects of daily gavage of Sidaxue at low, moderate and high doses (10, 20, and 40 g/kg, respectively) for 21 days, with Tripterygium glycosides (GTW) as the positive control, on swelling in the hind limb plantar regions by arthritis index scoring. Pathologies in joint synovial membrane of the rats were observed with HE staining, and serum TNF-α and IL-1β levels were detected with ELISA. The expressions of NF-κB p65, matrix metalloproteinase 1 (MMP1), MMP2 and MMP9 at the mRNA and protein levels in the synovial tissues were detected using real-time PCR and Western blotting. Network pharmacology analysis was conducted to identify the important target proteins in the pathways correlated with the therapeutic effects of topical Sidaxue treatment for RA, and the core target proteins were screened by topological analysis. Results Treatment with GTW and Sidaxue at the 3 doses all significantly alleviated plantar swelling, lowered arthritis index scores, improved cartilage and bone damage and reduced neovascularization in CIA rats (P<0.05), and the effects of Sidaxue showed a dose dependence. Both GTW and Sidaxue treatments significantly lowered TNF-α, IL-1β, NF-κB p65, MMP1, MMP2, and MMP9 mRNA and protein expressions in the synovial tissues of CIA rats (P<0.05). Network pharmacological analysis identified MMPs as the core proteins associated with topical Sidaxue treatment of RA. Conclusion Sidaxue alleviates articular bone and cartilage damages and reduces synovial neovascularization in CIA rats possibly by downregulating MMPs via the TNF-α/IL-1β/NF-κB-MMP1, 2, 9 signaling pathway, and MMPs probably plays a key role in mediating the effect of Sidaxue though the therapeutic pathways other than oral administration.

Objective To explore the inhibitory effect of Sidaxue, a traditional Miao herbal medicine formula, on articular bone and cartilage destruction and synovial neovascularization in rats with collagen-induced arthritis (CIA). Methods In a SD rat model of CIA, we tested the effects of daily gavage of Sidaxue at low, moderate and high doses (10, 20, and 40 g/kg, respectively) for 21 days, with Tripterygium glycosides (GTW) as the positive control, on swelling in the hind limb plantar regions by arthritis index scoring. Pathologies in joint synovial membrane of the rats were observed with HE staining, and serum TNF-α and IL-1β levels were detected with ELISA. The expressions of NF-κB p65, matrix metalloproteinase 1 (MMP1), MMP2 and MMP9 at the mRNA and protein levels in the synovial tissues were detected using real-time PCR and Western blotting. Network pharmacology analysis was conducted to identify the important target proteins in the pathways correlated with the therapeutic effects of topical Sidaxue treatment for RA, and the core target proteins were screened by topological analysis. Results Treatment with GTW and Sidaxue at the 3 doses all significantly alleviated plantar swelling, lowered arthritis index scores, improved cartilage and bone damage and reduced neovascularization in CIA rats (P<0.05), and the effects of Sidaxue showed a dose dependence. Both GTW and Sidaxue treatments significantly lowered TNF-α, IL-1β, NF-κB p65, MMP1, MMP2, and MMP9 mRNA and protein expressions in the synovial tissues of CIA rats (P<0.05). Network pharmacological analysis identified MMPs as the core proteins associated with topical Sidaxue treatment of RA. Conclusion Sidaxue alleviates articular bone and cartilage damages and reduces synovial neovascularization in CIA rats possibly by downregulating MMPs via the TNF-α/IL-1β/NF-κB-MMP1, 2, 9 signaling pathway, and MMPs probably plays a key role in mediating the effect of Sidaxue though the therapeutic pathways other than oral administration.

Background::Acute respiratory distress syndrome (ARDS) is a common cause of respiratory failure in many critically ill patients. Although inflammasome activation plays an important role in the induction of acute lung injury (ALI) and ARDS, the regulatory mechanism of this process is still unclear. When cells are stimulated by inflammation, the integrity and physiological function of mitochondria play a crucial part in pyroptosis. However, the underlying mechanisms and function of mitochondrial proteins in the process of pyroptosis are largely not yet known. Here, we identified the 18-kDa translocator protein (TSPO), a mitochondrial outer membrane protein, as an important mediator regulating nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome activation in macrophages during ALI.Methods::TSPO gene knockout (KO) and lipopolysaccharide (LPS)-induced ALI/ARDS mouse models were employed to investigate the biological role of TSPO in the pathogenesis of ARDS. Murine macrophages were used to further characterize the effect of TSPO on the NLRP3 inflammasome pathway. Activation of NLRP3 inflammasome was preformed through LPS + adenosine triphosphate (ATP) co-stimulation, followed by detection of mitochondrial membrane potential, reactive oxygen species (ROS) production, and cell death to evaluate the potential biological function of TSPO. Comparisons between two groups were performed with a two-sided unpaired t-test. Results::TSPO-KO mice exhibited more severe pulmonary inflammation in response to LPS-induced ALI. TSPO deficiency resulted in enhanced activation of the NLRP3 inflammasome pathway, promoting more proinflammatory cytokine production of macrophages in LPS-injured lung tissue, including interleukin (IL)-1β, IL-18, and macrophage inflammatory protein (MIP)-2. Mitochondria in TSPO-KO macrophages tended to depolarize in response to cellular stress. The increased production of mitochondrial damage-associated molecular pattern led to enhanced mitochondrial membrane depolarization and pyroptosis in TSPO-KO cells. Conclusion::TSPO may be the key regulator of cellular pyroptosis, and it plays a vital protective role in ARDS occurrence and development.

AIM:To investigate the effects and mechanism of Xin-Tong-Tai granule on oxidized low-density li-poprotein(ox-LDL),intercellular adhesion molecule-1(ICAM-1)and vascular cell adhesion molecule-1(VCAM-1)in ApoE-/-mice with atherosclerosis(AS).METHODS:A total of 72 SPF-grade healthy male ApoE-/-mice aged 6～8 weeks were fed with high-fat diet for 12 weeks to replicate AS models,and 12 SPF-grade healthy male C57BL/6J wild mice were fed with ordinary diet as the control group.After the corresponding drugs were administered for 8 weeks,the body weight and general condition of mice in each group were observed.The serum levels of total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C)and low-density lipoprotein cholesterol(LDL-C)were detected by biochemi-cal kits.The pathological structures of aorta were observed by HE and oil red O staining.The levels of serum ox-LDL and aortic ICAM-1 and VCAM-1 were detected by ELISA.The protein levels of NADPH oxidase 4(NOX4),NOX subunit p22phox,inhibitor of κB kinase-α(IKK-α),IKK-β and nuclear factor-κB(NF-κB)in aorta were detected by Western blot.RESULTS:Compared with control group,the mice in model group showed increased body weight(P<0.05),dull and lo-cal shedding hair,slow grasping response,increased serum TC,TG and LDL-C levels,decreased serum HDL-C level(P<0.05),increased the levels of serum ox-LDL and aortic ICAM-1 and VCAM-1(P<0.05),and increased protein expres-sions of NOX4,p22phox,IKK-α,IKK-β and NF-κB in aorta(P<0.05).Compared with model group,the body weight of mice in each treatment group decreased(P<0.05),the hair loss and the response flexibility were also improved.The se-rum levels of TC,TG and LDL-C decreased and HDL-C increased(P<0.05).The levels of serum ox-LDL and aortic ICAM-1(except the low-dose Xin-Tong-Tai granule group)and VCAM-1 decreased(P<0.05).The protein levels of NOX4,p22phox,IKK-α,IKK-β and NF-κB in aorta decreased(P<0.05).HE and oil red O staining showed that typical AS plaques could be seen in blood vessels of the model group,and the red-stained areas were widely distributed.The above lesions were alleviated to different degrees in each treatment group compared with model group.CONCLUSION:Xin-Tong-Tai granule reduces the atherosclerotic plaque area of ApoE-/-mice induced by high-fat diet,decreased serum TC,TG and LDL-C levels,increased HDL-C level,decreased the levels of serum ox-LDL and aorta ICAM-1 and VCAM-1,and inhibited protein expression of NOX4,p22phox,IKK-α and IKK-β in the aorta,thereby attenuating AS.

Pyroptosis is a programmed death of inflammatory cells triggered by pathogen invasion,dependent on caspase activation,through both classical and non-classical pyroptosis pathways.Cell pyroptosis is related to the occurrence and development of a variety of animal infectious diseases caused by microbial infection.After microorganisms invading,cells are stimulated by pathology-re-lated molecular patterns,causing strong immune response,stimulating inflammatory signaling pathways,and then activating inflammasome,leading to pyroptosis.The immune system has e-volved multiple mechanisms to fight microbial infections and regulate inflammatory responses.The innate immune system,by recognizing microbial molecules in pathogens and responding quickly by producing inflammasome and activating pyroptosis,helps clear pathogens to prevent infection and maintain the normal functioning of the body.A thorough study of the pathogenesis and immune es-cape mechanism of cell pyroptosis in animal infectious diseases will provide a new direction for the treatment of animal infectious diseases.

Objective:To investigate the prognostic factors for liver transplantation for hepatocellular carcinoma beyond UCSF criteria but without macrovascular invasion.Methods:A retrospective analysis was performed for the clinical data of the hepatocellular carcinoma patients without macrovascular invasion beyond UCSF criteria who underwent liver transplantation at our center from Jan 2018 to Jun 2023. The receiver operating characteristic curve analysis was performed to assess the predictive power of potential prognosis factors.Results:With this criteria, the 1-, 3-year overall survival rates were 94.1% and 75.0%, respectively, and the 1-, 3-year tumor free survival rates were 82.4% and 38.1%, respectively. The maximum tumor size, number of tumors, AFP, PIVKA-Ⅱ before transplantation, and whether undergo pretransplant down-stage therapy were significant prognostic factors ( P<0.05). Combining the above prognostic factors to construct the receiver operating characteristic curve yielded an area under the curve of 0.967, with a sensitivity and specificity of 0.932, 0.952, respectively. Further, the differentiation, MVI and Ki-67 were significant prognostic factors ( P<0.05). Combining pathological factors to construct the receiver operating characteristic curve yielded an area under the curve of 0.927, with a sensitivity and specificity of 0.769, 1, respectively. Conclusion:The maximum tumor diameter, number of tumors, AFP, PIVKA-Ⅱ before transplantation, and pretransplant down-stage therapy and tumor differentiation, MVI and Ki-67 are all prognostic factors of liver transplantation for hepatocellular carcinoma without macrovascular invasion beyond UCSF criteria.