Objective To understand the mortality and potential life loss due to coronary heart disease (CHD) and stroke in Wujiang District, Suzhou from 2011 to 2022, and to provide strategies and basis for the prevention and treatment of CHD and stroke. Methods We collected the data of death cases due to CHD and stroke from the death monitoring system in Suzhou from 2011 to 2022. The mortality of CHD and stroke, potential years of life lost (potential years of life lost , PYLL), average years of life lost (average years of life lost , AYLL) and potential years of life lost rate (potential years of life lost rate , PYLLR) were calculated to analyze the development trend of death and disease burden of CHD and stroke. Results From 2011 to 2022, the crude mortality of CHD was 31.91/10 million, and that of stroke was 118.93/10 million. CHD and stroke mortality rates both showed an upward trend（P＜0.05, a statistically significant trend）. From 2011 to 2022, the mortality rate of CHD and stroke in Wujiang District increased rapidly with the increase of age. From 2011 to 2022, the disease burden caused by CHD totaled 11005 person-years, with PYLLR of 1.26% and AYLL of 12.34 years per person. The PYLL caused by stroke was 13 587.5 people-years, the PYLLR was 1.55%, and the AYLL was 8.93 years per person. PYLL, PYLLR and AYLL all decreased in women（P<0.05）, with no significant change in men（P>0.05）. Conclusion From 2011 to 2022, the mortality rate of CHD and stroke in Wujiang District appeared a tendency towards a rise, effective intervention and prevention measures should be taken among elderly and male residents.

Gouty arthritis （GA） is an inflammatory disorder caused by monosodium urate （MSU） crystal deposition， accompanied by elevated oxidative stress and aberrant release of inflammatory cytokines， resulting in joint tissue damage and intense pain. Nuclear factor E₂-related factor 2 （Nrf2）， a key transcription factor regulating the antioxidant defence system， exerts cytoprotective effects through dissociation from Kelch-like ECH-associated protein 1 （Keap1） and activates downstream antioxidant response element （ARE）-mediated pathways. It can upregulate the expression of heme oxygenase-1 （HO-1）， NADH quinone oxidoreductase 1 （NQO1）， superoxide dismutase （SOD）， and glutathione transferase （GST） to preserve redox homeostasis. Moreover， Nrf2 can suppress activation of NOD-like receptor protein 3 （NLRP3） inflammasomes， reduce pro-inflammatory cytokine production and release， modulate nuclear factor-κB （NF-κB） transcriptional activity， regulate gut microbiota balance， enhance mitophagy， and inhibit apoptosis， so as to reduce joint inflammation and pain and promote body recovery. This review systematically examined recent advancements in traditional Chinese medicine （TCM） for GA prevention and treatment via regulating the Nrf2 signaling pathway. It delineated Nrf2's molecular mechanisms and its role in GA pathogenesis and elucidated how TCM intervenes in multiple pathways including Keap1/Nrf2/ARE， Nrf2/HO-1（NQO1）， and Nrf2/NF-κB/NLRP3 to exert therapeutic effects. The study demonstrated that TCM monomers and compounds effectively counteract oxidative damage， attenuate inflammatory responses， promote autophagy， and inhibit apoptosis via regulating the Nrf2 signaling pathway. These findings not only clarify the scientific basis of TCM in GA treatment but also offer strategic insights for developing novel Nrf2-targeted anti-gout drugs.

BACKGROUND: Doxorubicin hydrochloride (DOX) is extensively used in the treatment of various tumors. However, its clinical application is limited due to dose-dependent cardiotoxicity. Currently, few effective strategies exist to mitigate or eliminate DOX-induced cardiomyopathy (DIC). Although ferroptosis is implicated in DIC and its inhibition partially alleviates the condition, the direct targets of DOX in the progression of cardiotoxicity remain unclear. This study aimed to discover the direct targets of DOX in ferroptosis-mediated DIC. METHODS: A DOX pulldown assay was performed to identify proteins specifically binding to DOX in murine hearts, followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify candidate proteins. A cardiac injury mouse model was established by DOX treatment. Based on this, multiple ferroptosis biomarkers were detected by flow cytometry, quantitative real-time polymerase chain reaction, western blotting, immunochemistry, etc. Besides, specific activator and inhibitor of signaling pathways were applied to illuminate molecular mechanisms. RESULTS: Glutathione S-transferase P1 (GSTP1) was identified as a DOX target. GSTP1 activity was inhibited in DOX-treated cardiomyocytes, while its overexpression significantly alleviated DIC. Moreover, GSTP1 overexpression inhibited acyl-CoA synthetase long-chain family member 4 (ACSL4)-dependent ferroptosis. Mechanistically, GSTP1 overexpression suppressed c-Jun N-terminal kinase (JNK) phosphorylation, thereby reducing reactive oxygen species (ROS) production and inhibiting ferroptosis in DIC. CONCLUSIONS This study identifies the DOX/GSTP1/JNK axis as a critical pathway mediating ACSL4-dependent ferroptosis in DIC. GSTP1 is highlighted as a potential key mediator of ferroptosis and a promising therapeutic target for DIC.

One of the basic questions in the aging field is whether there is a fundamental difference between the aging of lower invertebrates and mammals. A major difference between the lower invertebrates and mammals is the abundancy of noncoding RNAs, most of which are not conserved. We have previously identified a noncoding RNA Terc-53 that is derived from the RNA component of telomerase Terc. To study its physiological functions, we generated two transgenic mouse models overexpressing the RNA in wild-type and early-aging Terc-/- backgrounds. Terc-53 mice showed age-related cognition decline and shortened life span, even though no developmental defects or physiological abnormality at an early age was observed, indicating its involvement in normal aging of mammals. Subsequent mechanistic study identified hyaluronan-mediated motility receptor (Hmmr) as the main effector of Terc-53. Terc-53 mediates the degradation of Hmmr, leading to an increase of inflammation in the affected tissues, accelerating organismal aging. adeno-associated virus delivered supplementation of Hmmr in the hippocampus reversed the cognition decline in Terc-53 transgenic mice. Neither Terc-53 nor Hmmr has homologs in C. elegans. Neither do arthropods express hyaluronan. These findings demonstrate the complexity of aging in mammals and open new paths for exploring noncoding RNA and Hmmr as means of treating age-related physical debilities and improving healthspan.
Animals ; Mice ; RNA, Untranslated/metabolism* ; Aging/genetics* ; Mice, Transgenic ; Telomerase/metabolism* ; RNA/genetics* ; Hippocampus/metabolism* ; Humans ; Mice, Inbred C57BL

Cells within tissues are subject to various mechanical forces,including hydrostatic pressure,shear stress,compression,and tension.These mechanical stimuli can be converted into biochemical signals through mechanoreceptors or cytoskeleton-dependent response processes,shaping the microenvironment and maintaining cellular physiological balance.Several studies have demonstrated the roles of Yes-associated protein(YAP)and its homolog transcriptional coactivator with PDZ-binding motif(TAZ)as mechanotransducers,exerting dynamic influence on cellular phenotypes including differentiation and disease pathogenesis.This regulatory function entails the involvement of the cytoskeleton,nucleoskeleton,integrin,focal adhesions(FAs),and the integration of multiple signaling pathways,including extracellular signal-regulated kinase(ERK),wingless/integrated(WNT),and Hippo signaling.Furthermore,emerging evidence substantiates the implication of long non-coding RNAs(lncRNAs)as mechanosensitive molecules in cellular mechanotransduction.In this review,we discuss the mechanisms through which YAP/TAZ and lncRNAs serve as effectors in responding to mechanical stimuli.Additionally,we summarize and elaborate on the crucial signal molecules involved in mechanotransduction.

Objective To explore the effects of dapnetin's regulation of STING/TBK1/IRF3 signaling pathway on immune inflammatory response in sepsis rats.Methods In this study,80 male Sprague Dawley(SD)rats were selected and randomly divided into four groups,20 rats in the sham-operation group,the remaining 60 mice with sepsis were constructed according to cecal ligation puncture(CLP)method and were intraperitoneally injected with different doses of dapnetin.They were divided into no-dapnetin model group(0 mg/kg),low-dose group(2.5 mg/kg),and high-dose group(5 mg/kg),with 20 mice in each group.The model group and sham-operation group were intraperitoneally injected with 0.1％DMSO.The survival rate of rats in each group after 72 h of CLP modeling was observed.Lung,kidney,liver and spleen tissues were collected for histopathological analysis.Serum inflammatory factors(TNF-α,IL-6,and IL-1β)were detected by ELISA,T lymphocyte subsets in peripheral blood were detected by flow cytometry,and STING/TBK1/IRF3 signaling pathway protein expression was detected by Western blotting.Results Compared with sham-operation group,the survival rate of rats in model group was reduced(P＜0.05),each organ tissue injury was significant,serum inflammatory factors(TNF-α,IL-6,and IL-1β)levels were increased(P＜0.05),CD4+ratio and CD4+/CD8+ratio in peripheral blood were decreased(P＜0.05),while CD8+ratio and Th1/Th2 ratio were increased(P＜0.05),the protein expressions of STING,p-TBK1/TBK1 and p-IRF3/IRF3 were downregulated(P＜0.05).Compared with the model group,dapnetin in high-dose group improved the survival rate of rats(P＜0.05),the injury of all organs and tissues was reduced,and the level of serum inflammatory factors was decreased(P＜0.05),CD4+ratio and CD4+/CD8+ratio in peripheral blood were increased(P＜0.05),while CD8+ratio and Th1/Th2 ratio were decreased(P＜0.05),the protein expressions of STING,p-TBK1/TBK1 and p-IRF3/IRF3 were increased(P＜0.05).Conclusion Dapnetin can improve the immune inflammatory response of sepsis rats by regulating STING/TBK1/IRF3 signaling pathway.

ObjectiveTo observe the effect of Zuoguiwan on ovarian reserve in the female offspring rat model of prenatal stress （PS） and explore the mechanism based on Toll-like receptor 4/nuclear factor-κB p65 （TLR4/NF-κB p65） signaling pathway. MethodThirty-two pregnant rats were prepared and randomized into four groups （n=8）： control， model， Zuoguiwan （18.9 mg·kg^-1）， and vitamin E （1.44 mg·kg^-1）. Except the control group， the other three groups were subjected to chronic unpredictable mild stress （CUMS） from day 11 of pregnancy， and the modeling was accompanied by gavage with corresponding drugs until delivery. The PS model was evaluated by the sucrose preference test， open field test， and serum corticosterone （CORT） level. The estrous cycle was monitored and the morphological changes in the ovarian tissue were observed. The serum levels of estradiol （E₂）， luteinizing hormone （LH）， follicle-stimulating hormone （FSH）， and anti-Mullerian hormone （AMH） in the 75-day-old offspring rats were measured by enzyme-linked immunosorbent assay （ELISA） to evaluate the ovarian reserve. The ovary and uterus indices were calculated. The serum levels of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） were measured by enzyme-linked immunosorbent assay （ELISA）. The morphology of the ovarian tissue in the offspring on the day of birth and day 75 after birth was observed by hematoxylin-eosin staining. The transport of NF-κB p65 to the nucleus in the ovaries of the 75-day-old offspring was detected by the immunofluorescence （IF） assay. The expression of TLR4， NF-κB p65 and other related proteins in the ovarian tissue was determined by Western blot. ResultCompared with the control group， the model group showed reduced primordial follicles in the offspring on the day of birth （P<0.01） as well as disturbed estrous cycle， decreased ovary index and uterus index （P<0.01）， reduced corpus luteum， increased atretic follicles （P<0.01）， lowered serum levels of AMH and E₂ （P<0.01）， elevated serum levels of LH， FSH， IL-1β， and TNF-α （P<0.05， P<0.01）， and up-regulated protein levels of TLR4， NF-κB p65， recombinant myeloid differentiation factor 88 （MyD88）， and phosphorylated NF-κB inhibitor （p-IκBα） （P<0.01） in the 75-day-old offspring rats. Compared with the model group， Zuoguiwan and vitamin E increased the primordial follicles in the offspring on the day of birth （P<0.01）. Moreover， they resumed the estrous cycle， increased the ovary and uterine indices （P<0.05， P<0.01） and corpus luteum （P<0.01）， reduced atretic follicles （P<0.01）， elevated the serum levels of AMH and E₂ （P<0.05， P<0.01）， lowered the serum levels of LH， FSH， IL-1β， and TNF-α （P<0.05， P<0.01）， and down-regulated the expression of TLR4， NF-κB p65， MyD88， and p-IκB-α （P<0.05， P<0.01） in the 75-day-old offspring. ConclusionZuoguiwan can improve the ovarian reserve in the offspring rat model of congenital kidney deficiency by regulating the TLR4/NF-κB p65 signaling pathway.

Objective To analyze the development trajectory and predictors of endocrine therapy associated arthralgia in breast cancer patients.Methods From January 2022 to July 2022,breast cancer patients in the breast medicine department or outpatients of a tertiary cancer hospital in Hunan Province were selected as respondents using a convenience sampling method.A baseline survey was conducted using the General Information Questionnaire,the Symptom Assessment Scale for Patients Treated with Endocrine Therapy for Breast Cancer,and the Self-Rating Anxiety Scale within 1 week prior to patient treatment.The Symptom Assessment Scale for Patients Treated with Endocrine Therapy for Breast Cancer was used to assess patients'arthralgia levels at 3,6,and 9 months after treatment,and data were analyzed using growth mixed model,univariate analysis of variance,and multiple logistic regression.Results A total of 418 breast cancer patients completed the follow-up,with 235 cases(56.22%)developing arthralgia.3 potential categories of arthralgia develop-ment trajectories were identified:high level-slowly increasing group(11.48%),low level-slowly increasing group(44.74%),and asymptomatic group(43.78%).The results of multifactorial analysis showed that anxiety,history of bone and joint disease,sleep duration,place of residence,monthly household income,and frequency of exercise were predictors of potential categories for the development of trajectory of arthralgia levels associated with endocrine therapy in breast cancer patients(P<0.05).Conclusion Arthralgia levels associated with endocrine therapy in breast cancer patients exhibit different trajec-tories,and clinical staff should emphasize the assessment and intervention of pain levels in patients with the anxiety,a history of bone and joint disease,poor sleep,poor finances,living in urban areas,and low frequency of exercise.

Objective To investigate the effects of galectin-3(Gal3)on skin abscess development and activation of mast cells(MC)in mice infected with methicillin-resistant Staphylococcus aureus(MRSA).Methods Wild type mice and Gal3-knockout(Gal3-/-)mice,at 6～8 weeks of age,were divided into four groups:Wild type mice+PBS group,Wild type mice+MRSA group,Gal3-/-mice+PBS group,Gal3-/-mice+MRSA group,were subcutaneously injected with MRSA or the same volume of phosphate buffer saline,with five mice per group.The development and pathological changes of skin abscess were monitored and recorded.The bacterial load in skin tissues was compared,and the expression of associated cytokines,degranulation of MC,and the distribution of MC activation marker 5-hydroxytryptamine(5-HT)were detected.Results The skin of Wild type mice showed progressive abscesses after subcutaneous infection with MRSA,but the Gal3-/-mice showed smaller abscess areas.Compared to the Wild type mice+MRSA group,the Gal3-/-mice+MRSA group showed lower bacterial loading in the skin tissues(P＜0.01)and fewer infiltrating inflammatory cells with histopathological observation.The expression of cytokines,including IL-1β,TNF-α,IL-33,TGF-β,and IL-10,were significantly lower in Gal3-/-mice than Wild type mice(P＜0.05).The toluidine blue staining showed a large number of degranulated MCs in the skin tissues of the wild type mice+MRSA group,whereas only a few degranulated MCs were observed in the Gal3-/-mice+MRSA group.It was further found that the expression of 5-HT in Gal3-/-mice+MRSA group was significantly lower than that in wild-type mice+MRSA group with immunohistochemical staining.Conclusion Gal3 deficiency reduced the activation and degranulation of mouse skin MC after MRSA infection,resulting in changes to inflammatory responses and alleviating the severity of skin tissue abscesses.