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

ObjectiveTo observe the clinical efficacy and safety of Shugan Bushen Yulin Decoction （疏肝补肾毓麟汤， SBYD） in the treatment of asthenospermia and infertility with liver constraint and kidney deficiency. MethodsA multicenter， randomized， controlled clinical study was conducted in three hospitals in central China. Totally 95 patients with asthenospermia and infertility were controlled. According to random number table， the patients were divided into treatment group （47 cases） and control group （48 cases）. The control group was given vitamin E soft capsules （100 mg per time， twice daily） orally， and the treatment group was given SBYD （one dose daily， 30 min after breakfast and dinner， about 200 ml each time） orally. The course of treatment was 12 weeks in both groups. After the treatment， the sperm concentration， percentage of forward motile sperm （PR）， and percentage of total sperm activity， that is PR + percentage of non-progressively motile sperm （NP） were compared between groups， and the clinical efficacy was judged. Traditional Chinese medicine （TCM） syndrome score （inlcuding 6 single symptom scores and total symptoms score） and 21-item depression， anxiety， and stress scale （DASS-21） scores （including depression， anxiety and stress scores） were compared between the two groups before and after treatment. The patients were followed up for 6 months， and the pregnancy status of spouse between groups was compared. The occurrence of adverse events and vital signs during the trial were recorded for safety assessment. ResultsTwo cases in the treatment group and three cases in the control group dropped out. Finally， 45 cases in each group were included in the statistical analysis. The total effective rate was 86.67% （39/45） in the treatment group， significantly higher than 73.74% （33/45） in the control group （P＜0.05）. After treatment， PR and PR + NP significantly increased in both groups， and were much higher in the treatment group than in the control group （P＜0.05）. The scores of lumbar and knee soreness， emotional disturbance， cold sperm， chest and rib-side and lesser abdomen distension and pain， frequent sighing， and the total TCM syndrome score in the treatment group decreased after treatment （P＜0.05）； and except for cold sperm， the scores of other symptoms mentioned above as well as the total TCM syndrome score in the treatment group were lower than those in the control group （P＜0.05）. The scores of depression， anxiety and stress of DASS-21 in the treatment group decreased after treatment， and were lower than those in the control group （P＜0.05）. After 6 months of follow-up， the spouses of 5 patients in the treatment group and 3 patients in the control group got pregnant （P＞0.05）. No adverse events occurred in both groups during the treatment， and their vital signs were stable. ConclusionSBYD can obviously improve sperm vitality and effectively improve the clinical symptoms， anxiety and depression， and is safe in treating asthenospermia and infertility with liver constraint and kidney deficiency.

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 investigate the dietary patterns of rural residents in the high-incidence areas of esophageal cancer (EC), and to explore the clustering and influencing factors of risk factors associated with high-incidence characteristics. Methods A special structured questionnaire was applied to conduct a face-to-face survey on the dietary patterns of rural residents in Yanting county of Sichuan Province from July to August 2021. Univariate and multivariate logistic regression models were used to analyze the influencing factors of risk factor clustering for EC. Results There were 838 valid questionnaires in this study. A total of 90.8% of rural residents used clean water such as tap water. In the past one year, the people who ate fruits and vegetables, soybean products, onions and garlic in high frequency accounted for 69.5%, 32.8% and 74.5%, respectively; the people who ate kimchi, pickled vegetables, sauerkraut, barbecue, hot food and mildew food in low frequency accounted for 59.2%, 79.6%, 68.2%, 90.3%, 80.9% and 90.3%, respectively. The clustering of risk factors for EC was found in 73.3% of residents, and the aggregation of two risk factors was the most common mode (28.2%), among which tumor history and preserved food was the main clustering pattern (4.6%). The logistic regression model revealed that the gender, age, marital status and occupation were independent influencing factors for the risk factors clustering of EC (P<0.05). Conclusion A majority of rural residents in high-incidence areas of EC in Yanting county have good eating habits, but the clustering of some risk factors is still at a high level. Gender, age, marital status, and occupation are influencing factors of the risk factors clustering of EC.

ObjectiveTo observe the effect of Youguiwan on the leptin/Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） signaling pathway in the lung tissue of the rat model of chronic obstructive pulmonary disease （COPD） due to kidney-Yang deficiency. MethodForty rats were modeled for COPD with the syndrome of kidney-Yang deficiency by intratracheal instillation of lipopolysaccharide on day 1 and day 14 and continuous fumigation for 6 weeks， during which hydrocortisone was injected intramuscularly at an interval of 3 days. The modeled rats were randomized into model， high- （11.7 g·kg^-1）， medium- （5.85 g·kg^-1）， and low-dose （2.93 g·kg^-1） Youguiwan， and aminophylline （0.054 g·kg^-1） group. In addition， 8 SD rats were set as the blank group. After the completion of modeling， the rats in each group were administrated with the corresponding drug by gavage for 28 consecutive days. After the last administration， samples were collected. A lung function analyzer was used to evaluate the lung function of rats. Enzyme-linked immunosorbent assay was employed to measure the levels of interleukin-17A （IL-17A）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in the bronchoalveolar lavage fluid （BALF）. Hematoxylin-eosin staining was employed to observe the pathological changes in the lung tissue， and Masson staining was employed to observe the deposition of blue collagen fibers around bronchi in the lung tissue and calculate the inflammation score. The immunofluorescence assay was employed to measure the protein content of collagen type Ⅰ （ColⅠ） and α-smooth muscle actin （α-SMA） in the bronchi. The protein and mRNA levels of leptin， IL-17A， JAK2， and STAT3 in the lung tissue were determined by Western blot and real-time fluorescence quantitative polymerase chain reaction， respectively. ResultCompared with the blank group， the model group showed decreased lung function （P<0.01）， elevated levels of IL-6， IL-17A， and TNF-α in the BALF （P<0.01）， and increased lung inflammation score， deposition of subcutaneous collagen fibers in the airway， and ColⅠ and α-SMA proteins （P<0.01）. Furthermore， the modeling up-regulated the proteins and mRNA levels of leptin， IL-17A， JAK2， and STAT3 in the lung tissue （P<0.01） and enhanced the phosphorylation of JAK2 and STAT3 （P<0.01）. Compared with the model group， high- and medium-dose Youguiwan improved the lung function， decreased the inflammation score， reduced collagen fiber deposition and ColⅠ and α-SMA proteins， lowered the levels of IL-6， IL-17A， and TNF-α in the BALF， down-regulated the mRNA and protein levels of leptin， JAK2， STAT3， and IL-17A， and weakened the phosphorylation of JAK2 and STAT3 （P<0.05， P<0.01）. The aminophylline group had higher IL-17A and TNF-α levels than the high-dose Youguiwan group， lower IL-17A level than the medium and low-dose Youguiwan groups， and lower TNF-α level than the low-dose Youguiwan group. Compared with the aminophylline group， the high- and medium-dose Youguiwan groups showed reduced deposition of collagen fibers and protein levels of ColⅠ and α-SMA around the bronchi in the lung tissue （P<0.05， P<0.01）， decreased inflammation score， and down-regulated protein and mRNA levels of leptin， JAK2， STAT3， and IL-17A in the lung tissue. ConclusionYouguiwan can prevent airway remodeling by inhibiting IL-17A to reduce inflammation and collagen deposition in COPD rats， which may be related to the inhibition of the leptin/JAK2/STAT3 signaling pathway.

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.