OBJECTIVE To investigate the application and influencing factors of sodium-dependent glucose transporters 2 inhibitors（SGLT-2i） in patients with heart failure with preserved ejection fraction（HFpEF） in the real world. METHODS Data from 358 patients with HFpEF who were hospitalized at the First Affiliated Hospital of Chongqing Medical University from May 2023 to May 2024 were retrospectively collected. The patients were divided into the SGLT-2i group and the non-SGLT-2i group based on whether they were prescribed SGLT-2i upon discharge. Baseline characteristics， comorbidities， and differences in drug treatment were compared between the two groups. Based on univariate analysis， multivariate Logistic regression analysis was performed to identify independent influencing factors of SGLT-2i use in patients with HFpEF， followed by further stratified analysis. RESULTS Among 358 HFpEF patients， the overall utilization rate of SGLT-2i was 33.5%. Combined with type 2 diabetes [OR＝9.063，95%CI（4.924-16.679） ] ， atrial fibrillation [OR＝3.135，95%CI（1.590-6.178） ] ， coronary artery heart disease [OR＝1.888，95%CI（1.072-3.327） ] and the use of loop diuretics [OR＝3.822， 95%CI （1.588-9.200） ] were all independent influencing factors for the use of SGLT-2i in patients with HFpEF （ P ＜0.05）. The results of the stratified descriptive analysis were consistent with those of the multivariate analysis， showing a higher utilization rate of SGLT-2i among patients with concomitant T2DM，atrial fibrillation， coronary artery heart disease， and those receiving loop diuretics （ P ＜0.05）； whereas the utilization rate of SGLT-2i was comparable across patients with different levels of renal function （ P ＞0.05）. CONCLUSIONS In the real-world clinical practice， the utilization of SGLT-2i in patients with HFpEF remains suboptimal， and treatment coverage still needs to be improved. Their use of SGLT-2i is primarily influenced by the presence of type 2 diabetes， atrial fibrillation， coronary artery heart disease， and the use of loop diuretics.

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.

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

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.

Objective To observe the effect of a Jianpi Huayu Jiedu formula on the NLRP3-mediated pyroptosis pathway in gastric precancerous lesion(GPL)associated with Helicobacter pylori(Hp)infection.Methods A GPL mouse model was prepared using Hp suspension gavage combined with Atp4a gene-deficient mice.The Jianpi Huayu Jiedu formula was administered as an intervention.Gastric mucosal tissue pathological damage was observed using hematoxylin and eosin(HE)staining.The presence of intestinal metaplasia(IM)was assessed using Alcian Blue-Periodic Acid Schiff(AB-PAS)staining.Ultrastructural changes in cell organelles were observed using transmission electron microscopy.Enzyme-linked immunosorbent assay(ELISA)was used to measure levels of gastrin-17(G-17),pepsinogen I(PGI),and proinflammatory cytokines IL-1β and IL-18.The expression of molecules related to the pyroptosis pathway was detected using Western blot and real-time quantitative PCR(RT-qPCR).Results Compared to the control group,Hp-related GPL mice exhibited gastric mucosal atrophy accompanied by IM and dysplasia.Damage to mitochondria and endoplasmic reticulum in parietal cells was observed.Levels of G-17,PGI,and proinflammatory cytokines IL-1β and IL-18 were elevated.The expression of molecules related to the pyroptosis pathway was increased.The Jianpi Huayu Jiedu formula significantly reduced gastric mucosal tissue pathological damage in GPL mice,decreased G-17 and PGI levels,mitigated inflammatory responses,and downregulated the expression of molecules related to the pyroptosis pathway.Conclusion The Jianpi Huayu Jiedu formula may exert its effects by inhibiting the NLRP3-mediated pyroptosis signaling pathway,thereby alleviating or even reversing the pathological damage of gastric mucosa in Hp-related GPL.

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.

[Purpose]To analyze the trends of disease burden for lung cancer worldwide and in China from 1990 to 2021.[Methods]Data of the disease burden of lung cancer and population demographics in 1990 and 2021 stratified by sex and age groups for global,five SDI quintiles re-gions,and eight countries including China,Japan,Republic of Korea,United Kingdom,France,United States,Canada,and Australia were extracted from the Global Burden of Disease Study 2021(GBD 2021)database.The age-standardized mortality rate(ASMR)and age-standard-ized disability-adjusted life year rate(ASDR)of lung cancer attributable to 7 level-3 risk factors in China for 1990 and 2021 were also extracted.Counterfactual analysis was used to decompose changes in lung cancer deaths and DALY from 1990 to 2021 into four contributing factors:popu-lation size,population structure,age-standardized incidence or prevalence,and lung cancer case fatality or disease severity.The percentage changes in lung cancer deaths and DALY attributed to these four factors were calculated respectively.[Results]In 2021,there were 934 704 new cases and 814 364 deaths of lung cancer in China.From 1990 to 2021,the incidence,preva-lence,mortality,and DALY rates of lung cancer in China increased faster than those worldwide and in high-middle SDI regions,which was similar to Japan and Republic of Korea.In contrast,the mortality rates of lung cancer decreased in United States and United Kingdom;and the DALY rates of lung cancer decreased in United States,United Kingdom,Canada and Australia.From 1990 to 2021,the age-related lung cancer deaths and DALY in China increased by 193.91％and 146.20％,respectively.The primary contributor to the increase in lung cancer deaths was population aging(102.82％)among men and rising age-standardized incidence(119.00％)among women,while the primary contributor to the increase in DALY was rising age-standardized prevalence for both men(153.12％)and women(218.77％).In 2021,the top three risk factors contributing to lung cancer ASMR and ASDR in China were smoking,particulate matter pollution and occupational carcinogen exposure.Compared with 1990,the ASMR of lung cancer and its proportion at-tributable to particulate matter pollution and low dietary fruits were decreased,while the propor-tions in ASDR of lung cancer attributable to smoking and secondhand smoke increased.[Conclu-sion]Lung cancer is a major public health challenge in China.Compared with worldwide,high-middle SDI regions and certain developed countries,China has experienced faster growth in the incidence,prevalence,mortality and DALY of lung cancer,especially among women.To reduce disease burden,sustained efforts on lung cancer prevention and control are urgently required in China.

Objective:To characterize COVID-19-associated skin diseases and explore their influencing factors.Methods:A cross-sectional survey was conducted via the online platform Wenjuanxing in Changsha area from February 16, 2023, to March 16, 2023. The convenience sampling method was employed to conduct a survey of outpatients with a history of COVID-19 infection from the Second Affiliated Hospital of Hunan University of Chinese Medicine, as well as individuals in certain areas of Changsha who met the inclusion criteria for past COVID-19 infections. Demographic characteristics, COVID-19 infection details, and the occurrence of skin conditions after COVID-19 infection were collected. The chi-square test was used for inter-group comparisons of categorical data, and multivariate logistic regression analysis was performed to investigate factors associated with skin diseases following COVID-19 infection.Results:A total of 357 valid questionnaires were collected, and 357 patients with a history of COVID-19 infection were involved, including 246 females (68.9%) and 111 males (31.1%). Among these patients, 260 (72.8%) were aged ≤ 35 years. After COVID-19 infection, skin diseases occurred in 96 patients (26.9%), with urticaria (27 cases, 31.0%), rosacea (27 cases, 31.0%), hair loss (18 cases, 20.7%), and Henoch-Sch?nlein purpura (15 cases, 17.2%) being the most common diseases. Additionally, 96 patients (26.9%) had a history of pre-existing skin diseases, among whom 36 experienced exacerbation of their pre-existing skin diseases due to COVID-19 infection. Univariate analysis showed that gender, history of chronic diseases, history of allergic diseases, COVID-19 vaccination, duration of COVID-19 infection, and exacerbation of pre-existing skin diseases were significantly associated with the development of new skin diseases following COVID-19 infection (all P < 0.05). Multivariate logistic regression analysis revealed that gender (compared with females, males: OR = 0.235, 95% CI: 0.113, 0.490), history of allergic diseases (compared with patients without a history of allergic diseases, those with the history: OR = 2.159, 95% CI: 1.239, 3.761), and duration of COVID-19 infection (compared with the duration of < 5 days, duration of 6 - 7 days: OR = 3.043, 95% CI: 1.495, 6.193; duration of 8 - 14 days: OR = 2.364, 95% CI: 1.105, 5.506; duration of ≥ 15 days: OR = 4.406, 95% CI: 1.972, 9.849) were influencing factors for skin diseases after COVID-19 infection (all P < 0.05) . Conclusions:COVID-19 infection may lead to skin diseases such as urticaria, rosacea, hair loss, and Henoch-Sch?nlein purpura. Females, individuals with a history of allergic diseases, and those with a relatively long duration of COVID-19 infection were more prone to develop skin diseases after COVID-19 infection.

Objective To explore the causal relationship between breast cancer and free fatty acid receptor 4(FFAR4)by using two-sample Mendelian randomization.Methods By using Genome-wide Association Studies and expression quantitative trait locus(eQTL)data,single nucleotide polymorphism sites closely related to breast cancer and FFAR4 were extracted.Causal effect values were calculated by using five methods:inverse variance weighting(IVW),MR-Egger,weighted median,simple mode and weighted mode.Cochran Q tests were used to detect heterogeneity,MR-Egger intercept tests and MR-PRESSO tests were used to assess level multiplicity,and the hold-out method was employed for sensitivity analysis to ensure robustness of the results.Additionally,Bayesian co-location analysis was used to evaluate whether FFAR4 expression shares the same causal genetic variant with breast cancer in given genomic region.Results A total of 12 eQTLs closely related to FFAR4 expression levels were included in this study.The results of IVW analysis showed that increased FFAR4 expression levels increased the risk of overall breast cancer,Luminal A,Luminal B/HER2-negative,and HER2-enhanced subtypes of breast cancer.The co-location analysis showed that the posterior probability of FFAR4 expression level and total breast cancer shared causal variation was 0.889.Conclusion There may be a causal relationship between FFAR4 expression and breast cancer.