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 investigate the protective effects of Gouqizi (Lycii Fructus, GQZ)-Danshen (Salviae Miltiorrhizae Radix et Rhizoma, DS) against hydrogen peroxide (H2O2)-induced oxidative injury in 661W retinal photoreceptor cells and to explore whether these effects involve angiopoietin-like 4 (ANGPTL4). Methods: Liquid chromatography-mass spectrometry (LC-MS) was used to identify the major components of GQZ-DS aqueous extract. An H2O2-induced oxidative injury model was established in 661W cells. Working concentrations of H2O2 and GQZ-DS were determined using the cell counting kit-8 (CCK-8) assay. Cells were subjected to GQZ-DS, ANGPTL4 knockdown, or ANGPTL4 overexpression as indicated. Flow cytometry was used to analyze cell cycle distribution, apoptotic rate, and intracellular reactive oxygen species (ROS). Colorimetric determination of malondialdehyde (MDA) content and superoxide dismutase (SOD) activity using the thiobarbituric acid (TBA) method was performed. The protein expression level of ANGPTL4 was assessed by immunofluorescence. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to quantify the mRNA level of ANGPTL4. Western blot was used to detect the protein levels of ANGPTL4 and cleaved caspase-3. Results: LC-MS identified five major constituents in the GQZ-DS aqueous extract: 2-O-β-D-glucopyranosyl-L-ascorbic acid, rutin, D-galactose, salvianolic acid A, and tanshinone IIA. The CCK-8 method selected 300 μmol/L H2O2 as the oxidative stress condition for experiments, and 0.05 and 0.1 g/mL were selected as the low and high doses of GQZ-DS, respectively, for subsequent experiments. The intervention with H2O2 resulted in reduced cell viability, elevated ROS and MDA levels, decreased SOD activity, increased apoptotic rate, upregulated cleaved caspase-3 expression, and G0/G1 phase cell cycle arrest of 661W cells. Both low and high doses of GQZ-DS alleviated these alterations, with high dose exhibiting stronger protective effects (P < 0.05 or P < 0.01). GQZ-DS also downregulated ANGPTL4 expression at both the mRNA and protein levels. Following plasmid transfection of cells, the study further revealed that ANGPTL4 knockdown mitigated oxidative stress and apoptosis-related injury, whereas ANGPTL4 overexpression exacerbated these pathological changes. Moreover, GQZ-DS partially reversed the degree of cellular oxidative damage induced by ANGPTL4 overexpression. Conclusion GQZ-DS can alleviate the H2O2-induced oxidative injury of 661W retinal photoreceptor cells, and the effects are related to the down-regulation of ANGPTL4 expression.

Large language models (LLMs) offer a modern approach to help inherit traditional Chinese medicine (TCM). This article discussed the progress of LLM applications in TCM and proposed future development directions by reviewing the existing research. We have found that LLMs and related technologies have excellent applications and performance in the management of TCM knowledge and data. They are often applied in information extraction, knowledge graph construction, and data standardization processing. However, data quality and security issues need to be given more attention. In clinical diagnosis and treatment, LLMs can imitate the thinking of TCM by disassembling and reconstructing its diagnostic process and can achieve functions such as prescription recommendation and question and answer (Q&A). However, this approach involves LLMs making inferences and predictions based on existing corpora and thus may not flexibly handle complex environments and tasks. Moreover, the current evaluation criteria for TCM LLMs can be summarized into 3 categories: general evaluation metrics, technical framework evaluation, and evaluation criteria for the characteristics of TCM (such as consistency rates of prescriptions and diagnostic suggestions). However, the lack of a unified and standardized evaluation system hinders the clinical application of TCM LLMs. The future progress of TCM LLMs should focus on the 3 aforementioned critical aspects to achieve technological breakthroughs. In addition, we are promoting the research on vertical TCM LLMs and application terminals. We believe this will bring new ideas to the research on TCM LLMs.

Objective:To investigate the change trend in the burden of 5 common malignant tumors of digestive system (esophageal cancer, gastric cancer, colorectal cancer, pancreatic cancer and liver cancer) in the Chinese population from 1990 to 2021.Methods:The descriptive epidemio-logic method was conducted. The number of new cases, crude incidence rate, age-standardized incidence rate, the number of deaths, crude mortality rate and age-standardized mortality rate of 5 common malignant tumors of digestive system in the Chinese population from 1990 to 2021 of the Global Burden of Disease were collected. The age-standardized rate was calculated based on the standardized demographics of the whole world in the Global Burden of Disease for the year 2021. Observation indicators: (1) The incidence of 5 common malignant tumors of digestive system in the Chinese population from 1990 to 2021; (2) the mortality of 5 common malignant tumors of digestive system in the Chinese population from 1990 to 2021; (3) the change trend of age-standardized incidence rate of 5 common malignant tumors of digestive system in the Chinese population from 1990 to 2021; (4) the change trend of age-standardized mortality rate of 5 common malignant tumors of digestive system in the Chinese population from 1990 to 2021. The Joinpoint regression model was constructed for trend analysis, specifically to calculate the annual percentage change, average annual percentage change (AAPC), and their 95% confidence interval ( CI) for age-standardized incidence and mortality rates for each cancer type at different time periods. Results:(1) The incidence of 5 common malignant tumors of digestive system in the Chinese population from 1990 to 2021. The number of new cases of esophageal cancer, gastric cancer, colorectal cancer, pancreatic cancer and liver cancer in the Chinese population changed from 207 495, 407 471, 158 389, 37 818 and 96 434 in 1990 to 320 805, 611 799, 658 321, 118 665 and 196 637 in 2021. The crude incidence rates of the above cancer types changed from 17.64/100 000, 34.64/100 000, 13.46/100 000, 3.21/100 000, 8.20/100 000 in 1990 to 22.55/100 000, 43.00/100 000, 46.27/100 000, 8.34/100 000, 13.82/100 000 in 2021. The new cases of esophageal cancer, stomach cancer, colorectal cancer, pancreatic cancer, and liver cancer all showed an increasing trend, with absolute changes of 54.61%, 50.15%, 315.64%, 213.78%, and 103.91%, respectively. (2) The mortality of 5 common malignant tumors of digestive system in the Chinese population from 1990 to 2021. The number of deaths of esophageal cancer, gastric cancer, colorectal cancer, pancreatic cancer and liver cancer in the Chinese population changed from 210 821, 374 066, 119 303, 38 883 and 94 937 in 1990 to 296 443, 445 013, 275 129, 119 602 and 172 068 in 2021. The crude death rates of the above cancer types changed from 17.92/100 000, 31.80/100 000, 10.14/100 000, 3.31/100 000, 8.07/100 000 in 1990 to 20.84/100 000, 31.28/100 000, 19.34/100 000, 8.41/100 000, 12.09/100 000 in 2021. Death cases of esophageal cancer, stomach cancer, colorectal cancer, pancreatic cancer, and liver cancer all showed an increa-sing trend, with absolute changes of 40.61%, 18.97%, 130.61%,207.59%, and 81.24%, respectively. (3) The change trend of age-standardized incidence rate of 5 common malignant tumors of digestive system in the Chinese population from 1990 to 2021. The change trends of age-standardized incidence rates of esophageal cancer, gastric cancer, colorectal cancer, pancreatic cancer, and liver cancer in the Chinese population were divided into 5, 5, 4, 5, and 5 periods, respectively, and the AAPCs of age-standardized incidence rates of the above cancer types were -1.60% (95% CI as -1.78% to -1.42%), -1.60% (95% CI as -1.78% to -1.43%), 1.66% (95% CI as 1.39% to 1.94%), 0.72% (95% CI as 0.36% to 1.08%), and -0.31% (95% CI as -0.39% to -0.23%). (4) The change trend of age-standardized mortality rate of 5 common malignant tumors of digestive system in the Chinese population from 1990 to 2021. The change trend of age-standardized mortality rates of esophageal cancer, gastric cancer, colorectal cancer, pancreatic cancer, and liver cancer in the Chinese population were divided into 5, 5, 4, 5, and 4 periods, respectively, and the AAPC of age-standardized mortality rates for each of the above mentioned cancer types were -1.96% (95% CI as -2.03% to -1.90%), -2.44% (95% CI as -2.50% to -2.38%), -0.49% (95% CI as -0.58% to -0.41%), 0.56% (95% CI as 0.48% to 0.63%), and -0.68% (95% CI as -0.89% to -0.52%). Conclusions:From 1990 to 2021, the disease burden of esophageal cancer, gastric cancer and liver cancer in the Chinese population show a downward trend. The standardized incidence of colorectal cancer shows an upward trend, and the standardized mortality rate shows a downward trend. The disease burden of pancreatic cancer shows an upward trend.

Objective:To investigate the clinical efficacy of open anterior myofascial repair surgery on abdominal wall incision hernia.Methods:The retrospective cohort study was conducted. The clinical data of 188 patients who underwent open anterior myofascial repair surgery on abdo-minal wall incision hernia at three medical centers, including Xiangya Hospital of Central South University et al, from December 2016 to December 2024 were collected. There were 85 males and 103 females, aged (62±12)years. Of the 188 patients, 55 cases had large incisional hernia and 133 cases had non-large incisional hernia. Observation indicators: (1) intraoperative conditions; (2) postopera-tive conditions; (3) follow-up. Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test or Fisher exact test. Comparison of ordinal data between groups was conducted using the nonparametic test. Results:(1) Intra-operative conditions. The operation time of the 55 patients with large incisional hernia was (145±40)minutes, and the volume of intraoperative blood loss was 40.0(22.5,55.0)mL, cases with fascial defect located in the central anterior abdominal wall, the superolateral quadrant, the inferolateral quadrant were 26, 7, 22, the fascial defect area was 140(99,169)cm2, cases used with self-fixating mesh and flat mesh were 29, 26. The above indicators of the 133 patients with non-large incisional hernia were (124±34)minutes, 35.0(30.0,45.0)mL, 47, 26, 60, 25(12,40)cm2, 67, 66, respectively. There were significant differences in operation time and fascial defect area between patients with large incisional hernia and non-large incisional hernia ( t=-3.651, Z=-10.339, P<0.05), and there was no significant difference in the volume of intraoperative blood loss, defect quadrant distribution, and mesh type ( Z=-0.501, χ2=2.692, 0.086, P>0.05). (2) Postoperative conditions. Of the 55 patients with large incisional hernia, 7 cases developed postoperative seroma, including 5 cases combined with concomitant surgical-site infection, and 4 additional cases developed with surgical-site infection. Of the 133 patients with non-large incisional hernia, 15 cases developed postoperative seroma, including 3 cases combined with concomitant surgical-site infection. There was a significant difference in surgical-site infection between patients with large incisional hernia and non-large incisional hernia ( χ2=10.707, P<0.05), and there was no significant difference in postoperative seroma ( χ2=0.079, P>0.05). The duration of postoperative hospital stay was 7(6, 9)days for the 55 patients with large incisional hernia and 5(4, 6)days for the 133 patients with non-large incisional hernia, showing a significant difference between them ( Z=-6.292, P<0.05). (3) Follow-up. All 188 patients were followed up for 43(range, 29-67)months. During the follow-up, 9 patients experienced hernia recurrence, including 7 patients with large incisional hernia and 2 patients with non-large incisional hernia. For the 7 patients of large incisional hernia with hernia recurrence, 4 cases underwent reoperation and 3 cases received conservative treatment. All 2 patients of non-large incisional hernia with hernia recurrence received conservative treatment. There was no significant difference in hernia recurrence between patients with large incisional hernia and non-large incisional hernia ( χ2=8.432, P<0.05). Results of chronic pain score at postoperative 3 month showed that among 55 patients with large incisional hernia, 40 cases had mild pain, 7 cases had moderate pain, and 8 cases had severe pain. Among 133 patients with non-large incisional hernia, the above indicators were 102, 28, and 3, respectively. There was no significant difference in chronic pain score at postoperative 3 month between patients with large incisional hernia and non-large incisional hernia ( Z=-0.968, P>0.05). Conclusions:Open anterior myofascial repair surgery can be used for the treatment of abdominal wall incision hernia. Compared with non-large incisional hernia, patients with large incisional hernia have longer operation time, are more prone to surgical-site infection, have longer postoperative hospital stay, and are more likely to experience hernia recurrence.

[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.

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

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.