OBJECTIVE To investigate the impact of dapagliflozin on contrast-induced acute kidney injury （CIAKI） and prognosis in patients with diabetes mellitus type 2 （T2DM） and acute coronary syndrome （ACS） who underwent percutaneous coronary intervention （PCI）. METHODS Retrospective selection of data on T2DM patients with ACS who underwent PCI treatment in the Cardiology Department of Tianjin Chest Hospital from January 1st 2021 to December 31st 2022. The patients were divided into dapagliflozin group （96 cases） and control group （148 cases） based on whether they received dapagliflozin or not. Renal function indicators were measured for all enrolled patients before PCI and at 48 h and 1 week after PCI， including blood urea nitrogen （BUN）， serum creatinine （Scr）， estimated glomerular filtration rate （eGFR）， cystatin-C （Cys-C）， kidney injury molecule-1 （KIM-1） and β2-microglobulin （β2-MG）. All patients were followed up for at least 1 year. The incidence of CIAKI and major adverse cardiac event （MACE） during follow-up were recorded for both groups. Logistic regression was used to analyze the impact of dapagliflozin on the occurrence of CIAKI， while the Log-rank test was applied to compare the incidence of MACE between the two groups. Cox regression was employed to analyze the impact of dapagliflozin on prognosis. RESULTS At 48 h and 1 week after PCI， serum levels of Cys-C， KIM-1 and β2-MG were significantly lower in the dapagliflozin group compared to the control group （P＜0.05）. The incidence of CIAKI was lower in the dapagliflozin group compared to the control group （6.25% vs. 14.86%， P＝0.042）. Logistic regression analysis revealed that dapagliflozin was an independent protective factor against CIAKI （OR＝0.280， 95%CI 0.101-0.780，P＝0.015）. During the follow-up period， the incidence of MACE was lower in the dapagliflozin group compared to the control group （7.29% vs. 17.57%， P＝0.049）. Cox regression analysis indicated that dapagliflozin reduced the occurrence of MACE after PCI （HR＝0.374， 95%CI 0.161-0.866， P＝0.022）. CONCLUSIONS With adequate hydration， the use of dapagliflozin does not increase the risk of CIAKI following PCI in T2DM patients with ACS.

ObjectiveTo study the mechanism of Huanglian Jiedutang （HLJDT） in treating mice with atherosclerosis （AS） by improving ferroptosis. MethodsA total of 10 SPF C57BL/6J mice were selected as a normal group， and 50 ApoE^-/- mice were randomly divided into five groups： model group， low-dose group of HLJDT， medium-dose group of HLJDT， high-dose group of HLJDT， and atorvastatin （ATV） group. ApoE^-/- mice were fed a high-fat diet for eight weeks to establish the AS model， and at the 9th week， they were given normal saline， low， medium， and high doses of HLJDT （3.9， 7.8， 15.6 g·kg^-1·d^-1）， and atorvastatin calcium tablets （0.01 g·kg^-1·d^-1）， respectively， for a total of eight weeks. The formation of aortic plaque in mice was observed by gross oil red O staining and Masson staining. The levels of total cholesterol （TC）， low-density lipoprotein cholesterol （LDL-C）， triglyceride （TG）， and high-density lipoprotein cholesterol （HDL-C） in blood fat were measured by the automatic biochemical analyzer， and the mitochondrial structure of the aorta was observed by transmission electron microscopy. The content of serum superoxide dismutase （SOD） in serum was detected by enzyme-linked immunosorbent assay （ELISA）. The content of reduced glutathione （GSH） in serum was detected by the microplate method， and that of malondialdehyde （MDA） in serum was detected by the TBA method. The protein expression of nuclear factor E₂-associated factor 2 （Nrf2）/glutathione peroxidase 4 （GPX4） signaling pathway was detected by Western blot. ResultsCompared with those of the normal group， the contents of TC， LDL-C， TG， HDL-C， and MDA in the serum and the aortic vascular plaque deposition of the model group were significantly increased （P<0.01）， while the expression levels of SOD and GSH in serum， as well as Nrf2， solute carrier family 7 member 11 （SLC7A11）， and GPX4 in aorta were significantly decreased （P<0.01）. Mice in the model group appeared mitochondrial fragmentation and vacuolation in the aorta， volume atrophy， mitochondrial crista reduction， or a loose and disorganized form. Compared with those in the model group， the aortic vascular plaque deposition was significantly decreased in the low-dose， medium-dose， and high-dose groups of HLJDT and ATV group， and the contents of serum TC， LDL-C， TG， and MDA in serum were significantly decreased （P<0.05， P<0.01）. The contents of serum SOD and GSH and the expression levels of Nrf2， SLC7A11， and GPX4 in the aorta were increased （P<0.05， P<0.01）， and the symptoms of aortic mitochondrial vacuolation were alleviated. The number of cristae was increased， and they were ordered neatly. ConclusionHLJDT can reduce aortic vascular plaque deposition， decrease blood lipid and MDA expression， increase SOD and GSH expression， and ameliorate the pathological changes of ferroptosis， the mechanism of which is related to the Nrf2/GPX4 signaling pathway.

This study aims to explore the effects of Buzhong Yiqi Decoction(BYD) on the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING) signaling pathway in the mouse model of autoimmune thyroiditis(AIT) and the mechanism of BYD in alleviating the immune injury. Forty-eight NOD.H-2~(h4) mice were assigned into normal, model, low-, medium-, and high-dose BYD, and selenium yeast tablets groups(n=8). Mice of 8 weeks old were treated with 0.05% sodium iodide solution for 8 weeks for the modeling of AIT and then administrated with corresponding drugs by gavage for 8 weeks before sampling. High performance liquid chromatography was employed to measure the astragaloside Ⅳ content in BYD. Hematoxylin-eosin staining was employed to observe the pathological changes in the mouse thyroid tissue. Enzyme-linked immunosorbent assay was employed to measure the serum levels of thyroid peroxidase antibody(TPO-Ab), thyroglobulin antibody(TgAb), and interferon-γ(IFN-γ). Flow cytometry was employed to detect the distribution of T cell subsets in the spleen. The immunohistochemical method was used to detect the expression of cGAS, STING, TANK-binding kinase 1(TBK1), and interferon regulatory factor 3(IRF3). Real-time PCR and Western blot were employed to determine the mRNA and protein levels, respectively, of markers related to the cGAS-STING signaling pathway in the thyroid tissue. The results showed that the content of astragaloside Ⅳ in BYD was(7.06±0.08) mg·mL~(-1). Compared with the normal group, the model group showed disrupted structures of thyroid follicular epithelial cells, massive infiltration of lymphocytes, and elevated levels of TgAb and TPO-Ab. Compared with the model group, the four treatment groups showed intact epithelial cells, reduced lymphocyte infiltration, and lowered levels of TgAb and TPO-Ab. Compared with the normal group, the model group showed increases in the proportions of Th1 and Th17 cells, a decrease in the proportion of Th2 cells, and an increase in the IFN-γ level. Compared with the model group, the four treatment groups presented decreased proportions of Th1 and Th17 cells and lowered levels of IFN-γ, and the medium-dose BYD group showed an increase in the proportion of Th2 cells. Compared with the normal group, the modeling up-regulated the mRNA levels of cGAS, STING, TBK1, and IRF3 and the protein levels of cGAS, p-STING, p-TBK1, and p-IRF3. Compared with the model group, the four treatment groups showed reduced levels of cGAS, STING, TBK1, and IRF3-positive products, down-regulated mRNA levels of cGAS, STING, and TBK1, and down-regulated protein levels of cGAS and p-STING. The high-dose BYD group showed down-regulations in the mRNA level of IRF3 and the protein levels of p-TBK1 and p-IRF3. The above results indicate that BYD can repair the imbalance of T cell subsets, alleviate immune injury, and reduce thyroid lymphocyte infiltration in AIT mice by inhibiting the cGAS-STING signaling pathway.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; Thyroiditis, Autoimmune/metabolism* ; Mice ; Membrane Proteins/metabolism* ; Mice, Inbred NOD ; Humans ; Female ; Nucleotidyltransferases/metabolism* ; Male ; Disease Models, Animal

Glucocorticoid-induced osteoporosis(GIOP) is a serious metabolic bone disease caused by long-term application of glucocorticoids(GCs). Traditional Chinese medicine(TCM) has unique advantages in improving bone microstructure and antagonizing hormone toxicity. This paper systematically reviews the theoretical research, clinical application, and basic research progress of TCM intervention in GIOP. In terms of theoretical research, the theory of "kidney governing bone and generating marrow" indicates that the kidney is closely related to bone development, revealing that core pathogenesis of GIOP is Yin-Yang disharmony, which can be discussed using the theories of "Yin fire", "ministerial fire", and "Yang pathogen damaging Yin". Thus, regulating Yin and Yang is the basic principle to treat GIOP. In terms of clinical application, effective empirical prescriptions(such as Bushen Zhuanggu Decoction, Bushen Jiangu Decoction, and Zibu Ganshen Formula) and Chinese patent medicines(Gushukang Capsules, Hugu Capsules, Xianling Gubao Capsules, etc.) can effectively increase bone mineral density(BMD) and improve calcium and phosphorus metabolism. The combination of traditional Chinese and western medicine can reduce the risk of fracture and play an anti-GIOP role. In terms of basic research, it has been clarified that active ingredients of TCM(such as fraxetin, ginsenoside Rg_1, and salidroside) reduce bone loss and promote bone formation by inhibiting oxidative stress, ferroptosis, and other pathways, effectively improving bone homeostasis. Additionally, classical prescriptions(Modified Yiguan Decoction, Modified Qing'e Pills, Zuogui Pills, etc.) and Chinese patent medicines(Gushukang Granules, Lurong Jiangu Dropping Pills, Gubao Capsules, etc.) can improve bone marrow microcirculation, promote osteoblast differentiation, and inhibit bone cell apoptosis through multiple pathways, multiple targets, and multiple mechanisms. Through the above three aspects, the TCM research status on GIOP is elucidated in the expectation of providing reference for its diagnosis and treatment using traditional Chinese and western medicine treatment programs.
Osteoporosis/physiopathology* ; Humans ; Glucocorticoids/adverse effects* ; Drugs, Chinese Herbal/administration & dosage* ; Animals ; Medicine, Chinese Traditional ; Bone Density/drug effects*

BACKGROUND: Recent studies have shown that sodium-glucose cotransporters-2 (SGLT2) inhibitors significantly improve major adverse cardiovascular events in heart failure with preserved ejection fraction (HFpEF) patients, but the exact mechanism is unknown. Ferritinophagy is a special form of selective autophagy that participates in ferroptosis. In this study, we aimed to investigate whether ferritinophagy was activated during the occurrence of HFpEF, and whether canagliflozin (CANA) could inhibite ferritinophagy. METHODS: We reared Dahl salt-sensitive (DSS) rats on a high-salt diet to construct a hypertensive HFpEF model, and simultaneously administered CANA intervention. Then we detected indicators related to ferritinophagy. RESULTS: The expression of nuclear receptor coactivator 4 (NCOA4), as well as microtubule-associated proteins light chain 3 (LC3), Bcl-2 interacting protein 1 (Beclin-1) and p62, were upregulated in HFpEF rats, accompanied by the downregulation of ferritin heavy chain 1 (FTH1), upregulation of mitochondrial iron transporter sideroflexin1 (SFXN1) and increased reactive oxygen species (ROS) production. Above changes were diminished by CANA. CONCLUSION Ferritinophagy is activated in HFpEF rats and then inhibited by CANA, leading to HFpEF benefits. The inhibition of ferritinophagy could provide new prospective targets for the prevention and treatment of HFpEF, and provide new ideas for investigating the mechanism of cardiovascular benefit of SGLT2 inhibitors.

Objective To investigate the effect and mechanism of Twist-related protein 1(TWIST1)on pulmonary vascular remodeling induced by monocrotaline(MCT)in pulmonary arterial hypertension(PAH)rats.Methods A total of 50 healthy male Sprague Dawley(SD)rats were randomly divided into five groups including control group,MCT-treated group,MCT and dimethyl sulfoxide(DMSO)-treated group,MCT and harmine-treated group MCT and hydroxychloroquine(HCQ)-treated group.The right ventricle systolic pressure(RVSP)was measured,right ventricular hypertrophy index(RVHI)and percentage of medial wall thickness(MT％)to assess the development of PAH.The protein levels of TW1ST1,autophagy markers LC3B and RND3 were determined using western blot.Results Compared with control group,expressions of TWIST1 and LC3B were increased by 2.32±0.22 folds and 0.87±0.19 folds in MCT-induced PAH group,with significant differences(t=15.812,11.227,all P＜0.00 1),while the protein level of RND3 in MCT-induced PAH rats was decreased by 0.32±0.07 folds compared with control group,with significant difference(t=-13.003,P＜0.001).Administration of TWIST1 inhibitor Harmine or autophagy inhibitor hydroxychloroquine significantly suppressed MCT-induced increase in LC3B and down-regulation of RND3 expression,and reduced RVSP,RVHI and MT％expressions in MCT-induced PAH rats,with significant differences(t=-24.277～16.636,all P＜0.001).Conclusion TWIST1 promotes pulmonary vascular remodeling by inducing autophagy activation,thus promoting the occurrence and development of PAH.

Objective:To analyze the surveillance data of population in rabies exposure and post-exposure prophylaxis (PEP) clinics in Shandong province from 2019 to 2023, explore risk factors for exposure, and provide a basis for further standardizing PEP.Methods:Based on surveillance data from the rabies exposure treatment clinic vaccination information system, population, and spatial administrative division data in Shandong province from 2019 to 2023, descriptive epidemiological methods were applied to analyze using SPSS 18.0.Results:The number of individuals receiving post-exposure treatment at PEP clinics in Shandong province from 2019 to 2023 was over 1 million annually and showed an increasing trend year by year, with the highest number of visits occurring from May to August each year. The number of female patients is increasing year by year. The 15-year-old and younger age group accounted for 31.69%-36.86% of clinic visits. Grade Ⅲ exposures accounted for 53.40%, and limbs accounted for approximately 89.81% of exposed areas. Approximately 1.94% is multi site exposure. The main injuring animals were dogs, followed by cats, and the proportion of cats is increasing year by year. The proportion of doctor′s office visitors who self-treated wounds increased from 32.32% to 45.46%, while the proportion of outpatient wound treatment decreased from 76.07% to 66.24%. The whole course vaccination rate after initial exposure is 63.79%. The whole course vaccination rate for the 15-29-year-old age group was lower than that for other age groups. The usage rate of passive immune preparations among grade Ⅲ exposed individuals is 35.66%. From 2019 to 2023, 8 cases of rabies were reported, none of whom received standard post-exposure treatment.Conclusions:The epidemic characteristics and exposure risk of people exposed to suspected rabies animals in Shandong province have changed. It is necessary to pay attention to the female population, the population with low vaccination rate between 15 to 29 years of age, cat bitten people, and carry out continuous monitoring on the exposed population, and timely adjust the prevention and control strategies.

For the treatment of atrial fibrillation,Professor WU Wei innovatively put forward the theory of heart-blood-vessels trinity and the theory of stasis-toxin causing palpitation.It is believed that atrial fibrillation is caused by stasis and toxin,and affects the heart,blood and vessels.The core pathogenesis of atrial fibrillation is due to qi stagnation,blood stasis and toxin.The treatment for atrial fibrillation should be closely based on the pathogenesis,the therapeutic principles of treating from the perspective of stasis and together by removing toxin gradually is advocated.And the therapy of regulating qi,activating blood and removing stasis is also the way to remove toxin.The medication is based on the modified Taoren Honghua Decoction,which is mainly composed of Persicae Semen,Carthami Flos,Chuanxiong Rhizoma,Corydalis Rhizoma,Rehmanniae Radix,Paeoniae Radix Rubra,Salviae Miltiorrhizae Radix et Rhizoma,Jujubae Fructus,Puerariae Lobatae Radix,Nardostachyos Radix et Rhizoma,Ostreae Concha,Poria,and Polygonati Odorati Rhizoma.According to the characteristics of Lingnan climate and atrial fibrillation mostly being easy to affect the emotions,the pungent drugs in the prescription are usually removed,and the specific herbal pair of Puerariae Lobatae Radix-Nardostachyos Radix et Rhizoma is added to remove toxin according to the differentiation of disease.Moreover,for the treatment of atrial fibrillation,Professor WU Wei also adopts traditional Chinese medicine(TCM)external treatment such as foot bath,acupuncture and moxibustion,and physical-breathing exercise as well as health-care methods for comprehensive regulation,relieving the toxin and restoring the original qi.During the treatment atrial fibrillation,Professor WU Wei follows the principle of precise intervention and comprehensive regulation with Chinese medicine,so as to achieve the purpose of eliminating symptoms,restoring sinus rhythm and improving physical constitution.The thoughts of Professor WU Wei for the syndrome differentiation and treatment of atrial fibrillation will provide reference for the treatment of atrial fibrillation with TCM.

Objective To investigate the clinical characteristics and prognosis of acute myeloid leukemia(AML)patients with PTPN11 gene mutation.Methods Total 115 adult AML patients who underwent initial diagnosis,treatment,and second-generation sequencing(NGS)detecting at hospital were recruited in this study.Clinical da-ta included disease characteristics,treatment efficacy,long-term prognosis,immune cell subpopulations,and leu-kemia stem cells were collected to analyze the clinical characteristics and prognosis of AML patients with PTPN11 gene mutation.Results PTPN11 gene mutation rate in newly diagnosed adult AML was 9.57％,and the mutation site mainly occurred in exon 3 region with all mutation type being point mutation.Compared with PTPN11 wild-type group,PTPN11 gene mutation group had a higher early mortality rate(18.18％vs 4.00％,P=0.048),a lower complete response rate(33.33％vs 67.71％,P=0.039),a higher recurrence rate(83.33％vs 42.31％,P=0.043),a shorter median overall survival time(9 months vs 20 months,P=0.026),a lower proportion of ef-fector T cells[(1.39±0.12)％vs(3.56±0.46)％,P=0.038],and a higher proportion of leukemia stem cells[(13.82±3.66)％vs(3.87±1.40)％,P=0.021].Conclusion PTPN11 gene mutation is a poor prognostic marker for AML.Those patients have a high early mortality rate,low complete remission rate,high recurrence rate,short median overall survival time,a low proportion of effector T cells,and a high proportion of leukemia stem cells.

Objective To investigate the effect of Hedyotis diffusa extract(HDE)on the proliferation of liver cancer cells and its relationship with sugar metabolism reprogramming and oxidative phosphorylation and analyze its possible mechanisms.Methods CCK-8 and EDU experiments were used to determine the effect of different concentrations(20,40,80 mg/mL)of HDE on the growth of liver cancer cell line SNU-368.Lactate dehydrogenase activity,glucose uptake,lactate production,extracellular pH,mitochondrial respiratory chain complex activity,and cellular oxygen consumption were measured to analyze the effect of HDE on aerobic glycolysis and oxidative phosphorylation in liver cancer cells.qRT-PCR experiments were used to detect the mRNA expressions of GLUT1,GLUT4,HK2,GPI,PFKL,ALDOA and HIF-1α in SNU-368 cells of different groups.Western blotting experiments were used to detect the protein expression of HIF-1α.A stable cell line overexpressing HIF-1αwas constructed by lentivirus transfection of liver cancer cells SNU-368 and then intervened with HDE;the expression of HIF-1α mRNA and protein was detected with qRT-PCR and Western blotting.Results CCK-8 results showed that the HDE exhibited a concentration-dependent inhibitory effect on the proliferation of liver cancer cells(all P＜0.05).Results from glucose metabolism-related tests indicated that the HDE could inhibit glucose uptake and lactate production,decrease lactate dehydrogenase activity,increase extracellular pH value,enhance cellular oxygen consumption,and elevate activities of mitochondrial respiratory chain complexes Ⅰ,Ⅱ,Ⅲ and Ⅳ(all P＜0.05).qRT-PCR results revealed that the HDE suppressed the mRNA expressions of GLUT1,HK2,GPI,and ALDOA(all P＜0.05).qRT-PCR and Western blotting experiments showed that compared to the control group,the expression of HIF-1α mRNA and protein in the HDE group was significantly reduced.However,when HIF-1α was overexpressed and HDE was added in the HIF-1α-LV group,the expression of HIF-1α mRNA and protein increased again compared to the HDE group.Conclusion HDE inhibits glycolysis and promotes oxidative phosphorylation to inhibit the proliferation of liver cancer cells,and its mechanism of action may be related to the inhibition of HIF-1α expression.