Objective: Exploring the effect and mechanism of Xinyang Tablet on reduction of ferroptosis in myocardial cells from mice with chronic heart failure. Methods: Sixty C57BL/6J mice were randomly assigned to the sham, model, Xinyang Tablet low-dose (0.34 g/kg), Xinyang Tablet medium-dose (0.68 g/kg), Xinyang Tablet high-dose (1.36 g/kg), and perindopril (0.607 mg/kg) groups using a random number table method (10 mice in each group). Except for the sham group, all other groups underwent aortic arch constriction surgery to construct a chronic heart failure model. On the third day after completion of the modeling, each treatment group was administered the corresponding medication by gavage, while the sham and model groups were administered equal volumes of water by gavage once a day for eight consecutive weeks. After treatment, cardiac ultrasound was used to detect the structure and function of the mouse heart. Hematoxylin and eosin staining was used to detect pathological changes in mouse heart tissue. Masson staining was used to detect the proportion of fibrotic area of mouse heart tissue. Realtime fluorescence PCR was used to detect the mRNA expression of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), collagen 3α (Col3α), and myosin heavy chain 7 (MYH7) in mouse myocardial tissue. Transmission electron microscope was used to detect the ultrastructure of myocardial cell mitochondria. Reactive oxygen species (ROS) staining was used to detect the mean fluorescence intensity of ROS in myocardial tissue. Micro-determination was used to detect superoxide dismutase (SOD) activity in myocardial tissue. An immunofluorescence assay was used to detect the mean fluorescence intensity of phosphorylated histone deacetylase 2 (p-HDAC2) in myocardial cell. Western blotting was used to detect the protein expression of nuclear factor-erythroid 2-related factor 2 (Nrf2), p-HDAC2, nicotinamide adenine dinucleotide phosphate oxidase 1 (NOX1), glutathione peroxidase 4 (GPX4), and cystine glutamate reverse transporter (xCT) in mouse myocardial tissue. Results: Compared to the sham group, the model group showed a decrease in left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), an increase in left ventricular end-systolic diameter(LVESD) and left ventricular end-diastolic diameter (LVEDD), an increase in the proportion of cardiac fibrosis area, an increase in relative expression levels of ANP, BNP, Col3α, and MYH7 mRNA, an increase in ROS mean fluorescence intensity, a decrease in SOD activity, an increase in mean fluorescence intensity of p-HDAC2, an increase in relative expression levels of p-HDAC2 and NOX1 proteins, and a decrease in relative expression levels of Nrf2, GPX4, and xCT proteins (P<0.05). Myocardial fibrosis lesions are obvious, with disordered mitochondrial arrangement, decreased volume and shrinkage, increased membrane density, and reduced mitochondrial cristae. Compared to the model group, the LVEF and LVFS of mice in each dose group of Xinyang Tablet and the perindopril group increased, LVESD and LVEDD decreased, the proportion of fibrotic area of heart tissue decreased, the relative expression levels of ANP, BNP, Col3α, MYH7 mRNA decreased, ROS mean fluorescence intensity decreased, SOD activity increased, mean fluorescence intensity of p-HDAC2 decreased, relative expression levels of p-HDAC2 and NOX1 proteins decreased, and relative expression levels of Nrf2 and xCT proteins increased (P<0.05). Myocardial fibrosis was reduced, the mitochondrial arrangement was more regular, the mitochondria enlarged, the membrane density was reduced, and mitochondrial cristae increased. Compared to the model group, the relative expression level of the GPX4 protein in myocardial tissue increased in the Xinyang Tablet medium-, high-dose, and the perindopril groups (P<0.05). Conclusion Xinyang Tablet can improve ferroptosis and ventricular remodeling in mice with chronic heart failure by regulating the HDAC2-mediated Nrf2 antioxidant pathway.

Objective To evaluate whether 6-gingerol(6G)can inhibit fibrosis and improve the cardiac and renal function and in rats with cardiorenal syndrome.Methods In the in vitro experiments of this study,the incorporation of isotope-labeled amino acids was used to detect the intervention of 6-gingerol on normal rat kidney-49F(NRK-49F)and normal rat kidney-52E(NRK-52E)cells.68 male SD rats weighing 200～250 g were used to establish a rat model of cardiorenal syndrome by ligating the left anterior descending coronary artery and performing 5/6 nephrectomy.The rats were randomly divided into a control group,a model group,a low dose 6-gingerol group(6 mg/kg),a high dose 6-gingerol group(30 mg/kg),and a losartan potassium group(20 mg/kg).The 6-gingerol group received intraperitoneal injection of 6-gingerol,while the control group and model group received intraperito-neal injection of an equal amount of physiological saline.The losartan group received oral administration of losartan potassium for a total of 6 weeks.After successful modeling,blood samples were taken for biochemical and cardiac ultrasound examinations.After the experiment,blood,heart,and kidney samples were taken for Masson,immuno-histochemistry,and Western blot.Results 6-gingerol 20 μmol/L can reduce NRK-49F collagen synthesis and inhibit NRK-52E protein synthesis.Biochemical results showed that the serum creatinine,urea nitrogen,and brain natriuretic peptide(BNP)levels of rats in the low and high dose 6-gingerol groups and the losartan group were all reduced,with high dose 6-gingerol groups and losartan group showing the most significant decrease(P<0.05).Echocardiographic parameters showed that the 6-gingerol group and losartan potassium group improved cardiac contractile function and ventricular remodeling in rats(P<0.05).Masson staining and Western Blot showed renal collagen deposition,with reduced expression of collagen I and α-SMA(P<0.05).Immunofluorescence showed a decrease in the expression of renal collagen deposition I,α-SMA,and TGF-β1(P<0.05).Conclusion 6-Gin-gerol may improve the cardiac and renal function and renal fibrosis in rats with cardiorenal syndrome.

Nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) is a cytosolic pattern recognition receptor that recognizes multiple pathogen-associated molecular patterns and damage-associated molecular patterns. It is a cytoplasmic immune factor that responds to cellular stress signals, and it is usually activated after infection or inflammation, forming an NLRP3 inflammasome to protect the body. Aberrant NLRP3 inflammasome activation is reportedly associated with some inflammatory diseases and metabolic diseases. Recently, there have been mounting indications that NLRP3 inflammasomes play an important role in liver injuries caused by a variety of diseases, specifically hepatic ischemia/reperfusion injury, hepatitis, and liver failure. Herein, we summarize new research pertaining to NLRP3 inflammasomes in hepatic injury, hepatitis, and liver failure. The review addresses the potential mechanisms of action of the NLRP3 inflammasome, and its regulation in these liver diseases.
Humans ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Inflammasomes/physiology* ; Animals ; Liver Diseases/metabolism* ; Liver/metabolism* ; Reperfusion Injury/metabolism*

Objective To investigate the role of circular RNAs(circRNA)in Alzheimer's disease(AD)and its potential mechanism.Methods Six-month-old APP/PS1 mouse model of AD and wild type(WT)mice were subjected and then randomly divided into WT group,WT+circ-Olfm1 knockout group,AD group(transgenic APP/PS1 mice),AD+circ-Olfm1 knockout group,AD+FOXO3a knockout group,with 3 mice in each group.① The total RNA of mouse brain was extracted,and the differential expression of circRNAs and mRNAs between the AD mice and WT mice was detected,and the obtained circRNAs and mRNAs were analyzed with gene ontology(GO)analysis.② RT-qPCR was used to detect the expression of the top 10 up-regulated and down-regulated circRNAs,as well as the expression of circ-Olfm1 and miR-330-5p.③ Lentiviral vectors were prepared and stereotaxically injected into the cortex or hippocampus of WT and AD mice to knock out circ-Olfm1 gene.Water maze test was used to evaluate the effect of circ-Olfm1 knockout on cognitive function,and immunofluorescence assay was employed to observe the deposition of amyloid β(Aβ)plaque in the brain.④ The interaction between circ-Olfm1 and miR-330-5p was verified by double luciferase reporter gene analysis.⑤ The protein levels of AMPK and FOXO3a were detected by Western blotting.⑥ Transmission electron microscopy was utilized to observe the mitochondria of the hippocampus.⑦ The levels of inflammatory factors IL-6,IL-1β and TNF-α were detected by ELISA.Results There were totally 52 differentially expressed circRNAs identified between the AD and WT mice,including 28 up-regulated and 24 down-regulated(fold change>1.5,P<0.05).These differentially expressed genes are mainly involved in signal transduction,learning and memory and other functions.circ-Olfm1 was identified as the most significantly differentially expressed circRNA,which is highly expressed in the neurons and up-regulated in the cerebral cortex and hippocampus of the AD mice.Knockout of circ-Olfm1 reduced the number of Aβ plaques in the cerebral cortex and hippocampus of AD mice(P<0.01).In starBase database,there are complementary sequences observed between circ-Olfm1 and miR-330-5p.Western blotting showed that the addition of Aβ42 significantly increased the expression of AMPK and FOXO3a in the neuronal cells(P<0.01).And silencing circ-Olfm1 led to decreased expression of AMPK and FOXO3a in neuronal cells+Aβ42(P<0.01).ELISA revealed that knockout of FOXO3a significantly increased the levels of inflammatory factors IL-6,IL-1β,and TNF-α(P<0.01).Transmission electron microscopy displayed that knocking FOXO3a out significantly aggravated mitochondrial damage(P<0.01).Conclusion circ-Olfm1 is up-regulated in the brain tissue and neurons+Aβ42 of AD rats,and the mechanism of cognitive impairment in AD rats may be through its regulating FOXO3a protein.

Left atrial appendage closure(LAAC)is an important intervention method for preventing thromboembolic events in patients with non-valvular atrial fibrillation(NVAF).However,incomplete endothelialization following the procedure can impact its long-term efficacy and safety.This article proposes the view of qi flourishment promoting tissue regeneration based on the traditional Chinese medicine(TCM)theory of qi and blood,and explores diagnostic and therapeutic strategies for post-LAAC incomplete endothelialization by examining the theoretical connotation of qi flourishment promoting tissue regeneration and the relationship between qi and vascular endothelial cells.It is proposed that the primary pathogenesis in patients after LAAC is due to qi deficiency.Guided by the view of qi flourishment promoting tissue regeneration,therapeutic approaches such as tonifying qi to promote granulation,supplementing qi to activate blood circulation,and harmonizing the viscera can be employed to address incomplete endothelialization in NVAF patients following LAAC.Clinically,the qi-supplementing and blood-activating classic formula Neituo Shengji San,mainly composed of Astragali Radix,Glycyrrhizae Radix et Rhizoma,Olibanum,Myrrha,Paeoniae Radix Alb,Trichosanthis Radix,Salviae Miltiorrhizae Radix et Rhizoma,etc.,is usually utilized for modified use.Depending on the specific symptom patterns or pathogenesis characteristics of patients with incomplete endothelialization,this basic formula may be used by combining with Shengmai San or augmented with qi-supplementing and blood-activating herbs such as Chuanxiong Rhizoma,Fici Simplicissimae Radix,and Notoginseng Radix et Rhizoma to promote endothelialization.Diagnosing and treating post-LAAC incomplete endothelialization in NVAF patients following the view of qi flourishment promoting tissue regeneration,it is expected to offer a novel TCM perspective and therapeutic strategy to enhance post-LAAC outcomes and address the challenge of incomplete endothelialization.This approach can further serve as a reference for TCM clinicians to manage endothelialization issues following implantation procedures.

Objective:To investigate the prognostic differences between endobronchial and invasive bronchial characteristics in patients with non-small cell lung cancer (NSCLC) undergoing sleeve lobectomy.Methods:This is a retrospective cohort study. A retrospective analysis was conducted on clinical data of 200 NSCLC patients who underwent sleeve lobectomy at the Department of Thoracic Surgery, Shanghai Pulmonary Hospital between January 2014 and December 2016. There were 181 males and 19 females, aged (61.3±8.1) years (range: 30 to 81 years). Based on imaging data, they were divided into the endobronchial group ( n=71) and the invasive bronchial group ( n=129). Clinical data and prognosis were collected and analyzed. Sex, age, hypertension, diabetes, smoking history, pathology type, tumor size, staging, surgical method, surgical site, and sleeve technique were included as covariates. Propensity score matching was performed with a 1∶1 ratio between the endobronchial and invasive bronchial groups using the nearest-neighbor matching method. The Kaplan-Meier method was used to plot survival curves, and the Log-rank test was applied to compare differences between groups. Independent sample t tests, Mann-Whitney U tests, χ2 tests, or Fisher′s exact tests was used for group comparisons. Results:After propensity score matching, 71 cases from each group (endobronchial and invasive bronchial) were included, with no significant differences in baseline characteristics between the two groups (all P>0.05). Endobronchial group showed significantly better overall survival (OS) and disease-free survival (DFS) compared to invasive bronchial group(Log-rank test: P=0.014,0.027). Further subgroup analysis revealed that in the minimally invasive surgery subgroup, the DFS of the endobronchial group was significantly better than that of the invasive bronchial group (Log-rank test: P=0.002), while in the open thoracotomy subgroup, there was no significant difference in DFS between the two groups (Log-rank test: P=0.290). In the right upper lobe sleeve resection subgroup, the endobronchial group had significantly better DFS than the invasive bronchial group (Log-rank test: P=0.039). For patients in the stage Ⅱ to Ⅲ subgroup, the endobronchial group had significantly better DFS than the invasive bronchial group (Log-rank test: P=0.005). Conclusion:In sleeve lobectomy, patients with endobronchial NSCLC have better OS and DFS compared to those with invasive bronchial type, particularly in patients undergoing minimally invasive surgery, right upper lobe sleeve lobectomy, and stage Ⅱ to Ⅲ patients.

Objective To evaluate whether 6-gingerol(6G)can inhibit fibrosis and improve the cardiac and renal function and in rats with cardiorenal syndrome.Methods In the in vitro experiments of this study,the incorporation of isotope-labeled amino acids was used to detect the intervention of 6-gingerol on normal rat kidney-49F(NRK-49F)and normal rat kidney-52E(NRK-52E)cells.68 male SD rats weighing 200～250 g were used to establish a rat model of cardiorenal syndrome by ligating the left anterior descending coronary artery and performing 5/6 nephrectomy.The rats were randomly divided into a control group,a model group,a low dose 6-gingerol group(6 mg/kg),a high dose 6-gingerol group(30 mg/kg),and a losartan potassium group(20 mg/kg).The 6-gingerol group received intraperitoneal injection of 6-gingerol,while the control group and model group received intraperito-neal injection of an equal amount of physiological saline.The losartan group received oral administration of losartan potassium for a total of 6 weeks.After successful modeling,blood samples were taken for biochemical and cardiac ultrasound examinations.After the experiment,blood,heart,and kidney samples were taken for Masson,immuno-histochemistry,and Western blot.Results 6-gingerol 20 μmol/L can reduce NRK-49F collagen synthesis and inhibit NRK-52E protein synthesis.Biochemical results showed that the serum creatinine,urea nitrogen,and brain natriuretic peptide(BNP)levels of rats in the low and high dose 6-gingerol groups and the losartan group were all reduced,with high dose 6-gingerol groups and losartan group showing the most significant decrease(P<0.05).Echocardiographic parameters showed that the 6-gingerol group and losartan potassium group improved cardiac contractile function and ventricular remodeling in rats(P<0.05).Masson staining and Western Blot showed renal collagen deposition,with reduced expression of collagen I and α-SMA(P<0.05).Immunofluorescence showed a decrease in the expression of renal collagen deposition I,α-SMA,and TGF-β1(P<0.05).Conclusion 6-Gin-gerol may improve the cardiac and renal function and renal fibrosis in rats with cardiorenal syndrome.

Objective:To investigate the prognostic differences between endobronchial and invasive bronchial characteristics in patients with non-small cell lung cancer (NSCLC) undergoing sleeve lobectomy.Methods:This is a retrospective cohort study. A retrospective analysis was conducted on clinical data of 200 NSCLC patients who underwent sleeve lobectomy at the Department of Thoracic Surgery, Shanghai Pulmonary Hospital between January 2014 and December 2016. There were 181 males and 19 females, aged (61.3±8.1) years (range: 30 to 81 years). Based on imaging data, they were divided into the endobronchial group ( n=71) and the invasive bronchial group ( n=129). Clinical data and prognosis were collected and analyzed. Sex, age, hypertension, diabetes, smoking history, pathology type, tumor size, staging, surgical method, surgical site, and sleeve technique were included as covariates. Propensity score matching was performed with a 1∶1 ratio between the endobronchial and invasive bronchial groups using the nearest-neighbor matching method. The Kaplan-Meier method was used to plot survival curves, and the Log-rank test was applied to compare differences between groups. Independent sample t tests, Mann-Whitney U tests, χ2 tests, or Fisher′s exact tests was used for group comparisons. Results:After propensity score matching, 71 cases from each group (endobronchial and invasive bronchial) were included, with no significant differences in baseline characteristics between the two groups (all P>0.05). Endobronchial group showed significantly better overall survival (OS) and disease-free survival (DFS) compared to invasive bronchial group(Log-rank test: P=0.014,0.027). Further subgroup analysis revealed that in the minimally invasive surgery subgroup, the DFS of the endobronchial group was significantly better than that of the invasive bronchial group (Log-rank test: P=0.002), while in the open thoracotomy subgroup, there was no significant difference in DFS between the two groups (Log-rank test: P=0.290). In the right upper lobe sleeve resection subgroup, the endobronchial group had significantly better DFS than the invasive bronchial group (Log-rank test: P=0.039). For patients in the stage Ⅱ to Ⅲ subgroup, the endobronchial group had significantly better DFS than the invasive bronchial group (Log-rank test: P=0.005). Conclusion:In sleeve lobectomy, patients with endobronchial NSCLC have better OS and DFS compared to those with invasive bronchial type, particularly in patients undergoing minimally invasive surgery, right upper lobe sleeve lobectomy, and stage Ⅱ to Ⅲ patients.

[摘 要] 目的：采用基于中国人群单核苷酸多态性位点开发的同源重组缺陷（HRD）检测工具评估云南地区卵巢癌患者的HRD状态和BRCA1/2基因突变频率并探讨其临床意义。方法：共纳入2021年1月至2023年5月间在云南省肿瘤医院收治的卵巢癌患者248例，HRD状态采用基因组瘢痕评分法（GSS）（主要依据拷贝数的长度、类型、位置及基因组断片）或HRD评分法（杂合性缺失、端粒等位基因失衡及大片段移位等基因组不稳定事件的总和）进行评估，当组织样本的GSS≥50分或HRD评分≥42分者或检测到有害的BRCA1/2基因突变时HRD被定义为阳性。分析患者HRD状态与临床病理特征的关系。结果：248名卵巢癌患者中70.97%的患者HRD呈阳性，其中BRCA1/2基因突变率为30.65%。Ⅲ~Ⅵ期、高级别浆液腺癌的卵巢癌患者具有更高的HRD阳性率（均P<0.01），HRD评分更高的患者其合并其他基因突变的频率也越高（P<0.05）。HRD状态与卵巢癌的病理类型、临床分期和其他基因突变均有关联（均P<0.01）。结论：云南地区卵巢癌患者HRD阳性率较高，HRD阳性的卵巢癌患者可以从聚ADP核糖聚合酶（PARP）抑制剂治疗中获得更大的收益。

Objective:To automatically synthesize Al 18F-1, 4, 7-triazacyclononane-1, 4, 7-triacetic acid (NOTA)-fibroblast activation protein inhibitor (FAPI)-04, perform PET/CT imaging in vivo, and evaluate its diagnostic efficacy on tumors. Methods:Al 18F-NOTA-FAPI-04 was produced in All-in-one automatic synthesis module and its quality control was conducted by high performance liquid chromatography (HPLC) equipped with a radioactive detector. Al 18F-NOTA-FAPI-04 PET/CT imaging was performed in normal BALB/c mice ( n=3) and 4T1 breast cancer models ( n=3) to determine its biodistribution. Then Al 18F-NOTA-FAPI-04 and 18F-FDG PET/CT imaging were performed in a hepatocellular carcinoma patient (male, 51 years old). Results:The synthesis time of Al 18F-NOTA-FAPI-04 was about 35 min, and the radiochemical yield was (25.2±1.9)% (attenuation correction, n=3). The product was colorless transparent solution with pH value of 7.0-7.5, and the specific activity was (46.11±3.07) GBq/μmol (attenuation correction, n=3). The radiochemical purity was above 99.0% and was still above 98.0% at room temperature after 6 h. PET/CT imaging in mice showed that physiological uptake of Al 18F-NOTA-FAPI-04 was mainly in biliary system and bladder, and Al 18F-NOTA-FAPI-04 highly concentrated in tumor xenografts. PET/CT imaging in the patient showed that Al 18F-NOTA-FAPI-04 obtained high tumor background ratio (TBR) values of 4.1, 8.9, 5.4, 4.8, 2.2 in parasternal lymph nodes, anterior diaphragmatic lymph nodes, hilar lymph nodes, pancreaticoduodenal ligament lymph nodes, abdominal aortic lymph nodes, respectively, while TBR values were 1.0, 2.8, 5.0, 2.1, 1.1 by 18F-FDG. Conclusions:Al 18F-NOTA-FAPI-04 can be synthesized with short time, high radiochemical yield and good stability using All-in-one module. Al 18F-NOTA-FAPI-04 PET/CT imaging has high contrast and excellent diagnostic efficacy on tumors.