OBJECTIVE To investigate the effects and potential mechanism of Qiangxin decoction on mitochondrion of rats with chronic heart failure （CHF）. METHODS The CHF model was established by ligating the left anterior descending branch of the coronary artery. Modeled rats were divided into model group， Qiangxin decoction low-dose and high-dose groups （12.25， 24.50 g/kg， calculated by crude drug）， and chemical medicine group （Sacubitril valsartan sodium tablets， 10.42 mg/kg）， with 10 rats in each group； control group was set up without treatment. Each group of rats was orally administered with the corresponding medication or normal saline twice a day for 28 consecutive days. After the last medication， the contents of N-terminal pro-brain natriuretic peptide （NT-proBNP） and adenosine triphosphate （ATP） in serum and phosphatidic acid （PA） and cardiolipin （CL） in myocardial tissue were all detected； the pathological damage and collagen fibrosis of rat myocardial tissue were observed； the apoptosis of myocardial cells was determined； the ultrastructure of myocardial tissue was observed； the protein expressions of mitofusin 1 （Mfn1）， Mfn2， optic atrophy protein 1 （OPA1） and dynamin-related protein 1 （Drp1） were all detected in myocardial tissue. RESULTS Compared with control group，the serum content of NT-proBNP， apoptotic rate of myocardial cells， and relative expressions of S-OPA1 and Drp1 proteins were all increased significantly； serum content of ATP，contents of PA and CL， and relative expressions of Mfn1， Mfn2 and L-OPA1 proteins were all significantly reduced （P＜0.05）. There were abnormal membrane tissue structure in various layers of myocardial tissue， degeneration and necrosis of myocardial cells， and severe fibrosis； the mitochondria were swollen， with reduced or absent cristae， and uneven matrix density. After intervention with Qiangxin decoction， the levels of the aforementioned quantitative indicators in serum and myocardial tissue of rats （excluding CL content in the Qiangxin decoction low- dose group） were significantly reversed （P＜0.05）； the pathological damage of myocardial tissue had significantly improved， fibrosis had significantly reduced， mitochondrial morphology tended to be normal， cristae had increased， and matrix density was uniform. CONCLUSIONS Qiangxin decoction can regulate myocardial mitochondrial function and structural integrity of CHF rats， thereby improving myocardial energy metabolism and antagonizing myocardial fibrosis， the mechanism of which may be associated with activating PA/Mfn/CL signaling pathway.

OBJECTIVE To investigate the effects and potential mechanism of Qiangxin decoction on mitochondrion of rats with chronic heart failure （CHF）. METHODS The CHF model was established by ligating the left anterior descending branch of the coronary artery. Modeled rats were divided into model group， Qiangxin decoction low-dose and high-dose groups （12.25， 24.50 g/kg， calculated by crude drug）， and chemical medicine group （Sacubitril valsartan sodium tablets， 10.42 mg/kg）， with 10 rats in each group； control group was set up without treatment. Each group of rats was orally administered with the corresponding medication or normal saline twice a day for 28 consecutive days. After the last medication， the contents of N-terminal pro-brain natriuretic peptide （NT-proBNP） and adenosine triphosphate （ATP） in serum and phosphatidic acid （PA） and cardiolipin （CL） in myocardial tissue were all detected； the pathological damage and collagen fibrosis of rat myocardial tissue were observed； the apoptosis of myocardial cells was determined； the ultrastructure of myocardial tissue was observed； the protein expressions of mitofusin 1 （Mfn1）， Mfn2， optic atrophy protein 1 （OPA1） and dynamin-related protein 1 （Drp1） were all detected in myocardial tissue. RESULTS Compared with control group，the serum content of NT-proBNP， apoptotic rate of myocardial cells， and relative expressions of S-OPA1 and Drp1 proteins were all increased significantly； serum content of ATP，contents of PA and CL， and relative expressions of Mfn1， Mfn2 and L-OPA1 proteins were all significantly reduced （P＜0.05）. There were abnormal membrane tissue structure in various layers of myocardial tissue， degeneration and necrosis of myocardial cells， and severe fibrosis； the mitochondria were swollen， with reduced or absent cristae， and uneven matrix density. After intervention with Qiangxin decoction， the levels of the aforementioned quantitative indicators in serum and myocardial tissue of rats （excluding CL content in the Qiangxin decoction low- dose group） were significantly reversed （P＜0.05）； the pathological damage of myocardial tissue had significantly improved， fibrosis had significantly reduced， mitochondrial morphology tended to be normal， cristae had increased， and matrix density was uniform. CONCLUSIONS Qiangxin decoction can regulate myocardial mitochondrial function and structural integrity of CHF rats， thereby improving myocardial energy metabolism and antagonizing myocardial fibrosis， the mechanism of which may be associated with activating PA/Mfn/CL signaling pathway.

Abstract： ObjectiveThe study aims to explore the effects and regulatory roles of glucose transporter 1 （GLUT1） on the proliferation， migration， adhesion， and angiogenesis of human umbilical vein endothelial cells （HUVECs） under ischemia-hypoxic conditions. MethodsIn vitro experiments were conducted to subject HUVECs to an ischemia-hypoxic-mimicking environment （1% O₂， 5% CO₂， 94% N₂）. The biological characteristics of HUVECs under normoxic and ischemia-hypoxic conditions were compared by assessing cell viability， proliferation capacity， and examining the expression changes of GLUT1， HIF-1α， and VEGFA proteins under ischemia-hypoxia using Western blot technology. Further， GLUT1 was overexpressed using plasmid transfection and the proliferation， migration， adhesion， and angiogenic capabilities of HUVECs were evaluated through scratch assays， cell adhesion assays， and tube formation assays. Mitochondrial morphological changes were observed by transmission electron microscopy，and oxygen consumption rate （OCR） was detected by Seahorse metabolic analyzer to evaluate mitochondrial function. ResultsCompared with normoxic conditions， the ischemia-hypoxic environment significantly inhibited the proliferation， cell viability， migration， and adhesion capabilities of HUVECs and impaired their angiogenic potential. The expression levels of GLUT1， HIF-1α and VEGFA proteins were also markedly reduced. However， when GLUT1 expression was upregulated， the migration， adhesion， and angiogenic capabilities of HUVECs were significantly improved， and the protein expression levels of HIF-1α， VEGFA and VEGFR were increased. Transmission electron microscopy revealed that ischemic-hypoxia leads to mitochondrial swelling and matrix damage， while GLUT1 overexpression significantly alleviates mitochondrial morphology abnormalities. OCR results suggest that GLUT1 overexpression may enhance oxidative phosphorylation of endothelial cells in ischemic-hypoxic environments to improve energy metabolism. These results suggest that GLUT1 may influence the function and angiogenic potential of HUVECs by regulating glucose metabolism and energy supply. ConclusionsThis study reveals the significant regulatory role of GLUT1 in the function of HUVECs under ischemia-hypoxic conditions， potentially through modulating cellular energy metabolism and signal transduction pathways， thereby affecting cell proliferation， migration， adhesion， and angiogenesis. These findings provide a new perspective on the role of GLUT1 in cardiovascular diseases and may offer potential targets for the development of new therapeutic strategies.

Objective:To observe the therapeutic effect of intraocular lens (IOL) protected phacoemulsification (PHACO) in patients with hard nucleus cataract.Methods:A randomized controlled clinical study was conducted.A total of consecutive 120 patients (120 eyes) with hard nucleus cataract of Emery grade Ⅳ or Ⅴ were enrolled from January 2019 to May 2022.The patients were randomly divided into PHACO group receiving routine PHACO, IOL protected PHACO group receiving PHACO under IOL protection, and extracapsular cataract extraction (ECCE) group receiving ECCE, with 40 cases (40 eyes) in each group.Finally, 99 patients completed the follow-up, including 30 cases (30 eyes) in PHACO group, 35 cases (35 eyes) in IOL protected PHACO group, and 34 cases (34 eyes) in ECCE group.The total operation time, intraoperative PHACO time and cumulative energy release of each patient were recorded.The corneal endothelial cell density (ECD), coefficient of variation in endothelial cell area (CV), hexagonal endothelial cell ratio (6A), corneal astigmatism and the number of eyes with different grades of uncorrected visual acuity were measured and compared after 3-month follow-up.The intraoperative and postoperative complications were recorded.This study adhered to the Declaration of Helsinki and was approved by the Ethics Committee of Yanbian University Hospital (NO.2023002).Patients were informed of study content and purpose and signed a consent form before treatment.Results:There was no significant difference in ultrasonic energy and time between PHACO group and IOL protected PHACO group ( P=0.691, 0.982).The total operation time was (38.81±2.73) and (36.45±3.45) minutes in PHACO group and IOL protected PHACO group, significantly shorter than (69.60±4.35) minutes in ECCE group (both at P<0.001).There was no significant difference in age, sex, lens nucleus hardness and other baseline data among the three groups before operation (all at P>0.05).Three months after operation, the number of patients with higher uncorrected visual acuity in PHACO group and IOL protected PHACO group was larger than that in ECCE group ( P=0.006, 0.007).The ECD and 6A in IOL protected PHACO group were (2 155.57±177.88)/mm 2 and (41.31±5.18)%, respectively, which were significantly higher than (1 912.64±224.11)/mm 2 and (36.18±3.27)% in PHACO group, and the CV in IOL protected PHACO group was (50.34±5.90)%, which was lower than (55.67±3.30)% in PHACO group, showing statistically significant differences ( P=0.007, 0.003, 0.005).At 1 week and 3 months after the operation, the corneal astigmatism was significantly lower in IOL-protected PHACO group than in ECCE group, but higher than in PHACO group, and the difference were statistically significant (all at P<0.05). Conclusions:Compared with conventional PHACO, IOL-protected PHACO can effectively reduce the damage of corneal endothelium caused by ultrasonic energy, shorten the operation time and reduce postoperative inflammatory reaction compared with ECCE, and does not significantly increase postoperative corneal astigmatism.IOL-protected PHACO is an effective improved surgical method for patients with hard nucleus cataract.

[摘 要] 目的：探究甘露糖结合凝集素2（LMAN2）在激素受体（HR）阳性乳腺癌组织中的表达水平与乳腺癌患者预后的关系及其对MCF-7 细胞增殖和迁移的影响。方法：通过TCGA、Bc-GenExMiner、GEPIA和Kaplan-Meier Plotter数据库分析LMAN2在乳腺癌组织和正常乳腺组织中的差异性表达及其与患者预后的关系。采用小RNA干扰技术将si-LMAN2#1、si-LMAN2#2及si-NC转染至MCF-7细胞，将过表达LMAN载体（pc-LMAN）及空载体pcDNA3.1阴性对照（pc-NC）转染至MCF-7细胞，实验分为si-LMAN2#1、si-LMAN2#2、si-NC、pc-LMAN2和pc-NC组。通过qPCR和WB实验检测各组细胞中LMAN2 mRNA和蛋白的表达水平，CCK-8、克隆形成、Transwell迁移、WB等实验检测敲低和过表达LMAN 2对MCF-7细胞增殖、克隆形成、迁移及AKT信号通路相关蛋白表达的影响。结果：LMAN2在乳腺癌组织中的表达水平显著高于正常乳腺组织（P<0.001）。HR阳性乳腺癌组织中LMAN2表达水平显著高于HR阴性乳腺癌组织（P<0.001）；LMAN2高表达与HR阳性乳腺癌患者不良预后有关联。敲低LMAN2可显著降低MCF-7细胞的增殖和迁移能力（P<0.01或P<0.001），过表达LMAN2可显著提高MCF-7细胞的增殖和迁移能力（均P<0.001）。敲低LMAN2组MCF-7细胞中PTEN和P21蛋白表达水平均显著升高，p-AKT蛋白表达水平显著降低（均P<0.01）。结论：LMAN2在乳腺癌组织和HR阳性乳腺癌组织中高表达，且与不良预后有关联。LMAN2高表达与MCF-7细胞增殖和迁移有关联，其作用机制可能涉及AKT信号通路。

OBJECTIVE To investigate the effects of Qiangxin decoction on myocardial mitochondrial and energy metabolism in rats with chronic heart failure （CHF） based on mitophagy. METHODS Male SD rats were collected to establish CHF model by ligating the left anterior descending branch of coronary artery. The successful modeling rats were divided into model group， Qiangxin decoction group [12.25 g/（kg·d）， calculated by crude drug]， captopril group [10.38 mg/（kg·d）]， and Qiangxin decoction+captopril group （the same usage and dosage as single drug group） according to a random number table method， with 8 rats in each group. Another 8 normal rats were selected and received threading in the left anterior descending branch of the coronary artery without ligation as the sham operation group. Starting from the second day after successful modeling， the rats in administration groups were given relevant drug intragastrically， twice a day， for consecutive 28 days. After the last medication， the levels of adenosine triphosphate （ATP）， adenosine monophosphate （AMP） and free fatty acid （FFA） in infarcted myocardial tissues were detected， the pathological changes and mitochondrial morphology of the infarcted myocardial tissue were observed， as well as the protein expressions of B cell lymphoma-2 （Bcl-2）， Bcl-2 related X protein （Bax）， TANK-binding kinase 1 （TBK1）， p62 were detected in each group. RESULTS Compared with the sham operation group， the infarcted myocardial tissue fibrosis was changed evidently， with a large number of mitochondrial swelling and fusion， and internal cristae rupture； the levels of AMP and FFA， the protein expressions of Bax and p62 were all increased or up-regulated significantly in infarcted myocardial tissue， while the level of ATP， and the protein expressions of Bcl-2 and TBK1 were all decreased or down-regulated significantly （P＜0.05）. Compared with the model group， the pathological changes of infarcted myocardial tissue and mitochondrial swelling had been improved； the levels of AMP and FFA， and the protein expressions of Bax and p62 in infarcted myocardial tissue were significantly decreased or down-regulated in administration groups， while the level of ATP， and the protein expressions of Bcl-2 and TBK1 were increased or up-regulated significantly （P＜0.05）. And the effect of Qiangxin decoction+captopril group was better than that of single drug group. CONCLUSIONS Qiangxin decoction can alleviate myocardial fibrosis and mitochondrial swelling in CHF rats， and improve their myocardial energy metabolism， which may be related to regulating the expression of Bcl-2， Bax， TBK1 and p62 proteins and promoting myocardial mitophagy.

Objective:To investigate the risk factors and distribution characteristics for skip lateral lymph node metastasis in patients of papillary thyroid carcinoma (PTC).Methods:Clinical data of 720 PTC patients with postoperative pathologically confirmed lymph node metastasis in the lateral cervical region at Xijing Hospital of Air Force Military Medical University from Jan 2014 to Dec 2021 were retrospectively analyzed. According to whether there is skip metastasis in the lymph nodes of the patients, patients were divided into skip metastasis group (92 cases) and non-skip metastasis group (628 cases).Results:The rate of lymph node skip metastasis in PTC in this study was 12.7% (92/720). Women ( OR=1.890, 95% CI:1.118-3.198, P=0.018), age ≥55 years ( OR=2.508, 95% CI:1.412-4.454, P=0.002), tumor involving the upper pole ( OR=1.919, 95% CI:1.220-3.018, P=0.005), and unilateral glandular lobe lesions ( OR=1.926, 95% CI:1.153-3.214, P=0.012) were independent risk factors for lymph node skip metastasis. Skip metastasis is most likely to occur in region Ⅲ, followed by region Ⅵ, Ⅱ and Ⅴ. Larger cancer tended to have more than one jumping metastases in regions Ⅲ and Ⅳ ( P=0.001, 0.016). Conclusion:In female PTC patients, age≥55 years , tumors involving upper pole, and unilateral lesions,are all the hazardous factor for skip metastasis in the lateral neck region.

Objective:To investigate the clinicopathologic features and prognostic factors of breast cancer patients with tumor deposits in the ipsilateral axillary region.Methods:We retrospectively analyzed the clinicopathologic data and follow-up results of 155 patients with breast cancer diagnosed for the first time and complicated with tumor deposits in the ipsilateral axillary region in the Department of Thyroid-Breast-Vascular Surgery of Xijing Hospital from January 2008 to September 2018. Kaplan-Meier method was used for survival analysis. Log rank test was used for the univariate analysis of prognostic factors, and Cox regression was used for multivariate analysis.Results:The median disease free survival (DFS), median distant metastasis free survival (DMFS), and median overall survival (OS) of the 155 patients were 52.0 months, 66.6 months, and 102.2 months, respectively. The 5-year and 10-year DFS rates were 45.7% and 23.1%, the 5-year and 10-year DMFS rates were 56.9% and 28.9%, and the 5-year and 10-year OS rates were 79.3% and 46.0%, respectively. Multivariate Cox regression analysis showed that family tumor history ( HR=0.362, 95% CI: 0.140-0.937), clinical T stage (T3: HR=3.508, 95% CI: 1.380-8.918; T4: HR=2.220, 95% CI: 1.076-4.580), estrogen/progesterone receptor status ( HR=0.476, 95% CI: 0.261-0.866), number of tumor deposits ( HR=1.965, 95% CI:1.104-3.500) and neoadjuvant chemotherapy ( HR=1.961, 95% CI: 1.032-3.725) were independent influencing factors for DFS. Molecular subtype [human epidermal growth factor receptor-2(HER-2) positive and hormone receptor negative: HR=7.862, 95% CI: 3.189-19.379], number of tumor deposits ( HR=2.155, 95% CI: 1.103-4.212), neoadjuvant chemotherapy ( HR=5.002, 95% CI: 2.300-10.880) and radiotherapy ( HR=2.316, 95% CI: 1.005-5.341) were independent influencing factors of DMFS. Histological grade ( HR=4.362, 95% CI: 1.932-9.849), estrogen/progesterone receptor expression ( HR=0.399, 95% CI: 0.168-0.945), HER-2 expression ( HR=2.535, 95% CI: 1.114-5.768) and neoadjuvant chemotherapy ( HR=4.080, 95% CI: 1.679-9.913) were independent influencing factors of OS. Conclusions:The presence of tumor deposits weakens the influence of axillary lymph node status and distant metastases on the prognosis of breast cancer patients. Therefore, a clinicopathological staging system taking into account tumor deposits should be developed. Since the number of tumor deposits affects the risk of recurrence and metastasis of breast cancer patients, we recommend that the number of tumor deposits should be reported in detail in the pathological report after breast cancer surgery.

OBJECTIVE To observe the changes of cardiac function,local inflammation level and macrophage M2 polarization in mice with acute myocardial infarction(AMI after electroacupuncture preconditioning at the Neiguan point,and to explore the possible mechanisms from the perspective of regulating the DNA-PK/Rictor/Myc signaling pathway.METHODS Male C57BL/6J mice were randomly divided into sham group,model group and electroacupuncture group,with 10 mice in each group.The electroacupuncture group received bilateral electroacupuncture interventions at the Neiguan points,sparse-dense wave,2/15 Hz,1 mA,20 min/time,once a day for 3 consecutive days,and AMI models were performed 0.5 h after the electroacupuncture interventions.The myocardial ischemia model was prepared by ligating the left anterior descending branch.Echocardiography was used to detect cardiac ejection frac-tion(EF and fractional shortening(FS to evaluate cardiac function;HE and TUNEL staining were used to observe the pathological morphology of myocardium and apoptosis of cardiomyocytes,and immunohistochemistry and ELISA were used to detect IL-1β,TNF-α and NLRP3 in infarcted myocardium and peripheral blood to evaluate the level of inflammation;flow cytometry was used to detect cardiac macrophage polarization status,and Western blot method to detect the protein expression levels of DNA-PK,p-DNA-PK,Rictor and Myc in infarcted myocardium.RESULTS Compared with the sham group,the model group showed significantly lower EF and FS(P<0.000 1,significant inflammatory cell infiltration,significantly higher cardiomyocyte apoptotic index(P<0.001,up-regulated expression of IL-1β,NLRP3 and TNF-α in the myocardium and serum(P<0.01,P<0.001,a significant increase in the percentage of macrophages(P<0.001,a decrease in the percentage of cardiac M2-type macrophages(P<0.000 1,and a significant decrease in the expression levels of p-DNA-PK,Rictor and Myc proteins in myocardium(P<0.05,P<0.000 1.Compared with the model group,EF and FS were significantly higher in the electroacupuncture group(P<0.000 1,inflammatory cell infiltration was re-duced,cardiomyocyte apoptotic index was decreased(P<0.01,and the expression of IL-1β,NLRP3 and TNF-α was down-regula-ted in myocardium and serum(P<0.05,P<0.01,P<0.001;the macrophage percentage was decreased(P<0.05,cardiac M2-type macrophage percentage was increased(P<0.01,and p-DNA-PK,Rictor and Myc protein expression was enhanced in myocardium(P<0.05,P<0.01,P<0.000 1.CONCLUSION Electroacupuncture preconditioning may promote macrophage M2 polarization,attenuate local inflammation,and reduce cardiomyocyte apoptosis by modulating the DNA-PK/Rictor/Myc signaling pathway,thus im-proving cardiac function and achieving myocardial protective effects.

Objective:To investigate the clinicopathologic features and prognostic factors of breast cancer patients with tumor deposits in the ipsilateral axillary region.Methods:We retrospectively analyzed the clinicopathologic data and follow-up results of 155 patients with breast cancer diagnosed for the first time and complicated with tumor deposits in the ipsilateral axillary region in the Department of Thyroid-Breast-Vascular Surgery of Xijing Hospital from January 2008 to September 2018. Kaplan-Meier method was used for survival analysis. Log rank test was used for the univariate analysis of prognostic factors, and Cox regression was used for multivariate analysis.Results:The median disease free survival (DFS), median distant metastasis free survival (DMFS), and median overall survival (OS) of the 155 patients were 52.0 months, 66.6 months, and 102.2 months, respectively. The 5-year and 10-year DFS rates were 45.7% and 23.1%, the 5-year and 10-year DMFS rates were 56.9% and 28.9%, and the 5-year and 10-year OS rates were 79.3% and 46.0%, respectively. Multivariate Cox regression analysis showed that family tumor history ( HR=0.362, 95% CI: 0.140-0.937), clinical T stage (T3: HR=3.508, 95% CI: 1.380-8.918; T4: HR=2.220, 95% CI: 1.076-4.580), estrogen/progesterone receptor status ( HR=0.476, 95% CI: 0.261-0.866), number of tumor deposits ( HR=1.965, 95% CI:1.104-3.500) and neoadjuvant chemotherapy ( HR=1.961, 95% CI: 1.032-3.725) were independent influencing factors for DFS. Molecular subtype [human epidermal growth factor receptor-2(HER-2) positive and hormone receptor negative: HR=7.862, 95% CI: 3.189-19.379], number of tumor deposits ( HR=2.155, 95% CI: 1.103-4.212), neoadjuvant chemotherapy ( HR=5.002, 95% CI: 2.300-10.880) and radiotherapy ( HR=2.316, 95% CI: 1.005-5.341) were independent influencing factors of DMFS. Histological grade ( HR=4.362, 95% CI: 1.932-9.849), estrogen/progesterone receptor expression ( HR=0.399, 95% CI: 0.168-0.945), HER-2 expression ( HR=2.535, 95% CI: 1.114-5.768) and neoadjuvant chemotherapy ( HR=4.080, 95% CI: 1.679-9.913) were independent influencing factors of OS. Conclusions:The presence of tumor deposits weakens the influence of axillary lymph node status and distant metastases on the prognosis of breast cancer patients. Therefore, a clinicopathological staging system taking into account tumor deposits should be developed. Since the number of tumor deposits affects the risk of recurrence and metastasis of breast cancer patients, we recommend that the number of tumor deposits should be reported in detail in the pathological report after breast cancer surgery.