Objective To compare the benefits and drawbacks of primary patch expansion versus pericardial tube right ventricular-pulmonary artery connection in patients diagnosed with pulmonary atresia with ventricular septal defect (PA/VSD). Methods A retrospective study was conducted on patients diagnosed with PA/VSD who underwent primary right ventricular-pulmonary artery connection surgery at our center between 2010 and 2020. Patients were categorized into two groups based on the type of right ventricular-pulmonary artery connection: a pericardial tube group and a patch expansion group. Clinical data and imaging findings were compared between the two groups. Results A total of 51 patients were included in the study, comprising 31 males and 20 females, with a median age of 12.57 (4.57, 49.67) months. The pericardial tube group included 19 patients with a median age of 17.17 (7.33, 49.67) months, while the patch expansion group consisted of 32 patients with a median age of 8.58 (3.57, 52.72) months. In both groups, the diameter of pulmonary artery, McGoon index, and Nakata index significantly increased after treatment (P<0.001). However, the pericardial tube group exhibited a longer extracorporeal circulation time (P<0.001). The reoperation rate was notably high, with 74.51% of patients requiring further surgical intervention, including 26 (81.25%) patients in the patch expansion group and 12 (63.16%) patients in the pericardial tube group. No statistical differences were observed in long-term cure rates or mortality between the two groups (P＞0.005). Conclusion In patients with PA/VSD, both patch expansion and pericardial tube right ventricular-pulmonary artery connection serve as effective initial palliative treatment strategies that promote pulmonary vessel development and provide a favorable foundation for subsequent radical operations. However, compared to the pericardial tube approach, the patch expansion technique is simpler to perform and preserves some intrinsic potential for pulmonary artery development, making it the preferred procedure.

Objective To introduce a modified technique of right ventricular outflow tract (RVOT) reconstruction using a handmade bicuspid pulmonary valve crafted from expanded polytetrafluoroethylene (ePTFE) and to summarize the early single-center experience. Methods Patients with complex congenital heart diseases (CHD) who underwent RVOT reconstruction with a handmade ePTFE bicuspid pulmonary valve due to pulmonary regurgitation at Guangdong Provincial People’s Hospital from April 2021 to February 2022 were selected. Postoperative artificial valve function and right heart function indicators were evaluated. Results A total of 17 patients were included, comprising 10 males and 7 females, with a mean age of (18.18±12.14) years and a mean body weight of (40.94±19.45) kg. Sixteen patients underwent reconstruction with a handmade valved conduit, with conduit sizes ranging from 18 to 24 mm. No patients required mechanical circulatory support, and no in-hospital deaths occurred. During a mean follow-up period of 12.89 months, only one patient developed valve dysfunction, and no related complications or adverse events were observed. The degree of pulmonary regurgitation was significantly improved post-RVOT reconstruction and during follow-up compared to preoperative levels (P<0.001). Postoperative right atrial diameter, right ventricular diameter, and tricuspid regurgitation area were all significantly reduced compared to preoperative values (P<0.05). Conclusion The use of a 0.1 mm ePTFE handmade bicuspid pulmonary valve for RVOT reconstruction in complex CHD is a feasible, effective, and safe technique.

ObjectiveTo explore the effects of modified Danggui Beimu Kushen pills on tumor growth and T-cell subsets in H22 hepatocellular carcinoma-bearing mice and to provide an experimental basis for the treatment of hepatocellular carcinoma with modified Danggui Beimu Kushen pills combined with immune checkpoint antibodies. MethodA H22 hepatocellular carcinoma-bearing mouse model was established. The modeled mice were randomized into model， cisplatin， low- （4 g·kg^-1·d^-1）， medium- （8 g·kg^-1·d^-1）， and high-dose （16 g·kg^-1·d^-1） modified Danggui Beimu Kushen pills groups. After continuous administration for 14 days， the mice were sacrificed on day 15. The tumor volume was measured on days 0， 4， 8， 12， 15 of drug administration. Tumors were weighed and thymus index and spleen index were calculated. Spleen lymphocytes were co-cultured with H22 hepatoma cells， and the tumor cell-killing rate was detected by the cell counting kit-8 （CCK-8）. Real-time polymerase chain reaction was carried to determine the mRNA levels of programmed cell death protein-1 （PD-1） and lymphocyte activation gene-3 （LAG-3） in spleen and tumor tissues. The number of CD4⁺ and CD8⁺ T cells and the expression of PD-1 and LAG-3 were detected by immunohistochemistry （IHC）. ResultOn day 8 of drug administration， tumor volumes in all treatment groups decreased compared with that in the model group. On day 15， both tumor volume and tumor weight were significantly lower in the treatment groups than in the model group （P<0.01）， with the cisplatin group showing the most pronounced reduction. Compared with the model and cisplatin groups， medium- and high-dose modified Danggui Beimu Kushen pills increased the thymus index （P<0.01）. Compared with the model group， all treatment groups showed increased spleen index （P<0.05， P<0.01）， with the cisplatin group showing the most significant increase. Compared with the model and cisplatin groups， all the groups of modified Danggui Beimu Kushen pills demonstrated increased number of CD4⁺ and CD8⁺ T cells and tumor cell-killing rate in the spleen and tumor tissues （P<0.01） and down-regulated mRNA and protein levels of LAG-3 （P<0.05， P<0.01）. The high-dose group of modified Danggui Beimu Kushen pills had lower mRNA level of PD-1 in the tumor tissue than the model and cisplatin groups （P<0.01）. ConclusionModified Danggui Beimu Kushen pills may promote the proliferation and tumor microenvironment infiltration of CD4⁺ and CD8⁺ T cells in H22 tumor-bearing mice by down-regulating LAG-3 expression， thereby improving T-cell immune activity and inhibiting tumor growth. This study provides an experimental basis for the combination of modified Danggui Beimu Kushen pills and immune checkpoint antibodies in the treatment of hepatocellular carcinoma.

Lung cancer， the most common malignant tumor， is characterized by a complex pathogenesis and high malignancy， and poses a significant threat to the health and lives of affected individuals. p53 signaling pathway plays a crucial role in the progression of lung cancer and is considered one of the potential targets for targeted therapy. In recent years， multiple studies have indicated that traditional Chinese medicine （TCM） can exert anticancer effects by modulating the p53 signaling pathway. Based on this， this article systematically summarizes the current status and progress of research on TCM intervening in lung cancer by regulating p53 signaling pathway. It was found that TCM formula and preparations， such as Qingjin desheng tablet， Tiaoqi xiaoji decoction， Bufei tongluo jiedu formula， Jianpi bushen formula and Yiqi fuzheng jiedu formula， can promote autophagy and apoptosis of lung cancer cells， inhibit the growth and metastasis of lung cancer cells and strengthen the immune function of the body by activating p53 signaling pathway， thereby inhibiting lung cancer. TCM monomers， such as pseudoginsenoside-Rh2， saikosaponin D， polyphyllin Ⅶ， dendrobiine， sophoridine， gambogic acid， triptolide and triptolide succinate monoester YJ-4， can accelerate cell apoptosis， inhibit the proliferation of lung cancer cells and regulate cell cycle by activating p53 signaling pathway， thereby inhibiting lung cancer.

Lung cancer， the most common malignant tumor， is characterized by a complex pathogenesis and high malignancy， and poses a significant threat to the health and lives of affected individuals. p53 signaling pathway plays a crucial role in the progression of lung cancer and is considered one of the potential targets for targeted therapy. In recent years， multiple studies have indicated that traditional Chinese medicine （TCM） can exert anticancer effects by modulating the p53 signaling pathway. Based on this， this article systematically summarizes the current status and progress of research on TCM intervening in lung cancer by regulating p53 signaling pathway. It was found that TCM formula and preparations， such as Qingjin desheng tablet， Tiaoqi xiaoji decoction， Bufei tongluo jiedu formula， Jianpi bushen formula and Yiqi fuzheng jiedu formula， can promote autophagy and apoptosis of lung cancer cells， inhibit the growth and metastasis of lung cancer cells and strengthen the immune function of the body by activating p53 signaling pathway， thereby inhibiting lung cancer. TCM monomers， such as pseudoginsenoside-Rh2， saikosaponin D， polyphyllin Ⅶ， dendrobiine， sophoridine， gambogic acid， triptolide and triptolide succinate monoester YJ-4， can accelerate cell apoptosis， inhibit the proliferation of lung cancer cells and regulate cell cycle by activating p53 signaling pathway， thereby inhibiting lung cancer.

Objective:To investigate the effect of total saponins of Panax japonicus(TSPJ) on ferroptosis of myocardial cells in diabetic cardiomyopathy(DCM) rats and underlying mechanism.Methods:Experiment 1: SD rats were divided into control group, DCM group, low-dose TSPJ group, high-dose TSPJ group, and metformin(Met) group, with 10 rats in each group. Experiment 2: SD rats were divided into control group, DCM group, TSPJ group, adenosine monophosphate-activated protein kinase(AMPK) inhibitor Compound C group, and TSPJ+ AMPK agonist AICAR group, with 10 rats in each group. Except for the control group, all rats were intraperitoneally injected with streptozotocin to construct a DCM model. After 8 weeks of corresponding drug intervention, the body weight as well as glucose and lipid metabolism of rats in each experimental group were assessed, and the cardiac function indicators were detected with echocardiography. The levels of serum lactate dehydrogenase(LDH), cardiac troponin I(cTnI) and creatine kinase isoenzyme MB(CK-MB) were detected by ELISA technique. The pathological changes of myocardial tissue were observed using hematoxylin-eosin(HE) staining. The levels of dismutase(SOD), glutathione(GSH), malondialdehyde(MDA), reactive oxygen species(ROS) and Fe 2+ in myocardial tissue were detected. Western blot was used to detect ferroptosis, ferritinophagy, and the AMPK/mammalian target of rapamycin/UNC-51-like kinase 1(mTOR/ULK1) signaling pathway related proteins expression in myocardial tissue. Results:Compared with control group, left ventricular ejection fraction(EF), left ventricular short axis shortening rate(FS), peak blood velocity ratio(E/A) between early and late diastolic periods were significantly decreased in DCM group, left ventricular inner diameter(LVEDd) was increased, and the serum LDH, cTnI, CK-MB were increased, the levels of SOD, GSH were decreased, MDA, ROS, Fe 2+ were increased in myocardial tissue, the expressions of TFR1, NCOA4 LC3-II/LC3-I, Beclin-1, phosphorylated AMPK and phosphorylated ULK1 were increased, the expressions of GPX4, SLC7A11 and phosphorylated mTOR were decreased. Compared with DCM group, the above indicators of rats were significantly improved in each treatment group. Compared with the TSPJ group, the AMPK agonist AICAR reversed the effects of TSPJ on ferroptosis and ferritinophagy mediated by the AMPK/mTOR/ULK1 pathway in DCM rat cardiomyocytes. Conclusion:TSPJ can inhibit ferroptosis in DCM rat cardiomyocytes and improve myocardial injury by regulating AMPK/mTOR/ULK1 mediated ferritinophagy.

[Objective]To explore the effects of electricity on sperm quality,sex hormone levels,and related proteins in TGF-β 1/smads signaling in testicular tissue.[Methods]Forty male SD rats were randomly divided into blank group,model group,electroacupuncture group,and positive drug group.Adenine gavage method was used to establish the model,in the electroacupuncture group,rats received electroacupuncture treatment at the acupoints Zhongji,Guanyuan,Zusanli,and Sanyinjiao once daily for 30 minutes;in the positive drug group,rats were administered L-carnitine oral solution via gavage at a dosage of 10 mL/kg,both intervention groups underwent continuous treatment for 28 days.After treatment,the changes of sperm number,sperm motility rate,follicle-stimulating hormone(FSH),luteizing hormone(LH)and serum sex hormone testosterone(T)were detected by HE staining,and the expression of TGF-β-1/smads signaling pathway in testicular tissue was examined by Western Blot.[Results]Compared to the blank group,the model group showed a significant decrease in sperm count and sperm motility rate(P<0.05),both the electroacupuncture group and the positive drug group exhibited significant increases compared to the model group(P<0.05).Compared to the blank group,the model group had a significant decrease in serum testosterone(T)levels(P<0.05),and significant increases in serum FSH and LH levels(P<0.05);in comparison to the model group,the electroacupuncture group and the positive drug group showed significant increases in serum T levels(P<0.05),and significant decreases in serum FSH and LH levels(P<0.05).The HE staining results showed typical pathological features of AR in the testicular tissue of model group rats,with varying degrees of improvement observed in electroacupuncture and positive drug group rats.Western Blot analysis revealed that in the model group,the protein levels of TGF-β,p-smad2,and p-smad3 in the TGF-β1/smads pathway in testicular tissue were significantly increased(P<0.05);in comparison to the model group,the electroacupuncture group and the positive drug group showed significant decreases in the protein levels of TGF-β,p-smad2,and p-smad3(P<0.05).[Conclusion]Acupuncture can improve the sperm number and sperm motility rate,regulate sex hormone level and improve the spermatogenic environment,and affect the spermatogenesis process via TGF-β 1/smads signaling pathway.

Objective To investigate the effect of PCSK9 inhibitors on the level of inflammation and ven-tricular remodeling after PCI in ST-elevation acute myocardial infarction.Methods A total of 220 patients with acute ST-segment elevation myocardial infarction who received percutaneous coronary artery intervention in the Emergency Center of Qingdao Central Hospital from April 2021 to July 2023 were randomly divided into two groups,110 patients in the control group were treated with conventional treatment,and 110 patients in the PCSK9i group were treated with PCSK9 inhibitors on the basis of conventional treatment.Compared before and after treatment left ventricular endsystolic diameter(LVESD)and left ventricular ejection fraction(LVEF)and triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),total cholesterol(TC).C-reactive protein(CRP),interleukin 6(IL-6),tumor necrosis factor α(TNF-α).The incidence of major adverse cardiovascular events(MACE)(including myocardial infarction,recurrence of heart failure,malignant arrhythmia,and cardiovascular death)was compared.Results After 6 months of treatment and follow-up,LVEDD(mm),LVESD(mm),TG(mmol/L),TC(mmol/L),LDL-C(mmol/L),CRP(mg/L),TNF-α(pg/mL)and JL-6(ng/mL)after PCSK9i treatment were significantly lower than those in the control group,and the difference was statistically significant[(51.32±5.84)vs.(54.43±2.91);(34.88±2.69)vs.(36.96±3.19);(1.41±0.61)vs.(2.13±1.26);(3.53±1.06)vs.(3.98±0.93);(0.95±0.36)vs.(1.79±0.27);(5.18±1.92)vs.(7.69±2.61);(36.43±9.41)vs.(57.79±14.43);(17.4±0.68)vs.(28.55±8.92),All P<0.01],and the LVEF(%)and HDL-C(mmol/L)in the PCSK9i group were higher than patients in the control group,and the difference was statistically significant[(46.69±3.63)vs.(41.34±3.42),P<0.05,(1.35±0.29)vs.(1.29±0.27),P<0.01].The incidence of MACE events in the PCSK9i group was obviously lower than patients in the control group(5.2%vs.13.6%,P<0.05).Conclusion The application of PCSK9 inhibitors after PCI in patients with ST-segment elevation acute myocardial infarction can better reduce blood lipids,stabilize coronary plaque,reduce local and circula-tory inflammatory responses after myocardial infarction,improve ventricular adverse remodeling after myocardial infarction,inhibit ventricular remodeling,and reduce the total incidence of MACE,worthing promoting use.

Objective:To investigate the causal relationship between trimethylamine N-oxide (TMAO) and its precursors (betaine, carnitine, and choline) and pancreatic diseases based on the Mendelian randomization (MR) method.Methods:Genome-wide association study data of TMAO, betaine, carnitine, choline, acute pancreatitis (AP), chronic pancreatitis (CP), pancreatic cancer (PC), and circulating immune cell characteristics (white blood cell, lymphocyte, monocyte, neutrophil, eosinophil and basophil) were collected. According to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE)-MR reporting guidelines, the available genetic variants [single nucleotide polymorphism (SNP)] were strictly screened. The causal relationship between exposure (TMAO and its precursors) and outcomes (pancreatic diseases and circulating immune cell characteristics) was evaluated using inverse variance weighting (IVW), MR-Egger regression and weighted median. The reliability of the results was evaluated by sensitivity analysis based on MR-Egger regression, MR-PRESSO, Cochrane's Q test and leave-one-out method. Results:A total of 36 SNP associated with TMAO and its precursors were included. Five of these were associated with TMAO, 13 with betaine, 12 with carnitine, and 6 with choline. ① MR analysis showed that TMAO may increase the risk of AP [odds ratio ( OR) = 1.100, 95% confidence interval (95% CI) was 1.008-1.200, P = 0.032], and choline may reduce the risk of alcoholic acute pancreatitis (AAP; OR = 0.743, 95% CI was 0.585-0.944, P = 0.015). The analysis results of MR-Egger regression and weighted median were consistent with the IVW results. There is no evidence to support a causal relationship between TMAO and its precursors and the risk of CP and PC. Sensitivity analysis indicated that SNP analyzed by MR showed no heterogeneity and low pleiotropy. The leave-one-out method analysis determined that after excluding any SNP, the effect intervals of the remaining SNP on the results were similar to the overall effect intervals, which suggested the robustness of MR results. ② There was a positive causal relationship between plasma TMAO level and circulating monocyte count ( OR = 1.017, 95% CI was 1.000*-1.034, P = 0.048, * represented that the data was obtained by correcting to 3 decimal places from 1.000 1). The causal effect obtained by MR-Egger regression and weighted median analysis was consistent with the results of IVW. Sensitivity analysis illustrated SNP analyzed by MR showed no heterogeneity and pleiotropy. The leave-one-out method analysis determined that after excluding any SNP, the effect intervals of the remaining SNP on the results were similar to the overall effect intervals, which suggested the robustness of MR results. Conclusion:TMAO and choline may change the risk of AP, and TMAO may contribute to the increase of circulating monocyte count in AP.

OBJECTIVE To study the way in which hypidone hydrochloride(code:YL-0919)improves motor function after ischemic stroke(IS)and explore the related mechanism.METHODS Adult male SD rats were used to establish a middle cerebral artery occlusion(MCAO)model that simulated acute IS.All animals were randomly divided into four groups:sham group,MCAO group,MCAO+YL-0919 group,and MCAO+YL-0919+erastin(Era,ferroptosis inducer)group.The drug administration groups received the first ip injection 6 h after operation,followed by continuous ip injection once per day.After 7-10 d of drug administration,the effect of YL-0919 on motor function after IS were evaluated via neu-rological function test,adhesive-removal test,rotarod test,balance beam test and open field test.After 7 d of drug administration,TTC staining was used to detect the cerebral infarction area while the colo-rimetry method was used to measure the contents of glutathione(GSH),malondialdehyde(MDA),and ferrous ions(Fe2+)in the penumbra of the cerebral cortex.Western blotting was used to detect the expression levels of glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(xCT),acyl-CoA synthetase long-chain family member 4(ACSL4),and transferrin receptor 1(TFR1)in the cortical penumbra.RESULTS Compared with the sham group,the MCAO group showed higher neurological function scores(P<0.01),with notably prolonged time for tape removal and first contact with the right forepaw(P<0.01),spent significantly more time crossing the balance beam(P<0.01)but endured a notably shorter duration on the rotarod(P<0.01),reduced the movement distance in the open field(P<0.01),had a remarkably increased infarct area(P<0.01)but significantly level of GSH in the cortical penumbra region decreased(P<0.01),while MDA and Fe2+levels were markedly increased(P<0.01).Protein expression levels of GPX4 and xCT were reduced(P<0.05),while those of ACSL4 and TFR1 were elevated(P<0.05).Compared with the MCAO group,these changes were significantly reversed after YL-0919 administration.However,when Era and YL-0919 were administered simultaneously,the reversal effect of YL-0919 was significantly weakened.CONCLUSION YL-0919 can improve motor function impairment and reduce cerebral infarction areas in rats after IS,and the mechanism may be related to the inhibition of ferroptosis.