Colorectal cancer(CRC) is a common malignant tumor worldwide. Due to the treatment intolerance and side effects, CRC rank the top among various cancers regarding the incidence and mortality rates. Therefore, exploring new therapies is of great significance for the treatment of CRC. Aerobic glycolysis(AEG) plays an important role in the microenvironment formation, proliferation, metastasis, and recurrence of CRC and other tumor cells. It has been confirmed that intervening in the AEG pathway can effectively curb CRC. The active ingredients and compound prescriptions of traditional Chinese medicine(TCM) can effectively inhibit the proliferation, metastasis, and drug resistance and regulate the apoptosis of tumor cells by modulating AEG-associated transport proteins [eg, glucose transporters(GLUT)], key enzymes [hexokinase(HK) and phosphofructokinase(PFK)], key genes [hypoxia-inducible factor 1(HIF-1) and oncogene(c-Myc)], and signaling pathways(MET/PI3K/Akt/mTOR). Accordingly, they can treat CRC, reduce the recurrence, and improve the prognosis of CRC. Although AEG plays a key role in the development and progression of CRC, the specific mechanisms are not yet fully understood. Therefore, this article delves into the intrinsic connection of the targets and mechanisms of the AEG pathway with CRC from the perspective of tumor cell glycolysis and explores how active ingredients(oxymatrine, kaempferol, and dioscin) and compound prescriptions(Quxie Capsules, Jiedu Sangen Decoction, and Xianlian Jiedu Prescription) of TCM treat CRC by intervening in the AEG pathway. Additionally, this article explores the shortcomings in the current research, aiming to provide reliable targets and a theoretical basis for treating CRC with TCM.
Humans ; Colorectal Neoplasms/genetics* ; Drugs, Chinese Herbal/therapeutic use* ; Glycolysis/drug effects* ; Animals ; Medicine, Chinese Traditional ; Signal Transduction/drug effects*

Prostate cancer(PCa) is a common malignant tumor among elderly men, with high incidence and mortality rates worldwide, posing a serious threat to human health. Traditional treatments face limitations, highlighting the urgent need for novel therapeutic strategies. Recent studies on the regulatory mechanisms of micro ribonucleic acid(microRNA, miRNA) in tumor development has identified miRNA as new targets for PCa diagnosis and treatment. Traditional Chinese medicine(TCM), with its multi-mechanism, multi-target, and multi-pathway regulatory properties, shows promising potential in miRNA-based PCa therapy. This review summarized recent findings on miRNA' roles in PCa and research progress of TCM intervention and found that a variety of miRNA played important regulatory roles in cell differentiation, proliferation, apoptosis, invasion, metastasis, immune microenvironment, and drug resistance, and their potential as biomarkers for PCa diagnosis, prognosis, and therapy, indicating the potential to be a biomarker for the diagnosis, prognosis evaluation, and treatment of PCa. The review concluded that the active components of TCM(terpenoids, flavonoids, alkaloids, and others) and compounds(Yishen Tonglong Decoction, Shenhu Decoction, Zhoushi Qiling Decoction, Fuzheng Yiliu Decoction, and Qilan Formula) could regulate the expression of their downstream target genes by acting on specific miRNA and affect the above biological behaviors of PCa cells, thus playing a role in the treatment of PCa. This review aims to provide a theoretical basis for miRNA as potential biomarkers and therapeutic targets for PCa and suggest new avenues for further development of targeted therapy strategies against miRNA.
Humans ; MicroRNAs/metabolism* ; Prostatic Neoplasms/metabolism* ; Male ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Animals ; Gene Expression Regulation, Neoplastic/drug effects*

Objective:To investigate the impact of flow diverter (FD) malapposition at the aneurysm neck on clinical outcomes and complications of intracranial aneurysms, and identify the influencing factors for intraoperative FD malapposition.Methods:A retrospective study was performed; 153 patients with unruptured saccular aneurysms at the C4-C7 segments of the internal carotid artery accepted single FD implantation at Department of Interventional Radiology, First Affiliated Hospital of Zhengzhou University from June 2022 to March 2024 were chosen. Intraoperative high-resolution C-arm CT was utilized to assess FD apposition at the aneurysm neck. (1) Based on FD apposition at the aneurysm neck as shown, these 153 patients were divided into a malapposition group ( n=23, including 16 patients with malapposition being identified as residual malapposition after intraoperative corrective measures such as microwire massage and 7 patients with malapposition being newly detected in this study) and a complete apposition group ( n=130). Perioperative and follow-up complications were recorded. Clinical outcomes were assessed using modified Rankin Scale (mRS) at the final follow-up (mRS score of 0-2 as favorable outcome), and angiographic outcomes were evaluated by DSA at the final follow-up. Differences in clinical and angiographic outcomes and complication rate were compared between the malapposition group and complete apposition group. (2) Based on FD apposition at the aneurysm neck as shown, these 153 patients were divided into an intraoperative malapposition group ( n=74, including 67 patients with malapposition being detected during surgery and 7 patients with malapposition being newly detected in this study) and an intraoperative complete apposition group ( n=79). Univariate analysis was performed to compare the clinical variables between the intraoperative malapposition group and intraoperative complete apposition group; multivariate Logistic regression was further employed to identify the independent influencing factors for FD malapposition at the aneurysm neck. Results:(1) Four patients (all from the malapposition group) developed perioperative acute in-stent thrombosis. Nine patients experienced ischemic or hemorrhagic stroke during the follow-up, including 6 from the malapposition group and 3 from the complete apposition group; the complication rate in the malapposition group (6/23, 26.1%) was significantly higher than that in the complete apposition group (3/130, 2.3%) during the follow-up ( P<0.05). At the final follow-up, 2 patients (both from the malapposition group) had poor clinical outcome, while the remaining 151 patients had favorable outcome. Proportion of patients with favorable outcome between the two groups was statistically different (91.3%[21/23] vs. 100.0%[130/130], P<0.05). Delayed occlusion was detected in 46 patients (12 from the malapposition group and 34 from the complete apposition group) at the final angiographic follow-up. FD restenosis/re-occlusion was noted in 10 patients, including 6 from the malapposition group and 4 from the complete apposition group. Significant difference in delayed occlusion rate (52.2%[12/23] vs. 26.2%[34/130]) and long-term in-stent stenosis/occlusion rate (26.1%[6/23] vs. 3.1%[4/130]) was observed between the two groups ( P<0.05). (2) Significant difference in aneurysm neck diameter, FD angulation, parent artery stenosis, parent artery diameter ratio>1.2, and presence of branching vessels at the FD implantation site was noted between the intraoperative complete apposition group and intraoperative malapposition group ( P<0.05). Multivariate Logistic regression indicated that aneurysm neck diameter ( OR=1.431, 95% CI: 1.096-1.868, P=0.008), parent artery diameter ratio>1.2 ( OR=2.199, 95% CI: 1.083-4.463, P=0.029), and FD angulation ( OR=1.019, 95% CI: 1.002-1.036, P=0.027) were independent influencing factors for FD malapposition at the aneurysm neck. Conclusion:In FD implantation for intracranial aneurysms, FD malapposition at the aneurysm neck adversely affects delayed occlusion rate and complication rate; aneurysms with wider aneurysm neck diameter, parent artery diameter ratio>1.2, and greater FD angulation are trend to have FD malapposition at the aneurysm neck.

Objective To evaluate the safety and efficacy of valve-in-valve transcatheter mitral valve replacement(ViV-TMVR)in patients with bioprosthetic valve degeneration who are at high surgical risk.Methods This study is a multi-center,retrospective cohort analysis of 20 consecutive patients who underwent transseptal ViV-TMVR using the Edwards SAPIEN 3 transcatheter heart valve(THV).The primary endpoints include technical success and procedural success,both defined according to the Mitral Valve Academic Research Consortium(MVARC)criteria,as well as mortality and functional change assessed based on New York Heart Association(NYHA)classification at 30-days and six months post-procedure.Clinical follow-up assessments are conducted at 30-days and six months.Results From February 2021 to October 2022,a total of 20 patients with symptoms of bioprosthetic valve degeneration were enrolled across nine sites in China.The patients had a mean age of(73.5±5.5)years,with 85.0％being females and 70.0％classified as NYHA class Ⅲ/Ⅳ.The study achieved a 100.0％technical success rate and a 90.0％procedural success rate finally.All patients remained alive during the 30-day follow-up period.However,six months post-intervention,two patients(10.0％)were re-hospitalized due to heart failure,and sadly,one of them(5.0％)died.None of the patients reported any adverse events related to ViV-TMVR during the follow-up period.Notably,there was a significant improvement in NYHA class compared to baseline(P=0.0004)at six-month follow-ups.Conclusions The transseptal ViV-TMVR technique proved to be highly successful and was associated with significant improvement in NYHA class function.These findings strongly suggest that it serves as a safe and efficient treatment alternative for high-risk patients suffering from bioprosthetic valve degeneration.

Objective To evaluate the safety and efficacy of valve-in-valve transcatheter mitral valve replacement(ViV-TMVR)in patients with bioprosthetic valve degeneration who are at high surgical risk.Methods This study is a multi-center,retrospective cohort analysis of 20 consecutive patients who underwent transseptal ViV-TMVR using the Edwards SAPIEN 3 transcatheter heart valve(THV).The primary endpoints include technical success and procedural success,both defined according to the Mitral Valve Academic Research Consortium(MVARC)criteria,as well as mortality and functional change assessed based on New York Heart Association(NYHA)classification at 30-days and six months post-procedure.Clinical follow-up assessments are conducted at 30-days and six months.Results From February 2021 to October 2022,a total of 20 patients with symptoms of bioprosthetic valve degeneration were enrolled across nine sites in China.The patients had a mean age of(73.5±5.5)years,with 85.0％being females and 70.0％classified as NYHA class Ⅲ/Ⅳ.The study achieved a 100.0％technical success rate and a 90.0％procedural success rate finally.All patients remained alive during the 30-day follow-up period.However,six months post-intervention,two patients(10.0％)were re-hospitalized due to heart failure,and sadly,one of them(5.0％)died.None of the patients reported any adverse events related to ViV-TMVR during the follow-up period.Notably,there was a significant improvement in NYHA class compared to baseline(P=0.0004)at six-month follow-ups.Conclusions The transseptal ViV-TMVR technique proved to be highly successful and was associated with significant improvement in NYHA class function.These findings strongly suggest that it serves as a safe and efficient treatment alternative for high-risk patients suffering from bioprosthetic valve degeneration.

Objective:To investigate the impact of flow diverter (FD) malapposition at the aneurysm neck on clinical outcomes and complications of intracranial aneurysms, and identify the influencing factors for intraoperative FD malapposition.Methods:A retrospective study was performed; 153 patients with unruptured saccular aneurysms at the C4-C7 segments of the internal carotid artery accepted single FD implantation at Department of Interventional Radiology, First Affiliated Hospital of Zhengzhou University from June 2022 to March 2024 were chosen. Intraoperative high-resolution C-arm CT was utilized to assess FD apposition at the aneurysm neck. (1) Based on FD apposition at the aneurysm neck as shown, these 153 patients were divided into a malapposition group ( n=23, including 16 patients with malapposition being identified as residual malapposition after intraoperative corrective measures such as microwire massage and 7 patients with malapposition being newly detected in this study) and a complete apposition group ( n=130). Perioperative and follow-up complications were recorded. Clinical outcomes were assessed using modified Rankin Scale (mRS) at the final follow-up (mRS score of 0-2 as favorable outcome), and angiographic outcomes were evaluated by DSA at the final follow-up. Differences in clinical and angiographic outcomes and complication rate were compared between the malapposition group and complete apposition group. (2) Based on FD apposition at the aneurysm neck as shown, these 153 patients were divided into an intraoperative malapposition group ( n=74, including 67 patients with malapposition being detected during surgery and 7 patients with malapposition being newly detected in this study) and an intraoperative complete apposition group ( n=79). Univariate analysis was performed to compare the clinical variables between the intraoperative malapposition group and intraoperative complete apposition group; multivariate Logistic regression was further employed to identify the independent influencing factors for FD malapposition at the aneurysm neck. Results:(1) Four patients (all from the malapposition group) developed perioperative acute in-stent thrombosis. Nine patients experienced ischemic or hemorrhagic stroke during the follow-up, including 6 from the malapposition group and 3 from the complete apposition group; the complication rate in the malapposition group (6/23, 26.1%) was significantly higher than that in the complete apposition group (3/130, 2.3%) during the follow-up ( P<0.05). At the final follow-up, 2 patients (both from the malapposition group) had poor clinical outcome, while the remaining 151 patients had favorable outcome. Proportion of patients with favorable outcome between the two groups was statistically different (91.3%[21/23] vs. 100.0%[130/130], P<0.05). Delayed occlusion was detected in 46 patients (12 from the malapposition group and 34 from the complete apposition group) at the final angiographic follow-up. FD restenosis/re-occlusion was noted in 10 patients, including 6 from the malapposition group and 4 from the complete apposition group. Significant difference in delayed occlusion rate (52.2%[12/23] vs. 26.2%[34/130]) and long-term in-stent stenosis/occlusion rate (26.1%[6/23] vs. 3.1%[4/130]) was observed between the two groups ( P<0.05). (2) Significant difference in aneurysm neck diameter, FD angulation, parent artery stenosis, parent artery diameter ratio>1.2, and presence of branching vessels at the FD implantation site was noted between the intraoperative complete apposition group and intraoperative malapposition group ( P<0.05). Multivariate Logistic regression indicated that aneurysm neck diameter ( OR=1.431, 95% CI: 1.096-1.868, P=0.008), parent artery diameter ratio>1.2 ( OR=2.199, 95% CI: 1.083-4.463, P=0.029), and FD angulation ( OR=1.019, 95% CI: 1.002-1.036, P=0.027) were independent influencing factors for FD malapposition at the aneurysm neck. Conclusion:In FD implantation for intracranial aneurysms, FD malapposition at the aneurysm neck adversely affects delayed occlusion rate and complication rate; aneurysms with wider aneurysm neck diameter, parent artery diameter ratio>1.2, and greater FD angulation are trend to have FD malapposition at the aneurysm neck.

Benign prostatic hyperplasia(BPH) is a common disease in middle-aged and elderly men, with lower urinary tract symptoms as the main manifestation, severely affecting the quality of life of patients. The pathogenesis of BPH is not yet fully understood, and there are still some challenges and limitations in western medicine treatment for BPH. Therefore, finding new and more effective treatment strategies is urgent. In recent years, many basic and clinical studies have confirmed the important role of traditional Chinese medicine in the treatment of BPH. This article reviews the progress of basic and clinical research in the treatment of BPH with traditional Chinese medicine, and believes that basic research mainly focuses on the active ingredients of Chinese medicine [regulating pathways such as NF-E2-related factor 2(Nrf2)/antioxidant response element(ARE), nuclear factor κB(NF-κB), epidermal growth factor receptor(EGFR)/signal transducer and activator of transcription 3(STAT3), phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR), p38 mitogen-activated protein kinase(p38 MAPK)/forkhead box O subtype(FOXO3a), etc.], single Chinese herbs(regulating inflammatory factors, oxidative stress-related proteins, cell cycle-related proteins, and apoptotic factors, etc.), and Chinese herbal compounds and patent medicines [regulating extracellular signal-regulated kinase(ERK1/2), transforming growth factor-β(TGF-β)/Smad, mitogen-activated protein kinase(MAPK), PI3K/Akt, Nrf2, trefoil factor 2(TFF2)/Wnt, interleukin-6(IL-6)/Janus kinase 2(JAK2)/STAT3, hypoxia-inducible factor 1α(HIF-1α)/vascular endothelial growth factor receptor(VEGFR), etc.], and then play a therapeutic role by inhibiting BPH cell proliferation, oxidative stress, inflammatory response, promoting apoptosis, and inhibiting epithelial-mesenchymal transition. Clinical studies mainly focus on internal treatment, external treatment, combined internal and external treatment, and integrated Chinese and western medicine treatment as the main methods, aiming to improve traditional Chinese medicine syndrome scores, prostate symptom scores, residual urine volume, effective bladder volume, sexual quality of life, increase average urine flow rate, maximum urine flow rate, and promote balance of sex hormone secretion. Through this research, it is hoped to provide some reference ideas for clinical research and drug development for BPH.
Prostatic Hyperplasia/metabolism* ; Male ; Humans ; Drugs, Chinese Herbal/therapeutic use* ; Animals ; Signal Transduction/drug effects* ; Medicine, Chinese Traditional ; NF-E2-Related Factor 2/genetics*

Aim To compare the pharmacokinetics of pemirolast potassium tablets in healthy subjects in Chi-na under single fasting and postprandial conditions,and to evaluate the bioequivalence of the test prepara-tion(T)and the reference preparation(R).Methods A randomized,open-ended,single-dose,two-cycle,double-cross bioequivalence trial design was adopted,and 26 and 30 subjects were enrolled in the fasting group and the postprandial group,respectively,and 10 mg of the test preparation and the reference preparation were taken in the fasting or postprandial state each cy-cle,and venous blood was collected at the designed time points before and after the administration cycle.The concentration of pemirolast potassium in plasma was determined by LC-MS/MS method,and the phar-macokinetic parameters were calculated with PhoenixTM WinNonlin ?(8.3)software,and the bioequivalence analysis of the two preparations was performed.Re-sults The t1/2 of the test preparation and the reference preparation was(4.44±0.91)h and(4.49±0.93)h,respectively;the median tmax was(1.96±1.29)h and(2.18±1.25)h,respectively;the Cmax was(867.12±205.56)μg·L-1 and(863.35±172.03)μg·L-1,respectively;the AUC0-t was(5 513.23±1463.67)h·μg·L-1 and(5 661.32±1 628.65)h·μg·L-1,respectively;AUC0_∞ was(5 699.81±1477.68)h·μg·L-1 and(5 849.44±1 644.75)h·μg·L-1,respectively.The statistical results of the 90％confidence intervals of the main pharmacokinetic parameters Cmax,AUC0-t,and AUC0-∞ was 92.49％～107.53％,94.71％～100.67％and 95.28％～100.27％,respectively,all of which were within the range of 80.00％～125.00％,and the safety of the tested preparation and the reference preparation was good when taken orally on an empty stomach.The t1/2 of single oral administration after prandial administra-tion of the tested preparation and the reference prepara-tion was(4.46±0.78)and(4.51±0.84)h,respec-tively;the median tmax was(3.08±1.36)h and(3.28±1.28)h,respectively;the Cmax was(683.83±111.87)μg·L-1 and(689.77±110.24)μg·L-1,respectively;the AUC0-t was(5 695.99±1566.05)h·μg·L-1 and(5 773.60±1 551.04)h·μg·L-1,respectively;the AUC0-∞ was(5 914.06±1 551.86)h·μg·L-1 and(5 967.30±1552.89)h·μg·L-1,respectively.The 90％confi-dence interval of Cmax,AUC0-t,and AUC0-∞ was 93.56％～104.69％,96.43％～100.83％,and 97.29％～101.14％,respectively,which was in the range of 80.00％～125.00％,and the safety of the tested preparation and the reference preparation was good after meals.Conclusion In the state of fasting and postprandial single oral administration,the two kinds of pemirolast potassium tablets have good bio-equivalence.

[Objective]To explore the regulatory mechanism of hypoxia exposure on carbon metabolism pathway in spleen of mice.[Methods]C57BL/6 mice were raised at altitudes of 400 m and 4 200 m,with 5 mice in each group.After 30 days,spleen tissues were aseptically removed for analysis of differentially expressed genes,proteins,and metabolites using transcriptome sequencing,proteomics,and non-targeted metabolomics.GO and KEGG enrichment analysis were conducted to explore key pathways.The key genes and protein in the pathway were validated by RT-qPCR and Western blot.[Results]Transcriptome sequencing revealed a significant difference in the expression of 4 213 genes in hypoxic exposure,of which 1 947 were up-regulated and 2 266 were down-regulated.The analysis of differentially expressed proteins showed that 166 proteins were up-regulated and 39 proteins were down-regulated.The results of non-targeted metabolomics showed that 133 different metabolites were screened under high altitude hypoxia condition,of which 95 were up-regulated and 38 were down-regulated.KEGG enrichment analysis showed that differentially expressed genes,differentially expressed proteins and differentially expressed metabolites were enriched into the carbon metabolic pathway.Therefore,the key genes and proteins in the carbon metabolic pathway were verified.The mRNA and protein expressions of PGAM2、ENO3、PRPS2、PGLS、RPE、IDH3A、SUCLA2 and MDH2 were significantly down-regulated in the carbon metabolism pathway.[Conclusion]Low oxygen environment at high altitude weakens glycolysis,tricarboxylic acid cycle and pentose phosphate pathway by inhibiting the carbon metabolism pathway of the body,resulting in oxidative stress and energy metabolism imbalance.

Tranexamic acid is widely used in joint orthopedic surgery.At the same time,it has high safety and few adverse drug reactions.It can effectively improve intraoperative bleeding and promote early functional recovery of patients.This article reviews the mode of administration,safe dose,administration time and adverse drug reactions of tranexamic acid in the perioperative period of joint replacement and arthroscopic surgery,in order to provide reference for the clinical application of tranexamic acid.