ObjectiveTo investigate the mechanisms of Tongmai Yangxin pills （TMYX） and Tongxinluo capsules （TXL） in treating no-reflow （NR） after myocardial ischemia and reperfusion following the concept of treating the same disease with different methods， based on integrative pharmacology and experimental validation. MethodsEighty 8-week-old SPF-grade SD rats were randomly assigned into four groups （n=20）： sham operation， NR， TMYX （4 g·kg^-1）， and TXL （2 mg·kg^-1）. A rat model of myocardial ischemia-reperfusion no-reflow was established by in-situ ligation of the left anterior descending coronary artery. Gastric gavage was first performed 4 h after the operation， and samples were collected on day 7. Thioflavin S staining was used to observe the NR area in rat myocardium. Echocardiography was performed to examine the cardiac function. Hematoxylin-eosin （HE） staining was conducted to observe the pathological changes of the myocardial tissue. An automatic biochemical analyzer was adopted to measure myocardial enzyme activity. Then， integrated pharmacology was applied for Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis. Finally， Western blot was employed to quantify the protein levels of key targets in the myocardial tissue， including soluble guanylyl cyclase （sGC）， cyclic guanosine monophosphate （cGMP）/dependent protein kinase （PKG）， phosphorylated phosphatidylinositol 3-kinase （p-PI3K）， phosphorylated protein kinase B （p-Akt）， and hypoxia-inducible factor-1α （HIF-1α）. ResultsCompared with the sham operation group， the NR group showed increased NR area of myocardium， decreased left ventricular ejection fraction （EF）， left ventricular fractional shortening （FS）， left ventricular outflow tract peak velocity （LVOT Peak）， and left ventricular stroke volume （LVSV） （P<0.01）， fractured and disordered myocardial fibers as well as inflammatory cell infiltration in the myocardial tissue， enhanced activities of creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， and lactate dehydrogenase （LDH） in the myocardial tissue （P<0.01）， and downregulated protein levels of sGC， PKG， phosphorylated （p）-PI3K （Tyr458）， and p-Akt （Tyr315） in the myocardial tissue （P<0.05， P<0.01）. The expression level of HIF-1α protein showed a downward trend. Compared with the NR group， the TMYX group and TXL group exhibited a decreasing trend in myocardial NR area， EF， FS， and LVOT Peak significantly increased （P<0.05， P<0.01）， LVSV showed an upward trend， ameliorated myocardial pathological morphology and inflammatory infiltration， reductions in CK， CK-MB， and LDH activities （P<0.05， P<0.01）， and upregulated protein levels of sGC， PKG， p-PI3K （Tyr458） in myocardial tissue （P<0.05， P<0.01）， the protein expressions of p-Akt （Tyr315） and HIF-1α showed an upward trend. A comparison of the therapeutic effects between the two compound prescriptions showed that TMYX tended to exert a better effect in restoring cardiac function and protecting cardiac structure in NR rats， whereas TXL was more effective in reducing myocardial NR area and lowering myocardial enzyme activities in NR rats. Integrative pharmacology analysis combined with experimental verification demonstrated that both TMYX and TXL could alleviate NR through the following mechanisms： activating the cyclic cGMP/PKG signaling pathway to regulate vascular tone， activating the PI3K/Akt signaling pathway to dilate blood vessels， and activating the HIF-1 signaling pathway to inhibit oxidative stress. However， TMYX had an advantage in activating the cGMP/PKG pathway， while TXL was superior in activating the PI3K/Akt pathway. The two compound prescriptions exerted comparable effects on the HIF-1 signaling pathway， which might serve as their common therapeutic pathway. ConclusionBoth TMYX and TXL could alleviate NR damage. TMYX exerts its protective effect against NR mainly by activating the cGMP/PKG signaling pathway， while TXL exerts its effect mainly through the PI3K/Akt pathway. The HIF-1α signaling pathway may be a common pathway for the two compound prescriptions to exert their protective effects against NR. This study reveals the similarities and differences between TMYX and TXL in the treatment effect and mechanism for NR， providing an experimental basis and a theoretical basis for better clinical application of the two compound prescriptions.

This study aims to explore the synergistic effects of the main components in salvianolic acids for Injection(SAFI) on key pathological events in cerebral ischemia, elucidating the pharmacological characteristics of SAFI in neuroprotection. Two major pathological gene modules related to endothelial injury and neuroinflammation in cerebral ischemia were mined from single-cell data. According to the topological distance calculated in network medicine, potential synergistic component combinations of SAFI were screened out. The results showed that the combination of caffeic acid and salvianolic acid B scored the highest in addressing both endothelial injury and neuroinflammation, demonstrating potential synergistic effects. The cell experiments confirmed that the combination of these two components at a ratio of 1∶1 significantly protected brain microvascular endothelial cells(bEnd.3) from oxygen-glucose deprivation/reoxygenation(OGD/R)-induced reperfusion injury and effectively suppressed lipopolysaccharide(LPS)-induced neuroinflammatory responses in microglial cells(BV-2). This study provides a new method for uncovering synergistic effects among active components in traditional Chinese medicine(TCM) and offers novel insights into the multi-component, multi-target acting mechanisms of TCM.
Brain Ischemia/metabolism* ; Neuroprotective Agents/pharmacology* ; Animals ; Drugs, Chinese Herbal/administration & dosage* ; Benzofurans/pharmacology* ; Mice ; Drug Synergism ; Caffeic Acids/pharmacology* ; Polyphenols/pharmacology* ; Humans ; Alkenes/pharmacology* ; Endothelial Cells/drug effects* ; Depsides

Aim To explore the mechanism of the syn-ergistic effect of the ferroptosis inducer erastin com-bined with shikonin in promoting ferroptosis in human hypertrophic scar fibroblasts(HSFBs).Methods Hypertrophic scar tissues provided by the General Hos-pital of Ningxia Medical University were collected,and HSFBs were extracted.HSFBs were identified by HE staining and immunofluorescence.The inhibitory rates of Era and SHK on HSFBs at different concentrations were detected by CCK-8 assay,and the IC50 value was calculated.CompuSyn software was used to calculate the co-use index(CI).Control group,Erastin(Era)group,shikonin(SHK)group and Era+SHK group were set up,and the number and morphological chan-ges of cells were observed after 24 hours of interven-tion.The ability of cell migration and invasion was de-tected by scratch test and Transwell test.The changes of malondialdehyde(MDA),total iron ion and reactive oxygen species(ROS)were detected by corresponding biochemical kits.The expressions of collagen I,α-SMA and GOT1,SLC7A11,GPX4 and FTH1 were detected by Western blot.Results The IC50 value of Era and SHK of primary HSFBs was 2.22 μmol·L-1 and 3.94μmol·L-1 respectively,which was used as the single drug concentration for subsequent experiments.The CompuSyn software was employed to calculate the CI value when the two drugs were used in combination,and the concentrations corresponding to CI=0.39597(Era:1.2 μmol·L-1+SHK:1.5 μmol·L-1)were selected as subsequent combination concentrations(Because when CI was equal to 0.395 97,the concen-tration of each drug was lower than the concentration of single drug,and the inhibition rate of combined drug was greater than 50％).Compared with the monother-apy group,the number of HSFBs in the SHK+Era group was significantly reduced,cell membrane showed breakage and vesiculation,cell wrinkling became smal-ler,and cytoplasm was concentrated.The migration and invasion ability of HSFBs in the SHK+Era group were obviously weakened(P＜0.05),and the expres-sion of fibrosis-related proteins collagen Ⅰ and α-SMA was reduced(P＜0.05);the contents of MDA,total i-ron ions,and ROS in HSFBs of the SHK+Era group increased(P＜0.05),and the protein expression lev-els of SLC7A11,GOT1,GPX4,and FTH1 further de-creased(P＜0.05).Conclusions Erastin in combi-nation with shikonin can synergistically inhibit the pro-liferation,migration and fibrosis levels of HSFBs.The mechanism may be that erastin enhances the inhibition of shikotin on GOT1,increases the levels of cellular i-ron ions,ROS,and lipid peroxides,thereby promoting ferroptosis in HSFBs.

The transcription factor HOXB13 plays crucial roles in cancer development. HOXB13 is abnormally expressed in most cancers, which makes it a valuable therapeutic target for cancer therapy. The level of HOXB13 differs significantly between healthy and cancer tissues, which indicates that the level of HOXB13 is closely related to carcinogenesis. The regulatory network mediated by HOXB13 in cancer proliferation, metastasis, and invasion has been systematically investigated. Moreover, HOXB13 variants play distinct roles in different cancers and populations. By understanding the molecular mechanisms and mutation features of HOXB13, we provide a comprehensive overview of carcinogenesis networks dependent on HOXB13. Finally, we discuss advancements in anticancer therapy targeting HOXB13 and the roles of HOXB13 in drug resistance to molecular-targeted therapies, which serves as a foundation for developing HOXB13-targeted drugs for clinical diagnosis and cancer therapies.
Humans ; Neoplasms/metabolism* ; Homeodomain Proteins/metabolism* ; Carcinogenesis/genetics* ; Mutation ; Gene Expression Regulation, Neoplastic ; Molecular Targeted Therapy ; Drug Resistance, Neoplasm/genetics*

Objective To explore the effects of sacral neuromodulation (SNM) on urodynamic parameters during the storage phase in patients with neurogenic bladder (NB), so as to provide reference for evaluating the efficacy of SNM. Methods A total 49 NB patients undergoing SNM at our hospital during Oct.2012 and May 2025 were enrolled. Baseline data and video-urodynamic parameters were collected. Changes in maximum cystometric capacity, maximum detrusor pressure during storage phase, and bladder compliance before and after treatment were assessed. Improvements in detrusor overactivity (DO) and vesicoureteral reflux (VUR) were also analyzed. Results Among the 49 patients,27 were male and 22 were female, with a mean age of (37.41±15.15) years, a median disease duration of 5.0 (2.0,15.5) years, and a median follow-up of 11 (1,32) months. Up to 37 patients (75.5%) received permanent sacral nerve pulse generator implantation (permanent implant group), while the remaining 12 were classified as the non-permanent implant group. Before and after the test period, all patients showed a significant increase in maximum cystometric capacity [ (218.0 (93.0,358.5) mL vs.300.0 (238.5, 400.0) mL, P<0.001], a decrease in maximum detrusor pressure during the filling phase [32.0 (13.5,71.0) cmH_2 O vs. 20.0 (9.0,50.0) cmH_2 O, P<0.001], and an improvement in bladder compliance [11.8 (8.3,25.6) mL/cmH_2 O vs.26.7 (8.6,44.1) mL/cmH_2O, P<0.001]. In the permanent implant group, comparisons before and after the test period showed an increase in maximum bladder capacity [ (239.16±147.23) mL vs. (312.24±121.83) mL, P<0.001], a decrease in maximum detrusor pressure during filling[32.0 (15.0,58.0) cmH_2 O vs.15.0 (9.0,41.0) cmH_2 O, P<0.05], and improved bladder compliance [10.8 (8.3,23.6) mL/cmH_2 O vs.28.6 (8.6,41.4) mL/cmH_2 O, P<0.001]. No statistically significant differences in these parameters before and after the test period were observed in the non-permanent implant group (P>0.05). A total of 17 patients in the permanent implant group underwent follow-up video urodynamics. Compared to pre-test values, significant improvements were observed in maximum detrusor pressure during filling, and bladder compliance both at the end of the test period and at the last follow-up (P<0.05). However, no statistically significant differences were found in maximum cystometric capacity, maximum detrusor pressure during filling, and bladder compliance between the end of the test period and the last follow-up (P>0.05). Among the 49 patients,21 had DO and 20 had VUR. Both DO and VUR showed improvement after the test period and at the last follow-up. Conclusion SNM can effectively improve storage function in NB patients, ameliorate detrusor overactivity and bladder compliance, and relieve or eliminate VUR in some patients. Long-term follow-up confirms that SNM provides stable therapeutic effects, demonstrating significant clinical value.

Objective To evaluate the clinical outcome of neurosurgical robot-assisted stereotactic puncture and drainage for brain abscess.Methods A retrospective analysis was conducted on the clinical data of 53 patients with brain abscess admitted to our hospital from January 2018 to December 2024.Among them,29 cases underwent craniotomy for abscess resection(craniotomy group),while 24 cases received neurosurgical robot-assisted stereotactic puncture and drainage(robot-assisted group).The operation time,intraoperative blood loss,decompressive craniectomy rate,proportion of postoperative antibiotic regimen adjustment,postoperative hospital stay,incidence of postoperative complications,mortality rate and Glasgow outcome scale(GOS)scores 6 months after surgery of patients were compared between the two groups.Results Compared with the craniotomy group,the robot-assisted group demonstrated significantly shorter operation time,less intraoperative blood loss,and lower incidence of postoperative complication,the differences were all statistically significant(P<0.05).However,there were no statistically significant differences in terms of decompressive craniectomy rate,postoperative hospital stay,mortality rate,GOS score,or proportion of the postoperative antibiotic regimen adjustment between the two groups(P>0.05).Conclusion As a precise and minimally invasive surgical method,neurosurgical robot-assisted stereotactic puncture and drainage for patients with brain abscess can effectively improve the operational efficiency,shorten the operation time,reduce intraoperative injury,and lower the risk of postoperative complications.It has high clinical application value and potential for widespread adoption.

Objective To evaluate the clinical outcome of neurosurgical robot-assisted stereotactic puncture and drainage for brain abscess.Methods A retrospective analysis was conducted on the clinical data of 53 patients with brain abscess admitted to our hospital from January 2018 to December 2024.Among them,29 cases underwent craniotomy for abscess resection(craniotomy group),while 24 cases received neurosurgical robot-assisted stereotactic puncture and drainage(robot-assisted group).The operation time,intraoperative blood loss,decompressive craniectomy rate,proportion of postoperative antibiotic regimen adjustment,postoperative hospital stay,incidence of postoperative complications,mortality rate and Glasgow outcome scale(GOS)scores 6 months after surgery of patients were compared between the two groups.Results Compared with the craniotomy group,the robot-assisted group demonstrated significantly shorter operation time,less intraoperative blood loss,and lower incidence of postoperative complication,the differences were all statistically significant(P<0.05).However,there were no statistically significant differences in terms of decompressive craniectomy rate,postoperative hospital stay,mortality rate,GOS score,or proportion of the postoperative antibiotic regimen adjustment between the two groups(P>0.05).Conclusion As a precise and minimally invasive surgical method,neurosurgical robot-assisted stereotactic puncture and drainage for patients with brain abscess can effectively improve the operational efficiency,shorten the operation time,reduce intraoperative injury,and lower the risk of postoperative complications.It has high clinical application value and potential for widespread adoption.

Aim To explore the mechanism of the syn-ergistic effect of the ferroptosis inducer erastin com-bined with shikonin in promoting ferroptosis in human hypertrophic scar fibroblasts(HSFBs).Methods Hypertrophic scar tissues provided by the General Hos-pital of Ningxia Medical University were collected,and HSFBs were extracted.HSFBs were identified by HE staining and immunofluorescence.The inhibitory rates of Era and SHK on HSFBs at different concentrations were detected by CCK-8 assay,and the IC50 value was calculated.CompuSyn software was used to calculate the co-use index(CI).Control group,Erastin(Era)group,shikonin(SHK)group and Era+SHK group were set up,and the number and morphological chan-ges of cells were observed after 24 hours of interven-tion.The ability of cell migration and invasion was de-tected by scratch test and Transwell test.The changes of malondialdehyde(MDA),total iron ion and reactive oxygen species(ROS)were detected by corresponding biochemical kits.The expressions of collagen I,α-SMA and GOT1,SLC7A11,GPX4 and FTH1 were detected by Western blot.Results The IC50 value of Era and SHK of primary HSFBs was 2.22 μmol·L-1 and 3.94μmol·L-1 respectively,which was used as the single drug concentration for subsequent experiments.The CompuSyn software was employed to calculate the CI value when the two drugs were used in combination,and the concentrations corresponding to CI=0.39597(Era:1.2 μmol·L-1+SHK:1.5 μmol·L-1)were selected as subsequent combination concentrations(Because when CI was equal to 0.395 97,the concen-tration of each drug was lower than the concentration of single drug,and the inhibition rate of combined drug was greater than 50％).Compared with the monother-apy group,the number of HSFBs in the SHK+Era group was significantly reduced,cell membrane showed breakage and vesiculation,cell wrinkling became smal-ler,and cytoplasm was concentrated.The migration and invasion ability of HSFBs in the SHK+Era group were obviously weakened(P＜0.05),and the expres-sion of fibrosis-related proteins collagen Ⅰ and α-SMA was reduced(P＜0.05);the contents of MDA,total i-ron ions,and ROS in HSFBs of the SHK+Era group increased(P＜0.05),and the protein expression lev-els of SLC7A11,GOT1,GPX4,and FTH1 further de-creased(P＜0.05).Conclusions Erastin in combi-nation with shikonin can synergistically inhibit the pro-liferation,migration and fibrosis levels of HSFBs.The mechanism may be that erastin enhances the inhibition of shikotin on GOT1,increases the levels of cellular i-ron ions,ROS,and lipid peroxides,thereby promoting ferroptosis in HSFBs.

The prevalence rate of nonalcoholic fatty liver disease(NAFLD)in postmenopausal women is significantly higher than that in premenopausal women and even exceeds that in men of the same age group,and exercise intervention remains an effective method for the prevention and treatment of NAFLD in postmenopausal women.In addition,postmenopausal women with NAFLD often have comorbidities such as sarcopenia,osteoporosis,cardiovascular diseases,and diabetes,which requires targeted exercise prescriptions and proactive intervention for potential comorbidities.Through a literature review,this article provides targeted recommendations for exercise intervention prescriptions in postmenopausal women with NAFLD and related comorbidities.

AIM:To investigate the relationship among lens parameters and their correlation with ocular anatomic characteristics in myopia patients implanted with posterior-chamber phakic implantable collamer lens(Phakic-ICL).METHODS:Retrospective study. A total of 46 myopia patients(46 eyes)who underwent Phakic-ICL implantation were collected in the Wuxi Huaxia Eye Hospital from June 2022 to June 2023. Preoperative evaluation of ocular anatomical characteristics included corneal central thickness(CCT), anterior chamber depth(ACD), axial length(AL), white-to-white(WTW), horizontal sulcus to sulcus(STSH), horizontal angle to angle(ATAH), and vertical sulcus to sulcus(STSV), vertical angle to angle(ATAV). Furthermore, lens parameters included horizontal crystalline lens rise(CLRH), vertical CLR(CLRV)and vertical lens thickness(LTV). The difference, consistency and correlation of the above parameters were analyzed.RESULTS:Except for differences between WTW and STSV, STSH and ATAV, which were not statistically significant(all P>0.05), the other horizontal and vertical ocular anatomical characteristics were statistically significant(P<0.05). CLRH and CLRV had statistically significant difference(P<0.01), while LTH and LTV were not statistically significant difference(P>0.05). Bland-Altman results revealed that the anatomical characteristics in the horizontal or vertical diameters showed poor consistency. The consistency between CLRH and CLRV was poor. There was consistency between LTH and LTV, with the 95% limits of agreement(LoA)between the differences ranging from -0.21 to 0.28 mm, and the proportion of out-of-line points off the 95% LoA was 4.35%. Pearson correlation analysis revealed that there were correlations between the anatomical characteristics of the horizontal and vertical diameters(P<0.01). Meanwhile, there was no correlation between the anteroposterior diameters(P>0.05). There were correlations between the lens parameters(P<0.05), excepted for the CLRH, LTH and LTV, which had no correlation. AL correlated with the anatomical characteristics of the horizontal and vertical diameters(P<0.05), but it had no correlation with lens parameters(P>0.05). Multiple linear regression analysis revealed that LT=0.419+0.017×age-0.548×ACD+0.371×ATAH+0.884×CLRV, CLRH=-0.443+0.809×CLRV, CLRV=-0.092-0.200×ATAH+0.560×CLRH(corrected R2=0.458, 0.482, 0.589, respectively).CONCLUSION:Horizontal and vertical diameters were not interchangeable. CLRH and CLRV were not interchangeable, while LTH and LTV were interchangeable. Partial lens parameters, WTW, STS, and ATA were correlated with ACD. Finally, age, ACD, ATAH, and CLRV influenced LT.