Objective To explore the molecular mechanism of Jianfu mixture in the treatment of erectile dysfunction （ED） by network pharmacology and molecular docking techniques, and validate its core targets and mechanisms through in vitro experiments. Methods The active components and corresponding molecular targets of Jianfu mixture were searched by searching TCMSP and Batman-TCM databases, and the disease targets of ED were searched by using GeneCards database. Find the intersection of drug ingredient target and disease target. The interaction between intersected targets was described and analyzed by String database, and the analysis results were visualized by Cytoscape software to determine the core target and the corresponding active components. GO functional enrichment analysis and KEGG pathway enrichment analysis were performed for intersection targets; the core target within the intersection were found through MCODE plug-in on Cytoscape software and molecular docking was performed with the corresponding active ingredients. An endothelial dysfunction model was established by transfecting HUVECs with si-eNOS. Intervene with different concentrations of the Jianfu mixture for the model cells for 24 h. QPCR was used to detect mRNA expression of core targets （MAPK1, MAPK3, JUN, ESR1, MAPK8）; Western blot was used to analyze protein expression （eNOS, JUN, p-JUN, MAPK, p-MAPK） and phosphorylation levels. Results 144 effective active components and 168 active components target-disease targe intersection of Jianfu mixture were obtained. GO analysis revealed 200 5 biological processes, 151 molecular functions, and 63 cellular components. KEGG analysis yielded 181 pathways. 5 core targets including MAPK1, MAPK3, JUN, ESR1 and MAPK8 were screened out. The active components such as β-sitosterol, kaempferol, astapterocarpan had good binding affinity with the core target. In vitro experiments confirmed successful construction of the endothelial dysfunction model （eNOS expression significantly decreased after si-eNOS transfection）. Jianfu mixture dose-dependently inhibited mRNA expression of MAPK1, MAPK3, JUN, ESR1, and MAPK8. Additionally, it reduced phosphorylation levels of JUN and MAPK, indicating inhibition of the JNK/c-Jun and ERK/MAPK signaling pathways to improve endothelial function. Conclusion Jianfu mixture treats ED by suppressing abnormal activation of multi-target signaling pathways （MAPK/JUN/ESR1）, reducing endothelial apoptosis, and promoting NO synthesis. This mechanism aligns with the traditional Chinese medicine principle of “activating blood circulation, resolving stasis, tonifying Qi, and strengthening cardiovascular function.” The study provided molecular-level evidence for the therapeutic efficacy of Jianfu mixture in ED management.

Objective To explore the molecular mechanism of Jianfu mixture in the treatment of erectile dysfunction （ED） by network pharmacology and molecular docking techniques, and validate its core targets and mechanisms through in vitro experiments. Methods The active components and corresponding molecular targets of Jianfu mixture were searched by searching TCMSP and Batman-TCM databases, and the disease targets of ED were searched by using GeneCards database. Find the intersection of drug ingredient target and disease target. The interaction between intersected targets was described and analyzed by String database, and the analysis results were visualized by Cytoscape software to determine the core target and the corresponding active components. GO functional enrichment analysis and KEGG pathway enrichment analysis were performed for intersection targets; the core target within the intersection were found through MCODE plug-in on Cytoscape software and molecular docking was performed with the corresponding active ingredients. An endothelial dysfunction model was established by transfecting HUVECs with si-eNOS. Intervene with different concentrations of the Jianfu mixture for the model cells for 24 h. QPCR was used to detect mRNA expression of core targets （MAPK1, MAPK3, JUN, ESR1, MAPK8）; Western blot was used to analyze protein expression （eNOS, JUN, p-JUN, MAPK, p-MAPK） and phosphorylation levels. Results 144 effective active components and 168 active components target-disease targe intersection of Jianfu mixture were obtained. GO analysis revealed 200 5 biological processes, 151 molecular functions, and 63 cellular components. KEGG analysis yielded 181 pathways. 5 core targets including MAPK1, MAPK3, JUN, ESR1 and MAPK8 were screened out. The active components such as β-sitosterol, kaempferol, astapterocarpan had good binding affinity with the core target. In vitro experiments confirmed successful construction of the endothelial dysfunction model （eNOS expression significantly decreased after si-eNOS transfection）. Jianfu mixture dose-dependently inhibited mRNA expression of MAPK1, MAPK3, JUN, ESR1, and MAPK8. Additionally, it reduced phosphorylation levels of JUN and MAPK, indicating inhibition of the JNK/c-Jun and ERK/MAPK signaling pathways to improve endothelial function. Conclusion Jianfu mixture treats ED by suppressing abnormal activation of multi-target signaling pathways （MAPK/JUN/ESR1）, reducing endothelial apoptosis, and promoting NO synthesis. This mechanism aligns with the traditional Chinese medicine principle of “activating blood circulation, resolving stasis, tonifying Qi, and strengthening cardiovascular function.” The study provided molecular-level evidence for the therapeutic efficacy of Jianfu mixture in ED management.

ObjectiveTo investigate the value of liver stiffness measurement （LSM） and spleen stiffness measurement （SSM） measured by two-dimensional shear wave elastography （2D-SWE） in the diagnosis of severe portal hypertension （SPH） and high-risk varices （HRV）， and to provide a basis for noninvasive assessment of portal hypertension. MethodsA prospective study was conducted among 78 patients with cirrhotic portal hypertension who were treated in Liver Research Center of Beijing Friendship Hospital， Capital Medical University， from December 2019 to April 2023. According to hepatic venous pressure gradient （HVPG）， the patients were divided into 6 mmHg≤HVPG<12 mmHg group， 12 mmHg≤HVPG<20 mmHg group， and HVPG ≥20 mmHg group. All patients underwent gastroscopy and 2D-SWE within 1 week after HVPG measurement， and SWE-LSM and SWE-SSM measured by 2D-SWE were recorded. A one-way analysis of variance or the Kruskal-Wallis H test was used for comparison of continuous data between multiple groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. With HVPG and gastroscopy findings as the gold standard， the receiver operating characteristic （ROC） curve was plotted and the area under the ROC curve （AUC） was calculated to evaluate diagnostic performance， while the DeLong test was used for comparison of AUC. The Pearson or Spearman correlation analysis was used to investigate the correlation between variables， and the linear regression analysis and the Logistic regression analysis were used to investigate the influencing factors for HVPG and HRV. ResultsThe mean HVPG was 18.1±6.4 mmHg for the patients enrolled in this study， and HRV was observed in 62 patients （79.5%）. Both SWE-LSM and SWE-SSM were significantly positively correlated with HVPG （r=0.413 and 0.633， both P<0.001）， with an AUC of 0.812 and 0.902， respectively， in the diagnosis of HVPG≥12 mmHg and an AUC of 0.804 and 0.789， respectively， in the diagnosis of HVPG≥20 mmHg （all P>0.05）. The multivariate linear regression analysis showed that SWE-SSM was an independent influencing factor for HVPG （β=0.17， P<0.001）. In the diagnosis of HRV， only SWE-SSM showed a significant positive correlation with HRV （r=0.432， P<0.001）， with a better diagnostic performance than SWE-LSM in terms of AUC （0.808 vs 0.642， Z=2.775， P=0.006）. The multivariate Logistic regression analysis showed that platelet count was an independent influencing factor for HRV （odds ratio=0.97， P=0.014）. ConclusionSWE-SSM is closely correlated with both HVPG and HRV， showing a good performance in the diagnosis of SPH and HRV， and therefore， it is expected to become an effective noninvasive tool for assessing portal hypertension.

AIM: To compare the efficacy of small-incision lenticule extraction(SMILE)and femtosecond assisted laser in situ keratomileusis(FS-LASIK)in the treatment of patients with myopia and astigmatism.METHODS: Retrospective analysis. A total of 100 cases(200 eyes)of patients with myopia and astigmatism treated in our hospital from December 2021 to December 2022 were collected. Among them, 50 cases(100 eyes)were divided into SMILE group and 50 cases(100 eyes)were divided into FS-LASIK group according to the treatment plans. The visual acuity and astigmatism, corneal morphology parameters, subjective visual quality scores, ocular surface indicators, postoperative complications, and quality of life were compared between the two groups before and after surgery.RESULTS: There was no significant difference in uncorrected visual acuity(UCVA), best corrected visual acuity(BCVA), astigmatism, corneal asphericity Q value, corneal surface regularity index(SRI), corneal thickness, and corneal curvature between the two groups before surgery and at 1 d, 1, and 6 mo after surgery(all P>0.05). At 1 and 6 mo after surgery, the subjective visual quality score, the quality of life score, Schirmer I test(SⅠt)and tear film break-up time(BUT)in the SMILE group were better than that in the FS-LASIK group(all P<0.05). The incidence of complications in the SMILE group was lower than that in the FS-LASIK group at 6 mo after surgery(P=0.005).CONCLUSION: Both SMILE and FS-LASIK have good clinical effects in the treatment of myopia with astigmatism, but the SMILE could alleviate ocular surface injury, reduce the risk of complications and improve the quality of lifes for patients.

Diabetic nephropathy (DN) remains a leading cause of end-stage renal disease (ESRD), driven by chronic inflammation, oxidative stress, and apoptosis. Current therapies targeting glycemic and blood pressure control fail to address the underlying molecular mechanisms of DN. This study investigates the therapeutic potential of andrographolide (AD), a diterpenoid lactone from Andrographis paniculata, in mitigating DN by modulating key molecular pathways. Through integrative network pharmacology, molecular docking, and in vivo/in vitro experiments, 107 overlapping DN-related targets were identified, with STAT3, PI3K, and AKT1 emerging as core nodes. Molecular docking revealed high binding affinities between AD and these targets, supporting its modulatory potential. In vivo, AD significantly improved renal function in streptozotocin-induced DN rats, reducing proteinuria, glomerular hypertrophy, and renal fibrosis. AD also attenuated oxidative stress, decreased pro-inflammatory cytokine levels, and enhanced antioxidant enzyme activities, demonstrating systemic anti-inflammatory and antioxidative effects. In vitro studies further confirmed that AD alleviates podocyte oxidative stress and apoptosis under high glucose conditions by suppressing the RAGE-NF-κB and STAT3/PI3K/Akt pathways. Histological analyses revealed substantial improvements in renal architecture, including reductions in fibrosis and mesangial expansion. These results underscore AD’s multi-target mechanism, directly addressing DN’s core pathological drivers, including inflammation, oxidative stress, and apoptosis. As a natural compound with notable safety and efficacy, AD holds promise as an adjunct or standalone therapeutic agent for DN. This study establishes a robust preclinical foundation for AD, warranting further exploration in clinical trials and its potential application in other diabetic complications.

Objective We aimed to evaluate the efficacy and safety of Shengxuebao Mixture in the treatment of cancer-related anemia(CRA)presenting with syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood.Methods A randomized,double-blind,placebo-controlled,multicenter clinical trial was conducted.Eligible patients with malignant tumors meeting the inclusion and exclusion criteria were enrolled from 26 hospitals,including Dongzhimen Hospital,Beijing University of Chinese Medicine,Xiaogan Central Hospital,and Yangzhou Hospital of Traditional Chinese Medicine,from June 1,2022,to September 30,2024.Patients were allocated 1:1 to either the experimental group receiving Shengxuebao Mixture or the control group receiving its simulator(placebo)using a block randomization method under double-blind conditions.Both groups received 15 mL orally three times daily for 28 consecutive days.The primary efficacy indicators included the hemoglobin(Hb)improvement rate(RHb)and the traditional Chinese medicine(TCM)syndrome improvement rate(RTCM)at week 4 of treatment.The secondary efficacy indicators encompassed Hb and red blood cell(RBC)count,Karnofsky Performance Status(KPS)score,TCM syndrome score,individual TCM symptom scores,and changes in each of these indicators compared to the baseline period at weeks 2,4,and 6 of treatment.Safety evaluations were conducted at week 4 of treatment.Results A total of 239 patients were enrolled,with 225 cases included in the Full Analysis Set(FAS)(109 in the experimental group vs.116 control group),163 in the Per Protocol Set(PPS)(77 vs.86),and 225 in the Safety Set(SS)(109 vs.116).Baseline characteristics between groups showed no significant differences.Significant differences were observed between the experimental and control groups in RHb at week 4(FAS:49.51%vs.35.24%,P<0.05;PPS:53.25%vs.36.05%,P<0.05)and RTCM at week 4(FAS:61.54%vs.39.62%,P<0.01;PPS:64.94%vs.40.70%,P<0.01).At weeks 2,4,and 6,the experimental group showed greater improvements in Hb and RBC counts than the control group.Additionally,the TCM syndrome scores were lower in the experimental group than in the control group at these time points.Except for week 2 in PPS,the KPS improvement was better in the experimental group than in the control group(P<0.05).The experimental group also demonstrated a greater reduction in scores for individual TCM symptoms such as spiritlessness and weakness,poor appetite and reduced food intake at weeks 4 and 6 compared to the control group(P<0.05,P<0.01).Furthermore,the reduction in vertigo score was more pronounced in the experimental group at week 6(P<0.01).For the score of pale and lusterless complexion,only in the PPS was the reduction from baseline more significant in the experimental group than in the control group at weeks 4 and 6(P<0.05).No significant differences were observed between the experimental and control groups in the incidence of all adverse events or drug-related adverse reactions.Conclusion Shengxuebao Mixture demonstrates significant efficacy in patients with CRA presenting syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood,effectively increasing Hb levels,ameliorating TCM syndromes,alleviating clinical symptoms,and enhancing functional status,with no significant difference in adverse drug reactions compared to the placebo.

Aim To investigate the effect of Zhenwu decoction on inflammation,oxidative stress and apopto-sis of human glomerular epithelial cells(HGEC)in-duced by lipopolysaccharide(LPS)based on Nrf2/HO-1 signaling pathway,and to explore the underlying mechanism.Methods HGEC were treated with LPS(1.0 mg·L-1)for 24 h to construct an oxidative damage model.On this basis,2.5％,5％and 10％Zhenwu decoction-containing serum were added to the low,medium and high dose groups of Zhenwu decoc-tion,and a normal group was set up.The changes of cell activity were assessed by MTT method and LDH method.The contents of TNF-α,IL-6,IL-10,SOD,CAT,GSH-Px,ROS and MDA in each group were de-tected by ELISA.The apoptosis of each group was de-tected by flow cytometry.The mRNA and protein ex-pressions of Bax,Bcl-2,caspase-3,caspase-9 and Nrf2/HO-1 pathway were detected by RT-qPCR and Western blot,respectively.Results Compared to the normal group,the model group of HGEC exhibited increased levels of inflammatory cytokines,enhanced oxidative stress response and aggravated apoptosis;after inter-vention with various doses of Zhenwu decoction,the in-flammatory levels in HGEC were reduced,oxidative damage and apoptosis were effectively ameliorated,and the mRNA and protein expression levels of the Nrf2/HO-1 signaling pathway were upregulated.Conclu-sions Zhenwu decoction can protect HGEC from LPS-induced inflammation and oxidative damage and im-prove apoptosis.The mechanism may be related to the activation of Nrf2/HO-1 signaling pathway.

Objective To observe the effect of Kaixin Powder on neuroinflammation in APP/PS1 mice by regulating WDFY1/TLR4/NF-κB signaling pathway;To explore its mechanism of intervening in Alzheimer disease(AD).Methods APP/PS1 transgenic mice were randomly divided into model group,donepezil hydrochloride group(0.66 mg/kg),and Kaixin Powder low-,medium-and high-dosage groups(1.625,3.25,6.5 g/kg),C57BL/6J mice were set as blank control group,with 8 mice in each group,and corresponding drug intervention was given to medicaction group for 24 weeks.Morris water maze,Y maze and novel object recognition experiments were conducted to assess the cognitive function and learning and memory abilities of mice,immunohistochemical staining was used to detect the deposition of β-amyloid protein(Aβ)in hippocampus,the morphology and Nissl bodies of hippocampal CA1 neurons were observed using HE staining and Nissl staining,ELISA was used to detect the serum contents of interleukin(IL)-6,IL-17,IL-1β and tumor necrosis factor-α(TNF-α),Western blot was used to detect the protein expression of calcium-binding adapter molecule 1(Iba1),glial fibrillary acidic protein(GFAP),WDFY1,Toll like receptor 4(TLR4),Toll like receptor associated molecule(TRAM),TIR domain adapter protein(TRIF),NF-κB p65 and p-NF-κB p65 in hippocampal tissue,RT-qPCR was used to detect the mRNA expression of WDFY1,TLR4,TRAM,TRIF and NF-κB p65 in hippocampal tissue.Results Compared with the blank control group,the model group had significantly prolonged escape latency,reduced platform crossings,decreased autonomous reaction alternation rate and relative recognition index(P<0.05,P<0.01),with increased deposition of Aβ in hippocampal tissue(P<0.01),damaged morphological structure of neurons,reduced number of neurons and Nissl bodies,the serum contents of IL-6,IL-17,IL-1β and TNF-α significantly increased,the expression of Iba1,GFAP,WDFY1,TLR4,TRAM,TRIF,p-NF-κB p65 protein and WDFY1,TLR4,TRAM,TRIF mRNA in hippocampal tissue significantly increased(P<0.01).Compared with the model group,Kaixin Powder groups and donepezil hydrochloride group had significantly shortened escape latency and increased platform crossings,autonomous reaction alternation rate and relative recognition index(P<0.05,P<0.01),hippocampal Aβ deposition reduced in Kaixin Powder medium-,high-dosage groups and donepezil hydrochloride group,the morphological structure of neurons recovered,the number of neurons and Nissl bodies increased,the serum contents of IL-6,IL-17,IL-1β and TNF-α significantly decreased(P<0.05,P<0.01),and the protein expression of Iba1,GFAP,WDFY1,TLR4,TRAM,TRIF,p-NF-κB p65 and the mRNA expressions of WDFY1,TLR4,TRAM and TRIF in hippocampal tissue significantly decreased(P<0.05,P<0.01).Conclusion Kaixin Powder can improve cognitive function and learning and memory abilities in AD model mice,alleviate hippocampal neuron damage and Aβ deposition,inhibit the activation of microglia and astrocytes,and thereby reduce serum inflammatory cytokine release.Its mechanism may be related to regulating the WDFY1/TLR4/NF-κB signaling pathway to inhibit neuroinflammation.

Objective We aimed to evaluate the efficacy and safety of Shengxuebao Mixture in the treatment of cancer-related anemia(CRA)presenting with syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood.Methods A randomized,double-blind,placebo-controlled,multicenter clinical trial was conducted.Eligible patients with malignant tumors meeting the inclusion and exclusion criteria were enrolled from 26 hospitals,including Dongzhimen Hospital,Beijing University of Chinese Medicine,Xiaogan Central Hospital,and Yangzhou Hospital of Traditional Chinese Medicine,from June 1,2022,to September 30,2024.Patients were allocated 1:1 to either the experimental group receiving Shengxuebao Mixture or the control group receiving its simulator(placebo)using a block randomization method under double-blind conditions.Both groups received 15 mL orally three times daily for 28 consecutive days.The primary efficacy indicators included the hemoglobin(Hb)improvement rate(RHb)and the traditional Chinese medicine(TCM)syndrome improvement rate(RTCM)at week 4 of treatment.The secondary efficacy indicators encompassed Hb and red blood cell(RBC)count,Karnofsky Performance Status(KPS)score,TCM syndrome score,individual TCM symptom scores,and changes in each of these indicators compared to the baseline period at weeks 2,4,and 6 of treatment.Safety evaluations were conducted at week 4 of treatment.Results A total of 239 patients were enrolled,with 225 cases included in the Full Analysis Set(FAS)(109 in the experimental group vs.116 control group),163 in the Per Protocol Set(PPS)(77 vs.86),and 225 in the Safety Set(SS)(109 vs.116).Baseline characteristics between groups showed no significant differences.Significant differences were observed between the experimental and control groups in RHb at week 4(FAS:49.51%vs.35.24%,P<0.05;PPS:53.25%vs.36.05%,P<0.05)and RTCM at week 4(FAS:61.54%vs.39.62%,P<0.01;PPS:64.94%vs.40.70%,P<0.01).At weeks 2,4,and 6,the experimental group showed greater improvements in Hb and RBC counts than the control group.Additionally,the TCM syndrome scores were lower in the experimental group than in the control group at these time points.Except for week 2 in PPS,the KPS improvement was better in the experimental group than in the control group(P<0.05).The experimental group also demonstrated a greater reduction in scores for individual TCM symptoms such as spiritlessness and weakness,poor appetite and reduced food intake at weeks 4 and 6 compared to the control group(P<0.05,P<0.01).Furthermore,the reduction in vertigo score was more pronounced in the experimental group at week 6(P<0.01).For the score of pale and lusterless complexion,only in the PPS was the reduction from baseline more significant in the experimental group than in the control group at weeks 4 and 6(P<0.05).No significant differences were observed between the experimental and control groups in the incidence of all adverse events or drug-related adverse reactions.Conclusion Shengxuebao Mixture demonstrates significant efficacy in patients with CRA presenting syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood,effectively increasing Hb levels,ameliorating TCM syndromes,alleviating clinical symptoms,and enhancing functional status,with no significant difference in adverse drug reactions compared to the placebo.

Aim To investigate the effect of Zhenwu decoction on inflammation,oxidative stress and apopto-sis of human glomerular epithelial cells(HGEC)in-duced by lipopolysaccharide(LPS)based on Nrf2/HO-1 signaling pathway,and to explore the underlying mechanism.Methods HGEC were treated with LPS(1.0 mg·L-1)for 24 h to construct an oxidative damage model.On this basis,2.5％,5％and 10％Zhenwu decoction-containing serum were added to the low,medium and high dose groups of Zhenwu decoc-tion,and a normal group was set up.The changes of cell activity were assessed by MTT method and LDH method.The contents of TNF-α,IL-6,IL-10,SOD,CAT,GSH-Px,ROS and MDA in each group were de-tected by ELISA.The apoptosis of each group was de-tected by flow cytometry.The mRNA and protein ex-pressions of Bax,Bcl-2,caspase-3,caspase-9 and Nrf2/HO-1 pathway were detected by RT-qPCR and Western blot,respectively.Results Compared to the normal group,the model group of HGEC exhibited increased levels of inflammatory cytokines,enhanced oxidative stress response and aggravated apoptosis;after inter-vention with various doses of Zhenwu decoction,the in-flammatory levels in HGEC were reduced,oxidative damage and apoptosis were effectively ameliorated,and the mRNA and protein expression levels of the Nrf2/HO-1 signaling pathway were upregulated.Conclu-sions Zhenwu decoction can protect HGEC from LPS-induced inflammation and oxidative damage and im-prove apoptosis.The mechanism may be related to the activation of Nrf2/HO-1 signaling pathway.