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.

Objective:To investigate the efficacy of the nomogram model based on multiparametric MRI combined with clinical features for differential diagnosis of benign and malignant breast imaging reporting and data system (BI-RADS) 4 lesions.Methods:This study was a cross-sectional study. Clinical and imaging data of 56 patients (66 lesions) with pathologically confirmed BI-RADS 4 breast lesions from January 2020 to June 2022 at Second Affiliated Hospital of Shantou University Medical College were retrospectively analyzed. The patients were all females aged 42 (17, 71) years old. All patients underwent the breast MRI, including T 1WI, T 2WI, diffusion-weighted imaging, diffusion kurtosis imaging (DKI), and dynamic-enhanced MRI (DCE-MRI), and the patient clinical characteristics, imaging characteristics as well as relevant MRI quantitative parameters were recorded. Comparisons of the indicators of benign and malignant BI-RADS 4 lesions were performed by sample t-test , Mann-Whitney U, or χ 2 test. The least absolute shrinkage and selection operator regression was utilized to further select indicators with statistically significant differences in univariate analyses, and finally, nomogram models were constructed and reclassified all the lesions. Results:Of the 66 lesions in 56 patients, 24 lesions were found in 24 malignant patients and 42 lesions in 32 benign patients. The differences in age, body mass index, and menopausal status between benign and malignant patients were statistically significant (all P<0.05); the differences in tumor longest diameter, type of lesion enhancement, time-single intensity curve type, mean diffusivity and mean kurtosis (MK) between benign and malignant lesions were statistically significant (all P<0.05). After feature selection, MK ( OR=27.952, 95% CI 1.301-600.348, P=0.033), age ( OR=1.140, 95%CI 1.040-1.249, P=0.005), and the type of lesion enhancement ( OR=0.045, 95%CI 0.006-0.316, P=0.005) were the independent influences in predicting BI-RADS 4 malignant lesions. Using this to construct a nomogram model, its area under the curve for predicting BI-RADS 4 malignant lesions was 0.946, and the accuracy of reclassifying 66 BI-RADS 4 lesions as benign versus malignant was 86.36% (57/66). Conclusion:The nomogram model constructed with MK from DKI parameters, the type of lesion enhancement from DCE-MRI, and age is valuable in diagnosing the benign and malignant nature of BI-RADS 4 lesions.

BACKGROUND:It is known that N6-methyladenosine(m6A)plays a role in the pathogenesis of various diseases and studies have suggested its involvement in the pathologic changes of steroid-induced femoral head necrosis(SNFH).However,research on m6A methylation modifications in steroid-induced femoral head necrosis is limited. OBJECTIVE:Using bioinformatics methods to identify the differential expression of m6A-related genes in steroid-induced femoral head necrosis and to predict miRNAs associated with these genes to further elucidate the role and mechanism of m6A methylation in steroid-induced femoral head necrosis. METHODS:Differential gene expression between steroid-induced femoral head necrosis and control groups was analyzed using GSE123568 gene expression data and identified using the"limma"package in R.Functional enrichment analysis was performed on the differentially expressed genes.Differential analysis of the related genes was carried out using the"ggstatsplot"package in R.The differential genes were cross-validated using the GSE74089 dataset.An mRNA-miRNA regulatory network was constructed,and co-expression analysis was performed on the module genes followed by enrichment analysis.Differences in immune cell infiltration between steroid-induced femoral head necrosis and control groups were quantified using the ssGSEA method. RESULTS AND CONCLUSION:Correlation analysis revealed 13 m6A-related genes,and further analysis through the protein-protein interaction network identification and receiver operating characteristic curve analysis showed that YTHDF2 was expected to be a core differential gene as a potential early biomarker.Enrichment analysis indicated that differentially expressed genes were mainly involved in inflammation and immune response and were closely related to osteoclasts.Cross-validation analysis showed that differential gene expression results between the two datasets were consistent.mRNA-miRNA regulatory network analysis revealed that YTHDF2 was negatively correlated with miRNA-27a.Immune infiltration analysis revealed an increase in immune cell infiltration in steroid-induced femoral head necrosis,and YTHDF2 was positively correlated with the infiltration of CD4+T cells.To conclude,m6A-related gene YTHDF2 can serve as a potential biomarker of steroid-induced femoral head necrosis and is valuable for the early clinical diagnosis and treatment of steroid-induced femoral head necrosis.The negative correlation between YTHDF2 and mir-27a and the positive correlation between YTHDF2 and CD4+T cell infiltration provide new insights into the early diagnosis and treatment of steroid-induced femoral head necrosis and shed light on the mechanism of m6A in steroid-induced femoral head necrosis.

Objective The aim of this study was to explore the role and mechanism of ferroptosis in SiO2-induced cardiac injury using a mouse model. Methods Male C57BL/6 mice were intratracheally instilled with SiO2 to create a silicosis model.Ferrostatin-1(Fer-1)and deferoxamine(DFO)were used to suppress ferroptosis.Serum biomarkers,oxidative stress markers,histopathology,iron content,and the expression of ferroptosis-related proteins were assessed. Results SiO2 altered serum cardiac injury biomarkers,oxidative stress,iron accumulation,and ferroptosis markers in myocardial tissue.Fer-1 and DFO reduced lipid peroxidation and iron overload,and alleviated SiO2-induced mitochondrial damage and myocardial injury.SiO2 inhibited Nuclear factor erythroid 2-related factor 2(Nrf2)and its downstream antioxidant genes,while Fer-1 more potently reactivated Nrf2 compared to DFO. Conclusion Iron overload-induced ferroptosis contributes to SiO2-induced cardiac injury.Targeting ferroptosis by reducing iron accumulation or inhibiting lipid peroxidation protects against SiO2 cardiotoxicity,potentially via modulation of the Nrf2 pathway.

Objective:To investigate the value of multi-parameter MRI habitat imaging in differentiating human epidermal growth factor receptor 2 (HER2) expression in breast cancer.Methods:This study was cross-sectional. A retrospective analysis was conducted on the clinical and imaging data of 86 cases of primary invasive breast cancer confirmed by pathology at the Second Affiliated Hospital of Shantou University from August 2018 to July 2023. All patients were female, aged 33 to 74 (51±10) years. All patients underwent breast MRI examinations, including T 1WI, T 2WI, diffusion-weighted imaging and dynamic contrast-enhanced MRI. The fuzzy C-means clustering algorithm was applied to cluster analysis of the volume ratio of the extracellular extravascular space (V e), the rate constant (K ep), the volume transfer constant (K trans), and the apparent diffusion coefficient (ADC) for all lesions. Different habitat subregions were segmented based on breast cancer. Blood perfusion of the lesion was quantified through mean values of K trans and K ep, and cell proliferation was evaluated by the mean values of ADC and V e in each subregion. Additionally, the percentage of each subregion′s volume in relation to the total lesion volume was calculated. The Mann-Whitney U test was used to compare the differences in the volume percentages of various habitat subregions between different HER2 expression status. The diagnostic performance of statistically significant parameters in determining HER2 status was evaluated using receiver operating characteristic curves and the area under the curve (AUC). Results:Among the 86 patients with invasive breast cancer, 27 were HER2 positive and 59 were HER2 negative. Among the HER2 negative patients, 37 had low and 22 had zero HER2 expression. The volume percentages of habitat subregions 1, 2, and 3 showed statistically significant differences between HER2 positive and HER2 negative patients ( Z=2.90, P=0.004; Z=-2.04, P=0.042; Z=-2.19, P=0.029), with AUC values of 0.696, 0.638, and 0.648, respectively, for predicting HER2 positive expression. The volume percentage of habitat subregion 2 showed a statistically significant difference between low and zero HER2 expression patients ( Z=2.85, P=0.004), with an AUC value of 0.724 for predicting low versus zero HER2 expression. Conclusions:The volume percentage of habitat subregion 1 effectively distinguishes HER2 status, and the volume percentage of habitat subregion 2 effectively distinguishes between low and zero HER2 expression patients. It has significant clinical implications for identifying potential candidates for HER2-targeted therapy.

In recent years, modeling and simulation technology based on pharmacometrics has received increasing attention in the development of innovation drugs. In August of 2021, FDA issued a guidance named Pharmacokinetic-Based Criteria for Supporting Alternative Dosing Regimens of Programmed Cell Death Receptor-1 (PD-1) or Programmed Cell Death-Ligand 1 (PD-L1) Blocking Antibodies for Treatment of Patients with Cancer Guidance for Industry, claiming the necessity of using population PK-based simulation method for the optimization of dosing regimens, and the corresponding implementation standards. This article first summarized the existing therapeutic regimens of PD-1/PD-L1 blocking antibodies in clinic as well as the main content of the guidance, and then cited some actual examples where population PK-based simulation method did contribute to the approval of the alternative dosing regimens. Besides, some critical considerations for the dosing regimen optimization of PD-1/PD-L1 blocking antibodies were also analyzed. In our view, this guidance would have positive impacts on the development of PD-1/PD-L1 blocking antibodies in the future. We hope that this article may provide some references for the colleagues in China.

Objective: To analyze the related factors of postoperative complications after laparoscopic assisted D2 radical resection for advanced gastric cancer. Methods: From August 2015 to July 2017, 80 patients with advanced gastric cancer admitted to the First Hospital of Jiaxing were selected.All the patients were treated with laparoscopic-assisted D2 radical resection, and the risk factors related to postoperative complications were analyzed by logistic regression analysis model. Results: There were 33 cases (41.25%) with postoperative system complications, 19 cases (23.75%) with complications of level Ⅱ and above; 15 cases (18.75%) with postoperative local complications, among them 12 cases (15.00%) appeared level Ⅱ and above local complications.The number of concomitant diseases and age were related risk factors for systemic complications in patients with advanced gastric cancer after laparoscopic D2 radical resection (OR=1.982, 95%CI: 2.183-34.405, OR=6.587, 95%CI: 1.738-23.495, all P<0.05). The preoperative neoadjuvant chemotherapy, reconstruction method and age were the risk factors for local complications in patients with advanced gastric cancer after laparoscopic D2 radical resection (OR=8.273, 95%CI: 4.982-35.394, OR=12.304, 95%CI: 2.384-88.921, OR=6.365, 95%CI: 2.183-21.384, all P<0.05). Conclusion Treatment of advanced gastric cancer patients with laparoscopic D2 radical mastectomy, attention should be paid to control the patients' age, preoperative neoadjuvant chemotherapy, reconstruction mode, associated disease and other related risk factors.In order to ensure the safety of patients and to avoid postoperative complications.

Objective: To discuss the application of three dimentional(3D)visualization technologies in treatment plan of hepatic malignant tumor. Methods: The clinical data of 300 patients with liver malignant tumor who received treatment from January 2016 to January 2017 in the Third Department of Hepatic Surgery of Eastern Hepatobiliary Surgery Hospital was retrospectively analyzed in this study, including 221 male and 79 female patients aged from 7 to 76 years with median age of 54 years. The median height was 168 cm (115-183 cm), the median weight was 65 kg (20-105 kg) and the median tumor volume was 142 ml (23-2 493 ml). Three-dimensional visualization technology was used in all patients to reconstruct liver three-dimensional graphics. Also, two and three-dimensional methods were taken respectively to evaluate patients and develop treatment strategy. The change of treatment strategy caused by 3D evaluation, actual surgical plan, operation time, time of hepatic vascular occlusion, intraoperative blood loss, volumes of blood transfusion and postoperative complications was observed. Results: After three-dimensional visualization technology was applied, 75(25%) of 300 patients′ treatment strategies had been changed. The range of hepatectomy was extended in 25 patients. And 7 of them were due to hepatic venous variation, which resulted in increasing drainage area. In other 4 patients, liver resections were extended due to lack of perfusion of the liver parenchyma after the removal of portal vein. And hepatectomy was expanded in 14 patients in order to increase the surgical margin. The range of hepatectomy was reduced in 8 patients, 4 of which were due to hepatic venous variation, such as hepatic vein of segment 4 or lower right posterior hepatic vein. The remaining 4 cases were because of insufficient residual liver volume.The surgical resection was performed in 278 cases, 257 of which received operation directly. Left hepatectomy was performed in 24 patients and right hepatectomy was performed in 33 patients. Left trisectionectomy was carried out in 12 patients and right trisectionectomy was carried out in 11 patients. Caudate lobectomy was applied in 10 patients. There were 18 cases of left lateral sectionectomy, 7 cases of right anterior sectionectomy, 25 cases of right posterior sectionectomy and 18 cases of mesohepatectomy. Single or multi segment resection was performed in 99 patients. The treatment strategy of thirty-six patients was converted to staged hepatectomy (ALPPS 11 cases and portal vein embolization 25 cases). The median operation time was 130 minutes (90-360 minutes) and the median inflow blood occlusion time was 20 minutes (0-75 minutes). Median blood loss volume was 200 ml (20-1 600 ml). Thirty-seven of 278 patients received transfusions, and the average red blood transfusion volume was (4.4±1.7)units (0-8 units). Median hepatic resection volume was 530 ml(30-2 600 ml). There were 117 cases of pleural effusion after operation, including 3 patients needing invasive therapy. Ascites occurred in 23 patients, 6 of whom needed invasive therapy. Biliary leakage was observed in 30 patients. Eight patients occurred hepatic cutting surface hemorrhage, 6 of whom received blood transfusion, and 4 of whom underwent laparotomy to stop bleeding. Three patients had pulmonary infection after surgery and 3 patients appeared biliary obstruction. Deep vein thrombosis took place in 2 patients and portal vein thrombosis was observed in 4 patients. No postoperative liver failure and death ever happened in our study group. Conclusion Three-dimensional visualization technique can optimize the treatment strategy of patients with liver malignant tumor, improve surgical safety.

OBJECTIVE: To explore the epidemiological features of prehypertension in community of Changsha and its relevant risk factors.
 METHODS: A total of 15 000 participants from 5 communities in Changsha were surveyed by randomly stratified cluster sampling. The questionnaire interviews and physical examination were conducted for these people, and their serum biochemical indexes were also collected and analyzed.
 RESULTS: The prevalence of prehypertension was 34.6%. The prevalence for males was higher than that in females (44.7% vs 21.7%, P<0.01). The prevalence for males was declined in older age, but for females was increased. Central obesity, age, overweight, male, drinking, smoking, high-level total cholesterol, high-level triglyceride, high-level density-lipoprotein cholesterol, low-level density-lipoprotein cholesterol, high-level fasting blood glucose, high-level creatinine, high-level uric acid were the risk factors for prehypertension, while high level of education was a protective factor.
 CONCLUSION The prevalence for prehypertension is 34.6% in community of Changsha, and the prevalence for males is higher than that for females. It is important to strengthen the health publicity and education in community for earlier prevention.
Alcohol Drinking ; China ; Female ; Humans ; Male ; Overweight ; Prehypertension ; Prevalence ; Risk Factors ; Smoking ; Surveys and Questionnaires