This study aims to explore the mechanism of Buyang Huanwu Decoction(BHD) in promoting angiogenesis after oxygen-glucose deprivation/reoxygenation(OGD/R) of mouse brain microvascular endothelial cell line(brain-derived Endothelial cells.3, bEnd.3) based on the caveolin-1(Cav1)/Yes-associated protein 1(YAP1)/hypoxia-inducible factor-1α(HIF-1α) signaling pathway. Ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was used to analyze the blood components of BHD. The cell counting kit-8(CCK-8) method was used to detect the optimal intervention concentration of drug-containing serum of BHD after OGD/R injury of bEnd.3. The lentiviral transfection method was used to construct a Cav1 silent stable strain, and Western blot and polymerase chain reaction(PCR) methods were used to verify the silencing efficiency. The control bEnd.3 cells were divided into a normal group(sh-NC control group), an OGD/R model + blank serum group(sh-NC OGD/R group), and an OGD/R model + drug-containing serum group(sh-NC BHD group). Cav1 silent cells were divided into an OGD/R model + blank serum group(sh-Cav1 OGD/R group) and an OGD/R model + drug-containing serum group(sh-Cav1 BHD group). The cell survival rate was detected by the CCK-8 method. The cell migration ability was detected by a cell migration assay. The lumen formation ability was detected by an angiogenesis assay. The apoptosis rate was detected by flow cytometry, and the expression of YAP1/HIF-1α signaling pathway-related proteins in each group was detected by Western blot. Finally, co-immunoprecipitation was used to verify the interaction between YAP1 and HIF-1α. The results showed astragaloside Ⅳ, formononetin, ferulic acid, and albiflorin in BHD can all enter the blood. The drug-containing serum of BHD at a mass fraction of 10% may be the optimal intervention concentration for OGD/R-induced injury of bEnd.3 cells. Compared with the sh-NC control group, the sh-NC OGD/R group showed significantly decreased cell survival rate, cell migration rate, mesh number, node number, and lumen length, significantly increased cell apoptotic rate, significantly lowered phosphorylation level of YAP1 at S127 site, and significantly elevated nuclear displacement level of YAP1 and protein expression of HIF-1α, vascular endothelial growth factor(VEGF), and vascular endothelial growth factor receptor 2(VEGFR2). Compared with the same type of OGD/R group, the sh-NC BHD group and sh-Cav1 BHD group had significantly increased cell survival rate, cell migration rate, mesh number, node number, and lumen length, a significantly decreased cell apoptotic rate, a further decreased phosphorylation level of YAP1 at S127 site, and significantly increased nuclear displacement level of YAP1 and protein expression of HIF-1α, VEGF, and VEGFR2. Compared with the sh-NC OGD/R group, the sh-Cav1 OGD/R group exhibited significantly decreased cell survival rate, cell migration rate, mesh number, node number, and lumen length, a significantly increased cell apoptotic rate, a significantly increased phosphorylation level of YAP1 at S127 site, and significantly decreased nuclear displacement level of YAP1 and protein expression of HIF-1α, VEGF, and VEGFR2. Compared with the sh-NC BHD group, the sh-Cav1 BHD group showed significantly decreased cell survival rate, cell migration rate, mesh number, node number, and lumen length, a significantly increased cell apoptotic rate, a significantly increased phosphorylation level of YAP1 at the S127 site, and significantly decreased nuclear displacement level of YAP1 and protein expression of HIF-1α, VEGF, and VEGFR2. YAP1 protein was present in the protein complex precipitated by the HIF-1α antibody, and HIF-1α protein was also present in the protein complex precipitated by the YAP1 antibody. The results confirmed that the drug-containing serum of BHD can increase the activity of YAP1/HIF-1α pathway in bEnd.3 cells damaged by OGD/R through Cav1 and promote angiogenesis in vitro.
Drugs, Chinese Herbal/pharmacology* ; Animals ; Mice ; Signal Transduction/drug effects* ; Glucose/metabolism* ; Caveolin 1/genetics* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; YAP-Signaling Proteins ; Oxygen/metabolism* ; Endothelial Cells/metabolism* ; Cell Line ; Adaptor Proteins, Signal Transducing/genetics* ; Neovascularization, Physiologic/drug effects* ; Cell Hypoxia/drug effects* ; Angiogenesis

OBJECTIVE: To investigate the differential efficacy and safety profiles of oral mucosa (OM) grafts compared with acellular dermal matrix (ADM) grafts in the surgical management of long-segment urethral strictures. METHODS: A retrospective cohort study was conducted involving 27 patients who underwent graft urethroplasty for long-segment urethral strictures in Peking University First Hospital, spanning from May 2010 to September 2023. The patient cohort comprised 14 individuals who received OM grafts and 13 who underwent ADM grafts. The participants were stratified into two groups based on the type of grafts material utilized during surgery. The demographic and clinical baseline characteristics included an average age of (43.3±14.0) years in the OM group and (54.2±15.9) years in the ADM group. The mean body mass index (BMI) for the respective groups were (24.7±4.3) kg/m² for OM and (25.4±4.8) kg/m² for ADM. Etiological differences were noted, with idiopathic causes predominantly in the OM cohort and lichen sclerosus in the ADM cohort. RESULTS: The surgical interventions were successfully executed for all the patients. The median stricture length was 4.5 (2.5, 9.0) cm for the OM group and 5.0 (2.0, 14.0) cm for the ADM group (P=0.555). The median operative duration was 160 (71, 221) min for the OM group and 134 (112, 274) min for the ADM group (P=0.065). The catheterization durations was 1.5 (1.0, 6.0) months for the OM group and 3.0 (1.0, 3.0) months for the ADM group. The median postoperative follow-up duration was 12.5 (1.0, 170.0) months for the OM group and 59.0 (3.0, 142.0) months for the ADM group. The surgical success rates were 50.00% in the OM group and 53.85% in the ADM group. No statistically significant differences were observed in postoperative quality of life (QoL) or international prostate symptom score (IPSS) at the final follow-up. The stricture-free survival rates did not differ significantly (HR=0.875, 95%CI: 0.507-1.511, P=0.6). In terms of safety, three patients in the OM group experienced sexual dysfunction, and two had oral complications, whereas the ADM group had one case of postoperative infection. CONCLUSION The findings suggest that ADM grafts are comparable to OM grafts in terms of efficacy and safety for the treatment of long-segment urethral strictures, including complex cases attributed to lichen sclerosus. However, given the small sample size of this study, the above conclusions may have certain limitations. Larger cohort studies will be needed in the future to further validate these findings.
Humans ; Urethral Stricture/surgery* ; Acellular Dermis ; Mouth Mucosa/transplantation* ; Retrospective Studies ; Middle Aged ; Male ; Adult ; Treatment Outcome ; Skin Transplantation/methods* ; Aged

BACKGROUND: Recent studies have shown that sodium-glucose cotransporters-2 (SGLT2) inhibitors significantly improve major adverse cardiovascular events in heart failure with preserved ejection fraction (HFpEF) patients, but the exact mechanism is unknown. Ferritinophagy is a special form of selective autophagy that participates in ferroptosis. In this study, we aimed to investigate whether ferritinophagy was activated during the occurrence of HFpEF, and whether canagliflozin (CANA) could inhibite ferritinophagy. METHODS: We reared Dahl salt-sensitive (DSS) rats on a high-salt diet to construct a hypertensive HFpEF model, and simultaneously administered CANA intervention. Then we detected indicators related to ferritinophagy. RESULTS: The expression of nuclear receptor coactivator 4 (NCOA4), as well as microtubule-associated proteins light chain 3 (LC3), Bcl-2 interacting protein 1 (Beclin-1) and p62, were upregulated in HFpEF rats, accompanied by the downregulation of ferritin heavy chain 1 (FTH1), upregulation of mitochondrial iron transporter sideroflexin1 (SFXN1) and increased reactive oxygen species (ROS) production. Above changes were diminished by CANA. CONCLUSION Ferritinophagy is activated in HFpEF rats and then inhibited by CANA, leading to HFpEF benefits. The inhibition of ferritinophagy could provide new prospective targets for the prevention and treatment of HFpEF, and provide new ideas for investigating the mechanism of cardiovascular benefit of SGLT2 inhibitors.

In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics. Similarities and variations of components present significant analytical challenges. A two-dimensional (2D) liquid chromatography-mass spectrometr (LC-MS) method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium (CMS). A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated. For efficient and high-accuracy screening of CMS, a targeted method based on a self-constructed high resolution (HR) mass spectrum database of CMS components was established. The database was built based on the commercial MassHunter Personal Compound Database and Library (PCDL) software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening. On this basis, the unknown peaks in the CMS chromatograms were deduced and assigned. The molecular formula, group composition, and origins of a total of 99 compounds, of which the combined area percentage accounted for more than 95% of CMS components, were deduced by this 2D-LC-MS method combined with the MassHunter PCDL. This profiling method was highly efficient and could distinguish hundreds of components within 3 h, providing reliable results for quality control of this kind of complex drugs.

Objective To analyze the caregiver presence needs and their influencing factors among hospitalized elderly non-surgical patients and provide a basis for formulating relevant policies.Methods A descriptive qualitative study method was adopted.Through purposive sampling,semi-structured interviews were conducted on elderly non-surgical patients and their families and medical staff in Peking Union Medical College Hospital from September to October 2023.MAXQDA 2020 and the 7-step phenomenological analysis method of Colaizzi were used to classify and code the interview contents and identify themes.Results The categories of caregiver presence needs of elderly non-surgical patients included basic living assistance needs,disease monitoring needs,psychological support needs,as well as the needs for family members to provide economic support and participate in treatment decision-making.The influencing factors included advanced age,frailty,the lack of self-care ability in patients with comorbidities,the susceptibility of patients to sudden situations during the disease exacerbation period,the increased risk of unexpected events in patients with psychological distress,and patients' concerns about social support and medical decision-making.Conclusion The caregiver presence needs of elderly non-surgical patients during hospitalization are high and influenced by multiple factors.
Humans ; Caregivers/psychology* ; Aged ; Hospitalization ; Social Support ; Male ; Qualitative Research ; Female

Objective:Evaluate the safety and efficacy of aortic endovascular remodeling device (AERD) in the treatment of residual aortic dissection on Stanford type B aortic dissection patients after endovascular repair.Methods:Adopting a prospective cohort study design, according to the inclusion and exclusion criteria, a total number of 60 patients with Stanford B-type aortic dissection after TEVAR surgery from January 2022 to December 2023 were included. Collecting CTA imaging data of patients before and after endovascular treatment with AERD and using computer 3D reconstruction fluid dynamics to evaluate distal aortic remodeling.Results:The incidence of major adverse events and mortality rate associated with aortic dissection within 30 days were 0 after endovascular treatment with AERD. In the short term, AERD was safe for the treatment of residual aortic dissection on Stanford type B aortic dissection patients after endovascular repair. Endovascular treatment with AERD significantly increased the volume of the true lumen of the aorta in the dissection segment, with an increase of 88.44%. At the same time, endovascular treatment with AERD significantly reduced the volume of the false lumen of the aorta in the dissection segment, with a decrease of 61.04%. Endovascular treatment with AERD has no significant effect on the longest true lumen diameter of distal aorta of stent and upper margin aorta of superior mesenteric artery. Comparing to the longest diameter of the true lumen of the aorta, the change in the shortest diameter of the true lumen of the aorta is more significant, with the shortest diameter of true lumen of distal aortic of the stent increasing by 32.29%, the shortest diameter of true lumen of the narrowest part of the aorta increasing by 204.15%, the shortest diameter of true lumen of the upper margin aorta of superior mesenteric artery increasing by 80.76%, the shortest diameter of true lumen of the lower edge aorta of the renal artery increasing by 115.26%, the shortest diameter of the opening of the left iliac artery increasing by 152.01%, and the shortest diameter of opening of the right iliac artery increasing by144.21%.Conclusion:AERD is safe and effective in the treatment of residual aortic dissection on Stanford type B aortic dissection patients after endovascular repair. Endovascular treatment with AERD promotes true lumen dilation and false lumen reduction in the early postoperative stage and promotes benign remodeling of the distal aorta after TEVAR surgery.

Objective:To investigate the incidence of thyroid nodule in population of Yangzhou City and analyze the related influencing factors, so as to provide scientific basis for formulating prevention and control strategies for thyroid nodule.Methods:From January to August 2023, permanent residents (≥8 years old) of 36 towns/streets in 6 counties (cities and districts) of Yangzhou City were randomly selected as the survey subjects. A total of 2 033 subjects were included in the study for questionnaire survey, thyroid nodule was examined by B-ultrasound, and urinary iodine and salt iodine level were determined. SPSS 26.0 software was used for χ 2-test and multivariate logistic regression analysis. Results:Among 2 033 survey subjects, 705 patients with thyroid nodule were detected, the detection rate was 34.68%. The detection rate of thyroid nodule in female (40.37%, 480/1 189) was significantly higher than that in male (26.66%, 225/844), and the difference was statistically significant (χ 2 = 40.97, P < 0.001). The results of multivariate logistic regression analysis showed that women [odds ratio ( OR) = 2.07], age (40 - 59 and ≥60 years old: OR = 1.60, 3.17), hypertension ( OR = 1.62) and immediate family members with goiter/nodule ( OR = 2.77) were all positively correlated with the risk of thyroid nodule ( P < 0.05). Conclusion:The detection rate of thyroid nodule in population of Yangzhou City is relatively high, and special attention should be paid to women, those with hypertension, the elderly, and immediate family members with goiter/nodule.

Aim To investigate the serum levels of thrombin-antithrombin complex(TAT),tissue type plas-minogen activator-inhibitor complex(t-PAIC)and thrombomodulin(TM)in patients with intracranial atherosclerotic steno-sis(ICAS),and their correlations with the degree of stenosis.Methods A total of 196 ICAS patients(ICAS group)who underwent treatment in Cangzhou People's Hospital from January 2021 to February 2023 were enrolled as research sub-jects.Based on the degree of vascular stenosis,they were separated into three groups:mild group(n=78),moderate group(n.=64),and severe group(n=54).A group of 196 healthy outpatient with similar clinical basic data to ICAS patients was selected as controls.The serum levels of TAT,t-PAIC,and TM in each group were compared;Spearman method was applied to analyze the correlation between serum levels of TAT,t-PAIC,TM and stenosis severity in ICAS pa-tients;Multivariate Logistic regression was applied to analyze the influencing factors of severe stenosis in ICAS patients;ROC curve was applied to analyze the predictive value of serum TAT,t-PAIC,TM and total cholesterol(TC)levels for se-vere stenosis in ICAS patients.Results Compared with the control group,the serum levels of TAT,t-PAIC,and TM were significantly increased in the ICAS group(P＜0.05);the levels of serum TAT,t-PAIC,TM,and TC in the mild,moderate,and severe groups increased accordingly(P＜0.05).Spearman analysis showed that the serum levels of TAT,t-PAIC,and TM in ICAS patients were positively correlated with the degree of stenosis(r=0.574,0.695,0.628;all P＜0.05).Multivariate Logistic regression analysis showed that TAT,t-PAIC,TM,and TC were independent risk factors for severe stenosis in ICAS patients(P＜0.05).The ROC curve showed that the AUC of severe stenosis in ICAS patients predicted by combination of TAT,t-PAIC,TM,and TC was 0.927,with a sensitivity of 83.33％and a specificity of 86.62％,which was superior to the independent prediction of TAT,t-PAIC,TM and TC(Zcombined detection-TAT=4.617,Zcombined deteetion-t-PAIC=4.024,Zcombined detection-TM=4.004,Zcombined detection-TC=7.078,all P=0.000).Conclusion The ser-um levels of TAT,t-PAIC,and TM in the ICAS group were significantly increased,and were positively correlated with the severity of stenosis.The combination of the three and TC has a high predictive value for the occurrence of severe stenosis in ICAS patients.