ObjectiveTo investigate the effect of icariin （ICA） on steroid-induced ferroptosis in bone microvascular endothelial cells （BMECs）. MethodsRat BMECs were selected and treated with 500 mg·L^-1 hydrocortisone for 1.5 h to establish a ferroptosis model of BMECs. The experimental cells were divided into a blank group， hormone group （500 mg·L^-1 hydrocortisone）， ICA group （500 mg·L^-1 hydrocortisone + 34 mg·L^-1 ICA）， and ferroptosis agonist group （500 mg·L^-1 hydrocortisone + 34 mg·L^-1 ICA + 2.7 mg·L^-1 erastin）. Cell viability was detected by CCK-8. The levels of ferrous ion， glutathione （GSH）， malondialdehyde （MDA）， superoxide dismutase （SOD）， and reactive oxygen species （ROS） were detected by related kit species. The ferroptosis-related proteins， such as glutathione peroxidase 4（GPX4）， ferritin light chain （FTL）， and transferrin receptor protein1 （sTfR） were detected by Western blot， as well as autophagy-related proteins including microtubule-associated protein 1 light chain 3B （LC3B）， Beclin1， B-cell lymphoma-2 （Bcl-2）， and Caspase-3. Results500 mg·L^-1 hydrocortisone intervention for 1.5 h could effectively induce ferroptosis in BMECs， and ferroptosis levels could reach a peak as the intervention continued. In terms of cellular antioxidant capacity， compared with those in the blank group， the cell vitality， GSH in the hormone group decreased significantly， and the levels of ROS， SOD， MDA， and ferrous ions were significantly increased （P<0.01）. Compared with those in the hormone group， the cell viability， GSH were significantly increased， and the levels of ROS， SOD， MDA， and ferrous ions were decreased in the ICA group （P<0.01）. Compared with those in the ICA group， the cell vitality， GSH in the ferroptosis agonist group decreased significantly， and the levels of ROS， SOD， MDA， and ferrous ions increased significantly （P<0.01）. In terms of the relationship between ferroptosis and autophagy， compared with the blank group， the hormone group had significantly increased expression levels of LC3B， sTfR， Beclin1， and FTL and significantly decreased expression levels of GPX4 （P<0.01）. Compared with the hormone group， The ICA group had significantly decreased expression levels of LC3B， sTfR， and FTL and significantly increased expression levels of Beclin 1 and GPX4 （P<0.01）. Compared with those in the ICA group， the expression levels of LC3B， sTfR， and FTL increased in the rapamycin group， and those of Beclin 1 and GPX4 decreased （P<0.01）. In terms of cell ferroptosis and apoptosis，compared with the blank group， the hormone group had significantly increased expression levels of FTL， sTfR and Caspase-3 and significantly decreased expression levels of GPX4， and Bcl-2 （P<0.01）. Compared with the hormone group， the ICA group had significantly decreased expression levels of FTL， sTfR and Caspase-3 and significantly increased expression levels of GPX4， and Bcl-2 （P<0.01）. Compared with those in the ICA group， the expression levels of FTL， sTfR and Caspase-3 in the ferroptosis agonist group were increased， and the expression levels of GPX4， and Bcl-2 were decreased （P<0.01）. In terms of cell function，compared with that in the blank group， the ability of cell migration and tube formation was significantly decreased in the hormone group （P<0.01）. Compared with that in the hormone group， the cell migration and tube formation ability in the ICA group were significantly increased （P<0.01）. ConclusionFerroptosis is involved in steroid-induced damage in BMECs. ICA can inhibit steroid-induced ferroptosis in BMECs， and the mechanism may be associated with the inhibition of ferroptosis by regulating autophagy.

Steroid-induced osteonecrosis of the femoral head （SONFH） is a severe musculoskeletal disorder often induced by the prolonged or excessive use of glucocorticoids. Characterized by ischemia of bone cells， necrosis， and trabecular fractures， SONFH is accompanied by pain， femoral head collapse， and joint dysfunction， which can lead to disability in severe cases. The pathogenesis of SONFH involves hormone-induced osteoblast apoptosis， bone microvascular endothelial cell （BMEC） apoptosis， oxidative stress， and inflammatory responses. The phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway plays a pivotal role in the development of the disease. Modulating the PI3K/Akt signaling pathway can promote Akt phosphorylation， thereby stimulating the osteogenic differentiation of bone marrow mesenchymal stem cells and osteoblasts， promoting angiogenesis in BMECs， and inhibiting osteoclastogenesis. The research on the treatment of SONFH with traditional Chinese medicine （TCM） has gained increasing attention. Recent studies have shown that TCM monomers and compounds have potential therapeutic effect on SONFH by intervening in the PI3K/Akt signaling pathway. These studies not only provide a scientific basis for the application of TCM in the treatment of SONFH but also offer new ideas for the development of new therapeutic strategies. This review summarized the progress in Chinese and international research on the PI3K/Akt signaling pathway in SONFH over the past five years. It involved the composition and transmission mechanisms of the signaling pathway， as well as its regulatory effects on osteoblasts， mesenchymal stem cells， osteoclasts， BMECs， and other cells. Additionally， the review explored the TCM understanding of SONFH and the application of TCM monomers and compounds in the intervention of the PI3K/Akt pathway. By systematically analyzing and organizing these research findings， this article aimed to provide references and point out directions for the clinical prevention and treatment of SONFH and promote further development of TCM in this field. With in-depth research on the PI3K/Akt pathway and the modern application of TCM， it is expected to bring safer and more effective treatment options for patients with SONFH.

Objective:To investigate the current application of blood purification in the treatment of acute poisoning within Jiangsu Province and to evaluate the impact of extracorporeal blood purification on the clinical outcomes of critically poisoned patients.Methods:This multicenter, cross-sectional real-world observational study followed patients presenting with poisoning to the emergency departments of nine hospitals in Jiangsu Province between June 2015 and May 2019. Data were collected on demographic characteristics, vital signs within the first hour of emergency presentation, treatment modalities, length of hospital stay, and survival outcomes. Clinical data from patients who underwent extracorporeal blood purification were compared with those who did not, using the Wilcoxon rank-sum test and Chi-square test.Results:A total of 4 178 poisoning cases were included between June 2015 and May 2019. Among them, 21.7% (908/4 178) received blood purification therapy, while 78.3% (3 270/4 178) did not. Hemoperfusion (90.4%) was the most frequently employed method, followed by continuous renal replacement therapy (CRRT) (4.4%). In combined blood purification modalities, 4.8% underwent hemoperfusion combined with CRRT, 0.1% received hemoperfusion with plasma exchange, and another 0.1% underwent hemoperfusion combined with both CRRT and plasma exchange. Among patients who underwent blood purification, pesticide poisoning was the most prevalent (76.3%), with the most common toxic agents being paraquat (23.7%), dichlorvos (8.7%), methamidophos (5.2%), omethoate (4.0%), and glyphosate (3.7%). Compared to the non-blood purification group, patients in the blood purification group were more likely to present within the first hour with a low Glasgow Coma Scale (GCS) score (3-8) (22.6% vs. 9.7%, P <0.05), low mean arterial pressure (8.0% vs. 3.2%, P <0.05), longer hospital stays [5(3,9) days vs. 2(1,4) days, P <0.05] and a higher in-hospital mortality rate (21.1% vs. 5.3%, P <0.05). Follow-up via telephone 28 days after discharge revealed a survival rate of 78.9%, with a mortality rate of 21.1% in the blood purification group. Conclusions:Hemoperfusion is the most commonly utilized blood purification technique for treating poisoning in Jiangsu Province, with pesticides being the primary toxic agents treated. Although the mortality rate is higher in the blood purification group, the intervention may still contribute to improved patient outcomes.

ObjectiveTo investigate the impact of icariin （ICA） on autophagy in glucocorticoid-induced bone microvascular endothelial cells （BMECs） mediated by the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway. MethodBMECs were isolated and cultured from femoral heads obtained during total hip arthroplasty and identified using immunofluorescence staining. The experimental cells were divided into four groups： A control group， a glucocorticoid group （100 mg·L^-1 hydrocortisone）， an ICA group （100 mg·L^-1 hydrocortisone+6.7×10^-3 mg·L^-1 ICA）， and a Rapamycin group （100 mg·L^-1 hydrocortisone+6.7×10^-3 mg·L^-1 ICA+1 mg·L^-1 rapamycin）. Autophagy in BMECs was induced using 100 mg·L^-1 hydrocortisone. LC3 fluorescence staining was used to observe the peak of autophagy at different time points. Western blot analysis was employed to analyze the expression of autophagy-related proteins and PI3K/Akt/mTOR pathway proteins in each group. Electron microscopy was used to observe autophagosomes and autolysosomes in the cells. ResultHydrocortisone at 100 mg·L^-1 induced autophagy in BMECs， reaching a peak at around 5 hours， which then declined with further intervention. Compared to the control group， the glucocorticoid group showed cell membrane damage， disordered organelle arrangement， and a large number of autophagosomes and autolysosomes. Compared to the glucocorticoid group， the ICA group had more intact cell membranes， sparser organelle arrangement， and fewer autophagosomes and autolysosomes. Compared to the ICA group， the Rapamycin group showed cell membrane damage， disordered organelle arrangement， and more autophagosomes and autolysosomes. Compared to the control group， the glucocorticoid group had significantly increased expression of light chain 3B （LC3B）， Atg4B， and p62 （P<0.01）. Compared to the glucocorticoid group， the ICA group showed significantly decreased expression of LC3B， Atg4B， p62， and Beclin-1 （P<0.01）. Compared to the ICA group， the Rapamycin group had significantly increased expression of Atg4B and p62 （P<0.01）. Compared to the control group， the glucocorticoid group had significantly decreased expression of p-PI3K/PI3K， p-Akt/Akt， and p-mTOR/mTOR （P<0.01）. Compared to the glucocorticoid group， the ICA group showed significantly increased expression of p-PI3K/PI3K， p-Akt/Akt， and p-mTOR/mTOR （P<0.01）. Compared to the ICA group， the Rapamycin group had significantly decreased expression of p-PI3K/PI3K， p-Akt/Akt， and p-mTOR/mTOR （P<0.01）. Ubiquitination levels were significantly decreased in the glucocorticoid group compared to the control group （P<0.01）. Compared to the glucocorticoid group， ubiquitination levels were significantly increased in the ICA group （P<0.01）， and significantly decreased in the Rapamycin group compared to the ICA group （P<0.01）. ConclusionThe glucocorticoid-induced autophagy in BMECs is time-dependent. ICA inhibits glucocorticoid-induced autophagy in BMECs， and this effect may be related to the regulation of the PI3K/Akt/mTOR pathway.

Objective To observe the clinical efficacy of Sushen Jiubao decoction in the treatment of acute exacerbation of bronchial asthma and its effect on Th1/Th2 factors.Methods Ninety-eight patients with acute exacerbation of bronchial asthma treated in Sishengbianji Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University from February 2022 to May 2023 were selected and divided into treatment group and control group according to random number table method,with 49 cases in each group.The control group was given conventional treatment such as oxygen inhalation and atomization,and the treatment group was additionally treated with Sushen Jiubao decoctionon based on the treatment of control group.The clinical efficacy,TCM syndrome score,pulmonary function indicators[forced expiratory volume in first second(FEV1),peak expiratory flow(PEF)],and laboratory indicators[interleukin(IL)-4,IL-13,interferon-γ(IFN-γ),immunoglobulin E(IgE)].Results The total effective rate of treatment group was significantly higher than that of control group(χ2=9.287,P=0.010).After treatment,the TCM syndrome scores,serum IL-4,IL-13 and IgE levels of two groups were significantly lower than before treatment,and FEV1,PEF and IFN-γ were significantly higher than before treatment(P<0.05).The TCM syndrome score,serum IL-4,IL-13 and IgE levels in treatment group were significantly lower than those in control group,and FEV1,PEF and IFN-γ were significantly higher than those in control group(P<0.05).Conclusion Sushen Jiubao decoction can significantly improve clinical efficacy,reduce the level of inflammatory factors,and improve pulmonary function in the treatment of acute exacerbation of bronchial asthma.

Objective To develop an intelligent model for differential diagnosis of atrioventricular nodal re-entrant tachycardia(AVNRT)and atrioventricular re-entrant tachycardia(AVRT)using 12-lead wearable electrocardiogram devices.Methods A total of 356 samples of 12-lead supraventricular tachycardia(SVT)electrocardiograms recorded by wearable devices were randomly divided into training and validation sets using 5-fold cross validation to establish the intelligent classification model,and 101 patients with the diagnosis of SVT undergoing electrophysiological studies and radiofrequency ablation from October,2021 to March,2023 were selected as the testing set.The changes in electrocardiogram parameters before and during induced tachycardia were compared.Based on multiscale deep neural network,an intelligent diagnosis model for classifying SVT mechanisms was constructed and validated.The 3-lead electrocardiogram signals from Ⅱ,Ⅲ,and V1 were extracted to build new classification models,whose diagnostic efficacy was compared with that of the 12-lead model.Results Of the 101 patients with SVT in the testing set,68 were diagnosed with AVNRT and 33 were diagnosed with AVRT by electrophysiological study.The pre-trained model achieved a high area under the precision-recall curve(0.9492)and F1 score(0.8195)for identifying AVNRT in the validation set.The total F1 scores of the lead Ⅱ,Ⅲ,V1,3-lead and 12-lead intelligent diagnostic models in the testing set were 0.5597,0.6061,0.3419,0.6003 and 0.6136,respectively.Compared with the 12-lead classification model,the lead-Ⅲ model had a net reclassification index improvement of-0.029(P=0.878)and an integrated discrimination index improvement of-0.005(P=0.965).Conclusion The intelligent diagnostic model based on multiscale deep neural network using wearable electrocardiogram devices has an acceptable accuracy for classifying SVT mechanisms.

Objective To develop an intelligent model for differential diagnosis of atrioventricular nodal re-entrant tachycardia(AVNRT)and atrioventricular re-entrant tachycardia(AVRT)using 12-lead wearable electrocardiogram devices.Methods A total of 356 samples of 12-lead supraventricular tachycardia(SVT)electrocardiograms recorded by wearable devices were randomly divided into training and validation sets using 5-fold cross validation to establish the intelligent classification model,and 101 patients with the diagnosis of SVT undergoing electrophysiological studies and radiofrequency ablation from October,2021 to March,2023 were selected as the testing set.The changes in electrocardiogram parameters before and during induced tachycardia were compared.Based on multiscale deep neural network,an intelligent diagnosis model for classifying SVT mechanisms was constructed and validated.The 3-lead electrocardiogram signals from Ⅱ,Ⅲ,and V1 were extracted to build new classification models,whose diagnostic efficacy was compared with that of the 12-lead model.Results Of the 101 patients with SVT in the testing set,68 were diagnosed with AVNRT and 33 were diagnosed with AVRT by electrophysiological study.The pre-trained model achieved a high area under the precision-recall curve(0.9492)and F1 score(0.8195)for identifying AVNRT in the validation set.The total F1 scores of the lead Ⅱ,Ⅲ,V1,3-lead and 12-lead intelligent diagnostic models in the testing set were 0.5597,0.6061,0.3419,0.6003 and 0.6136,respectively.Compared with the 12-lead classification model,the lead-Ⅲ model had a net reclassification index improvement of-0.029(P=0.878)and an integrated discrimination index improvement of-0.005(P=0.965).Conclusion The intelligent diagnostic model based on multiscale deep neural network using wearable electrocardiogram devices has an acceptable accuracy for classifying SVT mechanisms.

Objective To analyze the dynamic changes in serum adiponectin (APN) levels after acute myocardial infarction (AMI) and its relationship with heart failure (HF) and major adverse cardiovascular events (MACE). Methods A total of 124 AMI patients who underwent percutaneous coronary intervention (PCI) in our hospital from January 2021 to December 2023 were enrolled as AMI group. Additionally, 30 patients with non-AMI coronary artery disease and 30 healthy individuals were included in non-AMI coronary artery disease group and healthy group, respectively. General information such as age, gender, smoking, alcohol consumption, hypertension, diabetes, and blood lipids were recorded for all subjects. Serum APN levels were measured using the enzyme-linked immunosorbent assay (ELISA) method; plasma brain natriuretic peptide (BNP) levels were determined by immunofluorescence; and left ventricular ejection fraction (LVEF) was assessed using echocardiography. Changes in serum APN levels and its relationship with BNP, LVEF, and MACE were recorded during a one-year follow-up period. Results AMI patients had lower serum APN levels than those in the non-AMI coronary artery disease group and the healthy group, while levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C); Lipoprotein-associated phospholipase A2 (Lp-PLA2), and the proportions of smokers and diabetics were higher(P < 0.05). A one-year follow-up of AMI patients revealed an upward trend in serum APN and BNP levels and a downward trend in LVEF levels at one week, one month, three months, six months, and one year postoperatively (P < 0.05). APN and BNP levels peaked one month after PCI, while LVEF reached its lowest level at the same time point. However, there were no statistically significant changes in these indicators in the subsequent 11 months (P>0.05). The incidence of MACE in AMI patients at one, three, six, and twelve months postoperatively was 2.8%, 3.2%, 4.6%, and 8.8%, respectively. Both preoperative and one-month postoperative serum APN levels had high predictive value for the occurrence of HF and MACE within one year in AMI patients, and the area under the curve for predicting HF and MACE one month postoperatively was larger than that preoperatively (P < 0.05). Conclusion Serum APN levels in AMI patients show an upward trend after PCI, peaking one month postoperatively. At this time point, serum APN levels have the highest predictive value for the occurrence of HF and MACE.

Objective To explore the clinical application of salpingectomy with preserving salpingum mesothelium under single-port laparoscopy and its influence on ovarian reserve function and assisted pregnancy outcome.Methods From January 2019 to January 2022,80 cases of salpingectomy in Shuangyashan Double Mine Hospital were selected and randomly divided into control group(n=40)and observation group(n=40).The control group was treated with multi-hole laparoscopic salpingectomy with salpingum mesothelium preserved,while the observation group treated with single-hole laparoscopic salpingectomy with salpingum mesothelium preserved.The operation conditions(operation time,intraoperative blood loss,exhaust time,etc.),anti-Mullerian hormone(AMH)before and one month after operation,ovarian function(basal sinus follicle count),postoperative complications,assisted pregnancy outcome and cosmetic effect were analyzed.Results The exhaust time and postoperative hospitalization time in the observation group were shorter than those in the control group,and the operation time was longer than that in the control group(P＜0.05).One month after operation,AMH in both groups decreased,and the number of sinus follicles in observation group A was lower than that in control group.The complication rate was lower than that of the control group(P＜0.05).After a one-year follow-up,there was no significant difference in ovulation rate and pregnancy rate between the two groups(P＞0.05).Follow-up for 3 months showed that the cosmetic effect of the observation group was better than that of the control group(95.00％vs 72.50％)(P＜0.05).Conclusion Single-port laparoscopic salpingectomy with salpingum mesothelium preservation is safe,cosmetic and minimally invasive,and has little adverse effect on ovarian reserve function,which is helpful for successful pregnancy assistance and worthy of clinical application and promotion.

OBJECTIVE: To summarize the clinical features and spectrum of genetic variants in 12 patients with Loeys-Dietz syndrome (LDS), and to explore the correlation between the type of genetic variants and clinical phenotypes. METHODS: Twelve patients suspected for LDS at Beijing Anzhen Hospital Affiliated to Capital Medical University from January 2015 to January 2022 were selected as the study subjects. Clinical data of the patients were collected. Genomic DNA was extracted from peripheral blood samples and subjected to genetic testing. Pathogenicity of candidate variants was analyzed. RESULTS: The clinical phenotypes of the 12 patients have mainly included cardiovascular, musculoskeletal, craniofacial, skin, ocular and other systemic signs. Four patients (patients 5-1, 5-2, 6, 7) have carried heterozygous missense variants of the TGFBR1 gene, 5 patients (patients 1-1, 1-2, 2, 3, 4) have carried heterozygous variants of the TGFBR2 gene, and 2 patients (patients 8-1, 8-2) had carried heterozygous frameshift variants of the TGFB3 gene. One patient (patient 9) had carried a heterozygous missense variant of the SMAD3 gene. Among these, TGFBR1 c.603T>G (p.1201M) and TGFB3 c.536delA (p.H179FS35) had not been reported previously. CONCLUSION Variants of the TGFBR1, TGFBR2, SMAD3, TGFB2, TGFB3 and SMAD2 genes are mainly associated with LDS. The severity of the disease phenotype caused by the same variant may vary, whilst the clinical phenotype caused by different variant sites may be specific.
Humans ; Loeys-Dietz Syndrome/genetics* ; Receptor, Transforming Growth Factor-beta Type I/genetics* ; Receptor, Transforming Growth Factor-beta Type II/genetics* ; Transforming Growth Factor beta3 ; Face