Objective: To explore the clinical and molecular genetic characteristics of complete androgen insensitivity syndrome (CAIS) caused by androgen receptor (AR) gene mutations. Methods: The clinical phenotype and postoperative gonadal pathological characteristics of a female XY patient with a chromosomal karyotype of 46 were analyzed, and full IDT testing was performed. Results: The patient had female appearance with underdeveloped vagina, but no normal uterine tissue was found on imaging examination. The pathological findings of gonadal tissue showed testicular tissue, including some spermatic cords. The AR gene was located on chromosome chrX: 66931243 exhibiting splicing site variation, and the variation site was c.1886-1G＞A (-). Conclusion: The clinical manifestations of androgen insensitivity syndrome are diverse, and AR deficiency is one of the important causes. This case study summarizes the clinical diagnosis and treatment principles of CAIS and analyzes the molecular genetic.

Objective To explore the safety and effects of alpha-lipoic acid (ALA) in patients with ischemic heart failure (IHF). Methods A randomized, double-blind, placebo-controlled trial was designed (ClinicalTrial.gov registration number NCT03491969). From January 2019 to January 2023, 300 patients with IHF were enrolled in four medical centers in China, and were randomly assigned at a 1∶1 ratio to receive ALA (600 mg daily) or placebo on top of standard care for 24 months. The primary outcome was the composite outcome of hospitalization for heart failure (HF) or all-cause mortality events. The second outcome included non-fatal myocardial infarction (MI), non-fatal stroke, changes of left ventricular ejection fraction (LVEF) and 6-minute walking distance (6MWD) from baseline to 24 months after randomization. Results Finally, 138 patients of the ALA group and 139 patients of the placebo group attained the primary outcome. Hospitalization for HF or all-cause mortality events occurred in 32 patients (23.2%) of the ALA group and in 40 patients (28.8%) of the placebo group (HR＝0.753, 95%CI 0.473-1.198, P＝0.231; Figure 1A-1C). The absolute risk reduction (ARR) was 5.6%, the relative risk reduction (RRR) associated with ALA therapy was approximately 19.4% compared to placebo, corresponding to a number needed to treat (NNT) of 18 patients to prevent one event. In the secondary outcome analysis, the composite outcome of the major adverse cardiovascular events (MACE) including the hospitalization for HF, all-cause mortality events, non-fatal MI or non-fatal stroke occurred in 35 patients (25.4%) in the ALA group and 47 patients (33.8%) in the placebo group (HR＝0.685, 95%CI 0.442-1.062, P＝0.091; Figure 1D). Moreover, greater improvement in LVEF (β＝3.20, 95%CI 1.14-5.23, P＝0.002) and 6MWD (β＝31.7, 95%CI 8.3-54.7, P＝0.008) from baseline to 24 months after randomization were observed in the ALA group as compared to the placebo group. There were no differences in adverse events between the study groups. Conclusions These results show potential long-term beneficial effects of adding ALA to IHF patients. ALA could significantly improve LVEF and 6MWD compared to the placebo group in IHF patients.

Objective:To summarize and analyze the clinical efficacy and experience of ultrasound-guided radiofrequency ablation (RFA) in the treatment of Kasabach-Merritt syndrome (KMS).Methods:A retrospective analysis was conducted on the data of pediatric patients with KMS who underwent ultrasound-guided RFA in Department of Hemangioma Surgery, the Third Affiliated Hospital of Zhengzhou University, between March 2018 and March 2024. Preoperative laboratory tests and imageological examination were performed. Under general anesthesia, the working tip of the RFA electrode needle was precisely reached the bottom of the lesion under ultrasound guidance. The electrode needle was then gradually withdrawn until the entire lesion area was covered by hyperechoic signals, indicating complete ablation. Postoperative symptomatic and supportive treatments, such as ice pack application and dressing changes, were administered to the surgical area. Platelet detection was performed immediately after the operation. Complications were closely monitored and regular follow-ups were carried out.Results:A total of 30 pediatric patients were included, comprising 14 males and 16 females, from 10 min to 5 months and 29 d after birth, with a median time of 6 d. Lesions were located in the limbs and trunk in 27 cases, and head and neck region in 3 cases, with lesion volumes ranged from 2.4 cm×2.3 cm×1.2 cm to 14.4 cm×9.3 cm×3.3 cm. The mean preoperative platelet count was 43×10 9/L, among them, the platelet values of 11 cases were (10-30) ×10 9/L, and those of 6 cases were lower than 10×10 9/L, other 13 cases with progressive thrombocytopenia. All patients successfully underwent RFA, achieving complete lesion ablation and normalization of platelet counts postoperatively. Platelet counts recovered to above 300×10 9/L in 15 patients, with no severe complications observed. The RFA area became slightly hardened within 7 d postoperatively but gradually returned to normal after consistent dressing changes for 2 weeks. During the follow-up period of 6 months to 2 years, complete lesion ablation was confirmed, with disappearance of the mass, no recurrence, good local function, mild local scar formation, and satisfactory cosmetic appearance. Conclusion:Ultrasound-guided RFA for KMS has advantages of favorable therapeutic outcomes, minimal tissue damage, no significant complications, and satisfactory cosmetic result.

Objective To explore the effects of Ginkgo biloba extract (GBE) on cardiac microvascular endothelial cells (CMECs) under oxygen and glucose deprivation/reperfusion (OGD/R) condition and its molecular mechanisms. Methods An OGD/R-induced injury model was established in CMECs. According to different intervention, CMECs were divided into four groups: normoxia blank control group (WT group), WT + GBE group, OGD/R group, and OGD/R + GBE group. Cell apoptosis was detected by flow cytometry technology in each group. The oxidative stress was examined by MitoSox staining. The migration abilities were measured by scratch assay. The expressions of PERK/eIF2α/CHOP, nuclear factor kappa B (NF-κB), and endothelial cell function markers were detected by Western blotting. Results Compared with the WT group, the endothelial cell apoptosis level in the OGD/R group significantly increased, with markedly aggravated cellular dysfunction. The expressions of p-NF-κB, vascular cell adhesion molecule-1 (VCAM-1), and intercellular cell adhesion molecule-1 (ICAM-1) were significantly upregulated (P＜0.05), and the activation of the CHOP signaling pathway was notably enhanced (P＜0.05). After intervention with GBE, endothelial cell apoptosis caused by OGD/R injury was significantly reduced, oxidative stress and inflammation levels were markedly downregulated, and the expression of p-NF-κB was considerably decreased (P＜0.05), while the CHOP signaling pathway was notably inhibited (P＜0.05). Furthermore, it was found that GBE could promote expression of SIRT6 to regulate the above molecules, thereby alleviating cardiac microvascular endothelial cell injury under OGD/R condition. On the contrary, when SIRT6 was knocked down, the protective effects were significantly reduced. Conclusions GBE improves endothelial cell dysfunction, endoplasmic reticulum stress, and endothelial cell apoptosis caused by OGD/R injury by promoting the expression of SIRT6 protein, thus regulating the NF-κB inflammatory pathway and CHOP signaling pathway.

[Objective] To report a new technique that combines microfracture surgery under local anesthesia with injection of platelet-rich plasma (PRP) at the fracture site, so as to improve fracture healing rates. [Methods] Data from patients who visited our hospital from March 2020 to June 2023 and underwent the treatment for delayed union of limb fractures were retrospectively analyzed. Under local infiltrative anesthesia, with the assistance of a C-arm X-ray machine or ultrasound, percutaneous loosening was done at the fracture site and the medullary cavity, followed by cortical drilling around the fracture. The previously prepared PRP was then injected locally at the fracture site. Patients were followed up and their postoperative recovery was recorded. [Results] All patients were followed up, and the fracture healing rate was 94.12% (16/17), with an average healing duration of (5.88±2.50) months. None of the patients experienced any neural or vascular injuries, nor adverse events such as wound infections or osteomyelitis. Before the operation and at the last follow-up, the patients' pain visual analogue scores were (5.12±1.11) vs (0.71±1.21) respectively. The postoperative VAS scores showed a significant decrease compared to preoperative values (P<0.05). The excellent and good rate for limb function on the affected side was 88.24% (14/17) at the last follow-up, which was a significant increase from 0.00% before surgery (P<0.05). [Conclusion] The injection of PRP at the fracture site combined with microfracture surgery at the fracture site is minimally invasive, simple to perform, and well-accepted by patients. It has demonstrated some clinical efficacy in treating delayed fracture healing.

Objective To explore the effects of Ginkgo biloba extract(GBE)on cardiac microvascular endothelial cells(CMECs)under oxygen and glucose deprivation/reperfusion(OGD/R)condition and its molecular mechanisms.Methods An OGD/R-induced injury model was established in CMECs.According to different intervention,CMECs were divided into four groups:normoxia blank control group(WT group),WT+GBE group,OGD/R group,and OGD/R+GBE group.Cell apoptosis was detected by flow cytometry technology in each group.The oxidative stress was examined by MitoSox staining.The migration abilities were measured by scratch assay.The expressions of PERK/eIF2α/CHOP,nuclear factor kappa B(NF-κB),and endothelial cell function markers were detected by Western blotting.Results Compared with the WT group,the endothelial cell apoptosis level in the OGD/R group significantly increased,with markedly aggravated cellular dysfunction.The expressions of p-NF-κB,vascular cell adhesion molecule-1(VCAM-1),and intercellular cell adhesion molecule-1(ICAM-1)were significantly upregulated(P＜0.05),and the activation of the CHOP signaling pathway was notably enhanced(P＜0.05).After intervention with GBE,endothelial cell apoptosis caused by OGD/R injury was significantly reduced,oxidative stress and inflammation levels were markedly downregulated,and the expression of p-NF-κB was considerably decreased(P＜0.05),while the CHOP signaling pathway was notably inhibited(P＜0.05).Furthermore,it was found that GBE could promote expression of SIRT6 to regulate the above molecules,thereby alleviating cardiac microvascular endothelial cell injury under OGD/R condition.On the contrary,when SIRT6 was knocked down,the protective effects were significantly reduced.Conclusions GBE improves endothelial cell dysfunction,endoplasmic reticulum stress,and endothelial cell apoptosis caused by OGD/R injury by promoting the expression of SIRT6 protein,thus regulating the NF-κB inflammatory pathway and CHOP signaling pathway.

Objective:To explore the possibility of using a inferior gluteal artery perforator flap (IGAPF) for breast reconstruction in the patient who did not have suitable donor site in back and abdomen.Methods:In November 2024, a 25-year-old unmarried and childless woman with right breast cancer received immediate right breast reconstruction by a right free IGAPF after modified right mastectomy in the Department of Breast and Thyroid Surgery, Second Affiliated Hospital of Hainan Medical University. The locations of perforators were confirmed by both Multi-detector computed tomography angiography (MDCTA) and portable Doppler blood flow detector before surgery. The IGAPF was designed to take the inferior gluteal wrinkle as the lower edge, the axis of the flap was parallel to the inferior gluteal wrinkle, and the width of the flap was estimated where the incision could be directly closed. The size of right IGAPF was 6.0 cm×19.0 cm. Sharp dissection was performed between the sarcolemma and muscle fibres of gluteus, then the perforators were dissected along the direction of muscle fibres of gluteus. The vascular pedicle was kept at about 8.0 cm in length. The diameter of artery was about 2.0 mm and that for the veins was about 1.5 mm. End-to-end anastomoses with the right thoracodorsal artery and vein were successfully carried out. The donor site was directly closed, and it was hidden in the inferior gluteal wrinkle. Postoperative outpatient clinical review was made.Results:Pathological examination reported: an invasive carcinoma of right breast, axillary lymph node metastasis (2/10). The patient recovered well and the flap survived without any complication, i.e. ischemic necrosis, infection and haematoma. The patient was off-bed at 3 days and discharged at 13 days after surgery. At the 40 days of postoperative follow-up, the patient achieved a good recovery and the lower limb activity was not affected by the surgery. The patient was satisfied with the reconstructed breast and donor site recovery. The patient followed with scheduled chemotherapy and subsequent radiotherapy. The volume of reconstructed breast was smaller than the other breast, of which the patient was fully informed before the surgery.Conclusion:A free IGAPF provides an alternative donor sites for achieving a breast reconstruction due to the reliable pedicle vessels and invisible donor scars.

Objective To investigate the efficacy of percutaneous transluminal angioplasty(PTA)in the treatment of dysfunction of autogenous arteriovenous fistula(AVF),and to analyze the factors influencing 12-month patency.Methods The data from maintenance hemodialysis patients who underwent PTA for AVF stenosis were collected.The technical success rate,clinical success rate,complications,and short-to medium-term AVF patency were evaluated.Univariate analysis and binary logistic regression were used to identify predictors of 12-month post-procedural patency.Results A total of 70 patients were included in this study.The technical and clinical success rates were 94.29%and 95.71%,respectively.The 3-,6-,and 12-month post-procedural patency rates of AVF were 97.1%,75.7%,and 61.4%,respectively.Independent protective factors for 12-month AVF patency included age＜60 years[odds ratio(OR)=0.277,95%confidence interval(CI)0.097-0.792]and statin use(OR=0.299,95%CI 0.101-0.887).Independent risk factors included diabetes mellitus(OR=5.167,95%CI 1.824-14.64),AVF usage≥1 year(OR=2.885,95%CI 1.061-7.840),and non-use of aspirin(OR=2.782,95%CI 1.016-7.615).Conclusion PTA is a safe and effective treatment for AVF stenosis,though long-term patency rates require further improvement.

Objective To explore the correlation between serum circularRNA-HOMER1(circHOMER1),microRNA(miR)-23a-3p levels with clinical stages and oxidative stress in patients with diabetic retinopathy(DR).Methods From January 2023 to July 2024,75 DR patients treated in Handan Central Hospital were included as the DR group.According to the clinical staging of DR,they were divided into non proliferative DR(NPDR group,n=43)and proliferative DR(PDR group,n=32).In addition,75 patients with simple type 2 diabetes who came to Handan Central Hospital were included as non DR group.The levels of serum circHOMER1,miR-23a-3p,malondialdehyde(MDA),superoxide dismutase(SOD),and reduced glutathione(GSH)were detect-ed.Clinical data of the subjects were collected.The TargetScan website was used to predict the targeting relationship between circHOMER1 and miR-23a-3p.Pearson method was used to analyze the correlation between serum circHOMER1,miR-23a-3p and MDA,SOD,GSH.Univariate and multivariate Logistic regression were used to analyze the influencing factors of progression of DR in type 2 diabetes patients.Receiver operating characteristic(ROC)carve was used to analyze the predictive value of serum circHOMER1 and miR-23a-3p in the progression of DR in patients with type 2 diabetes.Results There was a targeted relationship between circHOMER1 and miR-23a-3p.The serum MDA(28.66±4.52ng/ml)and circHOMER1(1.24±0.16)levels in the DR group were higher than those in the non DR group(16.95±3.27ng/ml,1.02±0.11),while SOD(45.39±7.84U/L),GSH(135.82±21.23μg/mL)and miR-23a-3p(0.88±0.07)levels were lower than those in the non DR group(81.65±11.47U/L,207.44±25.95μg/mL,1.01±0.09),and differences were statistically significant(t=9.813～22.602,all P<0.001).The serum MDA(33.28±4.96ng/ml)and circHOMER1(1.36±0.20)levels in the PDR group were higher than those in the NPDR group(25.23±3.58ng/ml,1.15±0.17),while SOD(34.39±7.15U/L),GSH(113.50±20.17μg/ml)and miR-23a-3p(0.79±0.07)levels were lower than those in the NPDR group(53.27±8.44U/L,152.43±23.99μg/ml,0.94±0.08),and the differences were statistically significant(t=4.906～10.376,all P<0.001).Spearman analysis showed that serum MDA and circHOMER1 were positively correlated with the severity of DR(r=0.533,0.473,all P<0.001),while SOD,GSH,miR-23a-3p were negatively correlated with the severity of DR(r=-0.552,-0.515,-0.529,all P<0.001).Pearson analysis showed that serum circHOMER1 was negatively correlated with miR-23a-3p,SOD,GSH,and positively correlated with MDA(r=-0.475,-0.460,-0.455,0.462,all P<0.001).Serum miR-23a-3p was positively correlated with SOD and GSH,and negatively correlated with MDA(r=0.428,0.437,-0.439,all P<0.001).Logistic regression analysis showed that high MDA,low SOD,low GSH,high circHOMER1,low miR-23a-3p,high FPG and high HbA1c were the risk factors of progression of DR in type 2 diabetes patients(OR=0.214～3.556,all P<0.05).The area under curve(AUC)of serum circHOMER1 and miR-23a-3p alone and jointhy predicting the progression of DR in type 2 diabetes patients were 0.751,0.797 and 0.903 respectively.The combined prediction was higher than that of serum circHOMER1 and miR-23a-3p alone(Z=3.179,2.335,P=0.002,0.020).Conclusion Serum MDA and circHOMER1 levels are higher in DR patients,while serum SOD,GSH and miR-23a-3p levels are lower.Abnormal expression of circHOMER1 and miR-23a-3p in serum is associated with progression of DR and oxidative stress.Combined detection of circHOMER1 and miR-23a-3p in serum can predict the progression of DR in patients with type 2 diabetes.

BACKGROUND: Salvianolate is a compound mainly composed of salvia magnesium acetate, which is extracted from the Chinese herb Salvia miltiorrhiza . In recent years, salvianolate injection has been widely used in the treatment of cardiovascular diseases, but the mechanism of how it can alleviate cardiotoxicity remains unclear. METHODS: The cardiac injury model was constructed by treatment with doxorubicin (Dox) or azithromycin (Azi) in zebrafish larvae. Heart phenotype, heart rate, and cardiomyocyte apoptosis were observed in the study. RNA-sequencing (RNA-seq) analysis was used to explore the underlying mechanism of salvianolate treatment. Moreover, cardiomyocyte autophagy was assessed by in situ imaging. In addition, the miR-30a/becn1 axis regulation by salvianolate was further investigated. RESULTS: Salvianolate treatment reduced the proportion of pericardial edema, recovered heart rate, and inhibited cardiomyocyte apoptosis in Dox/Azi-administered zebrafish larvae. Mechanistically, salvianolate regulated the lysosomal pathway and promoted autophagic flux in zebrafish cardiomyocytes. The expression level of becn1 was increased in Dox-induced myocardial tissue injury after salvianolate administration; overexpression of becn1 in cardiomyocytes alleviated the Dox/Azi-induced cardiac injury and promoted autophagic flux in cardiomyocytes, while becn1 knockdown blocked the effects of salvianolate. In addition, miR-30a, negatively regulated by salvianolate, partially inhibited the cardiac amelioration of salvianolate by targeting becn1  directly. CONCLUSION This study has proved that salvianolate reduces cardiomyopathy by regulating autophagic flux through the miR-30a/becn1 axis in zebrafish and is a potential drug for adjunctive Dox/Azi therapy.
Animals ; Zebrafish ; MicroRNAs/genetics* ; Autophagy/drug effects* ; Myocytes, Cardiac/metabolism* ; Cardiomyopathies/metabolism* ; Beclin-1/genetics* ; Apoptosis/drug effects* ; Plant Extracts/therapeutic use* ; Doxorubicin