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 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.

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

Objective To investigate the correlation between serum osteoblastin(OPN)and angiopoietin-like protein 8(ANGPTL8)levels and hepatic fibrosis(HF)after interventional therapy-transcatheter arterial chemoembolisation(TACE)in patients with primary hepatocellular carcinoma(PHC).Methods 166 patients with PHC admitted between March 2021 and June 2023 were selected and divided into 92 cases with HF(observation group)and 74 cases without HF(control group)according to whether or not HF occurred after interventional therapy;enzyme-linked immunosorbent assay(ELISA)was used to determine the serum OPN and ANGPTL8 levels and to analyse the predictive value of the OPN and ANGPTL8 levels on HF.Pearson correlation was used to analyze the correlation between OPN and ANGPTL8 levels and biochemical indexes.The factors influencing the occurrence of HF were analyzed by multi-factor Logistics regression.ROC curve was used to analyze the predictive value of OPN and ANGPTL8 for HF.Results Serum OPN[(74.56±11.56)ng/ml],ANGPTL[(42.78±5.23)ng/ml],ALT[(62.24±9.56)U/L],AST[(42.88±8.23)U/L],HA[(252.98±52.44)ng/L],LN[(152.64±26.45)ng/L],PC Ⅲ[(16.54±3.46)ng/L]and Ⅳ-C[(152.78±21.23)ng/L]in observation group were significantly higher than the control group[(57.89±9.68)ng/ml,(35.46±4.78)ng/ml,(49.46±7.46)U/L,(31.48±7.26)U/L,(192.56±23.88)ng/L,(124.48±11.23)ng/L,(11.26±2.23)ng/L and(126.45±18.56)ng/L].The differences between the two groups were statistically significant(P＜0.05).The AUC of serum OPN,ANGPTL8 and the combination of the two in predicting the occurrence of HF were 0.914,0.920 and 0.978,respectively,and the AUC of OPN combined with ANGPTL8 in predicting the occurrence of HF was higher than the AUC of the two separately(P＜0.05).Conclusion The levels of serum OPN and ANGPTL8 of patients with PHC are closely associated with the occurrence of HF,and the two are HF occurrence influencing factors and can be used as indicators to predict the occurrence of HF.

Background::Hypothermia therapy has been suggested to attenuate myocardial necrosis; however, the clinical implementation as a valid therapeutic strategy has failed, and new approaches are needed to translate into clinical applications. This study aimed to assess the feasibility, safety, and efficacy of a novel selective intracoronary hypothermia (SICH) device in mitigating myocardial reperfusion injury.Methods::This study comprised two phases. The first phase of the SICH was performed in a normal porcine model for 30 minutes ( n = 5) to evaluate its feasibility. The second phase was conducted in a porcine myocardial infarction (MI) model of myocardial ischemia/reperfusion which was performed by balloon occlusion of the left anterior descending coronary artery for 60 minutes and maintained for 42 days. Pigs in the hypothermia group ( n = 8) received hypothermia intervention onset reperfusion for 30 minutes and controls ( n = 8) received no intervention. All animals were followed for 42 days. Cardiac magnetic resonance analysis (five and 42 days post-MI) and a series of biomarkers/histological studies were performed. Results::The average time to lower temperatures to a steady state was 4.8 ± 0.8 s. SICH had no impact on blood pressure or heart rate and was safely performed without complications by using a 3.9 F catheter. Interleukin-6 (IL-6), tumor necrosis factor-α, C-reactive protein (CRP), and brain natriuretic peptide (BNP) were lower at 60 min post perfusion in pigs that underwent SICH as compared with the control group. On day 5 post MI/R, edema, intramyocardial hemorrhage, and microvascular obstruction were reduced in the hypothermia group. On day 42 post MI/R, the infarct size, IL-6, CRP, BNP, and matrix metalloproteinase-9 were reduced, and the ejection fraction was improved in pigs that underwent SICH.Conclusions::The SICH device safely and effectively reduced the infarct size and improved heart function in a pig model of MI/R. These beneficial effects indicate the clinical potential of SICH for treatment of myocardial reperfusion injury.

Objective To explore the diagnostic value of Likert score and EPE grade score based on multiparameter magnetic resonance imaging(mpMRI)for extracapsular extension in prostate cancer(PCa).Methods The MR imaging and histopathology data from 272 PCa patients were analyzed retrospectively.All patients underwent mpMRI examination within 2 months before radical prostatectomy.Two radiologists with over 10 years of experience assessed the mpMRI images according to the Likert score and EPE grade score,respectively,and compared with pathological findings.The consistency between the two radiologists was evaluated by weighted Kappa test.The statistical analysis was performed using MedCalc 20.0 software.The sensitivity,specificity and other indicators were calculated to analyze the optimal cut-off value of Likert score and EPE grade score for diagnosing extracapsular extension in PCa.The area under the curve(AUC)was used to compare the diagnostic performance of the two scoring systems for extracapsular extension in PCa.Results Among 272 PCa patients,there were 45 cases with extracapsular extension and 227 cases without extracapsular extension.The weighted Kappa coefficients were 0.730 and 0.820 for Likert score and EPE grade score,respectively,indicating good consistency.The optimal cut-off values for diagnosing extracapsular extension in PCa were Likert score 3 and EPE grade score 2.The sensitivity and specificity were 68.8%and 77.5%for Likert score 3,and 64.4%and 84.5%for EPE grade score 2,respectively.Both Likert score(AUC=0.780)and EPE grade score(AUC=0.797)had high accuracy in predicting extracapsular extension in PCa,with no significant difference(P>0.05).Conclusion Both Likert score and EPE grade score have good diagnostic performance in detecting extracapsular extension in PCa,which provides important diagnostic basis for clinical staging of PCa.

Objective To explore the effects of sodium oligomannate combined with high-frequency repetitive transcranial magnetic stimulation on the activity of daily living and intelligence level of patients with Alzheimer's disease.Methods A total of 100 patients with Alzheimer's disease admitted to Henan Provincial Staff Hospital from September 2021 to September 2023 were selected as the research subjects.These patients were divided into an observation group and a control group according to the random number table method,with 50 patients in each group.Patients in the control group were given high-frequency repetitive transcranial magnetic stimulation,and patients in the observation group were given sodium oligomannate combined with high-fre-quency repetitive transcranial magnetic stimulation.Enzyme-linked immunosorbent assay was used to detect the levels of amyloid β-protein(Aβ)142,tumor necrosis factor-a(TNF-a)and interleukin-6(IL-6)in patients of the two groups before and after treatment.Chemiluminescence was used to detect the levels of neurotransmitters in patients of the two groups before and after treatment.The mental symptoms of patients in the two groups before and after treatment were evaluated by the behavioral pathology in Alzheimer's disease rating scale,the intelligence level of patients in the two groups before and after treatment was evaluated by the mini-mental state examination(MMSE)scale and the Montreal cognitive assessment(MoCA)scale,the activity of daily living of patients in the two groups before and after treatment was evaluated by Alzheimer's disease cooperative study-activity of daily living(ADCS-ADL),and the quality of life of patients in the two groups before and after treatment was evaluated by the quality of life-Alzheimer's disease scale.Results Before treatment,the two groups showed no significant difference in the levels of Aβ1-42,TNF-α and IL-6(P＞0.05);after treatment,the levels of Aβ1-42,TNF-α and IL-6 in both groups were lower than those before treatment,and the levels of Aβ1-42,TNF-α and IL-6 in the observation group were lower than those in the control group(P＜0.05).Before treatment,there were no statistically significant differences in the levels of 5-hydroxytryptamine(5-HT),acetylcholine(ACh),γ-aminobutyric acid(GABA),and Alzheimer-associated neuronal thread protein(AD7c-NTP)between the two groups(P＞0.05);after treatment,the levels of 5-HT,ACh,and GABA in the two groups were higher than those before treatment,while the AD7c-NTP level was lower than that before treatment(P＜0.05);after treatment,the levels of 5-HT,ACh,and GABA in the observation group were higher than those in the control group,while the AD7c-NTP level was lower than that in the control group(P＜0.05).Before treatment,there were no significant differe-nces in the scores of paranoid and delusional ideas,hallucinations,behavioral disorders,aggressive behaviors,daily rhythm disorders,emotional disorders,anxiety and fear,and the total scores between the two groups(P＞0.05);after treatment,the scores of paranoid and delusional ideas,hallucinations,behavioral disorders,aggressive behaviors,daily rhythm disorders,emotional disorders,anxiety and fear,and the total scores of patients in the two groups were lower than those before treatment,and the scores of paranoid and delusional ideas,hallucinations,behavioral disorders,aggressive behaviors,daily rhythm disorders,emotional disorders,anxiety and fear,and the total scores of patients in the observation group were lower than those in the control group(P＜0.05).Before treatment,there were no significant differences in MMSE,MoCA and ADCS-ADL scores of patients between the two groups(P＞0.05);after treatment,the MMSE,MoCA and ADCS-ADL scores of patientsin the two groups were higher than those before treatment,and the MMSE,MoCA and ADCS-ADL scores of patientsin the observation group were higher than those in the control group(P＜0.05).Before treatment,there were no significant differences in the scores of physiological function,mental function,behavioral ability and interpersonal relationship,and the total scores of patients between the two groups(P＞0.05).After treatment,the scores of physiological function,mental function,behavioral ability and interpersonal relationship,and the total scores of patients in the two groups were higher than those before treatment,and the scores of physiological function,mental function,behavioral ability and interpersonal relationship,and the total scores of patients in the observation group were higher than those in the control group(P＜0.05).Conclusion Sodium oligomannate combined with high-frequency repetitive transcranial magnetic stimulation can improve the inflammatory state of patients with Alzheimer's disease,regulate neurotransmitter levels,alleviate psychiatric symptoms,enhance the intelligence level and the activity of daily living,and increase the quality of life.

Objective To compare the efficacy of modified Chevron osteotomy and Scarf osteotomy in the treatment of moderate to severe hallux valgus.Methods A total of 76 patients with moderate to severe hallux valgus admitted to the Department of Hand and Foot Microsurgery,the First Affiliated Hospital of Xinxiang Medical University from January 2018 to January 2022 were selected as the research subjects.According to the surgical method,the patients were divided into modified Chevron osteotomy group(n=39,41 feet)and Scarf osteotomy group(n=37 feet).The patients in the modified Chevron osteotomy group received modified Chevron osteotomy treatment,the patients in the Scarf osteotomy group received Scarf osteotomy treatment.The hallux valgus angle(HVA),the 1st and 2nd inter metatarsal angle(IMA)and the distal metatarsal articular angle(DMAA)under weight-bearing conditions of patients in the two groups before and 6 months after surgery were recorded.The orthopedic effect of patients was evaluated by using the American Orthopaedic Foot and Ankle Society(AOFAS)score,and the pain level of patients was evaluated by using the visual analogue scale(VAS)score before and 6 months after surgery.The osteotomy healing time and postoperative complications of patients were compared between the two groups.Results There was no statistically significant difference in HVA,IMA,DMAA and AOFAS,VAS scores of patients before and 6 months after surgery between the two groups(P＞0.05).Six months after surgery,the HVA,IMA,and DM A A of patients in the two groups were significantly lower than those before surgery(P＜0.05),the AOFAS score was significantly higher than that before surgery(P＜0.05),and the VAS score was significantly lower than that before surgery(P＜0.05).The osteotomy healing time of patients in the modified Chevron osteotomy group and Scarf osteotomy group was(3.23±0.49)and(3.49±0.69)months,respectively;there was no statistically significant difference in the osteotomy healing time of patients between the two groups(t=-1.874,P＞0.05).The patients in both groups did not experience any vascular or nerve damage during the surgery,the surgical incision and osteotomy healed in one stage,and there were no complications such as incision infection,delayed osteotomy healing,or nonunion.Two patients(4.9％)in the modified Chevron osteotomy group experienced postoperative metastatic metatarsal pain,and the symptoms were significantly improved after treatment with targeted therapies such as blocking and physical therapy.One patient in each of the two groups experienced discomfort caused by loose internal fixation.The recurrence rates of hallux valgus in the modified Chevron osteotomy group and Scarf osteotomy group were 19.5％(8/41)and 2.6％(1/38),respectively;the recurrence rate of hallux valgus in the Scarf osteotomy group was significantly lower than that in the modified Chevron osteotomy group(x2=5.567,P＜0.05).Conclusion The modified Chevron osteotomy and Scarf osteotomy have similar therapeutic effects in correcting deformities,improving ankle function,and alleviating pain in the treatment of moderate to severe hallux valgus,and both surgical methods have few postoperative complications.However,the recurrence rate of hallux valgus after modified Chevron osteotomy is significantly higher than that after Scarf osteotomy.