OBJECTIVE: To investigate the effect of moxibustion on central insulin resistance related proteins of the rats suffering from diabetic cognitive decline, and analyze the underlying mechanism of moxibustion for cognition improvement. METHODS: Using the intraperitoneal injection of STZ combined with a high-fat diet, the rat model of diabetic cognitive decline were prepared. Twenty successfully-modeled rats were assigned randomly into a model group and a moxibustion group, 10 rats in each one. Besides, a blank group was set up with 10 rats collected. In the moxibustion group, suspending moxibustion was applied to "Baihui" (GV20), "Shenting" (GV24) and "Dazhui" (GV14) at the same time, 20 min in each intervention, once a day, and 6 interventions were delivered weekly and the duration of treatment was consecutive 4 weeks. The random blood glucose was measured using glucometer, and the learning-memory ability was detected by water maze test. HE staining was used to observe the morphology of neurons in the hippocampal tissue, real-time PCR assay was to detect mRNA expression of insulin receptor substrate 1 (IRS1), phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) in the hippocampal tissue. The Western blot method was employed to detect the protein expression of IRS1, PI3K, AKT, phosphorylated IRS1 (p-IRS1), phosphorylated PI3K (p-PI3K) and phosphorylated AKT (p-AKT) in the hippocampal tissue, and the ratio of p-IRS1/IRS1, p-PI3K/PI3K and p-AKT/AKT was calculated separately. The immunofluorescence intensity of p-IRS1, p-PI3K, and p-AKT was measured using immunofluorescence. RESULTS: Compared with the blank group, the rats of the model group exhibited higher random blood glucose (P<0.001), longer escape latency (P<0.001), severe pathological damage in the hippocampus, lower mRNA expression of IRS1, PI3K, and AKT (P<0.001), reduced ratio of p-IRS1/IRS1, p-PI3K/PI3K and p-AKT/AKT (P<0.001), and declined immunofluorescence intensity of p-IRS1, p-PI3K, and p-AKT in the hippocampal tissue (P<0.001). In comparison with the model group, for the rats of the moxibustion group, the random blood glucose decreased (P<0.05), the escape latency was shortened (P<0.01), the hippocampal pathological damage was attenuated, the mRNA expression of IRS1, PI3K and AKT increased (P<0.01), the ratio of p-IRS1/IRS1, p-PI3K/PI3K and p-AKT/AKT was elevated (P<0.01, P<0.05), and the immunofluorescence intensity of p-IRS1, p-PI3K, and p-AKT in the hippocampal tissue was strengthened (P<0.01, P<0.05). CONCLUSION In diabetic rats experiencing cognitive decline, moxibustion can enhance the learning-memory ability, which may be attributed to modulating the protein expression of IRS1, PI3K, and AKT, and their phosphorylation, activating insulin signal transduction, and reducing central insulin resistance.
Animals ; Moxibustion ; Insulin Resistance ; Rats ; Male ; Insulin Receptor Substrate Proteins/genetics* ; Rats, Sprague-Dawley ; Humans ; Proto-Oncogene Proteins c-akt/genetics* ; Cognitive Dysfunction/genetics* ; Diabetes Mellitus, Experimental/therapy* ; Hippocampus/metabolism* ; Acupuncture Points ; Phosphatidylinositol 3-Kinases/genetics*

Objective To investigate the relationship between initial serum testosterone level and aggressive characteristics,progression and prognosis of metastatic prostate cancer(mPCa).Methods The clinical data of 302 mPCa patients diagnosed with biopsy and auxiliary examinations at the First Affiliated Hospital of Xinjiang Medical University during Aug.2010 and Aug.2022 were retrospectively analyzed,including 148 cases in the serum testosterone low level group(≤12 nmol/L)and 154 in the normal level group(＞12 nmol/L).The independent risk factors associated with aggressive features were analyzed with multifactorial logistic regression,survival was determined with Kaplan-Meier method,the independent risk factors affecting progression and prognosis were identified with multifactorial Cox regression modeling,and the value of initial serum testosterone level in predicting the progression and survival was assessed with receiver operating characteristic(ROC)curve.Results The low level group had a higher proportion of Gleason score ≥8,T stage＞3,initial prostate-specific antigen(PSA)＞200 ng/mL,high tumor load,visceral metastasis,PSA≥ 0.2 ng/mL after 6 months of treatment,and higher body mass index(BMI),but the PSA decline rate after 6 months of treatment was lower than that in the normal level group(P＜0.05).Multifactorial logistic regression showed that initial serum testosterone level＞12 nmol/L was a protective factor for high tumor load(OR=0.137,95％CI:0.070-0.265,P＜0.001),Gleason score ≥8(OR=0.371,95％CI:0.184-0.750,P=0.006)and visceral metastasis(OR=0.337,95％CI:0.175-0.652,P=0.001).The median progression-free survival was shorter in the low level group than in the normal level group(15 months vs.20 months,P＜0.001),and the median overall survival time was also shorter(45 months vs.86 months,P＜0.001).Multifactorial Cox regression analysis showed that Gleason score ≥8,high tumor load,PSA value at 6 months of treatment,and PSA decline rate were independent influencing factors for progression to castration resistant prostate cancer(CRPC)(P＜0.05).The risk of death in patients with high tumor load was 2.510 times higher than that of patients with low tumor load(95％CI:1.555-4.051,P＜0.001).ROC curves showed that initial serum testosterone level could predict the risk of progression to CRPC(AUC:0.645)and survival(AUC:0.595).Conclusion Low level initial serum testosterone is associated with an aggressive profile and poor prognosis of mPCa,and can predict the risk of progression and survival status of mPCa patients.