This paper reviewed the studies about the adult female's bone health management in recent 10 years, and summarized the im-plementation and the effects of the methods, such as health education, nutritional intervention, exercise intervention and comprehensive in-tervention.

Objective To investigate the effects of short term insulin pump intensive therapy on flow-mediated dilation (FMD) in type 2 diabetes mellitus (T2DM) patients with and without vascular complications. Methods Seventy-six patients with T2DM (T2DM group) were divided into 2 subgroups: T2DM1 subgroup (28 patients with vascular complications) and T2DM2 subgroup (48 patients without vascular complications). Meanwhile, 30 healthy cases were selected as NC group. All research subjects accepted high-frequency ultrasound detection on brachial artery for FMD. After insulin pump intensive therapy,FMD in T2DM group was reexamined, fasting insulin was detected and HOMA-IR was calculated. Results Compared with that in NC group, FMD in T2DM group was significantly lower(P＜ 0.01). However, glycosylated hemoglobin (HbA1c ), fasting plasma glucose (FPG ),H0MA-IR and blood fat were significantly higher (P＜0.01 or ＜0.05). Correlation analysis showed that FMD had negative correlation with HbA1c, FPG, HOMA-IR, triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C)(P＜0.01),and had positive correlation with high-density lipoprotein cholesterol (HDL-C). After 2 weeks of insulin pump therapy, the improvement of FMD between the two groups was different. FMD in T2DM1 subgroup increased from (4.25 ± 1.96)% to (4.96 ± 1.36)%(P＞0.05), and FMD in T2DM2 subgroup increased from (4.02 ± 2.35)% to (7.56 ± 2.34)%(P＜ 0.01). Conclusion Insulin pump intensive therapy can evidently improve FMD in T2DM patients without vascular complications.

Objective To evaluate the reliability of mannitol for fluid responsiveness test in the patients undergoing intracranial surgery.Methods Sixty-two ASA physical status Ⅰ or Ⅱ patients,aged 18-64 yr,with body mass index of 18-25 kg/m2,scheduled for elective intracranial surgery,were enrolled in the study.The patients were mechanically ventilated after induction of anesthesia.The radial artery and central vein were cannulated,and FloTracTM/VigileoTM system was connected for stroke volume variation monitoring.Before infusion of mannitol,effective circulating blood volume was confirmed according to stroke volume variation.20％ mannitol 250 ml was infused over 20 min starting from onset of craniotomy.The fluid responsiveness test was recorded at the end of mannitol infusion.Results The sensitivity of fluid responsiveness test was 43％,and the specificity of fluid responsiveness test was 44％.Conclusion Mannitol can not be used for fluid responsiveness test in the patients undergoing intracranial surgery.

Objective:To observe the effect of combining transcranial direct current stimulation (tDCS) with functional electrical stimulation-assisted cycling (FES-cycling) on lower limb motor function early after a stroke.Methods:Thirty-seven survivors of a recent stroke were divided into a tDCS treatment group ( n=18) and a pseudo-stimulation group ( n=19). While receiving routine rehabilitation training and clinical drug treatment, the tDCS treatment group also cycled in response to functional electrical stimulation while simultaneously receiving tDCS anode stimulation of the motor cortex M1 area. The pseudo-stimulation group followed the same protocol but with the tDCS stimulation inactivated. Both groups were treated for 20min daily, 5 days weekly for 4 weeks. Before and after the 4 weeks of treatment, the lower limb motor function, walking ability and ability in the activities of daily living of both groups were evaluated using the Fugl-Meyer assessment scale for the lower extremities (FMA-LE), the timed up and go test (TUGT) and the modified Barthel index (MBI) respectively. Transcranial magnetic stimulation was used to detect each subject′s cerebral cortex motor threshold (CMT) , cortical latency (CL) and central motor conduction time (CMCT) as well as the amplitude (Amp) of the motor evoked potential of the lower limb primary motor cortex (M1 area). Results:After 4 weeks of treatment, the average FMA-LE and MBI scores and TUGT times of the two groups had improved significantly compared with those before treatment. The average FMA-LE score and TUGT time of the tDCS group were significantly better than those of the pseudo-stimulation group. The average CMT, CL and CMCT in both groups were significantly lower than those before the intervention, while the average Amp had increased significantly, but there were significant differences in the average CMT, Amp, CL and CMCT between the two groups after the 4 weeks of treatment.Conclusions:Transcranial direct current stimulation combined with cycling assisted by functional electrical stimulation can effectively stimulate excitability in the motor cortex soon after a stroke. That should promote the recovery of nerve activity and lower limb function.

Cerebrovascular disease is a common disease that seriously endangers the health of Chinese people. White matter hyperintensities (WMHs) are the most common in elderly patients. Intravenous thrombolysis is currently the most effective drug treatment for acute ischemic stroke. Hemorrhagic transformation (HT) is the most common serious complication after intravenous thrombolysis in patients with acute ischemic stroke. The destruction of blood-brain barrier in patients of WMHs can increase the risk of HT after intravenous thrombolysis. Matrix metalloproteinases and S100B jointly participate in the destruction process of blood-brain barrier in WMHs and HT after intravenous thrombolysis. At present, the pathogenesis of WHM and HT is not completely clear, and whether mild and moderate WMHs will aggravate HT is still controversial. Nevertheless, WMHs are still the independent risk factor for HT.

OBJECTIVE： To study the hypoglycemic effect and mechanism of Zicui yin on type Ⅱ diabetic rats， and to provide theoretic basis for clinical application. METHODS： Eighty male rats were fed with high fat/sugar diet for 4 weeks， and then given intraperitoneal injected with streptozotocin （35 mg/kg） to induce type 2 diabetic model. Other 10 rats were included in normal group. Model rats were randomly divided into metformin group （positive control， 0.2 g/kg）， model group （constant volume of distilled water）， Zicui yin high-dose， medium-dose， low-dose groups （14.0， 7.0， 3.5 g/kg）， with 10 rats in each group. After 2 weeks of continuous intragastic administration， the fasting blood glucose of rats in each group was measured by automatic blood glucose meter. The serum insulin level was determined by ELISA. mRNA expression of JNK， Akt and IRS-1 were detected by RT-PCR； The phosphorylation of JNK， Akt and IRS-1 proteins in the pancreatic tissue of rats in each group was detected by Western blot method. RESULTS： Compared with normal group， the fasting blood glucose， mRNA expression of JNK， The phosphorylation of JNK and IRS-1 proteins in the pancreatic tissue of the model group were significantly increased （P＜0.05 or P＜0.01）， while the serum insulin content， mRNA expression of Akt and IRS-1， the phosphorylation of Akt protein were significantly decreased （P＜0.01）. Compared with model group， the fasting blood glucose of rats in metformin group and Zicui yin high-dose and middle-dose groups decreased significantly （P＜0.05）， the serum insulin content of rats in both metformin group and Zicui yin high-dose group increased significantly （P＜0.01）， and mRNA expression of JNK in pancreatic tissue of rats in metformin group and Zicui yin groups decreased significantly （P＜0.01）， while mRNA expression of Akt and IRS-1 increased significantly （P＜0.01）. The phosphorylation of JNK and IRS-1 proteins in metformin group and Zicui yin high-dose group decreased significantly （P＜0.01）， while the phosphorylation of        Akt protein were increased significantly （P＜0.01）. CONCLUSIONS： Zicui yin can significantly reduce blood glucose level， the mechanism of which may be related to decreasing the phosphorylation of JNK and IRS-1 proteins and increasing the phosphorylation of Akt proteins in pancreatic islets.

OBJECTIVE：To investigate the protective effect an d possible m echanism of Shenqi zhilong decoction （SZD） combined with Tripterygium polyglycoside tablets （TPT）on membranous nephropathy （MN）model rats. METHODS ：MN rat model was established by subcutaneous and caudal vein injecting cationic bovine serum albumin + incomplete Freund adjuvant emulsion for 6 weeks. At the 3rd week of modeling ，model rats were randomly divided into model control group ，SZD low-dose and high-dose groups （4，8 g/kg，by total crude drugs ），TPT group （9 mg/kg），low-dose and high-dose of SZD+TPT groups （same dose as single group ），with 10 rats in each group according to 24 h UTP and weight. Another 10 rats withoutmodeling were taken as blank control group. Blank control group was given equal amount of water intragastrically administration groups were given relevant medicine intragastrically，once a day ，for consecutive 4 weeks. The 24 h UTP of rats were detected one day before the last administration；1 h after the la st administration ，blood routine 中indexes（WBC，RBC，PLT），liver func tion indexes （TP，ALB，AST，ALT），blood lipid indexes （TC，TG，HDL-C，LDL-C）， the contents of glucose （GLU），urea nitrogen （BUN）and serum creatinine （Scr）were detected in each group. Uranyl acetate-lead citrate staining was used to observe ultrastructural changes of renal tissue. Immunohistochemical method was used to detect the protein expression of TGF-β1 and HPA- 1 in renal tissue. RESULTS ：Compared with blank control group ，in the model control group，the glomerular podocytes were widely fused or disappeared ，microvilli were formed ，basement membrane was heavily thickened，a large number of electron dense substance was deposited under the epithelium ，TGF-β1 and HPA- 1 positive cells were significantly increased ；24 h UTP ，PLT，the contents of TC ，TG and HDL-C ，the percentage of TGF-β1 and HPA- 1 positive cells were increased significantly ，while RBC ，the contents of TP and ALB were decreased significantly （P＜0.05 or P＜0.01）. Compared with model control group ，above ultrastructural changes of administration groups were improved to different extents ，and TGF-β1 and HPA- 1 positive cells were decreased. The 24 h UTP ，the percentage of TGF-β1 positive cells （except for SZD low-dose group），WBC（except for SZD alone groups and combination groups ），PLT and TC content （except for TPT group ），TG content （except for SZD low-dose alone and its combination group ），the percentage of HPA- 1 positive cells were decreased significantly ； the percentage of TGF-β1 positive cells in SZD high-dose+TPT group as well as the percentage of HPA- 1 positive cells in SZD+TPT groups were significantly lower than TPT group. RBC and GLU content （except for SZD low-dose group and TPT group ），TP and ALB content （except for SZD low-dose group ）were increased significantly ，while the content of GLU in SZD high-dose+TPT group was significantly higher than TPT tablets group （P＜0.05 or P＜0.01）. CONCLUSIONS ：SZD combined with TPT can relieve myelosuppression caused by TPT ，reduce proteinuria of MN model rats and improve pathological damage of renal tissue in rats. Its mechanism is related to the down-regulation of protein expression of TGF-β1 and HPA- 1，and the reduction of TC and TG content in the blood.

Osteoporosis （OP） is a skeletal metabolic disease characterized by bone loss and destruction of bone microstructure. Changes in estrogen levels are not the only pathogenic factors for the occurrence and development of OP. MicroRNA （miRNA） plays an important regulatory role in cells. The complementary sequences of miRNA and targeted mRNA combine to inhibit the expression of targeted mRNA through post-transcriptional regulation， forming a complex regulatory network. Research suggests that miRNA is closely related to the occurrence and development of various diseases， including inflammatory diseases， metabolic diseases， and cancer. Targeted mRNA participates in post-transcriptional gene expression regulation in OP， mainly regulating the balance among bone construction， bone resorption， and osteoblast differentiation. Therefore， miRNA-based gene therapy is a rapidly developing disease treatment strategy. Traditional Chinese medicine can improve bone metabolism by intervening in miRNA differential expression to target and regulate osteogenic/osteoclast differentiation. This article summarized the targeting effects of miRNAs in physiological and developmental processes such as bone cell proliferation， differentiation， survival， and apoptosis， reviewed and classified their mechanisms of action and targets， and sorted out the current treatment methods of traditional Chinese medicine for preventing and treating OP and drugs that exert bone protective functions through miRNAs. This review is expected to provide theoretical reference and research guidance for future research on OP treatment by regulating miRNA.

Activating humoral and cellular immunity in lymph nodes (LNs) of nanoparticle-based vaccines is critical to controlling tumors. However, how the physical properties of nanovaccine carriers orchestrate antigen capture, lymphatic delivery, antigen presentation and immune response in LNs is largely unclear. Here, we manufactured gold nanoparticles (AuNPs) with the same size but different shapes (cages, rods, and stars), and loaded tumor antigen as nanovaccines to explore their disparate characters on above four areas. Results revealed that star-shaped AuNPs captured and retained more repetitive antigen epitopes. On lymphatic delivery, both rods and star-shaped nanovaccines mainly drain into the LN follicles region while cage-shaped showed stronger paracortex retention. A surprising finding is that the star-shaped nanovaccines elicited potent humoral immunity, which is mediated by CD4⁺ T helper cell and follicle B cell cooperation significantly preventing tumor growth in the prophylactic study. Interestingly, cage-shaped nanovaccines preferentially presented peptide-MHC I complexes to evoke robust CD8⁺ T cell immunity and showed the strongest therapeutic efficacy when combined with the PD-1 checkpoint inhibitor in established tumor study. These results highlight the importance of nanoparticle shape on antigen delivery and presentation for immune response in LNs, and our findings support the notion that different design strategies are required for prophylactic and therapeutic vaccines.

OBJECTIVE To investigate the effects and mechanism of Danshen decoction influencing platelet physiological characteristics and function in hyperlipidemia model rats based on platelet membrane glycoprotein 4 （CD36）/phosphatidylinositol 3- kinase （PI3K）/protein kinase B （Akt） signaling pathway. METHODS The hyperlipidemia model rats were induced by feeding high- fat diet， and then randomly divided into model group， simvastatin group （0.004 g/kg）， Danshen decoction high-dose and low-dose groups （3.6， 0.9 g/kg）， and blank group （fed with basic feed）， with 10 rats in each group. Rats in each administration group were intragastrically administered with corresponding drugs every day， and the other groups were intragastrically administered with equal volume of normal saline for 4 weeks. After the last administration， the contents of blood lipid biochemical indexes [total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）]， whole blood viscosity， plasma viscosity and fibrinogen （FIB）content in plasma， platelet-related parameters [platelet count （PLT）， platelet distribution width （PDW） and mean plateletvolume （MPV）] were detected. The levels of plateletphysiological characteristics and function-related factors [von Willebrand factor （vWF）， fibronectin （Fn）， phospholipase A2（PLA2）， thromboxane B2 （TXB2）， 6-keto-prostaglandin F1α （6-keto-PGF1α）， thromboxane A2 （TXA2）， prostaglandin I2 （PGI2）， cyclic adenosine monophosphate （cAMP）， cyclic guanosine monophosphate （cGMP）， β-thromboglobulin （β-TG）]， platelet aggregation rate （maximum aggregation rate， 60 s aggregation rate， 180 s aggregation rate） and fibrinolytic system-related factors [tissue plasminogen activator （t-PA）， plasminogen activator inhibitor 1 （PAI-1）] and the expressions of CD36/PI3K/Akt signaling pathway-related proteins [CD36， focal adhesion kinase （FAK）， phosphatidylinositol 4-phosphate 5-kinase （PIP5K）， PI3K， phosphorylated Akt （p-Akt）， p-Akt1/2/3] in platelet were all determined. RESULTS Compared with blank group， the contents of TC， TG and LDL-C in plasma， whole blood viscosity， plasma viscosity， the plasma levels of FIB， PLT， MPV， vWF， Fn， PLA2， TXB2， TXA2， cGMP and β-TG， maximum platelet aggregation rate， 60 s aggregation rate， the expressions of PAI-1 in plasma， protein expressions of CD36， FAK， PIP5K， PI3K， p-Akt and p-Akt1/2/3 were significantly increased in the model group （P＜0.05）. The content of HDL-C and the levels of 6-keto-PGF1α， PGI2 and t-PA were significantly decreased （P＜0.05）. After the intervention of Danshen decoction， most of the above indexes were significantly reversed （P＜0.05）. CONCLUSIONS Danshen decoction can improve the physiological characteristics and function of platelets in hyperlipidemia model rats， and its mechanism may be related to the down-regulation of CD36/PI3K/Akt signaling pathway activity and the reduction of platelet activation.