HIF-1α,a key transcription factor for cellular adaptation to hypoxia,plays a significant role in the devel-opment of sarcopenia.In the context of long-term chronic hypoxia,the expression level of HIF-1α is abnormal.It functions in the development of sarcopenia by regulating multiple signaling pathways,including iron metabolism,mitochondrial function,angiogenesis,remodeling of the extracellular matrix,and protein synthesis and metabolism.Moreover,the overactivation of HIF-1α may lead to dysfunction of satellite cells,thereby reducing the capacity for muscle regeneration and repair.

Objective:To explore the cardioprotective effects of icariin (ICA) against radiation-induced cardiac disease (RICD) in C57BL/6 mice.Methods:A total of 48 female C57BL/6J mice aged 6-8 weeks were randomly divided into three groups: the control group (CON), the irradiation group (IR), and the irradiation combined with icariin group (IR+ ICA), with 16 mice in each group. The IR and IR+ ICA groups received a single cardiac irradiation at a dose of 30 Gy, while the CON group received no radiation treatment. The IR+ ICA group was treated with ICA (70 mg·kg -1·d -1) two weeks before irradiation until the end of the experiment through intragastric administration. In contrast, the CON and IR groups were treated with an equal volume of vehicle solution (0.5% sodium carboxymethyl cellulose, NaCMC) via intragastric administration. The mice′s mental status, food intake, body weight, and survival rates were monitored during the experiment. At two weeks post-irradiation, the venous blood of the mice was collected and serum was separated for the enzyme-linked immunosorbent assays (ELISA) of creatine kinase MB isoenzyme (CK-MB) and cardiac troponin T (cTnT/TNNT2). At 12 weeks post-irradiation, the cardiac function of the mice was assessed using echocardiography. After the mice were euthanized under anesthesia, the histopathological changes and fibrosis degree of their myocardial tissues were assessed using hematoxylin and eosin (HE) and Masson′s trichrome staining, followed by the calculation of collagen volume fraction (CVF). The differential gene expression of brain natriuretic peptide (BNP), transforming growth factor-β (TGF-β), and interleukin-6 (IL-6) in the cardiac tissues of the mice was detected using real-time reverse transcription-polymerase chain reaction (RT-PCR). Apoptosis-related proteins and proteins associated with the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway were determined using Western blotting. The survival curves of the mice were plotted using Kaplan-Meier, and the survival differences of the mice among various groups were compared using the log-rank test. Results:After irradiation, the mice in the IR group showed lethargy, as well as decreased food intake and activity, while these symptoms in the IR+ ICA group were significantly alleviated. At two weeks post-irradiation, the CK-MB and cTnT levels of the IR group were significantly elevated compared with the CON group ( t = 5.28, 8.89, P < 0.01). At 12 weeks post-irradiation, the mice in the IR group exhibited significantly decreased body weight ( t = 2.47, P < 0.05) and decreased survival rates ( HR = 8.25, 95% CI: 1.157-58.770, P < 0.05) compared with the CON group. Echocardiography revealed that the IR group featured decreased left ventricular ejection fraction (EF), decreased fractional shortening (FS), and increased left ventricular end-diastolic diameter (LVDD) compared with the CON group ( t = 7.02, 4.45, P < 0.05). Histopathological examination revealed that the IR group suffered from cardiomyocyte edema, disordered arrangement, and increased fibrosis, with an elevated CVF. The IR group exhibited significantly upregulated gene expression of BNP, TGF-β, and IL-6 in cardiac tissues compared with the CON group ( t = 4.23, 6.39, 4.61, P < 0.05). After-irradiation, the IR group exhibited upregulated apoptosis-related proteins Cleaved Caspase-3 and Bax ( t = 6.29, 9.54, P < 0.05), decreased Bcl-2 expression ( t = 8.20, P < 0.001), and decreased phosphorylation levels of PI3K and Akt ( t = 6.47, 3.42, P < 0.001). The symptoms of the mice were partially ameliorated after treatment with ICA. Specifically, the mice in the IR+ ICA group exhibited higher body weight ( t = 5.13, P < 0.001) and significantly higher survival rates ( HR = 0.121, 95% CI: 0.017-0.864, P < 0.05) than the IR group. Compared to the IR group, the IR+ ICA group showed elevated cardiac function indicators EF and FS( t = 3.23, 3.05, P < 0.05), and reduced LVDD ( t = 3.02, P < 0.05). The histopathological analysis revealed mitigated edema and disordered arrangement of cardiomyocytes in the IR+ ICA group. Furthermore, the IR+ ICA group exhibited significantly lower BNP, TGF-β, and IL-6 expression levels than the IR group ( t = 2.83, 4.15, 2.96, P < 0.05). The expression of apoptosis-related proteins Cleaved Caspase-3 and Bax was lower ( t = 3.23, 3.24, P < 0.05), Bcl-2 expression was higher ( t = 5.92, P < 0.001), and restored phosphorylation levels of PI3K and Akt ( t = 2.89, 8.35, P < 0.001). Conclusions:Icariin has protective effects against the RICD. It alleviates cardiomyocyte apoptosis possibly by upregulating the phosphorylation levels of PI3K and Akt.

Objective:To explore the cardioprotective effects of icariin (ICA) against radiation-induced cardiac disease (RICD) in C57BL/6 mice.Methods:A total of 48 female C57BL/6J mice aged 6-8 weeks were randomly divided into three groups: the control group (CON), the irradiation group (IR), and the irradiation combined with icariin group (IR+ ICA), with 16 mice in each group. The IR and IR+ ICA groups received a single cardiac irradiation at a dose of 30 Gy, while the CON group received no radiation treatment. The IR+ ICA group was treated with ICA (70 mg·kg -1·d -1) two weeks before irradiation until the end of the experiment through intragastric administration. In contrast, the CON and IR groups were treated with an equal volume of vehicle solution (0.5% sodium carboxymethyl cellulose, NaCMC) via intragastric administration. The mice′s mental status, food intake, body weight, and survival rates were monitored during the experiment. At two weeks post-irradiation, the venous blood of the mice was collected and serum was separated for the enzyme-linked immunosorbent assays (ELISA) of creatine kinase MB isoenzyme (CK-MB) and cardiac troponin T (cTnT/TNNT2). At 12 weeks post-irradiation, the cardiac function of the mice was assessed using echocardiography. After the mice were euthanized under anesthesia, the histopathological changes and fibrosis degree of their myocardial tissues were assessed using hematoxylin and eosin (HE) and Masson′s trichrome staining, followed by the calculation of collagen volume fraction (CVF). The differential gene expression of brain natriuretic peptide (BNP), transforming growth factor-β (TGF-β), and interleukin-6 (IL-6) in the cardiac tissues of the mice was detected using real-time reverse transcription-polymerase chain reaction (RT-PCR). Apoptosis-related proteins and proteins associated with the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway were determined using Western blotting. The survival curves of the mice were plotted using Kaplan-Meier, and the survival differences of the mice among various groups were compared using the log-rank test. Results:After irradiation, the mice in the IR group showed lethargy, as well as decreased food intake and activity, while these symptoms in the IR+ ICA group were significantly alleviated. At two weeks post-irradiation, the CK-MB and cTnT levels of the IR group were significantly elevated compared with the CON group ( t = 5.28, 8.89, P < 0.01). At 12 weeks post-irradiation, the mice in the IR group exhibited significantly decreased body weight ( t = 2.47, P < 0.05) and decreased survival rates ( HR = 8.25, 95% CI: 1.157-58.770, P < 0.05) compared with the CON group. Echocardiography revealed that the IR group featured decreased left ventricular ejection fraction (EF), decreased fractional shortening (FS), and increased left ventricular end-diastolic diameter (LVDD) compared with the CON group ( t = 7.02, 4.45, P < 0.05). Histopathological examination revealed that the IR group suffered from cardiomyocyte edema, disordered arrangement, and increased fibrosis, with an elevated CVF. The IR group exhibited significantly upregulated gene expression of BNP, TGF-β, and IL-6 in cardiac tissues compared with the CON group ( t = 4.23, 6.39, 4.61, P < 0.05). After-irradiation, the IR group exhibited upregulated apoptosis-related proteins Cleaved Caspase-3 and Bax ( t = 6.29, 9.54, P < 0.05), decreased Bcl-2 expression ( t = 8.20, P < 0.001), and decreased phosphorylation levels of PI3K and Akt ( t = 6.47, 3.42, P < 0.001). The symptoms of the mice were partially ameliorated after treatment with ICA. Specifically, the mice in the IR+ ICA group exhibited higher body weight ( t = 5.13, P < 0.001) and significantly higher survival rates ( HR = 0.121, 95% CI: 0.017-0.864, P < 0.05) than the IR group. Compared to the IR group, the IR+ ICA group showed elevated cardiac function indicators EF and FS( t = 3.23, 3.05, P < 0.05), and reduced LVDD ( t = 3.02, P < 0.05). The histopathological analysis revealed mitigated edema and disordered arrangement of cardiomyocytes in the IR+ ICA group. Furthermore, the IR+ ICA group exhibited significantly lower BNP, TGF-β, and IL-6 expression levels than the IR group ( t = 2.83, 4.15, 2.96, P < 0.05). The expression of apoptosis-related proteins Cleaved Caspase-3 and Bax was lower ( t = 3.23, 3.24, P < 0.05), Bcl-2 expression was higher ( t = 5.92, P < 0.001), and restored phosphorylation levels of PI3K and Akt ( t = 2.89, 8.35, P < 0.001). Conclusions:Icariin has protective effects against the RICD. It alleviates cardiomyocyte apoptosis possibly by upregulating the phosphorylation levels of PI3K and Akt.

AIM: To explore the effects of inflammatory conditions on the pharmacokinetics of methotrexate (MTX) and its related mechanisms. METHODS: The model of adjuvant induced arthritis (AIA) was established. The expression of organic anion transporter 3 (OAT3) in kidney was detected by immunohistochemistry, Western blotting and QPCR. The plasma concentration of MTX was detected by LC-MS/MS, and the pharmacokinetics of MTX after different administration time were compared by isolated rat kidney perfusion, kidney slices, in vitro cell uptake and transport experiments. RESULTS: The expression of OAT3 was significantly increased in the kidneys of AIA rats by immunohistochemistry, Western blotting and QPCR. At the same time, the concentration of MTX was detected by the optimized LC-MS/MS. The results showed that the uptake of MTX in the kidney slices of AIA rats was significantly increased, and Pro could reduce the excretion of MTX by inhibiting OAT3. Furthermore, it was demonstrated in vitro that inflammatory pathology can promote renal excretion of MTX by increasing the expression and functional activity of OAT3.CONCLUSION: Under inflammatory pathological conditions, it can increase the expression of OAT3 in the kidney, enhance its functional activity, accelerate the uptake of MTX by the kidney, and promote the excretion of MTX.

Objective:To investigate the changes of advanced glycosylation end product(AGEs)/sodium-glucose cotransporter-1(SGLT-1) in intestinal and renal tissues and intestinal flora of mice with diabetes kidney disease.Methods:Twenty KKay mice were divided into diabetic group(DM group, n=10) and diabetic kidney disease group(DKD group, n=10). The concentrations of serum AGEs, lipopolysaccharide(LPS), tumor necrosis factor-α(TNF-α), and intereukin-6(IL-6) were measured. Western blot technique was used to detect the protein expression of AGEs and SGLT-1 in kidney and intestinal tissue, and high-throughput sequencing was used to analyze the difference of intestinal flora. Results:The levels of inflammatory markers TNF-α, IL-6, and serum endotoxin in DKD group were significantly higher than those in DM group( P<0.05). The contents of AGEs in serum and intestine and kidney were increased, and the contents of SGLT-1 in intestine and kidney were increased( P<0.05). Metastats test showed that the abundance of Verrucomicrobia decreased and the abundance of Proteobacteria increased in DKD group( P<0.05). G - bacteria such as Aeromonas, Enterobacter, Morgan, Klebsiella, Serratia, and Burkholderia were relatively dominant, and the abundance of Akkermansia was significantly lower than that in DM group( P<0.05). Conclusion:The increase of AGEs in intestinal tract of DKD mice may induce intestinal dysbacteriosis, especially the increase of Proteobacteria, the decrease of Verrucosa and Wilhelm Ackermann, and the leakage of G-bacteria into the blood to produce intestinal endotoxemia and cause inflammatory reaction, this may be an important factor in the development of DKD. SGLT-1 is elevated in intestinal tissue, which may be involved in the development of DKD.

Objective: To evaluate ten year changes in deciduous teeth health and oral health behavior aged 5 year old children in Hainan province (during the year of 2005-2015), to provide basis for oral health promotion among 5 year old children in Hainan province. Methods: Through the comparison and analysis of the third and the fourth national oral health epidemiology survey,changes of dental caries prevalence rate, dietary habit, oral health behavior, and health seeking behavior were analyzed. Results: The prevalence of dental caries in 2005 was 76.1%, 2015 was 82.3% which had significant difference(χ2=6.23，P<0.05), the percentage of consuming sugary food and sweet drinks every day in 2005 was 13.4% and 6.1%, which increased to 30.0% and 7.4% respectively in 2015. The percentage of drinking milk and yoghurt with sugar was 47.6%, which decreased 36.5% in 2015 (χ2=12.76，P<0.05), the percentage of consuming sugary food and sweet drinks before going to bed in 2005 was17.8%, which decreased to 13.3% in 2015 (χ2=32.27，P<0.05). The percentage of brushing the teeth two or more times a day was 16.9%, which increased to 24.2% in 2015(χ2=20.50，P<0.05). The percentage of using fluoridated toothpaste decreased from 31.7% (2005) to 7.4% (2015) (χ2=229.13，P<0.05). No need to treatment for baby teeth and afraid of pain among children were the main reason for no health-seeking among parents which children of dental health problems,which deffered significantly between 2005 and 2015(χ2=6.05，9.34，P<0.05). Conclusion Children’s oral health behavior improved, while eating habits fluoridated toothpaste usage and health seeking behavior remain poor.Health education on child oral health should be strengthened.

Objective:To compare the efficacy of superior trunk block (STB) versus interscalene brachial plexus block (ISB) in the patients undergoing arthroscopic shoulder surgery with general anesthesia.Methods:Sixty American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients, aged 18-70 yr, undergoing elective arthroscopic shoulder surgery, were divided into 2 groups ( n=30 each) using a random number table method: ISB plus general anesthesia group (group IG) and STB plus general anesthesia group (group SG). In group IG and group SG, 0.375% ropiacaine 15 ml was injected around C 5-C 6 nerve roots and superior trunk, respectively.SpO 2, diaphragmatic excursion, diaphragmatic paralysis, dyspnea and Horner syndrome were recorded at 30 min after injection.General anesthesia with tracheal intubation was then performed in all the patients, and remifentanil or phenylephrine was used to maintain hemodynamics stable.The use of remifentanil was recorded at the end of operation, the visual analogue scale score was performed after patients regained consciousness, and the duration of sensory and motor blockade was recorded at 24 h after operation. Results:Compared with group IG, the decrease in the amplitude of SpO 2 was significantly decreased, and diaphragmatic excursion was increased, the incidence and degree of diaphragmatic paralysis were decreased, duration of sensory blockade was prolonged, the incidence of Horner syndrome and dyspnea was decreased ( P<0.05), and no significant change was found in the requirement for remifentanil, postoperative visual analogue scale score, and duration of motor blockade in group SG ( P>0.05). Conclusion:STB not only provides better perioperative analgesia, but also reduces the incidence of diaphragmatic paralysis when compared with ISB in the patients undergoing arthroscopic shoulder surgery with general anesthesia.

The key factor of chemotherapy for brain disorders is to penetrate brain blood barrier(BBB). Receptor mediated en-docytosis is one of the mechanisms for drug carriers to cross the BBB. Angiopep-2(ANG)can specifically bind to low density lipopro-tein receptor-related proteins 1(LRP-1)overexpressed on BBB and glioma cells,thus exhibits a higher LRP-mediated BBB penetra-tion capability. Its targeting efficiency is higher than that of other targeting molecules such as transferrin and(TF)lactoferrin(LF). This paper introduces the structure and function of ANG,and its application in brain targeting delivery systems,in order to provide references for research and development of brain targeting preparations and guidance for therapy of brain diseases.

Aim To investigate the protective effect of noble dendrobium polysaccharides ( NDP ) on lipopo-lysaccharide ( LPS)-induced neuron injuries in newborn rat cerebral cortex glial cells and neuron mixed cul-tures.Methods The primary cultures of newborn rat cortical neurons and glial cells were established and the existence of the neurons , astrocytes and microglia was verified respectively .NDP was given to LPS-induced mixed cultures , the mRNA levels of IL-1β, TNF-αand COX-2 were assayed by real time PCR .Results NDP reduced the glial cell activation and neuron dam-age after it was given to LPS-induced mixed cultures . The mRNA levels of IL-1β, TNF-α, COX-2 were re-duced .Conclusion NDP protects against LPS-in-duced neuron-inflammation in neurons and glial cells cultures.

Objective:To investigate the clinicopathological factors predictive of lymph node metastasis (LNM) in undifferentiat-ed early gastric cancer (EGC) and to expand the possibility of endoscopic therapy for treating undifferentiated EGC.Methods:The re-searchers collected the data of 90 undifferentiated EGC patients who had undergone surgery at the Xingtai People's Hospital, Xingtai, China. The relationship between LNM and clinicopathological factors was retrospectively analyzed using univariate and multivariate lo-gistic regression analyses. Results:Univariate analysis showed that tumor size, lymphatic vessel involvement (LVI), and cancer inva-sion depth were the significant and independent risk factors for LNM. The LNM rate was 57.1%in patients with the three clinicopatho-logical risk factors. LNM was not found in patients without the three risk factors. Conclusion:Tumor size, LVI, and invasion depth are independently associated with the presence of LNM in undifferentiated EGC. Endoscopic therapy can be used to treat the patients with-out risk factors.