Objective To explore the mechanism underlying the effects of gypenosides (GP) against photodamage. Methods Eighty BALB/c mice were equally divided into 8 groups, i.e., blank control group (untreated), UVB model group (irradiated with UVB), GP I group (irradiated with UVB before topical application of GP), GPⅡ group (irradiated with UVB followed by topical application of GP), VitE I group (irradiated with UVB after topical application of Vitamine E cream), VitE Ⅱ group (irradiated with UVB followed by topical application of Vitamine E cream), Vehicle group Ⅰ (irradiated with UVB after application of the drug vehicle),and Vehicle group Ⅱ (irradiated with UVB before application of the drug vehicle). UVB irradiation was performed once every other day for 14 days. Mice were sacrificed after the last irradiation and skin specimens were obtained from the irradiated sites, and the levels of p53 and p21 protein were measured by Western blot in the specimens. Results The expression level of p53 protein was significantly lower in the blank control group than in the UVB model group (0.11 ± 0.08 vs. 0.22 ± 0.12) and GP Ⅰ group (0.44 ± 0.23, P < 0.01),in the blank control group and UVB model group than in the GP Ⅱ group (0.48 ± 0.24, P < 0.01, 0.05). VitE Ⅰ group (0.49 ± 0.29) and VitE II group (0.50 ± 0.27) were similar to the GP groups in the expression of p53 protein. No statistical difference was observed in the expression of p21 protein between the eight groups. Conclusion The upregulation of p53 protein expression in epidermal cells may be related to the mechanisms underlying the protective effect of 1.5% GP cream against photodamage.

Objective To observe the effects of gypenosides (GP) on nuclear factor κB (NF-κB) and p38 mitogen activated protein kinase (p38MAPK) signaling pathways in photodamaged skin of mice,and to explore the mechanisms underlying the protective effects of GP against photodamage.Methods Eighty Balb/C female mice were randomly divided into 8 groups: blank control group receiving no treatment,ultraviolet B (UVB) model group receiving UVB irradiation for 60 seconds,GP group Ⅰ receiving topical GP treatment followed by UVB irradiation,GP group Ⅱ receiving UVB irradiation followed by topical GP treatment,VitE group Ⅰ receiving topical VitE treatment followed by UVB irradiation,VitE group Ⅱ receiving UVB irradiation followed by topical VitE treatment,matrix group Ⅰ receiving topical matrix treatment followed by UVB irradiation,matrix group Ⅱ receiving UVB irradiation followed by topical matrix treatment.UVB irradiation lasted 60 seconds at one time,and was given once every other day for 7 times to establish a skin model of photodamage.The interval between irradiation and topical treatment was 30 minutes in all the groups except the control group and UVB model group.After the last treatment,mice were sacrificed.Western blot was performed to measure the protein expressions of inhibitor of NF-κB(IκB),inhibitor of NF-κB kinase (IKK),p38MAPK as well as phosphorylated p38MAPK (pp38) in skin tissue from the mice.Results No expressions of IκB or IKK were observed in the blank control group.The expression level of IκB was 0.40 ± 0.07 in UVB model group,significantly lower than that in GP group Ⅰ (1.63 ± 0.85,P ＜ 0.05) and GP group Ⅱ (0.90 ± 0.40,P ＜ 0.05),whereas the level of IKK protein was higher in UVB model group than in the GP group Ⅰ and Ⅱ (2.01 ± 1.75vs.0.23 ± 0.12 and 0.45 ± 0.29,both P ＜ 0.05).No significant difference was observed in the expression of IκB or IKK proteins between the GP group Ⅰ,Ⅱ,VitE group Ⅰ and Ⅱ or in the expression of p38MAPK between the 8 groups.The phosphorylated p38MAPK expression in UVB model group was significantly higher than that in GP group Ⅰ and Ⅱ (0.835 ± 0.049 vs.0.425 ± 0.054 and 0.571 ± 0.090,both P＜ 0.05),but similar to that in VitE groups.Conclusions UVB can activate NF-κB and phosphorylated p38MAPK signaling pathways; GP 1.5％ cream can inhibit UVB-induced activation of NF-κB and p38MAPK pathways,which may be one of the mechanisms underlying its protective effects against inflammation and photodamage.

A two_dimensional HPLC method was developed for the determination of methotrexat ( MTX ) in human plasma. The samples were treated with trichloroacetate for sedimentation and high speed centrifugation, and the obtained supernatant was taken for analysis. The analytes in sample were separated on the first dimension column (ASTON C8 100 mm × 4. 6 mm, 5μm), and trapped on the middle column (ASTON SCX 20 mm × 4. 6 mm, 5 μm) using valve_switching technique for purification and storage. Finally, the trapped analytes were transferred to the second_dimension column (SAC C8 100 mm × 4. 6 mm, 5μm) for the second separation. The mobile phase used for the first dimension was 10 mmol/L ammonium acetate_acetonitrile(9∶1, V/V, pH=3. 8) with a flow rate of 1 mL/min and the mobile phase used for middle column was 10 mmol/L phosphoric acid ( pH=3 . 0 ) . The mobile phase used in second_dimension was a mixed solution of 50 mmol/L ammonium acetate and acetonitrile (87∶10, V/V, pH=5. 2). UV detection was carried out at 306 nm and completed in 4 min. The calibration curve showed a linearity range from 0. 0879 to 5. 154 μmol/L (r=0. 99998). The LOQ was 0. 005 μmol/L. The intra_and inter_day precisions were lower than 1. 5% and 1. 8%, respectively. The relative recovery and the absolute recovery were 99. 1% - 101. 2% and 85. 67%-86. 35%, respectively. The assay is simple, accurate, reproducible, and suitable for the therapeutic drug monitoring of MTX in the hospital and the study on the pharmacokinetics of MTX.

Objective: To analyze the serum concentration results of sodium valproate (VPA) and carbamazepine (CBZ) and explore the relationship between the serum concentration and age, clinical efficacy and adverse reactions to provide reference for the rational clinical use.Methods: Retrospective analysis was used to collect the clinical data of the patients from March 2015 to March 2016, including gender, age, clinical diagnosis, medication, usage and dosage, the last medication time, sampling time, blood concentration and the other related data, and the data were compared and analyzed.Results: Totally 2608 samples were collected, including 2 205 ones for VPA and 403 ones for CBZ.Totally 1 123 cases (50.93%) of VPA and 292 cases (72.46%) of CBZ were within the range of therapeutic windows.In the 2 205 cases of VPA, 1 814 cases (82.27%) were with single drug treatment, and the serum concentration lower than the lower limit of therapeutic window accounted for 790 cases (43.55%) with the effective rate of 43.55% for epilepsy.The serum concentration within the range of therapeutic window accounted for 921 cases (50.77%) with the effective rate of 88.27% for epilepsy, and that higher than the higher limit of therapeutic window accounted for 103 cases (5.68%) with the effective rate of 81.55%.As for CBZ, the number was 58 cases (22.39%) with the effective rate of 48.28%, 195 cases (72.29%) with the effective rate of 79.49% and 6 cases (2.32%) with the effective rate of 83.34%, respectively.Totally 391 cases (87.21%) of VPA combined with the other antiepileptic drugs, such as levetiracetam and lamotrigine.The effect of age on the serum concentration of VPA and CBZ was significant (P<0.05).Conclusion: There are great individual differences in serum concentration of VPA and CBZ among patients.The therapeutic effect and adverse reactions of VPA and CBZ are closely related to the serum concentration.Monitoring the serum concentrations may provide evidence for the rational administration and plays an important role in the treatment of epilepsy.

Ulcerative colitis(UC)is a common disease of the digestive system.Phosphatidylinositol-3-kinase(PI3K)/synuclein/threonine kinase(AKT)is closely related to cell survival,apoptosis,inflammation and other biological processes,and the expression levels of PI3K and AKT significantly increase during the course of UC,with accelerated apoptosis,improved inflammation,and damaged intestinal mucosal barrier function.In recent years,a large number of basic and clinical trials have been conducted on PI3K/AKT signaling pathway in TCM,and the results indicate that PI3K/AKT signaling pathway is expected to be an important potential target for UC treatment.This article analyzed the mechanism of the regulation of PI3K/AKT signaling pathway in TCM from monomer,extract,compound and acupuncture,and suggested that the regulation of this signaling pathway is of great significance for the prevention and treatment of UC,and provide reference for drug development.

Objective:To explore the effects of phased goal directed fluid therapy (GDFT) during anesthesia surgery on tissue perfusion and cognitive function in patients undergoing radical lung cancer surgery.Methods:A total of 108 lung cancer patients were prospectively selected and randomly divided into a control group and a study group using a random number table method. The control group received classical restrictive liquid therapy, while the study group received staged GDFT. We compared the surgical time, intraoperative blood loss, colloid fluid dosage, crystalloid fluid dosage, total output, and urine volume between two groups of patients; Two groups of patients were compared in terms of oxygenation index (OI), respiratory index (RI), central venous oxygen saturation (ScvO 2), lactate (Lac), central venous arterial carbon dioxide partial pressure difference (Pcv-aCO 2), oxygen supply index (DO 2I), and oxygen uptake rate (O 2ERe) before anesthesia induction (T 0), before single lung ventilation (T 1), 1 hour of single lung ventilation (T 2), immediate resumption of dual lung ventilation (T 3), 30 minutes of dual lung ventilation (T 4), and after surgery (T 5); The Mini Mental State Examination (MMSE) was used to evaluate the cognitive function scores of two groups of patients 1 day before surgery and 1 and 3 days after surgery, while recording the incidence of cognitive dysfunction (POCD) and pulmonary complications (including pulmonary infection, acute lung injury, pulmonary embolism, pulmonary edema, atelectasis, etc.) within 3 days after surgery. Results:The amount of crystal fluid and urine output in the research group was significantly lower than that in the control group, while the amount of colloidal fluid was significantly higher than that in the control group (all P<0.05). The OI of the study group T 1-T 5 was significantly higher than that of the control group, while the RI of T 2-T 5 was significantly lower than that of the control group (all P<0.05). The ScvO 2 of the study group T 1 to T 5 was significantly higher than that of the control group, and the Lac was significantly lower than that of the control group (all P<0.05); The MMSE scores of both groups of patients were significantly lower than those before surgery on day 1 and 3 after surgery, and the MMSE scores of the study group were significantly higher than those of the control group on day 1 and 3 after surgery (all P<0.05). The incidence of POCD within 3 days after surgery in the study group was 16.67%(9/54), lower than 37.04%(20/54) in the control group (χ 2=5.704, P=0.017); The incidence of pulmonary complications in the study group was lower than that in the control group (5.56% vs 22.22%, χ 2=4.955, P=0.026). Conclusions:The application of staged GDFT during anesthesia in patients undergoing radical lung cancer surgery can further improve tissue perfusion, improve microcirculation and oxygen supply-demand balance of systemic organs and tissues, including the brain, alleviate perioperative brain function damage, and reduce the occurrence of postoperative POCD compared to conventional liquid therapy.

Objective:To investigate the status of Corona Virus Disease 2019 (COVID-19) health literacy and associated factors in Inner Mongolia Autonomous Region.Methods:Based on the multi-stage stratified sampling method, the questionnaire survey of health literacy of COVID-19 were carried out in 55 599 local residents from12 prefecture-level cities of Inner Mongolia Autonomous Region between March 10 and 15, 2020. The questionnaire in details included not only knowledge, attitude and behavior, but also mental health, their scores were calculated using Decimal method. A ≥80% of the correct answer rate of the survey content was regarded as qualified for health literacy. There were 51 722 (93.0%) valid questionnaires, according to the ratio of medical staff to non-medical staff, 32 529 questionnaires were selected for analysis. The health literacy level was defined according to the proportion of qualified people.The credibility and availability of the questionnaires were evaluated by Cronbach′s α coefficient and KMO test. The associated factors were analyzed by Pearson χ 2 test and logistic regression. Results:In Inner Mongolia Autonomous Region, the whole level of health literacy of COVID-19 was 85.7%, and their scores were (26.30±2.48). Knowledge, attitude, and behavioral literacy levels were 61.6%, 95.6%, and 96.8%, respectively. Compared with the population of 15-25 years old, the health literacy level of 46-65 years old was the highest ( OR=2.00, 95% CI: 1.78-2.24). The health literacy level of medical staff group ( OR=2.54, 95% CI: 1.30-4.95) was far higher than the non-medical staff group; the population with college or above education level ( OR=10.22, 95% CI: 9.19-11.36) was significantly higher than the population with education level below college. The degree of anxiety was negatively correlated with education level. Conclusions:The health literacy level of COVID-19 in residents in Inner Mongolia Autonomous Region is relatively high, but the level of knowledge literacy needs to be improved. The main factors affecting the health literacy of COVID-19 among Inner Mongolia residents are age, occupation and education level.

OBJECTIVES: To investigate the role of autophagy in oxalate-induced toxicity of human proximal renal tubular epithelial cell (HK-2). METHODS: HK-2 cells were exposed to oxalate (1 mmol/L) for 2 h and 3-methyladenine (3-MA) was used to inhibit autophagy. Then Western blotting was used to measure the expression of autophagy-related protein LC3II. Cell viability and cell apoptosis were measured by MTT assay and flow cytometry assay, respectively. RESULTS: Cytoplasmic vacuolization was observed in HK-2 cells after treating with oxalate for 2 h. However, 3-MA showed no effects on the formation of cytoplasmic vacuolization regardless of the dose at 1 or 5 mmol/L. The expression of LC3II protein was significantly increased in the HK-2 cells in the presence of oxalate (0.62±0.03 vs 0.35±0.02, CONCLUSIONS Autophagy of HK-2 cells is enhanced by oxalate at the concentration of 1 mmol/L. Inhibition of 3-MA-induced autophagy protects HK-2 cells from the oxalate-induced cytotoxicity.
Apoptosis ; Autophagy ; Cell Line ; Epithelial Cells ; Humans ; Oxalates/toxicity*

ObjectiveTo observe the effect of icariin on the recombinant Ras homolog family member A （RhoA）/Rho-associated coiled-coil forming protein kinase （ROCK） signaling pathway in rats with Alzheimer's disease （AD）， and to explore the mechanism of icariin in ameliorating the neuronal and dendritic damage. MethodThe β-amyloid 1-42 （Aβ_1-42， 2.5 g·L^-1） was used to induce AD in rats via lateral ventricle injection， and the rats were divided into a model group， a low-dose icariin group （0.03 g·kg^-1）， a middle-dose icariin group （0.06 g·kg^-1）， a high-dose icariin group （0.09 g·kg^-1）， and a control group. The control group and the model group were given an equal volume of normal saline at a dose of 10 mL·kg^-1. The cognitive function of rats was assessed by the Morris water maze. The pathological morphology of the rat hippocampal CA1 area was observed by Nissl staining. Dendritic spine density and dendritic length in the CA1 region of the hippocampus were observed by Golgi-Cox staining. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression levels of tumor necrosis factor-α （TNF-α）， interleukin （IL）-1β， IL-6， RhoA， ROCK1， and ROCK2 in the hippocampus. Western blot assay was used to detect the protein expression levels of TNF-α， IL-1β， IL-6， RhoA， ROCK1， and ROCK2 in the hippocampus. ResultAs compared with the control group， the escape latency of the rats in the model group was increased （P<0.01）， while the number of crossing the platform and the dwelling time in the target quadrant were decreased （P<0.01）. As compared with the model group， the escape latency of the rats in the middle and high-dose icariin groups was decreased （P<0.05， P<0.01）， while the number of crossing the platform and the dwelling time in the target quadrant were increased （P<0.05， P<0.01）. As compared with the control group， the number of neurons， dendritic spine density， and dendritic length in the hippocampal CA1 area of the rats in the model group were decreased （P<0.01）. As compared with the model group， the number of neurons， dendritic spine density， and dendritic length in the hippocampus of the rats in the middle and high-dose icariin groups were increased （P<0.05， P<0.01）. As compared with the control group， the mRNA and protein expression levels of TNF-α， IL-1β， IL-6， RhoA， ROCK1， and ROCK2 in the hippocampus of the rats in the model group were increased （P<0.01）. As compared with the model group， the mRNA and protein expression levels of TNF-α， IL-1β， IL-6， RhoA， ROCK1， and ROCK2 in the hippocampus of the rats in the middle and high-dose icariin groups were decreased （P<0.05， P<0.01）. ConclusionIcariin improves cognitive function and neuronal and dendritic damage in AD by inhibiting the RhoA/ROCK signaling pathway.

Histone acetylation is a critical process in the regulation of chromatin structure and gene expression. Histone deacetylases (HDACs) remove the acetyl group, leading to chromatin condensation and transcriptional repression. HDAC inhibitors are considered a new class of anticancer agents and have been shown to alter gene transcription and exert antitumor effects. This paper describes our work on the structural determination and structure-activity relationship (SAR) optimization of tetrahydroisoquinoline compounds as HDAC inhibitors. These compounds were tested for their ability to inhibit HDAC 1, 3, 6 and for their ability to inhibit the proliferation of a panel of cancer cell lines. Among these, compound 82 showed the greatest inhibitory activity toward HDAC 1, 3, 6 and strongly inhibited growth of the cancer cell lines, with results clearly superior to those of the reference compound, vorinostat (SAHA). Compound 82 increased the acetylation of histones H3, H4 and tubulin in a concentration-dependent manner, suggesting that it is a broad inhibitor of HDACs.