Hypoxia occurs in chronic and acute vascular diseases and tumor formation. The ability of tumor cells to maintain a balance between an adaptation to hypoxia and cell death is regulated by a family of transcription factors called hypoxia-inducible factor 1 (HIF-1). Tumor hypoxia mediated by HIF-1 would facilitate the likelihood of resistance to chemotherapy and radiotherapy, proliferation, metastasis and the invasive potential; all of which culminate in a decrease in patient survival. And HIF-1 alpha subunit decides the activity of HIF-1, which is regulated by oxygen. So understanding the role of HIF in signal pathway, drug resistance mechanism and its feature is crucial for developing novel anticancer therapies. In recent years, more attentions have focused on HIF-1 alpha inhibitors. It is expected that development of more potent and selective HIF inhibitors will provide an effective treatment of cancer and other HIF-related diseases. So we will focus on the biological characteristics and mechanism of HIF-1 to review currently studied HIF-1 inhibitors.

Objective To study the clinical characteristics of primary Sj(o)gren's syndrome (pSS) patients with dry eyes.Methods Ninety-six pSS patients with dry eyes admitted to the Department of Rheumatology and Immunology,the Affiliated Hospital of Guilin Medical College from August 2009 to August 2011 were retrospectively analyzed.Results In all 96 patients,89 patients had symptoms,23 of whom had two or more symptoms.The tear-film break-up time (BUT) of 154 eyes were Less than 5 seconds,18 were between 5-10 second,and twenty were more than 10 seconds,with the average of 3.7±1.9 seconds.The length of tear flow of 154 eyes'width of tear mocus was less than 3 millimetres (mm),with the average of (0.21±0.10) mm.The average score of corneal fluorescein staining score was 5.2±2.4.The wet lengths of filter paper of 192 eyes were all less than 10 mm/5 min,with the average of (4.6±1.8) mm.The average score of meibomian gland function was 1.5±0.9.Conclusion In patients with pSS,the width of tear meniscus and the wet lengths of filter paper are reduced,which implies less tear secretion.At the same time,BUTs are short,and the Meibomian gland dysfunction are observed.Dry eyes of pSS are mixed in type,not only aqueous tear deficiency.

Objective:To evaluate the sealing ability of the 3.0th generation of polyamidoamine dendrimer(3.0 PAMAM)on hu-man dentinal tubules.Methods:1 6 extracted premolars were cut into 2 mm thick dentin slices to establish sensitive dentin model in vitro.Then 2 samples without any treatment were selected randomly into demineralized dentin group,and the remain 1 4 dentine pills were divided into 2 groups by the random number table(n=7).Samples in the experimental group were treated with 3.0 PAMAM, those in the control group were treated with deionized water.After having immersed in the artificial saliva for 2 and 4 weeks respec-tively,the dentin slices were examined by scanning electron microscope(SEM)and X-ray energy dispersive spectroscopy(EDS). Results:SEM showed that the minerals on the surfaces of the dentine disks in experimental group were formed gradually with the time,the dentinal tubules were blocked 4 weeks after treatment.The minerals on the sample surface in control group were less and the dentinal tubules remained open.EDS results showed that Ca/P(1 .49 ±0.1 6)of mineral deposition in the experimental group was higher than that in the control group (1 .1 8 ±0.20)(P<0.05).Conclusion:The 3.0th generation of PAMAMhas the occlu-ding ability by inducing remineralization on the dentine surface and it may be used in the treatment of dentin hypersensitivity.

Objective:To investigate the thoughts and methods of clinical pharmacists involving in the treatment of 2 cases of atyp-ical pathogen infection. Methods:The consultation cases of 2 patients with atypical pathogens infection were analyzed,and the consul-tation experience was summarized. Results: After the consultation, the treatment efficacy of the patients was obvious. Conclusion:Clinical pharmacists can assist doctors in improving the efficacy and safety of drug treatment.

In this studies, an anticancer peptide was isolated from the enzymatic hydrolysate of Mytilus coruscus.CCK-8 assay was used as guide in activity screening through the isolation process of membrane filtration, DEAEsepharose chromatography, Sephadex G-25 exclusive chromatography and RP-HPLC. An anticancer peptide was obtained and identified as Asp-Leu-Tyr.

Objective To investigate whether B-cell activating factor (BAFF) involved in the patho-genesis of lupus nephritis (LN) by regulating phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling. Methods Twenty-eight lupus nephritis patients and 20 controls were included in this study. The clinical data were collected. BAFF levels in plasma were measured by ELISA, and the relationship between systemic lupus erythematosus disease activity index (SLEDAI) and BAFF were analyzed. The mRNA and protein levels of BAFF, phosphorylated-PI3K (p-PI3K), phosphorylated-Akt (p-Akt), phosphorylated-mTOR (p-mTOR) and Bcl-2 in kidney tissues were measured using real-time polymerase chain reaction (RT-PCR) and Western blotting. Data were analyzed using Mann-Whitney U test and Spearman correlation analysis. Results ①Plasma BAFF levels were significantly higher in LN patients [(580 ±45) ng/L] compared with controls [(208 ±30) ng/L](Z=-5.856, P<0.01), and significant positive correlation was found between plasma BAFF levels with SLEDAI (r=0.723, P<0.01). ② Plasma BAFF level in LN patients was positively correlated with 24 h UP and anti-dsDNA titers (r=0.381, 0.461, P<0.05). The protein level of BAFF in kidney tissues was positively correlated with 24 h UP and anti-dsDNA titer (r=0.469, 0.489, P<0.05).③The mRNA levels of BAFF, p-PI3K, p-Akt, p-mTOR and Bcl-2 in kidney tissues were increased in patients compared to controls[5.8±1.8 vs 2.1±0.7, Z=-4.915, P<0.01;6.7±0.9 vs 1.71±0.53, Z=-5.857, P<0.01;5.6±0.9 vs 1.8 ±0.5, Z=-5.751, P<0.01; 5.6 ±1.4 vs 1.6 ±0.4, Z=-5.291, P<0.01; 2.11 ±0.36 vs 1.33 ±0.22, Z=-4.844, P<0.01].④The protein levels of BAFF, p-PI3K, p-Akt, p-mTOR and Bcl-2 in kidney tissues were increased in patients compared to controls [0.72±0.19 vs 0.31±0.05, Z=-4.747, P<0.01;0.73±0.11 vs 0.33±0.09, Z=-5.834, P<0.01;0.77±0.06 vs 0.22±0.07, Z=-5.855, P<0.01;1.18±0.27 vs 0.47±0.13, Z=-5.416, P<0.01;2.08±0.37 vs 1.32±0.18, Z=-4.998, P<0.01]. Conclusion The findings of this study indicate that BAFF may participate in the pathogenesis of LN by regulating PI3K/Akt/mTOR signaling.

Objective To explore the circadian rhythm of interleukin (IL)-6 in collagen induced arthritis (CIA) rats and investigate the effectiveness and safety of methotrexate (MTX) administered according to IL-6 rhythm.Methods Serum IL-6 concentrations of CIA and normal rats at different time points were measured by enzyme-linked immunosorbent assay (ELISA).CIA rats were randomly divided into the experimental group A,experimental group B and control group.MTX (1/7 mg·kg-1 ·d-1) was administered once a day when the IL-6 level began to increase or decrease in the experimental group,while MTX (1 mg/kg) administered once a week in the control group.Arthritis scores and leukocyte counts were observed.The production of IL-6 and C reactive protein (CRP) levels in the serum were measured.Moreover,histological changes in the ankle joint were examined.One-way analysis of variance (ANOVA),two independent sample t test were used to evaluate the experimental data.Results The plasma IL-6 levels in CIA rats were different at different time points,which began to increase at 18:00 and decrease at 6:00.Arthritis score in the experimental group A (4.8±0.7)was lower than that in the control group (5.8±1.0,t=2.256,P=0.0406) and experimental group B (5.5±0.5,t=2.393,P=0.0313).The levels of TNF-α [(185±21) ng/L],IL-6 [(99±6) ng/L],IL-1β[(20.1±1.6) ng/L] and CRP[(1251±282) μg/L] in the experimental group A were significantly lower than those in control group [TNF-α:(207±10) ng/L,t=2.726,P=0.016 4;IL-6:(100±6) ng/L,t=2.669,P=0.0183;IL-1β:(22.0±1.3) ng/L,t=2.814,P=0.0138;CRP:(1 417±278) μg/L,t=2.369,P=0.0327].The level of IL-6 in the experimental group A[(93±6) ng/L] was lower than that in the experimental group B [(99±6) ng/L,t=2.323,P=0.0358].Compared with the control group [(9650±1062)/μl],the counts of leukocyte in the experimental group A [(4595±603)/μl,t=3.841,P=0.0064] and experimental group B [(3833±585)/μl,t=4.442,P=0.003] were significantly lower.Compared with the control group (9.1 ±2.0),histopathology scores in the experimental group A (6.6±1.3,t=2.606,P=0.015) and experimental group B (7.4±1.3,t=3.857,P=0.0007) were significantly lower.Conclusion The plasma IL-6 levels in CIA rats have shown evident circadian rhythm.There-fore,once a day administration is better than once a week.The therapeutic effect of RA may be improved by administering MTX at the time points according to the circadian rhythm of IL-6.

Objective To investigate the effect of cytomegalovirus(HCMV) infection on infant bodyquality growth,and analysis of the correlation between children of all ages body-quality growth rate and copy number of the virus.Methods One hundred and sixty-eight children with HCMV infection were enrolled in the current study who were hospitalized from Oct.2012 to Oct 2013 in the Affiliated Hospital of Xuzhou Medical College.Children's urine HCMV-DNA copy number was measured by TaqMan probe fluorescence quantitative PCR.The retrospective study was conducted to compare the HCMV infection in children with weight-for-age and normal children.The correlation between children with body-quality growth rate and copy number of the virus was analyzed.Results All 168 urine specimens were positive regarding HCMV-DNA.The age of all distribution was from 1 month to 3 years.There was a negative correlation between the increase body weigh and the copies of virus of children with 3-6 months (r =-0.774,P ＜ 0.01).Conclusion The growth and development of children with HCMV at age before 6 months were slower than Children with the same age.The growth of cytomegalovirus infection increase gradually speeding when they were over 6 months and it was approaching to that same age when they are 2 years old.The growth rate is lower than that of normal children when HCMV children were before 1 years old.The correlation of body-quality growth rate and the number of copies of the virus was negative,especially from 3 months to 6 months.

Objective To investigate the cardiovascular risk factors in perimenopausal women and evaluate the risk for cardiovascular disease. Methods A total of 692 perimenopausal women permanent residents in a community of Zhengzhou from September, 2014 to May, 2015 were selected using multi-stage random sampling. Their age, blood pressure, body weight, smoking history, history of diabetes and fast-ing blood glucose, blood lipid and other information were collected. They were assessed with The National 10-Year Risk Assessment for Ischemic Cardiovascular Disease (ICVD). Results Prevalence of the cardiovascular risk factors screened for were as follow:hypertension 14.3%, dyslipidemia 32.1%, overweight or obesity 59.2%, type 2 diabetes mellitus 7.9%, smoking 0.6%. The absolute risk for ICVD in the next 10 years averaged as (2.01 ± 3.04)%, and increased with age. The incidence of high blood pressure, high total cholesterol, smoking, as well as the level of risk for ICVD were different among various age groups. Conclusion The cardiovascular factors are not controlled ideal-ly in the perimenopausal women, and result in high risk of cardiovascular disease, which need a set of intervention as their risk stratification.

Objective:To explore the association between platelet/lymphocyte ratio (PLR) and frequent peritoneal dialysis (PD) - associated peritonitis (PDAP) in PD patients.Methods:The data of PD patients with PDAP from Guizhou Provincial People's Hospital between January 2015 and June 2019 were analyzed retrospectively. The patients were divided into mono group (only once PDAP occurred in one year) and frequent group (2 or more PDAP occurred in one year) according to the frequency of PDAP. The demographic data including gender, age, height and weight, the clinical data including blood pressure, duration of PD, causes of peritonitis, the laboratory data at the first time of PDAP and the prognosis of PDAP were compared between two groups. Logistic regression analysis method was applied to analyze the relationship between PLR and frequent PDAP. The predictive power of PLR was evaluated by receiver operating characteristic curve (ROC).Results:A total of 78 PD patients with PDAP were enrolled, including 53 males and 25 females, with average age of 45.2 years. The total person-year was 765.1 person-years and the incidence of peritonitis was 0.10 case/person-year during the median follow-up of 16 months. All patients were divided into two groups: 53 patients in mono group and 25 patients in frequent group. Compared with mono group, the patients in frequent group had lower body mass index, longer dialysis duration, higher systolic blood pressure level, higher PLR level, lower uric acid level, and higher rate of drug-resistant bacteria in peritoneal effusion (all P<0.05). The extubation rate of the frequent group was 44.0%(11/25), which was significantly higher than that [15.1%(8/53)] of mono group ( P<0.05). Multivariate logistic regression analysis showed that higher PLR level was an independent related factor for frequent PDAP( OR=1.006, 95% CI 1.002-1.010, P=0.003), and the area under the ROC curve of PLR was 0.783(95% CI 0.663-0.904, P<0.001). Conclusions:High PLR level is an independent related factor of frequent PDAP for PD patients, and PLR can be a potential predictor of frequent PDAP.