Objective To explore the role of oxidative stress in the initiation and development of experimental diabetic nephropathy.Methods Levels of MDA and the total SOD activity were tested in the whole kidney at 1 month,3 months and 6 months of experimental rat diabetes induced by streptozotocin.The pathological changes of diabetic rats were examined by light microscopy.Results The MDA level increased significantly in the diabetic group as compared to control group at all time intervals(2.16?0.57 vs 1.18?0.18,P

“Multi-component Chinese medicine” was derived from effective clinical prescriptions, which is similar to natural medicines, and its form is similar to the fixed-dose compounds. The adaptable indications mainly cast chronic, intractable, and complex diseases. Its research targets of pharmacology mostly are diseases, symptoms or pathological process. Vivo and vitro experiments can be used in its researches. Its dose-effect relationship mostly shows non-linear relationship, and three elements (dose, efficacy and syndrome) are involved. However, the comprehensive evaluation method is still in the exploratory stag. In the safety evaluation, there were few general pharmacological researches, and the basis of toxicity and the relationship between amount and toxicity need further study. In combined optimization aspect, including identification of components and component ratio optimization, many methods have been developed, but it still needs to be developed in theory and systemic integration. Pharmacological mechanism researches focus on the multi-component, multi-target, multi-pathway, and multi-pharmacodynamics aspects, combined with new ideas and new technologies, such as systems biology, network pharmacology, etc. But as multi-component medicine, it should also be studied about the correspondence and network relationships of component and target, with a purpose to explain the contribution of each component in overall mechanism.

OBJECTIVE: To explore the correlation between the width of lingual varix and changes of hemodynamics of portal system in patients with primary liver cancer so as to supply the data for the forecast of portal hypertension by observing lingual varix. METHODS: The diameter of lingual vein (Dlv) was measured by vernier caliper as dependent variable, and the diameters and indexes of hemodynamics of portal vessels were measured by Doppler as independent variables, then a multipe stepwise analysis was performed. RESULTS: The diameters of portal vein (Dpv) and splenic vein (Dsv) entered the formula Dlv (mm) = 0.185 + 0.311 Dsv (mm) + 0.236 Dpv (mm) when the entry and removal values were alpha(in)=0.10 and alpha(out)=0.15, respectively. CONCLUSION: The width of lingual vein is closely correlated with the diameters of portal vein and splenic vein in patients with primary liver cancer.

Objective To observe the effect of low concentration Aβ1-42 monomer/oligomers and CORM-2 in different concentration on livability of SN56 cells. Methods SN56 cells were cultured in the 96-well plate with uniform concentration, and were divided into control group, Aβ1-42 group, Aβ1-42 + CORM-2 50μM group, and Aβ1-42 + CORM-2 100 μM group. Three lines of cells in Aβ1-42 group were cultured in the surroundings of 10nM,100nM and 1 μM Aβ1-42monomer/oligomers, respectively. Aβ1-42 + CORM-2 50μM group and Aβ1-42 + CORM-2 100μM group had the same culture condition as group Aβ1-42 ,except contain 50μM, and 100μM CORM-2, respectively. Control group didnt have any effect factor. Three days later,the livability of different groups was compared with MTT method. Results The livability of group Aβ1-42 with the increasing concentration of Aβ1-42 was (79.73 ±0.94)% ,(67.99 ±0.79)% ,(60.42 ±0.62)% , respectively. The higher the concentration of Aβ1-42 was,the lower the livability of SN56 cell was. The livability of group Aβ1-42 + CORM-2 50μM/100μM was( 75.15±0.096)%,(63.20 ±0.17)%, (55.33 ±0.19)%; (73.20 ±0.27)%, (64.34 ±0.11 )%, (54.17 ±0.12)% , respectively. Both were lower than group Aβ1-42. And different CORM-2 concentration had discrepancy in the ability of decreasing the cell livability. Conclusion Low concentration of Aβ1-42 can reduce the livability of SN56 cells, and higher concentration has more significant effect; CORM-2 in different concentration both can decrease the livability of SN56 cells,and there is a discrepancy in the intensity.

The purpose of this study is to explore the feasibility of wheat germ agglutinin (WGA) modified liposome as a vehicle for ophthalmic administration. Liposome loaded with 5-carboxyfluorescein (FAM) was prepared by lipid film hydration method. WGA was thiolated and then conjugated to the surface of the liposome via polyethylene glycol linker to constitute the WGA-modified and FAM-loaded liposome (WGA-LS/FAM). The amount of thiol groups on each WGA molecule was determined, and the bioactivity of WGA was estimated after it was modified to the surface of liposome. The physical and chemical features of the WGA-modified liposome were characterized and the ocular bioadhesive performance was evaluated in rats. The result showed that each thiolated WGA molecule was conjugated with 1.32 thiol groups. WGA-LS/FAM had a mean size of (97.40 +/- 1.39) nm, with a polydispersity index of 0.23 +/- 0.01. The entrapment efficacy of FAM was about (2.95 +/- 0.21)%, and only 4% of FAM leaked out of the liposome in 24 h. Erythrocyte agglutination test indicated that after modification WGA preserved the binding activity to glycoprotein. The in vivo ocular elimination of WGA-LS/FAM fitted first-order kinetics, and the elimination rate was significantly slower than that of the unmodified liposome, demonstrating WGA-modified liposome is bioadhesive and suitable for ophthalmic administration.
Absorption, Physicochemical ; Adhesiveness ; Administration, Ophthalmic ; Animals ; Drug Carriers ; Eye ; metabolism ; Fluoresceins ; chemistry ; Liposomes ; administration & dosage ; chemistry ; pharmacokinetics ; Male ; Particle Size ; Polyethylene Glycols ; chemistry ; Rats ; Rats, Sprague-Dawley ; Wheat Germ Agglutinins ; administration & dosage ; chemistry ; pharmacokinetics

Objective To study the effect and mechanisms of berberine (BBR) on the proliferation of papillary thyroid cancer K1 cells induced by high glucose.Methods K1 cells were cultured under 5.5 mmol/L or 25 mmol/L glucose condition with or without different concentration of BBR (0,10,40 and 80 μmol/L) for 24 hours.The proliferations of K1 cells in each condition were detected by MTT.Western blot was used to measure the expression of nuclear factor erythroid 2-related factor 2 (Nrt2),phosphoinositide 3-kinase (PI3K),protein kinase B (Akt) and phosphorylated-Akt (p-Akt).The distribution pattern of Nrf2 in K1 cells was determined using immunofluorescent staining.Results Compared with 5.5 mmol/L condition,the proliferation rate [(126.64 ± 5.41) ％ vs (87.31 ± 3.67) ％],expression levels of PI3K (0.425 ±0.019 vs 0.272 ±0.039),p-Akt/Akt (0.446 ±0.021 vs 0.168 ±0.035) and Nrf2 (0.597 ± 0.014 vs 0.308 ± 0.026),and Nrf2 distribution (93.0％ vs 23.1％) in nuclear of K 1 cells under 25 mmol/L condition were significantly elevated,respectively (all P ＜0.01).Addition of BBR in 25 mmol/L condition dose dependently (10,40,80 μmol/L) lowered the proliferation rate of K1 cells [(111.76 ± 4.10)％,(70.03 ±2.18)％,(32.41 ±3.76)％ vs (126.64 ±5.41)％,all P＜0.05],and suppressed the expression of PI3K,p-Akt/Akt,Nrf2,and Nrf2 nuclear distribution (P ＜ 0.05).Conclusions BBR dose dependently inhibited the proliferation of high glucose-induced K1 cells.This effect was associated with the suppression on of PI3K/Akt signaling activation,Nrf2 expression and its nuclear translocation.

OBJECTIVEWe studied the function of dendritic cells subsets and the cytokines levels in plasma in patients with different periods of returning (immune tolerance, hepatitis active and non-replicating period) and aimed to explore the possible reasons for HBV chronic infection.

METHODSThirty HBV infected patients in different stages of infection were enrolled and divided into three groups: the immune tolerance group (10 cases), the hepatitis active group (10 cases), and the non-replicating group (10 cases). Ten healthy people were enrolled and served as controls. Blood from the patients and controls were collected and the dendritic cells subsets function (The cytokine levels in different groups) were analyzed using statistical method.

RESULTSThe total IL-12 output and single nucleus IL-12 output of the total HBV infected patients were lower than that of the healthy control group (P value less than 0.01). The total IFNa output and single nucleus IFNa output of the total HBV infected patients had no significant difference between the total HBV infected patients and the healthy controls (P value more than 0.05). The total IL-12 output of the healthy control group was higher than that in others 3 groups of the HBV infected patients. (Z = -3.039, -2.967 ,-2.949, P value less than 0.01) and the single nucleus IL-12 output of the healthy control group was also higher than that in others 3 groups of the HBV infected patients. (Z =-3.027, -2.671 , -2.863, P value less than 0.01) . The total IFNa output and the single nucleus IFNa output of the healthy control group was higher than that in the hepatitis active group of HBV infected patients (Z = -3.016, -3.176, P value less than 0.01). While the plasma IFNa cytokine levels in the 3 HBV infection groups were higher than in the healthy control group (Z = -2.967, -2.896, -3.054, P value less than 0.01).

CONCLUSIONDifference existed between the function of dendritic cells subsets and the IFNa levels in different returning periods of HBV infected patients. The function of dendritic cells subsets has no significant difference in HBV patients with different periods of returning. The flawed function of dendritic cells subsets and the abnormal IFNa level may be one of the reasons for chronic HBV infection.

Adult ; Case-Control Studies ; Cytokines ; Dendritic Cells ; immunology ; Female ; Hepatitis B ; blood ; immunology ; Hepatitis B, Chronic ; blood ; immunology ; Humans ; Immune Tolerance ; Interferon-alpha ; blood ; Interleukin-12 ; blood ; Male ; Young Adult

italic>Psidium guajava Linn. is an evergreen shrub or small tree of Psidium Linnaeus in the Myrtaceae family. One new glycoside (1) together with 3 known meroterpenoids (2-4) and 9 known glycosides (5-13) were isolated from the fruits of Psidium guajava Linn.. The structure of the new compound was elucidated by the spectroscopic data analysis of HR-ESIMS, 1D- and 2D-NMR, and it was named psiguaoside A (1). The known compounds were identified as guajadial (2), 4,5-diepipsidial A (3), psidial A (4), chrysin-8-C-β-D-glucoside (5), 2,6-dihydroxy-3,5-dimethyl-4-O-β-D-glucopyranosyl-benzophenone (6), quercetin-3-O-β-D-glucopyranoside (7), quercetin-3-O-xyloside (8), guaijaverin (9), avicularin (10), guavinoside E (11), guavinoside B (12), guajaphenone A (13). In the bioactivity assay, compound 3 exhibited significant inhibitory activitiy of U87 with IC₅₀ values of 8.379 μmol·L^-1.

Abstract: Objective　To explore the correlation between monocyte to high-density lipoprotein cholesterol ratio (MHR) and insulin resistance (IR) in male patients with type 2 diabetes mellitus (T2DM) combined with metabolic-related fatty liver disease (MAFLD). Methods A total of 454 male patients with T2DM combined with MAFLD in National Metabolic Management Center (MMC) of the Affiliated Hospital of Jiangsu University from May 2018 to July 2020 were enrolled. The general clinical data of subjects were collected, blood routine and biochemical indexes were tested, homeostasis model insulin resistance index (HOMA-IR) was calculated, visceral fat area (VFA) and subcutaneous fat area (SFA) were measured. Accordingtothe MHR quartile, patients were divided into group Q1 (MHR≤0.38), group Q2 (0.380.64) to compare the differences in measured indicators above. In addition, patients were divided into two groups according to HOMA-IR, HOMA-IR<2.5 and HOMA-IR≥2.5, and the differences in MHR were compared. Results The patients were divided into four groups according to MHR:group Q1 (n=115), group Q2 (n=110), group Q3 (n=120) and group Q4 (n=109). Fasting insulin (FINS) were respectively 6.17(4.20,9.76), 7.73(4.94,10.66), 8.92(5.32,11.33) and 9.13(5.25,12.27) mU/L, 2-hour postprandial insulin were 22.75(12.87,39.59), 27.55(16.44,39.77), 30.98(17.46,43.11) and 31.28(18.54,45.92) U/L. HOMA-IR were 3.12(1.63,4.25), 3.72(2.26,4.66), 3.87(2.48,5.44) and 3.95(2.42,5.31). Neutrophil (Neu) were 3.10(2.60,3.70), 3.20(2.50,3.93), 3.60(2.80,4.28), 4.20(3.30,5.00)×109/L. Subcutaneous fat area (SFA) were (181.27±53.60), (192.64±62.41), (199.53±61.40) and (203.69±71.51) cm2. They all increased gradually. However, the levels of high-density lipoprotein cholesterol (HDL-c) [1.18(1.06,1.35), 1.02(0.86,1.17), 0.96(0.80,1.03) and 0.80(0.69,0.92) mmol/L] and low-density lipoprotein cholesterol (LDL-c) [(3.00±0.79), (2.76±0.83), (2.67±0.85) and (2.59±0.92) mmol/L] decreased gradually. Pearson's or Spearman's correlation analysis showed that MHR was positively correlated with FINS, 2-hour postprandial insulin (2hINS), HOMA-IR, VFA and SFA (r=0.190, 0.153, 0.184, 0.114, 0.127, P<0.05). The coronary heart disease history, systolic blood pressure,diastolic blood pressure,fasting plasmaglucose (FPG), FINS, alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood uric acid (Ur), body mass index (BMI), VFA, SFA and MHR of patients in group HOMA-IR≥2.5 were higher than group HOMA-IR<2.5 (P<0.05). Conclusion　MHR is positively correlated with IR in male patients with T2DM combined with MAFLD, and as MHR increases, the degree of IR is higher.

Adefovir dipivoxil is commonly used for treatment of chronic hepatitis B. The renal toxicity of adefovir dipivoxil is dose- and time-related, occurring often in patients with a daily dose over 30 mg and those with impaired renal function. We report a case of chronic hepatitis B with a history of taking adefovir dipivoxil at 10 mg/day for 4 years. The patient complained of lumbosacral and joint pain and had the diagnosis of ankylosing spondylitis (AS) or spondyloarthropathy in several hospitals before admission in our hospital. A diagnosis of acquired Fanconi syndrome and hypophosphatemia osteomalacia associated with progressive muscular weakness was made eventually. We reviewed the literature and found reports of only fewer than 10 similar cases. Clinical attention should be given to kidney damage induced by adefovir dipivoxil.
Adenine ; adverse effects ; analogs & derivatives ; therapeutic use ; Antiviral Agents ; adverse effects ; therapeutic use ; Bone Diseases, Metabolic ; chemically induced ; complications ; congenital ; Fanconi Syndrome ; chemically induced ; complications ; Hepatitis B, Chronic ; drug therapy ; Humans ; Hypophosphatemia ; chemically induced ; complications ; Male ; Muscle Weakness ; chemically induced ; complications ; Organophosphonates ; adverse effects ; therapeutic use ; Osteomalacia ; chemically induced ; complications ; Young Adult