AIM To explore the clinical effects of Shuilu Erxian Pills combined with Modified Didang Decoction on patients with early and middle stage diabetic nephropathy.METHODS Eighty-three patients were randomly assigned into control group(42 cases)for 12-week administration of Irbesartan Tablets,and observation group(41 cases)for 12-week administration of Shuilu Erxian Pills,Modified Didang Decoction and Irbesartan Tablets.The changes in clinical effects,TCM syndrome scores,blood glucose indices(FBG,HbA1c),blood lipid indices(TC,TG),renal function indices(BUN,Scr,24 h UTP,eGFR),inflammatory factors(IL-1β,hs-CRP,IL-6,TNF-α,IL-18,TGF-β1),immune function indices(lymphocyte,neutrophil,CD8+,CD3+,CD4+,CD4+/CD8+)and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05).After the treatment,the observation group displayed decreased TCM syndrome scores,blood glucose indices,blood lipid indices,BUN,Scr,24 h UTP,inflammatory factors,CD8+(P＜0.05),reduced lymphocyte,neutrophil(P＜0.05),and increased eGFR,CD3+,CD4+,CD4+/CD8+(P＜0.05),which were more obvious than those in the control group(except for HbA1c,TG,SCr,24 h UTP,lymphocyte,neutrophil)(P＜0.05).No significant difference in incidence of adverse reactions was found between the two groups(P＞0.05).CONCLUSION For the patients with early and middle stage diabetic nephropathy,Shuilu Erxian Pills combined with Modified Didang Decoction can safely and effectively improve clinical symptoms,whose mechanism may contribute to the reduction of inflammatory levels and improvement of immune functions.

OBJECTIVE: To investigate effects of physiological hypoxic conditions on suspension and adherence of embryoid bodies (EBs) during differentiation of human induced pluripotent stem cells (hiPSCs) and explore the underlying mechanisms. METHODS: EBs in suspension culture were divided into normoxic (21% O₂) and hypoxic (5% O₂) groups, and those in adherent culture were divided into normoxic, hypoxic and hypoxia + HIF-1α inhibitor (echinomycin) groups. After characterization of the pluripotency with immunofluorescence assay, the hiPSCs were digested and suspended under normoxic and hypoxic conditions for 5 days, and the formation and morphological changes of the EBs were observed microscopically; the expressions of the markers genes of the 3 germ layers in the EBs were detected. The EBs were then inoculated into petri dishes for further culture in normoxic and hypoxic conditions for another 2 days, after which the adhesion and peripheral expansion rate of the adherent EBs were observed; the changes in the expressions of HIF-1α, β-catenin and VEGFA were detected in response to hypoxic culture and echinomycin treatment. RESULTS: The EBs cultured in normoxic and hypoxic conditions were all capable of differentiation into the 3 germ layers. The EBs cultured in hypoxic conditions showed reduced apoptotic debris around them with earlier appearance of cystic EBs and more uniform sizes as compared with those in normoxic culture. Hypoxic culture induced more adherent EBs than normoxic culture (P < 0.05) with also a greater outgrowth rate of the adherent EBs (P < 0.05). The EBs in hypoxic culture showed significantly up-regulated mRNA expressions of β-catenin and VEGFA (P < 0.05) and protein expressions of HIF-1 α, β-catenin and VEGFA (P < 0.05), and their protein expresisons levels were significantly lowered after treatment with echinomycin (P < 0.05). CONCLUSION Hypoxia can promote the formation and maturation of suspended EBs and enhance their adherence and post-adherent proliferation without affecting their pluripotency for differentiation into all the 3 germ layers. Our results provide preliminary evidence that activation of HIF-1α/β-catenin/VEGFA signaling pathway can enhance the differentiation potential of hiPSCs.
Echinomycin/metabolism* ; Embryoid Bodies/metabolism* ; Humans ; Hypoxia/metabolism* ; Induced Pluripotent Stem Cells/metabolism* ; beta Catenin/metabolism*

Six new bisabolane-type phenolic sesquiterpenoids, including plakordiols A-D (1-4), (7R, 10R)-hydroxycurcudiol (5) and (7R, 10S)-hydroxycurcudiol (6) were isolated from the marine sponge Plakortis simplex collected from the South China Sea. Their structures were determined based on extensive analysis of spectroscopic data. Their configurations were assigned by coupling constant analysis, NOESY correlations, and the modified Mosher's method. Furthermore, their cytotoxic and antibacterial activities were evaluated.
Animals ; Anti-Bacterial Agents/pharmacology* ; China ; Molecular Structure ; Monocyclic Sesquiterpenes/pharmacology* ; Pacific Ocean ; Plakortis/chemistry*

BACKGROUND: Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease. OBJECTIVE: This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m MAIN OUTCOME MEASURES: The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment. RESULTS: A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group. CONCLUSION: SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone. TRIAL REGISTRATION NUMBER NCT02063100 on ClinicalTrials.gov.

In current study, we aimed to investigate whether the gentiopicroside (GPS) derived from Gentiana manshurica Kitagawa could block the progression of alcoholic hepatic steatosis to fibrosis induced by chronic ethanol intake. C57BL/6 mice were fed an ethanol- containing Lieber-DeCarli diet for 4 weeks. LX-2 human hepatic stellate cells were treated with GPS 1 h prior to transforming growth factor-β (TGF-β) stimulation, and murine hepatocyte AML12 cells were pretreated by GPS 1 h prior to ethanol treatment. GPS inhibited the expression of type I collagen (collagen I), α-smooth muscle actin (α-SMA) and tissue inhibitor of metal protease 1 in ethanol-fed mouse livers with mild fibrosis. In addition, the imbalanced lipid metabolism induced by chronic ethanol-feeding was ameliorated by GPS pretreatment, characterized by the modulation of lipid accumulation. Consistently, GPS inhibited the expression of collagen I and α-SMA in LX-2 cells stimulated by TGF-β. Inhibition of lipid synthesis and promotion of oxidation by GPS were also confirmed in ethanol-treated AML12 cells. GPS could prevent hepatic steatosis advancing to the inception of a mild fibrosis caused by chronic alcohol exposure, suggesting GPS might be a promising therapy for targeting the early stage of alcoholic liver disease.

Background:: Clinical remission is the treatment target in rheumatoid arthritis (RA). This study aimed to investigate clinical remission and related factors in a large cohort of patients with RA. Methods:: This study composed of 342 patients with RA. Data were collected by face-to-face interview of 1049 patients with RA who visited the Department of Rheumatology of three teaching hospitals from September 2015 to May 2016. The patients with RA were clinically assessed by rheumatologists and a four-page questionnaire was completed on site. Subsequently, patients fulfilled remission criteria were further analyzed. The practicability of different definitions of remission of RA was rated by a panel of rheumatologists. Sustained intensive disease modifying anti-rheumatic drug (DMARD) treatment was defined as a combination treatment with two or more DMARDs for at least 6 months. Results:: In this cohort of 342 patients with RA, the proportions of patients achieving remission were 38.0%, 29.5%, 24.9%, 21.1%, 19.0%, 18.1%, and 17.0%, based on criteria of disease activity score in 28 joints (DAS28) using CRP (DAS28-CRP), DAS28 using ESR (DAS28-ESR), routine assessment of patient index data 3 (RAPID-3), Boolean, simplified disease activity index (SDAI), clinical disease activity index, and the newly described clinical deep remission (CliDR), respectively. Boolean and CliDR are the best in practicability scored by rheumatologists (7.5 and 8.0, respectively). Compared with the non-sustained intensive group, sustained intensive treatment with DMARDs yielded higher remission rates of 25.6%, 23.8%, and 21.3% in patients with RA based on Boolean (χ²=3.937, P=0.047), SDAI (χ²=4.666, P=0.031), and CliDR criteria (χ²=4.297, P=0.038). The most commonly prescribed conventional synthesized DMARDs (csDMARDs) in patients with RA was leflunomide, followed by methotrexate, and hydroxychloroquine. Compared with the non-remission group, patients achieving remission had a longer median duration of DMARDs (45.0 [22.8–72.3] months, Z=-2.295, P=0.022). Conclusions: The findings in this study indicated that clinical deep remission is achievable in patients with RA. Sustained intensive DMARD treatment is needed to achieve a better outcome in RA.

BACKGROUND: Clinical remission is the treatment target in rheumatoid arthritis (RA). This study aimed to investigate clinical remission and related factors in a large cohort of patients with RA. METHODS: This study composed of 342 patients with RA. Data were collected by face-to-face interview of 1049 patients with RA who visited the Department of Rheumatology of three teaching hospitals from September 2015 to May 2016. The patients with RA were clinically assessed by rheumatologists and a four-page questionnaire was completed on site. Subsequently, patients fulfilled remission criteria were further analyzed. The practicability of different definitions of remission of RA was rated by a panel of rheumatologists. Sustained intensive disease modifying anti-rheumatic drug (DMARD) treatment was defined as a combination treatment with two or more DMARDs for at least 6 months. RESULTS: In this cohort of 342 patients with RA, the proportions of patients achieving remission were 38.0%, 29.5%, 24.9%, 21.1%, 19.0%, 18.1%, and 17.0%, based on criteria of disease activity score in 28 joints (DAS28) using CRP (DAS28-CRP), DAS28 using ESR (DAS28-ESR), routine assessment of patient index data 3 (RAPID-3), Boolean, simplified disease activity index (SDAI), clinical disease activity index, and the newly described clinical deep remission (CliDR), respectively. Boolean and CliDR are the best in practicability scored by rheumatologists (7.5 and 8.0, respectively). Compared with the non-sustained intensive group, sustained intensive treatment with DMARDs yielded higher remission rates of 25.6%, 23.8%, and 21.3% in patients with RA based on Boolean (χ = 3.937, P = 0.047), SDAI (χ = 4.666, P = 0.031), and CliDR criteria (χ = 4.297, P = 0.038). The most commonly prescribed conventional synthesized DMARDs (csDMARDs) in patients with RA was leflunomide, followed by methotrexate, and hydroxychloroquine. Compared with the non-remission group, patients achieving remission had a longer median duration of DMARDs (45.0 [22.8-72.3] months, Z = -2.295, P = 0.022). CONCLUSIONS The findings in this study indicated that clinical deep remission is achievable in patients with RA. Sustained intensive DMARD treatment is needed to achieve a better outcome in RA.
Adult ; Aged ; Antirheumatic Agents ; therapeutic use ; Arthritis, Rheumatoid ; drug therapy ; pathology ; Cross-Sectional Studies ; Female ; Humans ; Hydroxychloroquine ; therapeutic use ; Leflunomide ; therapeutic use ; Male ; Methotrexate ; therapeutic use ; Middle Aged ; Retrospective Studies ; Surveys and Questionnaires

Lilii Bulbus, which comes from many medicinal plants，is a frequently-used traditional Chinese medicine，the records in previous herbal literatures of it's origin and quality were inconstant. To trace back it's sources, we conducted a systematical study on it's origin and quality by textual research and investigation in this paper,The result showed that the origins of Lilii Bulbus are mainly source from white-flowers, red-yellow-flowers and red-flowers of Lilium， L. brownii var. viridulum, which were believed authentic or good quality in all previous herbal literatures,and L. pumilum and L. concolor which belong to white-flowers,and L. lancifolium which belong to red-yellow-flowers were believed low-quality and unfit for medicinal uses, or they were listed below and often have different effect with L. brownii var. viridulum. Among them, only L. concolor does not belong to Lilii Bulbus according to Chinese Pharmacopeia (2015 edition), The mainstream varieties of Lilii Bulbus became L. lancifolium now according to our practical investigation, which were very different from previous herbal literatures. Although chemical and pharmacological studies provided a reference for L. lancifolium，we should respect the actual records of the previous herbal literatures，the research of material foundation of efficacy should be more sufficient，and provide science evidence for clinical application of different species of Lilii Bulbus.

OBJECTIVETo evaluate the effect and safety of Kuanxiong Aerosol (, KA) on patients with angina pectoris.

METHODSBlock randomization was performed to randomly allocate 750 patients into KA (376 cases) and control groups (374 cases). During an angina attack, the KA group received 3 consecutive sublingual sprays of KA (0.6 mL per spray). The control group received 1 sublingual nitroglycerin tablet (NT, 0.5 mg/tablet). Log-rank tests and Kaplan-Meier estimations were used to estimate the angina remission rates at 6 time-points after treatment (1, 2, 3, 4, 5, and >5 min). Logistic regression analysis was performed to observe the factors inflfluencing the rate of effective angina remission, and the remission rates and incidences of adverse reactions were compared for different Canadian Cardiovascular Society (CCS) classes of angina.

RESULTSThe 5-min remission rates in the KA and control groups were not signifificantly different (94.41% vs. 90.64%, P>0.05). The angina CCS class signifificantly inflfluenced the rate of remission (95% confidence interval = 0.483-0.740, P<0.01). In the CCS subgroup analysis, the 3-and 5-min remission rates for KA and NT were similar in the CCSII and III subgroups (P>0.05), while they were signifificantly better for KA in the CCSI and II subgroups (P<0.05 or P<0.01). Furthermore, the incidence of adverse reactions was signifificantly lower in the KA group than in the control group for the CCSII and III subgroups (9.29% vs. 26.22%, 10.13% vs. 20.88%, P<0.05 or P<0.01).

CONCLUSIONSKA is not inferior to NT in the remission of angina. Furthermore, in CCSII and III patients, KA is superior to NT, with a lower incidence of adverse reactions. (Registration No. ChiCTRIPR-15007204).

Aerosols ; adverse effects ; therapeutic use ; Angina Pectoris ; drug therapy ; Case-Control Studies ; Drugs, Chinese Herbal ; adverse effects ; therapeutic use ; Female ; Humans ; Kaplan-Meier Estimate ; Logistic Models ; Male ; Middle Aged ; Remission Induction ; Treatment Outcome

The potential role of total saponins extracted from Lilium lancifolium bulbs (TSLL) on the proliferation, apoptosis, migration and invasion of human lung cancer A549 cells and its possible mechanism were discussed. Effect of TSLL on proliferation of A549 cells were detected by CCK-8, clone formation assay and EdU staining. Effect of TSLL on apoptosis morphology of A549 cells was observed by fluorescence microscope using Annexin V/PI double staining and Hoechst 33342 staining. Effect of TSLL on cell migration and invasion was detected by Transwell migration test and Transwell invasion test, respectively. Western blot was used to detect TSLL on the expression change of intracellular associated proteins. Results showed that TSLL intervention in A549 cells within 24, 48 or 72 h significantly inhibited cell growth, and its IC₅₀values were about 229, 173 and 71 mg·L⁻¹, respectively. TSLL significantly reduced the clone formation rate of A549 cells and decreased the DNA synthesis rate of A549 cells in a concentration dependent manner. TSLL induced A549 cells apoptosis and reduced the migratory behavior of A549 cells. TSLL decreased invasion of A549 cells to the artificial basement membrane. The expression level of intracellular PCNA and the ratio of Bcl-2/Bax protein were down-regulated and procaspase 3 was activated. In addition, TSLL had no obvious effect on epithelial mesenchymal transition (EMT) related marker proteins E-cadherin and vimentin expression. The above results indicated that TSLL possess inhibitory effects against proliferation, migration and invasion of lung cancer A549 cells and apoptosis-induced effect. The anti-proliferation effect of TSLL is very likely by inhibiting intracellular DNA synthesis through reducing the expression of PCNA in lung cancer cells. And the apoptosis induction of TSLL on lung cancer cells is associated with the regulation of Bcl-2 and Bax proteins expression. Nevertheless, there is no incontestable correlation between anti-invasion and metastasis effects of TSLL and EMT in lung cancer cells.
Apoptosis ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Epithelial-Mesenchymal Transition ; Humans ; Lung Neoplasms ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Saponins