BACKGROUND: We previously found that the intestinal epithelial chemokine (C-C motif) ligand 7 (CCL7) plays an important role in the development of toxin-induced acute liver damage. The detailed effects of intestinal epithelial CCL7 on chronic diseases; however, are still unclear. Here, we aimed to investigate the impact of intestinal epithelial CCL7 overexpression on high-fat diet (HFD)-induced obesity and steatohepatitis in mice. METHODS: Intestinal epithelial CCL7 overexpression (CCL7) mice and their wild-type (WT) littermates were fed with normal chow or HFD for 16 weeks to induce obesity and non-alcoholic fatty liver disease. Body weight gain, as well as adipose tissue index were assessed. Liver injury was monitored by histological analysis and real time polymerase chain reaction. Gut microbial composition was analyzed by 16S rRNA gene sequencing. RESULTS: We found that the CCL7 mice on a HFD had markedly decreased weight gain (8.9 vs. 17.0 g, P < 0.05) and a lower adipose tissue index that include mesenteric fat (1.0% vs. 1.76%, P < 0.05), gonadal fat (2.1% vs. 6.1%, P < 0.05), subcutaneous fat (1.0% vs. 2.8%, P < 0.05) compared to WT animals. HFD-induced glucose intolerance and insulin resistance were also significantly improved in CCL7 mice compared to WT. Furthermore, HFD-fed CCL7 mice displayed less hepatic lipid accumulation and lower expression of inflammatory factors than WT mice. 16S rRNA gene sequencing demonstrated that CCL7 overexpression in intestinal epithelial cells improved HFD-induced gut microbial dysbiosis. CONCLUSIONS Our study revealed that CCL7 overexpression in the intestinal epithelium protects mice against the progression of diet-induced obesity, hepatic steatosis, and enteric dysbiosis.

Quality marker(Q-marker) is a new concept and pattern for quality control of traditional Chinese medicine(TCM),which will lead the development direction for quality control of TCM.Among them,how to characterize the overall quality attribute of TCM and its biological effect,is a critical scientific problem in the study of Q-marker.In this paper,integrated pharmacology is utilized to screen out and confirm the Q-marker from the complex system of TCM,so as to solve the critical scientific problem.System biology in vivo is firstly applied to establish the correlation of chemical fingerprints of TCM,their metabolic fingerprints,network targets,biological effects and efficacy of TCM,which is used to preliminary screen out Q-marker of TCM.Following that,a pharmacological method in vitro,including intestinal absorption in vitro coupled with bioactivity assessment,is employed to simultaneously determine the absorbed doses of TCM and evaluate their biological activity.Furthermore,data mining is utilized to establish the exact quantitative mathematic model between Q-marker of TCM and bioactivity.Meanwhile,two representative examples,including Yuanhu Zhitong tablets,Xinsuning capsules,are introduced to identify Q-marker of TCM and establish their quality standards related with bioactivity,which will be beneficial to improve the level of quality control of TCM and ensure the effectiveness and safety of clinical applications.

Design space approach was applied in this study to optimize the lime milk precipitation process of Lonicera Japonica (Jinyinhua) aqueous extract. The evaluation indices for this process were total organic acid purity and amounts of 6 organic acids obtained from per unit mass of medicinal materials. Four critical process parameters (CPPs) including drop speed of lime milk, pH value after adding lime milk, settling time and settling temperature were identified by using the weighted standardized partial regression coefficient method. Quantitative models between process evaluation indices and CPPs were established by a stepwise regression analysis. A design space was calculated by a Monte-Carlo simulation method, and then verified. The verification test results showed that the operation within the design space can guarantee the stability of the lime milk precipitation process. The recommended normal operation space is as follows： drop speed of lime milk of 1.00-1.25 mL•min⁻¹, pH value of 11.5-11.7, settling time of 1.0-1.2 h, and settling temperature of 10-20 ℃..

During choosing non-steroidal anti-inflammatory drugs(NSAIDs), risk factors should be evaluated in elder patients with rheumatoid arthritis. The present study focused on biological therapies, and elderly patients should be more concerned about the risk of infection when used it. Traditional Chinese medicine has advantages of obvious curative effect, especially for tripterygium wilfordii, large clinical trial on western and Chinese medical accurate drug strategies for old patients with rheumatoid arthritis. Old patients are easier to suffer from cardiac diseases and interstitial lung disease, rheumatoid arthritis could be controlled along with the treatment for coexistent disease. The incidence of rheumatoid arthritis in old patients is the same with other RA, and need to treat to target based on the aim of relieve pain and reduce activity of diseases, while the clinical charteristic and treatment target in elder patients with rheumatoid arthritis were not similar with other aged patient, so treatment standard target would vary with aging. Resent clinical studies excluded old patients, lead to lack of evidence-based medicine data. Clinical study for elder patients with rheumatoid arthritis are energetically carrying out, and could provide base and guide for clinical treatment.

In this paper, a design space approach was applied to optimize the dropping process of Ginkgo biloba dropping pills. Firstly, potential critical process parameters and potential process critical quality attributes were determined through literature research and pre-experiments. Secondly, experiments were carried out according to Box-Behnken design. Then the critical process parameters and critical quality attributes were determined based on the experimental results. Thirdly, second-order polynomial models were used to describe the quantitative relationships between critical process parameters and critical quality attributes. Finally, a probability-based design space was calculated and verified. The verification results showed that efficient production of Ginkgo biloba dropping pills can be guaranteed by operating within the design space parameters. The recommended operation ranges for the critical dropping process parameters of Ginkgo biloba dropping pills were as follows: dropping distance of 5.5-6.7 cm, and dropping speed of 59-60 drops per minute, providing a reference for industrial production of Ginkgo biloba dropping pills.

Continuous pharmaceutical manufacturing is one of the development directions in international pharmaceutical technology. In this study, a continuous mixing technology of ethanol and concentrated extract in the ethanol precipitation of Salvia miltiorrhiza was realized by using a membrane dispersion method. The effects of ethanol flowrate, concentrated extract flowrate, and flowrate ratio on ethanol precipitation results were investigated. With the increase of the flowrates of ethanol and concentrated extract, retention rate of active phenolic acids components was increased, and the total solid removal rate was decreased. The purity of active components in supernatants was mainly affected by the ratio of ethanol flowrate and concentrated extract flowrate. The mixing efficiency of adding ethanol under continuous flow mixing mode in this study was comparable to that of industrial ethanol precipitation. Continuous adding ethanol by using a membrane dispersion mixer is a promising technology with many advantages such as easy enlargement, large production per unit volume, and easy control.

OBJECTIVETo investigate the potential role of deoxyribonuclease I (DNase I) in the pathogenesis of rheumatoid arthritis (RA).

METHODSDNase I activity was measured by radial enzyme-diffusion method in serum samples from 83 RA patients and 60 healthy volunteers and in the synovial fluid (SF) from 27 RA patients and 38 patients with other inflammatory arthritis. SF cfDNA level was measured with Pico Green Kit, and the correlation among DNase I activity, cfDNA level and clinical parameters of RA patients was analyzed.

RESULTSSerum DNase I activity was significantly lower in RA patients than in the healthy control subjects (0.3065∓0.1436 vs 0.4289∓0.1976 U/mL, P<0.001), and was negatively correlated with ESR (r=-0.2862, P=0.0122), CRP (r=-0.2790, P=0.0184) and neutrophil cell counts (r=-0.287, P=0.011). SF DNase I activity was almost negative in patients with RA, ankylosing spondylitis (AS) and gouty arthritis (GA). SF cfDNA level in RA patients was significantly higher than that in patients with osteoarthritis (100.81∓142.98 vs 18.98∓31.40 µg/mL, P=0.002), but similar to that in patients with AS (45.85∓47.67 µg/mL, P=0.428) and GA (162.95∓97.49 µg/mL, P=0.132). In patients with inflammatory arthritis, SF cfDNA level was positively correlated with ESR (r=0.4106, P=0.0116) and CRP (r=0.5747, P=0.0002).

CONCLUSIONImpairment of DNase I activity may be responsible for the enhanced NETs generation and plays a role in the pathogenesis of RA.

OBJECTIVETo compare the mid- to long-term outcomes of patients receiving isolated coronary artery bypass grafting (CABG) versus surgical ventricular restoration (SVR) plus CABG for left ventricular aneurysms.

METHODSThe clinical data were retrospectively analyzed in 205 patients with left ventricular aneurysms admitted to our hospital between January, 1997 and December, 2012, including 115 patients receiving SVR plus CABG and 90 undergoing isolated CABG. By matching preoperative echocardiographic parameters including aneurysm size, left ventricular ejection fraction (LVEF), left ventricular end-systolic volume index (LVESVI) and EuroSCORE risk factors, 32 patients receiving SVR plus CABG and another 32 with isolated CABG were enrolled in this study. The patients were compared for survival rates, major adverse cardiac or cerebrovascular events (MACCEs), left ventricular geometry and function at 1, 3 and 5 years of follow-up.

RESULTSCompared with the patients receiving isolated CABG, those receiving SVR and CABG showed greater improvements in echocardiographic parameters and NYHA functional class. The differences in the echocardiographic parameters between the two groups gradually reduced with time and became comparable at 5 years after the operation (P>0.05). No significant difference was found in the mid- to long-term survival or the incidence of MACCEs between the two groups (P>0.05).

CONCLUSIONCompared with isolated CABG, SVR plus CABG does not reduce the incidence of MACCEs or improve the mid- to long-term survival rate of patients with left ventricular aneurysm with a LVESVI <60 mL/m(2).

Aneurysm ; surgery ; Coronary Artery Bypass ; Echocardiography ; Heart Ventricles ; surgery ; Humans ; Incidence ; Retrospective Studies ; Risk Factors ; Stroke Volume ; Survival Rate ; Treatment Outcome ; Ventricular Function, Left

BACKGROUNDReactive oxygen species are thought to contribute to the development of renal damage. The P22phox subunit of nicotinamide adenine dinucleotide phosphate (NAPDH) oxidase, encoded by the cytochrome b245a polypeptide gene, CYBA, plays a key role in superoxide anion production. We investigated the association of CYBA rs7195830 polymorphism with estimated glomerular filtration rate (eGFR) and the role it plays in the pathogenesis of chronic kidney disease (CKD) in a Han Chinese sample.

METHODSThe Gaoyou study enrolled 4473 participants. Serum levels of creatinine were measured and eGFR was estimated using the Chronic Kidney Disease Epidemiology Collaboration equations. The CYBA polymorphisms were genotyped. Then we investigated the association between eGFR and the rs7195830 polymorphism in the recessive model.

RESULTSThe AA genotype of rs7195830 was associated with significantly lower values of eGFR compared with the GG and AG genotypes ((102.76 ± 17.07) ml×min(-1)×1.73 m(-2) vs. (105.08 ± 16.30) ml×min(-1)± 1.73 m(-2)). The association remained significant in the recessive model after adjusting for age, gender, body mass index, smoking, hypertension, diabetes mellitus, uric acid, triglyceride, low density lipoprotein cholesterol and high density lipoprotein cholesterol (β=1.666, P=0.031). The rs7195832 AA genotype was an independent risk factor for CKD: eGFR <60 ml×min(-1)×1.73 m(-2) (odds ratio=3.32; 95% CI=1.21-9.13).

CONCLUSIONThe AA genotype of rs7195830 is independently associated with lower estimated glomerular filtration rate and is significantly associated with CKD.

Adolescent ; Adult ; Aged ; Asian Continental Ancestry Group ; genetics ; Female ; Glomerular Filtration Rate ; genetics ; Humans ; Male ; Middle Aged ; NADPH Oxidases ; genetics ; Polymorphism, Genetic ; genetics ; Renal Insufficiency, Chronic ; epidemiology ; genetics ; Young Adult

The objective of this study was to evaluate the value of morphologic diagnosis for acute leukemia (AL), to explore the relation of morphologic diagnosis with immunology, cytogenetics and molecular biology diagnosis of AL and to analyze the onset characteristics of AL in 10 years. The samples of bone marrow and peripheral blood from 233 newly diagnosed cases of AL were collected during 2001-2011 years; the morphologic examination and immunologic, cytogenetic and molecular biologic examination (ICM) were carried out, the consistency of morphologic diagnosis with ICM diagnosis was compared, the onset characteristics of AL was analyzed. The results showed that: (1) the consistent rate of immunology, cytogenetics, molecular biology diagnosis with morphologic diagnosis was 84.3%. The order of consistent rat was AUL, M0 < M1 < HAL < M4 < M2 < M3 < M5 < ALL < M6, M7, AP; (2) Misdiagnosis always occurred among AUL, M0, M1, ALL and HAL or among M2a, M3v, M4 and M5. (3) In 233 cases, the highest ratio of blast was observed in M1 (92.5%), while the lowest ratio of blast was observed in M2 (49.5%). (4) AL occurred more frequently in males than that in female (147:86). (5) AL occurred in patients aged from 1 to 88 years. The median age was 41.5 for AUL, 40.8 for M0, 43.4 for M1, 46.3 for M2, 33.8 for M3, 42.6 for M4, 48.8 for M5, 77.3 for M6, 2.5 for M7, 65.0 for AP, 29.1 for ALL and 40.3 for HAL. (6) The number of patients in the later five years (139 cases) was significantly greater than that in the first five years (94 cases), especially the patients with M1, M2, M3, M4, and M5. It is concluded that morphologic diagnosis has important clinical value in the MICM diagnosis of AL. Attaching importance to the confusing cell morphology and onset characteristics of AL can improve the diagnostic accuracy.
Acute Disease ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; Cytogenetic Analysis ; Female ; Humans ; Infant ; Leukemia ; diagnosis ; pathology ; Male ; Middle Aged ; Molecular Biology ; Retrospective Studies ; Young Adult