Objective To investigate the effect of statin on trabecular bone microstructure by using trabecular bone score (TBS), a new type of bone microstructure evaluation index. Methods A total of 253 middle and aged patients hospitalized in the First Affiliated Hospital of Nanjing Medical University between January 2014 and March 2016 were retrospectively analyzed. According to whether statin was used or not, patients were divided into two groups: 90 patients in the statin use group (statin was use for more than 1 year) and 163 in the control group (not taken any statin). Serum biochemical indicators, such as triacylglycerol, total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, alkaline phosphatase, fasting blood glucose and 25 hydroxy vitamin D, were compared between the two groups. Dual energy X-ray absorptiometry (DXA) was used to measure the bone mineral density (BMD) of lumbar spine and femoral neck. TBS was calculated with TBS iNsight? software, and the DXA image of lumbar spine were analyzed. Results Values of total cholesterol and low density lipoprotein cholesterol were significantly lower in statin group compared with those of control group (P<0.001), while no significant differences in other biochemical indicators between two groups (P>0.05). There was higher lumbar spine BMD statin group compared to that of control group (g/cm2:1.04 ± 0.19 vs. 0.96 ± 0.14, P<0.01). There was higher lumbar spine BMD and higher TBS (1.31±0.09 vs. 1.26±0.09, P<0.01) in statin group than that of control group. There was no difference in the femoral neck BMD between the two groups (P>0.05). Conclusion Statin increases lumbar spine BMD and improves trabecular bone microstructure in middle and aged people.

OBJECTIVETo summarize the experience of surgical resection of 103 hilar cholangiocarcinoma.

METHODSOne hundred and three consecutive cases of hilar cholangiocarcinoma who underwent surgical resection at our hospital over the past ten years were reviewed retrospectively. The clinical data and long-term outcome were analyzed.

RESULTSOut of 103 cases, 43 patients underwent radical resection (41.7%), and 60 patients underwent palliative resection. There were 34 patients developed postoperative complications and 8 patients died in hospital. For the radical resection group, the median survival time was 29.9 months and 1-year, 3-year, 5-year survival rate was 69.6%, 42.0%, 20.9%, respectively, which was significant greater than 34.1%, 10.2%, 0 of the palliative resection group (P < 0.05). Over the past five years, 42 cases underwent pre-operative drainage of bile and the rate of combined liver resection reached 53.8%. The tumor radical resection rate has increased to 45.7%, the median survival time have reached 24.7 months (P < 0.05).

CONCLUSIONSImprovement of pre-operative management, intraoperative pathology for resection margin, and combined liver resection may help in increasing the radical resection rate. Radical resection can improve postoperative survival, and produce a satisfactory outcome for patient with hepatic hilar cholangiocarcinoma.

Adult ; Aged ; Bile Duct Neoplasms ; mortality ; surgery ; Bile Ducts, Intrahepatic ; Cholangiocarcinoma ; mortality ; surgery ; Digestive System Surgical Procedures ; methods ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Survival Rate

OBJECTIVEChinese jianpi herbal recipe Weichangan (WCA) could increase the survival rate of advanced gastric cancer. This study was designed to investigate the molecular mechanism of WCA in treatment of gastric cancer by cDNA array, real-time quantitative PCR and immunohistochemical technique.

METHODA human gastric adenocarcinoma cell line SGC-7901 grafted onto nude mouse was used as the animal model. The mice were divided into 3 groups, one control and the two representing experimental conditions. Animals in the two experimental groups received either WCA over a 34-day period or 5-fluorouracil (5-FU) over 6-day period starting at 8th day after grafting. Control animals received saline on an identical schedule. Animals were killed 41 days after being grafted. To assess the effect of therapy tumor weight was determined by a electron balance immediately after the animals killed. SP immunohistochemical method was used to detect the expression of proliferating cell nuclear antigen (PCNA) in xenografts. For detection of apoptotic cells, apoptotic indices (AI) were examined by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate fluorescence nick end labeling (TUNEL) method. SP method was also used to detect the expression of cleaved Caspase-3. The expression profiles in paired WCA treated gastric cancer samples and the N. S. control samples were studied by using a cDNA array representing 14, 181 cDNA clusters. The alterations in gene expression levels were confirmed by real-time quantitative PCR. SP method was used to detect the expression of Phospho-Stat3 (Tyr705) and bcl-2.

RESULTWhen compared with controls, tumor growth was significantly inhibited by treatment with the WCA or 5-FU (P < 0.01, respectively). The average of tumor inhibitory rate in WCA group was (44.32 +/- 5.67)% and 5-FU (47.04 +/- 11.33)%. The average labeling index (LI) for PCNA in WCA group and 5-FU group was significantly decreased compared with the control group respectively. AI of human gastric cancer xenografts in nude mice was significantly increased to (9.72 +/- 4.51)% using TUNEL method in WCA group compared with the controls (2.45 +/- 1.37)%. 5-FU group was also found a significantly increased AI compared with the controls. The expression of cleaved Caspase-3 in WCA group and 5-FU group was significantly increased compared with the control group respectively. There were 45 different expression ESTs among the control sample pool and WCA sample pool. There were 24 ESTs up-regulated in WCA samples and 21 ESTs down-regulated. These 45 ESTs contains 35 cloned genes and 11 unknown ESTs. By using Real-time Quantitative PCR, the expression level of Stat3 (2(-deltadeltaCT) = 0.16) , RIPX (2(-deltadeltaCT) = 0.18), ROD1 (2(-deltadeltaCT) = 0.23) and bcl-2 (2 (-deltadeltaCT) = 0.10) was lower in WCA group than that in control group respectively. The expression of Phospho-Stat3 (Tyr705) and bcl-2 in WCA group and 5-FU group was significantly decreased compared with the control group respectively.

CONCLUSIONChinese jianpi herbal recipe WCA could inhibit gastric cancer cell SGC-7901 growth in vivo. WCA could induce gastric cancer cell apoptosis and suppress proliferation. Its mechanisms might be involved in the down-regulation of Stat3, RIPX, ROD1 and bcl-2 gene.

Adenocarcinoma ; drug therapy ; genetics ; pathology ; Animals ; Antimetabolites, Antineoplastic ; pharmacology ; therapeutic use ; Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Drug Combinations ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; therapeutic use ; Expressed Sequence Tags ; Fluorouracil ; pharmacology ; therapeutic use ; Gene Expression Profiling ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Nerve Tissue Proteins ; metabolism ; Plants, Medicinal ; chemistry ; Polypyrimidine Tract-Binding Protein ; Proliferating Cell Nuclear Antigen ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; RNA-Binding Proteins ; metabolism ; STAT3 Transcription Factor ; metabolism ; Stomach Neoplasms ; drug therapy ; genetics ; pathology ; Xenograft Model Antitumor Assays ; methods

Dead heart is an important trait of pith-decayed Scutellariae Radix. The purpose of this study was to clarify the scientific connotation of the dead heart using multi-omics. Metabolomics and transcriptomics combined with multivariate statistical analysis such as principal component analysis(PCA) and partial least squares discriminant analysis(PLS-DA) were used to systematically compare the differences in chemical composition and gene expression among phloem, outer xylem and near-dead xylem of pith-decayed Scutella-riae Radix. The results revealed significant differences in the contents of flavonoid glycosides and aglycones among the three parts. Compared with phloem and outer xylem, near-dead xylem had markedly lowered content of flavonoid glycosides(including baicalin, norwogonin-7-O-β-D-glucuronide, oroxylin A-7-O-β-D-glucuronide, and wogonoside) while markedly increased content of aglycones(including 3,5,7,2',6'-pentahydroxy dihydroflavone, baicalin, wogonin, and oroxylin A). The differentially expressed genes were mainly concentrated in KEGG pathways such as phenylpropanoid metabolism, flavonoid biosynthesis, ABC transporter, and plant MAPK signal transduction pathway. This study systematically elucidated the material basis of the dead heart of pith-decayed Scutellariae Radix with multiple growing years. Specifically, the content of flavonoid aglycones was significantly increased in the near-dead xylem, and the gene expression of metabolic pathways such as flavonoid glycoside hydrolysis, interxylary cork development and programmed apoptosis was significantly up-regulated. This study provided a theoretical basis for guiding the high-quality production of pith-decayed Scutellariae Radix.
Drugs, Chinese Herbal/chemistry* ; Scutellaria baicalensis/chemistry* ; Glucuronides ; Multiomics ; Flavonoids/chemistry*

Due to numerous obstacles such as complex matrices, real-time monitoring of complex reaction systems (, medicinal herb stewing system) has always been a challenge though great values for safe and rational use of drugs. Herein, facilitated by the potential ability on the tolerance of complex matrices of extractive electrospray ionization mass spectrometry, a device was established to realize continuous sampling and real-time quantitative analysis of herb stewing system for the first time. A complete analytical strategy, including data acquisition, data mining, and data evaluation was proposed and implemented with overcoming the usual difficulties in real-time mass spectrometry quantification. The complex Fuzi (the lateral root of )-meat stewing systems were real-timely monitored in 150 min by qualitative and quantitative analysis of the nine key alkaloids accurately. The results showed that the strategy worked perfectly and the toxicity of the systems were evaluated and predicated accordingly. Stewing with trotters effectively accelerated the detoxification of Fuzi soup and reduced the overall toxicity to 68%, which was recommended to be used practically for treating rheumatic arthritis and enhancing immunity. The established strategy was versatile, simple, and accurate, which would have a wide application prospect in real-time analysis and evaluation of various complex reaction systems.

Drug metabolism and pharmacokinetics (DMPK) is an important branch of pharmaceutical sciences. The nature of ADME (absorption, distribution, metabolism, excretion) and PK (pharmacokinetics) inquiries during drug discovery and development has evolved in recent years from being largely descriptive to seeking a more quantitative and mechanistic understanding of the fate of drug candidates in biological systems. Tremendous progress has been made in the past decade, not only in the characterization of physiochemical properties of drugs that influence their ADME, target organ exposure, and toxicity, but also in the identification of design principles that can minimize drug-drug interaction (DDI) potentials and reduce the attritions. The importance of membrane transporters in drug disposition, efficacy, and safety, as well as the interplay with metabolic processes, has been increasingly recognized. Dramatic increases in investments on new modalities beyond traditional small and large molecule drugs, such as peptides, oligonucleotides, and antibody-drug conjugates, necessitated further innovations in bioanalytical and experimental tools for the characterization of their ADME properties. In this review, we highlight some of the most notable advances in the last decade, and provide future perspectives on potential major breakthroughs and innovations in the translation of DMPK science in various stages of drug discovery and development.