Background/Aims: Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. Methods: We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development. Results: Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. Conclusions Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.

According to folk usage of Aconitum carmichaelii Debx., the present study was designed to determine the feasibility of the stems and leaves of Aconitum carmichaelii Debx. as a new medicinal resource. Fourteen alkaloids in mother roots, fibrous roots, stems, and leaves of Aconitum carmichaelii Debx. were measured by HPLC-MS/MS. And multivariate analysis methods, such as clustering analysis and principal component analysis, were applied to analyze the difference among various parts. In addition, the acute toxicity, analgesia, and anti-inflammatory tests were carried out. The results suggested that the contents of alkaloids in mother roots and fibrous roots were approximate, but those of leaves and stems were different from mother roots and fibrous roots. The results of the acute toxicity testing demonstrated the toxicity of fibrous root was strongest, and mother roots were slightly less toxic than fibrous roots. The stems and leaves were far less toxic than mother and fibrous roots. In addition, the analgesia and inflammatory tests showed the effects of the various tissues had no difference each other. These results provided a basis for developing new complementary and alternative treatments for rheumatoid arthritis patients. Simultaneously, the approach may also turn wastes into treasure and promote the development of circular economy.
Aconitum ; chemistry ; Alkaloids ; administration & dosage ; chemistry ; toxicity ; Animals ; Anti-Inflammatory Agents ; administration & dosage ; chemistry ; toxicity ; Arthritis, Rheumatoid ; drug therapy ; Chromatography, High Pressure Liquid ; Drug Evaluation, Preclinical ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; toxicity ; Female ; Humans ; Male ; Mice ; Plant Leaves ; chemistry ; Plant Roots ; chemistry ; Plant Stems ; chemistry ; Tandem Mass Spectrometry

Objective: To investigate the anti-proliferation effect and mechanism of zoledronic acid (ZOL) on human colon cancer line SW480. Methods: SW480 cells were treated with 0, 12.5, 25, 50, 100 and 200 μmoL/L of ZOL for 48 h, and CCK-8 assay was employed to obtain the survival rate of SW480 cells. SW480 cells were treated with 25 μmoL/L of ZOL for 0, 12, 24, 48 and 72 h, and then the survival rate was obtained. SW480 cells of the ZOL group were treated with 25 μmoL/L of ZOL for 48 h, while cells of the CsA + ZOL group were pretreated with 10 μmoL/L of CsA for 0.5 h and then treated with 25 μmoL/L of ZOL for 48 h. Then the survival rates of SW480 cells of the control group, ZOL group and CsA + ZOL group were determined. Flow cytometry was employed to detect the apoptosis rate and the mitochondrial transmembrane potential (▵Ψm) of the three groups and Western blot was used to detect the expressions of cyt C in the cytosol of the three groups. Results: ZOL inhibited the proliferation of SW480 cells, and the inhibition rate positively correlated with the concentration of ZOL and the action time (P < 0.01). The cell survival rate and the ▵Ψm of the ZOL group were greatly lower than those of the control group, while the apoptosis rate and the expression of cyt C in the cytosol were obviously higher than those of the control group. All the differences showed distinctly statistical significances (P < 0.01). The cell survival rate and the ▵Ψm of the CsA + ZOL group were all lower than those of the control group, but substantially higher than those of the ZOL group; while the apoptosis rate and the expression of cyt C in the cytosol were higher than those of the control group, but distinctly lower than those of the ZOL group. All the differences were statistically significant (P < 0.01). Conclusions: ZOL can induce the apoptosis in human colon cancer line SW480 and then inhibit the proliferation of SW480 cells directly by opening the mitochondrial permeability transition pore abnormally, decreasing ▵Ψm, and releasing the cyt C into the cytosol. And the effect enhances with the increases of the concentration of ZOL and the action time.

To make a thorough investigation of the common She's nationality wild medicinal plants resources in our country, including the species, the distribution, the folk application and the endemic medicinal plant species, Field surveyed was conducted with 25 She people mainly lived area (county, district or city) throughout the country, the folk prescription and treatment cases provided by She's medical personnel, the drug usage and dosage, the commonly used traditional She's medicine and drug samples were collected. And the distribution, growing environment of these plants were investigated, their characteristics, photographs, GPS data and track were record , and the fresh wax leaf or plants specimens were collected. In total 1 600 varieties of folk medicine of She's nationality, 450 disease names and 1 016 prescriptions were collected. 520 kinds of these medicinal plants were commonly used, growing mainly distributed in the southeastern China, about 200 meters above sea level to 1 500 meters. There are 5 First-Grade State protection wild plants (medicinal), 15 second-Grade State protection wild plants (medicinal), and 11 She characteristic medicinal plants in our study, they belong to 144 families, 312 genera 494 species, 2 subspecies, 17 varieties, 3 forms and 1 cultivated varieties of She's nationality. Folk medicine usage is different from the traditional Chinese medicine and ethnic medicine. This survey finds out the common She's nationality wild medicinal plants resources in China, including the species, the distribution, the folk application and commonly used drugs, and found the rare and endangered medicinal plants and the She's nationality endemic medicinal plants, which provides a basis for further development and use the traditional She's medicine resources.
China ; ethnology ; Conservation of Natural Resources ; Drugs, Chinese Herbal ; analysis ; Ethnic Groups ; Humans ; Medicine, Chinese Traditional ; Plants, Medicinal ; chemistry ; classification ; growth & development

OBJECTIVETo evaluate the clinical efficacy and safety of treatment of chronic primary glomerulopathy (CPG) patients of Shen deficiency and dampness heat syndrome (SDDHS) by Yishen Qingli Granule (YQG) combined with low-dose Tripterygium Wilfordii multiglycoside Tablet (TWT).

METHODSTotally 231 CPG patients of SDDHS were enrolled in this study (including 60 patients from First Affiliated Hospital of Nanjing University of Chinese Medicine, 58 from First Affiliated Hospital of Nanjing Medical University, 46 from Xinqiao Hospital of Third Military Medical University, 35 from First Affiliated Hospital of Guangzhou University of Chinese Medicine, 14 from First Affiliated Hospital of Soochow University, and 18 from Wuxi Affiliated Hospital of Nanjing University of Chinese Medicine). They were randomly assigned to the control group (116 cases) and the trial group (115 cases) according to block group method. There were 217 cases in the safety analysis set (109 cases in the trial group vs 108 cases in the control group), and 203 cases in the full analysis set (99 cases in the trial group vs 104 cases in the control group). All patients received basic treatment such as ACEI/ARB. Furthermore, YQG (consisting of raw astragalus 10 g, prepared Polygonum Multiflorum 10 g, Pyrrosia 10 g, 1.5 g each package, containing 10 g of crude drugs) was additionally given to patients in the trial group, each package, twice daily. The TWT (10 mg) was given, twice a day. The TWT dose was adjusted according to 24 h urinary total protein (UTP). The placebos of YQG and TWT were administered to those in the control group. The treatment course consisted of 24 weeks and the follow-up visit lasted for 24 weeks. The biochemical indices were observed before and after treatment including 24 h UTP, urine red cell count (U(RBC)), renal functions (BUN, SCr), blood routine test (WBC), and liver functions (SGPT, SGOT). Reverse reactions such as gastrointestinal discomfort, skin rash, and irregular menstruation were also observed.

RESULTSCompared with the control group, the total effective rate was better in the trial group (82.83% vs 61.54%, P < 0.01). Results of stratified comparison of UTP showed better efficacy in the trial group (0.8-3.0 g/24 h, P < 0.01). The UTP decline occurred in the trial group after 8 weeks of treatment, with stable action, showing statistical difference when compared with the control group (P < 0.01). In the trial group, U(RBC) level decreased after treatment but changed more significantly. But there was no statistical difference in the changes when compared with the control group (P > 0.05). After treatment, there were no statistical difference in safety indicators such as WBC, SGPT, and SGOT between the two groups after treatment (P > 0.05).

CONCLUSIONOn the basis of basic treatment such as ACEI/ARB, application of YQG combined with low-dose TWT had better effect in controlling proteinuria of CPG patients, and could help stabilizing their conditions with less adverse reactions.

Adult ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Kidney Diseases ; diagnosis ; drug therapy ; Kidney Glomerulus ; pathology ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Phytotherapy ; methods ; Treatment Outcome ; Tripterygium

OBJECTIVETo study possible influences of 1,25(OH)(2)D(3) on endothelial cell proliferation, apoptosis and endothelial nitric oxide synthase (eNOS) expression of aorta in apolipoprotein E-deficient (apoE(-/-)) mice and to explore the relationship between vitamin D and atherosclerosis.

METHODEndothelial cell of aorta in apoE(-/-) mice were isolated and cultured, and the influence of 1,25(OH)(2)D(3) on endothelial cell proliferation were observed by MTT, apoptosis of cells were quantitated by terminal deoxynucleotidyl transferase mediated dUTP nick end labelling, Bcl-2 mRNA, fas mRNA and eNOS mRNA was detected by reverse transcription-polymerase chain reaction.

RESULTEndothelial cell proliferation rate of aorta did not significantly change in the two control groups (0.162 ± 0.031 vs. 0.158 ± 0.006, P > 0.05). Compared with control groups, 1,25(OH)(2)D(3) stimulated endothelial cell proliferation of aorta (P < 0.05), but endothelial cell proliferation rate did not significantly change in different 1,25(OH)(2)D(3) concentration groups [1,25(OH)(2)D(3) concentration: 10(-4)mol/L, 10(-5) mol/L, 10(-6) mol/L, 10(-7) mol/L, 10(-8) mol/L, endothelial cell proliferation rate: 0.189 ± 0.013 vs. 0.285 ± 0.011 vs. 0.296 ± 0.026 vs. 0.284 ± 0.017 vs. 0.233 ± 0.010, P > 0.05]. 1,25(OH)(2)D(3) research concentration as chosen as 10(-6) mol/L. In 1,25(OH)(2)D(3) 10(-6) mol/L group, the expression of Bcl-2, eNOS mRNA was significantly increased (0.78 ± 0.16 vs. 0.46 ± 0.21 vs. 0.42 ± 0.17, 0.56 ± 0.16 vs. 0.39 ± 0.13 vs. 0.35 ± 0.11, 0.46 ± 0.2 vs. 10.42 ± 0.17 vs. 0.78 ± 0.16, 0.79 ± 0.21 vs. 0.81 ± 0.20 vs. 0.43 ± 0.12), apoptotic index, Fas mRNA was significantly decreased (15.14 ± 3.19 vs. 18.94 ± 4.22 vs. 19.27 ± 4.58, 0.43 ± 0.12 vs.0.79 ± 0.21 vs. 0.81 ± 0.20)(P < 0.05). The quantity of eNOS gene expression was inversely associated with apoptosis index and Fas mRNA, was positively associated with Bcl-2 mRNA (r = -0.676, -0.758, 0.762, P < 0.01).

CONCLUSION1,25(OH)(2)D(3) stimulated endothelial cell proliferation, inhibited apoptosis and increased eNOS expression of aorta in apoE(-/-) mice. These results may deepen understanding of the pathogenesis of atherosclerosis.

Animals ; Aorta ; metabolism ; Apolipoproteins E ; deficiency ; Apoptosis ; drug effects ; Calcitriol ; pharmacology ; Cell Proliferation ; drug effects ; Cells, Cultured ; Endothelial Cells ; metabolism ; Female ; Male ; Mice ; Nitric Oxide Synthase Type III ; metabolism ; RNA, Messenger ; genetics

OBJECTIVETo construct lentivector carrying Tie2-Small interfering RNA (SiRNA), so as to study its influence on malignant melanoma cells.

METHODSRecombinant plasmid pSilencer 1.0-U6-Tie2-siRNA and plasmid pNL-EGFP were digested with XbaI, ligated a target lentiviral transfer plasmid of pNL-EGFP-U6-Tie2-I or pNL-EGFP-U6-Tie2-II, and then the electrophoresis clones was sequenced. Plasmids of pNL-EGFP-U6-Tie2-I and pNL-EGFP-U6-Tie2-II were constructed and combined with pVSVG and pHelper, respectively, to constitute lentiviral vector system of three plasmids. The Lentiviral vector system was transfected into 293T cell to produce pNL-EGFP-U6-Tie2- I and pNL-EGFP-U6-Tie2-II lentivirus. Then the supernatant was collected to determine the titer. Malignant melanoma cells were infected by both lentiviruses and identified by Realtime RT-PCR to assess inhibitory efficiency.

RESULTSThe recombinant lentiviral vectors of Tie2-RNAi were constructed successfully which were analyzed with restriction enzyme digestion and identified by sequencing. And the titer of lentiviral vector was 8.8 x 10(3)/ml, which was determined by 293T cell. The results of Realtime RT-PCR demonstrated that the lentiviral vectors of Tie2-RNAi could infect malignant melanoma cells and inhibit the expression of Tie2 genes in malignant melanoma cells (P<0.01). There was no significant difference in the expression level (P>0.05) between the two lentiviral vectors of Tie2-RNAi.

CONCLUSIONSLentivector carrying Tie2-SiRNA can be constructed successfully and inhibit the expression of Tie2 gene in vitro significantly. The study will supply the theory basis for the further research on the inhibition of tumor growth in vivo.

Cell Line, Tumor ; Genetic Vectors ; Humans ; Lentivirus ; genetics ; Melanoma ; genetics ; Plasmids ; RNA Interference ; RNA, Small Interfering ; genetics ; Receptor, TIE-2 ; genetics ; Transfection

The complete genomic sequence of a watermelon isolate of Cucumber green mottle mosaic virus (CGMMV-LN) in Liaoning province was determined and compared with other cucurbit-infecting tobamoviruses. The genomic RNA of CGMMV-LN comprised 6422 nt, and 5'- and 3'- noncoding regions consisted of 59 nt and 175 nt, respectively. The encoded four proteins were two replicase proteins of 186 kD and 129 kD, move protein of 29 kD and coat protein of 17.4 kD. The alignment results of complete nucleotide sequence showed that CGMMV-LN shared identities of 97.6%-99.3% with four other CGMMV isolates, but only shared identities of 61.7%-62.8% with three other tobamoviruses. Homology trees generated from replicase proteins of 186 kD and coat proteins suggested that cucurbit-infecting tobamoviruses could be separated into two subgroups: subgroup I comprising all the isolates of CGMMV and subgroup II comprising Cucumber fruit mottle mosaic virus, Kyuri green mottle mosaic virus and Zucchini green mottle mosaic virus.
Base Sequence ; China ; Citrullus ; virology ; Genome, Viral ; genetics ; Molecular Sequence Data ; Tobamovirus ; genetics

This study was aimed to investigate the characteristics of human bone marrow mesenchymal stem cells during ex-vivo expansion, MSCs were isolated from human bone marrow. At each passage, the characteristics of proliferation kinetics, osteogenic and adipogenic differentiation potential were analyzed, and cell morphology, surface markers were investigated as well. The karyotype analysis was done in different passage cells. The infection HIV, HCV, HBV and TP were detected by ELISA. Mycoplasma contamination in vitro was detected by PCR method. HLA-SBT was used to reanalyze the results of HLA antigens and alleles. STR genetic loci were detected by PCR in the MSC1, MSC2, MSC3 and MSC4. The results indicated that the proliferative ability and osteogenic potential decreased with the increase of passage number during culture expansion. The multiple differentiation potential of MSCs was maintained during their life span. Karyotype analysis showed that MSCs from 4 groups before passage 8 were normal. The expression of CD29, CD44, CD105, CD166 and CD73 were positive. The expression of CD14, CD34, CD45, CD80, CD86 were all negative. SBT was used to identify HLA-A, B, Cw, DRB1, DRPB1, DQ alleles in the MSC1, MSC2, MSC3, MSC4. The genetype of STR in the MSC1, MSC2, MSC3, MSC4 was different. MSC 3 was examined by TP-ELISA to confirm the infectious disease of TP. MSC2 was contaminated by mycoplasma at passage 5. It is concluded that culture expansion causes MSCs to gradually lose their stem cell properties. During ex-vivo expansion of MSCs, the osteogenic differentiation potential is decreased. MSCs before passage 8 can be a valuable subject for basic research and clinical application.
Adipogenesis ; Adult ; Bone Marrow Cells ; cytology ; Cell Differentiation ; physiology ; Cells, Cultured ; Female ; Humans ; Karyotyping ; Male ; Mesenchymal Stromal Cells ; cytology ; Osteogenesis

OBJECTIVETo improve the recognition and treatment of Chinese cutis verticis gyrata.

METHODSBased on the review of the etiopathology, clinical features, diagnosis, classification and treatment of the disease in the literatures, six patients with the cutis verticis gyrata were treated with the skin graft or the expanded scalp flap.

RESULTSThe operative effects were satisfactory during 6 months to 5 years of the follow-ups. No recurrence was found in all cases. Two patients treated with skin graft had lead to baldness, four patients treated with the expanded scalp flap had been good appearance.

CONCLUSIONSThe method of the expanded scalp flap is good and effective treatment for the cutis verticis gyrate.

Adolescent ; Adult ; Female ; Humans ; Male ; Middle Aged ; Scalp ; abnormalities ; Scalp Dermatoses ; pathology ; surgery ; Tissue Expansion ; methods ; Young Adult