OBJECTIVE: To investigate the pharmacokinetics of single and multiple oral doses of minocycline hydrochloride extended-release tablets and evaluate its extended-release characteristics by comparing with ordinary tablets. METHODS: Twelve healthy volunteers received a single oral dose of 45, 90 and 135 mg minocycline hydrochloride extended-release tablets respectively with a 10-day washout period. After the single-dose study, the volunteers participated in the multiple dose study in which each volunteer received 90 mg per day for 10 consecutive days. The ordinary tablets were administered by single and multiple doses as reference preparation in the end. The concentrations of minocycline in human plasma were determined by LC-MS method. RESULTS: The main pharmacokinetic parameters of a single dose of minocycline hydrochloride extended-release tablets of 45, 90 and 135 mg in 12 healthy volunteers were as follows: pmax (0.4770±0.1280), (1.011±0.191) and (1.500±0.281) μg · mL-1, tmax(3.3±1.1),(3.6±0.8) and (3.4±0.7) h, t1/2 (17.1±5.4), (18.3±4.9) and (17.9±3.4) h, AUC0-t (9.391±3.019), (20.01±3.07) and (31.81±6.80) μg · h · mL-1, respectively. And those of multiple-dose of minocycline hydrochloride extended-release tablets of 90 mg were as follows: pav(0.8440±0.2250) μg · mL-1, DF(1.1±0.2), pmax(1.438±0.383) μg · mL-1, tmax(3.5±0.8) h, t1/2 (19.3±4.4) h, AUC0-t(31.18±9.39) μg · h · mL-1. The main pharmacokinetic parameters of a single dose of ordinary minocycline hydrochloride tablets of 100 mg were as follows: pmax(1.418±0.427) μg · mL-1, tmax (2.6±0.7) h, t1/2 (16.9±3.9) h, AUC0-t(25.35±5.80) μg · h · mL-1, and those of multiple-dose of ordinary minocycline hydrochloride tablets at 100 mg were as follows: pav(1.229±0.377) μg · mL-1, DF(1.3±0.2), pmax(2.188±0.652) μg · mL-1, tmax(2.3±0.7) h, t1/2 (17.7±2.4) h, AUC0-t(44.83±16.29) μg · h · mL-1, respectively. CONCLUSION: In the range of 45-135 mg, the AUC0-t and pmax of minocycline hydrochloride extended-release tablets increased in a dose-dependent manner after single-dose administration, indicating linear pharmacokinetics. No significant gender differences were found. An accumulation of 50% in AUC0-t occurred after multiple-dose administration. The minocycline hydrochloride extended-release tablets have extended-release character comparing with ordinary tablets.

Acrocephalosyndactylia ; diagnosis ; genetics ; therapy ; Female ; Humans ; Infant

Objective To investigate the impact of compliance and quality of life of psychological intervention for cancer patients and their primary caregivers,as well as the correlation between the psychological issues of patients and their primary caregivers.Methods The enrolled patients were randomly divided into intervention group and control group.The patients in intervention group were given to standardize anti-tumor therapy,while the patients and their primary caregivers were given psychological intervention once a week.The patients in the control group only received standard anti-tumor therapy.By TDL determination of quality of life,anxiety rating scale (SAS) and self-rating depression scale (SDS),in front of the psychological intervention after 8 weeks of intervention,the two groups of patients and their primary caregivers were questionnaired,and recorded the completion of the treatment plan.By SPSS 12.0 software,the statistics were completed.Results 51 cases in intervention group and 38 cases in control group were able to complete the number of people expected to treat there was a statistically significant (P ＜ 0.05).TDL determination and quality of life scores in intervention group patients and their primary caregivers were significantly higher (P ＜ 0.05).SAS and SDS score in intervention group patients and their primary caregivers were significantly lower than control group (P ＜ 0.05).Conclusion The effective psychological intervention to cancer patients and their primary caregivers during the treatment of patients could improve the compliance of cancer patients,the quality of life of cancer patients and their primary caregivers.The psychological problems between the patients and primary caregivers are positive correlation.

Jin's three-needle technique is named after Professor JIN Rui. The connotation of Jin's three-needle technique is summarized by his followers through long-term teaching and clinical practice. His principle and method of point combination are based on syndrome differentiation of acupuncture. And his unique needling technique and treating principle of mental tranquilization also play an important role in his clinical practice.
Acupuncture Therapy ; instrumentation ; methods ; Humans ; Needles

Objective Multimeric cyclic RGD (Arg-Gly-Asp) peptides are capable of improving the integrin αvβ3-binding affinity due to the polyvalence effect.In this study,the authors prepare 99Tcm-la-bearing cyclic RGD tetramer E{E[c(RGDfK)]2}2,and evaluate its biodistribution and imaging in nude mice beating U87 MG human glioma xenografts with integrinαvβ3-positive.Methods 99Tcm-hydrazino-nictinamide (HYNIC)-E{E[c(RGDfK)]2}2 was prepared by two-step method,while HYNIC wag chosen as bifunctional chelator,and tricine and trisodium triphenylphosphine-3,3,3-trisuifonate (TPPTS) as coligands.The af-finity of c (RGDyK) monomer,HYNIC-E[c(RGDfK)]2 dimer and HYNIC-E{E[c(RGDfK)]2}2 tetramer to integrin αvβ3 was compared by in vitro competitive assay against binding of 125I-c(RGDyK)to integrin αvβ3.positive U87 MG human glioma cells.The biodistribution [the percentage of injection dose per gram of tissue(%ID/g)] and imaging were performed in nude mice bearing UB7MG human glioma xenografts.Re-suits The labeling yield of 99Tcm-HYNIC-E{E[c(RGDfK)2}2 was over 95%,and the radiochemical purity was more than 99%after purification with Sop-Pak C18 cartridge.The 50%inhibiting concentration (IC30) val-ues of c(RGDyk),HYNIC-E[c(RGDfK)]2 and HYNIC-E{E[c(RGDfK)]2}2 were 85.9,9.5 and 4.5 nmol/L, respectively.The result indicated that RGD tetramer possessed a significantly higher affinity to in-tegrinαvβ3.The biodistribution data showed that 99Tcm-HYNIC-E{E[c(RGDfK)]2}2 was excreted mainly through kidneys.The tumor uptake of 99Tcm-HYNIC-E{E[c(RGDfK)]2}2 was two times higher than 99Tcm- HYNIC-E[c(RGDfK)]2,at 1h postinjection,with the uptake of(10.32±0.07)%ID/g and(5.15±0.52)%ID/g,respectively,which was consistent with the in vitro competitive binding data.The tumor up-tale of 99Tcm-HYNIC.E{E[c(RGDfK)]2}2 was still as higher as(9.35±1.35)%ID/g at 4 h postinjec-tion, which demonstrated that the retention time of radiotracer in tumor was long enough.The imaging showed that tumor was clearly visualized at 1h postinjection,and the image at 4 h postinjection Was better.Conclusion The higher tumor uptake and longer retention time in tumor make 99Tem-HYNIC-E{E[c(RG-DfK)J 2}2 a promising radiotracer for integrinαvβ3-positive tumors imaging,furthermore,suggest that radi-onuelides(such as 90Y).1abeled RGD tetramer is more suitable for the therapy of integrin αvβ3-positive tumors.

Objective To provide valid data and useful genetic counseling in the clinical application of non‐invasive prenatal test (NIPT) ,fetal chromosomal disorder were screened by massive parallel sequencing and made a follow‐up study .Methods Preg‐nant women with Down screening in high‐risk were screened by NIPT ;NIPT verified high‐risk individuals were suggested for kary‐otyping ;and we follow up on whoever showed low risk by NIPT before and after their deliveries .Results (1)Totally 1 676 cases of pregnant women were tested by NIPT ,25 cases prompted to be abnormal ,with an abnormal rate of 1 .49% ,karyotype analysis re‐sults in 12 cases of abnormalit ,the accuracies of NIPT for T21 ,T18 ,XO ,XXY ,and XYY were 99 .93% ,100 .00% ,99 .66% , 100 .00% ,100 .00% respectively ;the accuracy of NIPT for women with advanced paternal age and twins were both 100 .00% ;kary‐otyping positive individuals underwent abortion ,which gives a prenatal intervention rate of 100 .00% .(2)Out of 1 651 cases of NIPT low risk testers ,1 468 cases were successfully followed up ,with a 88 .91% success rate .We found chromosome abnormality with one case of inversion of chromosome 9 (maternal) .(3)Ultrasound‐detection possessed 98 .17% accuracy and 7 .69% in detec‐tion rate;in high‐risk pregnant woman ,Down screening had an accuracy of 0 .88% and false positive rate of 99 .12% ;98 .71%women were avoided prenatal diagnosis via NIPT .Conclusion Compare to ultrasound and maternal plasma screening ,NIPT is a far more accurate prenatal screening approach .To build effective follow‐up and service systems of NIPT is necessary to reduce birth de‐fects in medical institutions .

OBJECTIVETo investigate the expression of suppressor of cytokine signaling(SOCS)-3 and caspase-3 and their correlative significance in endometriosis.

METHODSImmunohistochemical EnVision method was used to detect the SOCS-3 and caspase-3 protein expression in ectopic and eutopic endometrium (n = 32) of patients with endometriosis, as well as normal endometrium (n = 30) of women without endometriosis.

RESULTSSOCS-3 and caspase-3 proteins were expressed in all three groups and not affected by the menstrual cycles. The expression of SOCS-3 in ectopic endometrium (5.54 ± 2.12) was significantly lower than that in eutopic (7.39 ± 1.09, P = 0.001) and control group (7.48 ± 1.26, P < 0.01), but without difference between the eutopic and control group (P = 0.756). SOCS-3 expression in ectopic and eutopic endometrium was significantly lower in III/IV stages than that in I/II stages of endometriosis (P < 0.05). Significantly lower expression of caspase-3 protein was found in ectopic (3.20 ± 1.24) and eutopic endometrium (3.88 ± 1.93) as compared with the control group (6.49 ± 1.85, P < 0.01), however ectopic and eutopic endometrium showed no significant difference (t = 1.66, P = 0.10). There was no significant difference of the expression of caspase-3 in ectopic and eutopic endometrium at different disease stages (P > 0.05). Positive correlation was found between the expression of SOCS-3 and caspase-3 proteins in ectopic endometrium (r = 0.655, P < 0.01).

CONCLUSIONSOCS-3 may be involved in the development of endometriosis through inhibition of apoptosis of ectopic endometrial cells.

Adult ; Caspase 3 ; metabolism ; Endometriosis ; metabolism ; pathology ; Endometrium ; metabolism ; pathology ; Female ; Humans ; Immunohistochemistry ; Menstrual Cycle ; Middle Aged ; Suppressor of Cytokine Signaling 3 Protein ; Suppressor of Cytokine Signaling Proteins ; metabolism ; Uterine Diseases ; metabolism ; pathology ; Young Adult

BACKGROUNDThere is no validated blood biomarker available for glioma management. Invasive growth is the key feature of glioma. We assessed the clinical usefulness of plasma tissue inhibitor of metalloproteinase 1 (TIMP-1), which has less molecular weight than metalloproteinases, as a potential blood biomarker for glioma.

METHODSA total of 285 patients and 59 normal subjects were studied. Plasma concentration of TIMP-1 was measured with enzyme-linked immunosorbent assay. Plasma TIMP-1 was compared between normal and glioma patients, between patients with different pathological grades, and between patients with different prognoses. Longitudinal changes in plasma TIMP-1 during treatment were also evaluated. Plasma matrix metalloproteinase (MMP)-9 level was also assayed and its clinical usefulness was compared with that of TIMP-1.

RESULTSPlasma TIMP-1 and MMP-9 were both increased in glioma patients compared with normal controls (TIMP-1: P < 0.001; MMP-9: P = 0.007). Plasma TIMP-1 increases with increased tumor grade. In Grade IV gliomas, plasma TIMP-1 significantly increased after "successful removal" of the tumor (paired samples t-test, before operation vs. during chemotherapy without recurrence, t = -2.131, P = 0.038), but did not change significantly at the time of tumor recurrence (during chemotherapy without recurrence vs. after tumor recurrence, t = -0.652, P = 0.632). High plasma TIMP-1 level correlated with better survival in Grade IV glioma patients (hazard ratio: 0.550, 95% CI: 0.101-1.000, P = 0.036). In Grade IV gliomas, patients with higher plasma TIMP-1 had significantly longer survival time than those with lower plasma TIMP-1 level (25.23 vs. 18.95 months, log-rank P = 0.045). Plasma MMP-9 did not show significant association with either the pathological grade or the prognosis of glioma patients.

CONCLUSIONSPlasma TIMP-1 is associated with the diagnosis and prognosis of glioma patients. It appears to have better usefulness for guiding clinical decision making than plasma MMP-9. Further studies in an expanded patient population are needed to better define its clinical usefulness.

Adult ; Biomarkers, Tumor ; Case-Control Studies ; Female ; Glioma ; blood ; diagnosis ; Humans ; Male ; Middle Aged ; Tissue Inhibitor of Metalloproteinase-1 ; blood

BACKGROUNDBone metastasis is very common in lung cancer patients. Metastasis to spine can lead to paralysis and fracture, deteriorate the quality of patient's life. The objective of this study is to investigate the diagnostic values of bone scanning (NBS), MRI, CT and X-ray examination to discover bone meastasis of lung cancer, and the therapy of bone metastasis and the prognostic factors.

METHODSAbout 561 consecutive NSCLC cases were analyzed with NBS and compared with other radiological examinations (MRI, CT and X-ray).

RESULTSOut of the 455 positive patients by NBS, 300 cases were confirmed to be with bone metastases by dynamic follow-up, MRI, CT and X-ray, and 5 cases were false negative.The sensitivity and specificity of NBS was 98.36% and 39.45% respectively. The accuracy of NBS was 71.48%. Among the 305 patients with bone metastases, 23 patients had no records, 138 patients had bone pain, the incidence of asymptomatic bone metastasis was 47.21%. Multivariables analysis showed that asymptomatic bone metastasis, flat bone metastases, therapy with disodium pamidronate were significantly good prognostic factors, respectively (P < 0.05).

CONCLUSIONSA whole body NBS examination is preferred for the staging of NSCLC. NBS is necessary for patients with NSCLC. In order to exclude the possible false positive or false negative diagnosis by NBS, CT or MRI could be selected according to the sites of lesions.

OBJECTIVETo explore the antitumoral effect of indirubin on androgen-independent prostate cancer PC-3 cells and its possible mechanisms.

METHODSWe measured the inhibitory effect of indirubin on the proliferation of prostate cancer PC-3 cells using MTT assay, detected their cell cycles by flow cytometry, and determined the expressions of the cell cycle regulatory protein cyclin D1 and its related downstream gene c-myc by Western blot.

RESULTSThe viability of the PC-3 cells was significantly decreased by indirubin in a concentration-dependent manner, reduced to 52. 2% and 13. 6% at 5 and 10 µmol/L, respectively. The cell cycle of the PC-3 cells was markedly inhibited by indirubin at 5 µmol/L, with the cells remarkably increased in the G0 and G1 phases and decreased in the S and G2/M phases. Meanwhile, indirubin also inhibited the expressions of cyclin D1 and c-myc in the Wnt signaling pathway.

CONCLUSIONIndirubin can suppress the proliferation of androgen-independent prostate cancer PC-3 cells, which may be associated with its inhibitory effect on the cell cycle and Wnt signaling pathway.

Antibiotics, Antineoplastic ; administration & dosage ; pharmacology ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cell Survival ; drug effects ; Coloring Agents ; Cyclin D1 ; metabolism ; Dose-Response Relationship, Drug ; Genes, myc ; Humans ; Indoles ; administration & dosage ; pharmacology ; Male ; Prostatic Neoplasms, Castration-Resistant ; drug therapy ; pathology ; Proto-Oncogene Proteins c-myc ; metabolism ; Tetrazolium Salts ; Thiazoles