Huperzine A is a potent,reversible,and blood-brain barrier permeable acetylcholinesterase irhibitor.The aim of this study was to compare the pharmacokinetics,tolerability,and bioavailability of two formulations with the established reference formulation of huperzine A in a fasting,healthy Chinese male population.This was a randomized,single-dose,3-period,6-sequence crossover study.The plasma concentrations of huperzine A were determined by liquid chromatography tandem mass spectrometry.Tolerability was assessed based on subject interview,vital sign monitoring,physical examination,and routine blood and urine tests.The mean (SD) pharmacokinetic parameters of the reference drug were Cmax,1.550 (0.528) ng/mL;t1/2,12.092 (1.898) h;AUC0-72h,17.550 (3.794) ng.h/mL.Those of the test formulation A and test formulation B were Cmax,1.412 (0.467),1.521 (0.608) ng/mL;t1/2,12.073 (2.068),12.271 (1.678) h;AUC0-72h,15.286 (3.434) ng.h/mL,15.673 (3.586) ng.h/mL.The 90％ confidence intervals for the AUC0-72h and Cmax were between 0.80 and 1.25.No adverse events were reported by the subjects or found with results of clinical laboratory test.The test and reference products met the regulatory criteria for bioequivalence in these fasting,healthy Chinese male volunteers.All three formulations appeared to be well tolerated.

Objective: To analyze the effect of acupuncture versus hormone replacement therapy (HRT) for premature ovarian insufficiency (POI). Methods: China National Knowledge Infrastructure (CNKI), Wanfang Academic Journal Full-text Database (Wanfang), Chongqing VIP Database (CQVIP), China Biology Medicine Disc (CBM), Web of Science, Cochrane Library, PubMed, and Excerpta Medica Database (EMBASE) were searched up to January 31st, 2019 to identify randomized controlled trials (RCTs) evaluating the effect of acupuncture for POI. The primary outcome was the level of basal serum follicle- stimulating hormone (FSH). Secondary outcomes included serum levels of luteinizing hormone (LH), estradiol (E2) and anti-Müllerian hormone (AMH). Two authors extracted data independently and assessed the risk of bias and the methodological quality using the Cochrane's tool. Meta-analysis was conducted by RevMan version 5.3. Results: Eight eligible RCTs with a total of 496 POI patients were included in the meta-analysis. The pooled results showed that there was a significant reduction in the basal serum FSH level (MD=-5.82, 95％CI:-9.76 to -1.87, I2=82％, P=0.004) and a remarkable elevation in the basal E2 level (SMD=0.93, 95％CI: 0.34 to 1.52, I2=88％, P=0.002) in the acupuncture group when compared with the control. Subgroup analysis showed that compared with HRT, a significant decrease in the FSH level was observed in both acupuncture alone (MD=-4.53, 95％CI:-8.96 to -0.10, I2=73％, P=0.04) and acupuncture plus HRT (MD=-9.60, 95％CI:-17.60 to -1.61, I2=50％, P=0.02), while a remarkable elevation of E2 was only found in acupuncture plus HRT (SMD=1.43, 95％CI: 1.03 to 1.82, I2=0％, P<0.00001). There was no significant difference in the LH level between acupuncture and HRT (MD=-3.16, 95％CI:-9.41 to 3.10, I2=0％, P=0.32), only one trial reported AMH, and no significant difference was found between acupuncture and HRT. Conclusion: The present study indicated that acupuncture had an advantage over HRT in reducing serum FSH level and increasing serum E2 level in women with POI. However, evidence supporting the finding is limited due to the small sample size, potential methodological flaws and significant heterogeneity. Hence, this conclusion still needs to be verified by high-quality RCTs.

OBJECTIVE: To discuss forensic identification of floating shoulder injury (FSI). METHODS: To analyze fifteen cases of FSI which were accepted from Jan. 1993 to Jan. 2006, including 15 shoulder neck fracture, 13 clavide stem fracture and 2 distal end clavide fracture, the function of shoulder joint was evaluated six months after injure considering the following three aspects: result of forensic examination such as X-ray photograph, CT and MRI, the injurers' symptom, objective sign and joint function, shoulder joint territory, degree of pain and local muscle power. RESULTS: Basing on the curative effect standard of Herscovic, all cases were divided into good. Modest, worst, which included 2, 4, 9 cases respectively; referring the standard of GA35-92, GB18667-2002, all cases were divided into six, seven, eight, nine and ten degree, which included 2,9,2,1,1 cases respectively. CONCLUSION As a special powerful injure, FSI always companied with concurrent and multiple injure, and characterized by missed, incorrect and delayed diagnosis and infelicitous treatment, which lead to the high frequency and degree of injure. To prevent missed and incorrect forensic identification, we should have a full realization of the particularity of FSI, and evaluate the function of shoulder all-sidely, objectively and synseticaly.
Accidents, Traffic ; Adolescent ; Adult ; Clavicle/surgery* ; Female ; Forensic Dentistry/methods* ; Fractures, Bone/surgery* ; Humans ; Male ; Middle Aged ; Pain/pathology* ; Range of Motion, Articular ; Retrospective Studies ; Scapula/surgery* ; Shoulder Injuries ; Shoulder Joint/physiopathology* ; Tomography, X-Ray Computed ; Wounds and Injuries/surgery* ; Young Adult

To identify the active constituents in vitro and blood-absorbed ingredients in vivo from Yin Chen Hao decoction provides scientific evidence for probing its prevention and treatment mechanism on acute liver injury. An ultrahigh performance liquid chromatography quadrupole-time of flight-mass spectrometry (UPLC-QTOF/MS) method was applied for analysis of Yin Chen Hao decoction and the serum samples of mice with con-A induced acute liver injury after preventive oral administration for 14 days (the use of all laboratory animals in this study was approved by the Ethics Committee of the Naval Medical University, 19YF1459400). A total of 90 chemical constituents were identified from Yin Chen Hao decoction, mainly were flavonoids, terpenoids, tannins, quinones. 5 prototype compounds were identified in the serum, including chrysophanol, deoxyrhapontin-8-O-gallate, mussaenosidic acid, herniarin, emodin. The established UPLC-QTOF/MS method could efficiently and sensitively identify the constituents in vitro and blood-absorbed ingredients of Yin Chen Hao decoction, primarily clarify the material basis of its hepatoprotective effect, and provided a scientific basis for the quality marker selection and the pharmacodynamic material basis research on the decoction.

OBJECTIVETo analyze the clinical features of patients with newly diagnosed myeloma bone disease (MBD).

METHODClinical features of MBD in two hundred and five patients with newly diagnosed multiple myeloma (MM) were analyzed retrospectively. The relationship between outcome of different grades of MBD patients and their prognosis was compared.

RESULTS(1) Among the 205 patients, one hundred and fifty (72.7%) had bone pain as the first symptom. (2) According to X-ray evaluation, there were 23 (11.3%) of grade 0, 14 (6.9%) grade 1, 23 (11.3%) of grade 2, 68 (33.3%) grade 3 and 76 (37.2%) grade 4. (3) Patients with grade2-4 MBD had significantly higher ECOG performance score, marrow plasmacytes, marrow CD138(+) CD38(+) cell percentage and serum IL-6 level than those with grade 0 - 1 did (P < 0.05). Patients with grade 4 MBD presented with hypocalcemia (P < 0.05) more often than those with grades 0 - 3 diseases did. (4) There was no significant difference in response to initial induction chemotherapy among the five groups (P = 0.642). (5) Univariate analysis demonstrated that the time to progression (TTP) in grade 2 - 4 MBD groups was significantly shorter than that in grade 0 - 1 groups (P = 0.029). (6) Multivariable COX analysis did not indicate lytic bone changes was a independent prognostic factor for OS and TTP.

CONCLUSIONThere is a rather high incidence of MBD in MM patients in China. Patients with extensive X-ray bone lesions have more severe hematologic parameters than those without bone lesions did, and severe bone lesions is an important adverse prognostic factor for TTP.

Bone Diseases ; Bone Marrow ; Humans ; Interleukin-6 ; Multiple Myeloma ; Prognosis ; Retrospective Studies

genes.

Objective To explore the prevalence of mild cognitive impairment (MCI) among elderly veterans. Methods 2 674 veterans ( aged 60 years and over) from 26 military sanatorium in Shijiazhuang city were studied. The Mini-Mental State Examination, Global Deterioration Scale, Activity of Daily Living, Hachinski Ischemic Scale and Hamilton Depression Scale were served as screening tools. Results The prevalence of total MCI was 8 08% in elderly people. The standardized prevalence of MCI was 6 87% in male and 10 38% in female (P

BACKGROUNDStudies have suggested that use of prolonged dual antiplatelet therapy (DAPT) following new generation drug-eluting stent implantation may increase costs and potential bleeding events. This study aimed to investigate the association of DAPT status with clinical safety in patients undergoing everolimus-eluting stent (EES) implantation in the SEEDS study (A Registry to Evaluate Safety and Effectiveness of Everolimus Drug-eluting Stent for Coronary Revascularization) at 2-year follow-up.

METHODSThe SEEDS study is a prospective, multicenter study, where patients (n = 1900) with small vessel, long lesion, or multi-vessel diseases underwent EES implantation. Detailed DAPT status was collected at baseline, 6-month, 1- and 2-year. DAPT interruption was defined as any interruption of aspirin and/or clopidogrel more than 14 days. The net adverse clinical events (NACE, a composite endpoint of all-cause death, all myocardial infarction (MI), stroke, definite/probable stent thrombosis (ST), and major bleeding (Bleeding Academic Research Consortium II-V)) were investigated according to the DAPT status at 2-year follow-up.

RESULTSDAPT was used in 97.8% of patients at 6 months, 69.5% at 12 months and 35.4% at 2 years. It was observed that the incidence of NACE was low (8.1%) at 2 years follow-up, especially its components of all-cause death (0.9%), stroke (1.1%), and definite/probable ST (0.7%). DAPT was not an independent predictor of composite endpoint of all-cause death/MI/stroke (hazard ratio [HR]: 0.693, 95% confidence interval [CI]: 0.096-4.980, P = 0.715) and NACE (HR: 1.041, 95% CI: 0.145-7.454, P = 0.968). Of 73 patients who had DAPT interruption, no patient had ST at 12-month, and only 1 patient experienced ST between 1- and 2-year (1.4%). There was a high frequency of major bleeding events (53/65, 82.5%) occurred in patients receiving DAPT treatment.

CONCLUSIONSProlonged DAPT use was not associated with improved clinical safety. The study emphasized that duration of DAPT needs to be shortened in Chinese patients following EES implantation (ClinicalTrials.gov identifier: NCT 01157455).

Adolescent ; Adult ; Aged ; Aspirin ; therapeutic use ; Drug-Eluting Stents ; Everolimus ; Female ; Humans ; Male ; Middle Aged ; Platelet Aggregation Inhibitors ; therapeutic use ; Prospective Studies ; Sirolimus ; analogs & derivatives ; therapeutic use ; Thrombosis ; drug therapy ; Ticlopidine ; analogs & derivatives ; therapeutic use ; Treatment Outcome ; Young Adult

OBJECTIVETo explore the effects and the molecular mechanism of puerariae radix flavones (PRF) on acute myeloid leukemia cell line Kasumi-1 cells in vitro.

METHODSKasumi-1 cells treated by PRF for 48 hours were observed with Wright's and Hoechst 33258 dying. The apoptotic cells were analyzed by flow cytometry with AnnexinV/PI staining. The expression levels of bcl-2, Bim and Caspase-3/-8/-9 protein were assayed by Western blot and the AML1-ETO fusion gene was detected by real-time polymerase chain reaction.

RESULTSPRF could induce Kasumi-1 cells to apoptosis effectively. The proportion of apoptotic cells in 50, 200 and 500 µg/ml PRF treatment groups were (14.1 ± 0.8)%, (17.7 ± 1.3)% and (32.4 ± 1.4)%, respectively, and significantly higher than that of control \[(7.8 ± 0.7)%\]. The relative expression levels of the anti-apoptotic Bcl-2 protein were 0.85 ± 0.05, 0.62 ± 0.07 and 0.43 ± 0.05; the apoptotic Bim protein were 0.21 ± 0.06, 0.39 ± 0.04 and 0.75 ± 0.05; the caspase-3 and caspase-9 were 0.92 ± 0.04, 1.21 ± 0.07, 1.33 ± 0.04 and 0.35 ± 0.05, 0.53 ± 0.03, 0.69 ± 0.07, respectively. Compared to the blank control group, all these changes were significant (P < 0.01). Nevertheless, nearly no changes could be observed on the expression level of AML1-ETO fusion gene and caspase-8 protein.

CONCLUSIONApoptosis of Kasumi-1 cells induced by PRF might correlate to the down-regulation of Bcl-2 protein expression and the activation of caspase-3 and caspase-8 protein in the cells. It seemed that all these effects had no relationship with the AML1-ETO fusion gene.

Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Caspase 8 ; metabolism ; Cell Line, Tumor ; Core Binding Factor Alpha 2 Subunit ; genetics ; metabolism ; Flavones ; pharmacology ; Humans ; Oncogene Proteins, Fusion ; genetics ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Pueraria ; RUNX1 Translocation Partner 1 Protein

BACKGROUNDSingle nucleotide polymorphisms (SNPs) in the deoxycytidine kinase (dCK) gene are associated with chemosensitivity to nucleoside analogs. 2',2'-Difluoro 2'-deoxycytidine (gemcitabine) is a first-line nucleoside analog drug in the treatment of pancreatic cancer. However, the association between SNPs in the dCK gene and chemosensitivity to gemcitabine has not been fully established. Therefore, the present study aimed to investigate the relationship between SNPs in the dCK gene and chemosensitivity to gemcitabine in human pancreatic cancer cell lines.

METHODSSeven SNPs in the dCK gene were sequenced in six human pancreatic cancer cell lines. The chemosensitivity of these six cell lines to gemcitabine were evaluated in vitro with a Cell Counting Kit-8 (CCK-8) test. Inhibition rates were used to express the chemosensitivity of pancreatic cancer cell lines to gemcitabine.

RESULTSThe genotype of the A9846G SNP in the dCK gene was determined in six human pancreatic cancer cell lines. The cell lines BxPC-3 and T3M4 carried the A9846G SNP genotype AG, whereas cell lines AsPC-1, Mia PaCa2, SW1990 and SU86.86 carried the GG genotype. Cell lines with the AG genotype (BxPC-3 and T3M4) were more sensitive to gemcitabine compared with cell lines with the GG genotype (AsPC-1, Mia PaCa2, SW1990 and SU86.86) and significantly different inhibition rates were observed between cell lines carrying the AG and GG genotypes (P < 0.01).

CONCLUSIONSVariants in the A9846G SNP of the dCK gene were associated with sensitivity to gemcitabine in pancreatic cancer cell lines. The dCK A9846G SNP may act as a genetic marker to predict chemotherapy efficacy of gemcitabine in pancreatic cancer.

Antimetabolites, Antineoplastic ; pharmacology ; Cell Line, Tumor ; Cell Survival ; drug effects ; Deoxycytidine ; analogs & derivatives ; pharmacology ; Deoxycytidine Kinase ; genetics ; Genotype ; Humans ; Pancreatic Neoplasms ; enzymology ; genetics ; Polymorphism, Single Nucleotide ; genetics