italic>Salvia miltiorrhiza, a commonly used traditional Chinese medicine, has been widely recognized for its blood-activating and stasis-removing properties in the clinical treatment of cardiovascular and cerebrovascular diseases. The synthesis and regulatory mechanism of tanshinones, the key active constituents of Salvia miltiorrhiza, have been a hot topic of research. The paper summarized the research findings on the regulation of tanshinone biosynthesis by transcription factors such as AP2/ERF, bHLH, MYB, bZIP, and WRKY in recent years. The review identifies the existing issues in the transcriptional regulation studies of Salvia miltiorrhiza and discusses the research direction of transcription factors in the regulation of tanshinone biosynthesis, providing a theoretical basis for the further discovery and utilization of functional genes involved in the regulation of tanshinone bioactive constituents.

Purpose: Patients with advanced biliary tract cancer (BTC) have a poor survival. We aim to evaluate the efficacy and safety of nab-paclitaxel plus gemcitabine and cisplatin regimen in Chinese advanced BTC patients. Materials and Methods: Eligible patients with locally advanced or metastatic BTC administrated intravenous 100 mg/m2 nab-paclitaxel, 800 mg/m2 gemcitabine, and 25 mg/m2 cisplatin every 3 weeks. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS) and adverse events, while exploratory endpoint was the association of biomarkers with efficacy. Results: After the median follow-up of 25.0 months, the median PFS and OS of 34 enrolled patients were 7.1 months (95% confidence interval [CI], 5.4 to 13.7) and 16.4 months (95% CI, 10.9 to 23.6), respectively. The most common treatment-related adverse events at ≥ 3 grade were neutropenia (26.5%) and leukopenia (26.5%). Survival analyses demonstrated that carcinoembryonic antigen (CEA) levels could monitor patients’ survival outcomes. A significant increase in the number of infiltrating CD4+ cells (p=0.008) and a decrease in programmed death-1–positive (PD-1+) cells (p=0.032) were observed in the response patients. Conclusion In advanced BTC patients, nab-paclitaxel plus gemcitabine and cisplatin regimen showed therapeutic potential. Potential prognostic factors of CEA levels, number of CD4+ cells and PD-1+ cells may help us maximize the efficacy benefit.

italic>Ardisia crispa (Thunb.) A. DC. is a traditional Miao medicinal herb with significant therapeutic effects in the treatment of sore throat, tonsillitis, edema of nephritis and bruising and rheumatism, etc. Ardisia crispa var. amplifolia and Ardisia crispa var. dielsii are varieties of A. crispa. A. crispa var. amplifolia and A. crispa var. dielsii are controversial in terms of species evolutionary relationships and taxonomic identification. In this study, we sequenced the whole genome sequences of A. crispa var. amplifolia and A. crispa var. dielsii chloroplasts using Illumina platform, assembled, annotated and characterized them, compared the structural features and degree of variation among chloroplast genomes using bioinformatics methods, and also downloaded constructing phylogenetic trees to analyze the phylogenetic relationships of chloroplasts in Primulaceae and Myrsinaceae using whole genome sequence information. The results showed that the complete chloroplast genome sequences of A. crispa var. amplifolia and A. crispa var. dielsii were 156 749 bp and 156 748 bp in length, with 132 genes annotated, including 87 protein-coding genes; the codon preference of A/U was greater than that of G/C; The differences in the coding regions of rps15 and rpoB genes in the comparative genome analysis can be used as loci for molecular identification of the two species; the differences in the coding regions of ycf1, ycf2, rpoC1, ycf3, petD and rpl16 genes in the chloroplast genome compared with those of the same genus can be used as loci for identification of the genus. In the phylogenetic results, A. crispa var. amplifolia and A. crispa var. dielsii were clustered together with 100% support, indicating that they are closely related. In this research, we analyzed the chloroplast genome structure and phylogenetic relationships of A. crispa var. amplifolia and A. crispa var. dielsii, providing an important theoretical basis for their molecular identification, genetic variation, breeding and phylogenetic analysis.

Increased neuronal apoptosis is an important pathological feature of Alzheimer's disease (AD). The Bcl-2-interacting mediator of cell death (Bim) mediates amyloid-beta (Aβ)-induced neuronal apoptosis. Naturally-occurring antibodies against Bim (NAbs-Bim) exist in human blood, with their levels and functions unknown in AD. In this study, we found that circulating NAbs-Bim were decreased in AD patients. Plasma levels of NAbs-Bim were negatively associated with brain amyloid burden and positively associated with cognitive functions. Furthermore, NAbs-Bim purified from intravenous immunoglobulin rescued the behavioral deficits and ameliorated Aβ deposition, tau hyperphosphorylation, microgliosis, and neuronal apoptosis in APP/PS1 mice. In vitro investigations demonstrated that NAbs-Bim were neuroprotective against AD through neutralizing Bim-directed neuronal apoptosis and the amyloidogenic processing of amyloid precursor protein. These findings indicate that the decrease of NAbs-Bim might contribute to the pathogenesis of AD and immunotherapies targeting Bim hold promise for the treatment of AD.
Alzheimer Disease/pathology* ; Amyloid beta-Peptides/metabolism* ; Amyloid beta-Protein Precursor/metabolism* ; Animals ; Disease Models, Animal ; Humans ; Mice ; Mice, Transgenic

OBJECTIVE: To investigate the diagnostic value of diffusion kurtosis imaging (DKI) histogram analysis in hepatic fibrosis staging. MATERIALS AND METHODS: Thirty-six rats were divided into carbon tetrachloride-induced fibrosis groups (6 rats per group for 2, 4, 6, and 8 weeks) and a control group (n = 12). MRI was performed using a 3T scanner. Histograms of DKI were obtained for corrected apparent diffusion (D), kurtosis (K) and apparent diffusion coefficient (ADC). Mean, median, skewness, kurtosis and 25th and 75th percentiles were generated and compared according to the fibrosis stage and inflammatory activity. RESULTS: A total of 35 rats were included, and 12, 5, 5, 6, and 7 rats were diagnosed as F0–F4. The mean, median, 25th and 75th percentiles, kurtosis of D map, median, 25th percentile, skewness of K map, and 75th percentile of ADC map demonstrated significant correlation with fibrosis stage (r = −0.767 to 0.339, p < 0.001 to p = 0.039). The fibrosis score was the independent variable associated with histogram parameters compared with inflammatory activity grade (p < 0.001 to p = 0.041), except the median of K map (p = 0.185). Areas under the receiver operating characteristic curve of D were larger than K and ADC maps in fibrosis staging, although no significant differences existed in pairwise comparisons (p = 0.0512 to p = 0.847). CONCLUSION: Corrected apparent diffusion of DKI histogram analysis provides added value and better diagnostic performance to detect various liver fibrosis stages compared with ADC.
Animals ; Carbon ; Diagnosis* ; Diffusion* ; Fibrosis* ; Liver ; Liver Cirrhosis ; Magnetic Resonance Imaging* ; Rats ; ROC Curve

The effects of over-expression of testis-specific expressed gene 1 (TSEG-1) on the viability and apoptosis of cultured spermatogonial GC-1spg cells were investigated, and the immortal spermatogonial cell line GC-1spg (CRL-2053™) was obtained as the cell model in order to explore the function of TSEG-1. We transfected the eukaryotic vector of TSEG-1, named as pEGFP-TSEG-1 into cultured spermatogonial GC-1spg cells. Over-expression of TSEG-1 inhibited the proliferation of GC-1spg cells, and arrested cell cycle slightly at G0/G1 phase. Transfection of TSEG-1 attenuated the transcript levels of Ki-67, PCNA and cyclin D1. In addition, over-expression of TSEG-1 induced early and late apoptosis, and reduced the mitochondrial membrane potential of GC-1spg cells. Moreover, transfection of TSEG-1 significantly enhanced the ratio of Bax/Bcl-2 and transcript levels of caspase 9, and decreased the expression of Fas and caspase 8 in GC-1spg cells. These results indicated over-expression of TSEG-1 suppresses the proliferation and induces the apoptosis of GC-1spg cells, which establishes a basis for further study on the function of TSEG-1.
Animals ; Caspase 8 ; biosynthesis ; genetics ; Cell Line ; Cyclin D1 ; biosynthesis ; genetics ; G1 Phase ; physiology ; Histones ; genetics ; metabolism ; Ki-67 Antigen ; biosynthesis ; genetics ; Male ; Mice ; Proliferating Cell Nuclear Antigen ; biosynthesis ; genetics ; Resting Phase, Cell Cycle ; physiology ; Spermatogonia ; cytology ; metabolism ; bcl-2-Associated X Protein ; biosynthesis ; genetics

The effects of over-expression of testis-specific expressed gene 1 (TSEG-1) on the viability and apoptosis of cultured spermatogonial GC-1spg cells were investigated, and the immortal spermatogonial cell line GC-1spg (CRL-2053™) was obtained as the cell model in order to explore the function of TSEG-1. We transfected the eukaryotic vector of TSEG-1, named as pEGFP-TSEG-1 into cultured spermatogonial GC-1spg cells. Over-expression of TSEG-1 inhibited the proliferation of GC-1spg cells, and arrested cell cycle slightly at G0/G1 phase. Transfection of TSEG-1 attenuated the transcript levels of Ki-67, PCNA and cyclin D1. In addition, over-expression of TSEG-1 induced early and late apoptosis, and reduced the mitochondrial membrane potential of GC-1spg cells. Moreover, transfection of TSEG-1 significantly enhanced the ratio of Bax/Bcl-2 and transcript levels of caspase 9, and decreased the expression of Fas and caspase 8 in GC-1spg cells. These results indicated over-expression of TSEG-1 suppresses the proliferation and induces the apoptosis of GC-1spg cells, which establishes a basis for further study on the function of TSEG-1.

BACKGROUNDIt is the first multicenter clinical study in China to investigate zanamivir use among Chinese adolescents and adults with influenza-like illness (ILI) since 2009, when inhaled zanamivir (RELENZA(®)) was marketed in China.

METHODSAn uncontrolled open-label, multicentre study to evaluate the antiviral activity, and safety of inhaled zanamivir (as Rotadisk via Diskhaler device); 10 mg administered twice daily for 5 days in subjects ≥ 12 years old with ILI. Patients were enrolled within 48 hours of onset and followed for eight days. Patients were defined as being influenza-positive if the real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) test had positive results.

RESULTSA total of 400 patients ≥ 12 years old were screened from 11 centers in seven provinces from March 2010 to January 2011. Three hundred and ninety-two patients who took at least one dose of zanamivir were entered into the safety analysis. The mean age was 33.8 years and 50% were male. Cardiovascular diseases and diabetes were the most common comorbidities. All the reported adverse events, such as rash, nasal ache, muscle ache, nausea, diarrhea, headache, occurred in less than 1% of subjects. Mild sinus bradycadia or arrhythmia occurred in four subjects (1%). Most of the adverse events were mild and did not require any change of treatment. No severe adverse events (SAE) or fatal cases were reported. Bronchospasm was found in a 38 years old woman whose symptoms disappeared after stopping zanamivir and without additional treatment. All the 61 influenza virus isolates (43 before enrollment, 18 during treatment) proved to be sensitive to zanamivir.

CONCLUSIONSZanamivir is well tolerated by Chinese adolescents and adults with ILIs. There is no evidence for the emergence of drug-resistant isolates during treatment with zanamivir.

Adolescent ; Adult ; Antiviral Agents ; administration & dosage ; adverse effects ; therapeutic use ; Female ; Humans ; Influenza, Human ; drug therapy ; Male ; Middle Aged ; Treatment Outcome ; Zanamivir ; administration & dosage ; adverse effects ; therapeutic use

Objective To investigate the changes of cognitive impairment and its correlated factors in patients with first acute cerebral ischemic stroke.Methods Five hundred and sixty-eighty patients,admitted to our hospital from July 2010 to June 2011 and met the diagnostic criteria of first acute cerebral ischemic stroke,were chosen in our study; neuropsychological evaluation was conducted within 1 week of acute cerebral ischemic stroke.The comprehensive neuropsychological evaluation battery included mini-mental state examination (MMSE),Digit span,Mattis dementia scale,Rey complex figure test,stroop test,World Health Organization and University of California-Los Angeles auditory verbal learning test,semantic category verbal fluency test and clock drawing test,which contained tests for memory,attention,executive function,information processing capability,visuospatial and visuo constructive functions.Gender,age,histories of hypertension and smoking,and levels of blood pressure,random blood glucose,fasting blood glucose and 2-hour postprandial blood glucose,cholesterin,triglyceride,low density lipoprotein-C (LDL-C) and high density lipoprotein-C (HDL-C) were noted and the relations between cognitive function and both blood sugar and blood lipid levels were analyzed.Results (1) The abnormal rates of these patients in MMSE,Mattis dementia scale,attention deficit disorder,immediate logical memory disorder,delayed logical memory disorder,instant auditory memory disorder,delayed auditory memory disorder,visual memory disorder,executive function disorder,information processing disorder,and visuospatial and visuo constructive disorder were 78.2％,72.5％,26.5％,56.3％,60.9％,74.6％,98.2％,83.8％,62.7％,4.9％ and 77.7％,respectively.In patients with different blood glucose levels,significant differences were found on scores of MMSE,Mattis dementia scale,attention scale (P＜ 0.05); furthermore,the scores ofMMSE,Mattis dementia scale,attention scale in patients with impaired fasting glucose were obviously lower as compared with those in other groups (P＜0.05).The scale of above cognitive domains showed no significant difference in patients with different types of hyperlipidemias (P＞0.05); the scores of execution ability and visual space structure capability in patients with HDL-C were higher than those in normal density lipoprotein-C and LDL-C (P＜0.05),and the higher level of density lipoprotein-C,the higher scores of visual space structure capability (P＜0.05).Logistic regression analysis found that the total MMSE scores were associated with gender,age,and levels of fasting blood glucose and 2-hour postprandial blood glucose; the independent risk factors of executive function were gender,age and HDL-C level; the ability of memory was correlated with age and HDL-C level.Visuospatial and visuo constructive function was associated with gender,age and mRS scores; the information processing ability was only correlated with HDL-C level.Conclusion In patients with acute cerebral ischemic stroke,the cognitive impairment is extensive and severe,with a prevalence of about 75％,mainly having disorders in memory,executive ability,spatial structure; glucose levels,especially impaired fasting glucose level show most obvious influence in cognitive impairment;HDL-C level helps keep normal cognitive function; age,gender,HDL-C level are the most important factors of cognitive function.

OBJECTIVETo evaluate the clinical efficacy of treatment on the cases of severe hallux valgus by the first metatarsal basal osteotomy combined with Chevron-Gerbert operation.

METHODSFrom June 2004 to August 2008, 37 cases of severe hallux valgus (66 feet) underwent first metatarsal basal osteotomy combined with Chevron-Gerbert operation. There were 5 males (10 feet) and 21 females (38 feet), aged 21 - 76 years (mean 58 years). For all patients with follow-up, radiographic measurements of frontal and lateral position of foot were taken to measure the hallux valgus angle (HVA), the IMA (intermetatarsal angle) and the proximal articular set angle (PASA) preoperatively, postoperatively and in follow-up respectively. The measuring results were compared among the preoperative, the 6-week postoperative and the final follow-up. At the same time the patients were evaluated with the AOFAS Maryland score.

RESULTSOf the original 37 patients, 26 patients (48 feet) were followed up. The mean durations of follow-up was 2.3 years (range from 1 to 4 years). At final follow-up, HVA corrected 25.6° ± 3.8°, IMA corrected 8.6° ± 2.4°, and PASA corrected 4.7° ± 4.2°. According to AOFAS rating system, 91.7% patients were rated as excellent or good with excellent in 15 patients (28 feet), good in 8 patients (16 feet), and fair in 3 patients (4 feet).

CONCLUSIONSFirst metatarsal basal osteotomy combined with Chevron-Gerbert operation has good efficacy to the patients with severe hallux valgus. However there are disadvantages such as complexity relatively for multi-stage osteotomy and internal fixation.

Adult ; Aged ; Female ; Follow-Up Studies ; Hallux Valgus ; surgery ; Humans ; Male ; Metatarsal Bones ; surgery ; Middle Aged ; Osteotomy ; methods ; Treatment Outcome ; Young Adult