Biomarkers, Tumor ; metabolism ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; metabolism ; pathology ; Humans ; Lung Neoplasms ; drug therapy ; metabolism ; pathology ; Oncogene Proteins, Fusion ; chemistry ; metabolism ; Protein Kinase Inhibitors ; therapeutic use ; Pyrazoles ; therapeutic use ; Pyridines ; therapeutic use ; Pyrimidines ; therapeutic use ; Smoking

The feasibility of simultaneously loading both liposoluble and water-soluble components of Salvia miltiorrhiza in emulsion was discussed, in order to provide new ideas in comprehensive application of effective components in S. miltiorrhiza in terms of technology of pharmaceutics. With tanshinone II (A) and salvianolic acid B as raw materials, soybean phospholipid and poloxamer 188 as emulsifiers, and glycerin as isoosmotic regulator, the central composite design-response surface method was employed to optimize the prescription. The coarse emulsion was prepared with the high-speed shearing method and then homogenized in the high pressure homogenizer. The biphasic drug-loading intravenous emulsion was prepared to investigate its pharmaceutical properties and stability. The prepared emulsion is orange-yellow, with the average diameter of 241 nm and Zeta potential of -35.3 mV. Specifically, the drug loading capacity of tanshinone II (A) and salvianolic acid B were 0.5 g x L(-1) and 1 g x L(-1), respectively, with a good stability among long-term retention samples. According to the results, the prepared emulsion could load liposoluble tanshinone II (A) and water-soluble salvianolic acid B simultaneously, which lays a pharmaceutical foundation for giving full play to the efficacy of S. miltiorrhiza.
Chemistry, Pharmaceutical ; instrumentation ; methods ; Drugs, Chinese Herbal ; chemistry ; Emulsions ; chemistry ; Quality Control ; Salvia miltiorrhiza ; chemistry

OBJECTIVETo explore the regulatory effect and mechanism of Ningxin Hongqi Capsule on local ovarian autocrine and paracrine factors in peri-menopausal rats.

METHODSSD female rats aged 4 months were allocated in a normal control group (A) and those aged 14 months with vagino-cytologic figure of oestrus elongation were allocated in a senile female rat model group (B). Rats in Group B were subdivided into 5 groups randomly as the B1, B2 and B3 subgroups treated respectively with high, moderate and low dose Ningxin Hongqi Capsule, the B4 subgroup treated with estradiol and the B5 subgroup untreated for control. Rats' ovaries were obtained at the end of the experiment for observing the conditions of ovarian growing follicles and corpus luteum by HE staining, determining expressions of ovarian estradiol receptor (ER), progesterone receptor (PR), follicle-stimulating hormone (FSH), luteinizing hormone (LH), inhibin alpha (INHalpha), activin (ACT) alpha-beta, follistatin (FS), and insulin-like growth factor (IGF-1).

RESULTSAs compared with Group B5, the ovary index, number of growing follicle were higher and levels of FSH and LH were lower in Group B2 and B3, expression of ER was higher in Group B1 and B4, IGF-1 and INHalpha was higher in Group B2 and B3, and ACTalpha-beta and FS were lower (all P < 0.05).

CONCLUSIONNirigxin Hongqi Capsule could adjust and balance the local ovarian autocrine and paracrine factors to improve the ovarian function.

Animals ; Autocrine Communication ; drug effects ; physiology ; Capsules ; Drugs, Chinese Herbal ; pharmacology ; Female ; Humans ; Models, Animal ; Ovary ; drug effects ; metabolism ; physiology ; Paracrine Communication ; drug effects ; physiology ; Perimenopause ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptors, Estradiol ; biosynthesis ; Receptors, FSH ; biosynthesis ; Receptors, Progesterone ; biosynthesis

Background The excitotoxicity to retinal neurons caused by abnormal elevation of glutamate in retina is a common pathology concomitant with major blind-causing eye diseases.However,an effective approach to protect retinal neurons from glutamate-induced excitotoxicity is still lack.Intraperitoneal administration of α-melanocyte stimulating hormone(α-MSH)has been shown to protect hippocampal neurons from glutamate-induced excitotoxicity.Objective This study was to investigate the protective effect of α-MSH on glutamate-induced excitotoxicity in a chicken embryonic retinal explant culture system.Methods The retinas were isolated from chick embryos at embryonic day 9(E9) and cultured as explants.The explants at 3,5 and 7 days in vitro and the retinas at corresponding embryonic day 12,14 and 16(E12,E14,E16)were collected.The morphology of explant cultures was examined by hematoxylin and eosin staining,and the expression of melanocortin receptors (MCRs)was analyzed by real-time PCR.In the experiment of glutamate-induced excitotoxicity,the retinal explants at 4 days in vitro were treated with glutamate for 48 hours,α-MSH was incubated with the explants 30 minutes before and during the glutamate treatment period.Then the apoptotic cells were detected by TUNEL staining and quantified.The glutamate alone treated-explants and those treated with culture media were included as controls.The expression of glial fibrillary acidic protein(GFAP) at 48 hours after treatment in all retinal explants was analyzed by real-time PCR.Results Hematoxylin and eosin staining showed that the retinal explants exhibited similar morphology to those observed in the retinas from chick embryos at the corresponding developmental stages.The real-time PCR analyses of chick retinas showed that MC1R mRNA level at E9,E12,E14 and E16 was significantly lower than that in post-hatch day 1 (all P=0.000) ;whereas the transcript level of MC5R was significantly increased from E9 to E12 and E14 (both P =0.000),and then gradually decreased from E14 to P1.The expression of these genes showed similar temporal patterns in the retinal explant cultures.TUNEL staining revealed that treatment of the retinal explant cultures with α-MSH substantially and significantly reduced number of apoptotic cells induced by glutamate (P =0.000),which was accompanied by significant suppression of glutamate-induced GFAP up-regulation (P =0.000).Conclusions Application of α-MSH dramatically ameliorated glutamate-induced cell death in retinal explant cultures.This protective effect may be due to α-MSH-mediated suppression of astrogliosis caused by abnormal elevation of glutamate.

OBJECTIVETo investigate the mutation characteristics of paired box homeotic gene 9 (PAX9) and muscle segment homeobox gene 1 (MSX1) of patients with congenital oligodontia.

METHODSClinical manifestations were recorded by taking complete oral examinations in patients with congenital nonsyndromic oligodontia and some of his normal family members. Pedigree information was confirmed by extended interviews and a pedigree was constructed. Inheritance mode and clinical features were analyzed. Assessment of crown width compared to normal value of crown width in Chinese people was based on the registrations and measurements of study cast. Comparison of craniofacial form, malocclusion types and characteristics were conducted via cephalometric analysis by taking lateral cephalometric radiographics. Venous blood samples were collected and DNA was extracted from leukocytes. DNA sequencing and mutation analysis were analyzed in exon 1, 2, 3, 4 of PAX9 and exon 1, 2 of MSX1 coding region by polymerase chain reaction (PCR).

RESULTSThe teeth shape abnormality of the patient was noticed by a measured smaller crown width compared to normal values of crown width in Chinese people. The result of cephalometric analysis indicated no obvious inherited tendency in the proband in terms of facial osseo type and jaw bone pattern. One mutation was found in the proband and his mother in exon 3 of PAX9, the missense mutation G718C causing a conservative change A240P was present. Mutation was not found in MSX1.

CONCLUSIONThese findings suggest that the missense mutation G718C in exon 3 of PAX9 is likely the cause of oligodontia.

Adolescent ; Anodontia ; Asian Continental Ancestry Group ; DNA Mutational Analysis ; Female ; Humans ; Male ; Mutation ; PAX9 Transcription Factor ; Pedigree ; Polymerase Chain Reaction ; Sequence Analysis, DNA

BACKGROUND: Yaotu Granules have been proved to protect human nucleus pulposus cells and delay their degeneration. Notably, Yaotu Granules for lumbar disc herniation has achieved good clinical results.OBJECTIVE: To investigate the effect of the herbal compound formula Yaotu Granules on the Fas/FasL expression in a rabbit model of lumbar disc degeneration, and further elucidate the underling mechanism of preventing and treating lumbar disc degeneration.METHODS: Twenty New Zealand white rabbits were enrolled and the models of lumbar disc degeneration were established by minimally invasive puncture and rotation cutting, followed by randomized into normal saline, low-, middle-,and high-dose groups (n=5 per group). 10 mL of normal saline, 10, 20, and 40 mL of water decoction of Yaotu Granules were administered intragastrically into the normal saline, low-, middle-, and high-dose drug groups for 21 days, twice daily, respectively. Subsequently, the expression level of Fas/FasL in the rabbit nucleus pulposus cells in each group was detected.RESULTS AND CONCLUSION: The signal intensity of the rabbit lumbar disc on MRI was decreased, and ruptured annulus and posterior herniated disc were visible at 12 weeks after modeling. Masson staining showed that the nucleus pulposus cells arranged in disorder, and even ruptured. Additionally, safranin O staining found that the number of nucleus pulposus cells was decreased obviously. The order of the relative expression levels of Fas and FasL mRNA in the nucleus pulposus cells was as follows: normal saline group > low-dose drug group > middle-dose drug group > high-dose drug group (P < 0.05). These results suggest that Yaotu Granules delay the rabbit lumbar disc degeneration by downregulating the expression level of Fas/FasL.

OBJECTIVE: To find the mutation of disease-causing genes of sudden unexplained death syndrome (SUDS) in the young by whole exome sequencing in one case. METHODS: One SUDS case was found no obvious fatal pathological changes after conventional autopsy and pathological examination. The whole exome sequencing was performed with the Ion Torrent PGM™ System with hg19 as reference sequence for sequencing data. The functions of mutations were analyzed by PhyloP, PolyPhen2 and SIFT. A three-step bioinformatics filtering procedure was carried out to identify possible significative single nucleotide variation (SNV), which was missense mutation with allele frequency < 1% of myocardial cell. RESULTS: Four rare suspicious pathogenic SNV were identified. Combined with the analysis of conventional autopsy and pathological examination, the mutation MYOM2 (8_2054058_G/A) was assessed as high-risk deleterious mutation by PolyPhen2 and SIFT, respectively. CONCLUSION Based on the second generation sequencing technology, analysis of whole exome sequencing can be a new method for the death cause investigation of SUDS. The gene MYOM2 is a new candidate SUDS pathogenic gene for mechanism research.
Autopsy ; Brugada Syndrome/genetics* ; Cause of Death ; DNA Mutational Analysis/methods* ; Death, Sudden/etiology* ; Exome ; Gene Frequency ; Genetic Testing/methods* ; High-Throughput Nucleotide Sequencing/methods* ; Humans ; Molecular Biology ; Molecular Diagnostic Techniques/methods* ; Molecular Sequence Data ; Mutation

OBJECTIVETo summarize the echocardiographic features of a wide spectrum of congenital mitral valve anomalies.

METHODSThe medical records, echocardiograms, cardiac catheterization studies, and surgical reports were reviewed. The mitral valve anomalies evaluated in the study included parachute mitral valve, double orifice mitral valve, congenital mitral stenosis with 2 papillary muscles, anomalous papillary muscle rotation, and 3 commissures and papillary muscles in 15 cases. Surgeries were performed in 11 patients, and 1 patient underwent transcatheter closure of the patent ductus arteriosus.

RESULTSThe echocardiograms of 6 cases of parachute mitral valve were characterized by a hypoplastic mitral valve with short chordal attachments to a single posterior medial papillary muscle. The mitral valve demonstrated restricted motion. The double orifice mitral valve were featured by two separate mitral valve orifice, with each suborifice supported by its own tension apparatus in 4 patients. Asymmetric hypoplastic mitral valve stenosis with two papillary muscles was found in 1 patient with short and unbalanced chordal attachments to the anterior lateral major papillary muscle. Anomalous papillary muscle rotation was found in 1 patient. Mirtal anomaly with 3 major commissures and 3 papillary muscles was found in 3 patients.

CONCLUSIONSEchocardiography offers clear demonstration of the mitral valve thickness and chordal attachments, and allows visualization of the position and the number of the papillary muscles and interpapillary spaces for evaluation of the mobility of the valve leaflets, therefore can be a valuable diagnostic modality for congenital mitral valve anomalies, especially congenital mitral stenosis.

Adolescent ; Adult ; Child ; Child, Preschool ; Echocardiography, Doppler, Color ; Female ; Humans ; Infant ; Middle Aged ; Mitral Valve ; abnormalities ; diagnostic imaging ; Mitral Valve Stenosis ; congenital ; diagnostic imaging ; Papillary Muscles ; abnormalities ; diagnostic imaging ; Young Adult

OBJECTIVETo explore and sum up the characteristics of infection after cardiac transplantation and to discuss the prophylaxis and management.

METHODFrom May 2000 to April 2003, 36 patients received orthotopic heart transplantation, the clinical data were observed and analyzed.

RESULTSInfection occurred in 2 (6%) cases, both belonged to lung infection caused by human cytomegalovirus. The 2 cases were cured by ganciclovir intravenously.

CONCLUSIONGood prophylactic method may decrease post cardiac transplantation infection significantly. It is very important to early diagnose and treat infection.

Adolescent ; Adult ; Aged ; Antibiotic Prophylaxis ; Antiviral Agents ; therapeutic use ; Cytomegalovirus Infections ; drug therapy ; Female ; Follow-Up Studies ; Heart Transplantation ; Humans ; Male ; Middle Aged ; Postoperative Complications ; Postoperative Period

OBJECTIVETo study effective operation method of congenital velopharyngeal insufficiency by reviewing clinical data of 29 patients with pharyngoplasties.

METHODS29 patients (9 male and 20 female, ranged from 4 to 25 years old, mean age was 13.5) with congenital velopharyngeal insufficiency were available for this study. All cases received Chinese speech intelligibility test and blowing test before and after the pharyngeal flap surgery.

RESULTSChinese speech intelligibility of 29 cases who underwent pharyngoplasties was improved from 33.86% to 43.13%, and the blowing time was increased from 4.60 to 17.72 seconds, the degree of abnormal speech was reduced.

CONCLUSIONThe pharyngeal flap surgery is an effective method for congenital velopharyngeal insufficiency, which reduces hypernasality and increases oral pressure, improves the velopharyngeal function.

Female ; Humans ; Male ; Pharynx ; Retrospective Studies ; Surgical Flaps ; Velopharyngeal Insufficiency