Syringa oblata is a traditional Mongolian medicine mainly distributed in the Helan Mountains (the boundaries of Inner Mongolia and Ningxia, China) and the north of Yan Mountains (Aohan Qi, Inner Mongolia, China). It is clinically used to treat diseases caused by Heyi, such as heartache and heat pathogen in the heart. Phytochemical studies on S. oblata revealed the presence of iridoids, lignans, triterpenes, phenylpropanoids, phenylethanoids, and volatile components. Pharmacological investigations revealed a broad spectrum of bioactivities, such as antimicrobial, antioxidant, antiproliferative, and hepatoprotective effects. This article summarized the chemical components and pharmacological activities of S. oblata, providing a scientific rationale for its bioactive constituents, quality control, and utilization as an important medicine.

BACKGROUNDArrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable cardiac disease predominantly caused by mutations in desmosomal protein genes. Previous genetic analyses of the Chinese ARVC population are limited to small size and restriction to a single gene. This study was aimed to investigate the genotype in a large series of Chinese patients with ARVC through comprehensively screening nine ARVC-causing genes.

METHODSA total of 100 unrelated ARVC patients and 300 age, gender and ethnicity matched healthy controls were genetically tested with multiplexing targeted resequencing for nine previously reported ARVC-causing genes, including plakophilin-2, desmoplakin, desmoglein-2, desmocollin-2, plakoglobin, transforming growth factor beta-3, transmembrane protein 43, desmin and Lamin A/C.

RESULTSFifty-nine mutations were identified in 64% of the patients, among which, 93% were located in desmosomal protein genes. Plakophilin-2 mutations accounted for 54% of the total and 58% of the desmosomal mutations, with a truncating mutation type making up about 2/3 of the plakophilin-2 mutations. Only four mutations were found in non-desmosomal genes; two in transmembrane protein 43 and two in transforming growth factor beta-3. Two of them (one of each gene) appeared as single missense mutations. No mutation was identified in desmin or Lamin A/C. Multiple mutations were found in 23% of the patients, with plakophilin-2 being found in 57% of the multi-mutation carriers.

CONCLUSIONSPlakophilin-2 was the most common gene mutation that was identified in Chinese ARVC patients. Non-desmosomal genes should be added to desmosomal protein genes when performing molecular genetic screening in patients with suspected ARVC.

Adult ; Arrhythmogenic Right Ventricular Dysplasia ; genetics ; metabolism ; Asian Continental Ancestry Group ; Desmin ; genetics ; Desmoglein 2 ; genetics ; Female ; Humans ; Male ; Middle Aged ; Mutation ; Plakophilins ; genetics ; Young Adult ; gamma Catenin ; genetics

The main objective of the current study was to develop a universal method for a protein binding assay of complicated herbal components, and to investigate the possible relationship between compound polarity and protein binding using Schisadra lignans as an example. Firstly, the rat, dog and human plasma were spiked with three different concentrations of Schisandra chinensis extract (SLE), and ultramicrofiltration was used to obtain the unbound ingredients. Secondly, thirty-one Schisandra lignans in total plasma and ultrafiltered fluid were measured by LC-IT-TOFMS. Lastly, a relative exposure approach, which entailed calculating the relative concentrations of each Schisandra lignan from the corresponding calibration equation created from the calibration samples spiked with the stock solution of SLE, was applied in order to overcome the absence of authentic standards. The results showed that Schisandra lignans exhibited a high capability to bind with plasma protein, furthermore, the protein binding ratio of the lignan components increased proportionally with their individual chromatographic retention time, which indicated that the ratio of protein binding of lignans might increase accordingly with decreasing polarity. This study suggested that the compound polarity might be an important factor affecting the plasma protein binding of herbal components.
Animals ; Blood Proteins ; chemistry ; metabolism ; Chromatography, High Pressure Liquid ; methods ; Dogs ; Drugs, Chinese Herbal ; chemistry ; Humans ; Kinetics ; Lignans ; blood ; chemistry ; Male ; Mass Spectrometry ; methods ; Protein Binding ; Rats ; Schisandra ; chemistry

Background Biomaterials for corneal tissue engineering must demonstrate several critical features for potentialutility invivo, includingtransparency, mechanicalintegrity, biocompatibilityand slow biodegradation. Silk film biomaterial had been characterized to meet these functional requirements. ObjectiveThis study was to investigate the feasibility of physico-crosslink regenerated silk fibroin film as tissue engineered corneal scaffold. MethodsHuman corneal epithelial cells(CECs) links were cultured by regular method and CECs in logarithmic phase were than incubated on physico-crosslink regenerated silk fibroin film membrane. The shape of cultured human CECs was observed after 24,48 and 72 hours under the inverted microscope and scanning electron microscope( SEM ) ,and the CECs were cultured on culture plates as controls. The growth state of CECs on regenerated silk fibroin film was observed daily for 7 days by MTT, and cell cycle analysis and the presence of apoptosis of human CECs were examined by flow cytometry after incubation on regenerated silk fibroin film. Regenerated silk fibroin filmCECs (4 mm×3 mm) were implanted into the corneal stroma of the right eyes of New Zealand white rabbits. At the end of 4 and 8 weeks after implantation, the appearance of the ocular surface was examined using slit lamp and corneal neovascular area was measured. Corneal histopathological examination was carried out to assess the degradation of graft materials and immunohistochemistry was performed to detect the expression of CD34 in the corneal tissue after operation. ResultsThe morphology and structure of CECs were identical using the two cultured Methods when observed under the inverted microscope and SEM after 24,48 and 72 hours. No significant difference was found in the A490 value 1,2,3,4,5,6 or 7 days after incubation on regenerated silk membrane and in culture plates ( Fmethod =0. 641 ,P＞0.05 ). The apoptosis rates of CECs on regenerated silk membrane or culture plates were 1.8％ and 2.0％ and the amount of cells in G2/G1 phase was 1. 956 and 1. 945, respectively. Histopathological examination showed that the regenerated silk membrane material degraded and was replaced by regular collagen tissue 2 months after implantation,and the presence of neovascular area and inflammatory cells were less prominent in 2 months than 1 month post-implantation. The expression level of CD34 in corneal tissue was evidently lower 1 and 2 months after operation than the Ad-VEGF165-induced positive control group (P＜0. 05), and no significant differences were seen when compared with normal CECs(P＞0.05). ConclusionsPhysico- crosslink regenerated silk fibroin film is an excellent biomaterial for tissue engineered corneal scaffold with good biocompatibility.

Objective To evaluate the clinical features in Chinese patients with apical hypertrophic cardiomyopathy (AHCM) and typical hypertrophic cardiomyopathy (HCM). Methods This retrospective analysis included 160 patients hospitalized in Fuwai hospital. Patients were divided into three groups: apical hypertrophic cardiomyopathy ( AHCM, n = 41 ) group, non-obstructive typical hypertrophic cardiomyopathy group[NOHCM, LVOT ＜30 mm Hg(1 mm Hg =0. 133 kPa) at rest, n =52] and obstructive typical hypertrophic cardiomyopathy (OHCM, LVOT ≥ 30 mm Hg at rest, n = 67). Clinical features, diagnosis,therapy, and plasma levels of biomarkers of these three groups were analyzed. Results ( 1 ) The age at disease onset was older in AHCM group than in OHCM group [(49. 9 + 13. 6) years vs. (41.4± 14. 6)years, P ＜ 0. 01]. Exertional dyspnea appered more often in HCM patients than in AHCM patients, NT-proBNP level was significantly lower in AHCM patients than in OHCM patients (P =0. 001 ). Plasma CK-MB, LDH, TnI and MYO levels were similar among the three groups. (2) Thirty-three AHCM patients were first hospitalized for suspected coronary heart disease (CHD) and CHD was excluded in 18 cases (43.9%).(3) The frequency of giant negative T waves (depth≥10 mm) on ECG was 43.9%, 13.5% and 4.4%(P ＜ 0. 01 ) in AHCM, NOHCM and OHCM respectively. Half of AHCM patients showed left ventricular high voltage on ECG. (4) Cardiac magnetic resonance imaging is superior to echocardiography on correctly diagnosing AHCM. Conclusion AHCM patients differ from typical OHCM patients in clinical characteristics. There were significant differences on echocardiography and electrocardiography features among three groups. Cardiac magnetic resonance imaging and giant negative T waves on ECG are helpful for the diagnosis of AHCM.

Objective To identify the disease-causing gene mutations and to reveal the relationship between the genotype and the phenotype in Chinese patients with hypertrophic cardiomyopathy ( HCM). Methods One hundred unrelated patients with HCM and 120 controls were enrolled in this study. The full encoding exons and flanking sequences of the cardiac myosin binding protein C gene ( MYBPC3 ) were amplified with PCR and the products were sequenced. Results A novel missense mutation c. 706T > C was identified in exon 6 of MYBPC3 gene in three HCM patients, which resulted a Serine (S) to Glycine (G) exchange at amino acid residue 236 (S236G). The clinical phenotypes of the three patients were different (2 obstructive HCM, 1 non-obstructive HCM ). The 120 controls were normal in the genetic test Conclusions The novel S236G mutation in MYBPC3 gene was a hot-spot mutation in Chinese patients with HCM.

Objective To reveal genotype-phenotype correlation of disease-causing gene mutations in Chinese hypertrophic cardiomyopathy(HCM)pedigree.Methods Peripheral venous blood samples were collected from two Chinese HCM families and 120 healthy subjects were recruited as normal control.The full encoding exorts and flanking sequences of the cardiac troponin T gene(TNNT2),beta-myosin heavy chain gene(MYH7)and myosin binding protein C gene(MYBPC3)were amplified with the polymerase chain reaction method,DNA sequencing was used to detect the mutation.Results In ZZJ family,mutation G12101 A was identified in exon 21 of MYBPC3 gene in 4 family members [the arginine(R)converted to histidine(H)].in this pedigree,three out of eight family members were diagnosed as HCM and with a penetrance of 75%.In FHL family,mutation G15391A was identified in exon 23 of MYH7 gene in 3 family membeF8[the glutamic acid(E)convened to iysine(K)].In this pedigree,three out of six family members were diagnosed as HCM and with a penetrance of 100%.Echocardiography showed obstruction of left ventficular ontflow tract in two out of the three HCM patients.Conclusions Our results showed that the G12101 A mutation of MYBPC3 gene is the causal mutation of familial HCM with mild phenotype.The G15391 A mutation of MYH7 gene is the causal mutation of familial HCM with malignant phenotype and a penetrance of 100%.Screening mutations in the MYH7 gene should be viewed as a reasonable procedure in obstructive HCM patients.

OBJECTIVETo study the disease-causing gene mutation in Chinese patients with hypertrophic cardiomyopathy (HCM) and to analyze the genotype and phenotype correlation.

METHODSOne family (n = 27) affected with HCM were chosen for the study. The full encoding exons and flanking sequences of beta-myosin heavy chain gene (MYH7) and cardiac myosin-binding protein C gene (MYBPC3) were amplified with PCR and the products were sequenced. The clinical data including symptom, physical, echocardiography and electrocardiography examinations were collected.

RESULTSWe identified a 13261 G > A mutation, which causes a missense mutation (G758D) in exon 23 of MYBPC3 in 9 family members. One mutation carrier suffered from dilated cardiomyopathy (DCM) with asymmetric interventricular septal hypertrophy (14 mm). Another mutation carrier was diagnosed as HCM.

CONCLUSIONSThe 13261 G > A mutation is associated with a DCM-like HCM and HCM phenotype in this Chinese family affected with HCM.

Adult ; Cardiomyopathy, Hypertrophic ; genetics ; Carrier Proteins ; genetics ; China ; Female ; Humans ; Male ; Middle Aged ; Mutation, Missense ; Pedigree ; Phenotype

OBJECTIVETo evaluate the long-term effect of sodium glycididazole (CMNa) as a hypoxic radiosensitizer on the radiotherapy for nasopharyngeal carcinoma.

METHODSBetween May 1999 and May 2002, 211 patients with pathologically confirmed nasopharyngeal carcinoma were randomized into group-A treated by radiotherapy plus CMNa or group-B by radiotherapy alone. The staging was determined according to 92' Fuzhou staging systerm. The type, procession and dosage of radiotherapy were identical in both groups. The early adverse effect grade was assessed based on the CTC2.0 criteria and the late adverse effects were evaluated according to the RTOG/EORTC criteria. The median follow-up time was 52 months. All the data was analyzed by the SPSS 13.0 software. Characteristics and adverse events of these patients were compared between the two groups using t-test and the Wilcoxin rank sum test. Time-to-event curves were estimated using the Kaplan-Meier method. The prognostic parameters were analyzed using univariate analysis and the Cox multivariate regression analysis.

RESULTSThe clinical data of the two groups were comparable. The 3-year survival was 88.4% in group-A, while 75.2% in group-B, with a statistically significant difference between two groups (P = 0.010). Univariate analysis showed that the 3-year survival was statistically correlated with N-staging ((N0-1, 86.9%, N2-3 73.8%, P < 0.001), T-staging (T1-2 85.6%, T3-4 79.3%, P = 0.014), TNM staging (P = 0.039), and whether using CMNa or not during rediotherapy (Group-A 88.4%, Group-B 75.2%, P = 0.010). The 5-year recurrence-free survival, 5-year metastasis-free survival and 5-year overall survival were 75.8%, 74.9% and 77.7% in Group-A, while 63.0%, 63.0% and 62.4% in Group-B with a statistically significant difference between two groups (0.013, 0.022 and 0.010, respectively). If stratified in the subgroups, the overall survival of stage III - IV patients was statistically different between group A and B (P = 0.009), however, not of stage I - II patients (P = 0.502). Cox multivariate regression analysis showed that the independent prognostic parameters for survival were N-stage (RR = 3.288) , T-stage (RR = 2.147) and use of CMNa during rediotherapy (RR = 0.407). However, there was no statistically significant difference between two groups in acute or late adverse effects on nervous system or heart, which suggested that use of CMNa during radiotherapy would not aggravate the toxicity caused by radiotherapy.

CONCLUSIONSodium glycididazole is well tolerable effective as a hypoxic radiosensitizer, which can improve the efficacy of radiotherapy and the long-term result of nasopharyngeal carcinom a patients, especially for the stage III - IV patients.

Adolescent ; Adult ; Aged ; Female ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Male ; Metronidazole ; adverse effects ; analogs & derivatives ; therapeutic use ; Middle Aged ; Multivariate Analysis ; Nasopharyngeal Neoplasms ; pathology ; radiotherapy ; Neoplasm Staging ; statistics & numerical data ; Prognosis ; Proportional Hazards Models ; Radiation-Sensitizing Agents ; adverse effects ; therapeutic use ; Time Factors ; Treatment Outcome ; Vomiting ; chemically induced

OBJECTIVETo detect the disease-causing gene mutation of hypertrophic cardiomyopathy (HCM) in a Chinese family and to analyze the correlation of the genotype and the phenotype.

METHODSOne family affected with HCM was studied. The clinical data including symptom, physical examination, echocardiography and electrocardiography were collected. The full encoding exons and flanking sequences of beta-myosin heavy chain gene (MYH7) and cardiac myosin-binding protein C gene (MYBPC3) were amplified with PCR and the products were sequenced.

RESULTSA G8887A mutation, which is an acceptor splicing site of intron 15 (IVS15-1G > A) in MYBPC3 (gi: Y10129) was identified in 6 out of 11 family members. Three mutation carriers developed HCM at 48 - 75 years old with mild chest pain, chest distress and asymmetric septal hypertrophy (13 - 14 mm) and remaining mutation carriers are free of HCM. No mutation was identified in MYH7 gene.

CONCLUSIONHCM caused by the IVS15-1G > A mutation is a benign phenotype. It is helpful to screen MYBPC3 gene mutation in late-onset HCM patients with mild symptoms.

Adult ; Aged ; Cardiac Myosins ; genetics ; Cardiomyopathy, Hypertrophic, Familial ; genetics ; Carrier Proteins ; genetics ; Case-Control Studies ; Genotype ; Humans ; Middle Aged ; Mutation ; Myosin Heavy Chains ; genetics ; Pedigree ; Phenotype ; Polymerase Chain Reaction