OBJECTIVEFabry disease is a rare lysosome storage disease featuring X-linked recessive inheritance. The study was to explore potential mutations of alpha-galactosidase A (GLA) gene and their correlation with clinic manifestations in three Chinese pedigrees with Fabry disease.

METHODSAll exons and flanking sequences of GLA gene were amplified with PCR. Potential mutations were detected with bidirectional DNA sequencing. Correlation between particular mutations and clinic features were analyzed.

RESULTSA unreported missense mutation, c.797A>C (D266A) in GLA exon 5 was identified in pedigree 1. Also in exon 5, a missense mutation c.644A>G (N215S) was found in pedigree 2. In pedigree 3, a nonsense mutation c.355C>T (Q119X) was found in exon 2. The c.797A>C mutation was not detected in 200 unrelated male controls. The probands of pedigrees 1 and 3 had presented mainly with skin damage and chronic renal insufficiency, whilst the proband of pedigree 2 had presented with hypertrophic cardiomyopathy.

CONCLUSIONThe unreported c.797A>C (D266A) mutation is the sixth missense type mutation of the 266th codon of GLA gene, and all other 5 missense mutations reported previously had been confirmed to be responsible for Fabry disease. The c.797A>C mutation, not found in 200 unrelated male controls, may be the causative mutation in pedigree 1. The c.644A>G and c.355C>T mutations were first detected in Chinese patients. Variable phenotypes of Fabry disease may be in part attributed to the natures of particular mutations of GLA gene.

Adult ; Fabry Disease ; genetics ; Humans ; Male ; Middle Aged ; Mutation ; Pedigree ; alpha-Galactosidase ; genetics

OBJECTIVETo understand the epidemiological, clinical and etiological characteristics of an Echovirus type 6 meningitis outbreak in Jinzhai county, Liu'an city in Anhui, and to find out the proper way in controlling the aseptic meningitis outbreak.

METHODSA surveillance system for aseptic meningitis was established in Jinzhai to confirm the case definition. Stool or cerebrospinal fluid (CSF) specimens from some cases were collected for entero-viruses isolation and identification. Case-control study was conducted. The case group involved patients while the controls would include: patients' classmate with same gender and the age difference was not over one year. Neutralization antibody in serum specimens were collected and tested in cases and in healthy people.

RESULTS105 cases were distributed in 17 of the 30 towns in Jinzhai county while 41.0% of the cases were in Banzhuyuan town with an incidence rate of 203/10(5). Cases were clustered by school and classroom with age ranging from 3 to 15 years old and the highest as 10.9/10(5) in the 6 to 10 group. The incidence in males was 24.2/10(5) compared to 8.4/10(5) in females. The main clinic characteristics of cases were: fever, headache and vomiting. Echovirus type 6 from 25 of the 72 CSF samples (35%) was isolated. When comparing the cases group with control group, the OR of drinking home-made beverages was 4.1 (95% CI: 1.4-12.0), especially the beverages sacked by plastic bag: 3.3 (95% CI: 1.3-8.8). 6 out of 7 workers engaging in producing home-made beverages were detected to have carried Echovirus type 6 from their stool specimens. The Echovirus type 6 neutralization antibody positive rate in cases (73.5%) was significantly higher than that in 100 healthy people (46.0%) (X2 = 12. 526, P = 0.000).

CONCLUSIONThis episode of meningitis outbreak was caused by Echovirus type 6. The proportion of drinking home-made beverages, especially the beverages sacked by plastic bag in cases group was higher than in control group.

Adolescent ; Child ; Child, Preschool ; China ; epidemiology ; Echovirus 6, Human ; pathogenicity ; Echovirus Infections ; epidemiology ; etiology ; pathology ; virology ; Female ; Humans ; Male ; Meningitis ; epidemiology ; etiology ; pathology ; virology ; Prejudice

To evaluate the immunogenicity of inactivated SARS coronavirus (SARS-CoV), three groups of rabbits were immunized three times at 2-week intervals with inactivated vaccine + adjuvant, adjuvant,and normal saline respectively. Eight batchs of serum were sampled from the auricular vein at day 7 to day 51, and specific IgG antibody titers and neutralizing antibody titers were detected by indirect ELISA and micro-cytopathic effect neutralizing test. Antibody specificity was identified by proteinchip assay.Histopathological changes were detected by H&E staining. The results showed that, rabbits in the experimental group immunized with inactivated SARS-CoV all generated specific IgG antibodies with neutralizing activity, which suggested the inactivated SARS-CoV could preserve its antigenicity well and elicit an effective humoral immune responses. The peak titer value of specific IgG antibody and neutralizing antibody reached 1:40960 and 1:2560 respectively. In the experimental group, no obvious histopathological changes was detected in the H&E stained slides of heart, spleen, kidney and testis samples, but the livers had slight histopathological changes, and the lungs presented remarkable histopathological changes. These findings are of importance for SARS-CoV inactivated vaccine development.

OBJECTIVETo introduce one-staged correction of nasal deformity and unilateral complete cleft lip in infancy and to observe the nasal development after the operation.

METHODSThe unilateral complete cleft lip and nasal deformity were corrected in one stage in27 cases. They were followed up for several years. With post-operative photos, the anthropometric method was used to analyze the nasal development.

RESULTSThe long-term results were excellent in 10 cases, good in 14 cases, and poor in 3 cases.

CONCLUSIONSBased on the anatomic findings of nasal blood supply, one-staged correction of nasal deformity and unilateral complete cleft lip in infancy can be performed with no obvious interference with nasal development. The secondary nasal deformity before school age can be alleviated or avoided.

Abnormalities, Multiple ; surgery ; Child ; Child, Preschool ; Cleft Lip ; surgery ; Female ; Follow-Up Studies ; Humans ; Infant ; Lip ; growth & development ; Male ; Nasal Septum ; growth & development ; Nose ; abnormalities ; growth & development ; Rhinoplasty ; methods ; Surgical Flaps ; Treatment Outcome

BACKGROUNDThe etiologic agent of severe acute respiratory syndrome (SARS) has been confirmed to be a novel coronavirus (CoV), namely SARS-CoV. Developing safe and effective SARS-CoV vaccines is essential for us to prevent the possible reemergence of its epidemic. Previous experiences indicate that inactivated vaccine is conventional and more hopeful to be successfully developed. Immunogenicity evaluation of an experimental inactivated SARS-CoV vaccine in rabbits was conducted and reported in this paper.

METHODSThe large-scale cultured SARS-CoV F69 strain was inactivated with 0.4% formaldehyde and purified, then used as the immunogen combined with Freund's adjuvant. Eight adult New Zealand rabbits were immunized four times with this experimental inactivated vaccine. Twelve sets of rabbit serum were sampled from the third day to the seventy-fourth day after the first vaccination. The titers of specific anti-SARS-CoV IgG antibody were determined by indirect enzyme-linked immunosorbent assay, and the neutralizing antibody titers were detected with micro-cytopathic effect neutralization test.

RESULTSRapid and potent humoral immune responses were induced by the inactivated SARS-CoV vaccine in all the eight test rabbits. Titers of both specific IgG antibody and neutralizing antibody peaked at about six weeks after first vaccination, with the maximum value of 1:81 920 and 1:20 480, respectively. After that, serum antibody levels remained at a plateau or had a slight decrease, though two boosters were given in the succedent 4 to 5 weeks. Cross neutralization response existed between SARS-CoV F69 strain and Z2-Y3 strain.

CONCLUSIONSThe inactivated SARS-CoV vaccine made from F69 strain owns strong immunogenicity, and the cross neutralization response between the two different SARS-CoV strains gives a hint of the similar neutralizing epitopes, which provide stable bases for the development of inactivated SARS-CoV vaccines.

Animals ; Antibodies, Viral ; blood ; Immunoglobulin G ; blood ; Neutralization Tests ; Rabbits ; SARS Virus ; immunology ; Vaccines, Inactivated ; immunology ; Viral Vaccines ; immunology

Alkaloids ; pharmacology ; Animals ; Antiviral Agents ; pharmacology ; Benzylisoquinolines ; Cercopithecus aethiops ; Dose-Response Relationship, Drug ; SARS Virus ; drug effects ; Vero Cells

OBJECTIVETo ascertain the causation of a pregnant woman with undefined pneumonia reported from the People's Hospital of Tongling city in Anhui province on November 2005.

METHODSEpidemiological and clinical information of the case was collected from the keypersons close to the case and referring to the medical record. A medical observation was carried out on the close contacts of the case and sick or dead poultry. Tracheal aspirates being collected were tested by both RT-PCR and real-time PCR to detect viral nucleic acids of A/H5N1, and were inoculated into special pathogen free (SPF) embryonated hens' eggs.

RESULTSThe pregnant woman was found to have been contacted with the sick/dead poultry directly on the 4th day before onset of illness. All the 122 close contacts were healthy after a 10-day medical observation. The major clinical features of the case were viral pneumonia with rapidly developed leukopenia and lymphopenia. The progress to acute respiratory distress syndrome and multiple organ dysfunction syndromes was found at clinical presentation. HA and NA gene of A/H5N1 virus were positive. The 8 gene fragments of A/Anhui/1/2005 (H5N1) isolated from the tracheal aspirates had not carried genes from a human virus through reassortment, and the receptor-binding site of the hemagglutinin was polybasic cleavage site.

CONCLUSIONThis was the first documented case of H5N1 infection in pregnant woman. The immunotolerant state of pregnancy might have predisposed to the fatal outcome of the patient.

Adult ; China ; Fatal Outcome ; Female ; Humans ; Influenza A Virus, H5N1 Subtype ; genetics ; isolation & purification ; Influenza, Human ; complications ; pathology ; Multiple Organ Failure ; Pneumonia ; virology ; Polymerase Chain Reaction ; Pregnancy ; Pregnancy Complications, Infectious ; virology ; Respiratory Distress Syndrome, Adult ; Trachea ; virology

According to the structure and effect differences of Panax notoginseng saponin components(PNSC), subcomponent division and network pharmacological characterization were conducted to provide a research basis for the medicinal properties of P.notoginseng saponin subcomponents and the technical design of unit preparations. PNSC were screened by the TCMSP database and subcomponents were classified according to systematic clustering. Then the subcomponents obtained were subjected to target prediction and attribution analysis by PharmMapper server, GeneCards, DisGeNET and HOME-NCBI-GENE database. A subcomponent target interaction network was constructed by using the STRING database. KEGG and GO enrichment analysis were performed on each subcomponent target using the DAVID database. The subcomponents-targets-pathways visualization network was constructed by Cytoscape. The subcomponent targets and pathways involved were compared to analyze the differences in anti-myocardial ischemic drug mechanisms and the rationality of subcomponent division. Eighteen compounds of PNSC were screened out, and classified into three subcomponents A, B, and C according to their properties, involving 67 targets and 17 common anti-myocardial ischemic pathways directly or indirectly related to myocardial ischemia. Subcomponent A had the highest number of targets and the target interaction was dense, possibly indicating its key role in the mechanism of pharmacodynamics. Subcomponents A, B, and C had similar basic structures, and KEGG and GO analysis showed that they all can enhance the heart function and protection of cardiomyocytes by inhibiting apoptosis, promoting angiogenesis and regulating inflammatory response to play the effect on myocardial ischemia. This study fully reflected the differences in the efficacy of various subcomponents in preventing and treating myocardial ischemia due to the different physical properties of P. notoginseng saponin subcomponents. To some extent, the differences in the efficacy of each subcomponent in the prevention and treatment of myocardial ischemia could verify the rationality of the division of P. notoginseng saponin subcomponents according to the structural properties, realizing the characterization of P. notoginseng saponin subcomponents based on structure and effect differences.
Apoptosis ; Coronary Artery Disease ; Humans ; Myocardial Ischemia ; Panax notoginseng ; Saponins

Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P>0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P<0.001), smaller maximum tumor diameter (t=3.969, P<0.001), less number of metastatic lymph nodes (t=1.343, P<0.001), lower ratio of vessel invasion (χ(2)=11.897, P=0.001) and nerve invasion (χ(2)=12.338, P<0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P=0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P=0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P<0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P<0.05); patients over 45 years of age (P<0.05) and with normal body mass (P<0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly (P<0.05); patients with signet ring cell carcinoma benefited little (P>0.05); tumors in the gastric body and gastric antrum benefited more significantly (P<0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.
Chemotherapy, Adjuvant ; Female ; Gastrectomy ; Humans ; Male ; Neoadjuvant Therapy ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Stomach Neoplasms/surgery*