AIM: To observe the efficacy and safety of intravitreal injection of Conbercept for the treatment of wet age-related macular degeneration( AMD) .
METHODS:Retrospective analysis. A total of 20 patients involving 22 eyes were diagnosed of wet AMD and confirmed by routine ophthalmic examination, fundus fluorescein angiography ( FFA ) and optical coherence tomography. All these affected eyes received intravitreal injection of 10 mg/ml of 0. 5mg Conbercept, once monthly, for 3 successive times during the initial treatment. The need for repeated treatment was determined according to patients'disease conditions. The patients were followed up once monthly for ≥6mo. The changes in best corrected visual acuity ( BCVA ) , central retinal thickness ( CRT ) and choroidal neovascularization ( CNV) lesion leakage of the affected eyes before and after treatment were compared and analyzed.
RESULTS:Within 1, 3 and 6mo after treatment, the mean BCVA ( logMAR ) of the affected eyes increased when compared with before treatment;the difference was statistically significant(P<0. 01). In 1, 3 and 6mo after treatment, the mean CRT of the affected eyes decreased when compared with before treatment;the difference was statistically significant(P<0. 01). During the last follow-up, FFA showed that macular CNV lesion leakage disappeared in 20 eyes(90%) while leakage mitigated in 2 eyes ( 9%) . During the follow - up, there were no treatment - related serious ocular complications and systemic serious adverse reactions.
CONCLUSION: Clinically, intravitreal injection of Conbercept for the treatment of wet AMD can increase visual acuity of the affected eyes. It also can decrease CRT of the affected eyes, and inhibit neovascular leakage. There are no treatment-related adverse reactions.

Objective Using methodology of molecular genetics to explore the origin,phylogen,and gene flow of Mycobacterium tuberculosis (MTB) Beijing lineage in the five provinces from northern China,including Heilongjiang,Jilin,Liaoning,Neimenggu and Ningxia.Methods 234 MTB Beijing lineage strains were genotyped by 24 Variable Number Tandem Repeat (VNTR),and the h (the allelic diversity) value of each VNTR locus was calculated.On individual level of phylogeny,it was constructed Neighbor-Joining (N-J) tree and minimum spanning tree (MST).Phylogenetic tree was built at the population level,and the most recent common ancestor (TMRCA)was estimated through Bayesian model.Molecular variance (AMOVA) was used to understand the gene flow among strains discovered from the five provinces.Results Allelic diversities of the 24VNTR loci were low (h:0.000-0.744).234 strains of MTB Beijing lineage were dispersed in individual branch of the N-J tree,with 62.0％ (145) of them grouped to the same "colonial complexes" in MST.At the population level,the evolution relationship of 234 strains appeared the closest to Beijing lineage,which was from MIRU-VNTRplus database,and the bootstrap was 100.The TMRCA was 5308 (95％ CI:4263-6470) years.Differences of pairwise Fst values acquired by AMOVA between Jilin and Heilongjiang,Liaoning,Neimenggu and Ningxia,were not statistically significant (P＞0.05).Conclusion The genetic similarity of Beijing lineage MTB from the five provinces of northern China was high.The phylogeny branches had no characteristic dispersal in each province.It was speculated that these strains showed an evolution from a clone of MTB Beijing lineage (about 5000 years ago).The gene flow was taking place between neighboring zones.

OBJECTIVE: To investigate the invason of trophoblasts in the placenta bed and the change of spiral arteries and microvessels in pre-eclampsia and normal pregnancy. METHODS: Twenty cases of normal pregnancies, mild pre-eclampsia and severe pre-eclampsia were chosen as Group A, Group B, and Group C. HE staining and immunohistochemistry staining (SP method) were used to observe the depth and the density of trophoblasts invading the placenta bed and the change of spiral arteries and microvessels. RESULTS: The significant difference in the degree of invasion was in the superficial myometrial segment. Group C was the most superficial in the 3 groups (P<0.01). The density of trophoblasts which invaded the placenta bed in the lower half of the basal decidual segment and the myometrial segment showed us Group C was the lowest (P<0.01). There was statistical difference among the 3 groups (P<0.01). The average lumen area of the spiral arteries in the decidual segment and the superficial myometrial segment of the placenta bed was the smallest in Group C among the 3 groups(P<0.01) and there was statistical difference among the 3 groups (P<0.01). The spiral arteries were the thickest in Group C with statistical difference among the 3 groups (P<0.01). The physiological and pathological change of the spiral arteries was mainly in the superficial myometrial segment. The incidence rate of physiological changes in the spiral arteries was the lowest in Group C with statistical difference among the 3 groups (P<0.01). The incidence rate of pathological changes was the highest in Group C (P<0.01) and the normal group was the highest. There was significant difference among the 3 groups(P<0.01). There was positive correlation between the physiological change of the spiral arteries and the invaing degree of the trophoblasts (P<0.05), there was negative correlation between the pathological change of the spiral arteries and the invasion depth as well as the invasion density of the trophoblasts(P<0.05). There was negative correlation between the physiological change and the pathogenetic condition of pre-eclampsia(P<0.05)while there was positive correlation between the pathological change and the pathogenetic condition degree of pre-eclampsia(P<0.05). There was negative correlation between the invasion depth as well as density in uteruso superficial myometrial segment by trophoblast and the pathogenetic condition degree of pre-eclampsia(P<0.05). There was invasion trophoblast in 62.50% lumen wall of spiral arteries in uterus superficial myometrial segment of the placental bed in normal pregnancy while 27.5% was seen in severe pre-eclampsia. Microvascular density in the decidual segment and the superficial myometrial segment of the placenta bed in Group C was the lowest among the 3 groups with statistical difference (P<0.01). CONCLUSION The invasion depth of the trophoblasts in pre-eclampsia was more superficial than normal pregnancy.The changes of the invasion of the trophoblasts and the pathological changes of the spiral arteries in the placenta bed mainly existed in the superficial myometrial segment which was closely related to the severity of the illness. That microvascular density in the placental bed of pre-eclampsia started to decrease from the basal decidual segment shows that the microvessel development in the placenta bed is impaired in pre-eclampsia.
Adult ; Arteries ; pathology ; Capillaries ; pathology ; Female ; Humans ; Placenta ; blood supply ; pathology ; Pre-Eclampsia ; pathology ; Pregnancy ; Trophoblasts ; pathology

Objective To investigate the effect of Ginkgo biloba extract (EGB) on changes of activities of platelet phosphodiesterase (PDE) and nucleotide cyclase (adenylate cyclase [AC] and guanylate cyclase [GC]), and levels of cyclic nucleotide (cylic adenosine monophosphate [cAMP] and cyclic guanosine monophosphate [cGMP]), and investigate the mechanism of platelet anti-aggregation with EGB. Methods Blood samples from 3 healthy volunteers, not taken any drugs within 2 weeks of the experiments, were anticoagulated with 3.8% sodium citrate. After isolating and washing, platelet was given various concentrations of EGB, and then applied for measurement of the levels cAMP and cGMP and the activities of PDE, AC and GC isolated from platelet sonic homogenates. Controls were given the same volume of bulk drug solvent. Results EGB dose-dependence was noted: the higher the level of EGB, the higher the cAMP level and the more active the PDE3. EGB at high-dose could slightly inhibit the PDE5 activity. EGB in any dosages could not affect the cGMP level, and activities of PDE2, AC and GC. Conclusion EGB has platelet anti-aggregation effect through inhibiting the PDE3 activity and increasing the cAMP level.

Objective To observe the changes of activities of platelet phosphodiesterase(PDE)subtypes in patients with acute cerebral infarction,and explore their influencing factors.Methods The platelet PDE activity,cyclic nucleotide level and[Ca2+]i concentration of 30 patients with acute cerebral infarction were detected on the 1st, 4th,8th and 15th d of onset.Ten healthy individuals of the same age ranges were chosen as control group.Results On the 1st,4th and 8th d of onset,as compared with those in the healthy individuals,the activities of platelet PDE2 and PDE3 and the level of cyclic adenosine monophosphate(cAMP)were obviously decreased,and the[Ca2+]i level was significantly increased in patients with acute cerebral infarction(P<0.05); while the PDE5 activity and cyclic gnanosine monophosphate(cGMP)level in patients with acute cerebral infarction did not change obviously.[Ca2+]iwas linearly correlated with cAMP(R2=0.921,P<0.05);however,the activities of PDE2 and PDE3 showed no correlation with both levels of[Ca2+]i and cAMP. Conclusion Decreased cAMP level and increased[Ca2+]i concentration are noted in patients with acute cerebral infarction,and the platelet is activated at this time points.Platelet PDE2 and PDE3 play protect roles in acute cerebral infarction through decreasing their activities,slowing the cAMP decreased level and inhibiting the activity of platelet.

OBJECTIVETo investigate the main components of inner ear antigens inducing autoimmune Meniere's disease (AIMD) in guinea pigs.

METHODSThe guinea pigs were immunized with isologous crude inner ear antigens (ICIEAg). Then, the hearing function was measured with auditory brainstem response (ABR), the vestibular function was measured with electronystagmography (including spontaneous nystagmus and caloric test), and inner ear histopathological changes were observed by inner ear celloidin section with haematoxylin-eosin staining and observed under light microscope. According to these results, the AIMD-model animals from non-AIMD-model ones were distinguished. The special antibodies against ICIEAg in sera were measured with ELISA. The antigen-antibody reactions against different components of ICIEAg were detected by Western blotting with sera of AIMD and non-AIMD guinea pigs respectively. Then, we analysed the contrast between them and found the main components of the ICIEAg that were positive reaction in AIMD guinea pigs and negative reaction in non-AIMD guinea pigs.

RESULTSThe result of ELISA demonstrated that the sera of both the AIMD and non-AIMD guniea pigs contained the special antibodies against ICIEAg after immunized with ICIEAg. The difference of the amount of antibody against ICIEAg between AIMD guinea pig group and non-AIMD guinea pig group was not significant. Western blotting assay showed only the sera of AIMD guinea pig contained the antibodies against the specific antigens with the molecular of 68 000, 58 000, 42 000 and 28 000.

CONCLUSIONSICIEAg contain many different components, the AIMD might only happen in the guinea pigs in which the special immunization against the main components that could induce this kind of disorder appeared. The inner ear antigens with molecular of 68 000, 58 000, 42 000 and 28 000 might be the main components inducing AIMD in guinea pigs.

Animals ; Autoantigens ; immunology ; Autoimmune Diseases ; immunology ; Disease Models, Animal ; Ear, Inner ; immunology ; Guinea Pigs ; Labyrinth Diseases ; immunology

The aim of this study was to set up a new method for 5, 10-Methylenetetrahydrofolate reductase (MTHFR) single nucleotide polymorphisms (SNP) genotyping, and to investigate the hereditary susceptibility of hematological malignancy. Prepared an aimed gene microarray based on cDNA microarray theory, dual-color fluorescence hybridization was used to detect SNP loci, and DNA sequencing was performed to confirm the results. The MTHFR C677T SNP loci of 157 controls and 127 patients with hematological malignancies (30 multiple myeloma, 28 non-Hodgkin's lymphoma, 22 acute lymphoblastic leukemia, 40 acute myeloid leukemia, 7 chronic myeloid leukemia) from Jiangsu province were detected. The results showed that after overlapping, homozygous wild type, heterozygote type and homozygous mutant type yielded green, yellow and red fluorescence, respectively. DNA sequencing validated these results. The allele frequency of 677C and 677T in patients and controls were 58.7% and 66.9%, 41.3% and 33.1% respectively, showing statistically significant difference (chi2 = 4.077, P = 0.043). 677TT genotype showed a significantly higher risk of MM (OR = 4.21; 95% CI = 1.50 - 11.83; P = 0.006). It is concluded that this microarray-based method is accurate, high-throughput and inexpensive, suitable for SNP genotyping in a large number of individuals. C677T polymorphisms influence the risk of hematological malignancies. 677TT genotype is susceptive to MM.
Adult ; Aged ; Base Sequence ; Female ; Genetic Predisposition to Disease ; genetics ; Genotype ; Hematologic Neoplasms ; enzymology ; genetics ; Humans ; Male ; Methylenetetrahydrofolate Reductase (NADPH2) ; genetics ; Middle Aged ; Molecular Sequence Data ; Oligonucleotide Array Sequence Analysis ; Polymorphism, Single Nucleotide

OBJECTIVETo assay the expression of KiSS-1 and GnRH in the male rat hypothalamus at different developmental stages, and to explore the significance of KiSS-1 in sex development onset and normal reproduction regulation.

METHODSExpression analyses of KiSS-1 and GnRH genes were conducted in the rat hypothalamus at different developmental stages with RT-PCR and real time-PCR. The testosterone level was assayed by chemoluminescence technique.

RESULTSKiSS-1 mRNA rose gradually during sex development in the rat hypothalamus, highest at puberty and lowered a little at adulthood. KiSS-1 mRNA of the prepubertal, early pubertal, pubertal and adult rats was 1.7, 2.1, 3.5 and 2.0 times higher than that of the infantile rats respectively. The expression of GnRH and KiSS-1 correlated positively (r = 0.905, P < 0.05). But the activation of GnRH neuron was later than KiSS-1. The expression of GnRH was the highest in the puberty rats. GnRH mRNA of the prepubertal, early pubertal, pubertal and adult rats was 1.1, 1.94, 2.42 and 1.92 times higher than that of the infantile rats respectively. The level of testosterone in the adult rats was significantly higher than that at the earlier stage and was the highest at the adult stage.

CONCLUSIONThe expression of KiSS-1 correlates positively with that of GnRH. KiSS-1 may participate in the regulation of GnRH and is relevant to puberty onset and the regulation of reproduction function.

Animals ; Gonadotropin-Releasing Hormone ; biosynthesis ; genetics ; Hypothalamus ; metabolism ; Kisspeptins ; Male ; Proteins ; metabolism ; RNA, Messenger ; biosynthesis ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction

BACKGROUNDCurrently, migration has become one of the risk factors of high burden of tuberculosis in China. This study was to explore the influence of mass migration on the dynamics of Mycobacterium (M.) tuberculosis in Beijing, the capital and an urban area of China.

METHODSThree hundred and thirty-six M. tuberculosis strains from the Changping district, where the problem of urban migrants was more pronounced than in other Beijing regions, were genotyped by Spoligotyping, large sequence polymorphisms (LSPs 105 and 181), and variable number tandem repeat (VNTR) typing. Based on the genotype data, the phylogeny of the isolates was studied.

RESULTSIn Changping district, the proportion of Beijing lineage M. tuberculosis isolates amounted to 89.0% (299/336), among which 86.6 % (252) belonged to the modern lineage. The frequency of modern Beijing lineage strains is so high (around 75% (252/336)) that associated risk factors affecting the tuberculosis epidemic cannot be determined. The time to the most recent common ancestor (TMRCA) of the Beijing lineage strains was estimated to be 5073 (95% CI: 4000-6200) years. There was no significant difference in the genetic variation of Beijing isolates from urban migrants and local residents.

CONCLUSIONSThe clone of modern Beijing lineage M. tuberculosis, which is dominant in the Beijing area, most likely started to expand with the five thousand-year-old Chinese civilization. In the future, with the urbanization in the whole of China, modern Beijing lineage M. tuberculosis may gain the larger geographical spread.

China ; Genetics, Population ; Genotype ; Humans ; Mycobacterium tuberculosis ; classification ; genetics ; Phylogeny ; Transients and Migrants

Intestinal flora is the largest microbial community in human body， which consists of more than 1 000 species. Its structure and metabolites change dynamically with the age， diet and intestinal environment of the host. Study shows that the intestinal microbes play a pivotal role in regulating human physiological and pathological processes， and intestinal flora imbalance may be the key factors affecting the occurrence and development of bone and joint diseases， including osteoporosis， osteoarthritis， rheumatoid arthritis and gouty arthritis. At present， calcitonin， estrogen， nonsteroidal anti-inflammatory drugs， immunosuppressants， xanthine oxidase inhibitors and other western drugs are mostly used to treat the above diseases. However， long-term use of western drugs leads to poor compliance and obvious gastrointestinal adverse reactions among patients. Traditional Chinese medicine （TCM） predominates in the treatment of bone and joint diseases due to its low price， high efficacy and slight side effects， with the advantages of multi-targets， multi-mechanism and multi-levels. In recent years， many scholars have carried out experiments and clinical studies on the treatment of bone and joint diseases by TCMs on the basis of the liver and kidney theory such as "tonifying liver and kidney and strengthening muscles and bones". Gratifying results have been achieved. However， the mechanism of action has not been fully clarified. Intestinal flora becomes a hot spot in medical research， and a close relationship between intestinal flora and bone and joint diseases has been unveiled. Relevant literature in China and abroad showed that TCM has a significant effect on the treatment of bone and joint diseases by regulating intestinal flora. In this paper， the relationship between intestinal flora and bone and joint diseases was summarized and the intervention of TCM active ingredients and compounds on intestinal flora was reviewed to facilitate the prevention and treatment of bone and joint diseases by TCM.