Objective The surgery time for patients with infective endocarditis (IE) has been transformed.It has been supported that,for the patients with surgical indications,the surgery time should be as early as possible to improve the clinical outcome.The purpose of the research is to identify whether the patients with IE could get further benefit from early surgery.Methods Between June 1996 and July 2011,135 IE patients'data has been collected retrospectively,all of whom were verified through the modified Duke categories.The patients were devided into group A( the new therapeutic schedule group after 2008 ) and group B( the traditional therapeutic schedule group before 2008 ) by the year of 2008.The end points of observation were death associated with IE,cardiac failure,embolism,and re-infection.The comparison between the groups was by means of non-parameter rank and inspection test,variance analysis,t test,chi-square test,fisher exact test.The outcome comparison between the groups was via the Kaplan-Meier survival analysis.Results There were no significant differences in baseline data between the groups.No survival differences could be observed via the Kaplan-Meier analysis( Log Rank P =0.189).During the following-up visit,compared with the patients in group B,the mortality in group A is lower(9.4％ vs.23.0％,P=0.016),the incidence of heart failu re was less in group A (5.4％ vs.26.2％,P ＜0.001 ).No differences could be found in re-infection between the two groups(0 vs.4.9％,P =0.112 ). More patients in group A underwent surgery (67.6％ vs.32.8％,P ＜0.001 ).Conclusion The new therapeutic sehedule of IE coull reduce the mortality rate and promote the cardiae funetion.The incidence of re-infeetion didn't increase.

Objective:To evaluate the effect of berberine on the volume and weight of, cell proliferation and apoptosis in transplanted cutaneous squamous cell carcinoma (cSCC) in nude mice inoculated with A431 cells, and to explore the possible mechanism underlying the inhibitory effect of berberine on cSCC.Methods:A431 cells were cultured, and A431 cell suspension was subcutaneously injected into the back of 20 nude mice to establish a nude mouse model of transplanted cSCC. On day 15 after inoculation, these tumor-bearing mice were randomly and equally divided into 4 groups: low-, medium- and high-dose berberine groups intraperitoneally injected with 10, 20 and 25 mg/kg berberine solution respectively, and control group intraperitoneally injected with sodium chloride physiological solution. The treatment was performed once a day for 35 consecutive days. The tumor volume was measured before, and on days 7, 14, 21, 28 and 35 after the start of treatment. After the end of the experiment, the nude mice were sacrificed, and the tumors were removed and weighed to calculate the tumor growth inhibition rate. Histopathological examination was performed in these transplanted tumors, immunohistochemical study was conducted to determine the expression of Ki67, TUNNEL staining was conducted to determine the number of apoptotic cells in the transplanted tumor tissues, fluorescence-based quantitative PCR and Western blot analysis were employed to determine the mRNA and protein expression of apoptosis-related proteins Bax, Bcl-2, caspase-3 and Ezrin respectively. One-way analysis of variance was used for comparisons among multiple groups, and Dunnett- t test for comparisons of each berberine group with the control group. Results:Along with the increase in the dose of berberine and treatment duration, the tumor growth curve gradually became flat, the tumor growth was inhibited to different degrees in the berberine groups, and the high-dose berberine showed the strongest inhibitory effect on the tumor growth. The tumor growth inhibition rate was 31.05%, 66.68%, 76.49% in the low-, medium-, and high-dose berberine groups respectively, and the tumor weight was significantly lower in the 3 berberine groups than in the control group ( t = 4.07, 6.33, 7.26, respectively, all P < 0.01) . Along with the increase in the dose of berberine, histopathological examination of the transplanted tumors showed that the extent and area of tumor cell necrosis increased, while immunohistochemical study showed that the number of Ki67-positive cells gradually decreased. Moreover, the number of Ki67-positive cells was significantly lower in the low-, medium- and high-dose berberine groups than in the control group (all P < 0.01) , but the number of apoptotic cells was significantly higher in the berberine groups than in the control group ( P < 0.05 or < 0.01) . The mRNA and protein expression of Bax, Bcl-2, caspase-3 and Ezrin significantly differed among the 4 groups (all P < 0.01) . In addition, the mRNA expression of Bcl-2 was significantly lower in the low-, medium- and high-dose berberine groups than in the control group (all P < 0.01) , and the protein expression of Bcl-2 was significantly lower in the medium- and high-dose berberine groups than in the control group (both P < 0.01) ; Bax mRNA expression in the high-dose berberine group and caspase-3 mRNA expression in the medium- and high-dose berberine groups were significantly higher than the corresponding mRNAs in the control group respectively ( P < 0.05 or < 0.01) , and the protein expression of Bax and caspase-3 was significantly higher in the low-, medium- and high-dose berberine groups than in the control group (all P < 0.01) ; Ezrin mRNA expression was significantly higher in the high-dose berberine group than in the control group ( P < 0.01) , but its protein expression was significantly lower in the low-, medium-, and high-dose berberine groups than in the control group (all P < 0.01) . Conclusion:Berberine can inhibit the proliferation of A431 cells and promote their apoptosis in the transplanted cSCC of the nude mice, and then suppress the growth of transplanted cSCC in the nude mice to a certain extent, which may be related to the upregulation of Bax and caspase-3 and downregulation of Bcl-2 and Ezrin.

OBJECTIVETo investigate the role of MT-ND1 m.3635G>A mutation in the pathogenesis of Leber's hereditary optic neuropathy (LHON).

METHODSBiochemical characteristics including the activity of complex Ⅰ, ATP production and oxygen consumption rate among lymphoblastoid cell lines derived from 3 carriers, 3 affected matrilineal relatives of the families and 3 controls were compared.

RESULTSComparison of mitochondrial functions in lymphoblastoid cell lines of the carriers, patients and controls showed a 51.0% decrease in the activity of complex Ⅰ in patients compared with controls (P<0.05). The m.3635G>A mutation has resulted in decreased efficiency of ATP synthesis (P<0.05). Comparison of oxygen consumption rate showed that the basal OCR (P<0.05), ATP-linked OCR (P<0.05) and the maximum OCR (P<0.05) have all reduced to some extent compared with the controls.

CONCLUSIONThese results showed that m.3635G>A, as a LHON-associated mutation, can lead to mitochondrial dysfunction.

Adenosine Triphosphate ; genetics ; Asian Continental Ancestry Group ; genetics ; Female ; Humans ; Male ; Mitochondria ; genetics ; Mutation ; genetics ; NADH Dehydrogenase ; genetics ; Optic Atrophy, Hereditary, Leber ; genetics ; Pedigree

OBJECTIVETo report on clinical, genetic and molecular characterization of two Chinese families with Leber's hereditary optic neuropathy.

METHODSOphthalmological examinations have revealed variable severity and age at onset of visual loss among the probands and other matrilineal relatives of both families. The entire mitochondrial genome of the two probands was amplified with PCR in 24 overlapping fragments using sets of oligonucleotide primers.

RESULTSThe ophthalmological examinations showed that penetrance was 12.5% and 30.0% respectively in the two families. Sequence analysis of the complete mitochondrial genomes in these pedigrees has identified unreported homoplasmic T8821G mutation in the ATPase 6 gene and distinct sets of polymorphisms belonging to haplogroups M10a. The T8821G mutation has occurred at the extremely conserved nucleotide (conventional position 99) of the ATPase6. Thus, this mutation may alter structural formation of ATPase6, thereby leading to failure in the synthesis of ATP involved in visual impairment.

CONCLUSIONAbove observations have suggested that the ATPase6 T8821G mutation may be involved in the pathogenesis of optic neuropathy in these families.

Adolescent ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; China ; DNA, Mitochondrial ; genetics ; Female ; Humans ; Male ; Mitochondrial Proton-Translocating ATPases ; genetics ; Molecular Sequence Data ; Optic Atrophy, Hereditary, Leber ; enzymology ; genetics ; Pedigree ; Point Mutation ; Young Adult