Objective To evaluate the safety and efficacy of Voriconazole on invasive fungal infections in very elderly patients.Methods Clinical data of 24 very elderly patients with invasive fungal infections who had sought treatment at the Department of Geriatrics of our hospital from April 2013 to April 2014 were retrospectively investigated.The classifications and quantities of fungi,accompanying symptoms,adverse reactions,blood tests,and liver and kidney function indicators were recorded and analyzed before and after treatment.Results Each of the 24 cases was found to have been infected with one or more of 17 fungal strains belonging to the genus of Candida.The rate of complete fungal elimination after treatment was 70％ (12/17).Of the 24 cases,5 achieved a full recovery(20.8 ％),10 (41.7 ％) had significant improvement,5 (20.8 ％) had some improvement,and 4 cases(16.7％)showed no therapeutic benefits,with a total effectiveness rate of 62.5 ％.There was no significant difference in liver and kidney function before and after treatment(P＞0.05).A transient increase in serum creatinine occurred in 1 case and defective vision in another patient during Voriconazole treatment.Conclusions The incidence of invasive fungal infections is high in very elderly patients,with Candida as the main pathogen.Voriconazole is effective in treating invasive fungal infections in very elderly patients,and close monitoring of liver and kidney function is required during voriconazole treatment.

Objective To observe the protective effects of lovastatin against lung injury and the expression changes of adiponectin in the septic rats.Methods Fifty four male Wistar rats weighting 250-300g were randomly divided into the three groups:sham operation group ( group Sham) ,sepsis group ( group CLP) and lovastatin interven tion group (group LOV).Rats were injected with lovastatin (4mg/kg) or 0.5%CMC (vehicle) for five days and then subjected to CLP.At 4h,12h and 24h after operation.BALF was collected to determine the levels of TNF-αand IL-6,lung tissue was obtained to observe histopathological changes,and to detect the content of MPO and MDA,the blood sample was obtained to detect the level of adiponectin.Results In the group Sham,at 4h,12h and 24h time points,the levels of TNF-αwere (1.80 ±0.13)pg/mL,(2.04 ±0.15)pg/mL and (1.930.19)pg/mL;the levels of IL-6 were (20.56 ±0.23)pg/mL,(18.35 ±0.15) pg/mL and (21.23 ±0.20) pg/mL;the contents of MPO were (2.82 ±0.14) U/g tissue,(2.88 ±0.07) U/g tissue and (2.76 ±0.18) U/g tissue;and the levels of MDA were (3.32 ±0.12)nmol/mg,(3.09 ±0.11)nmol/mg and (3.21 ±0.08)nmol/mg;the concentrations of adiponectin were (2.68 ±0.14)μg/mL,(2.80 ±0.07)μg/mL and (2.86 ±0.18)μg/mL.Compared with group Sham,both LOV group and CLP group had increased pulmonary damage:(1)the levels of TNF-α[4h,12h and 24h were (4.23 ± 0.18)pg/mL,(5.62 ±0.24)pg/mL and (5.14 ±0.10)pg/mL,t=28.41,30.98 and 36.62]and IL-6[4h,12h and 24h were (39.12 ±0.17) pg/mL,(47.25 ±0.21) pg/mL and (44.690.27) pg/mL,t =158.90,273.40 and 127.28] of the CLP group in BALF were both increased,and MPO[4h,12h and 24h were (4.85 ±0.13) U/g tissue, (6.17 ±0.08)U/g tissue and (7.84 ±0.10)U/g tissue,t=26.39,79.40 and 60.43]and MDA[4h,12h and 24h were (6.24 ±0.06)nmol/mg,(7.56 ±0.15)nmol/mg and (8.43 ±0.10)nmol/mg,t=53.31,58.86 and 90.06] concentrations in lung homogenate were raised with the decreased expression of serum adiponectin[4h,12h and 24h were (1.35 ±0.10)μg/mL,(1.17 ±0.07)μg/mL and (1.24 ±0.11)μg/mL,t=19.86,12.75 and 18.81](all P<0.05);(2) meanwhile the levels of TNF-α[4h,12h and 24h were (2.85 ±0.17) pg/mL,(3.720.13) pg/mL and (3.240.09)pg/mL,t=12.02、20.73 and 16.68]and IL-6[4h,12h and 24h were (30.75 ±0.22)pg/mL, (37.52 ±0.29)pg/mL and (32.43 ±0.26)pg/mL,t=78.42,68.29 and 83.67]in BALF of the LOV group were all increased,the contents of MPO[4h,12h and 24h were(3.59 ±0.05)U/g tissue,(4.67 ±0.11)U/g tissue and (5.33 ± 0.05)U/g tissue,t=12.03,33.63 and 33.70]and MDA[4h,12h and 24h were (4.45 ±0.10)nmol/mg,(5.01 ± 0.11)nmol/mg and (5.83 ±0.04) nmol/mg,t =17.72,30.23 and 71.75] were also increased with the serum adiponectin concentrations[4h,12h and 24h were (2.09 ±0.08)μg/mL,(2.07 ±0.05)μg/mL and (2.03 ± 0.10)μg/mL,t=8.96,20.79 and 6.30]dicreased(all P<0.05).There were less histopathological changes in the LOV group,and the levels of TNF-α(t=13.46,17.05 and 15.43),IL-6(t=73.70,64.10 and 80.12),MPO(t=22.16,27.01and 32.86) and MDA(t=37.59,42.72 and 59.13) were lower than those in CLP group,also the level of adiponectin(t=14.15,8.10 and 3.19) increased siginificantly(all P<0.05).Conclusion Administration of lovastatin could attenuate lung injury of the sepsis by down-regulate the level of TNF-αand IL-6,with reduced inflam-matory response and oxidative stress,and could upregulate the level of adiponectin in serums of rats with sepsis.

Objective To investigate the influence of prepubertal exposure to estradiol benzoate (EB)in the male reproductive system of the rats and the natural process of tissue repair,and to clarify the possible mechanism of the reproductive toxicity of exogenous estrogen.Methods Ninety 2 1-day-old male Wistar rats were randomly divided into 2 experimental groups (low dose of EB group and high dose of EB group,n=30)and control group (n=30). The rats in the experimental groups were injected with EB dissolved in peanut oil at 15(low dose of EB group)and 15 000μg·kg-1 (high dose of EB group)respectively,the rats in control group received equal vehicle injection only,once every other day for two weeks from postnatal day(PND)21 to 34.All of them were normally fed after the drug usage was stopped.The testes were harvested at the stages of PND 60 and PND 125(n=15 at each stage).The serum levels testosterone of (T),follicle-stimulating hormone(FSH),luteinizing hormone(LH),prolactin (PRL)and estradiol(E2)of the rats in various groups were detected with radioimmunology method and the weights of the rats in various groups were recorded;the histological changes of the testes tissue were observed with light microscope.Results On PND60,compared with control group,the T levels in low dose of EB group and high dose of EB group were decreased(P<0.05 or P<0.01);the FSH,LH and E2 levels were increased (P<0.05 or P<0.01),and the PRL levels had no change(P>0.05);the weights of testes were decreased(P<0.01);the histological changes of the testes of the rats in experimental groups included seminiferous tubules maldevelopment, decreased cell number of seminiferous epithelia.Compared with low dose of EB group,the T and FSH levels in high dose of EB group were decreased (P<0.05 or P<0.01),the E2 and LH levels were increased(P<0.01),the PRL level had no change (P>0.05 ), and the weight of testes was decreased (P<0.01 );the diameters of seminiferous tubules were smaller,there was no sperm in high dose of EB group while there were a few sperms in low dose of EB group.On PND125,compared with control group,the T,FSH and PRL levels in low dose of EB group and high dose of EB group were decreased(P<0.01),the E2 levels were increased (P<0.01);the LH level in low dose of EB group was increased(P<0.05),the LH level in high dose of EB group was decreased(P<0.01), and the weights of testes in high dose of EB group were decreased(P<0.01);the diameters of seminiferous tubules and the cell number of seminiferous epithelia were increased but not apparent change.Compared with low dose of EB group,the T,LH levels in high dose of EB group were decreased (P<0.01),the E2 and FSH levels were increased(P<0.01),the PRL level had no change(P>0.05),and the weight of testes was decreased(P<0.01);there was still no sperm in high dose of EB group, the number of sperms was increased in low dose of EB group, but it was still lower than that in control group.Conclusion EB is harmful to the reproductive system and can change the normal serum sex hormone levels,even induces the irreversible injury.

Objective To summarize the clinical features,treatment and prognosis of bullous systemic lupus erythematosus (BSLE).Methods Clinical data were collected from 6 cases of BSLE between May 2009 and September 2015,and were analyzed retrospectively.Results Among the 6 patients,2 were male and 4 were female.The mean age of onset was 34 years.All the 6 patients presented with tense blisters and bullae arising on an erythematous base or normal skin,which were arranged in an annular pattern in 3 patients.The SLE Disease Activity Index (SLEDAI) score was ＞ 4 in all the 6 patients.Histopathological examination showed subepidermal blisters or fissures in all the patients.Direct immunofluorescence (DIF) revealed continuous linear deposition of immunoglobulin G (IgG),IgM and IgA in all the patients,linear deposition of C3 in 4 patients,and linear deposition of Clq in 2 patients at the basement membrane zone (BMZ).All the 6 patients were treated with oral glucocorticoids and hydroxychloroquine,and 2 patients were additionally treated with cyclophosphamide.During the follow-up period,adverse reactions to different extents were observed in the 6 patients.Conclusions BSLE mainly occurs in young and middle-aged people.Histopathologically,subepidermal blisters or fissures can be observed with linear deposition of IgG,IgM,IgA,or C3 along the basement membrane zone on DIF.

ObjectiveTo evaluate the efficacy of sphenopalatine ganglion stimulation with acupuncture for moderate-to-severe perennial allergic rhinitis.MethodsA total of 50 patients were recruited into a sphenopalatine ganglion stimulation group and a routine acupuncture group according to order of presentation, with 25 in each group. The sphenopalatine ganglion stimulation group received sphenopalatine ganglion stimulation with filiform needle, 1-2 sessions/week for 4 weeks. The routine acupuncture group received traditional acupuncture, withyingxiang(LI 20),yintang(GV29),fengchi(GB20),fengfu(GB16),zusanli(ST36) as the maln points, andyingxiang(LI 20),yintang(GV29),fengchi(GB20),fengfu(GB16),zusanli(ST36) as the adjunct points, 1-2 points from both the maln and adjunct points in each session, 2 sessions/week for 4 weeks. The nasal symptom score (2004 version), the total nasal symptom score (TNSS) and the total non-nasal symptom score (TNNSS) were used to evaluate symptom improvement. The Rhinoconjunctivitis Quality of Life Questionnalre (RQLQ) was used to assess the patients’ quality of life. The time to symptom alleviation, duration of symptom alleviation in every session and the recurrence duration during 1 month after the treatment were compared between the two groups.Results After the treatment, the score of the nasal symptom score (99.74 ± 31.89vs.196.83 ± 31.22;t=-4.912,P=0.001), TNSS (33.63 ± 12.37vs.71.82 ± 19.21;t=-3.463,P=0.003), TNNSS (33.63 ± 12.37vs.71.82 ± 19.21,t=-3.463,P=0.003) in the sphenopalatine ganglion stimulation were significant lower than those in the routine acupuncture group. Compared with the routine acupuncture group, the time to symptom alleviation was significant shorter (13.85 ± 4.21 minvs.45.63 ± 7.87 min;t=-1.763,P=0.008), while the duration of symptom alleviation was significant longer (37.92 ± 9.94 hvs.3.35 ± 1.23 h;t=7.637,P<0.01) after each session in the sphenopalatine ganglion stimulation group. Four weeks after the treatment, RQLQ score in the sphenopalatine ganglion stimulation group was significant lower than that in the routine acupuncture group (8.48 ± 3.71vs.37.68 ± 12.46;F=-7.312,P<0.01). The recurrence duration during 1 month after the treatment in the sphenopalatine ganglion stimulation group was significant longer than that in the routine acupuncture group (4.12 ± 2.15 dvs.23.53 ± 4.63 d;t=-8.879,P=0.003).ConclusionSphenopalatine Ganglion stimulation is superior to routine acupuncture in treatment of patients with moderate-to-severe perennial allergic rhinitis.

Objective:To detect the change of composition of immune cells in the spleen of miR-126 knockdown(miR-126KD) mice and preliminarily explore its significance .Methods: The expression level of miR-126 in spleens of miR-126KD mice was deter-mined by Realtime PCR.And the total number of splenocytes was calculated.The pathologic morphology change of the spleen was observed by HE staining.And the changes on proportion of DCs ,macrophages cells ,γδ T cells and NK T cells,CD3+T cells and its subgroup ,as well as CD19+B cells in spleens of miR-126KD mice were analyzed by Flow cytometry and calculated respectively.The level of phosphorylated AKt and NF-κB was analyzed by Western blot assay.Results:Compared with those of WT mice ,the expression level of miR-126 decreased obviously ( P<0.05 ) and the total number of cells increased obviously in spleen of miR-126 KD mice ( P<0.05).Moreover,the pathologic morphology of miR-126KD mice was significantly changed.The proportion and number of NK T cells in the inherent cells were significantly increased ( P<0.05 ) , but the proportion of Mφcells were significantly decreased ( P<0.05 ) . Meanwhile,the proportion and number of CD3+T cells and CD4+T cells in the adaptive immune cells were significantly increased (P<0.05),while the total number of CD19+B cells were significantly decreased (P<0.05).Last,the level of phosphorylation Akt and NF-κB increased obviously in spleen of miRNA-126 knockdown mice.Conclusion: Change obviously on the composition of immune cells subsets in the spleen of miRNA-126 knockdown mice ,which it may be related to the altered level of phosphorylated AKt and NF-κB and provides a preliminary experimental basis for the further exploring the roles of miR -126 in immune response.

Objective:To investigate the change of expression of miR-7 in activated CD4+ T cells in vitro, and preliminary explore its possible significance. Methods: CD4+CD62L+T cells was purified from splenocytes of FVB mice by magnetic cell sorting system (MACS). After stimulation with anti-CD3/CD28 antibody,the relative expression of miR-7 was examined by Real-time PCR, and the expression level of CD69 molecular was analyzed by FACS. Furthermore,the relative expression of miR-7 in CD4+T cells was detected at different time points during stimulation. With the treatment of ERK inhibitor PD98059,change of miR-7 expression was de-termined by Real-time PCR. Meanwhile, the proliferation of CD4+T cells was examined by CCK-8 assay and the expression level of CD69 and CD62L molecular were analyzed by FACS. Finally,the expression of cytokines IL-6,IL-10,and IFN-γ were determined by Real-time PCR. Results:Compared with control group,the relative expression of miR-7 was increased significantly after stimulation with anti-CD3/CD28 antibody,as well as expression level of CD69 molecular was augmented(P<0. 05). In contrasted with 0 h and 24 h,the expression of miR-7 was significantly increased after 48 h and 72 h during stimulation(P<0. 05). Furthermore,the relative expression of miR-7 was significantly declined in CD4+T cells in ERK inhibitor PD98059 treatment group. Finally, the expression level of CD69 molecular,as well as cytokines IL-6, IL-10 and IFN-γ, were also decreased significantly ( P<0. 05 ) . Conclusion: The relative expression of miR-7 was significantly increased in activated CD4+T cells,closely related to ERK pathway,which provided an important foundation for successive research work on exploring the functional role of miR-7 in the CD4+T cells.

Objective The aim of the study was to observe the features of nail fold microcirculation in systemic sclerosis (SSc) patients and to compare these findings in SSc patients with patients with other connective tissue diseases.Methods Forty patients with SSc and thirty-seven patients with other connective tissue diseases were included in the study and all the patients reported symptoms of Raynaud's phenomenon in the hands were also included.Nail fold capillaroscopy (NFC) was performed and the abnormality of nail fold microcirculation between the two groups were compared.The relations between nail fold capillaroscopic findings and clinicolaboratory parameters in SSc patients were analyzed.Statistical analysis were carried out by t-test and Chi-square.Results The loss of capillaries and dilated and giant capillaries and hemorrhage as well as neoangiogenesis were hallmarks of the scleroderma capillary findings,which could be detected by nail fold capillaroscopy.The abnormalities of nail fold microcirculation in SSc patients were more severe and more specific than those in other connective tissue disease patients.The total scores of nail fold capillaroscopy test were obviously higher in SSc patients with lung or esophagus involvement than those patients without these organ involvement,meanwhile,the total scores of nail fold capillaroscopic findiugs were elevated in SSc patients with anti-Scl70 antibody than those with negative group.Conclusion The nail fold capillaries of patients with SSc have specific abnormalities,and nail fold capill-aroscopy could distinguish between SSc and other connective tissue diseases,therefore it could be used as a promising tool for early detection of patients who may have the potential to develop scleroderma and it is also helpful in assessing disease severity.

Objective To evaluate the effects of rapamycin combined with rosiglitazone on lung injury in septic rats.Methods One hundred and twenty healthy male Wistar rats were randomly divided into 5 groups (n =6 each):sham operation group (group S); cecum ligation and punture (CLP) group; rapamycin group (group RPM) ; rosiglitazone group (group RGZ) ; rapamycin plus rosiglitazone group (group RPM + RGZ).The rats were anesthetized with intraperitoneal 10% chloral hydrate 100 mg/kg.Sepsis was induced by CLP in groups CLP,RPM,RGZ and RPM + RGZ.At 30 min before CLP,rapamycin 0.4 mg/kg was injected subcutaneously in RPM group,rosiglitazone 0.3 mg/kg was injected via the femoral vein in RGZ group,and rapamycin 0.4 mg/kg was injected subcutaneously and rosiglitazone 0.3 mg/kg was injected via the femoral vein in group RPM + RGZ.While the equal volume of normal saline was given instead in CLP group.Six rats were sacrificed at 2,6,24 and 48 h after CLP in each group,and lungs were removed and cut into sections which were stained with haematoxylin and eosin and examined under microscope.The pathological changes of lungs were scored.The myeloperoxidase (MPO) activity and signal transducer and activator of transcription 3 (STAT3)-DNA binding activity in lung tissues were measured.Results Compared with group S,the pathological scores,MPO activity and STAT3-DNA binding activity were significantly increased in groups CLP,RPM,RGZ,RPM + RGZ (P ＜ 0.05).The pathological scores,MPO activity and STAT3-DNA binding activity were significantly lower in groups RPM,RGZ and RPM +RGZ than in group CLP,and in group RPM + RGZ than in groups RPM and RGZ (P ＜ 0.05).Conclusion Rapamycin combined with rosiglitazone offers additional benefit to attenuating lung injury induced by sepsis over rapamycin or rosiglitazone alone,and inhibition of activation of STAT3 pathway is involved in the mechanism.

Objective To research the relationship between miR-21 and radiation sensitivity of cervical cancer HeLa cells,and to elucidate the possible action mechanism of miR-21 in apoptosis and autophagy of cells.Methods The HeLa cells were divided into mock groups (transfected with miR-21 NC,mimics,inhibitor NC or inhibitor)and 4 Gy irradiation groups (transfected with miR-2 1 NC, mimics,inhibitor NC or inhibitor with irradiation). The miR-2 1 expression was detected by real-time PCR;colony-forming assay was used to detect the changes of radiation sensitivity;the apoptosis and autophagy were analyzed by FACS assay;the target gene of miR-2 1 was predicted by bioinformatics methods;Dual-luciferase Reporter Assay was used to demonstrate the binding of miR-2 1 and targets;the expression of beclin1 protein was measured by Western blotting method. Results After 4 Gy radiation,compared with mock group,the expression of miR-21 was increased remarkably (P<0.05). Colony-forming assay showed that there were no changes of radiation sensitivity of HeLa cells after overexpressing or inhibiting miR-21 compared with miR-21 NC or miR-21 inhibitor NC groups(P>0.05).Compared with miR-21 NC+4 Gy group,the apoptotic rate of HeLa cells in miR-21 mimics+4 Gy group was increased (P<0.05).After transfection with miR-21 inhibitor,compared with miR-21 inhibitor NC group,the apoptotic rate of HeLa cells in duced by radiation was decreased (P<0.05 ). Compared with miR-21 NC group, the autophagy rate was increased after transfection with miR-21 mimics (P<0.05).After transfection with miR-21 mimics and radiation, the expression level of beclin1 protein was increased (P<0.05 ) compared with miR-21 NC+4 Gy group. Conclusion Beclin1 is the target gene of miR-21 in HeLa cells. Overexpression of miR-21 can increase the radiation-induced apoptosis and autophagy,but has on influence in radiation sensitivity of HeLa cells.