Objective To investigate the difference of amplitude of low-frequency fluctuation (ALFF) and fraction of amplitude of low-frequency fluctuation(fALFF) between Alzheimer's disease (AD)patients and normal aging (NA) controls by voxel-based analysis.Methods Thirty-one AD patients and 44 NA controls were enrolled in the study.Blood oxygen level dependent functional (BOLD) EPI data were obtained during resting-state by using 32-channel head coil.Data were realigned,normalized and then smoothed with 8 mm FWHM kernel.Resting-state fMRI toolkit(version 1.6) was used to generate ALFF and fALFF images.Independent two sample t-test was performed with SPM5 to compare ALFF and fALFF of AD and NA controls.Pearson correlation analysis was performed to examine the relationship between MMSE score and ALFF,fALFF parameters.The significance level was set to be uncorrected O.001 on the voxel level and 0.05 on the cluster level.Results AD patients showed increased ALFF in left temporal lobe (0.492 ±0.119) and right cingulated cortex (0.434 ± 0.093) of AD patients,which were 0.443 ± 0.068 and 0.380 ±0.081 in NA controls (t =2.658,2.227,P ＜ 0.05).Decreased fALFF was found in bilateral posterior cingulate cortices (1.167 ± 0.203) and increased fALFF was found in bilateral temporal lobes (left 1.226 ±0.127,right 1.146 ±0.214) with left side dominance,which were 1.453 ±0.269,1.134 ±0.088,1.014 ± O.132 in NA controls (t =5.001,3.695,3.285,P ＜ 0.05).Bilateral temporal ALFF and fALFF correlated with MMSE positively (r =0.768—0.909,P ＜ 0.05) with left dominance.Conclusion AD patients showed increased resting-state functional MRI changes correlated with MMSE score in the temporal lobes with left dominance,which indicated left temporal lobe may be the best location for the observation of disease progression in AD patients.

Objective To investigate the expression and distribution of the downstream substrate of extracellular regulated protein kinase(ERK1/2) pathway, ternary complex factor phospho-Elk-1, in rat brains with chronic fluorosis, and reveal the mechanism of the impaired learning and memory ability caused by chronic fluorosis. Methods Seventy-two SD rats, weighing 100 - 120 g, were randomly divided into 3 groups, 24 in each group (half male and half female). The rats in control group were fed with tap water (fluoride < 0.5 mg/L); low- and high-dose fluoride groups were fed with tap water with different concentrations of NaF(5.0,50.0 mg/L F-, respectively). After 6 months, body weight was weighed, dental fluorosis was determined by observation and urinary fluoride and bone fluoride were detected by fluorine ion-selective electrode; the learning ability of rats was measured by navigation test of Morris water maze, and memory ability by spatial probe test in Morris water maze; the expression and distribution of phospho-Elk-1 in different brain regions were detected by immunohistochemistry method. Results In low- and high-fluoride groups, the body weight of rat[(449.2 ± 77.1), (312.8 ± 89.7)g] was significantly decreased than that of control [(635.5 ± 76.2 )g, all P< 0.05], the varying degrees of dental fluorosis were observed(x2 = 7.83, P<0.05), urinary fluoride[(2.56 ±0.91),(5.73 ±3.14)mg/L] and bone fluoride[(709.2 ± 37.4) ,(1306.3 ± 102.4) mg/kg] were significantly higher than those in controls[(0.92 ± 0.30)mg/L,(348.5 ± 89.2)mg/kg, all P< 0.05]. The escape latency of low- and high-fluoride groups[ (7.4 ± 4.1), (12.2 ± 5.7)s] was longer than that of control [(4.8 ± 2.7 )s, all P < 0.05] and the escape latency in high-fluoride group was significantly longer than that in other groups (all P < 0.05); in spatial probe test, the time of first crossing platform was longer in rats with fluorosis [(4.18 ± 1.10),(5.89 ± 0.56)s] as compared to control[(1.17 ± 0.75)s, all P< 0.05]. Expressions of phospho-Elk-1 in the hippocampus CA1(167.4 ± 8.3,163.2 ± 9.4), CA2(175.7 ± 5.0,183.3 ± 4.2), CA3(165.2 ± 11.6,162.9 ± 4.4), CA4(168.7± 6.9,169.5 ±5.3), fascia dentate (185.2 ±4.0,193.1 ±6.1) and caudate putamen( 181.4 ± 3.8, 179.8 ± 5.5) in low- and high-fluoride groups were higher than those of controls(142.4 ± 8.1,144.9 ± 8.4,143.6 ± 5.8, 116.8 ± 9.1,140.2 ± 7.8,163.1 ± 13.1, all P< 0.05). Conclusion Chronic fluorosis can cause increased expression of phospho-Elk-1 in the hippocampus and caudate putamen region of rat brains, which might be related to the mechanisms of decreased learning and memory ability of rats overexposed to fluoride.

To discover an efficient strategy for the conversion of the antibacterial activity of fluoroquinolones into the antitumor activity, the three series of C-3 s-triazole-based derivatives including sulfide ketones (6a-6g), thiosemicarbazones (7a-7g) and fused heterocyclic thiazolotriazoles (8a-8g) were synthesized from ciprofloxacin (1), respectively. The structures were characterized by elemental analysis and spectral data. The antitumor activity was tested against three tumor cell lines (Hep-3B, Capan-1 and HL60) using the MTT assay. The three types of compounds all exhibited stronger anti-proliferative activities than ciprofloxacin in the test. The order of their activities was in compounds 7>8>6, and the order of selectivity against cancer cell lines was Capan-1, Hep-3B and HL60. Meanwhile, the SAR revealed that some compounds with electron-drawing group substituted such as fluoro- and nitro-phenyl compounds (6f, 7f, 8f) and (6g, 7g, 8g) displayed more significant activity than the control compounds, especially the IC50 values of thiosemicarbazone compounds 7f and 7g against Capan-1 was comparable to doxorubicin. Thus, a five-membered triazole as the C-3 bioisostere modified with the functionalized side-chain of sulfide-ketone thiosemicarbazone warrants special attention and further investigation.
Anti-Bacterial Agents ; chemistry ; Antineoplastic Agents ; pharmacology ; Cell Line, Tumor ; Ciprofloxacin ; chemistry ; Doxorubicin ; pharmacology ; HL-60 Cells ; Humans ; Ketones ; pharmacology ; Sulfides ; pharmacology ; Triazoles ; pharmacology

OBJECTIVE: To investigate the application of CT hepatic volume measurement combined with CT perfusion imaging (CTPI) by Spiral CT in evaluating the hepatic functional reserve in cirrhosis. METHODS: CT volume measurement of livers was performed in 32 patients with cirrhosis and 20 patients with normal livers. CTPI had been taken in 25 patients with cirrhosis and 20 patients with normal livers. The hepatic volume, parameter of blood flow perfusion, and liver volume-perfusion index were observed and analyzed. Correlations between graded fractions of hepatic function and liver volume, parameter of perfusion, and liver volume-perfusion index were also analyzed. RESULTS: The values of liver volumes (LV, LVs) reduced gradually (P<0.01) among the groups of hepatic function Grade A, B, and C. The values of the hepatic portal perfusion (HPP), total liver perfusion (TLP), hepatic arterial perfusion index (HAI), and portal perfusion index (PPI) of the cirrhosis group were significantly lower than those of the normal ones (P<0.01). The values of the HPP reduced gradually among Grade A, B, and C (P<0.05 or P<0.01). The values of PPI reduced significantly between Grade C and Grade A, B (P<0.05 or P<0.01). The liver volume-perfusion indexes (VPI, VPIs, VPPI, VPPIs) reduced gradually among Grade A, B, and C (P<0.05 or P<0.01). The correlation between liver volume-perfusion indexes and graded fractions of hepatic function was higher than other indexes, among which the correlation of VPPIs was the highest. CONCLUSION Changes of volume and blood flow perfusion of the liver are related to the clinical grade of hepatic function. The CT volume measurement combined with CTPI will be a more comprehensive way in evaluating hepatic functional reserve.
Adult ; Aged ; Female ; Humans ; Liver ; diagnostic imaging ; pathology ; physiopathology ; Liver Cirrhosis ; diagnostic imaging ; pathology ; physiopathology ; Male ; Middle Aged ; Perfusion ; Tomography, Spiral Computed ; methods

Objective To study the synergistic effects of gentiopicroside combined with pabolizumab on photodynamic therapy in mice with breast cancer.Methods MCF-7 cells were injected subcutaneously to establish a tumor bearing mouse model of breast cancer and were randomly divided into model group,control group,positive control group,experimental group and combination group,with 10 mice in each group.The control group was intraperitoneally injected with 50 mg·kg-1 of 5-aminolevulinic acid and irradiated with 200 J·cm-2 laser for 20 min,once a week.The positive control group was intraperitoneally injected with 100μg·kg-1 pabolizumab,twice a week,and photodynamic therapy once a week,the experimental group was intragastric given 100 mg·kg-1 gentiopicroside,once a day,and photodynamic therapy once a week,the combined group was intraperitoneally injected with pabolizumab(100 μg·kg-1),twice a week,and gavage of gentiopicroside(100 mg·kg-1)once a day and photodynamic therapy once a week.Five groups of mice were given the drug for 3 weeks.The tumor inhibition rate of each group was compared,and the levels of interleukin(IL)-12,interferon(INF)-γand tumor necrosis factor(TNF)-α were measured by enzyme-linked immunosorbent assay.The levels of B-cell lymphoma-2 associated gene(Bax),B-lymphoblastoma-2 gene(Bcl-2)and vascular endothelial growth factor(VEGF)protein in tumor tissues were determined by Western blot.Results The tumor inhibition rates of control,positive control,experimental and combined groups were(22.38±2.26)％,(42.27±3.21)％,(38.16±2.17)％and(60.24±2.84)％,respectively.The serum IL-12 levels of model,control,positive control,experimental and combined groups were(127.13±1.25),(132.29±2.31),(155.27±1.48),(163.31±2.67)and(185.24±1.71)pg·mL-1;INF-γ levels were(724.16±3.63),(891.12±4.45),(1 043.19±3.85),(1 082.34±4.51)and(1 492.13±6.57)pg·mL-1;TNF-α levels were(83.81±4.52),(65.26±3.77),(41.07±3.85),(43.59±3.94)and(27.12±3.93)pg·mL-1;the relative protein expression levels of Bax were 0.30±0.08,0.47±0.05,0.67±0.11,0.89±0.06 and 1.03±0.10;the relative protein expression levels of Bcl-2 were 0.99±0.04,0.86±0.06,0.71±0.05,0.46±0.06 and 0.31±0.08;the relative protein expression levels of VEGF were 1.06±0.04,0.92±0.03,0.76±0.04,0.49±0.04 and 0.29±0.08.The differences of above indexes between the combined group and the control,positive control group and experimental groups were statistically significant(all P＜0.05).Conclusion Gentiopicroside combined with pembrolizumab can significantly enhance the tumor inhibition effect of photodynamic therapy on breast cancer mice,promote the apoptosis of breast cancer cells,and then inhibit the tumor progression of breast cancer mice.

Objective:To observe the effect of customized orthotic insoles on the gait and balance of hemiplegic stroke survivors.Methods:Sixty stroke survivors with gait abnormalities were randomly divided into a group fitted with ankle foot orthoses (AFO) ( n=30) and a group who received customized orthotic insoles ( n=30). All received conventional rehabilitation training for 4 weeks. Before the fitting, as well as 8 hours and 4 weeks afterward, both groups were evaluated using the Tinetti gait scale (TGS), the plantar pressure balance index, the difference in length between their right and left step, step width, the Timed Up and Go test (TUGT), the Fugl-Meyer lower extremity assessment (FMA-LE), the 6-minute walk test (6MWT), a trunk impairment scale (TIS), the Berg Balance Scale (BBS) and the Barthel Index (BI). Results:At 8 hours after the fitting all of the insole group′s measurements were better than those of the AFO group, on average, but the differences were not statistically significant. After 4 weeks the average TGS, balance index barefoot and wearing the orthosis, step length difference, BBS and BI of the insoles group were significantly better than the AFO group′s averages. The other indicators were not significantly different.Conclusions:Customized orthotic insoles are more effective than an AFO in relieving the biomechanical abnormalities in hemiplegic patients′ feet and ankles, and enhancing their balance and gait.

Objective:To investigate the role of levofloxacin combined with recombinant human granulocyte colony-stimulating factor(G-CSF)or only G-CSF supportive therapy in preventing infection in autologous hematopoietic stem cell transplantation(ASCT),and to analyze the length of hospital stay,hospitalization cost and post-transplant survival of the patients.Methods:A retrospective analysis was performed in the patients with hematological malignancies who accepted ASCT at our hospital from January 2012 to July 2022,the febrile neutropenia,the incidence of bacterial infection and the use rate of intravenous antibiotics in the levofloxacin+G-CSF group and only G-CSF support group during ASCT were observed.The length of hospital stay,total cost during hospitalization and survival after 90 days of transplantation between the two groups were compared.Results:A total of 102 cases were included in this study,including 57 cases of multiple myeloma,36 cases of acute leukaemia,7 cases of lymphoma,3 cases of myelodysplastic syndrome,1 case of light chain amyloidosis,and 1 case of POEMS syndrome.47 patients received levofloxacin+G-CSF antibacterial prophylaxis,and 55 patients received G-CSF supportive therapy.In the levofloxacin+G-CSF group,40 cases(85.11％)developed febrile neutropenia,and 13 cases(27.66％)were confirmed as bacterial infection.In the G-CSF group,44 cases(80.00％)developed febrile neutropenia,and 16 cases(29.09％)were bacterial infection.There was no statistically significant difference in the incidence of febrile neutropenia and bacterial infection between the two groups(x2=0.46,P=0.50;x2=0.03,P=0.87).The use rate of intravenous antibiotics in the levofloxacin+G-CSF group was 85.11％(40/47),which was not statistically different from 85.45％(47/55)in the G-CSF group(X2=0.04,P=0.84).The detection rates of levofloxacin-resistant bacteria in the levofloxacin+G-CSF group and G-CSF group were 8.57％(3/35)and 21.43％(6/28),respectively,with no statistical difference(x2=0.65,P＞0.05).The median length and median cost of hospitalization in the levofloxacin+G-CSF group and G-CSF group were 25 d vs 22 d and 78 216.24 yuan vs 80 724.38 yuan,with no statistically significant differences(t=3.00,P=0.09;t=0.94,P=0.09).Within 90 days after transplantation,two cases(4.26％)died in the levofloxacin+G-CSF group and one case(1.82％)died in the G-CSF group,with no statistically significant difference between the two groups(x2=0.53,P=0.47).Conclusion:Application of levofloxacin+G-CSF showed no significant benefit compared to G-CSF support for the prevention of bacterial infections during ASCT.

BACKGROUNDTo determine the etiologic agent of an atypical pneumonia human case admitted to Xiangtan City hospital, Hunan Province in Oct. 2005.

METHODSThe patient's respiratory tract samples and serum were collected. Throat swabs were tested by microneutralization and hemagglutination-inhibition assays.

RESULTSThe results of nucleic acid detection of all respiratory samples were negative and virus isolation was also negative. The H5-specific antibodies of convalescence showed a 4-fold greater rise than acute phase.

CONCLUSIONThe atypical pneumonias case was confirmed as the first human case of avian influenza A (H5N1) infection in the mainland of China.

Animals ; Antibodies, Viral ; blood ; Cell Line ; Chick Embryo ; Child ; China ; Clinical Laboratory Techniques ; Hemagglutination Inhibition Tests ; Hemagglutinin Glycoproteins, Influenza Virus ; genetics ; immunology ; Humans ; Influenza A Virus, H5N1 Subtype ; genetics ; immunology ; isolation & purification ; Influenza, Human ; diagnosis ; virology ; Male ; Neutralization Tests ; Pneumonia, Viral ; diagnosis ; virology ; Reagent Kits, Diagnostic ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Analysis, DNA

Objective To study the epidemiological characteristics on the clustering nature of pandemic (H1N1) 2009 in China.Methods Time and place distribution of pandemic (H1N1) 2009on the nature of clustering through data from Public Health Emergency Management Information System were described.Results As of August 10,2010,2773 pandemic (H1N1) 2009 clusters,a total of 77363 cases (including 20 deaths) were reported in the mainland of China.The most reported number of clusters was from schools and kindergartens with the total number of 2498 (accounted for 90.08％ of the total number).Middle schools appeared the have the most clusters (1223,accounting for 48.96％ ).The number of clusters reported in the southern provinces (cities) accounted for 77.03％ of the total,and was more than that in the northern provinces (cities).Two reported peaks in the southern provinces (cities) were in June and November,2009,respectively.There was only one reported peakin the northern provinces in September,2009.Conclusion Time and place distribution characteristics on the clusters of pandemic (H1N1) 2009 were similar to the seasonal influenza,but the beginning of winter peak was much earlier and intensity of reporting was much higher on the clusters of pandemic (H1N1 ) 2009 than that of seasonal influenza.

OBJECTIVETo ascertain the causation of a family cluster involving two undefined pneumonia cases, a 12-year-old girl and her brother, reported October, 2005 in Xiangtan county, Hunan province.

METHODSInformation on epidemiology and clinical manifestation of the cases was collected from interviewing the keyman and referring to related medical records. The environment exposure of the cases to their households and the timeline of the illness were reproduced, using this information. Medical check-up was undergone among the close contacts of the cases and on sick/dead poultry. Throat swab of the cases were collected and tested by both RT-PCR and real-time PCR to detect viral nucleic acids of A/H5N1, and were then inoculated into special pathogen free (SPF) embryonated hens' eggs. Serum of the cases including acute and convalescent phases were also collected and tested by microneutralization and haemagglutination-inhibition (HI) assays to detect H5-specific antibodies.

RESULTSBoth the girl and her brother developed fever 2 and 4 days after sudden deaths of chickens being raised in the same house. Both of them had developed pneumonia and the girl died from acute respiratory distress syndrome (ARDS) complicated with multi-organ failure. The boy survived and subsequently discharged from hospital. An eighth-day serum from the girl tested H5 antibody negative, while 4-fold and greater increased in antibody titers were detected in serum from the boy using microneutralization and HI assays in sequential acute and convalescent sera. Of 192 cases, only one doctor who cared for the girl during hospitalization had upper respiratory symptoms but tested negative for H5N1 by microneutralization assay.

CONCLUSIONThe boy was the first confirmed human case of avian influenza A (H5N1) in the mainland of China and his sister was diagnosed clinically. The most probable explanation of these two cases was that the transmission of H5N1 virus from infected poultry within the same household environment. No evidence of human-to-human transmission was noted in the family cluster.

Animals ; Chickens ; Child ; China ; Fatal Outcome ; Female ; Humans ; Influenza A Virus, H5N1 Subtype ; immunology ; isolation & purification ; Influenza in Birds ; transmission ; Influenza, Human ; complications ; diagnosis ; transmission ; Male ; Pneumonia ; virology ; Respiratory Distress Syndrome, Adult ; virology