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The oral Janus kinases inhibitor (JAKi) has improved the management of skin manifestations in systemic sclerosis (SSc), and our study aimed to explore the efficacy of non-selective JAKi tofacitinib in ameliorating interstitial lung disease (ILD) in the patients with SSc. The hospitalization data of the SSc-ILD patients from April 2019 to April 2021 were collected, and the changes of pulmonary function and the radiological findings in pulmonary high-resolution CT (HRCT) from the 9 patients who received tofacitinib for at least 6 months and a matched group of 35 SSc-ILD patients treated with conventional immunosuppressants or glucocorticoids, were compared and analyzed. There were no significant differences in demographic data and clinical characteristics between the tofacitinib-treated group (tofa-group) and the matched group. However, in the tofa-group, the changes in serum lactate dehydrogenase (LDH) concentration and serum interleukin-6 levels were significantly lower than those in the matched group. Moreover, the tofa-group showed amelioration in decreased diffusing capacity of the lung for carbon monoxide (DLCO) (62.05 ± 9.47 vs. 66.61 ± 12.39, p = 0.046), reductions in ground-glass attenuation involvement (1.00 ± 0.86 vs. 0.33 ± 0.50, p = 0.024) and irregular pleural thickening (1.33 ± 0.50 vs. 0.67 ± 0.51, p = 0.004) in pulmonary HRCTs, alleviated modified Rodnan skin score (mRSS) of skin sclerosis (9.22 ± 3.81 vs. 7.11 ± 3.92, p = 0.048), and reduced HRCT scores of pulmonary fibrosis (15.00 ± 3.87 vs. 12.66 ± 4.92, p = 0.009). Logistic regression analysis showed that the involvement of ground-glass attenuation (OR 11.43) and the add-on therapy of tofacitinib (OR 9.98) were the relevant factors in the amelioration of HRCT. Our results indicate that the use of JAKi (tofacitinib) may be relevant to significant improvement of the sclerosis and early radiological abnormalities in SSc-ILD patients. Further studies are needed to confirm these findings and to explore its efficacy more precisely. Key Points ⢠The currently available therapies for SSc-ILD have limited therapeutic benefits. ⢠The add-on therapy of the oral JAK inhibitor is available in the real world. ⢠The tofacitinib was promising in the improvement of the sclerosis and early radiological abnormalities in SSc-ILD patients.
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Inhibidores de las Cinasas Janus , Enfermedades Pulmonares Intersticiales , Esclerodermia Sistémica , Humanos , Inhibidores de las Cinasas Janus/uso terapéutico , Estudios Retrospectivos , Esclerosis/patología , Pulmón , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/etiología , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/tratamiento farmacológico , Esclerodermia Sistémica/patologíaRESUMEN
Objective:To investigate the value of ultrasound and Ki-67 for early predicting pathological complete response (pCR) of triple negative breast cancer(TNBC) after neoadjuvant chemotherapy (NAC).Methods:Retrospective analysis was performed in 190 patients with TNBC who underwent surgery after NAC treatment at the Cancer Hospital of Fudan University from January 2019 to December 2022. All patients underwent ultrasound examination before and after 2 and 4 cycles of NAC treatment. According to the operation pathological results after NAC, the patients were divided into pCR group and non-pCR group. The differences in ultrasound and Ki-67 parameters were compared between the pCR and non-pCR groups, and binary Logistic regression analysis was performed to determine the independent predictors for pCR. The ROC curve was plotted to evaluate the diagnostic efficacy.Results:Tumor maximum diameter, relative change rates of tumor maximum diameter after 2-cycle and 4-cycle NAC (ΔD2, ΔD4), relative change rate of lymph node short diameter after 2-cycle NAC (ΔS2), T-stage, N-stage and Ki-67 showed statistically significant differences between the pCR group and the non-pCR group (all P<0.05). Logistic regression analysis showed that ΔD4, T-stage, N-stage and Ki-67 were independent predictors for pCR ( OR=1.029, P=0.011; OR=0.300, P=0.009; OR=0.653, P=0.048; OR=1.028, P=0.001). The area under the curve (AUC) of pCR was 0.804 (95% CI=0.742-0.866), the sensitivity and specificity were 67.5% and 83.2% respectively. Conclusions:The combination parameters of ΔD4, T-stage, N-stage and Ki-67 have certain clinical value for predicting pCR of TNBC.
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Objective:To study the correlation between echogenic foci pattern of papillary thyroid carcinoma(PTC) solitary nodule and lateral cervical lymph node metastasis.Methods:The clinical data of 475 patients with echogenic foci in preoperative ultrasound and pathologically confirmed PTC solitary nodule from January to December 2014 in Fudan University Shanghai Cancer Center were retrospectively analyzed, which was categorized into lateral cervical lymph node metastasis group and lateral cervical lymph node non-metastasis group. Echogenic foci was classified into five types: local punctate echogenic foci, diffused punctate echogenic foci, coarse echogenic foci, mixed echogenic foci, peripheral annular and eggshell echogenic foci. The related clinical characteristics and the ultrasonic features were also involved. Chi-Square test and Logistic regression analysis were performed to analyze the correlation.Results:Age, preoperative human thyroglobulin (HTG) level, maximum diameter, location and echogenic foci pattern distributed to lateral cervical lymph node metastasis of PTC solitary nodule in 475 cases, according to univariate analysis ( P<0.05). Multivariate Logistic regression analysis showed diffused punctate echogenic foci, age≤35 years old, maximum diameter >10 mm and upper part were risk factors of lateral cervical lymph node metastasis of PTC solitary nodule. Conclusions:Diffused punctate echogenic foci in PTC solitary nodule, patients younger than 35 years old, maximum diameter larger than 1 cm and nodule location at upper part of the thyroid promote to lateral cervical lymph node metastasis.
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Objective To investigate the effects of self-made rehabilitation on lower extremity motor function in patients with stroke hemiplegia. Methods In total, 60 stroke patients with hemiplegia who were unable to walk, were randomly assigned to the traction training belt plus routine rehabilitation group (experimental group) and routine rehabilitation group (control group),30 cases respectively. There were five outcomes: Fugl-Meyer Motor Assessment of the lower extremity(FMA-LE), Kendall method for Manual Muscle Testing(MMT), Berg Balance Scale(BBS), Functional Ambulation Classitication(FAC) and Activity of Daily Living(ADL). Results For patients on therapy for 12 weeks, the results of both groups were statistically significant(t=-19.185--7.971, P <0.01). The levels of FMA-LE, BBS and FAC were 29.6 ± 3.7 and 24.9 ± 5.9(t=3.609, P<0.05), 31(21, 40) and 22(10, 32)( t=-2.194, P<0.05) , 3(3, 4) and 3 (2, 3)(t=-2.270, P<0.05)in the test group and the control group,respectively. There was no significant difference in the levels of MMT and ADL (P >0.05). Conclusions The application of traction training belt tested in this study are significant efficacy in rehabilitation effects on lower extremity motor function, muscle strength, balance function and walking ability in stroke patients with hemiplegia, and is worth being promoted.
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Objective@#To investigate the effects of self-made rehabilitation on lower extremity motor function in patients with stroke hemiplegia.@*Methods@#In total, 60 stroke patients with hemiplegia who were unable to walk, were randomly assigned to the traction training belt plus routine rehabilitation group (experimental group) and routine rehabilitation group (control group),30 cases respectively. There were five outcomes: Fugl-Meyer Motor Assessment of the lower extremity(FMA-LE), Kendall method for Manual Muscle Testing(MMT), Berg Balance Scale(BBS), Functional Ambulation Classitication(FAC) and Activity of Daily Living(ADL).@*Results@#For patients on therapy for 12 weeks, the results of both groups were statistically significant (t=-19.185--7.971, P <0.01) . The levels of FMA-LE, BBS and FAC were 29.6 ± 3.7 and 24.9 ± 5.9 (t=3.609, P <0.05) , 31(21, 40) and 22(10, 32)(t=-2.194, P <0.05), 3(3, 4) and 3(2, 3) (t=-2.270, P <0.05) in the test group and the control group, respectively. There was no significant difference in the levels of MMT and ADL (P >0.05).@*Conclusions@#The application of traction training belt tested in this study are significant efficacy in rehabilitation effects on lower extremity motor function, muscle strength, balance function and walking ability in stroke patients with hemiplegia, and is worth being promoted.
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Objective To provide experimental materials for exploring the function of breast cancer susceptibility gene 2(BRCA2) gene by establishing of an mouse immortalized mammary gland epithelial cell line as a cell model system.Methods In this study,the primary mouse mammary epithelial cells were isolated and purified by enzyme digestion and differential centrifugation.The resulting primary mouse mammary gland epithelial cells were transducted with lentivirus expressing human telomerase (hTERT) gene,and screened by hygromycin B.The surviving epithelial cells were further characterized by morphology observations and cytokeratin marker detection.Results Immortalized mouse mammary epithelial cells were obtained by infection of MMECs with lentivirus expressing human telomerase(hTERT) gene,screened by hygromycin B.Morphology observations and detection of the cytokeratin marker showed the immortalized MMECs had a typical morphology of luminal epithelial cells with strong expression of cytokeratin 14.Conclusion An immortalized mouse luminal epithelial cell line is successfully established with an uniform morphology,which provides a cell model system for the future exploration on BRCA2-related tumorigenesis.
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Objective@#To investigate the effects of calcium supplementation during the pregnancy and early infancy stage on body mass index (BMI) and gut microbiota in the infants.@*Methods@#A total of 1 752 healthy pregnant women and their infants (breast feeding) in two maternal and child health care hospitals of Beijing were chosen as the subjects in this study from May to October 2016. Questionnaires were used to obtain the general information and supplementation of calcium and vitamin D in mothers and their infants. The body length and weight of infants at birth and 6 months were recorded to calculate the BMI. The random number table method was used to randomly select 40 infants from each group for gut microbiota analysis (If less than 40 infants were all included in this study, 23 infants in the pregnancy and early infancy would be all treated with calcium supplements. There were 6 infants who was not added calcium during the pregnancy but added in the early infancy). Then it was compared that the effects of calcium supplementation during the pregnancy and early infancy on the BMI and gut microbiota composition of infants were determined at birth and 6 months.@*Results@#Compared to the group with no calcium supplementation during the pregnancy ((12.76±1.23), (17.68±0.76)kg/m2), the BMI of infants at birth and 6 months in the group with calcium supplementation during the pregnancy ((13.51±0.47), (17.91±0.23)kg/m2) were significantly higher(P<0.05). In the group with maternal calcium supplementation, the BMI at 6 months ((18.63±0.52)kg/m2), BMI increment ((5.71±0.54)kg/m2) and the content of lactobacillus (21.04%±3.68%) in the only calcium supplementation subgroup in the early infancy were higher than those in only vitamin D supplementation subgroup ((17.69±0.89) kg/m2, (4.17±1.01) kg/m2 and 12.28%±3.86%) (P<0.05). In the group without maternal calcium supplementation, the content of lactobacillus (20.15%±4.87%) in the only calcium supplementation subgroup were also higher than those in only vitamin D supplementation subgroup (14.64%±3.71%) (P<0.05).@*Conclusion@#Appropriate calcium supplementation during the pregnancy is good for the growth and development of the fetus. Calcium supplementation in the early infancy could increase the BMI of infants, and promote the growth of intestinal lactobacillus.
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Objective: To investigate the effects of docosahexenoic acid (DHA) supplementation on infant's growth and BMI during pregnancy. Methods: A total of 1 516 healthy pregnant women delivered their babies in two maternal and child health care hospitals in Beijing and were chosen as the subjects in this cohort study from May to October 2015. Self-developed questionnaires were used to gather general information of the subjects, including age, height, weight, weight gain during pregnancy, delivery mode, DHA supplementation etc., before giving birth. Information on body length, weight, head circumference and BMI at birth and 6 months postnatal, of the infants were recorded. Breast milk was collected to test the fatty acid profiles by using the gas chromatography (GC) method at one to three months postnatally. Results: The overall rate of DHA supplementation was 47.76% among the pregnant women, in which introduction of DHA from the early and second stage of the pregnancy accounted for 49.31% and 39.64% respectively. When DHA supplementation began from the early pregnant stage, the DHA concentration showed an increase in the milk (P<0.05), whereas the supplementation began from the second and third stages did not affect the milk DHA concentration (P>0.05). Higher height and lower BMI were seen in the infants at birth and 6 months in the supplementation group when comparing to the non-supplementary group (P<0.05), with the greatest effects noticed in the earliest supplementation group. Specifically, the head circumference appeared larger from the early pregnant stage in the DHA supplementary group, than that in the non-supplement group (P=0.001). The increment of head circumference was larger than that in the other groups when the infants were 6-month old (P<0.01). Results from the partial regression analysis showed that during pregnancy, there were positive correlations between DHA supplementation and height (r=0.324, r=0.216), head circumference (r=0.221, r=0.302) as well as the increment of head circumference (r=0.276) at birth and 6 months (P<0.05). Whereas, a negative correlation was shown between DHA and the infants' BMI (r=-0.310, r=-0.371) (P<0.05) when supplementation was given during maternal pregnancy. Conclusions: When DHA supplementation program was carried out during maternal pregnancy, it could increase the height and head circumference and inhibit the rapid increase of BMI in the infants BMI. Our findings seemed helpful in promoting brain development and preventing the childhood obesity.
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Femenino , Humanos , Lactante , Embarazo , Estatura , Índice de Masa Corporal , Peso Corporal , Desarrollo Infantil/efectos de los fármacos , Estudios de Cohortes , Suplementos Dietéticos , Ácidos Docosahexaenoicos/farmacología , Recién Nacido/fisiología , Intercambio Materno-Fetal , Parto , Resultado del Embarazo , Atención Prenatal , Aumento de PesoRESUMEN
Objective To investigate the effects of docosahexenoic acid (DHA) supplementation on infant's growth and BMI during pregnancy.Methods A total of 1 516 healthy pregnant women delivered their babies in two maternal and child health care hospitals in Beijing and were chosen as the subjects in this cohort study from May to October 2015.Self-developed questionnaires were used to gather general information of the subjects,including age,height,weight,weight gain during pregnancy,delivery mode,DHA supplementation etc.,before giving birth.Information on body length,weight,head circumference and BMI at birth and 6 months postnatal,of the infants were recorded.Breast milk was collected to test the fatty acid profiles by using the gas chromatography (GC) method at one to three months postnatally.Results The overall rate of DHA supplementation was 47.76% among the pregnant women,in which introduction of DHA from the early and second stage of the pregnancy accounted for 49.31% and 39.64% respectively.When DHA supplementation began from the early pregnant stage,the DHA concentration showed an increase in the milk (P<0.05),whereas the supplementation began from the second and third stages did not affect the milk DHA concentration (P>0.05).Higher height and lower BMI were seen in the infants at birth and 6 months in the supplementation group when comparing to the non-supplementary group (P<0.05),with the greatest effects noticed in the earliest supplementation group.Specifically,the head circumference appeared larger from the early pregnant stage in the DHA supplementary group,than that in the non-supplement group (P=0.001).The increment of head circumference was larger than that in the other groups when the infants were 6-month old (P<0.01).Results from the partial regression analysis showed that during pregnancy,there were positive correlations between DHA supplementation and height (r=0.324,r=0.216),head circumference (r=0.221,r=0.302) as well as the increment of head circumference (r=0.276) at birth and 6 months (P<0.05).Whereas,a negative correlation was shown between DHA and the infants' BMI (r=-0.310,r=-0.371) (P<0.05) when supplementation was given during maternal pregnancy.Conclusions When DHA supplementation program was carried out during maternal pregnancy,it could increase the height and head circumference and inhibit the rapid increase of BMI in the infants BMI.Our findings seemed helpful in promoting brain development and preventing the childhood obesity.
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Objective The objective of this study was to investigate the effect of salinomycin on proliferation and autophagic flux of human melanoma M21 cells. Methods The cell survival rate was determined by MTS assay and IC50values( half inhibitory concentration)were calculated. The morphological changes of cells after salinomycin administration were observed under optical micro-scope. Flow cytometry was used to examine the apoptosis rate of M21 cells. Western blot was used to detect the expression of autophag-ic-related protein LC3B and p62 in M21 cells. The presence of autophagosomes in M21 cells after salinomycin administration was ob-served under transmission electron microscope. Western blot and immunofluorescence were used to detect the level of p62 protein and localizing changes in M21 cells. Results Salinomycin significantly inhibited proliferation of M21 cells, and the IC50values were (1. 38 ± 0. 18)μM. After salinomycin administration,the proliferation rate of M21 cells was slowed down,and obvious vacuoles ap-peared in the cells. Salinomycin could not only induce cell apoptosis,but it also increased the ratio of LC3B-Ⅱ/LC3B-Ⅰ in M21 cells. The increase and accumulation of autophagosomes were directly observed under transmission electron microscope. The level of p62 protein was slightly elevated after salinomycin treatment and gradually aggregated into the cytoplasm,indicating that autophagic flux was inhibited. Conclusion Salinomycin can inhibit the proliferation of human malignant melanoma M21 cells,and its mechanism may be related to the accumulation autophagosomes granules and inhibition of autophagic flux.
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Objective To explore the effects of acupuncture combined with rehabilitation training on neural function,motor function and quality of life in patients with cerebral apoplexy.Methods From September 2015 to September 2017,ninety-four patients with stroke rehabilitation in Zhejiang Provincial Taizhou Hospital were selected and divided into observation group and control group according to random number table ,with 47 cases in each group. The control group was treated with rehabilitation training ,and the observation group was treated with acupuncture and moxibustion on the basis of the control group.The two groups were treated for 8 weeks.The changes of nerve function , motor function,balance function,daily living ability and quality of life before and after treatment were compared between the two groups.Results After 4 weeks and 8 weeks of treatment,the NIHSS score,FMA score,BBS score and BI index score of the two groups decreased compared with before treatment (observation group:t=21.481,36.045,10.726, 21.961,14.040,26.501,25.827,42.266;control group:t=12.011,20.519,5.527,15.644,7.201,18.719,15.836, 29.852,all P<0.05),and at 8 weeks after treatment,the NIHSS score,FMA score,BBS score and BI index score decreased compared with those at 4 weeks after treatment(observation group:t=17.791,11.558,12.486,13.867;control group:t=10.352,9.721,11.028,11.129,all P<0.05).The NIHSS scores of the observation group after 4 weeks and 8 weeks of treatment were lower than those of the control group [(8.94 ±1.02) points vs.(10.56 ± 1.20)points,(5.61 ±0.78)points vs.(8.23 ±0.97)points,t=7.052,14.431,all P<0.05].The FMA scores of the observation group after 4 weeks and 8 weeks of treatment were lower than those of the control group [(18.54 ± 3.24)points vs.(15.03 ±2.71)points,(27.39 ±4.13)points vs.(21.03 ±3.25)points,t=5.697,8.297,all P<0.05].The BBS scores of the observation group after 4 weeks and 8 weeks of treatment were lower than those of the control group[(35.27 ±3.67)points vs.(31.09 ±3.15)points,(45.86 ±4.51)points vs.(38.98 ±3.76)points,t=5.925,8.033,all P<0.05].The BI index scores in the observation group after 4 weeks and 8 weeks of treatment were lower than those in the control group[(63.26 ±5.68)points vs.(56.18 ±6.02)points,(79.21 ±5.47)points vs.(68.77 ±4.89)points,t=5.865,9.755,all P<0.05].Conclusion Acupuncture combined with rehabilitation training can improve the neurological function ,motor function and quality of life of patients with cerebral apoplexy.
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VP1 gene encoded by the newly identified caprine enterovirus CEV-JL 14 was amplified and cloned to prokaryotic expression vector pGEX-4T-1.Recombinant GST-VP1 fusion protein was expressed,purified,emulsified with Freund's complete adjuvant and used to immunize the BALB/c mice following a standard procedure.The spleen cells from immunized mice were collected and fused with myeloma cells after its antibody titer reached over 104 times detected by indirect ELISA.Hybridoma cell clones secreting monoclonal antibodies against VP1 were screened and their stability and specificity were further determined.The identified hybridoma cells were injected to mice intraperitoneally and ascites were collected at 7 DPI.Isotypes of the monoclonal antibodies against the recombinant VP1 protein were characterized to be either IgG1 or IgG2b,which showed a high specificity for detection of caprine enterovirus antigens by immunoperoxidase monolayer assay,thus laying a solid basis for future study related to viral pathogenesis,detection and diagnostics for caprine enterovirus infection.
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The development trend, countries, institutions, co-authors, and subjects in MEDLINE-covered papers were analyzed by Excel, Ucinet and SciMAT respectively in order to understand the current situation in studies on precision medicine, which showed that precision medicine is in a rapid development stage, the impact power of pa-pers on precision medicine published in United States of America is high, the source journals published in United States of America are the core journals in precision medicine, the academic level of papers on precision medicine published in United States of America is high. Co-authors analysis showed that the co-authors network is of the small world effect. Subject evolution analysis revealed that the subjects involved in studies on precision medicine are increasingly rich with genomics, drug treatment and oncology accounted a large proportion. Analysis of the evo-lution in genomics, drug treatment and oncology displayed that the subjects involved in studies on precision medi-cine have experienced macro-stage, micro-stage, and combined macro- and micro-stage.
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Objective To observe the expression of ZNF139 and MMP-7 in endometrial adenocarcinoma tissues and discuss the correlation with clinical pathological significances.Methods In 71 patients diagnosed as endometrial adenocarcinoma,71 cancer tissues(adenocarcinoma group) and 71 adjacent normal tiuues(adjacent cancer group) were collected in operations.Immunohistochemical methods was used to detect the expression of ZNF139 and MMP-7 in the two groups,the relationship between the two genes and communication with clinicopathological indexes were discussed.Western blot and qRT-PCR were used to detected the expression of ZNF139 and MMP-7 at protein and mRNA level.Results The positive rates of ZNF139 was 66.20% in adenocarcinoma group,higher than in adjacent cancer group(21.42%,P=0.016);the positive rates of MMP-7 was 74.65% in adenocarcinoma group,higher than7 than in adjacent cancer group(26.76%,P=0.012).The expression of ZNF139 and MMP-7 was correlated with lymph node metastasis,muscle invasion and FIGO stage(P=0.028,0.031;P=0.004,0.016;P=0.008,0.011).Spearman rank correlation analysis showed there was positive correlation between ZNF139 and MMP-7 in adenocarcinoma tissues(r=0.716,P=0.039).Western blot showed that ZNF139 and MMP-7 expression in adenocarcinoma group were higher than in adjacent cancer group(t=6.92,7.34;P<0.01);qRT-PCR showed that ZNF139 mRNA and MMP-7 mRNA expression in adenocarcinoma group were higher than in adjacent cancer group(t=4.27,4.06;P<0.05).Conclusion ZNF139 and MMP-7 are correlated with malignant pathological characteristics in endometrial adenocarcinoma,they may modulate the malignant behavior together.
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Objective To evaluate the clinical curative effect of ulinastatin combined with CRRT in the treatment of multiple organ dysfunction syndrome(MODS).Methods Sixty eight patients with MODS who were admitted to ICU from July 2013 to July 2015 were randomly divided into three groups:control group,CRRT group,combined group;Patients' APACHE Ⅱ,SOFA scores level of inflammatory markers were recorded before treatment and after treatment of 72 hours and 7 days.The mortality of the three groups in ICU were compared.Results After 72 hours and a week of treatment,the level of IL-10,IL-6,TNF-α,WBC、PCT、CRP in CRRT group and combined group were significantly better than that of control group(P<0.05),and combined group were significantly better than that of CRRT group.Compared with the control group,the oxygen index,lactic acid,ALT significantly im proved in CRRT group and combined group were better than control group,after 72 hours and a week of treatment(P<0.05),and the cornbined group was the most obvious.After a week of treatment,the mortality rate of CRRT group and combined group was significantly better than the control group (P<0.05),while there was no statistical differences between CRRT group and combined group(P>0.05).Conclusion Ulinastatin combined with CRRT is an effective method for the treatment of MODS.
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Objective To observe the effect of everolimus on proliferation,cycle and apoptosis of endometrial cancer cells and discuss the mechanism.Methods Proliferation of RL95-2 interfered with everolimus in different concentration and time was observed by MTT assay.Cell cycle and apoptosis affected by everolimus was detected by flow cytometry.PI3K-Akt-mTOR signaling pathway was detected by Western blot.Results (1) MTT assay showed that,cell viability in everolimus group was time-dependent decreased,compared with control group,there were significant differences in 48 h,72 h and 96 h ((64.36±4.78)%,(48.18±5.93) %,(42.72±6.91) %;F inner grouP =3.278,P< 0.05;F between groups =12.327,P< 0.01;F across groups=7.729,P<0.05).Cell viability in everolimus group was dose-dependent decreased(F=3.264,P<0.05).Compared with control group,RL95-2 cells in G1 phase and G2 phase was (69.28±2.61)% and (4.75±0.84) %,decreased in everolimus group,and in S phase (27.31±0.69) % was increased (t=5.743,P<0.05;t =4.528,P<0.05;t=6.209,P<0.05).The apoptosis in everolimus group was 29.78%,higher than in control group (47.29%),the difference was significant (t =19.381,P<0.01).(2) Western blot showed that both mTOR and p-Akt in everolimus group were dose-dependent decreased (F=3.589,P<0.05;F =5.292,P<0.05),Akt was dose-dependent increased (F =4.294,P<0.05).Conclusion Everolimus decrease the cell viability and promote apoptosis via target inhibiting mTOR expression.
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Objective To investigate the mortality risk factors of nosocomial infection patients in intensive care unit (ICU), and to guide clinicians to take effective control measures. Methods A retrospectively cohort study was conducted. The relevant information of patients with nosocomial infection treated in ICU of Hengshui Harrison International Peace Hospital Affiliated to Hebei Medical University from June 2009 to December 2015 was analyzed. The patients who admitted to ICU again, with length of ICU stay less than 48 hours, without first etiology of screening within 48 hours of ICU admission, or without complete pathogenic information were excluded. The gender, age, diagnosis, length of ICU stay, invasive operation, nutritional status, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score, sequential organ failure assessment (SOFA) score, distribution and drug resistance of the pathogens, and procalcitonin (PCT) levels at 7 days after nosocomial infection were recorded. The risk factors leading to death in patients with nosocomial infection were analyzed by logistic regression, and the receiver operating characteristic curve (ROC) was drawn to evaluate the predictive value of all risk factors on the outcome of patients with nosocomial infection. Results In 864 enrolled patients with male of 54.75% and mean age of (63.50±15.80) years, 732 (84.72%) patients survived and 132 (15.28%) died. Compared with survivors, the non-survivors had higher age (years: 65.47±15.32 vs. 58.15±13.27), incidence of urgent trachea intubation (32.58% vs. 22.81%), deep venous catheterization (83.33% vs. 63.25%), and multiple drug-resistant infection (65.91% vs. 33.20%), longer length of ICU stay (days: 13.56±4.29 vs. 10.29±4.32) and duration of coma (days: 7.36±2.46 vs. 5.48±2.14), lower albumin (g/L: 23.64±8.47 vs. 26.36±12.84), higher APACHEⅡ score (19.28±5.16 vs. 17.56±5.62), SOFA score (8.55±1.34 vs. 6.43±2.65), and PCT (μg/L: 3.06±1.36 vs. 2.53±0.87, all P 0.05). The low respiratory tract was the most common site of infection followed by urinary tract and bloodstream in both groups. It was shown by logistic regression analysis that prolonged ICU stay [odds ratio (OR) = 2.039, 95% confidence interval (95%CI) = 1.231-3.473, P = 0.002], APACHEⅡ score (OR = 1.683, 95%CI= 1.002-9.376, P = 0.000), SOFA score (OR = 2.060, 95%CI = 1.208 -14.309, P = 0.041), PCT (OR = 2.090, 95%CI = 1.706-13.098, P = 0.004), and multi-drug resistant pathogens infection (OR = 5.245, 95%CI = 2.213-35.098, P = 0.027) were independent risk factors for ICU mortality in patients with nosocomial infection. The area under ROC curve (AUC) of length of ICU stay, APACHEⅡ score, SOFA score, and PCT level for predicting death of nosocomial infection patients was 0.854, 0.738, 0.786, and 0.849, respectively, the best cut-off value was 16.50 days, 22.45, 6.37 and 3.38 μg/L, respectively, the sensitivity was 83.6%, 90.0%, 81.1%, and 89.6%, and the specificity was 70.3%, 75.6%, 71.3%, and 85.4%, respectively. Conclusions Prol onged ICU stay, nosocomial infection with secondary sepsis and multiple organ dysfunction syndrome were the leading causes of death for nosocomial infection patients in ICU. Prolonged ICU stay, APACHE Ⅱ score, SOFA score, and PCT level could effectively predict death risks for nosocomial infection patients.
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Objective To establish a mouse model of genital human papillomavirus (HPV) pseudovirion (PsV) transmission and evaluate the protective potency of HPV16 VLP vaccine.Methods HPV16 PsV with the encapsidated luciferase expressing plasmid Luc were generated from 293FT cells and purified by size-exclusion chromatography.The endpoint titers of HPV16 PsV-Luc were determined on 293FT cells, denoted as TRLU/mL.For in vivo genital challenge, mice were synchronized in a diestrus-like status by a subcutaneous injection with 0.1 μg β-estradiol and then with 3mg DepoProvera after 24 hours.Six hours prior to HPV16 PsV-Luc challenge, deeply anesthetized mice were intravaginally pretreated with 50 μL of 4%nonoxynol-9 ( N-9 ).HPV16 PsV-Luc was thoroughly mixed with 20 μL solution containing 4%carboxymethylcellulose ( CMC ) and intravaginally instilled using a positive-displacement pipette.Forty-eight hours after PsV-Luc challenge, mice were anesthetized and D luciferin was intravaginally instilled.After 3 minites, bioluminescence was measured with a cryogenically cooled Xenogen IVIS camera system.Then,the murine genital challenge model was used to determine the potency that HPV16 VLP vaccine is efficient at preventing HPV infection.Results HPV16 PsV-Luc was generated and purified from 293FT cells.HPV16 PsV-Luc was verified to containe L1 and L2 protein by Western blot.HPV 16 PsV-Luc successfully infected vaginal epithelial cells of mouse and the murine genital challenge model was established.To achieve consistent bioluminescence, the minimal dose of HPV16 PsV-Luc was 1.7 ×104 TRLU.The protective potency of HPV16 VLP vaccine was shown using this murine model.Our data showed that immune serum with over neutralizing antibody titer of 256-fold was sufficient to confer protection against HPV PsV genital infection .Conclusion The murine genital challenge model of HPV16 was successfully established, and the model is used to evaluate the potency of HPV16 VLP vaccine against in vivo genital HPV16 PsV challenge.Our model will benefit for the investigation of HPV neutralization and the potency evaluation of the HPV vaccine .
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Objective: To analyze the risk factors of ischemic stroke prevalence in elder patients with non-valvular atrial ifbrillation (AF). Methods: A total of 180 AF patients treated in our hospital from 2010-01 to 2014-12 were retrospectively studied. The diagnosis of ischemic stroke was conifrmed by CT/MRI, and the patients were divided into 2 groups: AF with ischemic stroke group,n=120 and AF alone group,n=60. The CHA2DS2-VASc score, CHADS2 score, plasma levels of homocysteine (HCY), ifbrinogen (FIB), left atrial diameter (LAD), blood lipid proifle and renal function were examined and compared between 2 groups. Results: There were signiifcant differences on CHA2DS2-VASc score, CHADS2 score, HCY, FIB and LAD between AF with ischemic stroke group and AF alone group,P Conclusion: The CHA2DS2-VASc score and CHADS2 score system combining with plasma levels of HCY, FIB and LAD have the important clinical predictive value for the occurrence of ischemic stroke in elder patients with AF. CHA2DS2-VASc score is more appropriate for screening the low-risk patients, and CHADS2 score is rather appropriate for screening the high-risk patients.
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Objective To explore the effect of the transcutaneous tracheostomy tube in patients with pneumothorax and its clinical value. Methods A prospective randomized controlled trial was conducted. Thirty-two patients with pneumothorax admitted to Department of Critical Care Medicine of Harrison International Peace Hospital of Hebei Medical University from June 2010 to June 2014 were enrolled. The patients were divided into control group and observation group,with 16 cases in each group. Beside the treatment for primary disease,the patients in control group received thoracic close drainage with traditional silica gel tube as performed by thoracic surgeons,and those in observation group received thoracic close drainage with transcutaneous tracheostomy tube by intensive care doctors. The curative effect and complications of the two groups were observed. Results Compared with control group,the time from diagnosis to operation(minutes:8.00±1.36 vs. 23.06±3.83,t=14.790,P=0.000)and the operation time were significantly shortened(days:5.37±1.02 vs. 7.31±1.70,t=7.286,P=0.000),the frequency of drainage tube replacement(times:0.18±0.40 vs. 3.87±1.14,t=12.128,P=0.000)and the times of repeated chest radiography(times:1.12±0.34 vs. 2.93±0.77,t=8.589,P=0.000)in observation group were significantly reduced,the length of hospital day was significantly shortened(days:8.30±1.37 vs. 24.56±5.62,t=17.289, P=0.000),the rates of dislocation of drainage tube(0 vs. 3 cases),obstruction of the tube(0 vs. 5 cases),and subcutaneous emphysema(3 vs. 16 cases)were reduced obviously,but there was no difference in incidence of incision infection(1 vs. 3 cases)and infection of thoracic cavity(0 vs. 2 cases). Conclusions The usage of transcutaneous tracheostomy tube in patients with pneumothorax is safe and simple. Doctors in ICU can independently do this procedure,and its effect is positive.