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Objective:To explore the risk factors of acute kidney injury(AKI)after liver transplantation(LT), examine its prognostic impact and construct a clinical prediction model.Methods:Clinical data are retrospectively reviewed for 220 LT recipients.They are divided into two groups of AKI(93 cases)and non-AKI(127 cases)according to the occurrence of AKI post-LT.Clinical data of two groups are compared.The variables with statistically significant inter-group differences in univariate analysis are included for multivariate analysis for obtaining the independent risk factors for AKI post-LT.Then the independent risk factors are employed for fitting a prediction model and a visual nomogram is constructed.At the same time, discrimination and calibration of the prediction model are evaluated.Extubation time, length of intensive care unit(ICU)stay, continuous renal replacement therapy(CRRT)rate, length of hospital stay, in-hospital mortality, estimated glomerular filtration rate(eGFR)at discharge, incidence of chronic renal failure(CRF)and readmission times are compared between two groups.Survival analysis is also performed between AKI and non-AKI groups and AKI 0/1 and AKI 2/3 stages.Results:The incidence of AKI post-LT is 42.3%.Age( OR=1.036, 95% CI: 1.001~1.073), preoperative serum creatinine level( OR=1.030, 95% CI: 1.011~1.049), platelet count( OR=0.992, 95% CI: 0.985~0.999), Child-Pugh class C( OR=2.678, 95% CI: 1.031~6.952), postoperative abdominal infection( OR=2.271, 95% CI: 1.120~4.603)and abdominal hemorrhage( OR=3.869, 95% CI: 1.016~14.72)are independent risk factors for AKI post-LT.The AUC/C-index of nomogram prediction model is 0.789 with a Brier score of 0.183, showing decent discrimination and calibration.According to the nomogram score, the recipients with a risk of AKI>50% are included into high-risk group while those with a risk of AKI<50% into low-risk group.Postoperative survival of low-risk group is better than that of high-risk group( P<0.001).Compared with non-AKI group, AKI group had a later extubation time( P=0.003), a longer length of ICU stay( P<0.001)and hospital stay( P=0.001), a higher rate of CRRT usage( P<0.001)and in-hospital mortality( P<0.001), a lower eGFR at discharge( P<0.001)and a higher incidence of CRF( P<0.001).Postoperative survival of non-AKI group was better than that of AKI group( P=0.048).Postoperative survival of patients with AKI 0/1 is better than that of those with AKI 2/3( P=0.002). Conclusions:Advanced age, high preoperative serum creatinine, low preoperative platelet, poor preoperative liver function, postoperative abdominal infection and abdominal hemorrhage may elevate the risks of AKI post-LT.And the nomogram prediction model based upon the above risk factors has a high value of clinical application.
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Objective:To investigate the effects of hydrogen rich-saline (HRS) on intestinal mucosal barrier in rat with intestinal ischemia/reperfusion injury (IIRI).Methods:Twenty-four healthy male Sprague-Dawley rats, aged 8 weeks, were randomly divided into 3 groups (8 in each group) by random number table method: sham group, model group and HRS group.Rats in HRS group were intraperitoneally injected with HRS (10 mL/kg) at 30 min of ischemia, and the same amount of normal saline was intraperitoneally injected in model group.After 45 min of ischemia and 6 h of reperfusion, rats were sacrificed.Serum and ileum were collected for further detection.Tumor necrosis factor alpha (TNF-α), interleukin (IL)- 1β and IL-17A expression levels in serum were detected by conducting enzyme-linked immunosorbent assay (ELISA). The localization expressions of tight junction protein Occludin was detected by immunohistochemical staining (IHC), while the localization expression of tight junction protein zonula occluden-1 (ZO-1) were detected by immunofluorescence staining (IF). The protein expression of Occludin, ZO-1, and Lysozyme were detected by performing Western blot.The mRNA expression of Lysozyme and α-defensin were detected by real-time PCR (qPCR).Results:ELISA results proved that the levels of serum TNF-α and IL-1β in HRS group rats were significantly lower than those in model group [(62.02±29.97) ng/L vs.(113.40±44.58) ng/L, (21.68±0.35) ng/L vs.(28.29±3.49) ng/L], while the level of IL-17A increased [(28.18±5.28) ng/L vs. (15.10±3.60) ng/L] (all P<0.05). IHC staining: compared with model group, the expression of Occludin in HRS group was uniform and continuous, and the staining was darker.IF results: compared with model group, the fluorescence signal intensity of ZO-1 in HRS group rats significantly increased, and the distribution was clear and continuous.Wes-tern blot results: compared with model group, the expression levels of Occludin and ZO-1 proteins in HRS group rats remarkably increased (0.79±0.06 vs. 0.54±0.04, 0.91±0.11 vs. 0.51±0.13), while Lysozyme protein decreased (1.50±0.40 vs. 2.99±0.80) (all P<0.05). qPCR results revealed that the expression level of Lysozyme mRNA in HRS group rats was lower than that in model group (1.64±0.33 vs. 2.20±0.40), while α-defensin mRNA obviously increased (0.82±0.19 vs. 0.47±0.13) (all P<0.01). Conclusions:HRS protects intestinal mucosal barrier by inhibiting the expression of tight junctions and the secretion of antimicrobial peptides in rat suffering from IIRI.
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Objective:To explore the effects of compound radix scutellariae gargle combined with periodontal non-surgical treatment on periodontal state and levels of visceral fat specific serine protease inhibitor (vaspin), interleukin-1β (IL-1β) and matrix metalloproteinase-3 (MMP-3) in gingival crevicular fluid of patients with periodontitis and type 2 diabetes mellitus (T2DM).Methods:Sixty patients with periodontitis and T2DM in North China University of Science and Technology Affiliated Hospital were selected and divided into two groups based on the principle of voluntariness. 30 patients in single group were given periodontal non-surgical treatment, and 30 patients in combined group were given compound radix scutellariae gargle + periodontal non-surgical treatment, and they were treated for 2 months. The tranditional Chinese medicine (TCM) symptoms scores (gingival pain and swelling, gingival atrophy, dry mouth, bad breath and scorched tongue, constipation), periodontal status-related indicators [gingival index (GI), sulcus bleeding index (SBI), periodontal pocket probing depth (PD), plaque index (PLI), clinical attachment loss (CAL), tooth mobility (TM)] and gingival crevicular cytokines (vaspin, IL-1β, MMP-3) were compared between the two groups, and the adverse reactions during treatment were observed and recorded.Results:After treatment, the scores of gingival pain and swelling, gingival atrophy, dry mouth and scorched tongue, bad breath and constipation were significantly decreased in the two groups ( P<0.05), and the scores in combined group after treatment were lower than those in single group ( P<0.05). The GI, SBI, PD, PLI, CAL and TM were significantly decreased in the two groups ( P<0.05), and the indexes in combined group after treatment were better than those in single group ( P<0.05). The levels of vaspin, IL-1β and MMP-3 in gingival crevicular fluid were significantly decreased in the two groups ( P<0.05), and the levels in combined group after treatment were lower than those in single group ( P<0.05). And there was no significant difference in the incidence of adverse reactions between the two groups ( P>0.05). Conclusions:Compound radix scutellariae gargle combined with periodontal non-surgical treatment can significantly relieve the symptoms of periodontitis with T2DM, improve the periodontal status, reduce levels of vaspin, IL-1β and MMP-3 in gingival crevicular fluid, and control disease progression.
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Objective ToinvestigatethevalueofDWIhyperintensityinvenoussinusindiagnosisandrecanalizationpredictionof cerebralvenoussinusthrombosis(CVST).Methods Clinicaland MRIdataof19patientswithCVST wereanalyzedretrospectively. BasedonDWIsignalcharacteristicsoftheCVST,thepatientsweredividedintoasthehyperintensegroupandthenon-hyperintense group.TheintervaltimebetweenthefirstMRIexaminationandtheonset,andtherecanalizationratewithin1 monthand3 months werecomparedbetweenthetwogroups.Results Therewere76 CVSTinthe19patients,withhyperintensein16venoussinus (21%)andin11patients(57.9%).Theintervaltimewaslongerinthehypertensegroupthanthenon-hypertensegroupbutnosta-tisticalsignificance[(12.81±11.10)daysversus(5.70±7.82)days,P=0.165].17patientsunderwentthesecond MRIexamination in1month,andtherecanalizationrateoftheobstructedsinuswaslowerinthehypertensegroupthanthenon-hypertensegroupwith nostatisticalsignificance(P=0.130).14patientsunderwenttheMRIexaminationafter3 months,andtherecanalizationrateofthe obstructedsinuswaslowerinthehypertensegroupthanthenon-hypertensegroupwithstatisticalsignificance(P=0.047).Conclu-sion ThehypertenseonDWIhashighsensitivityforthedetectionofsubacuteCVST.Thepresenceofhypertenseinoccludedsinus onDWIhasthepredictivevalueforvesselrecanalization.
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Objective To evaluate the clinical characteristics and the clinical outcomes of perianal abscess (PA) in neonates.Methods A retrospective review was performed on the collected data of 185 patients of PA in neonates prospectively admitted to Binzhou Medical University Hospital from January 2008 to December 2015.Patients were divided into 2 groups on the parents' intention:nonsurgical treatment and surgical treatment,the standard surgical treatment for PA was incision and drainage with the use of packing.The standard surgical treatment for PA was surgical incision drainage of lower abscess under local anesthesia by the use of filling tamponade iodoform gauze,while the patients receiving conservative treatment took hip bath perianally with topical 1 ∶ 5 000 potassium permanganate,besmearing erythromycin eye ointment outside locally.Incision-thread-drawing procedure was recommended in fistula-in-ano (FIA) after 6 months.Antibiotics were administered in all patients in the early days.The clinical data of age,gender,accompanying diseases,abscess amount and location,treatment approach,healing time and recurrence rates were analyzed with statistical method.Results All patients were boys,time of visiting hospital was 1-25 day,the average time 7.5 days;60 cases (32.4％)had neonatal diarrhea,45 cases (24.3％)had neonatal jaundice,but no patients had severe fever.A single skin lesion was present in 145 patients (78.4％),2 lesions in 30 patients (16.2％),and 10 patients had 3 lesions (5.4％).The most commonly affected sites were at 9 o'clock clockwise direction with 115 (62.2％)lesions on lithotomy position,followed by 3 o'clock clockwise direction with 65(35.1％) lesions by 1 o'clock clockwise direction with 3 (1.6％) lesions and 6 o'clock clockwise direction with 2 (1.1％) lesions.Bacteria cultures were obtained from 123 patients (90.4％,123/136 cases) of surgical treatment and 35 patients (71.4％,35/49 cases) of nonsurgical treatment obtained the results of bacteria culture.The average healing time was (21 ±2) days (10-60 days) in the surgical treatment group,and (36 ± 3) days (9-90 days) in the nonsurgical treatment group,7 out of 136(5.1％) patients had a recurrence with surgical treatment,incision drainage was performed again with the use of packing,and FIA was not found,10 out of 49 (20.4％) patients had a recurrence with nonsurgical treatment group,and 6 out of 49 (12.2％) were spontaneously resolves within the first year of life,4 out of 49 (8.1％) developed into FIA,incision-thread-drawing procedure was performed after 6 months.The significant difference was observed between and nonsurgical treatment and surgical treatment in healing time (t =-6.707,P =0.000),recurrence (x2 =11.347,P =0.001) and FIA formation rate (x2 =10.054,P=0.002).Conclusions PA is an entity in neonates.Incision and drainage of PA is an effective and safe therapy in the early days.Surgery for PA may result in low recurrence rates,a low rate of evolution toward FIA,and a short healing time,which should be considered as the primary treatment.The key procedure is to keep the drainage unobstructed by the use of filling gauze drainage to prevent crissum abscess recurrence.Postoperative care with antibiotics is effective to shorten hospital stays.
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Objective To investigate the expression of inositol requiting enzyme1 α (IRE1 α) and tumor necrosis factor receptor-associated factor 2 (TRAF2) and its significance through establishing models of intestinal ischemia reperfusion injury (IIRI) in rats.Methods According to the random number table,50 male SD rats were randomly divided into 2 groups:sham operation group (n =10) and ischemia reperfusion (I/R) group (n =40).Sham group animals underwent laparotomy.I/R group rats were subjected to occlusion of the superior mesenteric artery for 30 min;then the blood flow was restored.I/R group animals were divided into 4 subgroups:2 h,6 h,12 h,24 h according to the time of reperfusion.Eight rats were examined based on the number of live rats in each subgroup.The HE staining pathological changes in intestinal samples were observed by the light microscope.The small intestinal epithelial cell apoptosis index (AI) was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL).The expression levels of intestinal tissues tumor necrosis factor α (TNF-α) and plasma intestinal fatty acid-binding protein (Ⅰ-FABP) were detected by ELISA tests.Situ end labeling method was used to detect intestinal cell AI.Western blot was applied to investigate the expression of endoplasmic reticulum stress(ERS) proteins IRE1α,phosphorylation IREIα (p-IRE1 α) and TRAF2 in all group rats intestinal tissues.Results (1)The pathological changes showed that the intestinal injury of I/R groups was more severe than that of sham group,especially at 6 h.(2) Compared with sham group,the expression levels of TNF-α [sham group (16.41 ± 4.44)ng/ L,2 h group:(79.71 ± 8.20) ng/L,6 h group:(131.70 ± 11.59) ng/L,12 h group:(94.23 ±7.66) ng/L,24 h group:(69.78 ± 9.58) ng/L],AI[sham group:(3.93 ±0.77)％,2 h group:(16.24 ± 1.97)％,6 h group:(42.19 ±2.40)％,12 h group:(37.79 ± 2.34)％,24 h goup:(10.38 ±1.46)％] and plasma Ⅰ-FABP [sham group:(0.65 ±0.10) × 103 ng/L,2 h group:(1.47 ±0.10) ×103 ng/L,6 h group:(2.36 ±0.17) ×103 ng/L,12 h group:(37.79 ±2.34) ×103 ng/L,24 group:(l.41 ±0.09) × 103 ng/L] were higher (F =231.462,149.032,162.491,all P ＜ 0.01).(3) The expression of TRAF-2 protein and p-IRE1 α/IRE1 α could be up-regulated after IIRI (F =40.473,59.59,P ＜ 0.01).The expression of these proteins was up-regulated 2 h after reperfusion,peaking at 6-12 h reperfusion,and then decreased at 24 h,and the variation tendencies of all groups were the same.Conclusions IIRI could induce ERS,activate IRE1 α and up-regulate TRAF2.IRE1α/TRAF2 mediating ERS might be involved in regulating the cell inflammation,apoptosis and increasing intestinal permeability after IIRI.
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In view of the spread of hepatitis C virus(HCV),it still lacks an efficient anti-HCV drug or treatment until now.HCV non-structural proteins 3(NS3) protease is an important drug target in the research of the antiHCV drugs in recent years.This article reviews the active mechanism and peculiarity of HCV NS3 protease inhibitor.
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In this study, we produced a biphasic absorbable calcined bone (CB) of beta-TCP/HAP, and evaluated its function as a carrier of bone marrow derived mesenchymal stem cells(BMSCs) in BMP-2 gene medicine. Biphasic CB was manufactured and its surface was coated by collagen. X-ray diffraction analysis, scanning electron microscopy and biomechanical measurement were performed on the product. Heterotopic bone induction of product as carrier of BMP-2 gene transferred BMSCs and its biodegradability were tested in nude mice and goats. X-ray diffraction analysis showed biphasic patterns of HAP and beta-TCP. Scanning electron microscopy showed the porosity were similar to those of the cancellous bone, and the adhesion of cells on the CB surface were better after surface-coating with collagen. It had certain biomechanical strength and appropriate biodegradability. Biphasic CB loaded with Adv-hBMP-2 transduced BMSCs could induce much bony callus at the subcutaneous site of nude mice and the tibial bone defects of goats. The results showed biphasic CB is a superior carrier of cells in BMP-2 gene medicine.
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Animals , Mice , Biodegradation, Environmental , Bone Morphogenetic Protein 2 , Bone Morphogenetic Proteins , Genetics , Bone Regeneration , Bone Substitutes , Chemistry , Pharmacology , Calcium Phosphates , Pharmacology , Cell Differentiation , Goats , Hydroxyapatites , Pharmacology , Materials Testing , Mesenchymal Stem Cells , Cell Biology , Mice, Nude , Transfection , Transforming Growth Factor betaABSTRACT
Objective To evaluate effectiveness of bone marrow derived mesenchymal stem cells(BMSCs) transduced by adenovirus mediated human bone morphogenetic protein-2 (Adv-hBMP-2) gene in the repair of diaphysic segmental bone defects of goats. Methods The tibial bone defects (2.1 cm) of 22 goats, who weighted from 18.1 kg to 29.5 kg, were established and divided into 4 groups: groupⅠ, Adv-hBMP-2 transduced BMSCs group (n=8); groupⅡ, adenovirus mediated ?-galactosidase(Adv-?gal)gene transduced BMSCs group (n=6); groupⅢ, non-transduced BMSCs group (n=6); groupⅣ, untreated group (n=2). Roentgenography, histomorphometrical analysis and biomechanical measurement were studied at various times. Results Roentgenography showed more callus in the bone defect site of group Ⅰ. At 24th week after implantation, the healing rates of group Ⅰ,Ⅱ,Ⅲ, and Ⅳ were 6/7, 1/5, 2/5, and 0/1 respectively. There was statistic significant difference of X-ray grading between groupⅠand groupⅡor Ⅲ. Histomorphometrical analysis showed much more total new trabecular bone area (TBA) of groupⅠthan that of other groups. Biomechanical strength of groupⅠwas superior to that of groupⅡand Ⅲ. Conclusion Adenovirus mediated BMP-2 gene transferred BMSCs can repair segmental bone defect in goat without osteoconductive scaffold.