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Objective To evaluate the effect and mechanism of nicotinamide mononucleotide (NMN) on ischemia-reperfusion injury (IRI) induced by donor liver after cardiac death in rat models. Methods Rat models of orthotopic liver transplantation were established by "magnetic ring + double cuff" method. SD rats were randomly divided into the sham operation group (Sham group), orthotopic liver transplantation group (OLT group), NMN treatment + orthotopic liver transplantation group (NMN group), NMN+sirtuin-3 (Sirt3) inhibitor (3-TYP) + orthotopic liver transplantation group (NMN+3-TYP group), respectively. Pathological changes and hepatocyte apoptosis of the rats were observed in each group. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were determined. Superoxide dismutase (SOD) and malondialdehyde (MDA) contents in liver tissues were detected. The expression levels of Sirt3, microtubule-associated protein 1 light chain 3 (LC3)Ⅱ, PTEN-induced putative kinase 1 (PINK1), Parkin and translocase of the outer mitochondrial membrane 20 (TOMM20) in liver tissues were measured. Postoperative survival of the rats in each group was analyzed. Results Compared with the Sham group, serum ALT and AST levels were higher in the OLT group. Compared with the OLT group, the levels of ALT and AST were decreased in the NMN group. Compared with the NMN group, the levels of ALT and AST were increased in the NMN +3-TYP group (all P < 0.05). The liver tissue structure of rats in the Sham group was basically normal. In the OLT group, pathological changes, such as evident congestion, vacuolar degeneration and hepatocyte necrosis, were observed in the liver tissues. Compared with the Sham group, Suzuki score and apoptosis rate were higher in the OLT group. Suzuki score and apoptosis rate in the NMN group were lower than those in the OLT group. Suzuki score and apoptosis rate in the NMN+3-TYP group were higher compared with those in the NMN group (all P < 0.05). Compared with the Sham group, the SOD content was decreased, whereas the MDA content was increased in the OLT group. Compared with the OLT group, the SOD content was increased, whereas the MDA content was decreased in the NMN group. Compared with the NMN group, the SOD content was decreased, whereas the MDA content was increased in the NMN+3-TYP group (all P < 0.05). Compared with the Sham group, the relative expression levels of Sirt3 and TOMM20 proteins were down-regulated, whereas those of PINK1, Parkin and LC3Ⅱproteins were up-regulated in the OLT group. Compared with the OLT group, the relative expression levels of Sirt3, PINK1, Parkin and LC3Ⅱproteins were up-regulated, whereas that of TOMM20 protein was down-regulated in the NMN group. Compared with the NMN group, the relative expression levels of PINK1, Parkin and LC3Ⅱproteins were down-regulated, whereas that of TOMM20 protein was up-regulated in the NMN+3-TYP group (all P < 0.05). In the Sham group, the 7 d survival rate of rats was 100%, 50% in the OLT group, 75% in the NMN group and 58% in the NMN+3-TYP group, respectively. Conclusions NMN may enhance the antioxidative capacity of the liver, induce PINK1/Parkin-mediated mitochondrial autophagy, and alleviate IRI of the liver by up-regulating Sirt3, thereby playing a protective role in the donor liver after cardiac death.
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Objective To explore the present situation and characteristics of depression in patients with non-small cell lung cancer (NSCLC),and to analyze the mediating role of resilience in the relationship between self-perceived burden and depressive symptom,so as to provide evidence for improving depression in patients. Methods A total of 306 subjects from 5 tertiary hospitals in Changsha,Hunan Province were se-lected by simple random sampling method. Before their discharge from hospital,those subjects were investiga-ted by self-made social demographic questionnaire,Self-rating Depression Scale(SDS),Self-perceived Bur-den Scale of Lung Cancer(SPBS-LC) and Connor&Davidson Resilience Scale(CD-RISC). Pearson analysis was used to analyze the correlation among the variables,and Amos 7. 0 was used to establish the structural e-quation model and test the mediating effect. Results ( 1) The total score of depression was ( 59. 10 ± 8. 37). The total scores of resilience and self-perception burden were (52. 77±10. 12) and (49. 64±8. 55) in newly-diagnosed advanced non-small cell lung cancer patients. (2) Pearson analysis showed that the total score of depression was negatively correlated with the total score of resilience,optimism,self-improvement and tenacity (P<0. 05). The total score of depression was positively correlated with the total score of self-percep-tion burden, physical burden, emotional burden, disease symptoms, social and economic dimensions (P<0. 05). (3) Structural equation model analysis showed that resilience played a partial role in mediating be-tween self-perceived burden and depression and mediating effect accounted for 29. 8% of the total effect. Conclusion The depressive symptom of the NSCLC patients is at the mild to moderate level. Reducing their self-perceived burden and promoting the resilience of lung cancer patients could alleviate their depressive symptom.
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In recent years, with the high incidence of lung cancer and mortality, the disease-relevant mental health problems such as depression began to attract attention. A growing number of studies have also begun to hypothesize and confirm the relationship between depression and survival or mortality in patients with lung cancer, and have made some progress in basic research, prospective cohort research and intervention research. In basic research, cancer can cause depression due to mediating the production of inflammatory factors, and the genotype of tumor epidermis growth factor receptor (EGFR) can explain the high mortality and risk of depression in patients with lung cancer from a certain point of view. Different studies in prospective cohort studies argue that depression is an important predictor of survival in patients with lung cancer and need to be further studied. In the aspect of intervention research, although some studies have confirmed the potential of antidepressants in anti-tumor oxidative therapy, there is no enough evidence in psychological intervention and drug intervention to prove their effectiveness in improving the survival outcome of lung cancer. In the future, it is necessary to further explore the possible mechanisms for antidepressants and psychological intervention to improve the survival time of the patients.
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Humans , Cohort Studies , Depression , Depressive Disorder , Lung Neoplasms , Prospective StudiesABSTRACT
Objective@#To investigate the value of platelet count in predicting the efficacy of rituximab treatment in chronic primary immune thrombocytopenia (ITP).@*Methods@#A retrospective study was conducted in 103 chronic ITP patients hospitalized in our medical center between January 2011 and December 2014. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) of platelet count in different time points were analyzed for the predictor of treatment response. Optimal cutoff values were established using ROC analysis.@*Results@#A total of 103 patients were included in the study. There were 46 males and 57 females, with a median age of 30 (18-67) years. At day 1, 3 and 7 after the first dose of rituximab, there was no significant difference in platelet counts between the success group (PLT≥50×109/L after treatment) and the failure group (PLT≤50×109/L after treatment) (P>0.05). At day 14 after rituximab treatment (PTD 14), platelet counts became significantly different in the success and failure groups[41(8-384)×109/L vs 23(0-106)×109/L, P=0.003], and remained different thereafter, with increasing significance in the subsequent follow-ups. Patients were divided further using an optimal cut-off platelet count of 50×109/L on PTD 14, PTD 30, and PTD 60, and PPV and NPV values were calculated for predicting eventual success and failure.@*Conclusion@#Response can be predicted by obtaining platelet counts at 14, 30 and 60 days after rituximab treatment. The study proposed a protocol that guides patient monitoring and management planning.
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Objective To investigate the role of Calcineurin binding protein 1(Cabin1)in podocyte mito-chondrial dysfunction. Methods Cultured podocytes were injured by AngiotensinⅡ(AngⅡ).Cells were harvest-ed after 0 h,24 h and 48 h after AngⅡstimulating.Immunofluorescence staining was used to observe the disrup-tion of actin cytoskeleton,as well as the distribution of Cabin1.Western bolt was applied to detect the level of cyto-chrome c and Cabin1 protein in podocytes. Results AngⅡremarkably caused podocyte damage in a time depen-dent manner. Phalloidin staining displayed strong and long bundles of intracellular actin filaments in untreated cells. AngⅡ induced the loss of the cytoplasmic cytoskeleton and the reorganized of actin cytoskeleton at 24 and 48h. In normal podocytes,Cabin1 evenly localized in the cytoplasm and nuclei. AngⅡinduced strong staining of Cabin1 in podocytes nuclei. Cytochrome c and Cabin1 protein expression apparently increased in AngⅡ injuried podocyte.Ctyochrome c protein obviously increased in cells at 24 h and 48 h after AngⅡstimulating,which were as 1.51 and 1.87 times as the normal control group(P < 0.05). Similarly,the expression of Cabin1 were as 1.33 and 1.67 times respectively in 24 h and 48 h while compared to the normal control group(P < 0.05). Conclu-sion Cabin1 was overexpressed during podocyte mitochondrial dysfunction.It could be a crucial factor which regu-lates mitochondrial function during podocyte damage.
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Objective To investigate the role of Calcineurin binding protein 1(Cabin1)in renal tubular epithelial cells(RTECs)injury. Methods The male Sprague-Dawley rats were randomly divided into Sham-oper-ated and 5/6 nephrectomized group. Nephrectomized rats were further divided into two groups ,which were 4 and 8 weeks after operation,including 6 rats in each group. Rats were sacrificed at 4 or 8 weeks after nephrectomy,then control or remnant kidneys were harvested. 2μm sections of kidney tissues were collected and stained with Masson's trichrome and were graded for tubulointerstitial lesion score (TILS). RTECs mitochondrial morphology changes were detected by electron microscope. Western blot was applied to detect Cabin1 protein level in the renal tissue. Results At 8 weeks after the operation,plenty of RTECs fell off from the basement membrane,accompanied with interstitial fibrosis and the infiltration of inflammatory cells. Moreover ,TILS were significantly increased in rats at 8 weeks after operation while compared to sham-operated rats(7.16 ± 0.52 vs. 0.00 ± 0.00,P<0.05). RTECs mi-tochondria begun to swell at 4 weeks after 5/6 nephrectomy,while the disruption of cristae could be found in rats at 8 weeks. Cabin1 protein expression apparently increased in the remnant kidney. Cabin1 protein obviously increased in rats at 8 weeks after the surgery compared to sham-operated rats(0.97 ± 0.09 vs. 0.22 ± 0.07,P<0.05)and rats at 4 weeks after nephrectomy(0.97 ± 0.09 vs. 0.45 ± 0.03,P<0.05). Conclusions Cabin1 is overexpressed during RTECs injury in 5/6 nephrectomized rats. It can be a crucial factor regulating the damage of RTECs.
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Objective To investigate the role of Calcineurin binding protein 1(Cabin1)in renal tubular epithelial cells(RTECs)injury. Methods The male Sprague-Dawley rats were randomly divided into Sham-oper-ated and 5/6 nephrectomized group. Nephrectomized rats were further divided into two groups ,which were 4 and 8 weeks after operation,including 6 rats in each group. Rats were sacrificed at 4 or 8 weeks after nephrectomy,then control or remnant kidneys were harvested. 2μm sections of kidney tissues were collected and stained with Masson's trichrome and were graded for tubulointerstitial lesion score (TILS). RTECs mitochondrial morphology changes were detected by electron microscope. Western blot was applied to detect Cabin1 protein level in the renal tissue. Results At 8 weeks after the operation,plenty of RTECs fell off from the basement membrane,accompanied with interstitial fibrosis and the infiltration of inflammatory cells. Moreover ,TILS were significantly increased in rats at 8 weeks after operation while compared to sham-operated rats(7.16 ± 0.52 vs. 0.00 ± 0.00,P<0.05). RTECs mi-tochondria begun to swell at 4 weeks after 5/6 nephrectomy,while the disruption of cristae could be found in rats at 8 weeks. Cabin1 protein expression apparently increased in the remnant kidney. Cabin1 protein obviously increased in rats at 8 weeks after the surgery compared to sham-operated rats(0.97 ± 0.09 vs. 0.22 ± 0.07,P<0.05)and rats at 4 weeks after nephrectomy(0.97 ± 0.09 vs. 0.45 ± 0.03,P<0.05). Conclusions Cabin1 is overexpressed during RTECs injury in 5/6 nephrectomized rats. It can be a crucial factor regulating the damage of RTECs.
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Objective@#To analyze the difference of bleeding frequency, plain radiographic (X-ray) , risk factors in hemophilic arthropathy progression and the Arnold-Hilgartner classification.@*Methods@#A retrospective study was conducted in 211 hemophilia patients hospitalized in our medical center between January 2007 and December 2010, some patients with hemarthrosis were followed up for 5 years.@*Results@#All patients were male, including 150 hemophilia A (HA) and 61 hemophilia B (HB) . The HA patients bled more frequently than HB patients with annualized total bleeding rate 20.5 (0-48) vs 13 (1-40) ; annualized joint bleeding rate 13.5 (0-38) vs 8 (0-33) , especially in moderate hemophilia [26 (1-48) vs 12 (1-36) , P<0.001; 18 (0-36) vs 7.5 (0-26) , P=0.001], but severe hemophilia had no difference in bleeding frequency [33 (1-41) vs 26 (1-40) , P=0.702; 22 (0-36) vs 18 (0-33) , P=0.429]. The condition of the affected joints of 108 HA and 54 HB was evaluated on roentgenography. In HA patients, the Arnold-Hilgartner classification increased with the severity ratings (r=0.063, P=0.004) . However, similar associations were not found in HB patients (r=0.045, P=0.082) . Five years later, 36 HA and 19 HB patients received the same joint X-ray, there were no significant differences in joints radiographic progression between the total HA and HB groups (z=1.941, P=0.052) . However, significant difference between moderate HA and HB was observed (z=0.076, P=0.002) . Multivariate unconditioned Logistic analysis showed that annualized joint bleeding rate [P<0.001, OR=1.166 (95%CI 1.097-1.239) ] and articular structural injuries [P=0.018, OR=2.842 (95% CI 1.196-6.755) ] were independent risk factors for the joints radiographic progression.@*Conclusion@#The study suggests that there was a difference in bleeding phenotype between HA and HB, especially in moderate hemophilia. HB patients showed mild but progressive development over time, compared with HA patients. Annualized joint bleeding rate and articular structural injuries were independent risk factors for the joints radiographic progression.
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Objective@#To evaluate the role of the revised International Prognostic Score of Thrombosis (IPSET-thrombosis) in predicting the occurrence of thrombotic events in Chinese patients with essential thrombocythemia (ET) and to develop a thrombosis predicting model more applicable to Chinese ET patients.@*Methods@#Medical records of 746 adult patients with an initial diagnosis of ET were retrospectively analyzed.@*Results@#The median age at diagnosis was 52 (18-87) years, with 305 males and 441 females. According to the revised IPSET-thrombosis model, the number of very low-, low-, intermediate-, and high-risk patients were 271 (36.3%) , 223 (29.9%) , 63 (8.4%) and 189 (25.3%) , respectively. The four groups exhibited significantly different thrombosis-free survival (χ2=72.301, P<0.001) . Thirty-six patients were reclassified as intermediate-risk according to the revised IPSET-thrombosis instead of low-risk as per the original IPSET-thrombosis. Nineteen intermediate-risk patients as per the original IPSET-thrombosis were upgraded to high-risk according to the revised IPSET-thrombosis. Fifty-one high-risk patients as per the original IPSET-thrombosis were reclassified as low-risk in the revised IPSET-thrombosis. It suggests that the revised IPSET-thrombosis potentially avoids over- or under-treatment. In low-risk patients as per the revised IPSET-thrombosis, the rate of thrombosis in patients with cardiovascular risk factors (CVF) was higher than that in those without (16.3% vs 5.2%, χ2=5.264, P=0.022) , and comparable with intermediate-risk patients as per the revised IPSET-thrombosis (16.3% vs 14.3%, χ2=0.089, P=0.765) . As a result, a new revised IPSET-thrombosis model more applicable to Chinese ET patients was developed in which patients with CVF in the low-risk group as per the revised IPSET-thrombosis were reclassified as intermediate-risk group.@*Conclusion@#For predicting the occurrence of thrombotic events, the revised IPSET-thrombosis model was better than the original IPSET-thrombosis model. The revised IPSET-thrombosis was optimized and a new revised IPSET-thrombosis model more applicable to Chinese ET patients was developed, and the new evidence for risk stratification and treatment of ET in Chinese was provided.
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Objective To investigate the function and molecular mechanism of tacrolimus in podocyte injury and restoration.Methods Cultured podocytes were stimulated by Angiotensin Ⅱ (Ang Ⅱ) or Ang Ⅱ plus tacrolimus.Cells were collected at different time points (0 h,12 h and 24 h).The distribution of F-actin was observed after immunofluorescence staining,and the protein expression of nephrin and podocin were detected by Western Blot (WB).Results In normal control podocytes,F-actin was arranged in cytoplasm powerfully.Ang Ⅱ induced the disruption and discontinuity of F-actin.Tacrolimus inhibited the effect of Ang Ⅱ,stabilized the regular arrangement the F-actin.Compared to normal cells,the protein expression of nephrin in Ang Ⅱ group significantly decreased at 24 h after stimulation (0.76 ± 0.32 in AngⅡ group vs.1.18 ± 0.40 in normal group,P ＜ 0.05).And tacrolimus stabilized the expression of nephrin protein (1.00 ± 0.19 in treatment group vs.0.76 ± 0.32 in Ang Ⅱ group,P ＜ 0.05).Ang Ⅱ and tacrolimus did not affect the expression of podocin protein.Conclusion Tacrolimus inhibits podocyte injury induced by Ang Ⅱ,stabilizes the regular arrangement of cytoskeleton and protein expression of nephrin.
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Objective To establish an inductively coupled plasma‐mass spectrometry (ICP‐MS) method for analysis of elements in peripheral blood of children .Methods A total of 474 healthy children in Hunan area were enrolled in this study ,and six ele‐ments ,including Ca ,Mg ,Fe ,Cu ,Zn and Pb ,in peripheral blood specimens were detected by using ICP‐MS method .Results The levels of elements ,including Ca ,Mg ,Fe ,Cu ,Zn and Pb ,in peripheral blood of healthy children showed skewed distributions ,and no significant differences were found in levels of these elements between male and female children(P>0 .05) .The reference intervals of Ca ,Mg ,Fe ,Cu ,Zn and Pb in peripheral blood of healthy children in this area were 57 .30 -81 .40 mg/L ,30 .40 -44 .80 mg/L , 361 .20-531 .40 mg/L ,848 .10-1 469 .20 μg/L ,2 .68 -6 .54 mg/L and 0 .00 -100 .00 μg/L respectively .Conclusion The ICP‐MS method for simultaneously detecting Ca ,Mg ,Fe ,Cu ,Zn and Pb in peripheral blood of children and reference interval of each ele‐ment are successfully established .
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<p><b>OBJECTIVE</b>To analyze clinical and molecular characteristics of low-risk essential thrombocythemia (ET) in a large cohort of Chinese patients and to explore risk factors for major thrombosis and treatment strategies.</p><p><b>METHODS</b>Medical records of patients with an initial diagnosis of ET from March 1982 to May 2012 in our hospital were retrospectively analyzed.</p><p><b>RESULTS</b>A total of 604 low-risk ET patients were enrolled with a median follow-up of 49 months (range:0-338). 43(7.1%) patients experienced major thrombotic events. Cox proportional hazards regression revealed JAK2 V617F mutation (HR=2.279; P=0.035) and cardiovascular risk factors (CVF) (HR=2.541; P=0.006) to be risk factors for total thrombotic events, while only CVF (HR=2.633; P=0.008) was risk factor for arterial thrombosis. None of the evaluated factors was related to venous thrombosis. Patients with both JAK2 V617F mutation and CVF had a worse thrombosis- free survival than those with only one risk factor (P<0.05). In patients with JAK2 V617F or CVF alone, antiplatelet treatment (P=0.016) significantly decreased the risk of thrombosis, while those with both JAK2 V617F and CVF could benefit from cytoreductive agents (P=0.018).</p><p><b>CONCLUSION</b>Chinese low-risk ET patients have a lower risk of thrombosis than Caucasian low-risk ET patients. JAK2 V617F mutation and CVF are the most significant risk factors for thrombosis. Existence of both risk factors further increases the thrombotic risk. Treatment strategies on low-risk ET patients should be made based on presence or absence of risk factors.</p>
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Humans , Asian People , Janus Kinase 2 , Mutation , Retrospective Studies , Risk Factors , Thrombocytopenia , Thrombosis , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To investigate the technique for unilateral cleft lip nasal deformities.</p><p><b>METHODS</b>Through the traditional columella margin incision, the alar cartilage and the lateral nasal cartilage were exposed. After the mucosa between the two cartilages was divided, a mucosa-cartilage flap was developed and anchored, moving the lateral crus upwardly and medially, correcting the nasal deformity.</p><p><b>RESULTS</b>52 cases of primary nasal deformities and 18 cases of secondary nasal deformities were corrected with this technique. Satisfactory results were achieved.</p><p><b>CONCLUSION</b>This technique is recommendable, which is more likely to restore the physiological characters of the nose than the conventional technique.</p>
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Adolescent , Adult , Child , Child, Preschool , Humans , Infant , Cleft Lip , General Surgery , Rhinoplasty , MethodsABSTRACT
<p><b>OBJECTIVE</b>To investigate the effects of Matrine on apoptosis of fibroblasts and the expression of apoptotic modulation related protein in the hypertrophic scar.</p><p><b>METHODS</b>Hypertrophic scar was produced on the ear of 24 New Zealand white rabbits, which were employed as the model, and were randomly and equally divided into control (CC) and Matrine (M) groups (12 in each group). Matrine (50 g/L) was injected into the ear scar in M group and with normal saline in C group once every four days. At 2, 4, 6, 8 and 12 weeks after the injection, the apoptotic fibroblast count in the scar was determined by TUNEL method, and the expressions of apoptosis related modulation proteins p53, bcl-2, bax were detected by immunohistochemistry method.</p><p><b>RESULTS</b>The apoptotic fibroblast count was much larger in M group than that in C group at all test time points (P < 0.05). Furthermore, the bax expression was increased and that of p53 and bcl-2 was decreased significantly in M group. In adding, the scar became flat in M group.</p><p><b>CONCLUSION</b>Matrine might obviously enhance the fibroblast apoptosis in rabbit ear hypertrophic scar, and up-regulate the expression of apoptosis related modulation protein bax and down-regulate the expression of p53 and Bcl-2.</p>
Subject(s)
Animals , Female , Male , Rabbits , Alkaloids , Pharmacology , Apoptosis , Cicatrix, Hypertrophic , Metabolism , Pathology , Fibroblasts , Immunohistochemistry , Proto-Oncogene Proteins , Proto-Oncogene Proteins c-bcl-2 , Quinolizines , Tumor Suppressor Protein p53 , bcl-2-Associated X ProteinABSTRACT
Objective:To study the pharmacokinetics,thissue distribution and secretion of nerve growth factor(NGF)in mice.Methods:The conecntration of NGF in various body fluids and tissue were determined by isotope tracer combined SDSPAGE method.Results:The plasma concenmtration-time curve was in accordance with the two-compartment pharmacokinetic model.The elimation half-life(t1/2β)was 3.1.The half-life of distribution(t1/2ka)was 5min.Tpeak was 25 min.AUC was 72.4 mg·kg-1·h-1.The concentrations of NGF were high in thyroid,blood,submaxillary glands,superior cervical ganglion,adrenasl and kidneys.Conclusion:NGF has a wide distribution,high tissue concentrationa nd excrtet mainly through the urine.