Advances in bronchoscopic diagnosis and treatment for peripheral pulmonary lesions / 中国胸心血管外科临床杂志

@#The detection of peripheral pulmonary lesions has increased gradually with the popularity of CT. Rapid and accurate diagnosis, and individualized treatment are two aspects we need to pay great attention to. These situations also raise higher request for the technique in diagnosis and treatment. At present, the commonly used transthoracic methods can increase the risk of complications such as pneumothorax and bleeding. The newly bronchoscopic approaches for diagnosis and treatment make less injury via natural lumen and have been applied widely in clinics. This review will introduce the worth expecting progress in bronchoscopic diagnosis and treatment for peripheral pulmonary lesions.

Leptin relieves ischemia/reperfusion induced acute kidney injury through inhibiting apoptosis and autophagy / 中南大学学报(医学版)

OBJECTIVES@#Acute kidney injury (AKI) can be caused by ischemia/reperfusion (I/R), nephrotoxin, and sepsis, with poor prognosis and high mortality. Leptin is a protein molecule that regulates the body's energy metabolism and reproductive activities via binding to its specific receptor. Leptin can inhibit cardiomyocyte apoptosis caused by I/R, but its effect on I/R kidney injury and the underlying mechanisms are still unclear. This study aims to investigate the effect and mechanisms of leptin on renal function, renal histopathology, apoptosis, and autophagy during acute I/R kidney injury.@*METHODS@#Healthy adult male mice were randomly divided into 4 groups: a sham+wild-type mice (ob/+) group, a sham+leptin gene-deficient mice (ob/ob) group, an I/R+ob/+ group, and an I/R+ob/ob group (n=8 per group). For sham operation, a longitudinal incision was made on the back of the mice to expose and separate the bilateral kidneys and renal arteries, and no subsequent treatment was performed. I/R treatment was ischemia for 30 min and reperfusion for 48 h. The levels of BUN and SCr were detected to evaluate renal function; HE staining was used to observe the pathological changes of renal tissue; TUNEL staining was used to observe cell apoptosis, and apoptosis-positive cells were counted; Western blotting was used to detect levels of apoptosis-related proteins (caspase 3, caspase 9), autophagy-related proteins [mammalian target of rapamycin (mTOR), phosphorylated mTOR (p-mTOR), LC3 I, LC3 II], mTOR-dependent signaling pathway proteins [phosphate and tension homology (PTEN), adenosine monophosphate-activated protein kinase (AMPK), protein kinase B (AKT), extracellular regulated protein kinase (ERK), phosphorylated PTEN (p-PTEN), phosphorylated AMPK (p-AMPK), phosphorylated AKT (p-AKT), phosphorylated ERK (p-ERK)].@*RESULTS@#There was no significant difference in the levels of BUN and SCr between the sham+ob/+ group and the sham+ob/ob group (both P>0.05). The levels of BUN and SCr in the I/R+ob/+ group were significantly higher than those in the sham+ob/+ group (both P<0.05). Compared with the mice in the sham+ob/ob group or the I/R+ob/+ group, the levels of BUN and SCr in the I/R+ob/ob group were significantly increased (all P<0.05). There was no obvious damage to the renal tubules in the sham+ob/+ group and the sham+ob/ob group. Compared with sham+ob/+ group and sham+ob/ob group, both the I/R+ob/+ group and the I/R+ob/ob group had cell damage such as brush border shedding, vacuolar degeneration, and cast formation. Compared with the I/R+ob/+ group, the renal tubules of the mice in the I/R+ob/ob group were more severely damaged. The pathological score of renal tubular injury showed that the renal tubular injury was the most serious in the I/R+ob/ob group (P<0.05). Compared with the sham+ob/+ group, the protein levels of caspase 3, caspase 9, PTEN, and LC3 II were significantly up-regulated, the ratio of LC3 II to LC3 I was significantly increased, and the protein levels of p-mTOR, p-PTEN, p-AMPK, p-AKT, and p-ERK were significantly down-regulated in the I/R+ob/+ group (all P<0.05). Compared with the sham+ob/ob group, the protein levels of caspase 3, caspase 9, PTEN, and LC3 II were significantly up-regulated, and the ratio of LC3 II to LC3 I was significantly increased, while the protein levels of p-mTOR, p-PTEN, p-AMPK, p-AKT, and p-ERK were significantly down-regulated in the I/R+ob/ob group (all P<0.05). Compared with the I/R+ob/+ group, the levels of p-mTOR, p-PTEN, p-AMPK, p-AKT were more significantly down-regulated, while the levels of caspase 3, caspase 9, PTEN, and LC3 II were more significantly up-regulated, and the ratio of LC3 II to LC3 I was more significantly increase in the I/R+ob/ob group (all P<0.05).@*CONCLUSIONS@#Renal function and tubular damage, and elevated levels of apoptosis and autophagy are observed in mice kidneys after acute I/R. Leptin might relieve I/R induced AKI by inhibiting apoptosis and autophagy that through a complex network of interactions between mTOR-dependent signaling pathways.

Evaluation and thinking on the clinical theoretical exam of phased examination for medical practitioner qualification / 中华医学教育探索杂志

Objective:To analyze the performance of clinical theoretical examination of the five year clinical medical students in a medical school, and to explore the existing problems and direction involving in the medical education.Methods:The difficulty coefficient and degree of discrimination were used to analyze the quality of this test, and F test and LSD- t test were conducted with SPSS 24.0 to analyze the mastery rate of various modules and secondary disciplines including basic medicine, medical humanities, clinical medicine and preventive medicine. Results:The overall difficulty coefficient of the test was 0.74, and the degree of discrimination was 0.37. The coefficient of difficulty of each module is more than 0.70, and the degree of discrimination is about 0.40. The mastery rates of each module were all greater than 70%, with clinical medicine being the highest and medical humanities and basic medicine being the lowest, and the mastery rate of each secondary discipline was more than 60%, with a significant difference.Conclusion:This exam is sample, the degree of discrimination is good, and the overall knowledge is well mastered. However, it is still necessary to innovate education reform and improve the teaching quality based on weak points.

Application of virtual laboratory in infectious disease teaching of medical students / 中华医学教育探索杂志

Objective:To explore the influence of virtual simulation experiment project on the experimental teaching effect of infectious diseases.Methods:Ten experimental contents were selected, including 3 703 students majoring in clinical five-year program, eight-year program, anesthesia, psychiatry and other majors of Medicine School of Central South University. The teaching effect and students' satisfaction were evaluated through examination and personal questionnaire survey. The measurement data was expressed by (mean ± standard deviation), the counting data was illustrated by percentage. The rate is compared by Chi-square test, and the difference is statistically significant when P<0.05. Results:All the students took part in the examination of 10 items. Except for item 8, the scores of students in all items had a large variance, with almost same number of high score students and low score students. Learning attitude is closely related to learning effect. Among the students who think it's necessary to learn, 20.5% and 53% have excellent learning effect and good learning effect, respectively. Compared with offline experiment teaching, virtual simulation teaching has both advantages and disadvantages, and needs to further improve the satisfaction of students.Conclusion:Virtual simulation teaching of infectious diseases is unable to completely replace offline teaching, and the combination of virtual and reality is more conducive to improving the quality of medical students.

The exploration and practice of concentrated training model to medical students before clinical practice / 中华医学教育探索杂志

Clinical practice, the necessary way which must be passed by medical students, is a key period of medical education and a vital part to realize the goal of higher medical education. Our hospital has taken a series of effective measures to strengthen clinical practice teaching for many years, and we are ex-ploring the concentrated training model to medical students all the time. Every year before clinical practice, the Inspection Section develops theoretical and basic clinical skills training courses, selects experienced teachers to teach, check and evaluate the training result according to students' performance in medical and teaching activities in the ward, the clinical practice syllabus and Medical Qualification Examination aims to improve medical students' theoretical knowledge, skills, medical ethics, humanity, and clinical thinking, etc. Effect evaluation shows that our training model has played a positive role in improving overall qualities of medical students and got good feedback from them.

Characteristics and immune mechanisms of CD71+ CD235a+ nucleated erythroid cells in elderly / 中华老年医学杂志

Objective To explore the immune property and possible mechanism of the CD71+ CD235a+ nucleated erythroid cells from peripheral blood in elderly,as compared with those of healthy young.Methods Peripheral blood obtained by venipuncture from healthy young(n=59,mean age=28 years) and elderly(n=78,mean age=68 years)donors were measured by flow cytometry to evaluate the frequency of the CD71+ CD235a+ cells in peripheral blood mononuclear cells (PBMC).In vitro assays,CD71+ CD235a+ cells were sorted by flow cytometry and T cells were sorted using CD4+T cell isolation kit,then the T cell proliferation assays were conducted by following groups:T cell + CFSE group;T cell +CFSE co-cultured with CD71+ CD235a+ cells from the young donors;T cell + CFSE co-cultured with CD71+ CD235a+ cells from the older donors.Real-time PCR were used to identify the expression of the immune cytokine secreted by CD71+ CD235a+ cells.Results (1)the results showed a significant increase in the percentage of CD71+ CD235a+ cells in the elderly compared with the young [(9.93± 2.95)％ vs (1.96 ± 1.16)％,t =3.37,P ＜ 0.001];(2)the CD71+ CD235a+ cells from the older donors could suppress the proliferation of the T cells (t =2.91,P＜ 0.05)while from the young group we could not observe this phenomenon(t =0.387,P＞0.05).(3)The results of Real-time PCR revealed that,compared with CD71+ CD235a+ cells from the young,CD71+ CD235a+ cells from the elderly expressed higher levels of Arg-2 (t =9.04,P＜0.01),IL-1β,IL-6 and TGF-β(t =4.51,5.46,6.92,all P＜0.05).Conclusions There are higher frequencies of CD71+ CD235a+ cells in aged samples than the young.And the CD71+CD235a cells from the elderly could secrete more Arg-2,IL-1β,IL-6 and TGF-β to suppress the T cell proliferation.

The effect of 137Cs γ-rays on the differentiation of human peripheral blood mononuclear cells to osteoclast-like cells / 中华放射医学与防护杂志

Objective To study the effect of γ-rays irradiation on the differentiation potential of the human peripheral blood monocytes (PBMCs) into osteoclast-like cells (OCLs) in vitro.Methods PBMCs were isolated by density gradient centrifugation,treated by receptor activator of nuclear factor-κ B ligand (RANKL) and macrophage-colony stimulating factor (M-CSF) and exposed to 137Cs γ-rays with different radiation doses (0,0.75,2 Gy).After seven days of incubation,the cells were stained for tartrate resistant acid phosphatase (TRAP) and bone slices were stained by toluidine blue on the tenth day.Meanwhile,the characteristic osteoclast markers including Cathepsin K and integrin β3 were analyzed by real-time PCR.Tartrate resistant acid phosphatase 5b (TRAcP-5b) in the culture supernatant wasdetermined by ELISA.Results PBMCs were differentiated into OCLs by the treatments of RANKL and MCSF.The number of TRAP positive multinucleated OCLs was significantly higher in the dose of 0.75 Gy group than in control (0 Gy) group (t =3.451,P ＜ 0.05).Compared with the control group,the expression levels of Cathepsin K and integrin β3 and the concentration of TRAcP-5b were significantly elevated (t =2.343,2.728,3.631,P ＜ 0.05).However,in the 2 Gy group,there was a decrease in the number of osteoclasts,mRNA expression level of osteoclast characteristic markers and TRAcP-Sb,but no statistically significant differences compared with the control group.Conclusions Ionizing radiation may influence the osteoclastogenesis during the PBMCs differentiation to OCLs.At low dosage,ionizing radiation promotes osteoclastogenesis and enhances the resorptive activity of osteoclasts,but a decline of differentiation potential was observed at high dosage of radiation.

Effects of TIMP-1 on PTEN expression on renal tubular epithelial cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the role of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in regulating both angiogenesis and the expressions of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) and vascular endothelial growth factor (VEGF)/Flk-1 expression in human proximal tubular epithelial cells (HKC).</p><p><b>METHODS</b>HKC cells were transfected with two recombinant plasmids containing sense and antisense full-length TIMP-1 cDNA (TIMP-1S-pcDNA3.0 and TIMP-1AS-pcDNA3.0, respectively) constructed previously, or treated with 100 µmol/L MMP-2/MMP-9 inhibitor III (with similar cellular enzyme suppression activity with sense TIMP-1 plasmid). The mRNA expression of TIMP-1, MMP-2, MMP-9, PTEN, VEGF and Flk-1 were examined by RT-PCR. In each group, the expression of PTEN, VEGF and Flk-1 were also detected using an indirect immunofluorescence assay.</p><p><b>RESULTS</b>Compared with non-transfected cells and cells transfected with the empty vector, sense TIMP-1-transfected cells showed obviously upregulated PTEN expression (P<0.05) and significantly lowered gelatinase activity (P<0.05) and VEGF and Flk-1 expressions (P<0.05). Transfection with the antisense TIMP-1 plasmid produced the reverse results (P<0.05). MMP-2/MMP-9 inhibitor III did not obviously affected the expression of PTEN, VEGF or Flk-1 as compared with the non-transfected or empty vector-transfected cells.</p><p><b>CONCLUSION</b>In the aging progress, the renal tissues express high levels of TIMP-1 to upregulate PTEN expression via a MMP-independent pathway, and subsequently down-regulates the expression of VEGF and Flk-1 to cause aging-related impairment of renal angiogenesis. These findings provide new evidence for understanding the role of TIMP-1 in renal aging.</p>

Indoleamine-pyrrole 2,3-dioxygenase might be a prognostic biomarker for patients with renal cell carcinoma / 中南大学学报(医学版)

Objective:To explore the role of indoleamine-pyrrole 2,3-dioxygenase (IDO),an immunomodulatory enzyme,in renal cell carcinoma (RCC).Methods:A total of 40 patients diagnosed as RCC in the Second Xiangya Hospital were included in this study.All patients received nephrectomy.The histopathological features of samples were assessed semi-quantitatively.IDO mRNA level in RCC and non-RCC renal tissues was determined by real-time quantitative PCR (RT-qPCR).And the expression of IDO protein in endothelial cells was examined by immunohistochemistry; a Kaplan-Meier survival curves was calculated on the basis of IDO mRNA level.Results:Level of IDO mRNA in RCC samples was significantly higher than that in tumor-free samples with P＜0.001.Patients with high IDO expression had an significantly longer survival time than those with low IDO expression (P=0.01).There was a statistically significant inverse correlation between IDO and proliferation marker Ki67.Patients with high IDO level were of low Ki67 level,and vice versa (P＜0.01).Conclusion:IDO might be a prognostic biomarker for patients with RCC.

Multi-frequency low-dose intravenous iron on oxidative stress in maintenance hemodialysis patients / 中南大学学报(医学版)

OBJECTIVE@#To investigate the effect of different intravenous iron treatment regimens on anemia and oxidative stress in maintenance hemodialysis (MHD) patients.@*METHODS@#A total of 58 MHD patients were randomly divided into a multi-frequency low-dose intravenous iron group (iron sucrose 25 mg, twice a week for 8 weeks, n=19), a less-frequency regular-dose intravenous iron group (iron sucrose 100 mg, once every two weeks for 8 weeks, n=19), and a non-iron group (n=20). Another 20 healthy people served as a control group (n=20). The changes of hemoglobin (Hb), hematocrit (HCT), serum ferritin (SF) and transferrin saturation (TSAT), as well as the oxidative stress parameters of malon-dialdehyde (MDA), superoxide dismutase (SOD) and myeloperoxidase (MPO) were detected before and after the treatment.@*RESULTS@#After 8 weeks, compared with the non-iron group, the levels of Hb, HCT, SF and TSAT in the two iron groups were significantly elevated (P0.05). After the single dialysis, the two iron groups had higher level of serum MDA, MPO and lower level of serum SOD than that of the non-iron supplementation group (P0.05).@*CONCLUSION@#Multi-frequency low-dose intravenous iron can effectively improve anemia in MHD patients, whose acute oxidative stress is lower than that of less-frequency regular-dose intravenous iron, and is a relatively safe and effective intravenous iron treatment regimen.

Placement of peritoneal catheters with the assistance of X-ray fluoroscopy / 中南大学学报(医学版)

OBJECTIVE@#To evaluate the value of X-ray fluoroscopy in preventing catheter dysfunction during catheterization of peritoneal dialysis.@*METHODS@#A total of 168 patients with end-stage renal failure were nonrandomized into group A (the conventional catheterization group) and group B (the conventional catheterization + bedside fluoroscopy group). All patients were followed up for 1 year after the catheterization. Details of the patients' general information, catheter-related complications and incidence of catheter dysfunction were analyzed.@*RESULTS@#Hemorrhagic complications occurred in 9 patients (5.36%), including 2 incision hematomas, 4 bloody fluid drainages, 1 bladder perforation and 1 intestinal perforation (1.20%). Dialysate leakages occurred in 4 patients (2.38%): 2 right pleural effusion and 2 scrotal edemas. Infection-related complications (2.98%) in 5 patients were observed: 1 infectious peritonitis and 4 catheter exit infections. All peritoneal dialysis-related infections were cured after the treatment. There was no significant difference in the incidence of mechanical and infectious complications between the two groups (P> 0.05). No immediate catheter dysfunction was found in all patients, but late catheter dysfunction was observed in 14 patients (8.33%), including 9 catheter migrations (5.36%), 5 of which were induced by other reasons (2.98%). Catheter dysfunction in 11 out of the 14 patients occurred within 30 days post-catheterization, whereas 2 occurred over 30 days (caused by constipation). In group A, 12 patients developed delayed catheter dysfunction (11.65%), 10 of which (83.33%) were induced by catheter migration and the other 2 by other reasons. In group B, 2 (11.65%) delayed catheter dysfunctions were observed, including 1 catheter migration and 1 constipation. The incidence of catheter dysfunction in group A was significantly higher than that in group B (P<0.05). The success rate of catheterization in group B was 91.3%.@*CONCLUSION@#Catheter dysfunction is a common complication in peritoneal dialysis. X-ray fluoroscopy during catheter insertion helps to monitor the location of the catheter, which can effectively prevent late catheter dysfunction and increase the success of catheterization in peritoneal dialysis.

Basic experimental and clinical research on peritoneal dialysis in the past 16 years / 中南大学学报(医学版)

To summarized the experiences from our basic experimental and clinical research on peritoneal dialysis. In the past 16 years, peritoneal fibrosis rat models and rabbit models of peritonitis were first established successfully in our laboratory in China. Peritoneal mesothelial cells were also separated and identificated. Besides, we assessed the biocompatibility of peritoneal dialysis fluid and analyzed the molecular mechanism of peritoneal mesothelial cell injury. We demonstrated the key role of transforming growth factor-beta1 (TGF-beta1), connective tissue growth factor (CTGF) and peroxisome proliferative activated receptor-gamma (PPAR-gamma) in the pathogenesis of peritoneal fibrosis, as well as their regulation of molecular mechanism. Furthermore, we transfected the plasmids encoding TGF-beta1-shRNA or pCTGF-shRNA into peritoneal cells and tissues by nanocarrier technologies. In clinical research, the positioning of peritoneal dialysis catheters, peritoneal dialysis treatment modalities and the prevention and treatment of its complications were studied. The characteristics and mechanism of solute transport in peritoneal dialysis was also explored.

Ultrasound-mediated microbubble destruction enchances β-galactosidase gene transfection and expression in HKCs / 中南大学学报(医学版)

Objective To investigate the efficiency and safety of ultrasound-mediated microbubble destruction in enhancing β-galactosidase gene (β-gal gene) transfer into human proximal tubular cells(HKCs). Methods β-gal gene was transfected to HKCs as a mark gene with ultrasound-mediated microbubble destruction. Cultured HKCs were grouped to receive the following 7 treatments respectively: ultrasound alone; microbubble alone; naked plasmid; ultrasound and plasmid; microbubble and plasmid; ultrasound, microbubble, and plasmid; and VigoFect and plasmid. In Group 6, HKCs were exposed to ultrasound under different sound intensities and time. X-gal stainning, typan blue stainning, and Hochest stainning were used to detect the transfection efficiency, cell survival rate, and cell apoptosis rate, respectively.Results β-galactosidase expression could be observed in the ultrasound-mediated microbubble destruction groups. Along with the increasing of sound intensity and exposure time, the cell survival rate of HKCs decreased, and the cell apoptosis rate increased gradually. The transduction efficiency and survival rate in middle intensity (0.3 W/cm~2×60 s) of ultrasound exposure were higher than those of other groups, similar to those of Group 7.Conclusion Under optimum sound intensity and exposure time, ultrasound-mediated microbubble destruction can increase gene transfer into HKCs. This non-invasive gene transfer method may be a useful tool for clinical gene therapy.

Study on the changes of mammalian target of rapamycin with aging in rat kidneys / 中华老年医学杂志

ObjectiveTo investigate the changes in mammalian target of rapamyein (mTOR) with aging in rat kidneys.MethodsMale Wistar rats at the ages of 3, 12, 24 months were used for this study. Therenaltissuesandmesangialcellswereprocessedfor senescenceassociated β-galactosidase (SA-β-gal) staining. The expression and location of roTOR in kidneys and mesangial cells were studied by immunohistochemistry and immunocytochemistry, respectively. The mRNA and protein levels of the roTOR and p-roTOR were detected by Western blot assay and RT-PCR,respectively.ResultsThe expression of neutral β-galactosidase activity was increased in kidneys and mesangial cells with advancing age. Percentages of SA-β-gal staining positive ceils were (11.9±3.6)% versus ( 39.0±4.0)% versus ( 86.9±7.4) % in young, middle and aging glomerular mesangial cells (P<0.05). The mTOR staining appeared in the mesangial matrix and interstitium in kidneys, while the mTOR protein showed localization in cytoplasm and nucleus in mesangial cells. The staining intensity of mTOR in kidneys and mesangial cells in aged rats was markedly increased as compared to that in young and middle aged rats (P<0.05). The mRNA level of roTOR was significantly increased in kidneys and mesangial cells of agedrats versus young and middle aged rats,meanwhile, the roTOR and p-mTOR protein expressions were dramatically increased with advancing age (P<0.05 ).ConclusionsmTOR expression is increased with aging, which may play an important role in the aging process of kidneys.

Alteration of the expression of PTEN in rats with aging / 重庆医科大学学报

Objective:To investigate the alteration of the expression of PTENin rats with aging.Methods:Wistar rats were divided into 3 groups:3-month-old group,12-month-old group and 24-month-old group(n=6).Immunohistochemistry of CD34 was employed to detecte angiogenesis in the kidneys with aging.The protein expression of PTEN was examined by Western Blot.Immunohistochemistry was also employed to detect the expression of PTEN in the kidneys with aging.Results:(1)Compared with 3-month-old rats and 12-month-old rats,the level of PTEN protein expression in kidneys of 24-month-old rats was higher than that of 3-month-old rats and 12month-old rats,as examined by Western Blot(P