Application Progress of Eccentric Exercise Training in Rehabilitation(review) / 中国康复理论与实践

This article introduced the characteristics of eccentric contraction and its mechanism,as well as its application in the re-habilitation of chronic heart disease,chronic obstructive pulmonary disease,sports injuries,elderly sarcopenia,anterior cruciate ligament repair,cancer survivor,type 2 diabetes and nervous system diseases,etc.

Primary mediastinal germ cell tumors: the clinicopathologic analysis of 56 cases / 临床与实验病理学杂志

Purpose To investigate the clinicopathologic features of primary mediastinal germ cell tumors and to improve the diagnosis and treatment guidance. Methods The clinical features, histologic findings, molecular detection and biological behaviors of 56 PMGCT cases were analyzed retrospectively. Results The age of patients ranged from 9 to 48 years (median age 29.1 years), and mature teratoma(76.8％, 43/56) were the most common type.3 cases of mature teratoma were prepubertal patients.53 cases of postpubertal patients included 40 cases of mature teratoma, 2 cases of nonmature teratoma, 2 cases of yolk sac tumor, 5 cases of seminoma, 4 cases of mixed germ cell tumor. All malignant PMGCTs were male, and mature teratoma was found in the female. Histopathologic morphology and immune phenotype of primary mediastinal germ cell tumors were consistent with those of sexual gland. The isochromosome 12p was detected in various component of malignant GCTs, not in mature teratoma. All patients underwent surgical resection, with additional chemotherapy for malignant germ cell tumor cases. The prognosis of mature teratoma regardless of prepubertal or postpubertal patients was benign, but PMGCTs (except mature teratoma) of postpubertal type were malignant. Conclusion Primary mediastinal germ cell tumors are rare and mature teratoma is most common. The malignant PMGCTs mostly occur in young men. The abnormal 12p detected by FISH is helpful to differential diagnosis and guide the treatment.

Effects of dasatinib on the proliferation and invasion and metastasis of breast cancer / 中国现代普通外科进展

Objective:Our study attempts to investigate the effects and the mechanism of dasatinib on the proliferation,invasion and metastasis of triple-negative breast cancer (TNBC) cells.Method:TNBC Hs578T cells were tested for the sensitivity to dasatinib in vitro using PrestoBlueTM reagent and mammosphere assay.Transwell assay and wound-healing assay were used to determine invasion and metastasis ability of Hs578T cells.The p-STAT3 and STAT3 expressions of dasatinib]treated Hs578T cells were measured by Western blot.Results:Dasatinib exhibited growth inhibition of Hs578T cells.Mammosphere assay showed that dasatinb treatment led to less mammosphere formation of TNBC cells.More importantly,migration and invasion ability of Hs578T cells was also decreased by dasatinib treatment.Western blot analysis revealed that the p-STAT3 level was decreased significantly in Hs578T cells after dasatinib treatment,compared with control group.Conclusions:Dasatinib prevents the proliferation,invasion and metastasis ability of TNBC cells via inhibiting STAT3 pathway.

Dysplastic cerebellar gangliocytoma/Lhermitte-Duclos disease: report of 6 cases and review of the literatures / 临床与实验病理学杂志

Purpose To investigate the clinicopthologic features of dysplastic cerebellar gongliocytoma/Lhermitte-Duclos disease (LDD) and to discuss the diagnosis and differential diagnosis of the tumor.Methods Histopathological characteristics and immunohistochemical of SP results of 6 cases of LDD were studied and the relevant literatures were reviewed.Results 6 cases ranged in age from 23 to 56 years old,with an average of 34 years.The clinical manifestations were intracranial hypertension with or without cerebellar signs.MRI manifestations were characteristic by "tiger spots".Histology showed local cerebellar structure disorders,granulocytes and Purkinje cells decreased and replaced by a large number of abnormal ganglion cells.2 cases were followed up for 5 to 8 years recurrence,the remaining 4 cases recovered well.Conclusion LDD is a rare primary benign lesions of the cerebellum.Diagnosis depends on imaging and histopathological examination.The gross total resection is the best treatment choice.

Type II enteropathy-associated T-cell lymphoma: a clinicopathologic study / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features, immunohistochemical findings, differential diagnosis and prognosis of type II enteropathy-associated T-cell lymphoma (EATL).</p><p><b>METHODS</b>Fourteen cases of type II EATL encountered in Department of Pathology, Nanjing General Hospital were retrospectively reviewed. The clinical data, histologic features, immunohistochemical findings and follow-up information were analyzed, with literature review.</p><p><b>RESULTS</b>There were altogether 12 males and 2 females. The median age of patient was 49 years. The sites of involvement included jejunum (10 cases) and ileum/colon (4 cases). The patients often presented with an abdominal mass, abdominal pain, diarrhea and constitutional symptoms such as fever, night sweating and cachexia. There was no clinical evidence of gluten-sensitive enteropathy. Histologically, the lymphoma cells showed full-thickness infiltration of the intestinal wall. They contained round hyperchromatic nuclei and pale cytoplasm. The stroma was minimally inflamed, with or without associated coagulative necrosis. A remarkable finding was the presence of villous atrophy, cryptal hyperplasia and intraepithelial lymphocytosis. Immunohistochemical study showed that the tumor cells expressed CD3, CD43 and CD8 (14/14). Some of them were also positive for CD56 (11/14) and CD30 (2/14). The staining for CD4, CD20, CD79a and myeloperoxidase was negative. A high proliferation index was demonstrated by Ki-67 immunostain. In-situ hybridization for EBER was negative. Follow-up data were available in 9 cases. The duration of follow-up ranged from 6 months to 36 months. Seven patients died within 14 months.</p><p><b>CONCLUSIONS</b>EATL is a rare type of lymphoma with intestinal involvement. Associated enteropathy is not demonstrated, in contrast to cases encountered in Nordic countries. A correct diagnosis requires evaluation of clinical manifestations, pathologic features and ancillary study results.</p>

Immunohistochemistry using epidermal growth factor receptor mutation-specific antibodies of delE746-A750 and L858R in lung adenocarcinomas / 中华病理学杂志

<p><b>OBJECTIVE</b>To evaluate the immunohistochemical detection of epidermal growth factor receptor(EGFR) mutations using two EGFR mutation-specific monoclonal antibodies: delE746-A750 and L858R.</p><p><b>METHODS</b>A total of 175 paraffin-embedded lung adenocarcinoma tissue samples previously genotyped by directive DNA sequencing were subject to immunostaining using delE746-A750 and L858R antibodies.</p><p><b>RESULTS</b>There was no significant difference of mutation detection between DNA sequence analysis and delE746-A750 and/or L858R immunostaining (33.7% vs 30.9%, P > 0.05). The overall sensitivity, specificity, positive predictive value and negative predictive value of immunostaining using these two EGFR mutation-specific antibodies were 83.1%, 95.7%, 90.7% and 90.9%, respectively.</p><p><b>CONCLUSION</b>With high sensitivity and good specificity, immunohistochemistry using EGFR mutation-specific monoclonal antibodies is an adequate, easy and cost-effective prescreening method to detect EGFR mutations using paraffin-embedded tissue specimens of lung adenocarcinomas.</p>

Immunohistochemical study of perivascular epithelioid cell neoplasms / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features, immunophenotype and genetic changes of perivascular epithelioid cell neoplasms (PEComa).</p><p><b>METHODS</b>A total of 25 cases of PEComa located in various anatomic sites were selected for immunohistochemical staining (SP or EnVision method). TFE3 fluorescence in-situ hybridization was also performed to determine the TFE3 gene status.</p><p><b>RESULTS</b>The age of patient ranged from 21 to 61 years (mean = 43 years). The male-to-female ratio was 1: 1.3. Histologically, 22 cases represented conventional angiomyolipomas, composed of a mixture of adipose tissue, spindle element, epithelioid smooth muscle cells and abnormal thick-walled blood vessels in various proportions. Three cases involving lung, soft tissue and broad ligament had subtle but distinctive morphologic features. Nested or sheet-like architecture with epithelioid or spindle cells was observed. Immunohistochemical study showed that HMB 45, melan A, smooth muscle actin and cathepsin K were expressed in 80% (20/25), 88% (22/25), 88% (22/25) and 100% (25/25) of PEComa, respectively. Within positive cases, the average proportion of positive tumor cells was 36%, 41%, 35% and 90% respectively for HMB 45, melan A, smooth muscle actin and cathepsin K. TFE3 was negative in all of the 22 renal and hepatic PEComa studied, while it was positive in the 3 cases of extra-hepatorenal PEComa. None of the 25 cases exhibited evidence of TFE3 gene fusion or amplification.</p><p><b>CONCLUSIONS</b>Extra-hepatorenal PEComa have distinctive morphologic features and are associated with TFE3 overexpression. Cathepsin K immunostaining demonstrates high sensitivity and specificity in PEComa, better than other commonly employed immunomarkers. This marker is thus useful in diagnosis of PEComa and distinction with other neoplasms.</p>

Relevance of molecular alterations in histopathologic subtyping of lung adenocarcinoma based on 2011 International Multidisciplinary Lung Adenocarcinoma Classification / 中华病理学杂志

<p><b>OBJECTIVE</b>To evaluate the relevance of molecular alterations and histopathological subtypes of lung adenocarcinoma according to 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society International Multidisciplinary Lung Adenocarcinoma Classification.</p><p><b>METHODS</b>Mutations of epidermal growth factor receptor (EGFR) 18-21 exons (E18-21), KRAS 12/13 codons and EML4-ALK fusion in 212 cases of lung adenocarcinoma which underwent complete tumor resection, were detected by immunohistochemistry, PCR-amplifying and gene sequencing. The relevance of the molecular alterations to histopathological subtypes based on the new classification and 2004 WHO classification were further characterized.</p><p><b>RESULTS</b>Mutations of EGFR were observed in 49.6% of lung adenocarcinomas, involving mainly E21 (52.4%, 55/105) and E19 (36.2%, 38/105). Mutations of KRAS were detected in 8% cases of adenocarcinoma, involving mainly codon 12 (15/17). EML4-ALK fusions were found in 6.1% of lung adenocarcinoma, the most common fusion mutation was type V1 (E13; A20) (7/13), followed by type V3a/b (E6a/b; A20) (4/13). Based on the new classification, 7/10 lepidic, 63.2% (48/76) papillary, and 5/8 micropapillary predominant adenocarcinomas harbored EGFR mutations. EGFR mutations showed significant difference among different histological subtypes (P = 0.008). KRAS mutations were most frequently found in invasive mucinous adenocarcinoma (1/2), followed by colloid predominant adenocarcinoma (3/7). There was significant difference of KRAS mutations among different histological subtypes (P = 0.003). EML4-ALK fusions were most frequently found in the solid predominant with mucin production subtype (15.4%, 6/39), followed by colloid predominant adenocarcinoma (1/7), and no significant difference of EML4-ALK fusions was found among different histological subtypes (P = 0.181). Significant TTF-1 overexpression was observed in adenocarcinomas harbored EGFR mutations (P = 0.008), and no or significantly lower level expression of TTF-1 was observed in adenocarcinomas harbored KRAS mutations (P = 0.000). However, there was no association between TTF-1 expression and EML4-ALK fusions (P = 0.274). Based on the 2004 WHO classification, mutations of KRAS (P = 0.002) and EML4-ALK (P = 0.000), rather than EGFR (P = 0.502), showed significant differences among different subtypes. According to both classification systems, the difference of "triple negative" adenocarcinomas was not significant among different subtypes (P = 0.684, P = 0.449, respectively).</p><p><b>CONCLUSIONS</b>The new classification, combined with TTF-1 immunomarker, can help to predict the molecular alterations of EGFR and KRAS genes, but can not indicate the EML4-ALK fusion in lung adenocarcinoma. Lepidic, papillary, and micropapillary predominant adenocarcinomas with TTF-1 expression are closely related to the presence of EGFR mutation, and invasive mucinous adenocarcinoma, while colloid predominant adenocarcinoma without TTF-1 expression is closely related to the presence of KRAS mutation.</p>

Protective effect of Annexin 5 on human sperm membrane and DNA integrity / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the role of Annexin 5 in protecting human sperm membrane and DNA integrity.</p><p><b>METHODS</b>We collected 53 semen samples based on the criteria of sperm density > 20 x 10(6)/ml and motility > 60%, and divided them into an experimental group (2.5 microl 10(-6) mol/L Annexin 5 added to 47.5 microl semen), a negative control group (2.5 microl 1 mol/L Tris-HCl [pH 8.0, 25 degrees C] added to 47.5 microl semen), and a blank control group (2.5 microl 0.01 mol/L PBS [pH 7.4] added to 47.5 microl semen). After 20 minutes of incubation, we evaluated the sperm membrane integrity using the hypoosmotic swelling test and, after another 60 minutes of treatment with H2O2 at 2.5 microl 10.02 mol/L, measured the sperm nuclear DNA integrity by acridine orange fluorescent staining.</p><p><b>RESULTS</b>After 20 minutes of treatment with Annexin 5, the experimental group showed extremely significant difference in the percentage of hypoosmotic swelling sperm ([66.17 +/- 12.02] %) from the blank control ([58.13 +/- 13.08]%, P < 0.01) and the negative control group ([59.94 +/- 11.91]%, P < 0.01), but there was no significant difference between the latter two. Treatment with H2O2 remarkably increased DFI in the experimental group (6.39 +/- 1.07) as compared with the blank control (11.16 +/- 1.16) and the negative control group (10.86 +/- 1.05, P < 0.01), but no significant difference was observed between the latter two.</p><p><b>CONCLUSION</b>Annexin 5 can increase the percentage of hypoosmotic swelling sperm in vitro and protect sperm membrane integrity, and it can also protect sperm DNA from H2O2 damage.</p>

Expression of rat annexin 5 and its effect on human sperm motility in vitro / 中华男科学杂志

<p><b>OBJECTIVE</b>Gonadotropin releasing hormones (GnRH) regulate the expression of annexin 5 in Leydig cells, and annexin 5 is supposed to be a signal molecule in regulating testosterone secretion. This study aimed to investigate the function of annexin 5 in male reproduction by observing its effect on human sperm motility in vitro.</p><p><b>METHODS</b>The encoding sequence of rat annexin 5 was chemically synthesized and inserted into the HIS fusion expression vector pET28a. The expression of the fusion protein HIS-annexin 5 was induced by isopropyl-beta-D-thiogalactoside (IPTG) under the control of the T7 promoter, and the products were purified by affinity chromatography. The anticoagulant activity of annexin 5 was determined by the modified activated partial thromboplastin time (APTT) test. Semen samples from 15 donors were assigned to a control and an annexin 5 group, the latter treated with recombinant annexin 5 at the concentration of 10(-8) mol/L. Sperm motility and the percentage of grade a + b sperm were measured by computer-assisted semen analysis (CASA) after 20 and 60 min exposure, and the sperm ascending experiment was done after 20 min treatment.</p><p><b>RESULTS</b>The product of the synthesized target gene was 947 bp in length, and the inserted sequence corresponded to the published encoding sequence of rat annexin 5. The plasmid pET28a-annexin 5 was transformed into E. coli BL21(DE3) and IPTG induced a fusion protein with a relative molecular weight of about 36,000, a purity of 95% and a high anticoagulant activity. Compared with the control group, sperm motility and the percentage of grade a + b sperm were increased by 40% (P < 0.01) and 21% (P < 0.01), respectively, after 20 min treatment with annexin 5, but neither showed any significant improvement after 60 min. The sperm ascending altitude was remarkably elevated after annexin 5 treatment, with extremely significant difference from the control group (37.84 +/- 6.35 vs. 49.5 +/- 12.27, P < 0.01).</p><p><b>CONCLUSION</b>An annexin 5 recombinant expression vector was successfully constructed. The protein annexin 5 can be efficiently expressed in E. coli and effectively improve human sperm motility in vitro.</p>

Effects of GnRH analogues on MAPK pathway in rat Leydig cells / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the effects of GnRH analogues GnRHa and GnRHant on the MAPK pathway in rat Leydig cells.</p><p><b>METHODS</b>Rat Leydig cells were primarily cultured for 24 hours in vitro and serum-starved for 2 hours, followed by treatment with GnRHa (10(-7) mol/L) or GnRHant (10(-6) mol/L) for 0, 5, 15, 30, 60 and 90 minutes, with the 0 min group as the control. Then the protein levels of phosphorylated ERK (p-ERK) and phosphorylated p38 (p-p38) were detected by Western blot, and that of p-ERK determined by the same means after co-incubation of GnRHa or GnRHant with the PKC inhibitor GF109203X at 1, 5, 10 and 20 micromol/L.</p><p><b>RESULTS</b>After stimulation of the Leydig cells with GnRHa or GnRHant for different times, the protein level of p-p38 showed no significant difference from that of the control group (P > 0.05). Then the Leydig cells were treated with GF109203X at different concentrations for 20 minutes and with addition of GnRHa for another 10 minutes. The level of p-ERK was significantly decreased (P < 0.05) by GF109203X at 10 and 20 micromol/L. Compared with the control, the p-ERK expression was increased by 65% at 15 minutes (P < 0.05) in the GnRHant stimulation group, by 81% (to the peak) at 30 minutes (P < 0.05), began to fall at 60 minutes, and returned to the base level at 90 minutes. The p-ERK level exhibited no significant difference from that of the control (P > 0.05) after treatment of the Leydig cells with different concentrations of GF109203X for 20 minutes and then with GnRHant for 30 minutes.</p><p><b>CONCLUSION</b>The ERK MAPK activation induced by GnRHa depends on the PKC pathway, but not that induced by GnRHant. The p-38 MAPK pathway may not be involved in the effect of GnRH analogues on rat Leydig cells.</p>

Effect of sophocarpine on HERG K+ channels / 药学学报

Human ether-a-go-go-related gene (HERG) encodes the rapid component of the cardiac delayed rectifier K+ current, which has an important effect on both proarrhythmia and antiarrhythmia. To investigate the effect of sophocarpine (SC) on HERG channel stably expressing in human embryonic kidney-293 (HEK293) cells, whole-cell patch-clamp technique was used to record HERG current and kinetic curves. As the result, it was found that SC inhibited HERG current in a concentration-dependent manner (10, 30, 100, and 300 micromol x L(-1)). At 0 mV, 10, 30, 100, and 300 micromol x L(-1) SC respectively inhibited IHERG by Istep ( 10.7 +/- 2.8)% , (11.3 +/- 5.5)% , (47.0 +/- 2.3)% and (53.7 +/- 2.5)% , and Itail (1.1 +/- 3.0)%, (17.1 +/- 3.3)%, (32.7 +/- 1.9)% (P < 0.05, n = 12) and (56.0 +/- 2.4)% (P < 0.05, n = 13). The time constants of inactivation, recovery from inactivation and onset of inactivation were accelerated. SC did not change other channel kinetics (activation and deactivation). It is concluded that SC inhibited the transfected HERG channels by influencing the inactivation state, which is the probable anti-arrhythmic mechanism.

Effect of cardiopulmonary bypass on CD11/CD18 expression of neutrophils in children undergoing cardiac surgery / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the changes in perioperative expression level of CD11/CD18 of neutrophils in children undergoing cardiac surgery with cardiopulmonary bypass (CPB).</p><p><b>METHODS</b>Thirty children patients with congenital heart disease underwent cardiac surgery with CPB (CPB group) and the control group consisted of 20 children who received thoracic or general surgery without CPB. Blood samples were drawn at the following time points: pre-surgery, 15 min after onset of CPB, immediately after CPB, 2 h after surgery and on the 1st, 2nd, 3rd postoperative day. D11/CD18 expression on neutrophils and serum concentration of IL-6 and IL-8 were analyzed by flow cytometry and enzyme-linked immunosorbent assay, respectively.</p><p><b>RESULT</b>In CPB group plasma levels of IL-6 and IL-8 increased significantly and peaked at 2 h after initiation of CPB (P<0.05), and descended to the after-anesthesia level at 3rd day after operation. In non-CPB group there was a similar trend of changes in IL-6 and IL-8, but to a much lesser extent. The level of CD11b/CD18 in CPB group began to increase significantly and peaked at 15 min after initiation of CPB (P <0.05), and descended to the after-anesthesia level at 2 h after operation. There was no significant changes of CD11b/CD18 in control group (P >0.05). No significant differences were detected at any time points with respect to expression of CD11a/CD18 and CD11c/CD18 in both groups (P >0.05).</p><p><b>CONCLUSION</b>CPB surgery of children can cause increasing of the CD11b/CD18 expression level of neutrophil but has no significant effect on CD11a/CD18 and CD11c/CD18. CD11b/CD18 may play an important role in the systemic inflammation induced by CPB.</p>

Interleukin 10.G microsatellite in the promoter region of the interleukin-10 gene in severe sepsis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The highly polymorphic interleukin 10.G (IL10.G) microsatellite located in the promoter region of the interleukin-10 (IL-10) gene exerts a positive transcriptional regulatory effect on IL-10 gene expression and correlates with the in vitro IL-10 secretion. This study was conducted to investigate whether IL10.G microsatellite is associated with the incidence and/or the outcome of severe sepsis.</p><p><b>METHODS</b>One hundred and fifteen patients with severe sepsis who had been treated at the intensive care unit of the university hospital were studied. One hundred and forty-one healthy individuals served as controls. IL10.G microsatellite genotyping was performed with the following two methods: fluorescent based polymerase chain reaction (PCR) techniques and silver staining of the amplified DNA fragment in polyacrylamide gel. Alleles were defined according to the size of the amplified DNA product.</p><p><b>RESULTS</b>Ten alleles and 36 genotypes were detected both in the patients with severe sepsis and in the healthy controls. Allele IL10.G9 and allele IL10.G13 were the commonest alleles with the frequencies of 32.6% and 21.3% respectively in the patients with severe sepsis, and 34% and 27% respectively in the healthy controls. The allele frequencies of IL10.G microsatellite were neither different between the patients with severe sepsis and the healthy controls (P > 0.05), nor between survivors and non-survivors (P > 0.05). However, the frequency of one common allele IL10.G13 was slightly lower in the patients with severe sepsis than in the healthy controls (21.3% vs 27%, P > 0.05), and the frequency of allele IL10.G9 was slightly higher in the non-survivors than in the survivors (37.1% vs 28.1%, P > 0.05).</p><p><b>CONCLUSION</b>IL10.G microsatellite may neither contribute to the susceptibility to severe sepsis nor to the fatal outcome of severe sepsis.</p>