[Clinicopathologic features of glomus tumor of the kidney].

Objective: To investigate the clinicopathologic and differential diagnostic features of glomus tumor of the kidney. Methods: Four cases of glomus tumor of the kidney were collected from the archives of Peking University Third Hospital, the Second Hospital of Tianjin Medical University, Ningbo Yinzhou Second Hospital and Zhejiang Provincial People's Hospital between January 2012 to June 2017; the clinical and radiologic features, histomorphology, immunohistochemistry, ultrastucture and prognosis were analyzed and the relevant literature was reviewed. Results: Patients consisted of 2 men and 2 women with ages ranging from 37 years to 66 years (mean 55 years). Three patients had history of hypertensive disease (grade Ⅱ, 3 to 10 years). The tumors measured in maximum diameter from 3.0 cm to 4.0 cm (mean 3.6 cm) and showed gray-white to yellow and tan on cut surface. Macroscopical examinations showed all tumors were circumscribed but non-encapsulated. Histologically, 1 tumor presented as glomus tumor with extensive myxoid change, 1 as cellular and solid pattern glomus tumor, 1 as glomangioma with focal myopericytoma-like pattern and 1 as symplastic glomus tumor with areas resembling myopericytoma. The tumor cells in two cases showed scant cytoplasm and uniform, bland-appearing nuclei without mitoses. In one case, the tumor cells were epithelioid with abundant eosinophilic cytoplasm and relatively well-defined cell borders. There was an increased mitosis of 4/50 HPF; however, no evidence of atypical mitosis or nuclear atypia was noted. In the symplastic glomus tumor the tumor cells showed frequently nuclear pleomorphism without mitoses. By immunohistochemistry, all tumors showed strong and diffuse reactivities to at least 3 of the 4 muscle-associated markers (SMA, h-Caldesmon, MSA and Calponin), 3 tumors strongly and diffusely expressed collagen Ⅳ, 2 expressed CD34 and 1 focally expressed desmin; whereas markers including epithelial, neuroendocrine, nephrogenic, melanoma-associated, STAT6, S-100 protein, CD117 and ß-catenin all were negative in all the 4 tumors. Ultrastuctural analysis was done in 2 cases and showed prominent cytoplasmic actin bundles and pericellular basement membrane, and lacking of rhomboid renin crystals in both tumors. The hypertension persisted after surgical resection for all the 3 patients with this medical history. Follow-up information (range: 6-64 months, mean: 44 months)showed that no evidence of local recurrence or distant metastasis was identified in all 4 patients. Conclusions: Glomus tumor rarely occurs in the kidney and usually has a good prognosis. Careful attention to its morphology with the judicious use of immunohistochemistry and ultrastuctural analysis can be helpful for its diagnosis and differential diagnosis.

[Platelet to lymphocyte ratio in peripheral blood and body mass index: novel independent prognostic factors in patients with melanoma].

Objective: To investigate whether platelet to lymphocyte ratio (PLR) in peripheral blood and body mass index (BMI) can be independent prognostic factors in patients with melanoma. Methods: Clinical date of 140 patients with melanoma in the Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital from January 1, 2010 to December 31, 2015 were analyzed retrospectively.Receiver operating characteristic (ROC) curve was performed the optimal cut-off value for PLR.The 140 patients were divided into high PLR group and low PLR group.According to "Guidelines for prevention and control of overweight and obesity in Chinese adults" , the patients were divided into high BMI group and low BMI group.The relationship between PLR, BMI with overall survival (OS), progression free survival (PFS) and disease free survival (DFS) were analyzed.The Kaplan-Meier method and Log rank test was used for univariate survival analysis and Cox proportional hazards regression model for multivariate analysis. Results: The optimal cut-off value of PLR determined by ROC curve was PLR=120.15, and BMI threshold was 24.Univariate survival analysis showed that PLR, BMI and clinical stage were the factors affecting the OS in patients (P<0.05). The median survival time (MST) was 21 months in the whole group and 17 months in the high PLR group, 34 months in the low PLR group, respectively; the MST in the high and low BMI group were 29 months and 13 months, respectively.The difference was statistically significant (P<0.05). The effects of PLR and BMI on PFS and DFS were not statistically significant.Cox multivariate analysis showed that PLR, BMI and clinical stage were independent prognostic factors of OS (P<0.05). And BMI was the only independent protective factor for OS, the risk of death decreased by 0.611 times, with each unit increased for BMI.Clinical subgroup analysis showed that PLR also was risk factor to the prognosis of patients with stage Ⅱ, Ⅲ, and Ⅳ (P<0.05). Conclusions: PLR is an independent prognostic risk factor for patients with melanoma, and BMI is an independent protective factor.PLR and BMI are important factors in prognostic evaluation of melanoma.

[Association between long term systolic blood pressure variability index and cognitive function in middle-aged and elderly people].

OBJECTIVE: To investigate the association between different long term systolic blood pressure variability (SBPV) and cognitive function in middle-aged and elderly people. METHODS: A total of 101 510 employees from the Tangshan Kailuan Group participated in the 2006-2007 annual physical examination, 5 440 cases were selected by simple randomly sampling method. After excluding participants who did not underwent 2012-2013 examination and without complete blood pressure and mini-mental state examination (MMSE) score, 3 002 participants (1 627 males, (50.86±9.93) years old) with integrated data were included into the study. The long term SBPV was calculated by standard deviation(SD), maximum-minimum difference(MMD), average real variability (ARV) of mean systolic blood pressure measured in 2006-2007, 2008-2009, 2010-2011 and 2012-2013. Participants were grouped by the quartile of the different SBPV index. Multiple linear regressions analysis was used to analyze the correlation between the long term SBPV and cognitive function status. RESULTS: (1) The score of MMSE was 28.03±2.65. (2) The observation population was divided into four groups according to quartiles of different SBPV, respectively. The MMSE scores of SD<5.53 mmHg (1 mmHg=0.133 kPa)group, SD 5.53-8.90 mmHg group, SD 8.91-12.79 mmHg group and SD>12.79 mmHg group were 28.21±2.18, 28.26±3.09, 28.10±2.40 and 27.56±2.79, respectively(P<0.05). The MMSE scores of MMD<12.00 mmHg group, MMD 12.00-20.00 mmHg group, MMD 20.01-30.00 mmHg group and MMD>30.00 mmHg were 28.27±2.17, 28.25±3.09, 27.99±2.42 and 27.49±2.81, respectively(P<0.05). The MMSE scores of ARV<6.67 mmHg group, ARV 6.67-10.22 mmHg group, ARV 10.23-15.56 mmHg group and ARV>15.56 mmHg group were 28.27±2.20、28.28±3.20、28.00±2.42、27.57±2.65, respectively(P<0.05). (3) Adjusted for age, gender, baseline systolic blood pressure, body weight index, total cholesterol, fasting blood glucose, triglyceride, C reactive protein, smoke, drink, physical activity , the step-wise regressions analysis showed that SD(B=-0.129, P<0.05), MMD(B=-0.131, P<0.05), ARV(B=-0.125, P<0.05) had significant negative linear relationship with the MMSE score in the objects not taking the anti-hypertension drugs, and SD(B=-0.329, P<0.05), MMD(B=-0.314, P<0.05), but not ARV(B=-0.233, P>0.05), had significant negative linear relationship with the MMSE score in the objects taking the anti-hypertension drugs. CONCLUSION: The long term SBPV indexes (SD, MMD, ARV ) are negatively correlated with the MMSE score in middle-aged and elderly people not taking the anti-hypertension drugs, and SD, MMD are negatively correlated with the MMSE score in people taking the anti-hypertension drugs. Clinical Trail Registry: Chinese Clinical Trail Registry, ChiCTRTNC-11001489.

Genetic transformation and expression of transgenic lines of Populus x euramericana with insect-resistance and salt-tolerance genes.

We characterized new transgenic varieties of poplar with multiple insect-resistant and salt stress tolerant genes. Two insect-resistant Bacillus thuringiensis (Bt) genes, Cry1Ac and Cry3A, and a salt-tolerant gene, Betaine aldehyde dehydrogenase (BADH) were inserted into a vector, p209-Cry1Ac-Cry3A-BADH. The clone of Populus x euramericana was transformed by the vector using the Agrobacterium-mediated method. Three transgenic lines were assessed using genetic detection and resistance expression analysis. PCR revealed that exogenous genes Cry1Ac, Cry3A, BADH and selective marker gene NPTII were present in three transgenic lines. Quantitative real-time PCR (qPCR) showed significant differences in the transcriptional abundance of three exogenous genes in different lines. Results of assays for Bt toxic proteins showed that the Cry1Ac and Cry3A toxic protein content of each line was 12.83-26.32 and 2108.91-2724.79 ng/g, respectively. The Cry1Ac toxic protein content of different lines was significantly different; the Cry3A toxic protein content was about 100 times higher than that of the Cry1Ac toxic protein. The insect-resistance test revealed the mortality rate of transgenic lines to Hyphantria cunea L1 larvae varied by 42.2-66.7%, which was significantly higher than non-transgenic lines. The mortality rate of L1 and L2 Plagiodera versicolora larvae was 100%. The insecticidal effect of transgenic lines to P. versicolora larvae was higher than that to H. cunea larvae. NaCl stress tolerance of three transgenic lines under 3-6% NaCl concentration was significantly higher than that of non-transgenic lines.

Effects of lead contamination on the clonal propagative ability of Phragmites australis (common reed) grown in wet and dry environments.

Clonal propagation is important for the survival and maintenance of the common reed Phragmites australis. Pot culture experiments were conducted to investigate the effects of lead (Pb) concentration (0, 500, 1500, 3000, 4500 mg·kg(-1) ) and water stress on the clonal reproductive ability of this species. The Pb concentration found in plant organs, in decreasing order, was roots >shoots >rhizomes. There was a negative relationship between the growth of clonal propagative modules (excluding axillary shoot buds) and Pb concentrations, which caused a decrease in biomass, rhizome growth and number of axillary and apical rhizome buds. Daughter axillary shoots exhibited a tolerance strategy, with no significant change in their number; the axillary and apical rhizome buds, daughter apical rhizome shoots and rhizomes exhibited compensatory growth during the late stage of Pb (excluding 4500 mg·kg(-1) ) treatment in a wet environment. Pb applications above 500 mg·kg(-1) reduced these parameters significantly in the drought treatment, except for the number of axillary shoot buds, which did not change. Our results indicate that clonal propagative resistance to Pb contamination can occur via tolerance strategies, compensatory growth and a Pb allocation strategy, enabling these reeds to maintain population stability in wet environments. However, clonal modular growth and reproductive ability were inhibited significantly by the interaction between drought and Pb, which would cause a decline in P. australis populations in a dry environment. Lead concentrations of 4500 and 500 mg·kg(-1) in soils might meet or exceed the Pb tolerance threshold of clonally propagated reeds in wet and dry environments, respectively.

Meta-analysis confirms that a common G/C variant in the pre-miR-146a gene contributes to cancer susceptibility and that ethnicity, gender and smoking status are risk factors.

Evidence has shown that miR-146a is involved in carcinogenesis, and a common G/C variant (rs2910164) in the pre-miR-146a gene has been associated with various types of cancer. We summarized the data from 22 published case-control studies on the association between rs2910164 and cancer risk and performed subgroup analyses by ethnicity, gender and smoking status. We found a significant association between the pre-miR-146a polymorphism and cancer risk in Caucasian populations (odds ratio (OR) = 0.93, 95% confidence interval (CI) = 0.88-0.99 for G- vs C-allele), while the significance was borderline in Asian populations (OR = 1.11, 95%CI = 1.00-1.23 for G- vs C-allele). A significantly increased risk of cancer was found in males with GG/GC genotypes (OR = 1.23, 95%CI = 1.10- 1.37), and the significance was more pronounced in smokers (OR = 1.82, 95%CI = 1.32-2.51) than in non-smokers (OR = 1.24, 95%CI = 1.01-1.53). We conclude that there is evidence that the pre-miR-146a polymorphism contributes to cancer susceptibilities and that gender and smoking status affect the probability of cancer in individuals with this polymorphism.

Reliable measurement of elastic modulus of cells by nanoindentation in an atomic force microscope.

The elastic modulus of an oral cancer cell line UM1 is investigated by nanoindentation in an atomic force microscope with a flat-ended tip. The commonly used Hertzian method gives apparent elastic modulus which increases with the loading rate, indicating strong effects of viscoelasticity. On the contrary, a rate-jump method developed for viscoelastic materials gives elastic modulus values which are independent of the rate-jump magnitude. The results show that the rate-jump method can be used as a standard protocol for measuring elastic stiffness of living cells, since the measured values are intrinsic properties of the cells.

Nonsteroidal selective glucocorticoid modulators: the effect of C-5 alkyl substitution on the transcriptional activation/repression profile of 2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinolines.

The preparation and characterization of a series of selective glucocorticoid receptor modulators are described. The preliminary structure-activity relationship of nonaromatic C-5 substitution on the tetracyclic quinoline core showed a preference for small lipophilic side chains. Proper substitution at this position maintained the transcriptional repression of proinflammatory transcription factors while diminishing the transcriptional activation activity of the ligand/glucocorticoid receptor complex. The optimal compounds described in this study were the allyl analogue 18 and cyclopentyl analogue 32. These candidates showed slightly less potent, highly efficacious E-selectin repression with significantly reduced levels of glucocorticoid response element activation in reporter gene assays vs prednisolone. Allyl analogue 18 was evaluated in vivo. An oral dose of 18 showed an ED(50) = 1.7 mg/kg as compared to 1.2 mg/kg for prednisolone in the Sephadex-induced pulmonary eosinophilia model and an ED(50) = 15 mg/kg vs 4 mg/kg for prednisolone in the carrageenan-induced paw edema model.

Synthesis and characterization of non-steroidal ligands for the glucocorticoid receptor: selective quinoline derivatives with prednisolone-equivalent functional activity.

A novel class of functional ligands for the human glucocorticoid receptor is described. Substituents in the C-10 position of the tetracyclic core are essential for glucocorticoid receptor (GR) selectivity versus other steroid receptors. The C-5 position is derivatized with meta-substituted aromatic groups, resulting in analogues with a high affinity for GR (K(i) = 2.4-9.3 nM) and functional activity comparable to prednisolone in reporter gene assays of glucocorticoid-mediated gene transcription. The biological activity of these novel quinolines was also prednisolone-equivalent in whole cell assays of glucocorticoid function, and compound 13 was similar to prednisolone (po ED(50) = 2.8 mpk for 13 vs ED(50) = 1.2 mpk for prednisolone) in a rodent model of asthma (sephadex-induced eosinophil influx).

[Clinical analysis of 36 cases with amebic liver abscess].

OBJECTIVE: To investigate the clinical features of amebic liver abscess, the causes of misdignosis and the effect of medical and surgical therapy on patient's prognosis. METHODS: The clinical features of 36 patients with amebic liver abscess admitted from 1982 to 1997 in our hospital were retrospectively reviewed. RESULTS: The major clinical manifestations were: abdominal pain (86.1%), fever (86.1%), hepatomegaly with tenderness (83.3%) and right intercostal tenderness (58.3%). Leukocytosis was observed in 61.1%, and increased of ESR in 88.5% (23/28). Serologies against Entamoeba histolytica were noted in 92.6%. Ultrasonography showed single lesions in 75% and right-lobe involvement in 75%. All patients were treated with metronidazole and 27 patients received treatment with needle aspiration or draining at the same time. After treatment, 10 patients were cured, 25 patients were improved significantly and effective rate was 97.2%. One patient died of hepatic failure. CONCLUSION: Medical therapy alone was excellent for small abscesses, while percutaneous needle aspiration or draining was a successful approach in patients with large abscesses.

Low frequency of the ccr5delta32 HIV-resistance allele in mainland China: identification of the first case of ccr5delta32 mutation in the Chinese population.

A 32-bp deletion on the CCR5 gene (ccr5delta32) confers resistance to HIV-1 infection. This deletion is common in Caucasians, but rare in Asians. Since the frequency of the ccr5delta32 allele of Chinese in mainland China has been unknown we investigated the ccr5delta32 mutation in a cohort of 407 Chinese people in this area. A 225-bp fragment of CCR5 encompassing the 32-bp region was analysed by PCR, hybridization and sequencing. Only 1 out of 407 subjects was heterozygous for ccr5delta32 and no homozygotes were detected. The frequency of ccr5delta32 in this cohort is thus 0.00123, i.e. much lower than that of Caucasians. The ccr5delta32 heterozygote is a healthy young man. To our knowledge this is the first ccr5delta32 mutant found in Chinese people. The results indicate that ccr5delta32 does exist in Chinese people, but at very low frequency. This suggests that ccr5delta32 is not a significant factor for the genetic resistance to HIV-1 in Chinese people.

The M4M5 cytoplasmic loop of the Na,K-ATPase, overexpressed in Escherichia coli, binds nucleoside triphosphates with the same selectivity as the intact native protein.

Escherichia coli was used to overexpress the large cytoplasmic loop of the rat Na,K-ATPase. A 1260-base DNA segment encoding Lys354-Lys774 of the rat alpha1-subunit was constructed via polymerase chain reaction. The polymerase chain reaction product was successfully subcloned into the expression vector pET-28 (Novagen), which produces an N-terminal 6-histidine-tagged fusion protein. The pET-28 vector containing rat alpha-loop, i.e. pAN, was used to transform calcium-competent E. coli BL21(DE3) cells, and positive clones were selected by kanamycin resistance. Bacterial cultures were grown, and protein synthesis was induced with isopropyl beta-D-thiogalactoside. Cells were harvested and lysed, revealing production of the His-tagged fusion protein ( approximately 46 kDa). The fusion protein was affinity-purified from other soluble cellular proteins via a Ni-NTA column, which routinely yielded approximately 20 mg of soluble His6-alpha-loop/L cell culture. The His6-alpha-loop retained significant native structure, as evidenced by the ability of ATP and ADP (but not AMP, CTP, GTP, or UTP) to protect against chemical modification by either fluorescein isothiocyanate or maleimidylanilinonapthalene sulfonic acid. More specifically, circular dichroism spectroscopy was used to estimate the secondary structure of the His6 loop, revealing an ordered folding composed of 23% alpha-helix, 23% antiparallel beta-sheet, 4% parallel beta-sheet, 19% beta-turn, and 32% random coil. The 6-histidine loop bound the fluorescent ATP analog trinitrophenyl-ATP with high affinity, as determined by measuring the fluorescence changes associated with binding. Affinities for ATP ( approximately 350 microM) and ADP ( approximately 550 microM) were determined by their ability to compete with and displace 2',3'-O-[2,4,6,-trinitrophenyl]-ATP. These nucleotide affinities are similar to those observed for the E2 conformation of the intact Na,K-ATPase.

Synthesis and immunosuppressant activity of pyrazole carboxamides.

A series of novel pyrazole carboxamides is disclosed that demonstrate strong immunosuppressant activity in rodent and human mixed leukocyte response (MLR) assays (IC50 < 1 microM). The synthesis, biological activity, mode of action, and pharmacokinetic properties of this new lead series are discussed.

Clinical pharmacokinetics and therapeutic efficacy of ceftriaxone in Chinese adults.

The pharmacokinetics of ceftriaxone were studied in 5 healthy Chinese volunteers who received single doses of 1 or 2 g by intravenous infusion at 2-weekly intervals. Only 50 microliters of plasma was required for the determination of plasma ceftriaxone concentrations using an improved high-performance liquid chromatography method. The interday variation was less than 5% and the relationship between peak height ratio and concentration was linear over the range 1-500 micrograms/ml. The distribution of ceftriaxone best fitted a two-compartment pharmacokinetic model, and the pharmacokinetic parameters were similar for the two doses. Furthermore, these pharmacokinetic parameters were similar in 20 adult Chinese patients who had received ceftriaxone, 1 g twice daily or 2 g once daily, for various severe bacterial infections. These parameters were, however, dependent on renal function. The rate of elimination and clearance of ceftriaxone were similar to the values reported for other nationalities. The therapeutic outcomes for patients receiving 1 g twice daily were two cures, three improvements and one failure, and for those receiving 2 g once daily, seven cures, four improvements and one failure. Once daily infusion of ceftriaxone therefore seems to be effective in the treatment of severe bacterial infections in Chinese patients.

[Etiological features and abnormal cerebrospinal fluid findings in 101 patients with suspected intracranial infections].

101 patients (44 males, 57 females) with suspected intracranial infections were admitted to PUMC Hospital from 1988 to 1993. Their age ranged from 16 to 65 years (mean 29). Based on etiological categories, viral meningitis or encephalitis was diagnosed in 37.6% of the patients, purulent meningitis in 20.8%, tuberculous meningitis in 19.8%, cryptococcal meningitis in 5.9%, cerebral cysticercosis in 5.9%, infections of unknown etiology in 5.0%, and noninfectious diseases in 4.0%. During hospitalization, the mortality rate for cryptococcal, tuberculous and purulent meningitis was 33.3%, 20.0% and 14.3% respectively. This study also showed that cerebrospinal fluid examination was helpful for etiological analysis or differential diagnosis of intracranial infections.

[Bacterial sepsis and nosocomial infection: a study of 70 patients].

74 episodes of bacterial sepsis in 70 patients were analysed from July 1988 to June 1989. The incidence of sepsis is 0.7% of the whole admitted patients. Compared to a similar previous study from April 1982 to March 1983, the incidence of sepsis decreased (P less than 0.01), and the incidence of nosocomial sepsis remained unchanged, whereas its mortality decreased (P less than 0.05). The host defenses are important in predisposing to sepsis and determining prognosis. Antibiotic sensitivity test revealed that some bacterial strains were resistant to new beta-lactam antibiotics.

[Clinical analysis of 130 patients with fever of unknown origin].

Hospital records of 130 patients with fever of unknown origin (FUO) from 1985 to 1989 were studied. Etiologic diagnoses were made in 117 (90%) patients, 60 (46.1%) patients had infections, 22 (16.9%) neoplasms, 19 (14.6%) connective tissue diseases, and 16(12.3%) various diseases grouped under "miscellaneous", 10% of the FUO cases remained undiagnosed and the death rate was 13.8%. This clinical analysis showed that infection was the most frequent cause of FUO in this series.