Revolution spectral CT for urinary stone with a single/mixed composition in vivo: a large sample analysis.

PURPOSE: To analyze various compositions of urinary stones using revolution spectral CT (rapid kV switching dual-energy CT) in vivo. METHODS: 202 patients with urinary stones underwent spectral CT before surgery. Zeff peak, overall scope and CT values were detected. Moreover, water/iodine attenuating material images were obtained. Removed stones were subjected to infrared spectroscopy after surgery. The results of infrared spectroscopy were compared with CT. RESULTS: 28 stones (14.08%) with single composition, 165 stones with two mixed compositions (81.68%), and 9 stones with three mixed compositions (4.46%) were observed. When Zeff peaks of stones with single/mixed compositions were summarized together, 146 peaks of calcium oxalate monohydrate, 119 peaks of calcium oxalate dihydrate, 55 peaks of carbapatite, 38 peaks of urate, 16 peaks of struvite, and 11 peaks of brushite were totally observed. 93.8% of calcium oxalate monohydrate had Zeff peaks between 13.3 and 14.0. 91.6% of calcium oxalate dihydrate had peaks between 12.0 and 13.3. For carbapatite, 90.9% of stones had peaks from 14.0 to 15.0. A total of 94.8% of urate had peaks between 7.0 and 11.0. 93.8% of struvite had peaks between 11.0 and 13.0, and 90.9% of brushite had peaks between 12.0 and 14.0. Moreover, densities of urate, struvite and brushite were low density in iodine-based images and high-density in water-based images. CONCLUSION: The in-vivo analysis of spectral CT in urinary stone revealed characteristics of different compositions, especially mixed compositions. An in-vivo predictive model may be constructed to distinguish stone compositions.

Atypical extraventricular neurocytoma: A case report.

Atypical extraventricular neurocytoma (EVN) is a rare condition characterized by diffuse tumor cell hyperplasia, increased neovascularization, increased necrosis, and aggressive characteristics. A case of a 25-year old man who presented with atypical EVN in his left parietal - occipital flaps is reported. Magnetic resonance imaging (MRI) revealed a well-defined globular mass with heterogeneous signals in the left parietal lobe, and mild perilesional edema. After left parietal craniotomy and tumor excision, pathologic examination of the resected tissue revealed that the lesion was localized mainly in the white matter and imbued with tumor cells possessing round hyperchromatic nuclei with perinuclear halos and increased microvascular proliferation. The patient underwent radiotherapy at 21st postoperative day. Over the past 26 months, the patient has been regularly followed up, and so far no neurologic deficits have been observed. The latest MRI showed that the tumor bed was stable with slight peritumoral edema. The results of clinical, histopathological and immunohistochemical examinations indicate that atypical EVN is a rare neoplasm with unique radiographic and pathologic characteristics. It possesses more aggressive properties than typical EVN.

PARP1 interacts with HMGB1 and promotes its nuclear export in pathological myocardial hypertrophy.

High-mobility group box 1 (HMGB1) exhibits various functions according to its subcellular location, which is finely conditioned by diverse post-translational modifications, such as acetylation. The nuclear HMGB1 may prevent from cardiac hypertrophy, whereas its exogenous protein is proven to induce hypertrophic response. This present study sought to investigate the regulatory relationships between poly(ADP-ribose) polymerase 1 (PARP1) and HMGB1 in the process of pathological myocardial hypertrophy. Primary-cultured neonatal rat cardiomyocytes (NRCMs) were respectively incubated with three cardiac hypertrophic stimulants, including angiotensin II (Ang II), phenylephrine (PE), and isoproterenol (ISO), and cell surface area and the mRNA expression of hypertrophic biomarkers were measured. the catalytic activity of PARP1 was remarkably enhanced, meanwhile HMGB1 excluded from the nucleus. PARP1 overexpression by infecting with adenovirus PARP1 (Ad-PARP1) promoted the nuclear export of HMGB1, facilitated its secretion outside the cell, aggravated cardiomyocyte hypertrophy, which could be alleviated by HMGB1 overexpression. PE treatment led to the similar results, while that effect was widely depressed by PARP1 silencing or its specific inhibitor AG14361. Moreover, SD rats were intraperitoneally injected with 3-aminobenzamide (3AB, 20 mg/kg every day, a well-established PARP1 inhibitor) 7 days after abdominal aortic constriction (AAC) surgery for 6 weeks, echocardiography and morphometry of the hearts were measured. Pre-treatment of 3AB relieved AAC-caused the translocation of nuclear HMGB1 protein, cardiac hypertrophy, and heart dysfunction. Our research offers a novel evidence that PARP1 combines with HMGB1 and accelerates its translocation from nucleus to cytoplasm, and the course finally causes cardiac hypertrophy.

mTORC2 facilitates endothelial cell senescence by suppressing Nrf2 expression via the Akt/GSK-3ß/C/EBPα signaling pathway.

Vascular endothelial cell senescence is a leading cause of age-associated and vascular diseases. Mammalian target of rapamycin complex 2 (mTORC2) is a conserved serine/threonine (Ser/Thr) protein kinase that plays an important regulatory role in various cellular processes. However, its impact on endothelial senescence remains controversial. In this study we investigated the role and molecular mechanisms of mTORC2 in endothelial senescence. A replicative senescence model and H2O2-induced premature senescence model were established in primary cultured human umbilical vein endothelial cells (HUVECs). In these senescence models, the formation and activation of mTORC2 were significantly increased, evidenced by the increases in binding of Rictor (the essential component of mTORC2) to mTOR, phosphorylation of mTOR at Ser2481 and phosphorylation of Akt (the effector of mTORC2) at Ser473. Knockdown of Rictor or treatment with the Akt inhibitor MK-2206 attenuated senescence-associated ß-galactosidase (ß-gal) staining and expression of p53 and p21 proteins in the senescent endothelial cells, suggesting that mTORC2/Akt facilitates endothelial senescence. The effect of mTORC2/Akt on endothelial senescence was due to suppression of nuclear factor erythroid 2-related factor 2 (Nrf2) at the transcriptional level, since knockdown of Rictor reversed the reduction of Nrf2 mRNA expression in endothelial senescence. Furthermore, mTORC2 suppressed the expression of Nrf2 via the Akt/GSK-3ß/C/EBPα signaling pathway. These results suggest that the mTORC2/Akt/GSK-3ß/C/EBPα/Nrf2 signaling pathway is involved in both replicative and inducible endothelial senescence. The deleterious role of mTORC2 in endothelial cell senescence suggests therapeutic strategies (targeting mTORC2) for aging-associated diseases and vascular diseases.

Defective Metal-Organic Frameworks Incorporating Iridium-Based Metalloligands: Sorption and Dye Degradation Properties.

Artificial control and engineering of metal-organic framework (MOF) crystals with defects can endow them with suitable properties for applications in gas storage, separation, and catalysis. A series of defective iridium-containing MOFs, [Zn4 (µ4 -O)(Ir-A)2(1-x) (Ir-B)2x ] (ZnIr-MOF-dx ), were synthesized by doping heterostructured linker Ir-BH3 into the parent [Zn4 (µ4 -O)(Ir-A)2 ] (ZnIr-MOF), in which Ir-AH3 represents [Ir(ppy-COOH)3 ] (ppyCOOH=3-(pyridin-2-yl)benzoic acid) and Ir-BH3 is [Ir(ppy-COOH)2 (2-pyPO3 H)] (2-pyPO3 H2 =2-pyridylphosphonic acid). Samples with different degrees of defects were characterized by SEM, IR and NMR spectroscopy, powder XRD measurements, and thermal and elemental analyses. ZnIr-MOF-d0.3 was selected as a representative for gas (N2 , CO2 ) or vapor (H2 O, alcohol) sorption studies. The results demonstrate that defective ZnIr-MOF-d0.3 possesses multiple pore size distributions, ranging from micro- to mesopores, unlike the parent material, which shows a uniform micropore distribution. The hydrophilicity of the interior surface is also increased after defect engineering. As a result, ZnIr-MOF-d0.3 shows an enhanced adsorption capability toward n-butanol, relative to that of the parent compound. Optical studies reveal that both ZnIr-MOF and ZnIr-MOF-d0.3 have low band gaps (2.35 and 2.40 eV), corresponding to semiconductors. ZnIr-MOF-d0.3 exhibits dramatically increased photocatalytic efficiency for dye degradation.

Macrophage migration inhibitory factor promoter polymorphisms (-794 CATT5-8): Relationship with soluble MIF levels in coronary atherosclerotic disease subjects.

BACKGROUND: We analyzed the relationship of -794 CATT5-8 MIF polymorphisms with soluble MIF in Coronary Atherosclerotic Disease (CAD) patients. METHODS: A total of 256 patients selected, on which 186 normal-coronary and 70 Coronary artery disease subjects, were recruited in the study (Retrospectively registered). Genotyping of -794 CATT5-8 polymorphisms were performed by PCR and DNA sequencing. Serum MIF levels were measured using an ELISA kit. Patients were classified by coronary angiogram, and CAD based on Gensini's integral degree (angiographic scoring system). RESULTS: The allele frequency and genotype frequency of -794 CATT5-8 did not show any differences in normal-coronary subjects and CAD subjects. In CAD patients, serum MIF levels was lower in CATT (5) subjects than in CATT (7) subjects, while the genotype of -794 CATT5-8 did not show differences in serum MIF levels. In addition, we found a decrease in serum MIF levels in carriers of the (5/5) genotypes the -794 CATT5-8 MIF polymorphisms, although it was not significant. There was no relationship of CAD class and the allele frequency of -794 CATT5-8. CONCLUSIONS: This study found no association between CAD class and -794 CATT5-8 MIF polymorphisms with soluble MIF levels in CAD Subjects. TRIAL REGISTRATION: NCT01750502 (November 2012, Retrospectively registered).

Where is the exact origin of narrow premature ventricular contractions manifesting qR in inferior wall leads?

BACKGROUND: In recent years, radiofrequency catheter ablation(RFCA) has been established as an effective therapy for idiopathic premature ventricular contractions (PVCs), however, its effect on the narrow PVCs (QRS duration < 130 msec) with qR pattern in inferior leads, may not been fully concluded. METHODS: Characteristics of 12-lead electrocardiogram (ECG) and electrophysiologic recordings were analyzed in 40 patients with symptomatic PVCs manifesting narrow QRS complex with qR pattern in inferior leads. The procedure of RFCA was performed based on pace mapping and activation mapping. RESULTS: Among the 40 patients with narrow PVCs, complete elimination of PVCs was achieved by RFCA in 35 patients during a median follow-up period of 23 months. Successful ablation was achieved on 19 patients at the sites where earliest Purkinje potentials were recorded in left ventricular anterosuperior septum, thus PVCs arising from left anterior fascicle (LAF) were confirmed, for these PVCs, the QRS morphology were right bundle branch and left posterior fascicle block (RBBB + LPFB) with rightward axis, the average QRS duration 116.07 ± 7.96 ms, R or rsR'in lead V1,with transition zone ahead of lead V1 in precordial leads. Another 16 successful RFCA were achieved by energy delivery at interleaflet triangle(ILT) between right coronary cusp(RCC) and left coronary cusp(LCC) where no Purkinje potentials were recorded, for narrow PVCs arising from the L-RCC ILT, the QRS morphology were similar to the PVCs arising from LAF but much narrower in QRS duration (100.44 ± 3.49 vs. 116.07 ± 7.96 ms, p < 0.05), they were also R or Rs in lead V1 with the transition zone ahead of lead V1. For 5 symptomatic narrow PVCs failed to the procedure of RFCA, their electrocardiographic characteristics showed that the narrowest QRS duration (91.80 ± 6.94 vs. 100.44 ± 3.49, 116.07 ± 7.96 ms, p < 0.05), rs or rS (r/s or r/S≦1) morphology in lead V1 with the precordial transition zone behind lead V3. CONCLUSIONS: Most of idiopathic PVCs of narrow QRS duration (<130 msec) with qR pattern in inferior leads can be cured by the procedure of RFCA. On the basis of our study, we proposed that for narrow PVCs presenting qR pattern in inferior leads, when the ablation procedure failed at proximity of LAF within left anterosuperior septum, mapping and ablation in L-RCC ILT can be tried. The present findings can be helpful for planning catheter ablation for narrow PVCs manifesting qR in inferior leads.

Gastrointestinal manifestations of critical ill heatstroke patients and their associations with outcomes: A multicentre, retrospective, observational study.

BACKGROUND: Extreme heat exposure is a growing health problem, and the effects of heat on the gastrointestinal (GI) tract is unknown. This study aimed to assess the incidence of GI symptoms associated with heatstroke and its impact on outcomes. AIM: To assess the incidence of GI symptoms associated with heatstroke and its impact on outcomes. METHODS: Patients admitted to the intensive care unit (ICU) due to heatstroke were included from 83 centres. Patient history, laboratory results, and clinically relevant outcomes were recorded at ICU admission and daily until up to day 15, ICU discharge, or death. GI symptoms, including nausea/vomiting, diarrhoea, flatulence, and bloody stools, were recorded. The characteristics of patients with heatstroke concomitant with GI symptoms were described. Multivariable regression analyses were performed to determine significant predictors of GI symptoms. RESULTS: A total of 713 patients were included in the final analysis, of whom 132 (18.5%) patients had at least one GI symptom during their ICU stay, while 26 (3.6%) suffered from more than one symptom. Patients with GI symptoms had a significantly higher ICU stay compared with those without. The mortality of patients who had two or more GI symptoms simultaneously was significantly higher than that in those with one GI symptom. Multivariable logistic regression analysis revealed that older patients with a lower GCS score on admission were more likely to experience GI symptoms. CONCLUSION: The GI manifestations of heatstroke are common and appear to impact clinically relevant hospitalization outcomes.

Limits to sustained energy intake. XIX. A test of the heat dissipation limitation hypothesis in Mongolian gerbils (Meriones unguiculatus).

We evaluated factors limiting lactating Mongolian gerbils (Meriones unguiculatus) at three temperatures (10, 21 and 30°C). Energy intake and daily energy expenditure (DEE) increased with decreased ambient temperature. At peak lactation (day 14 of lactation), energy intake increased from 148.7±5.7 kJ day(-1) at 30°C to 213.1±8.2 kJ day(-1) at 21°C and 248.7±12.3 kJ day(-1) at 10°C. DEE increased from 105.1±4.0 kJ day(-1) at 30°C to 134.7±5.6 kJ day(-1) at 21°C and 179.5±8.4 kJ day(-1) at 10°C on days 14-16 of lactation. With nearly identical mean litter sizes, lactating gerbils at 30°C exported 32.0 kJ day(-1) less energy as milk at peak lactation than those allocated to 10 or 21°C, with no difference between the latter groups. On day 14 of lactation, the litter masses at 10 and 30°C were 12.2 and 9.3 g lower than those at 21°C, respectively. Lactating gerbils had higher thermal conductance of the fur and lower UCP-1 levels in brown adipose tissue than non-reproductive gerbils, independent of ambient temperature, suggesting that they were attempting to avoid heat stress. Thermal conductance of the fur was positively related to circulating prolactin levels. We implanted non-reproductive gerbils with mini-osmotic pumps that delivered either prolactin or saline. Prolactin did not influence thermal conductance of the fur, but did reduce physical activity and UCP-1 levels in brown adipose tissue. Transferring lactating gerbils from warm to hot conditions resulted in reduced milk production, consistent with the heat dissipation limit theory, but transferring them from warm to cold conditions did not elevate milk production, consistent with the peripheral limitation hypothesis, and placed constraints on pup growth.

An in-vitro animal experiment on metal implants' thermal effect on radiofrequency ablation.

BACKGROUND: To explore metal implants' thermal effect on radiofrequency ablation (RFA) and ascertain distance-thermal relationship between the metal implants and radiofrequency (RF) electrode. METHODS: Metal implants models were established in seven in-vitro porcine livers using silver clips or 125I seeds. RFA were conducted centering the RF electrode axis1 cm away from them, with one side containing a metal implants model the test group and the other side the control group. The thermometric needles were used to measure multi-point temperatures in order to compare the time-distance-temperature difference between the two groups. The gross scopes of the ablation of the two groups were measured and the tissues were analyzed for microscopic histology. RESULTS: At the ablation times of 8, 12, and 15 min, the average multi-point temperatures of the test group and the control group were 48.2±18.07°C, 51.5±19.57°C, 54.6±19.75°C, and 48.6±17.69°C, 52.2±19.73°C, 54.9±19.24°C, respectively, and the differences were not statistically significant (n=126, P>0.05). At the ablation times of 12 and 15 min, the ablation scopes of the test group and the control group were (horizontal/longitudinal diameter) 1.55/3.48 cm, 1.89/3.72 cm, and 1.56/3.48 cm, 1.89/3.72 cm, respectively, and the differences were not statistically significant (n=14, P>0.05). The two groups had the same manifestations in microscopy. CONCLUSIONS: Metal implants do not cause significant thermal effect on RFA.

[Morphology, immunohistochemistry and hTERC gene in-situ hybridization in Barrett's esophagus].

OBJECTIVE: To study the clinicopathologic features and differential diagnosis of proximal gastric mucosa and mucosa of Barrett's esophagus (BE) in biopsy specimens. METHOD: Thirty-eight cases of Barrett's esophagus (diagnosed using WHO criteria) and 44 cases of proximal gastric mucosa were studied by immunohistochemistry (for CK7, CK20, CK4, CK8, S-100 protein, MUC6, COX2 and bcl-2) and fluorescence in-situ hybridization (FISH) (for hTERC gene). The pathologic features were analyzed. RESULTS: The differences in expression of CK7, CK20, MUC6, COX2 and bcl-2 between BE and proximal gastric mucosa with intestinal metaplasia were not statistically significant (P > 0.05). There was however a statistically significant difference in expression of S-100 protein (P < 0.05). The expression of CK7/CK4 and CK7/CK8 in BE showed positive correlation (P < 0.05). However, such correlation was not demonstrated in proximal gastric mucosa (P > 0.05). The results of hTERC gene expression by FISH showed a statistically significant difference between the two groups: 57.9% (22/38) in BE and 13.6% (6/44) in proximal gastric mucosa (P < 0.05). CONCLUSIONS: The significance of CK7 and CK20 expression is uncertain in the differential diagnosis between BE and proximal gastric mucosa. On the other hand, positivity for CK7/CK4/CK8 may support the diagnosis of BE and play a role in distinguishing between the two groups. S-100 protein expression and detection of hTERC gene amplification also contribute to the diagnosis of BE.

Is Gangliocytic Paraganglioma Designated as a Subtype of Composite Paragangliomas and Originated From Pancreas Islet? A Case Report and Review of Literature.

Gangliocytic paraganglioma (GP) is quite rare, and origin and entity remain to be elucidated. A 51-year-old man presented with GP as a sessile polyp with a smooth surface that measured about 1 cm in diameter in the descending portion of duodenum. Pathological examination displayed that a neoplasm was predominantly located in the submucosa and infiltrated mucosa focally. The tumor consisted of epithelioid, ganglion-like, and spindle cells admixing in a haphazard way. The epithelioid cells resembled paraganglioma in cytological and architectural features. The ganglion-like cells were scattered and merged with the bland spindle cells in fascicular clusters, which resembled ganglioneuroma. Synaptophysin (Syn), microtubule-associated protein-2 (MAP-2), and chromogranin A (CgA) were positive in the epithelioid and ganglion-like cells in variety, and neurofilament (NF) staining highlighted the ganglion-like cells. S-100 and SOX-10 were positive in the spindle cell proliferation and around the epithelioid cells. Progesterone receptor (PR) was positive in the epithelioid cells. The polyp was resected, and no adjuvant therapy was given. The patient remained with no recurrence in 2 years' follow-up. Origin of GP is presumed to be related to pancreas islet. GP is distinguished from neuroendocrine tumor (NET) G1 and designated as paraganglioma-ganglioneuroma, a kind of composite paragangliomas.

K63 Ubiquitination of P21 Can Facilitate Pellino-1 in the Context of Chronic Obstructive Pulmonary Disease and Lung Cellular Senescence.

Chronic obstructive pulmonary diseases (COPD) is a kind of age-related, airflow-obstruction disease mostly caused by cigarette smoke. However, the relationship between COPD and lung cellular senescence is still not fully understood. Here, we found silencing Pellino-1 could inhibit the protein level of P21. Then, through constructing cell lines expressed ubiquitin-HA, we found that the E3 ubiquitin ligase Pellino-1 could bind to senescence marker p21 and modify p21 by K63-site ubiquitination by co-IP assays. Furthermore, we found that p21-mediated lung cellular senescence could be inhibited by silencing Pellino-1 in a D-galactose senescence mice model. Moreover, by constructing a COPD mouse model with shPellino-1 adenovirus, we found that silencing Pellino-1 could inhibit COPD and inflammation via reduction of SASPs regulated by p21. Taken together, our study findings elucidated that silencing E3 ligase Pellino-1 exhibits therapeutic potential for treatment to attenuate the progression of lung cellular senescence and COPD.

[Serrated lesions of colon and their malignant potential].

OBJECTIVE: To study the serrated lesions of colon and to compare the malignant potential between traditional serrated adenomas (TSA) and conventional adenomas (CAD). METHODS: A total of 5347 cases of colorectal polyps encountered in five regional hospitals during a five-year period were retrospectively reviewed. The serrated lesions were classified on the basis of histologic examination. One hundred and eighty-seven cases of CAD (including 160 cases of tubular adenoma and 27 cases of villous adenoma) and 36 cases of invasive adenocarcinoma were randomly selected as the controls. The degree of dysplasia and expressions of Ki-67, p53 and beta-catenin in TSA and CAD were compared. RESULTS: Amongst the 5347 colorectal polyps studied, 258 cases (4.8%) of serrated lesions were found, which included 112 cases (43.4%, 112/258) of hyperplastic polyp, 78 cases (30.2%, 78/258) of TSA and 26 cases (10.1%, 26/258) of sessile serrated adenoma. Sixty-two cases of TSA were identified from 3 hospitals, in which moderate dysplasia was found in 13 cases. High-grade intraepithelial neoplasia and ICA were found in 6 cases (9.6%). Compared with the 187 cases of CAD, moderate dysplasia were found in 27 cases and high-grade intraepithelial neoplasia and invasive adenocarcinoma were found in 25 cases (13.3%, χ(2) = 19.373, P = 0.000). There was statistically significant difference between TSA and CAD in the degree of dysphasia. The expression of Ki-67, p53 and beta-catenin in TSA and CAD showed no significant difference (P > 0.05). CONCLUSIONS: The incidence of serrated lesions is lower in northern Chinese population than that in Caucasians. TSA has obvious malignant potential; but the rate associated with high-grade intraepithelial neoplasia and invasive adenocarcinoma is lower than that in CAD.

[Clinicopathological and immunohistochemical features of colorectal sessile serrated adenoma].

OBJECTIVE: To investigate the clinicopathological characteristics and expression status of Ki67, p53, CEA, CDX, CK7 in colorectal sessile serrated adenoma (SSA). METHODS: The clinicopathological data of 11 cases of SSA, 51 cases of hyperplastic polyp (HP) and one case with mixed HP/SSA were reviewed and analyzed retrospectively. The expression of Ki67, p53, CEA, CDX and CK7 were detected by immunohistochemistry. RESULTS: The major histological features in SSA were architectural abnormality in crypts, dilatation of serrated crypt bases like an inverted "T" or "L" shape adjacent to muscularis mucosa. Atypical cells containing round to oval nuclei and nucleoli were also observed. The immunohistochemical staining showed that the expression of p53 increased gradually from HP to TA: 11.8% in HP, 20.0% in SSA, 41.2% in VTA and 75.0% in TA, with a significant difference among the groups (chi(2) = 17.996, P = 0.000). However, no significant difference in the expression of CDX and CK7 was observed between HP and SSA. Of the 10 SSA cases, positive expression of Ki67 was found in cells located in the base or middle part of crypt in 6 cases, positive cells index was 26% - 50% in 5 cases, and > 50% in 3. Compared with the expression of Ki67 in the HP, VTA and VA, SSA showed a significant difference in both the positive cell number and in the positive regions. (positive number: chi(2) = 34.601, P = 0.000; positive regions: chi(2) = 63.077, P = 0.000). CONCLUSION: Morphological diagnosis of SSA was mainly based on crypt architectural and cellular abnormalities, and the crypt architectural abnormality may be more important than cellular features. Detection of p53 and Ki67 expression may be helpful in differential diagnosis and understanding the nature of SSA.

[A study on microsatellite instability status for colorectal serrated lesions].

OBJECTIVE: To verify the traditional serrated pathway by comparing microsatellite instability (MSI) status among traditional serrated adenoma, traditional adenoma, serrated colorectal cancer and non-serrated colorectal cancer. METHODS: Seventy-five paraffin-embedded tissue samples, including 15 with serrated adenocarcinoma (Sca), 20 with non-serrated adenocarcinoma (N-Sca), 20 with traditional serrated adenoma (TSA) and 20 with villous adenoma (AD) were collected from the pathology department of our hospital. Genomic DNA was extracted from these samples and then amplified with fluorescently-labeled primer specific for BAT25 and BAT26. The MSI status was detected with DNA automatic sequencer. RESULTS: Six of 18 samples with TSA harbored MSI-H and twelve MSI-L/MSS; 18 samples with conventional adenoma were exclusively of MSS; 3 of 13 samples of serrated carcinoma harbored MSI-H and ten MSI-L/MSS; 18 of 19 N-Sca samples harbored MSI-L/MSS and only one MSI-H. With Chi-square test, the MSI frequency in AD group and N-Sca group was significantly lower than that in TSA group and Sca group (P<0.05); but with no statistical difference between the TSA group and Sca groups (P>0.05). CONCLUSION: MSI-H frequency in AD group and N-Sca group was obviously lower than that of TSA group and Sca group. It is concluded that there might be a new traditional serrated neoplasia pathway which is different from the conventional adenoma-carcinoma carcinogenesis pathway, but we still need prospective follow-up studies to verify its existence.

[Clinicopathologic features and proliferative status of colorectal serrated lesions: a study of 104 cases].

OBJECTIVE: To study the clinicopathologic features and proliferative status of colorectal hyperplastic polyp (HP), sessile serrated adenoma (SSA) and traditional serrated adenoma (TSA). METHODS: One hundred and four cases colorectal serrated lesions were collected from 2628 cases of colorectal polyps during the period from November, 2002 to December, 2007. The clinicopathologic features and expression of proliferation marker Ki-67 were studied. RESULTS: On the basis of morphologic examination, 60 cases were classified as HP, 20 cases as TSA, 11 cases as SSA, 7 cases as mixed HP/SSA/TSA, and 6 cases as mixed serrated polyp/adenoma and tubular adenoma. Immunohistochemical study for Ki-67 showed that 40 cases (78%) of the 51 cases of HP were either mostly negative or rarely (<25% cells) positive. Most of the positive cells were located at crypt bases. Among the 15 cases of TSA, 11 of them revealed positive cryptal cells (25% to 50% or>50% positivity). Most of the positive cells were located in mid portion of crypts. The number and distribution of Ki-67 positive cells in SSA were similar to those in TSA but were significantly different from those in tubular adenoma and adenocarcinoma (chi2=34.601, P=0.000; chi2=63.077, P=0.000, respectively). CONCLUSIONS: HP, SSA and TSA have their morphologic characteristics, with some overlapping features noted. The distinction between SSA and HP can be difficult. Diagnosis of SSA relies mostly on architectural rather than cytologic features. The distinction between TSA and SSA depends mainly on the presence of dysplasia. Ectopic crypt formation is almost exclusively seen in TSA. The distribution and percentage of Ki-67-positive cells are also helpful in subtyping of various colorectal serrated lesions. In general, the proliferative index is lower in serrated adenoma (TSA or SSA) than in tubular adenoma.

Overexpression of thermostable meso-diaminopimelate dehydrogenase to redirect diaminopimelate pathway for increasing L-lysine production in Escherichia coli.

Dehydrogenase pathway, one of diaminopimelate pathway, is important to the biosynthesis of L-lysine and peptidoglycan via one single reaction catalyzed by meso-diaminopimelate dehydrogenase (DapDH). In this study, the thermostable DapDH was introduced into diaminopimelate pathway that increased the final titer (from 71.8 to 119.5 g/L), carbon yield (from 35.3% to 49.1%) and productivity (from 1.80 to 2.99 g/(L∙h)) of L-lysine by LATR12-2∆rpiB::ddhSt in fed-batch fermentation. To do this, the kinetic properties and the effects of different DapDHs on L-lysine production were investigated, and the results indicated that overexpression of StDapDH in LATR12-2 was beneficial to construct an L-lysine producer with good productive performance because it exhibited the best of kinetic characteristics and optimal temperature as well as thermostability in reductive amination. Furthermore, ammonium availability was optimized, and found that 20 g/L of (NH4)2SO4 was the optimal ammonium concentration for improving the efficiency of L-lysine production by LATR12-2∆rpiB::ddhSt. Metabolomics analysis showed that introducing the StDapDH significantly enhanced carbon flux into pentose phosphate pathway and L-lysine biosynthetic pathway, thus increasing the levels of NADPH and precursors for L-lysine biosynthesis. This is the first report of a rational modification of diaminopimelate pathway that improves the efficiency of L-lysine production through overexpression of thermostable DapDH in E. coli.

Cyclometalated Iridium(III) Complexes Incorporating Aromatic Phosphonate Ligands: Syntheses, Structures, and Tunable Optical Properties.

The incorporation of phosphonate ligands into the cyclometalated iridium(III) complexes can not only tune their electronic and optical properties but also provide the possibility of anchoring these molecules on the semiconductor surfaces for further applications. Herein, we report the first examples of mononuclear cyclometallated iridium(III) complexes incorporating phosphonate ligands, namely, [Ir(ppy)2(HL1)]·0.5H2O (1), [Ir(ppy)2(HL2)]·0.5H2O (2), [Ir(dfppy)2(HL1)] (3), and [Ir(dfppy)2(HL2)]·3.5H2O (4) (ppy = 2-phenylpyridine, dfppy = 2-(2,4-difluorophenyl)pyridine, H2L1 = 2-pyridylphosphonic acid, H2L2 = 2-quinolinephosphonic acid). Luminescent spectra are studied both in solution and in the solid state, and significantly red-shifted broad emission bands are observed in complexes 2 and 4. The experimental and density functional theory (DFT) time-dependent-DFT calculation results indicate that the expansion of the aromatic conjugation length in the ancillary phosphonate ligands decreases the lowest unoccupied molecular orbital energy levels of the systems, originating from the triplet state associated with the ancillary ligand such as 3MLCT, 3LC, and 3LLCT charge-transfer transitions.

[BRAF mutation in colorectal serrated lesions].

OBJECTIVE: To investigate the viral oncogene homolog B1 (BRAF) mutation frequency in serrated colorectal adenocarcinoma (Sca), and to verify the existence of a new serrated pathway indirectly. METHODS: 75 paraffin-embedded tissue samples, including 15 cases of Sca, 20 cases of traditional serrated adenoma (TSA), 20 cases of non-serrated adenocarcinoma (NS-ca), and 20 cases of villous adenoma, were reviewed. Nest-PCR was used to amplify the exon 15 fragment of BRAF gene. RFLP assay was used to detect the BRAF V600E mutation. The positive samples were verified by direct sequencing. RESULTS: Four of the 11 successfully amplified Sca specimens (4/11, 36.4%), and 4 of the 15 TSA samples (4/15, 26.7%) harbored BRAF V600E mutation. However, no BRAF V600E mutation was found in the 14 NS-ca samples and the 11 villous adenoma specimens. The BRAF V600E mutation frequencies of the villous adenoma group and NS-ca group were significantly lower than those of the TSA group and Sca group (P = 0.0084); however, there was no statistical difference in the frequency of BRAF V600E mutation between the Sca and TSA groups (P > 0.05). CONCLUSION: BRAF V600E mutation frequency is significantly higher in the Sca and TSA patients than in the NS-ca and villous adenoma patients. There is actually a new serrated neoplasia pathway different from the traditional adenoma-carcinoma carcinogenesis pathway.