Abinukitrine A, a unique 17,18-cyclolanostane triterpenoid from Abies nukiangensis.

Abinukitrine A (1), a novel triterpenoid, was isolated from Abies nukiangensis. Comprehensive spectroscopic analysis revealed that 1 is the first example of 17,18-cyclolanostane bearing a unique 6/6/6/5/3 ring system. Its absolute configuration was unequivocally assigned by Cu-Kα X-ray single-crystallography. Compound 1 showed a potent anti-hepatitis C virus (HCV) effect.

Clinical characterization and mutation spectrum in patients with familial adenomatous polyposis in China.

BACKGROUND AND AIM: Familial adenomatous polyposis (FAP) is the most common adenomatous polyposis syndrome. Patients with FAP are screened for germline mutations of two genes, APC and MUTYH. However, limited data exist on the clinical characterization and genotypic spectrum of FAP in China. This study was aimed to determine APC and MUTYH mutational status in a small cohort of FAP probands in China and to characterize the genotype-phenotype correlation in mutated patients. METHODS: Mutation screening of 46 unrelated probands was performed using multigene panels by next-generation sequencing. Clinical data of the index were used to assess genotype-phenotype correlations. RESULTS: Overall, 42 out of 46 (91.30%) unrelated probands found mutations, including 35 (76.09%) with APC mutations, 3 (6.52%) with MUTYH mutations, and 4 (8.70%) with both APC and MUTYH mutations. Ten APC genetic alterations variants were novel. The hereditary pattern of the family with both APC and MUTYH mutations was autosomal dominant inheritance. Upper gastrointestinal polyp was the most common extracolonic manifestations. The onset time for patients with both APC and MUTYH mutations was earlier than MUTYH mutation carriers and similar to APC mutation carriers. But the age of carcinogenesis for patients with both APC and MUTYH mutations was later than APC mutation carriers and similar to MUTYH mutation carriers. CONCLUSION: In this study, we show the importance of using multigene panels that allow for a parallel comprehensive screening. We suggest that genetic testing of patients with suspected adenomatous polyposis syndromes should include APC and MUTYH gene mutation analyses simultaneously.

Up-regulation of receptor interaction protein 140 promotes glucolipotoxicity-induced damage in MIN6 cells.

The receptor interaction protein 140 (RIP140) cofactor is a key regulator of metabolic balance, but its function in glucose- and lipid-mediated damage in islet ß cells is unknown and was investigated in this study. RIP140 expression and distribution was evaluated in MIN6 cells under high glucose and lipid conditions using real-time Polymerase Chain Reaction (PCR), western blotting and confocal laser scanning microscopy. Cells were separately treated with 500 µM palmitic acid and 25 mM glucose when RIP140 expression was upregulated or downregulated, and cell viability, apoptosis rate, the level of oxidative stress and insulin secretion was assessed, as was the expression of related genes. Increased glucose and palmitic acid elevated RIP140 expression and distribution in nuclei. Overexpression of RIP140 promoted apoptosis but inhibited cell viability in MIN6 cells, and basal insulin secretion and glucose-stimulated insulin secretion levels were altered following treatment with glucose and palmitic acid. In addition, oxidative stress was elevated, phosphorylated extracellular signal-regulated kinases 1/2 and uncoupling protein 2 messenger RNA (mRNA) abundance were increased, B-cell lymphoma-2 protein levels were decreased, and peroxisome proliferators activated receptor gamma co-activator 1 alpha, phosphoenolpyruvate carboxykinase , and pancreatic and duodenal homeobox-1 mRNA levels were downregulated. Furthermore, glucolipotoxicity-induced damage was reversed when RIP140 expression was downregulated by small interfering RNA (SiRNA). RIP140 promotes islet ß cells damage caused by glucolipotoxicity.

A Strong Donor-Acceptor System Based on a Metal Chalcogenide Cluster and Porphyrin.

Although great progress has been made for charge transfer (CT) compounds of various organic donor-acceptor systems, no CT compounds containing both inorganic chalcogenide cluster anions and organic porphyrin cations have been reported. Herein, a germanium chalcogenide cluster (Ge4S104-) is chosen as an electron donor and a methylated tetrakis(4-pyridyl)porphyrin (5,10,15,20-tetrakis(N-methyl-4-pyridyl)porphyrin, TMPyP) is selected as an electron acceptor to create chalcogenide cluster-porphyrin CT compounds (TMPyP-Ge4S10)·5H2O (1) and (MnTMPyP-Ge4S10)·13H2O (2). Their crystal structures have been characterized by single-crystal X-ray diffraction. Compound 1 is an ionic CT salt assembled through interion interactions, and compound 2 is a neutral CT dyad formed by metal-ligand axial coordination of the chalcogenide cluster with manganese porphyrin. The strong charge transfer properties are revealed by electronic spectra, theoretical calculations, 1H NMR, and ESR. The CT intensity of the chalcogenide cluster-porphyrin system can be modulated by metalation. The fluorescence and photocurrent response properties of 1 and 2 are related to the CT intensity.

An ionic charge-transfer dyad prepared cost-effectively from a tetrathiafulvalene carboxylate anion and a TMPyP cation.

Great progress has been made in combining a TTF moiety with a porphyrin unit by covalent bonds, but only a few examples were reported in which TTF and porphyrin assembled by noncovalent interactions. In contrast to the energy- and time-consuming synthetic procedures for the covalent system, the assembly of a non-covalent ionic system would be a cost-effective way to construct donor-acceptor ensembles. Herein a new type of ionic TTF-porphyrin dyad is obtained. A methylated tetra(4-pyridyl) porphyrin (5,10,15,20-tetrakis-(N-methyl-4-pyridyl)-porphyrin, TMPyP) is selected as the cation, and TTF-bicarboxylate (L(1)) or TTF-tetracarboxylate (L(2)) is used as the anion. Crystal structures of two TTF-TMPyP ionic D-A compounds, TMPyP-(HL(1))4·3H2O (1) and TMPyP-(H2L(2))2·5H2O (2), were characterized by single-crystal X-ray diffraction. The strong ionic interaction enhances the charge-transfer between the regular mixed-stacking donors and acceptors, which are investigated comprehensively by spectral, electrochemical and theoretical studies. The variation in properties between L(1) and L(2) is of great advantage to understand the influence factors for charge-transfer. The charge-transfer properties can be modulated not only by the nature of the donor or the acceptor, but also the cation-anion ratio in the salt, which shows great flexibility of the D-A ionic dyad in the design and preparation of new charge-transfer systems.

Effect of CPAP therapy on cardiovascular events and mortality in patients with obstructive sleep apnea: a meta-analysis.

PURPOSE: Continuous positive airway pressure (CPAP) therapy may decrease the risk of mortality and cardiovascular events in patients with obstructive sleep apnea. However, these benefits are not completely clear. METHODS: We undertook a meta-analysis of randomized clinical trials identified in systematic searches of MEDLINE, EMBASE, and the Cochrane Database. RESULTS: Eighteen studies (4146 patients) were included. Overall, CPAP therapy did not significantly decrease the risk of cardiovascular events compared with the control group (odds ratio (OR), 0.84; 95 % confidence intervals (CI), 0.62-1.13; p = 0.25; I (2) = 0 %). CPAP was associated with a nonsignificant trend of lower rate of death and stroke (for death: OR, 0.85; 95 % CI, 0.35-2.06; p = 0.72; I (2) = 0.0 %; for stroke: OR, 0.56; 95 % CI, 0.18-1.73; p = 0.32; I (2) = 12.0 %), a significantly lower Epworth sleepiness score (ESS) (mean difference (MD), -1.78; 95 % CI, -2.31 to -1.24; p < 0.00001; I (2) = 76 %), and a significantly lower 24 h systolic and diastolic blood pressure (BP) (for 24 h systolic BP: MD, -2.03 mmHg; 95 % CI, -3.64 to -0.42; p = 0.01; I (2) = 0 %; for diastolic BP: MD, -1.79 mmHg; 95 % CI, -2.89 to -0.68; p = 0.001; I (2) = 0 %). Daytime systolic BP and body mass index were comparable between the CPAP and control groups. Subgroup analysis did not show any significant difference between short- and mediate-to-long-term follow-up groups with regard to cardiovascular events, death, and stroke. CONCLUSIONS: CPAP therapy was associated with a trend of decreased risk of cardiovascular events. Furthermore, ESS and BP were significantly lower in the CPAP group. Larger randomized studies are needed to confirm these findings.

Overexpression of survivin is correlated with increased invasion and metastasis of colorectal cancer.

BACKGROUND: The aim of this study was to investigate the association of survivin expression with metastasis of colorectal cancer (CRC). METHODS: RT-PCR and Western blot assays were performed to detect survivin expression in CRC cells and normal intestinal epithelial cell. The expression of survivin gene was also detected in 15 CRC tissues, surrounding and adjacent colon tissues. Moreover, survivin expression in 48 CRC tissues with or without lymph node metastasis was analyzed. Multivariate analysis for lymph node metastasis was performed using logistic regression model. RNA interference was used to inhibit survivin expression in CRC cells and analyze its effect on invasion and metastasis of CRC cells. RESULTS: The expression levels of survivin mRNA and protein were higher in CRC cells than in normal intestinal epithelial cell line. The average levels of survivin mRNA and protein were higher in CRC tissues than surrounding or adjacent colon tissues (P < 0.05). High survivin expression was an independent factor for predicting lymph node metastasis of CRC (P = 0.043). RNAi-mediated survivin knockdown could significantly inhibit in vitro invasion and in vivo metastasis of CRC cells, which might be inactivation of matrix metalloproteinases. CONCLUSION: Targeting survivin will be a potential strategy to suppress metastasis of CRC.

N-Alkyl Linkers for DNA-Encoded Chemical Libraries.

A series of novel N-alkyl linkers that connect small-molecule library members with their encoding DNA oligonucleotides has been developed. In comparison with the standard amide linker (usually constructed with oligo-AOP-NH2 ), the N-alkyl linker is not only more chemically stable, but also provides better structural diversity at the linkage point. Chemical variety in the vicinity of the polyglycol terminus, in particular, could affect binding interactions with the target protein. It could have been neglected in previous DNA-encoded chemical library (DEL) synthesis and screening studies due to the limited linkage alternatives. With these linkers, one can produce versatile key intermediates as Cycle 1 products directly amenable to Cycle 2 chemistry without the use of protecting groups. As a result, a DEL synthesis process that uses the fewest chemical conversions, such as 3-step, 3-cycle DELs, can achieve higher synthetic efficiency while creating less DNA tag degradation, resulting in higher quality DELs.

[Hyperspectral image compression technology research based on EZW].

Along with the development of hyperspectral remote sensing technology, hyperspectral imaging technology has been applied in the aspect of aviation and spaceflight, which is different from multispectral imaging, and with the band width of nanoscale spectral imaging the target continuously, the image resolution is very high. However, with the increasing number of band, spectral data quantity will be more and more, and these data storage and transmission is the problem that the authors must face. Along with the development of wavelet compression technology, in field of image compression, many people adopted and improved EZW, the present paper used the method in hyperspectral spatial dimension compression, but does not involved the spectrum dimension compression. From hyperspectral image compression reconstruction results, whether from the peak signal-to-noise ratio (PSNR) and spectral curve or from the subjective comparison of source and reconstruction image, the effect is well. If the first compression of image from spectrum dimension is made, then compression on space dimension, the authors believe the effect will be better.

Submucosal hematoma with a wide range of lesions, severe condition and atypical clinical symptoms: A case report.

BACKGROUND: Submucosal hematoma (SH) is one of the rare causes of upper gastrointestinal bleeding. As a rare and critical disease in clinical practice, it should be paid more attention to by clinicians to avoid missed diagnosis and misdiagnosis. Most of the esophageal submucosal hematomas have clear causes, including retrosternal pain, dysphagia, etc. Here, we report a rare case of SH extending from the hypopharynx to the lower esophagus caused by oral administration of hirudin and panax notoginseng powder, with atypical clinical manifestation. Such a long submucosal hematoma has rarely been reported. CASE SUMMARY: The patient was a 60-year-old male with a history of gastritis, hypertension, coronary heart disease, and coronary stent implantation. The patient developed chest tiredness and heartburn after taking 10 capsules of a homemade mixture of hirudin and notoginseng powder in the previous 2 d. He did not have hematemesis or black stool. Gastroscopy and chest computed tomography confirmed the diagnosis of SH, which ranged from the pharynx to the lower esophagus and was 35-40 cm in length. After the diagnosis was confirmed, we performed active conservative treatment on the patient, and the patient recovered well and remained asymptomatic during the 26-mo follow-up. CONCLUSION: SH is rare, and cases with atypical clinical symptoms may lead to misdiagnosis and missed diagnosis. Ignorance of this disease can lead to serious clinical consequences. Conservative therapy is effective and the prognosis is good.

Untargeted metabolomics characteristics of nonobese nonalcoholic fatty liver disease induced by high-temperature-processed feed in Sprague-Dawley rats.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases in the world. In our early clinical data and questionnaire analysis of NAFLD, it was found that the body mass index of some patients did not meet the diagnostic criteria for overweight or obesity. The consumption of high-temperature-processed foods such as fried food, hot pot and barbecue is closely related to the occurrence of nonobese NAFLD. Reducing the intake of this kind of food can reduce disease severity and improve prognosis. AIM: To explore the untargeted metabolomics characteristics of nonobese nonalcoholic fatty liver disease in Sprague-Dawley rats induced by high-temperature-processed feed. METHODS: Fifty-four male Sprague-Dawley rats were divided into three groups: The control group received a standard diet; the nonfried soybeans (NDFS) group received 60% NDFS and 40% basic feed and the dry-fried soybeans (DFS) group received 60% DFS and 40% basic feed. Six rats were sacrificed at week 4, 8, and 12 in each group. The food intake, body weight, Lee's index, liver index, serological index and hepatic histopathology were assessed. Untargeted metabolomics characteristics were used to analyze the changes in liver metabolites of rats at week 12. Correlations between metabolites and pathology scores between the DFS and control groups and between the DFS and NDFS groups were analyzed. We selected some of the metabolites, both within the pathway and outside of the pathway, to explain preliminarily the difference in liver pathology in the three groups of rats. RESULTS: There were no statistically significant differences in the food intake, body weight, Lee's index or serological index between the DFS group and the control group (P > 0.05). At week 8 and week 12, the steatosis scores in the DFS group were significantly higher than those in the other two groups (P < 0.05). At week 12, the liver index of the DFS group was the lowest (NDFS group vs DFS group, P < 0.05). The fibrosis score in the DFS group was significantly higher than those in the other two groups (P < 0.05). The correlation analysis of the liver pathology score and differential metabolites in the DFS and NDFS groups showed that there were 10 strongly correlated substances: Five positively correlated substances and five negatively correlated substances. The positively correlated substances included taurochenodeoxycholate-3-sulfate, acetylcarnitine, 20a,22b-dihydroxycholesterol, 13E-tetranor-16-carboxy-LTE4 and taurocholic acid. The negatively correlated substances included choline, cholesterane-3,7,12,25-tetrol-3-glucuronide, nicotinamide adenine dinucleotide phosphate, lysoPC [16:1 (9Z)] and glycerol 3-phosphate. The correlation analysis of the liver pathology score and differential metabolites in the DFS and control groups showed that there were 13 strongly correlated substances: Four positively correlated substances and 9 negatively correlated substances. The positively correlated substances included 4-hydroxy-6-eicosanone, 3-phosphoglyceric acid, 13-hydroxy-9-methoxy-10-oxo-11-octadecenoic acid and taurochenodeoxycholate-3-sulfate. The negatively correlated substances included lysoPC [16:1(9Z)], S-(9-hydroxy-PGA1)-glutathione, lysoPC [20:5 (5Z, 8Z, 11Z, 14Z, 17Z)], SM (d18:1/14:0), nicotinamide adenine dinucleotide phosphate, 5,10-methylene-THF, folinic acid, N-lactoyl-glycine and 6-hydroxy-5-methoxyindole glucuronide. CONCLUSION: We successfully induced liver damage in rats by using a specially prepared high-temperature-processed feed and explored the untargeted metabolomics characteristics.

Hollow mesoporous carbon nanospheres for imaging-guided light-activated synergistic thermo-chemotherapy.

Carbon-based light-activated materials can absorb optical energy to generate photoacoustic (PA) signals for imaging or transduce optical photons to thermal energy, which holds great promise for biomedical applications. Herein, we synthesize hollow and mesoporous carbon nanospheres (HMCNs) with uniform size on a large scale. The properties of hollow cavity and mesoporous structures make the HMCNs achieve high drug loading (480 mg DOX per g HMCNs). The present intense near infrared (NIR) absorbance achieves excellent photoacoustic imaging ability and photothermal conversion efficacy (32.0%). More interestingly, the encapsulated drugs can have a triggered release under NIR irradiation. The investigations in vitro and in vivo demonstrate that HMCNs have excellent biocompatibility, and accumulate in tumors by the enhanced permeability and retention (EPR) effect. Moreover, under NIR irradiation, in vivo evaluation shows that HMCNs can perform strong PA imaging, and induce great tumor inhibition by the combination of chemotherapy and PTT under the guidance of photoacoustic imaging. The present study provides new insight for design of novel biocompatible light-activated carbons for cancer nanotheranostics.

Activation of CD3+ T cells by Helicobacter pylori DNA vaccines in potential immunotherapy of gastric carcinoma.

Most of gastric carcinoma (GC) is attributed to infection by Helicobacter pylori (H. pylori) but there is increasing evidence that the positive H. pylori status correlates with better prognosis in GC. The H. pylori-induced cellular immune response may suppress cancer and in this work, recombinant pcDNA3 plasmids encoding various fragments of H. pylori virulence genes of cagA, vacA and babA are constructed and combined into groups to immunize BALB/c mice. The activated splenic CD3+ T cells are purified and the anticancer effects are investigated in vitro and in vivo. The H. pylori DNA vaccines induce a shift in the response from Th1 to Th2 that mimicks the immune status in patients of GC with chronic H. pylori infection. The stimulated CD3+ T cells inhibit the growth of human GC cells in vitro and adoptive transfusions of the CD3+ T cells suppress the growth of GC xenograft in vivo. The effects may be caused by the larger ratios of infiltrated CD8+/CD4+ T cells, reduced infiltration of regulatory FOXP3+ T cells, and enhanced apoptosis induced by upregulation of Caspase-9/Caspase-3 and downregulation of Survivin. Our results reveal the potential immunotherapeutic value of H. pylori vaccine-activated CD3+ T cells in those with advanced GC.

Autoimmune responses induced by Helicobacter pylori improve the prognosis of gastric carcinoma.

Gastric carcinoma (GC) remains one of most serious malignant tumors worldwide, with Helicobacter pylori being the definite carcinogen. The H. pylori components, cytotoxin-associated gene A (CagA), vacuolating toxin A (VacA) and blood-group antigen-binding adhesin gene (BabA), can mimic and bind to specific receptors or surface molecules both on gastric epithelial cells and platelets, in which CagA and VacA may also be directly involved in loosening of tight junctions in monolayers of polarized gastric epithelial cells. It has been shown that a history of H. pylori infection is found in the majority of patients with GC, and that anti-CagA, anti-VacA and anti-BabA antibodies targeting both H. pylori components and host mimic molecules can be detected in them with increased levels. Patients with GC who are positive for H. pylori prospectively have a better outlook than those negative. The stimulation of mentioned autoantibodies in antigen processing and presentation and subsequent T-cell activation and proliferation improves host immune status. On the other hand, in an autoimmune response, autoantibodies can induce the cross-reaction against those localized or circulating GC cells, which are characterized by mimic or absorbed H. pylori antigens, and lead to the killing and even suppressing of metastasis of cancer cells. Therefore, we here hypothesize that autoimmune responses induced by H. pylori components may play a key role in improving the prognosis of patients with gastric carcinoma.

Mammalian cell entry protein of Mycobacterium tuberculosis induces the proinflammatory response in RAW 264.7 murine macrophage-like cells.

Mammalian cell entry (Mce1A) protein of Mycobacterium tuberculosis (Mtb) is involved in bacterial entry and survival in macrophages, which has been shown to induce production of tumor necrosis factor alpha (TNF-alpha). It remains unclear whether and how Mce1A functions upon the type I interleukin-1 receptor-associated protein kinase (IRAK-1) and TNF receptor-associated factor 6 (TRAF-6) of important proinflammatory cytokines. In this study, His-tagged Mce1A was expressed and purified. Also, two pieces of small interfering RNA (siRNA) were designed and synthesized by in vitro transcription, which exhibit specific and efficient silencing effect on mce1a expression. Furthermore, RAW 264.7 murine macrophage-like cells were exposed to His-tagged Mce1A or co-transfected with the Mce1A-expressing plasmid and efficient siRNA, and levels of IRAK-1 and TRAF-6 were then determined by Western blot. We show here that Mce1A induces up-regulations of IRAK-1 and TRAF-6 in macrophages in a dose-dependent manner. The level of Caspase-3 closely related with apoptosis was also determined, whereas no changes were observed. These results indicate that Mtb Mce1A protein induces a proinflammatory response in macrophages.

Inhibition of CXCL12/CXCR4 axis as a potential targeted therapy of advanced gastric carcinoma.

The whole outcome for patients with gastric carcinoma (GC) is very poor because most of them remain metastatic disease during survival even at diagnosis or after surgery. Despite many improvements in multiple strategies of chemotherapy, immunotherapy, and targeted therapy, exploration of novel alternative therapeutic targets is still warranted. Chemokine receptor 4 (CXCR4) and its chemokine ligand 12 (CXCL12) have been identified with significantly elevated levels in various malignancies including GC, which correlates with the survival, proliferation, angiogenesis, and metastasis of tumor cells. Increasing experimental evidence suggests an implication of inhibition of CXCL12/CXCR4 axis as a promising targeted therapy, although there are rare trials focused on the therapeutic efficacy of CXCR4 inhibitors in GC until recently. Therefore, it is reasonable to infer that specific antagonists or antibodies targeting CXCL12/CXCR4 axis alone or combined with chemotherapy will be effective and worthy of further translational studies as a potential treatment strategy in advanced GC.

Rare Gingival Metastasis by Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) uncommonly metastasizes to the gingiva, which always means a poor outcome. We reported a rare HCC case with multiple metastases to gingiva, lungs, and brain. A 60-year-old man was initially diagnosed as HCC with metastases to double lungs. He was subjected to a transarterial chemoembolization (TACE) (5-fluorouracil, 750 mg) and two cycles of intravenous chemotherapy (gemcitabine 1.8 g at days 1 and 8, oxaliplatin 200 mg at day 2, every 4 weeks). However, the volume of liver tumor still increased. A bean-size gingival nodule growing with occasional bleeding was also found. TACE (5-fluorouracil 750 mg, perarubicin 40 mg, cisplatin 20 mg) was performed again and an oral sorafenib therapy (400 mg, twice per day) was adopted. The disease maintained relatively stable for about 6 months until a second obvious progress. The gingival nodule was then palliatively excised and identified as a poorly differentiated metastatic HCC by histopathological examination. Best supportive treatments were made since the performance score was too bad. Finally, cerebral metastases occurred and the patient died of systemic failure. Upon review of previous reports, we discussed risk factors, clinical and pathological characteristics, treatments, and prognosis of gingival metastasis by HCC.

Risk factors for hypocalcemia and hypoparathyroidism following thyroidectomy: a retrospective Chinese population study.

BACKGROUND: Hypocalcemia is one of the most common postoperative complications following thyroid surgery in clinical practice. The occurrence of hypocalcemia is mainly attributed to hypoparathyroidism when parathyroid glands are devascularized, injured, or dissected during the surgery. The aim of this study was to analyze the risk factors for hypocalcemia and hypoparathyroidism following thyroidectomy. PATIENTS AND METHODS: A total of 278 patients who underwent thyroid surgery were analyzed retrospectively. Univariate analysis and multivariable logistic regression were performed to discover the risk factors for hypocalcemia and hypoparathyroidism. RESULTS: Postoperative hypocalcemia occurred in 76 (27.3%) patients and hypoparathyroidism occurred in 42 (15.1%) patients. Seven factors were significantly related to the presence of postoperative hypocalcemia, namely, age (P=0.049), gender (P=0.015), lateral lymph node dissection (P=0.017), operation type (P<0.001), preoperative parathyroid hormone (PTH) level (P=0.035), operation time (P=0.001), and applying carbon nanoparticles (CNs; P=0.007). Our result revealed that gender (P=0.014), lateral lymph node dissection (P=0.038), operation type (P<0.001), operative time (P<0.001), and applying CNs (P=0.001) had a significant correlation with postoperative hypoparathyroidism. CONCLUSION: These findings were crucial for guiding surgeons to prevent the occurrence of hypocalcemia and hypoparathyroidism.

Effect and Safety of TNF Inhibitors in Immunoglobulin-Resistant Kawasaki Disease: a Meta-analysis.

Previous studies showed that tumor necrosis factor (TNF) inhibitors might decrease the rate of coronary artery abnormalities in pediatrics with intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD). Therefore, we aimed to evaluate the effect and safety of TNF inhibitors in IVIG-resistant KD. We undertook a meta-analysis of clinical trials identified in systematic searches of PubMed, EMBASE, Cochrane Database, and Google scholar through May 2016. Five studies were included. Overall, rate of coronary artery aneurysm was comparable between groups (relative risk (RR), 1.05; 95 % confidence interval (95 % CI), 0.60 to 1.81; P = 0.87). No significant differences were recorded between groups in coronary artery Z scores (standardized mean difference (SMD), 0.27; 95 % CI, -0.30 to 0.85; P = 0.35). Meanwhile, TNF inhibitors were not associated with a significant decreased risk of treatment resistance compared with IVIG treatment (RR, 0.65; 95 % CI, 0.37 to 0.15; P = 0.14). However, days of fever was significantly reduced in the TNF inhibitor group (SMD, -0.66; 95 % CI, -0.90 to -0.41; P < 0.001). Additionally, risk of serious adverse events was similar between groups. Therefore, TNF inhibitors could shorten the duration of fever in IVIG-resistant KD. However, TNF inhibitors appear to have no cardioprotective effect in patients with IVIG-resistant KD.

Cronkhite-Canada syndrome polyps infiltrated with IgG4-positive plasma cells.

Cronkhite-Canada syndrome (CCS) is a rare but serious protein-losing enteropathy, but little is known about the mechanism. Further more, misdiagnosis is common due to non-familiarity of its clinical manifestation. A 40-year-old male patient was admitted to our hospital because of diarrhea and hypogeusia associated with weight loss for 4 mo. On physical examination, skin pigmentation, dystrophic nail changes and alopecia were noted. He had no alike family history. Laboratory results revealed low levels of serum albumin (30.1 g/L, range: 35.0-55.0 g/L), serum potassium (2.61 mmol/L, range: 3.5-5.5 mmol/L) and blood glucose (2.6 mmol/L, range: 3.9-6.1 mmol/L). The erythrocyte sedimentation rate was elevated to 17 mm/h (range: 0-15 mm/h). X-ray of chest and mandible was normal. The endoscopic examination showed multiple sessile polyps in the stomach, small bowel and colorectum. Histopathologic examination of biopsies obtained from those polyps showed hyperplastic change, cystic dilatation and distortion of glands with inflammatory infiltration, eosinophilic predominance and stromal edema. Immune staining for IgG4 plasma cells was positive in polyps of stomach and colon. The patient was diagnosed of CCS and treated with steroid, he had a good response to steroid. Both histologic findings and treatment response to steroid suggested an autoimmune mechanism underling CCS.