To evaluate the usefulness of a fasting plasma glucose (FPG) at 24–28 weeks’ gestation to screen for gestational diabetes mellitus (GDM).
RESEARCH DESIGN AND METHODS
The medical records and results of a 75-g 2-h oral glucose tolerance test (OGTT) of 24,854 pregnant women without known pre-GDM attending prenatal clinics in 15 hospitals in China were examined.
FPG cutoff value of 5.1 mmol/L identified 3,149 (12.1%) pregnant women with GDM. FPG cutoff value of 4.4 mmol/L ruled out GDM in 15,369 (38.2%) women. With use of this cutoff point, 12.2% of patients with mild GDM will be missed. The positive predictive value is 0.322, and the negative predictive value is 0.928.
FPG at 24–28 weeks’ gestation could be used as a screening test to identify GDM patients in low-resource regions. Women with an FPG between ≥4.4 and ≤5.0 mmol/L would require a 75-g OGTT to diagnose GDM. This would help to avoid approximately one-half (50.3%) of the formal 75-g OGTTs in China.
Acute myeloid leukemia (AML) is the second most common form of leukemia in children. Aberrant DNA methylation patterns are a characteristic feature in various tumors, including AML. Metallothionein III (MT3) is a tumor suppresser reported to show promoter hypermethylated in various cancers. However, the expression and molecular function of MT3 in pediatric AML is unclear.
Eleven human leukemia cell lines and 41 pediatric AML samples and 20 NBM/ITP (Norma bone marrow/Idiopathic thrombocytopenic purpura) control samples were analyzed. Transcription levels of MT3 were evaluated by semi-quantitative and real-time PCR. MT3 methylation status was determined by methylation specific PCR (MSP) and bisulfite genomic sequencing (BSG). The molecular mechanism of MT3 was investigated by apoptosis assays and PCR array analysis.
The MT3 promoter was hypermethylated in leukemia cell lines. More CpG’s methylated of MT3 was observed 39.0% pediatric AML samples compared to 10.0% NBM controls. Transcription of MT3 was also significantly decreased in AML samples compared to NBM/ITP controls (P < 0.001); patients with methylated MT3 exhibited lower levels of MT3 expression compared to those with unmethylated MT3 (P = 0.049). After transfection with MT3 lentivirus, proliferation was significantly inhibited in AML cells in a dose-dependent manner (P < 0.05). Annexin V assay showed that apoptosis was significantly upregulated MT3-overexpressing AML cells compared to controls. Real-time PCR array analysis revealed 34 dysregulated genes that may be implicated in MT3 overexpression and apoptosis in AML, including FOXO1.
MT3 may be a putative tumor suppressor gene in pediatric AML. Epigenetic inactivation of MT3 via promoter hypermethylation was observed in both AML cell lines and pediatric AML samples. Overexpression of MT3 may inhibit proliferation and induce apoptosis in AML cells. FOXO1 was dysregulated in MT3-overexpressing cells, offering an insight into the mechanism of MT3-induced apoptosis. However, further research is required to determine the underlying molecular details.
Metallothionein III; Pediatric acute myeloid leukemia; Methylation; Tumor suppressor
Primary hyperoxaluria type 1 is a rare autosomal recessive disease of glyoxylate metabolism caused by a defect in the liver-specific peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT) that leads to hyperoxaluria, recurrent urolithiasis, and nephrocalcinosis.
Two unrelated patients with recurrent urolithiasis, along with members of their families, exhibited mutations in the AGXT gene by PCR direct sequencing.
Two heterozygous mutations that predict truncated proteins, p.S81X and p.S275delinsRAfs, were identified in one patient. The p.S81X mutation is novel. Two heterozygous missense mutations, p.M1T and p.I202N, were detected in another patient but were not identified in her sibling. These four mutations were confirmed to be of paternal and maternal origin.
These are the first cases of primary hyperoxaluria type 1 to be diagnosed by clinical manifestations and AGXT gene mutations in mainland China. The novel p.S81X and p.I202N mutations detected in our study extend the spectrum of known AGXT gene mutations.
AGXT gene; Chinese children; Mutational analysis; Novel mutation; Primary hyperoxaluria type 1
Schwannomas occurring in the gallbladder are extremely rare. Preoperative diagnosis of gallbladder schwannomas appears to be very difficult because they are normally asymptomatic and are often found incidentally. Until now, only five cases have been reported in the literature. To our knowledge, the contrast-enhanced ultrasound (CEUS) features of gallbladder schwannomas have not been reported before in other studies. We treated a 55-year-old male patient with gallbladder schwannoma in China. He had no symptoms, and the lesion was incidentally found by conventional ultrasound (US) when performing a health examination. The patient had normal liver function; moreover, serum carcinoembryonic antigen and alpha-fetoprotein were within the normal ranges. The lesion showed no blood flow signals on color Doppler US, and the wall beneath the lesion was intact on CEUS. The lesion was believed to be a benign entity; in addition, gallbladder adenomyomatosis was suspected. A laparoscopic cholecystectomy was performed to remove the mass. Pathological examination revealed that the tumor was mainly composed of spindle-shaped cells; neither atypical cells nor signs of malignancy were found. Immunohistochemical staining showed a strong positive S-100 protein reaction. Vimentin and CD56 staining were also positive, whereas CD34 and CD117 were negative. Finally, the lesion was diagnosed as schwannoma. Herein, we report the case; the associated literature is also reviewed.
Schwannoma; Gallbladder; Ultrasound; Contrast-enhanced ultrasound
We used resting-state functional magnetic resonance imaging (RS-fMRI) to investigate the acute effects of methylphenidate hydrochloride (MPH) on spontaneous brain activity in children with attention deficit hyperactivity disorder (ADHD). In all, 23 boys with ADHD were scanned twice, under either 10 mg dose of MPH or placebo, in a randomized, cross-over, counterbalanced placebo-controlled design. 32 Matched healthy controls were scanned once for comparison. Seven of the 23 ADHD boys participated in a follow-up 8-week MPH treatment. A regional homogeneity (ReHo) method was applied to characterize the local synchronization of spontaneous brain activity. ADHD boys under placebo compared with controls showed decreased ReHo in bilateral dorsolateral prefrontal cortices and increased ReHo in bilateral sensorimotor and parieto-visual cortices. Relative to placebo, MPH upregulated ReHo in bilateral ventral prefrontal cortices and cerebellar vermis, and downregulated ReHo in right parietal and visual areas that overlapped with the abnormally enhanced activities. When under MPH, ReHo differences between patients and controls were no longer observed. The preliminary prediction analysis revealed that the decreased ReHo in right parietal cortex after the acute MPH was positively correlated with the decreased symptom scores after the 8-week MPH treatment in the seven patients. We show that an acute dose of MPH normalized all fronto-parieto-cerebellar dysfunctions in boys with ADHD during the resting state. Preliminary findings furthermore suggest the potential of RS-fMRI as a prognostic imaging tool to identify response to MPH treatment.
attention deficit hyperactivity disorder; functional magnetic resonance imaging; Imaging; Clinical or Preclinical; methylphenidate hydrochloride; Psychiatry & Behavioral Sciences; Psychopharmacology; Psychostimulants; regional homogeneity; resting state; methylphenidate hydrochloride (MPH); attention deficit hyperactivity disorder (ADHD); resting state; functional magnetic resonance imaging (fMRI); regional homogeneity (ReHo); treatment response prediction.
Effectiveness of drinking water treatment, in particular pathogen control during the water treatment process, is always a major public health concern. In this investigation, the application of PCR-DGGE technology to the analysis of microbial community structures and dynamics in the drinking water treatment process revealed several dominant microbial populations including: α-Proteobacteria, β-Proteobacteria, γ-Proteobacteria, Bacteroidetes, Actinobacteria Firmicutes and Cyanobacteria. α-Proteobacteria and β-Proteobacteria were the dominant bacteria during the whole process. Bacteroidetes and Firmicutes were the dominant bacteria before and after treatment, respectively. Firmicutes showed season-dependent changes in population dynamics. Importantly, γ-Proteobacteria, which is a class of medically important bacteria, was well controlled by the O3/biological activated carbon (BAC) treatment, resulting in improved effluent water bio-safety.
drinking water; advanced treatment; bacteria; microbial community structures
C-terminally truncated hepatitis B virus (HBV) middle size surface proteins (MHBst) has been shown to be a transcriptional activator and may be relevant to hepatocarcinogenesis by transactivating gene expression. In the present study, a pcDNA3.1(−)-MHBst167 vector coding for MHBst truncated at amino acid 167 (MHBst167) was constructed and transfected into the HepG2 hepatoma cell line. mRNA and protein expression of MHBst167 in the cells was detected by reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis. A cDNA library of genes transactivated by the truncated protein in HepG2 cells was made in pGEM-T Easy using suppression subtractive hybridization. The cDNAs were sequenced and analyzed with BLAST searching against the sequences in GenBank. The results showed that certain sequences, such as that of human proto-oncogene c-Myc, may be involved in tumor development. An expression vector pCAT3/c-Myc containing the chloramphenicol acetyltransferase (CAT) gene under the control of a c-Myc promoter was generated, and the transcriptional transactivating effect of MHBst167 on the c-Myc promoter was investigated by RT-PCR and western blotting. MHBst167 was found to upregulate the transcriptional activity of the promoter, as well as transcription and translation of c-Myc. MHBst167 was also shown to transactivate SV40 immediate early promoter, and transcriptionally transactivate the expression of human c-Myc. These findings provide new directions for studying the biological functions of MHBst167, and for a better understanding of the tumor development mechanisms of HBV infection.
MHBst167; transactivation; SV40 early promoter; suppression subtractive hybridization; proto-oncogene c-Myc
The field of structural health monitoring is concerned with accurately and reliably assessing the integrity of a given structure to reduce ownership costs, increase operational lifetime, and improve safety. In structural health monitoring systems, fiber Bragg grating (FBG) is a promising measurement technology for its superior ability of explosion proof, immunity to electromagnetic interference, and high accuracy. This paper is a study on the dynamic characteristics of fiber Bragg grating (FBG) sensors applied to a submarine pipeline, as well as an experimental investigation on a laboratory model of the pipeline. The dynamic response of a submarine pipeline under seismic excitation is a coupled vibration of liquid and solid interaction. FBG sensors and strain gauges are used to monitor the dynamic response of a submarine pipeline model under a variety of dynamic loading conditions and the maximum working frequency of an FBG strain sensor is calculated according to its dynamic strain responses. Based on the theoretical and experimental results, it can be concluded that FBG sensor is superior to strain gauge and satisfies the demand of dynamic strain measurement.
The diagnosis of dementia with Lewy bodies (DLB) is often challenging in elderly individuals, not only for its various clinical features, sometimes, but also for its rare changes of periodic synchronous discharges (PSD) in electroencephalogram ( EEG). So, we reported one case of DLB and gave a detailed analysis.
A Chinese patient (Female, 56 years old) presented with progressive cognitive decline and complex visual hallucinations. Several days after admission, she gradually showed focal myoclonic jerks. Mini-Mental State Examination (MMSE) score was 19/30, EEG revealed PSD, Cerebrospinal fluid and 14-3-3 brain protein was negative, Magnetic resonance imaging (MRI) showed diffuse atrophy. To differentiate the PSD derived from DLB or from late-onset Absence Status Epilepticus, we have given the treatment with intravenous valproate (1200 mg/24 h) and diazepam 20 mg under the EEG monitor, a clinical improvement was absent and PSD in EEG did not disappear. Two weeks later, the patient showed akinetic-rigid syndrome and PSD in EEG persisted for a long time. According to her history and therapy, a clinical diagnosis of DLB has been made, but no autopsy for confirmation, and in the following visit, she has a poor prognosis.
PSD in EEG may occasionally be recorded in neurodegenerative disorders such as AD, DLB other than CJD or NCSE. Hence it should not dissuade clinicians from the diagnosis of DLB where the clinical and neuropsychological findings were consistent with suggested diagnostic criteria for DLB.
Visual hallucinations; Periodic synchronous discharges (PSD); Nonconvulsive status epilepticus (NCSE); Dementia with Lewy bodies (DLB)
AIM: To verify that the T stage has greater weight than the N stage in the staging of colorectal cancer.
METHODS: Open data from the Surveillance, Epidemiology, and End Results program were reviewed and analyzed according to the T stage, N stage, and patients’ observed survival (OS). The relative weights of the T and N stages were calculated by multiple linear regressions based on their impact on survival. Risk scores for 25 TN categories were then calculated from the T and N stage relative weights, and a rearranged tumor node metastasis (TNM) staging system was proposed via a cluster analysis of the TN scores.
RESULTS: Both T and N stages significantly affect the OS of patients with colorectal cancer. Moreover, the T stage has greater weight than the N stage in the TNM staging system of colorectal cancer. For colon cancer, the relative T and N stage weights were 0.58 and 0.42, respectively, and for rectal cancer, the relative T and N stage weights were 0.61 and 0.39, respectively. On the basis of cluster analysis of the TN scores, T1N1a was classified to stage I, and T2N1a-1b and T1N1b-2a were classified to stage II in our revised TNM staging system for both colon and rectal cancer. For colon cancer, T4bN0 was classified to stage IIIa, but for rectal cancer, it was classified to stage IIIb.
CONCLUSION: As the T stage affects colorectal cancer survival more significantly than the N stage, the TNM staging should be revised by relative T stage weight.
Colorectal cancer; Neoplasm staging; Cluster analysis; Survival analysis; Observational study
We obtain an extremely high current sensitivity by wrapping a section of microfiber on a thin-diameter chromium-nickel wire. Our detected current sensitivity is as high as 220.65 nm/A2 for a structure length of only 35 μm. Such sensitivity is two orders of magnitude higher than the counterparts reported in the literature. Analysis shows that a higher resistivity or/and a thinner diameter of the metal wire may produce higher sensitivity. The effects of varying the structure parameters on sensitivity are discussed. The presented structure has potential for low-current sensing or highly electrically-tunable filtering applications.
microfiber; current sensor; sensitivity; chrome-nickel wire
The required for Mla12 resistance (RAR1) protein is essential for the plant immune response. In rice, a model monocot species, the function of Oryza sativa RAR1 (OsRAR1) has been little explored. In our current study, we characterized the response of a rice osrar1 T-DNA insertion mutant to infection by Magnaporthe oryzae, the causal agent of rice blast disease. osrar1 mutants displayed reduced resistance compared with wild type rice when inoculated with the normally virulent M. oryzae isolate PO6-6, indicating that OsRAR1 is required for an immune response to this pathogen. We also investigated the function of Os-RAR1 in the resistance mechanism mediated by the immune receptor genes Pib and Pi5 that encode nucleotide binding-leucine rich repeat (NB-LRR) proteins. We inoculated progeny from Pib/osrar1 and Pi5/osrar1 heterozygous plants with the avirulent M. oryzae isolates, race 007 and PO6-6, respectively. We found that only Pib-mediated resistance was compromised by the osrar1 mutation and that the introduction of the OsRAR1 cDNA into Pib/osrar1 rescued Pib-mediated resistance. These results indicate that OsRAR1 is required for Pib-mediated resistance but not Pi5-mediated resistance to M. oryzae.
immune receptor; NB-LRR; OsRAR1; resistance; rice
Streptococcus iniae is a Gram-positive bacterium and a severe pathogen to a wide range of economically important fish species. In addition, S. iniae is also a zoonotic pathogen and can cause serious infections in humans. In this study, we identified from a pathogenic S. iniae strain a putative bacteriocin, Sil, and examined its biological activity. Sil is composed of 101 amino acid residues and shares 35.6% overall sequence identity with the lactococcin 972 of Lactococcus lactis. Immunoblot analysis showed that Sil was secreted by S. iniae into the extracellular milieu. Purified recombinant Sil (rSil) exhibited a dose-dependent inhibitory effect on the growth of Bacillus subtilis but had no impact on the growths of other 16 Gram-positive bacteria and 10 Gram-negative bacteria representing 23 different bacterial species. Treatment of rSil by heating at 50°C abolished the activity of rSil. rSil bound to the surface of B. subtilis but induced no killing of the target cells. Cellular study revealed that rSil interacted with turbot (Scophthalmus maximus) head kidney monocytes and inhibited the innate immune response of the cells, which led to enhanced cellular infection of S. iniae. Antibody blocking of the extracellular Sil produced by S. iniae significantly attenuated the infectivity of S. iniae. Consistent with these in vitro observations, in vivo study showed that administration of turbot with rSil prior to S. iniae infection significantly increased bacterial dissemination and colonization in fish tissues. Taken together, these results indicate that Sil is a novel virulence-associated bacteriostatic and an immunoregulator that promotes S. iniae infection by impairing the immune defense of host fish.
Background: Intestinal barrier function failure from ischemia/reperfusion (I/R) and acute hypoxia has been implicated as a critical determinant in the predisposition to intestinal inflammation and a number of inflammatory disorders. Here, we identified the role of Adenosine A2B receptor (A2BAR) in the regulation of intestinal barrier function under I/R and acute hypoxic conditions. Methods: C57BL/6J mice were used, and were randomized into three groups: Sham, I/R, IR+PSB1115 (a specific A2BAR antagonist) groups. After surgery, the small bowel was harvested for immunohistochemical staining, RNA and protein content, and intestinal permeability analyses. Using an epithelial cell culture model, we investigated the influence of hypoxia on the epithelial function, and the role of A2BAR in the expressions of tight junction and epithelial permeability. The expressions of Claudin-1, occludin and ZO-1 were detected by RT-PCR and Western-Blot. Epithelial barrier function was assessed with transepithelial resistance (TER). Results and conclusions: The A2BAR antagonist, PSB1115, significantly increased tight junction protein expression after intestinal I/R or acute hypoxia conditions. PSB1115 also attenuated the disrupted distribution of TJ proteins. Furthermore, inhibition of A2BAR attenuated the decrease in TER induced by I/R or acute hypoxic conditions, and maintained intestinal barrier function. Antagonism of A2BAR activity improves intestinal epithelial structure and barrier function in a mouse model of intestinal I/R and a cell model of acute hypoxia. These findings support a potentially destructive role for A2BAR under intestinal I/R and acute hypoxic conditions.
Ischemia/reperfusion; hypoxia; adenosine A2B receptor; tight junction; claudin-1; occludin; ZO-1; TER
Vasculogenic mimicry (VM) formation is important for invasion and metastasis of tumor cells in gastric adenocarcinoma (GAC). The present study aimed to investigate the association between signal transducer and activator of transcription-3 (STAT3), phosphor-STAT3 (p-STAT3), hypoxia-inducible factor-1α (HIF-1α) and VM formation in GAC, and discuss their clinical significance and correlation with the prognosis of patients with GAC. The expression levels of STAT3, p-STAT3, HIF-1α and VM were assessed in 60 cases of patients with GAC and 20 cases of patients with gastritis on tissue microarrays by immunohistochemical methods. The expression levels of STAT3, p-STAT3, HIF-1α and VM were higher in patients with GAC (particularly in poorly differentiated GAC) than in those with gastritis (P<0.05). The expression levels of STAT3, p-STAT3 and HIF-1α were higher in VM tissues compared with non-VM tissues (P<0.05). Positive correlations existed between STAT3, p-STAT3, HIF-1α and VM expression (P<0.05). The expression levels of STAT3, p-STAT3 and HIF-1α, VM, status of lymph node metastasis and tumor differentiation degree were associated with the overall survival time of patients with GAC (P<0.05). However, only p-STAT3 and VM expression were identified as the independent risk factors of GAC OS when analyzed with multivariate analysis. p-STAT3 and VM play a significant role in indicating the prognosis of patients with GAC. STAT3 activation may play a positive role in VM formation of GAC by the STAT3-p-STAT3-HIF-1α-VM effect axis.
gastric adenocarcinoma; signal transducer and activator of transcription-3; phosphor-signal transducer and activator of transcription-3; hypoxia-inducible factor-1α; vasculogenic mimicry; prognosis
Familial hypercholesterolemia is an autosomal dominant inherited disease characterized by elevated plasma low-density lipoprotein cholesterol (LDL-C). It is mainly caused by mutations of the low-density lipoprotein receptor (LDLR) gene. Currently, the methods of whole genome sequencing or whole exome sequencing for screening mutations in familial hypercholesterolemia are not applicable in China due to high cost. We performed targeted exome sequencing of 167 genes implicated in the homozygous phenotype of a proband pedigree to identify candidate mutations, validated them in the family of the proband, studied the functions of the mutant protein, and followed up serum lipid levels after treatment. We discovered that exon 9 c.1268 T>C and exon 8 c.1129 T>G compound heterozygous mutations in the LDLR gene in the proband derived from the mother and father, respectively, in which the mutation of c.1129 T>G has not been reported previously. The mutant LDL-R protein had 57% and 52% binding and internalization functions, respectively, compared with that of the wild type. After 6 months of therapy, the LDL-C level of the proband decreased by more than 50% and the LDL-C of the other family members with heterozygous mutation also reduced to normal. Targeted exome sequencing is an effective method for screening mutation genes in familial hypercholesterolemia. The exon 8 and 9 mutations of the LDLR gene were pedigree mutations. The functions of the mutant LDL-R protein were decreased significantly compared with that of the wild type. Simvastatin plus ezetimibe was proven safe and effective in this preschool-age child.
The microscopic structure of frozen aqueous sucrose solutions, over concentrations of 0–75% (w/v), is characterized by using multiple continuous-wave and pulsed electron paramagnetic resonance (EPR) spectroscopic and relaxation techniques and the paramagnetic spin probe, TEMPOL. The temperature dependence of the TEMPOL EPR lineshape anisotropy reveals a mobility transition, specified at 205 K in pure water and 255 ±5 K for >1% (w/v) added sucrose. The transition temperature is >>Tg, where Tg is the homogeneous water glass transition temperature, which shows that TEMPOL resides in the mesoscopic domain (mesodomain) at water-ice crystallite boundaries, and that the mesodomain sucrose concentrations are comparable at >1% (w/v) added sucrose. Electron spin echo envelope modulation (ESEEM) spectroscopy of TEMPOL-2H2-sucrose hyperfine interactions also indicates comparable sucrose concentrations in mesodomains at >1% (w/v) added sucrose. Electron spin echo (ESE) – detected longitudinal and phase memory relaxation times (T1 and TM, respectively) at 6 K indicate a general trend of increased mesodomain volume with added sucrose, in three stages: 1-15, 20-50, and >50% (w/v). The calibrated TEMPOL concentrations indicate that the mesodomain volume is less than the predicted maximally freeze-concentrated value [80 (w/w); 120% (w/v)], with transitions at 15-20% and 50% (w/v) starting sucrose. An ordered sucrose hydrate phase, which excludes TEMPOL, and a disordered, amorphous sucrose-water glass phase, in which TEMPOL resides, are proposed to compose a heterogeneous mesodomain. The results show that the ratio of ordered and disordered volume fractions in the mesodomain is exquisitely sensitive to the starting sucrose concentration.
To explore whether intensified, multifactorial intervention could prevent macrovascular disease in patients with recently diagnosed type 2 diabetes.
RESEARCH DESIGN AND METHODS
A total of 150 type 2 diabetic patients, with disease duration of <1 year and without clinical arteriosclerotic disease or subclinical atherosclerotic signs confirmed by ultrasonographic scanning of three conducting arteries, were randomized into an intensive intervention group and a conventional intervention group. They then received intensive, multifactorial intervention or conventional intervention over 7 years of follow-up. The patients’ common carotid intima-media thicknesses (CC-IMTs) were measured every year. The primary outcome was the time to the first occurrence of CC-IMTs ≥1.0 mm and/or development of atherosclerosis plaques in the carotid artery. The secondary outcome was clinical evidence of cardiovascular disease.
A total of 70 patients in the intensive group and 68 patients in the conventional group completed the 7-year follow-up. Subclinical macrovascular (primary) outcomes occurred in seven cases in the intensive group and 22 cases in the conventional group for a cumulative prevalence of 10.00 and 32.35%, respectively (P < 0.05). No significant differences between the two groups were observed regarding the secondary outcome.
Primary prevention of macrovascular diseases can be achieved through intensified, multifactorial intervention in patients with short-duration type 2 diabetes. Type 2 diabetic patients should undergo intensive multifactorial interventions with individual targets for the prevention of macrovascular diseases.
Edwardsiella tarda is a Gram-negative bacterial pathogen with a broad host range that includes fish and humans. In this study, we examined the activity and function of the lysozyme inhibitor Ivy (named IvyEt) identified in the pathogenic E. tarda strain TX01. IvyEt possesses the Ivy signature motif CKPHDC in the form of 82CQPHNC87 and contains several highly conserved residues, including a tryptophan (W55). For the purpose of virulence analysis, an isogenic TX01 mutant, TXivy, was created. TXivy bears an in-frame deletion of the ivyEt gene. A live infection study in a turbot (Scophthalmus maximus) model showed that, compared to TX01, TXivy exhibited attenuated overall virulence, reduced tissue dissemination and colonization capacity, an impaired ability to replicate in host macrophages, and decreased resistance against the bactericidal effect of host serum. To facilitate functional analysis, recombinant IvyEt (rIvy) and three mutant proteins, i.e., rIvyW55A, rIvyC82S, and rIvyH85D, which bear Ala, Ser, and Asp substitutions at W55, C82, and H85, respectively, were prepared. In vitro studies showed that rIvy, rIvyW55A, and rIvyH85D were able to block the lytic effect of lysozyme on a Gram-positive bacterium, whereas rIvyC82S could not do so. Likewise, rIvy, but not rIvyC82S, inhibited the serum-facilitated killing effect of lysozyme on E. tarda. In vivo analysis showed that rIvy, but not rIvyC82S, restored the lost pathogenicity of TXivy and enhanced the infectivity of TX01. Together these results indicate that IvyEt is a lysozyme inhibitor and a virulence factor that depends on the conserved C82 for biological activity.
Due to improvements in early detection, treatment, and supportive care, the number of colorectal cancer (CRC) survivors is increasing; therefore, careful attention should always be paid to the second primary cancer (SPC) in treating these CRC patients. The present study attempts to determine the correlation and clinical aspects of CRC to other cancers in patients suffering from SPC involving CRC.
From January 2002 and June 2010, 1,679 cancer cases, CRC was accompanied by SPC in 89 patients (5.3%), including 16 (18%) synchronous and 73 (82%) metachronous SPC patients. These patients were subsequently classified into two groups: the first group had CRC diagnosed first as CRC first (CRCF); and the second group had another type of cancer diagnosed before the diagnosis of CRC as other cancer first (OCF). Of these 73 patients, 22 (30.1%) were in the group of CRCF, whereas 51 (69.9%) were in the group of OCF. Patients’ clinicopathological characteristics and clinical outcomes were analyzed and compared between the two groups.
There was a significant difference in the sites of cancers between the two groups: 14 (27.5%) patients in the OCF group had gastric cancer, compared to one (4.5%) patient in the CRCF group (P = 0.026). Although there was no difference of hepatitis B virus (HBV) or hepatitis C virus (HCV) carriers between the OCF and CRCF groups (P = 0.165), there were six (27.3%) CRC patients with hepatocellular carcinoma (HCC) in the CRCF group, which was significantly higher than the two (3.9%) patients in the OCF group (P = 0.003). Furthermore, the cancer-specific survival rate of the CRCF patient group was significantly higher than that of the OCF patient group (P = 0.036).
In this retrospective analysis, gastric cancer patients compared to other secondary cancers were at a higher risk of developing subsequent CRC as SPC; alternatively, patients with CRC were at a higher risk of developing HCC as SPC subsequently, no matter whether patients were HBV or HCV carriers. Therefore, careful attention should always be paid to the possibility of secondary CRC to construct effective surveillance when treating cancer patients.
Colorectal cancer; Second primary cancer; Prognosis
The present study was conducted to clarify whether treatment with L-serine can improve the brain repair and neurorestoration of rats after permanent middle cerebral artery occlusion (pMCAO). After pMCAO, the neurological functions, brain lesion volume, and cortical injury were determined. GDNF, NGF, NCAM L1, tenascin-C, and Nogo-A levels were measured. Proliferation and differentiation of the neural stem cells (NSCs) and proliferation of the microvessels in the ischemic boundary zone of the cortex were evaluated. Treatment with L-serine (168 mg/kg body weight, i.p.) began 3 h after pMCAO and was repeated every 12 h for 7 days or until the end of the experiment. L-Serine treatment: 1) reduced the lesion volume and neuronal loss; 2) improved the recovery of neurological functions; 3) elevated the expression of nerve growth-related factors; and 4) facilitated the proliferation of endogenous NSCs and microvessels activated after pMCAO and increased the number of new-born neurons. 5) D-cycloserine, an inhibitor of serine hydroxymethyltransferase, blunted the effects of L-serine on NSC proliferation, differentiation, microvascular proliferation. In conclusions, L-serine treatment in pMCAO rats can reduce brain injury and facilitate neurorestoration which is partly associated with the improvement of proliferation of NSCs and microvessels, reconstruction of neurovascular units and resultant neurorepair. The effects of L-serine on endogenous NSC proliferation and microvascular proliferation are partly mediated by the action of L-serine as a substrate for the production of one-carbon groups used for purine and pyrimidine synthesis and modulation of the expression of some nerve growth-related factors.
Streptococcus iniae is a Gram-positive bacterium that is reckoned one of the most severe aquaculture pathogens. It has a broad host range among farmed marine and freshwater fish and can also cause zoonotic infection in humans. Here we report for the first time the complete genome sequence as well as the host factor-induced proteomic profile of a pathogenic S. iniae strain, SF1, a serotype I isolate from diseased fish. SF1 possesses a single chromosome of 2,149,844 base pairs, which contains 2,125 predicted protein coding sequences (CDS), 12 rRNA genes, and 45 tRNA genes. Among the protein-encoding CDS are genes involved in resource acquisition and utilization, signal sensing and transduction, carbohydrate metabolism, and defense against host immune response. Potential virulence genes include those encoding adhesins, autolysins, toxins, exoenzymes, and proteases. In addition, two putative prophages and a CRISPR-Cas system were found in the genome, the latter containing a CRISPR locus and four cas genes. Proteomic analysis detected 21 secreted proteins whose expressions were induced by host serum. Five of the serum-responsive proteins were subjected to immunoprotective analysis, which revealed that two of the proteins were highly protective against lethal S. iniae challenge when used as purified recombinant subunit vaccines. Taken together, these results provide an important molecular basis for future study of S. iniae in various aspects, in particular those related to pathogenesis and disease control.
Keratocystic odontogenic tumors (KCOT) are benign, locally aggressive intraosseous tumors of odontogenic origin. KCOT have a higher stromal microvessel density (MVD) than dentigerous cysts (DC) and normal oral mucosa. To identify genes in the stroma of KCOT involved in tumor development and progression, RNA sequencing (RNA-Seq) was performed using samples from KCOT and primary stromal fibroblasts isolated from gingival tissues. Seven candidate genes that possess a function potentially related to KCOT progression were selected and their expression levels were confirmed by quantitative PCR, immunohistochemistry and enzyme-linked immunosorbent assay. Expression of lysyl oxidase-like 4 (LOXL4), the only candidate gene that encodes a secreted protein, was enhanced at both the mRNA and protein levels in KCOT stromal tissues and primary KCOT stromal fibroblasts compared to control tissues and primary fibroblasts (P<0.05). In vitro, high expression of LOXL4 could enhance proliferation and migration of the human umbilical vein endothelial cells (HUVECs). There was a significant, positive correlation between LOXL4 protein expression and MVD in stroma of KCOT and control tissues (r=0.882). These data suggest that abnormal expression of LOXL4 of KCOT may enhance angiogenesis in KCOT, which may help to promote the locally aggressive biological behavior of KCOT.
angiogenesis; keratocystic odontogenic tumor; lysyl oxidase-like 4; RNA-sequencing; tumor stromal fibroblast
The aim of this study was to investigate the interaction effects of pri-let-7a-1 rs10739971 with pepsinogen C (PGC) and excision repair cross complementing group 6 (ERCC6) gene polymorphisms and its association with the risks of gastric cancer and atrophic gastritis. We hoped to identify miRNA polymorphism or a combination of several polymorphisms that could serve as biomarkers for predicting the risk of gastric cancer and its precancerous diseases.
Sequenom MassARRAY platform method was used to detect polymorphisms of pri-let-7a-1 rs10739971 G→A, PGC rs4711690 C→G, PGC rs6458238 G→A, PGC rs9471643 G→C, and ERCC6 rs1917799 in 471 gastric cancer patients, 645 atrophic gastritis patients and 717 controls.
An interaction effect of pri-let-7a-1 rs10739971 polymorphism with ERCC6 rs1917799 polymorphism was observed for the risk of gastric cancer (Pinteraction = 0.026); and interaction effects of pri-let-7a-1 rs10739971 polymorphism with PGC rs6458238 polymorphism (Pinteraction = 0.012) and PGC rs9471643 polymorphism (Pinteraction = 0.039) were observed for the risk of atrophic gastritis.
The combination of pri-let-7a-1 rs10739971 polymorphism and ERCC6 and PGC polymorphisms could provide a greater prediction potential than a single polymorphism on its own. Large-scale studies and molecular mechanism research are needed to confirm our findings.
The purpose of this study was to report our approach of partial nephrectomy (PN) using a supra-12th rib mini-flank incision. We compared mini-incision open partial nephrectomy (MI-OPN) with open partial nephrectomy (OPN) and laparoscopic partial nephrectomy (LPN) to verify whether MI-OPN can be an alternative to OPN and LPN.
This was a retrospective single-center study including 194 patients who underwent partial nephrectomy (PN) between February 2005 and December 2010. Demographic, perioperative, and complication data were compared among the MI-OPN group, OPN group and LPN group.
No statistical differences were reported in either group for age, sex, BMI, tumour side (right or left kidney), RENAL nephrometry scores, PADUA score and preoperative eGFR. The operative time was longer in LPN group when compared with MI-OPN and OPN group (all P<0.001). The warm ischemia time of LPN group was longer than MI-OPN group (P = 0.032) and OPN group (P = 0.005). The length of stay of LPN group was shorter than OPN group (P = 0.018), but was similar to MI-OPN group (P = 0.094). The incidence of renal artery clamping was lower in OPN group when compared with MI-OPN and LPN group (all P<0.001). More estimated blood loss was found in OPN group when compared with MI-OPN group (p = 0.003) and LPN group (P = 0.014). The overall incidence of postoperative complications was similar.
The approach of MI-OPN can couple the benefits of both minimally invasive and open partial nephrectomy techniques with less estimated blood loss, shorter operative time, shorter length of stay, less postoperative complications, and a smaller incision. MI-OPN may be an effective alternative to laparoscopic or traditional open approaches, which maybe more suitable for the tumors with high RENAL nephrometry score or PADUA score.