A Parotid Gland Mammary Analogue Secretory Carcinoma in a 4-Year-Old Boy: Case Report and Literature Review.

Background: Mammary analogue secretory carcinoma (MASC) is characterized by similar histologic, immunohistochemical, and molecular features with breast secretory carcinoma. MASC usually occurs in adults. Case report: A 4-year-old boy presented with a right infra-auricular mass. Features of the tumor include solid, tubular, and papillary growth patterns, with homogenous eosinophilic secretions inside microcystic structures. Immunohistochemical stains showed strong, diffuse staining for CK7, S100, pan-TRK protein. P63 was positive in a peripheral pattern. Fluorescence in situ hybridization (FISH) analysis showed the characteristic ETV6-NTRK3 gene fusion. Conclusion: Typical histological, immunohistochemical, and molecular features are present in MASC occurring early in childhood.

Ribosome assembly factor URB1 contributes to colorectal cancer proliferation through transcriptional activation of ATF4.

Ribosome assembly factor URB1 is essential for ribosome biogenesis. However, its latent role in cancer remains unclear. Analysis of The Cancer Genome Atlas database and clinical tissue microarray staining showed that URB1 expression was upregulated in colorectal cancer (CRC) and prominently related to clinicopathological characteristics. Silencing of URB1 hampered human CRC cell proliferation and growth in vitro and in vivo. Microarray screening, ingenuity pathway analysis, and JASPAR assessment indicated that activating transcription factor 4 (ATF4) and X-box binding protein 1 (XBP1) are potential downstream targets of URB1 and could transcriptionally interact through direct binding. Silencing of URB1 significantly decreased ATF4 and cyclin A2 (CCNA2) expression in vivo and in vitro. Restoration of ATF4 effectively reversed the malignant proliferation phenotype of URB1-silenced CRC cells. Dual-luciferase reporter and ChIP assays indicated that XBP1 transcriptionally activated ATF4 by binding with its promoter region. X-box binding protein 1 colocalized with ATF4 in the nuclei of RKO cells, and ATF4 mRNA expression was positively regulated by XBP1. This study shows that URB1 contributes to oncogenesis and CRC growth through XBP1-mediated transcriptional activation of ATF4. Therefore, URB1 could be a potential therapeutic target for CRC.

Prevalence of and risk factors for depressive symptoms among people living with HIV/AIDS receiving antiretroviral treatment in Wuhan, China: a short report.

We aimed to explore the prevalence of and risk factors for depressive symptoms (DS) among people living with HIV/AIDS (PLWHA) receiving antiretroviral treatment (ART) in Wuhan, Hubei, China. A cross-sectional study evaluating adult PLWHA receiving ART in nine designated clinical hospitals was conducted from October to December 2015. The validated Beck Depression Inventory (BDI) was used to assess DS in eligible participants. Socio-demographical, epidemiological and clinical data were directly extracted from the case reporting database of the China HIV/AIDS Information Network. Multinomial regression analysis was used to explore the risk factors for DS. 394 participants were finally included in all analyses. 40.3% were found to have DS with 13.7% having mild DS and 26.6% having moderate to severe DS. The results of multinomial regression analysis suggested that being married or living with a partner, recent experience of ART-related side effects, and/or history of HCV infection were positively associated with mild DS, while increasing age was positively associated with moderate to severe DS.

Association between all-cause mortality and vascular complications in U.S. adults with newly diagnosed type 2 diabetes (NHANES 1999-2018).

AIMS: The impact of macrovascular and microvascular complications, the common vascular complications of type 2 diabetes, on long-term mortality has been well evaluated, but the impact of different complications of newly diagnosed type 2 diabetes (diagnosed within the past 2 years) on long-term mortality has not been reported. We aimed to investigate the relationship between all-cause mortality and vascular complications in U.S. adults (aged ≥ 20 years) with newly diagnosed type 2 diabetes. METHODS: We used data from the 1999-2018 National Health and Nutritional Examination Surveys (NHANES). Cox proportional hazard models was used to assess hazard ratios (HR) and 95% confidence intervals for all-cause mortality. RESULTS: A total of 928 participants were enrolled in this study. At a mean follow-up of 10.8 years, 181 individuals died. In the fully adjusted model, the hazard ratio (HR) (95% confidence interval [CI]) of all-cause mortality for individuals with any single complication compared with those with newly diagnosed type 2 diabetes without complications was 2.24 (1.37, 3.69), and for individuals with two or more complications was 5.34 (3.01, 9.46).Co-existing Chronic kidney disease (CKD) and diabetic retinopathy (DR) at baseline were associated with the highest risk of death (HR 6.07[2.92-12.62]), followed by CKD and cardiovascular disease (CVD) (HR 4.98[2.79-8.89]) and CVD and DR (HR 4.58 [1.98-10.57]). CONCLUSION: The presence of single and combined diabetes complications exerts a long-term synergistic adverse impact on overall mortality in newly diagnosed U.S. adults with type 2 diabetes, underscoring the importance of comprehensive complication screening to enhance risk stratification and treatment.

Transient embolization with microspheres of polyhydroxyalkanoate renders efficient adenoviral transduction of pancreatic capillary in vivo.

BACKGROUND: Our previous study showed an efficient targeting of islets of Langerhans by adenoviral injection via the celiac trunk. Unexpectedly, none of the endothelial cells was infected given the direct contact between adenoviruses and the capillary wall. The present study intended to provide an efficient approach for adenoviral targeting of the microcapillary endothelial cells in the pancreas. METHODS: We prepared microspheres of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) with a size comparable to the diameter of capillary (5-10 µm). Scanning electron microscopy was applied to verify that adenoviruses carrying a green fluorescence protein gene were complexed with PHBHHx-microspheres after 30 min of co-incubation. The complexes were then injected into the pancreas of mice via the celiac trunk. RESULTS: Approximately 40% of endothelial cells in the pancreas were labeled 5 days after surgery. Islet cells were labeled occasionally, whereas labeling of the acinar and ductal tissues was barely detectable. Endothelium targeting was inefficient in other internal organs. Consistent with the reported superior tissue compatibility of PHBHHx, no discernable microspheres were found in all of the organs examined. Furthermore, splenocyte activation was dampened when adenoviruses were complexed with the microspheres. CONCLUSIONS: The present study has established an approach for efficient pancreatic capillary targeting by using microsphere-adenoviral complexes. This procedure could be invaluable for the treatment of capillary-related diseases.

Emotional and neurobehavioural status in chronic pain patients.

OBJECTIVE: To investigate the emotional and neurobehavioural status of patients suffering from chronic pain. METHODS: Fifteen male patients with chronic lower back pain and 15 healthy control subjects were studied for approximately six months. Pain was measured using a visual analogue scale. The WHO Neurobehavioral Core Test Battery (NCTB) was used to assess neurobehavioural effects of environmental and occupational exposures. RESULTS: Visual analogue scale results demonstrated a modest range of reported pain (mean [± SD] 62.0 ± 10.8) in chronic pain patients, whereas control subjects reported no measurable pain. With the NCTB, it was found that scores of negative mood state, including anger-hostility, depression-dejection, fatigue-inertia and tension-anxiety in pain patients were significantly higher than scores in the control subjects. By contrast, scores of positive mood state (vigour-activity) in chronic pain patients were lower than those in the control group. The NCTB scores of the Santa Ana Dexterity and Pursuit Aiming II tests in chronic lower back pain patients were lower than those of the control group. Scores for other NCTB subtests, including the Digit Span, Benton Visual Retention and Digit Symbol tests, were not significantly different compared with controls. Assuntos Emoções , Transtornos das Habilidades Motoras/etiologia , Dor/complicações , Dor/psicologia , Tempo de Reação/fisiologia , Adulto , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Dor/diagnóstico , Medição da Dor , Estimulação Luminosa , Retenção Psicológica/fisiologia , Inquéritos e Questionários

Diagnostic performance of two specific schistosoma japonicum immunological tests for screening schistosoma haematobium in school children in Zambia.

Dipstick Dye Immunoassay (DDIA) and Indirect Haemagglutination Assay (IHA), are two commercially available kits which have been widely used for screening Schistosoma japonicum in P.R. China. Whether they can be used for screening of Schistosoma haematobium are not clear. In order to evaluate the diagnostic efficiency of DDIA and IHA for screening Schistosoma haematobium, serum samples were collected from pupils in endemic areas in Zambia, Southern Africa, and tested by DDIA and IHA by single-blind manner. Meanwhile, the pupils were microscopically examined by infection with Schistosoma and soil-transmitted helminths, visually observed for parasite eggs. Of the enrolled 148 pupils, 61% tested positive for S. haematobium infection, while 31% and 36% of pupils were infected with hookworm and Ascaris respectively. Regarding the parasitological tests as reference standard, for the diagnosis of S. haematobium infection, IHA performed higher sensitivity (74%, 95% CI: 65%-83%) than that of DDIA (60%, 95%CI: 49%-70%). The sensitivities of IHA and DDIA are significant higher in 10-14 years old students than those of 7-9 years old group. The specificity of DDIA and IHA were 61% (95%CI: 49%-74%) and 72% (95%CI: 60%-84%), respectively. The co-infection with STHs decreased the specificity of DDIA but had no impact on that of IHA. Our study indicated that IHA has more potential as an alternative diagnostic tool for identifying schistosomiasis haematobium but need further improvement.

An overview of type E botulism in China.

The geographical distribution of C. botulinum type E and its associated disease, type E botulism in China, is different from that in other areas of the world. Cases of type E botulism generally arise in costal regions. In China, however, type E botulism is found primarily in the Qinghai-Tibet plateau of northwest China far from the ocean, at an altitude of approximately 4-5 km. The foods most commonly associated with the disease are fermented grain and beans as well as raw meat. A suspected outbreak of type E botulism poisoning in the central costal region of China in the 1990s prompted the collection and analysis of samples of mud, sand, and fish from the region. The toxin produced by type E botulinum was found in these samples. Surprisingly, though, upon further analysis, the strain isolated from the samples was identified not as type E C. botulinum, but as the neurotoxigenic bacterium Clostridium butyricum.

[Effects of Tcd A on Rho GTPases and the Cytoskeleton of Leukemia Cell Line K562].

OBJECTIVE: To investigate the effect of clostridium difficile toxin A(TcdA) on the Rho GTPases and the cytoskeleton in K562 cells. METHODS: K562 cells were cultured in vitro with different concentration of TcdA.The effect of TcdA proliferation of cells was detected by MTT method after the K562 cells were stimulated with TcdA for 24,48 and 72h; the expression of cdc42, RhoA, Rac1 mRNA was assessed by RT-PCR; the changes of the microtubule, the microfilament were observed by confocal laser scanning microscopy. RESULTS: The proliferation of K562 cells was inhibited after exposure to TcdA for 24, 48 and 72h, and the inhibitory rate was 47.67% in the treatment for 48 h. the cdc42，RhoA and Rac1 mRNA expressions in the experimental groups decreased after treated with TcdA(P<0.05), which positively correlated with concentration of TcdA. Also, the microfilament decreased ,which was observed by confocal laser scanning microscopy. CONCLUSION: TcdA inhibites K562 cell proliferation and induces apoptosis, TcdA can change the cytoskeleton structure through the cytoskeletal protein genes cdc42 and RhoA, Rac1 mRNA expression,. It is related with cell microfilament content decreasing.

Dynamical information encoding in neural adaptation.

Adaptation refers to the general phenomenon that a neural system dynamically adjusts its response property according to the statistics of external inputs. In response to a prolonged constant stimulation, neuronal firing rates always first increase dramatically at the onset of the stimulation; and afterwards, they decrease rapidly to a low level close to background activity. This attenuation of neural activity seems to be contradictory to our experience that we can still sense the stimulus after the neural system is adapted. Thus, it prompts a question: where is the stimulus information encoded during the adaptation? Here, we investigate a computational model in which the neural system employs a dynamical encoding strategy during the neural adaptation: at the early stage of the adaptation, the stimulus information is mainly encoded in the strong independent firings; and as time goes on, the information is shifted into the weak but concerted responses of neurons. We find that short-term plasticity, a general feature of synapses, provides a natural mechanism to achieve this goal. Furthermore, we demonstrate that with balanced excitatory and inhibitory inputs, this correlation-based information can be read out efficiently. The implications of this study on our understanding of neural information encoding are discussed.

Modeling the oxidation kinetics of sono-activated persulfate's process on the degradation of humic acid.

Ultrasound degradation of humic acid has been investigated in the presence of persulfate anions at ultrasonic frequency of 40 kHz. The effects of persulfate anion concentration, ultrasonic power input, humic acid concentration, reaction time, solution pH and temperature on humic acid removal efficiency were studied. It is found that up to 90% humic acid removal efficiency was achieved after 2 h reaction. In this system, sulfate radicals (SO4⁻·) were considered to be the mainly oxidant to mineralize humic acid while persulfate anion can hardly react with humic acid directly. A novel kinetic model based on sulfate radicals (SO4⁻·) oxidation was established to describe the humic acid mineralization process mathematically and chemically in sono-activated persulfate system. According to the new model, ultrasound power, persulfate dosage, solution pH and reaction temperature have great influence on humic acid degradation. Different initial concentration of persulfate anions and humic acid, ultrasonic power, initial pH and reaction temperature have been discussed to valid the effectiveness of the model, and the simulated data showed new model had good agreement with the experiments data.

[Investigation on endemic situation of schistosomiasis in infection-controlled regions in Anhui Province].

OBJECTIVE: To understand the epidemic situation of schistosomiasis in 27 counties (cities, districts) that reached the criteria of schistosomiasis infection controlled in Anhui Province. METHODS: According to the requirement of The National Assessment Scheme of Schistosomiasis, 81 administrative villages where the schistosomiasis epidemic situation was relatively heaver in above-mentioned 27 counties (1 village per town, 3 towns per county) were sampled and investigated. RESULTS: From 2012 to 2014, 81 villages were investigated, and 34,293 residents received the serum examinations, and 1,086 were positive with a positive rate of 3.17% (0.65%-9.58%), and the positives received stool examinations and the average stool positive rate was 0.37% (0-4.0%). The calculated prevalence of human infection was 0.01%. A total of 3 057 domestic animals were investigated including 438 cattle, 2,550 sheep, and 69 other animals, and no infections were detected. A total of 11,261 living Oncomelania hupensis snails were collected and detected, but no schistosome infected snails were found. Before this investigation, no infected snails were detected for more than 2 years [average 2.3 (2-6) years], and no acute schistosome infection cases were found for more than 2 years [average 4.9 (2-9) years]. CONCLUSION: The infection rates of schistosomiasis in residents and domestic animals are relatively low, and no schistosome infected snails are found in the regions.

Development of an ELISA kit using monoclonal antibody to Clostridium difficile toxin A.

AIM: To establish an ELISA kit using monoclonal antibodies against Clostridium difficile (C. difficile) toxin A. METHODS: An indirect sandwich ELISA was described using the purified rabbit monospecific antiserum as capturing antibody. After the polystyrene microtitre plates with 96 flat-bottomed wells were coated with rabbit antiserum, the wells were blocked with 100 g/L BSA in PBS-T. C. difficile toxin A or culture filtrates were added to each well and then monoclonal antibodies IgG-horseradish peroxidase conjugate was added as detecting antibody, tetramethylbenzidine was used as substrate and A450 of the stopped reacting product was recorded in an automated plate reader. RESULTS: The tested specimens included culture filtrates of 2 strains of toxigenic C. difficile, 2 strains of non-toxigenic C. difficile, 26 strains of E. coli, 2 strains of S. dysenteriae, 1 strain of Bif. infantis, 5 strains of V. cholera, 2 strains of S. typhi, 7 strains of C. botulinum, 1 strain of toxigenic C. sordllii, and 1 strain of C. butyricum. A total of 47 strains of culture filtrates were all negative except for 2 strains of toxigenic C. difficile. The detective limitation of toxin A was 0.1 ng/mL. CONCLUSION: An ELISA kit with high specificity and excellent sensitivity for the rapid detection of C. difficile toxin A was established. It will be a useful tool for diagnostic test of C. difficile toxin A.

Simplified purification method for Clostridium difficile toxin A.

AIM: To establish the purification method for Clostridium difficile (C. difficile) toxin A. METHODS: C. difficile VPI 10463 filtrate was cultured anaerobically by the dialysis bag methods. And then the toxin A was purified by precipitation with 500 g/L (NH4)2SO4 and acid precipitation at pH 5.5, followed by ion-exchange chromatography on DEAE-Toyopearl. RESULTS: Purified toxin A exhibited only one band on native polyacrylamide gel electrophoresis (native-PAGE) and Ouchterlony double immunodiffusion. The molecular weight of toxin A was estimated to be 550,000. The purified toxin A had a protein concentration of 0.881 mg/mL. The minimum lethal dose was 1X10(6) MLD/mL (i.p.mice). The cytotoxic titer was 10(7) CU/mg. The haemagglutinate activity was at a concentration of 1.72 microg/mL. The ratio of fluid volume (mL) accumulated to the length (cm) of the loop was 2.46. CONCLUSION: The modified method for purification of toxin A of C. difficile was simple and convenient. It may be even more suitable for purification of toxin A on large scales.

Induced apoptosis of osteoblasts proliferating on polyhydroxyalkanoates.

The mechanism study on behaviors of cells influenced by biomaterial surface properties can provide profound guidances for functional tissue engineering scaffolds design. In this study, regulation of integrin-mediated cell-substrate interactions using rat osteoblasts incubated on PHA films was investigated. Compared with tissue culture plate (TCP), poly-3-hydroxybutyrate (PHB), copolymer of 3-hydroxybutyrate and 3-hydroxyvalerate (PHBV) and copolymer of 3-hydroxybutyrate and 3-hydroxyhexanoate (PHBHHx), osteoblasts inoculated on a terpolymer of 3-hydroxybutyrate, 3-hydroxyvalerate and 3-hydroxyhexanoate (PHBVHHx) were found to have higher apoptosis rates. Several integrin subunits in osteoblasts grown on PHBVHHx showed altered expressions. Simultaneously, extracellular matrics (ECM) were also remodeled on the material surface. Osteoblasts showed a higher expression of integrin subunit ß3 and αv on PHBVHHx films compared with that on TCP. On the other hand, less vitronectin, osteopontin and fibronectin, the main ligands for integrin ß3 were expressed and deposited in ECM. The unligated integrin ß3 could recruit caspase-8 to the membrane and activate its downstream signaling which was proven by the caspase-8 activation assay. It was therefore concluded that the induced apoptosis of osteoblasts on PHBVHHx was regulated by recruitment of caspase-8 to the unligated integrin ß3.

[Progress of researches on diagnostic antigens of schistosomiasis japonica].

The development of immunodiagnosis makes important contributions to the control of schistosomiasis. The most common way of diagnosis is to detect unknown antibodies through the known antigens, those are divided into soluble antigens, purified antigens and recombinant antigens. The diagnostic antigens which have high-sensitivity and high-specificity, and have the value of early diagnosis become the focus of researches, and are studied by many scholars. This article reviews the progress of the reaearches on diagnostic antigens of schistosomiasis japonica in recent years.

An assessment of the risks of carcinogenicity associated with polyhydroxyalkanoates through an analysis of DNA aneuploid and telomerase activity.

Polyhydroxyalkanoates (PHA) are aliphatic polyesters synthesized by many bacteria. Because of their flexible mechanical strengths, superior elastic property, biodegradability and biocompatibility, PHA have been developed for applications as medical implants, drug delivery matrices, and devices to support cell growth. Lots of studies showed that PHA matrices improved cell proliferation and tissue regeneration. However, the possibility of whether rapid cell proliferation on PHA matrices will induce tumor formation is unclear. Here we confirmed that proliferating rat osteoblasts grown on films of various PHA including PHB, PHBV, P3HB4HB, PHBHHx and PHBVHHx did not lead to cancer induction at least for p8th. Cell proliferation was evaluated by the incorporation of 5-bromodeoxyuridine (BrdU), the transcript expression of cancer related genes Ki67, p53 and c-Fos was monitored by quantitative Real-time PCR, the results showed the cells proliferating on the PHA films were under normal cell cycle regulation. Moreover, DNA aneuploid and telomerase activity were only detected in the positive control UMR-108 cells; compared with cells grown on films, UMR-108 cells had longer telomeres, further demonstrated the normal status of cells proliferating on the PHA films. It indicated that the above PHA family members could be used to support cell growth without indication of susceptibility to tumor induction. These results will be important for promoting the application of PHA as new members of biomaterials.

Nicotinic acid inhibits glucose-stimulated insulin secretion via the G protein-coupled receptor PUMA-G in murine islet ß cells.

OBJECTIVES: Chronic administration of nicotinic acid (NA), a potent antilipidemic compound, aggravates glycemic control in diabetic patients. It is not known if NA has direct effects on islet ß cells. METHODS: Real-time reverse transcriptase-polymerase chain reaction, in situ hybridization, and immunofluorescence techniques were used to examine the expression of NA receptor PUMA-G, a member of the G protein-coupled receptor (G-PCR) family, in murine islet ß cells. Calcium transient was measured using confocal microscopy, whereas the intracellular cyclic adenosine monophosphate and glucose-stimulated insulin secretion (GSIS) from isolated islets were determined by the enzyme-linked immunosorbent assay. RESULTS: High levels of PUMA-G transcripts and protein were detected in all ß cells, and about 40% of α cells. PUMA-G transcripts increased more than 3-fold in islets incubated with interferon γ. Cyclic adenosine monophosphate accumulation, induced by IBMX/forskolin, was inhibited by NA; however, the inhibition was completely abolished by pretreatment of the culture with pertussis toxin. No calcium transient was detected in islet cells in the presence of NA. Static incubation of islets with NA led to an approximately 30% reduction of GSIS. CONCLUSIONS: The results indicated that PUMA-G stimulation by NA in islet ß cells inhibited GSIS likely via activation of the Gi signaling pathway.

The use of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) scaffolds for tarsal repair in eyelid reconstruction in the rat.

Tarsal repair is an important part for eyelid reconstruction. Presently traditional clinic treatments do not produce satisfactory repair effects. The key is to find a proper tarsal repair material. Microbial poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) was studied for application as tarsal substitute in this study. PHBHHx scaffolds were implanted into tarsal defects of Sprague-Dawley rats. Eyelid samples of implanted materials and blank defect controls were collected for histological examination at weekly intervals post surgery. Results were compared among PHBHHx scaffolds, commercial acellular dermal matrices (ADM) and blank defect controls. Both PHBHHx scaffolds and ADM provided satisfactory repair results compared with the blank controls even though the implanted PHBHHx scaffolds showed a 2 weeks inflammation. Fibrous encapsulation and scaffold degradation were observed for the PHBHHx implants. Combined with its strong, elastic mechanical properties, the tissue compatible and biodegradable PHBHHx was proven to be a suitable candidate for tarsal repair.

The behaviour of neural stem cells on polyhydroxyalkanoate nanofiber scaffolds.

Polyhydroxyalkanoates (PHA) have demonstrated their potentials as medical implant biomaterials. Neural stem cells (NSCs) grown on/in PHA scaffolds may be useful for repairing central nervous system (CNS) injury. To investigate this possibility, nanofiber matrices (scaffolds) prepared from several PHA via a novel phase separation process were studied to mimic natural extracellular matrix (ECM), and rat-derived NSCs grown in the PHA matrices were characterized regarding their in vitro differentiation behaviors. All three PHA materials including poly(3-hydroxybutyrate) (PHB), copolymer of 3-hydroxybutyrate and 4-hydroxybutyrate (P3HB4HB), and copolymer of 3-hydroxybutyrate and 3-hydroxyhexanoate (PHBHHx) supported NSC growth and differentiation both on their 2D films and 3D matrices. Among three PHA nanofiber matrices, PHBHHx one showed the strongest potentials to promote NSC differentiation into neurons which is beneficial for CNS repair. Compared to the 2D films, 3D nanofiber matrices appeared to be more suitable for NSC attachment, synaptic outgrowth and synaptogenesis. It was suggested that PHBHHx nanofiber scaffolds (matrices) that promote NSC growth and differentiation, can be developed for treating central nervous system injury.