Effects of phenylephrine on systemic and cerebral circulations in humans: a systematic review with mechanistic explanations.

We conducted a systematic review of the literature reporting phenylephrine-induced changes in blood pressure, cardiac output, cerebral blood flow and cerebral tissue oxygen saturation as measured by near-infrared spectroscopy in humans. We used the proportion change of the group mean values reported by the original studies in our analysis. Phenylephrine elevates blood pressure whilst concurrently inducing a reduction in cardiac output. Furthermore, despite increasing cerebral blood flow, it decreases cerebral tissue oxygen saturation. The extent of phenylephrine's influence on cardiac output (r = -0.54 and p = 0.09 in awake humans; r = -0.55 and p = 0.007 in anaesthetised humans), cerebral blood flow (r = 0.65 and p = 0.002 in awake humans; r = 0.80 and p = 0.003 in anaesthetised humans) and cerebral tissue oxygen saturation (r = -0.72 and p = 0.03 in awake humans; r = -0.24 and p = 0.48 in anaesthetised humans) appears closely linked to the magnitude of phenylephrine-induced blood pressure changes. When comparing the effects of phenylephrine in awake and anaesthetised humans, we found no evidence of a significant difference in cardiac output, cerebral blood flow or cerebral tissue oxygen saturation. There was also no evidence of a significant difference in effect on systemic and cerebral circulations whether phenylephrine was given by bolus or infusion. We explore the underlying mechanisms driving the phenylephrine-induced cardiac output reduction, cerebral blood flow increase and cerebral tissue oxygen saturation decrease. Individualised treatment approaches, close monitoring and consideration of potential risks and benefits remain vital to the safe and effective use of phenylephrine in acute care.

[Analysis of risk factors associated with acute Stanford type B aortic dissection complicated with pleural effusion and observation of the curative effect after intracavitary repair].

Objective: To investigate the risk factors of acute Stanford type B aortic dissection (TBAD) complicated with pleural effusion (PE) and the short-term and long-term outcomes of thoracic endovascular aortic repair (TEVAR). Methods: A case-control study. The clinical and imaging data of 1 083 patients with acute TBAD admitted to the General Hospital of Northern Theater Command from April 2002 to December 2020 were retrospectively analyzed, including 211 cases with pleural effusion and 872 cases without pleural effusion. The baseline analysis of the two groups of patients was performed. The risk factors associated with pleural effusion were analyzed by binary logistic regression, and the results were expressed as odds ratio (OR) and 95% confidence interval (CI). According to the quantity of pleural effusion, they were simultaneously divided into small pleural effusion group and medium large pleural effusion group, to compare the short-term and long-term effects of TEVAR patients with different amounts of pleural effusion. Results: The incidence of pericardial effusion (17.5% vs. 3.8%, P<0.001), anemia (21.3% vs. 12.5%, P=0.001), aortic spiral tear (49.8% vs. 37.8%, P=0.002), dissection tear over diaphragm (57.8% vs. 48.1%, P=0.011), serum creatinine [85 (69, 111) vs. 81 (67, 100) µmol/L, P=0.011] and white blood cell levels[(11.3±4.2)×109/L vs. (10.3±4.2)×109/L, P=0.002] in acute TBAD pleural effusion group were significantly higher than those in non-pleural effusion group, and the hemoglobin level was significantly lower than that in non-pleural effusion group [(128±20) vs. (133±17) g/L, P<0.05]. Logistic stepwise regression analysis showed that pericardial effusion (OR=5.038,95%CI 2.962-8.568,P<0.001), anemia (OR=2.047,95%CI 1.361-3.079,P=0.001), spiral tear (OR=1.551,95%CI 1.030-2.336, P=0.002) and elevated white blood cell (OR=1.059,95%CI 1.011-1.102, P=0.005) were independent risk factors for TBAD complicated with pleural effusion. The incidences of all-cause death (4/19 vs. 1.5% vs. 0.9%, P<0.001), aortogenic death (4/19 vs. 0.7% vs. 0.7%, P<0.001) and aortic related adverse events (4/19 vs. 1.5% vs. 1.1%, P<0.001) in patients with large pleural effusion during TEVAR operation were significantly higher than those in patients with small pleural effusion and those without pleural effusion, and the differences were statistically significant. At 1 month follow-up after TEVAR, the incidence of all-cause death (4/16 vs. 3.3% vs. 1.6%, P<0.001), aortogenic death (4/16 vs. 0.8% vs.0.7%, P<0.001), aorta related adverse events (4/16 vs. 4.1% vs. 4.7%, P=0.013) and overall clinical adverse events (4/16 vs.9.8% vs. 6.7%, P=0.014) in the medium and large thoracic group were significantly higher than those in the small pleural effusion group and no pleural effusion group, and the differences were statistically significant. At 1 year follow-up after TEVAR, the incidence of all-cause death (4/15 vs. 4.9% vs. 3.9%, P=0.004), aortogenic death (4/15 vs.2.5% vs. 2.1%, P<0.001), aorta related adverse events (5/15 vs. 11.5% vs. 9.4%, P=0.012) and overall clinical adverse events (5/15 vs. 18.9% vs. 13.1%, P=0.029) in the medium and large thoracic group were significantly higher than those in the small pleural effusion group and no pleural effusion group, and the differences were statistically significant. Conclusions: Single center data showed that pericardial effusion, anemia, spiral tear and elevated white blood cell were independent risk factors for acute TBAD complicated with pleural effusion; the early (1 month) and long-term (1 year) rates of all-cause death, aortic mortality, aortic adverse events and overall clinical adverse events were significantly higher in TBAD patients with moderate pleural effusion after TEVAR, and moderate and large pleural effusion was an independent risk factor for near and long-term aortic related adverse events after TEVAR surgery.

Noninvasive prenatal diagnosis for pregnancies at risk for ß-thalassaemia: a retrospective study.

OBJECTIVE: To evaluate the clinical feasibility of noninvasive prenatal diagnosis (NIPD) for ß-thalassaemia using circulating single molecule amplification and re-sequencing technology (cSMART). DESIGN: Through carrier screening, 102 pregnant Chinese couples carrying pathogenic HBB gene variants were recruited to the study. Pregnancies were managed using traditional invasive prenatal diagnosis (IPD). Retrospectively, we evaluated the archived pregnancy plasma DNA by NIPD to evaluate the performance of our cSMART assay for fetal genotyping. SETTING: Chinese prenatal diagnostic centres specialising in thalassaemia testing. POPULATION: Chinese carrier couples at high genetic risk for ß-thalassaemia. METHODS: Fetal cell sampling was performed by amniocentesis and HBB genotypes were determined by reverse dot blot. NIPD was performed by a newly designed HBB cSMART assay and fetal genotypes were called by measuring the allelic ratios in the maternal cell-free DNA. MAIN OUTCOME MEASURES: Concordance of HBB fetal genotyping between IPD and NIPD and the sensitivity and specificity of NIPD. RESULTS: Invasive prenatal diagnosis identified 29 affected homozygotes or compound heterozygotes, 54 heterozygotes and 19 normal homozygotes. Compared with IPD results, 99 of 102 fetuses (97%) were correctly genotyped by our NIPD assay. Two of three discordant samples were false positives and the other sample involved an incorrect call of a heterozygote carrier as a homozygote normal. Overall, the sensitivity and specificity of our NIPD assay was 100% (95% CI 88.06-100.00%) and 97.26% (95% CI 90.45-99.67%), respectively. CONCLUSIONS: This study demonstrates that our cSMART-based NIPD assay for ß-thalassaemia has potential clinical utility as an alternative to IPD for pregnant HBB carrier couples. TWEETABLE ABSTRACT: A new noninvasive test for pregnancies at risk for ß-thalassaemia.

[Relationship between serum folate and CIN1 prognosis and its interaction with HR-HPV infection].

Objective: To evaluate the relationship between serum folate and the prognosis of cervical intraepithelial neoplasia grade I (CIN1) and the interaction between folate and high risk human papillomavirus (HR-HPV) infection. Methods: From a community-based married women cohort established in Jiexiu and Yangqu County of Shanxi Province from June to December 2014, a total of 564 eligible women with CIN1 by pathologically diagnosed were recruited. The pathological examination was performed again 12 months later. According to the prognosis of CIN1, participants were divided into CIN1 regression group, persistence and progression group, respectively. Nested case-control study was used to explore the relationship between serum folate and CIN1 prognosis, and additive model was used to analyze the interaction between serum folate and HR-HPV infection. Results: Among 564 CIN1 patients, 479 cases underwent pathological examination again, 331 were divided in CIN1 regression group and other 148 in persistence and progression group. The levels of serum folate in CIN1 regression group and persistence and progression group were (18.890±8.360) and (15.640±5.550) nmol/L, respectively, and the difference was statistically significant (Z=-6.937, P<0.001). HPV infection was detected in 154 patients, including 148 cases of HR-HPV infection and 6 cases of low risk human papillomavirus (LR-HPV) infection. Univariate analysis showed that there were significant differences in the age, passive smoking, frequency of pudendal cleaning, frequency of cleaning after sex, frequency of changing underwear, serum folate and HR-HPV infection between regression group and persistence and progression group (P<0.05). Multivariate logistic regression analysis showed that the frequency of pudendal cleaning (OR=0.422, 95%CI: 0.238-0.750), frequency of changing underwear (OR=0.574, 95%CI: 0.355-0.928), serum folate (13.06-16.78nmol/L: OR=4.806, 95%CI: 2.355-9.810; ≤13.05nmol/L: OR=8.378, 95%CI: 4.024-17.445), HR-HPV infection (OR=1.852, 95%CI: 1.170-2.933) were the independent influencing factors of CIN1 prognosis. Interaction analysis showed that the relative excess risk of low serum folate level and HR-HPV infection for the CIN1 persistence and progression was 4.992 (95%CI: 0.189-9.796), attributable proportion due to interaction was 0.552 (95%CI: 0.279-0.824), synergy index was 2.632 (95%CI: 1.239-5.588), aOR of serum folate≤16.78 nmol/L and HR-HPV infection positive was 9.055 (95%CI: 4.878-16.807). Conclusion: Low serum folate level could increase the risk of CIN1 persistence and progression, and might enhance the risk when combined with HR-HPV infection.

[Clinical characteristics of congenital nephrogenic diabetes insipidus].

The purpose of this study was to improve the ability to visualize and diagnose congenital nephrogenic diabetes insipidus (CNDI). The clinical manifestations, laboratory examination findings, imaging features and treatment outcomes of 22 patients with CNDI admitted to the First Affiliated Hospital of Zhengzhou University from May 2013 to May 2020 were retrospectively analyzed. Among the 22 patients with CNDI, 86.4% (19 cases) were male. The age of the 22 patients ranged from 2 months to 47 years old, in which 20 cases were younger than 30 years old and 2 cases were older than 30 years old. The clinical manifestations were polydipsia and polyuria, accompanied with various degrees of fever, defects in growth and development, and increased serum creatinine in some patients. Fifteen patients (68.2%) had different degrees of bilateral kidney and ureteral hydronephrosis, and increased residual urine volume in the bladder. Pituitary magnetic resonance imaging (MRI) enhanced scan showed that the high signal intensity in the posterior pituitary lobe was not detectable in 5 cases (22.7%), and blurred in 6 cases (27.3%). Seven tested patients were all found AVPR2 gene mutation. For patients with suspected CNDI, water-inhibiting vasopressin test and genetic testing should be performed in time so as to confirm diagnosis and treat as early as possible.

Large-scale network dysfunction in vascular cognitive disorder supports connectional diaschisis in advanced arteriosclerosis.

BACKGROUND AND PURPOSE: The interrelation of cognitive performance, cerebrovascular damage and brain functional connectivity (FC) in advanced arteriosclerosis remains unclear. Our aim was to investigate the associations between FC, white matter damage and cognitive impairment in carotid artery disease. METHODS: Seventy-one participants with a recent cerebrovascular event and with written informed consent underwent resting-state functional magnetic resonance imaging and the Addenbrooke's Cognitive Examination - Revised (ACE-R). Network and inter-hemispheric FC metrics were compared between cognitively normal and impaired subjects, and interrelated with cognition. In order to explore the nature of FC changes, their associations with microstructural damage of related white matter tracts and cognitive performance were investigated, followed by mediation analysis. RESULTS: Participants with global cognitive impairment showed reduced FC compared to the cognitively intact subjects within the central executive network (CEN), and between hemispheres. Patients with executive dysfunction had decreased CEN FC whilst patients with memory loss demonstrated low FC in both the CEN and the default mode network (DMN). Global performance correlated with connectivity metrics of the CEN hub with DMN nodes, and between hemispheres. Cingulum mean diffusivity (MD) was negatively correlated with ACE-R and CEN-DMN FC. The cingulum MD-cognition association was partially mediated by CEN-DMN FC. CONCLUSIONS: Long-range functional disconnection of the CEN with DMN nodes is the main feature of cognitive impairment in elderly subjects with symptomatic carotid artery disease. Our findings provide further support for the connectional diaschisis concept of vascular cognitive disorder, and highlight a mediation role of functional disconnection to explain associations between microstructural white matter tract damage and cognitive impairment.

[Isolation and Identification of two Escherichia albertii strains in Shanxi Province, China].

Objective: To investigate the prevalence of Escherchia albertii in Shanxi province. Methods: The chicken intestines were enriched in EC broth. The eae gene was detected by PCR, and the eae-positive EC enrichments were inoculated in MacConkey agar plate. The eae-positive lactose non-fermenting isolates were presumed as Escherchia albertii, and then analyzed by triplex-PCR, 16S rDNA sequencing and MLST. Results: Two suspected Escherchia albertii were isolated from 250 samples of chicken intestines. It was identified as Escherchia albertii by phenotypic, specific genes,16S rDNA sequencing, and MLST analyses. The cytolethal distending toxin B (cdtB) showed positive by PCR,and they were clusted to Ⅱ/Ⅲ/Ⅴ group by sequencing. Conclusion: This study showed that the Escherchia albertii was existed in Shanxi province, China.

On-line quantitative analysis of heavy metals in water based on laser-induced breakdown spectroscopy.

Heavy metal pollution from industrial wastewater is an important source. A method for heavy metals determination in industrial wastewater based on laser-induced breakdown spectroscopy (LIBS) technique was studied and the on-line monitoring system that used automatic graphite enrichment and spatial plasma confinement detection was developed and field demonstrated. The limits of detection (LOD) of heavy metal elements (Cd, Cr, Cu, Ni, Pb, Zn) could reach several µg/L. In Tongling, the on-line heavy metal monitor was field demonstrated. The calibration curves of copper and zinc were built on site, and then on-line monitoring was conducted. The measurement results of this monitor were compared with ICP-OES and had a good correlation. The results showed that the heavy metal monitor could be used for on-line detection of heavy metals in wastewater and had a good reliability.

Cerebral blood flow abnormalities in neuropsychiatric systemic lupus erythematosus.

OBJECTIVE: To investigate the clinical characteristics, imaging changes and early diagnostic methods of neuropsychiatric systemic lupus erythematosus (NPSLE). METHODS: Thirty-five SLE patients, of which 16 had overt neuropsychiatric symptoms, underwent examination for multiple autoantibodies, including anti-double-stranded DNA (anti-dsDNA) antibody, anti-nucleosome antibody, anti-cardiac-phospholipid antibody (aCL)-IgG, aCL-IgM, anti-ß2-glycoprotein I antibody and anti-ribosomal P antibody, and the SLEDAI score of every patient was recorded. All patients further received neuropsychological tests, including the Mini-Mental State Examination, the Self-Rating Anxiety Scale and the Self-Rating Depression Scale. Imaging examination using 3D arterial spin labeling was performed on 3.0 T MRI scanners. After processing the 3D arterial spin labeling image, the cerebral blood flow map was obtained and the cerebral blood flow value was calculated. RESULTS: The values of anti-dsDNA, anti-nucleosome antibody, aCL-IgG and anti-ß2-glycoprotein I antibodies were significantly higher in the NPSLE group than those in the SLE group. The SLEDAI scores of the NPSLE group were significantly higher than those of the SLE group. There were no significant differences between the NPSLE group and the SLE group in the directional ability, memory, attention, numeracy, recall ability or language ability scores on the Mini-Mental State Examination scale. Furthermore, there were no symptoms of anxiety or depression in any of the patients, according to the Self-Rating Anxiety Scale and Self-Rating Depression Scale. In the 35 patients with SLE, decreases in blood perfusion were seen in some areas, and were unilateral and asymmetrically distributed. There was obvious asymmetry between sides in areas including the frontal lobe, temporal lobe, parietal lobe and occipital lobe. The incidence of perfusion decreases in frontal lobe in the NPSLE group was significantly higher than in the SLE group. CONCLUSION: Neurological lesions in SLE patients can be detected by arterial spin labeling. Cerebral blood flow abnormalities may be helpful for the early diagnosis of neurological lesions in NPSLE.

Correlation between composition, microstructure, and emission properties in Nd-doped Si-rich Si oxynitride films: investigation into the nature of the sensitizer.

Rare earth (RE) ions doped in Si-based materials, compatible with Si technology, are promising compounds with regards to optical communication and energy conversion. In this article, we show the emission properties of Nd-doped Si-rich Si oxynitride (Nd-SRSON) films, and their dependence on the dangling bond density and the nature of the sensitizer. These films were prepared by reactive magnetron sputtering and post-annealing. The film composition, microstructure, and emission properties were investigated as a function of deposition parameters and annealing temperatures. Both Fourier transform infrared (FTIR) and ellipsometry spectroscopy measurements have confirmed that the sample composition (Si/N ratio) can be carefully tuned by varying the ratio of reactive nitrogen to argon in the sputtering plasma. Moreover, FTIR and x-ray photoelectron spectroscopy measurements demonstrate the existence of both nitrogen and oxygen dangling bonds (N· and O·) in as-deposited samples. These dangling bonds were passivated during annealing. Under non-resonant excitation at 488 nm, the films exhibit a significant photoluminescence (PL) signal from Nd3+ ions demonstrating the occurrence of an effective sensitization of Nd3+ ions in the host matrix. Both PL excitation and ellipsometry results (the energy band gap from new amorphous model) exclude the sensitization by an exciton with energy over the band gap, whereas the presence of Si agglomerates, at the atomic scale, have been identified as effective sensitizers towards Nd3+ ions. This work not only provides knowledge to optimize Si-based materials for favorable emission properties, but also, presents a universal methodology to investigate the nature of sensitizers for RE emitters. This allows one to find correlations between composition, microstructure, and emission properties.

[Genetic characteristics of five human adenovirus type 53 strains isolated from Taiyuan city in 2016, China].

Objective: The genetic characteristics of the human adenovirus type 53 (HAdV-53) strains isolated from Taiyuan city of Shanxi Province were studied to obtain the baseline data of their molecular characteristics. Methods: Conjunctival swabs (n=79) were collected from epidemic keratoconjunctivitis (EKC) patients in Shanxi eye Hospital in 2016, and five HAdV-53 strains were obtained after virus isolation and identification based on the three major capsid genes sequences including Penton base, Hexon and Fiber gene. And the corresponding sequences of global epidemic HAdV-53 strains and the strains with the same genetic origin as HAdV-53 were also downloaded from GenBank database, and then the three gene database were established, respectively. With the database, phylogenetic tree was constructed, and the genetic and molecular evolutionary characteristics were analyzed with bioinformatics software. Results: Five HAdV-53 strains in Shanxi Province in 2016 showed high consistency with the HAdV-53 strains prevalent in other countries in 1996-2014 (>99.8%). All HAdV-53 strains were in the same evolutionary branch with their recombinant source genotypes (HAdV-37 and HAdV-8) in Penton base and Fiber gene, respectively, and maintained a high degree of consistency in gene sequences. In Hexon gene, HAdV-53 strains were more closed to its recombinant source genotype HAdV-22, the nucleotide and amino acid sequences between two types were highly homologous, while HAdV-53 and HAdV-22 belonged to different evolutionary branches, and the evolution rate of HAdV-53 based on Hexon gene was 3.51×10(-5) substitution/site/year. Conclusion: HAdV-53 has become an important new ocular infectious pathogen of Taiyuan. HAdV-53 strain are relatively conservative and stable based on Penton base, Hexon, and Fiber gene.

Molecular detection and genetic diversity of porcine bocavirus in piglets in China.

Porcine bocavirus (PBoV) is a recently discovered, non-enveloped and single-stranded DNA virus that can infect pigs. In order to understand PBoV infection and its genetic characterization in piglets in Xinjiang China, PBoV was detected by PCR in 156 clinical samples from 1-month-old piglets. PBoV was detected in 9 clinical samples, with a prevalence rate of 5.77% (9/156). Then nonstructural protein NS1 gene was amplified, sequenced and used for phylogenetic analysis. The results showed that the prevalence rate in the sick piglets was 9.33% (7/75), which is significantly higher than that in the healthy piglets (2.47%, 2/81). The nucleotide sequences of NS1 gene share high identities (96.1-99.2%) within the same groups of PBoVs. Phylogenetic analysis based on complete nucleotide sequence of NS1 gene showed that PBoV strains can be classified into three genetic groups, among which group I contains PBoV1 strains, group II contains PBoV2 strains, and group III contains PBoV3, PBoV4 and PBoV5 strains. Porcine/XJ-12, porcine/XJ-27, porcine/XJ-65, and porcine/XJ-145 had close genetic distance with subgroup 1, belonging to group I; strains porcine/XJ-79 and porcine/XJ-134 were clustered with subgroup 2, belonging to group II, while porcine/XJ-8, porcine/XJ-52 and porcine/XJ-96 were clustered with subgroup 3, which belonged to group III. This study demonstrated for the first time that PBoV strains in Xinjiang belong to three subgroups of three different genetic groups, indicating a substantial genetic diversity of the epidemic strains circulating in China, which provided the useful epidemiological data for scientific control and prevention of this disease in farm pigs. Keywords: porcine bocavirus; molecular detection; genetic characterization; piglets.

Mesiotemporal atrophy and hippocampal diffusivity distinguish amnestic from non-amnestic vascular cognitive impairment.

BACKGROUND AND PURPOSE: The role of clinical factors, cerebral infarcts and hippocampal damage in vascular cognitive impairment (VCI) subtypes remains unclear. METHODS: Non-demented patients with carotid stenosis and recent transient ischemic attack/stroke had cognitive assessment and brain magnetic resonance imaging (MRI). Amnestic VCI was defined as memory impairment; non-amnestic VCI was any other subdomain impairment. Associations of MRI metrics [log-transformed total ischemic lesion load (log TILL), mesiotemporal atrophy (MTA) score, hippocampal mean diffusivity (hipMD)] with cognitive performance were assessed. RESULTS: A hundred and eight patients, 47 with amnestic VCI and 21 with non-amnestic VCI, were assessed. A higher MTA (odds ratio 12.89, P = 0.001) and left hipMD (odds ratio 4.43, P = 0.003) contributed to amnestic VCI versus normal. Age-adjusted fluency correlated with log TILL (P = 0.002). Age-adjusted memory was associated with left hipMD (P = 0.001), MTA (P < 0.001) but not log TILL (P = 0.14). Left hipMD, MTA and smoking showed classification potential between amnestic VCI versus normal (area 0.859, P < 0.001). CONCLUSIONS: Neuroimaging assists stratification in amnestic VCI characterized by hippocampal changes and in non-amnestic VCI by higher ischemic burden. MTA and hippocampal diffusivity show diagnostic biomarker potential.

MicroRNA-203 inhibits tumour growth and metastasis through PDPN.

OBJECTIVE: MicroRNAs play an important role in regulating hypopharyngeal cancer development. miR-203 has been previously shown to possess antitumour capabilities in many cancers, but not in hypopharyngeal cancer. DESIGN: Using human normal and hypopharyngeal cancer specimens, we explored the expression levels of miR-203 in the two groups and further correlated them with different stages of cancer and lymph node metastasis. SETTING AND PARTICIPANTS: Applying human pharynx FaDu cancer cells and lentiviral transduction technique, we investigated the effects of miR-203 on cancer cell viability, migration and invasion. Moreover, we studied the novel relationship between miR-203 and podoplanin (PDPN) in hypopharyngeal cancer. RESULTS: The downregulated levels of miR-203 in human hypopharyngeal cancer tissues were associated with advanced cancer stages and lymph node metastasis. High levels of miR-203 inhibited cell viability, migration and invasion of hypopharyngeal cancer cells. Further studies suggested miR-203 directly targeted and inhibited PDPN expression. PDPN silencing suppresses hypopharyngeal cancer cell abilities. In addition, PDPN overexpression was able to reverse miR-203 inhibitory effects on cell viability, migration and invasion. CONCLUSION: PDPN acts as an oncogene to promote hypopharyngeal cancer cell viability, migration and invasion. miR-203 directly targets PDPN to suppress its expression, thus exerting inhibitory effects on cancer metastasis.

Tumor vasculogenic mimicry predicts poor prognosis in cancer patients: a meta-analysis.

BACKGROUND: Vasculogenic mimicry (VM) is the formation of vascular channels by tumor cells or tumor cell-derived, trans-differentiated cells in highly aggressive, solid tumors. However, the disease features and prognostic value of VM for overall survival of cancer patients remain controversial. METHOD: To systematically investigate the roles of VM in cancer progression and its prognostic values, we performed a meta-analysis based on 36 studies (33 eligible articles) including 3609 patients. The pooled hazard ratios (HRs) with 95 % confidence intervals (95 % CIs) were used to assess the relationship between VM and overall survival in cancer patients. RESULTS: Vasculogenic mimicry was significantly associated with cancer differentiation, lymph node metastasis, distant metastasis, and TNM stage. The prognostic value of VM was significant in overall survival (HR 2.16; 95 % CI 1.98-2.38; P < 0.001). Analyses stratified by confounders, such as cancer type, ethnicity, VM detection methods, sample size, and Newcastle-Ottawa quality score, found similar significant results. CONCLUSIONS: The presence of VM predicts poorer survival outcomes in cancer patients.

MicroRNA-1280 modulates cell growth and invasion of thyroid carcinoma through targeting estrogen receptor α.

Thyroid cancer (TC) is one of the most common endocrine malignancies, with a steadily increasing incidence and lethality over the last several decades. ERα is a nuclear hormone receptor that has a key role in different cellular process and participates in the development and progression of thyroid cancer. ERα is the predicted target gene of microRNA-1280 (miR-1280). The present study was designed to delineate the role and underlying mechanism of miR-1280 in regulating thyroid cancer through targeting ERα. In our study, we analyzed the expression level of miR-1280 in thyroid cancer and detected significantly lower miR-1280 levels in TC tissue and cell lines compared with adjacent normal tissue or healthy cell line. We then overexpressed miR-1280 by miRNA mimic transfection and inhibited miR-1280 by miRNA inhibitor transfection. The inhibition of miR-1280 significantly elevated proliferation and invasion ability, whereas overexpression of miR-1280 inhibited cell growth and invasion in TC cells. Additionally, the luciferase reporter assay confirmed a targeting reaction between miR-1280 and ERα. Furthermore, overexpression of miR-1280 inhibited ERα and ERK pathway expression in TC cells, indicating that miR-1280 acts as a tumor suppressor by inhibiting the expression of ERα. Taken together, we demonstrated that overexpressed miR-1280 levels in TC cells may promote cell proliferation and invasion by inhibiting ERα, which might provide a new therapeutic target for thyroid cancer.

[Protective effect of hydrogen on the lung of sanitation workers exposed to haze].

Objective: To study the protective effect of hydrogen inhalation on the lungs of sanitation workers exposed to haze. Methods: In this randomized, double-blind, placebo controlled clinical trial, 96 sanitation workers living in Shijiazhuang urban area were recruited during January to February, 2016. All enrolled participants were randomized to 2 groups; the treatment group inhaled H2∶O2 mixture (66.67%∶33.33%) 1 hour per day for 30 days, while the control group inhaled N2∶O2 mixture (66.67%∶33.33%) 1 hour per day for 30 days. Respiratory symptoms were evaluated and fractional exhaled nitric oxide(FeNO), biochemical indexes, lung function were measured at baseline(the 0th day) and during treatment (the 8th day, 15th day, and 30th day). Results: (1)The FeNO levels of the treatment group (16±5)×109 were lower than those of the control group(21±14)×109 on 8th day of treatment, with significant difference(F=6.94, P<0.05). (2)The levels of FEV1 were significantly higher in participants from the treatment group as compared to the control group on both 8th [(96±13)% vs(94±14)%(F=3.96, P<0.05)] and 30th day [(97±14)% vs (95±12)%(F=8.5, P<0.05)] of treatment, while PEF was also increased on 15th day [(73±15)% vs(67±18)%(F=8.68, P<0.05)]. (3)The sputum levels of MMP-12 and SOD3 were consistently lower in the treatment group as compared to the control group at each time point, and the levels of IL-10 were higher in the treatment group as compared to the control group on the 15th and 30th day. MDA and IL-2 levels were lower in the treatment group than in the control group on the 30th day(P<0.05). The sputum levels of CRP and TGF-ß1 at each time point were not different between the 2 groups (P>0.05). (4)The serum levels of IL-2 and SOD3 were lower in the treatment group as compared to the control group while IL-10 was higher than in the control group at each time point, and MMP-12 was lower in the treatment group than that in the control group on the 30th day(P<0.05). The relative ratios of CRP, TGF-ß1 and MDA in serum at each time point between the 2 groups were not significantly different (P>0.05). (5)Hydrogen inhalation improved respiratory symptoms such as cough. Conclusions: Inhalation of hydrogen gas could alleviate airway inflammation and oxidative stress of sanitation workers exposed to air pollution. There was even a significant inhibitory effect on the level of systemic inflammatory response. Importantly, inhalation of hydrogen could improve respiratory symptoms such as cough.

Estrogen deficiency inducing shifted cytokines profile in bone marrow stromal cells inhibits Treg cells function in OVX mice.

The study aims to reveal the effect of estrogen deficiency on Treg cells population in bone marrow in the development of osteoclastogenis with comparing the differences about Treg cells phenotypes and cytokines related with the homeostasis and functions maintenance of Treg cells in bone marrow in OVX mice and health control group. Wide—type C57BL/6 mice were operated OVX to mimic estrogen deficiency in PMO women. Treg cells population and their surface markers expressions were detected by flow cytometry. Cytokines profiles in bone marrow with examined by real—time PCR and ELISA analysis. Signal pathways and key modulators responsible to inflammatory cytokines expressions in bone marrow stromal cells were also detected with using western blotting. Estrogen deficiency in OVX mice decreased Treg cells and their functions, and cytokines profile in bone marrow were found shifted in bone marrow when compared with control group. Consistent to these observations, signal pathways in bone marrow stromal cells were reported altered by estrogen deficiency in our model. Estrogen deficiency effects Treg cells population and their functions in OVX mice with altering cytokines profile in bone marrow stromal cells.

Expression and role of cyclophilin B in stomach cancer.

We elucidated the expression of ciclosporin protein B (cyclophilin B) in stomach cancer tissue and the correlation between cyclophilin B and clinicopathological parameters, and determined the effect of cyclophilin B on growth and proliferation of stomach cancer cells. Pathological sections of stomach cancer and paracancerous tissue were collected for detecting the expression and distribution of cyclophilin B, using immunohistochemistry, and for analyzing the relationship between the expression levels of cyclophilin B in stomach cancer and the clinical pathological parameters of the patients. A cyclophilin BsiRNA lentiviral (LV-cyclophilin B-siRNA) and corresponding control vector (LV-siRNA-con) were constructed. MTT and cell cycle assays were used to detect the effect of downregulation of cyclophilin B expression on in vitro growth and proliferation and clone formation capacity of BGC823 and SGC7901 cells. The cyclophilin B-positive rate of stomach cancer tissue was 84.29% (59/70) and that of paracancerous tissue was 56.00% (28/50). The expression of cyclophilin B in stomach cancer tissue was significantly higher than that in paracancerous tissue (P < 0.05). Staining for cyclophilin B was primarily present in the cytoplasm and was seldom present in the cell nuclei. Downregulation of cyclophilin B significantly inhibited growth and proliferation of stomach cancer cells, cell cycle progression, and in vivo tumorigenicity capacity. Cyclophilin B has a high diagnostic value for stomach cancer and its downregulation can effectively inhibit the growth of stomach cancer cells. Thus, cyclophilin B may be a potential therapeutic target for stomach cancer treatment.

Mutational analysis of podocyte genes in children with sporadic steroid-resistant nephrotic syndrome.

Recent studies have demonstrated that mutations in 4 podocyte genes, NPHS1, NPHS2, CD2AP, and WT1, are associated with the pathogenesis of steroid-resistant nephrotic syndrome (SRNS). Systematic investigation of all 4 genes for sporadic SRNS in China has not been performed. We examined 10 Chinese children with sporadic SRNS who showed no response to immunosuppressive agents and 20 SRNS controls who exhibited a response to prolonged steroid or immunosuppressive treatment and achieved complete remission. We analyzed mutations in the 4 podocyte genes, NPHS1, NPHS2, CD2AP, and WT1. Mutational analysis was performed using polymerase chain reaction and direct sequencing. Of the 10 SRNS children who showed no response to immunosuppressive agents, the compound heterozygous NPHS1 mutations 2677A>G (T893A) and *142T>C were identified in 1 patient, while a heterozygous mutation in WT1, 1180C>T (R394W), was found in another patient. Of the 20 SRNS children showing complete remission who responded to prolonged steroid therapy or immunosuppressive agents, 4 heterozygous NPHS1 mutations, 928G>A, IVS8+30C>T, IVS21+14G>A, and IVS25-23C>T, were identified in 4 patients and a heterozygous CD2AP mutation, IVS7-135G>A, was identified in 1 patient. Our results indicate the necessity of genetic examination for mutations in podocyte genes in Chinese SRNS children who show no response to immunosuppressive agents.