BACKGROUND: Arsenic trioxide (ATO) is indicated as a broad-spectrum medicine for a variety of diseases, including cancer and cardiac disease. While the role of ATO in hepatic ischemia/reperfusion injury (HIRI) has not been reported. Thus, the purpose of this study was to identify the effects of ATO on HIRI. METHODS: In the present study, we established a 70% hepatic warm I/R injury and partial hepatectomy (30% resection) animal models in vivo and hepatocytes anoxia/reoxygenation (A/R) models in vitro with ATO pretreatment and further assessed liver function by histopathologic changes, enzyme-linked immunosorbent assay, cell counting kit-8, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Small interfering RNA (siRNA) for extracellular signal-regulated kinase (ERK) 1/2 was transfected to evaluate the role of ERK1/2 pathway during HIRI, followed by ATO pretreatment. The dynamic process of autophagic flux and numbers of autophagosomes were detected by green fluorescent protein-monomeric red fluorescent protein-LC3 (GFP-mRFP-LC3) staining and transmission electron microscopy. RESULTS: A low dose of ATO (0.75 μmol/L in vitro and 1 mg/kg in vivo ) significantly reduced tissue necrosis, inflammatory infiltration, and hepatocyte apoptosis during the process of hepatic I/R. Meanwhile, ATO obviously promoted the ability of cell proliferation and liver regeneration. Mechanistically, in vitro  studies have shown that nontoxic concentrations of ATO can activate both ERK and phosphoinositide 3-kinase-serine/threonine kinase (PI3K-AKT) pathways and further induce autophagy. The hepatoprotective mechanism of ATO, at least in part, relies on the effects of ATO on the activation of autophagy, which is ERK-dependent. CONCLUSION Low, non-toxic doses of ATO can activate ERK/PI3K-AKT pathways and induce ERK-dependent autophagy in hepatocytes, protecting liver against I/R injury and accelerating hepatocyte regeneration after partial hepatectomy.
Animals ; Arsenic Trioxide ; Autophagy/physiology* ; Reperfusion Injury/prevention & control* ; Mice ; Male ; Proto-Oncogene Proteins c-akt/physiology* ; Arsenicals/therapeutic use* ; Oxides/therapeutic use* ; Liver/metabolism* ; Extracellular Signal-Regulated MAP Kinases/metabolism* ; Mice, Inbred C57BL

Claudin18.2(CLDN18.2)is a tight junction protein that is overexpressed in a variety of solid tumors such as gastrointestinal cancer and oesophageal cancer.It has been identified as a promising target and a potential biomarker to diagnose tumor,evaluate efficacy,and determine patient prognosis.TST001 is a recombinant humanized CLDN18.2 antibody that selectively binds to the extracellular loop of human Claudin18.2.In this study,we constructed a solid target radionuclide zirconium-89(89Zr)labled-TST001 to detect the expression of in the human stomach cancer BGC823CLDN18.2 cell lines.The[89Zr]Zr-des-ferrioxamine(DFO)-TST001 showed high radiochemical purity(RCP,＞99％)and specific activity(24.15±1.34 GBq/μmol),and was stable in 5％human serum albumin,and phosphate buffer saline(＞85％RCP at 96 h).The EC50 values of TST001 and DFO-TST001 were as high as 0.413±0.055 and 0.361±0.058 nM(P＞0.05),respectively.The radiotracer had a significantly higher average standard uptake values in CLDN18.2-positive tumors than in CLDN18.2-negative tumors(1.11±0.02 vs.0.49±0.03,P=0.0016)2 days post injection(p.i.).BGC823CLDN18.2 mice models showed high tumor/muscle ratios 96 h p.i.with[89Zr]Zr-DFO-TST001 was much higher than those of the other imaging groups.Immunohistochemistry results showed that BGC823CLDN18.2 tumors were highly positive(+++)for CLDN18.2,while those in the BGC823 group did not express CLDN18.2(-).The results of ex vivo biodistribution studies showed that there was a higher distribution in the BGC823CLDN18.2 tumor bearing mice(2.05±0.16％ID/g)than BGC823 mice(0.69±0.02％ID/g)and blocking group(0.72±0.02％ID/g).A dosimetry estimation study showed that the effective dose of[89Zr]Zr-DFO-TST001 was 0.0705 mSv/MBq,which is within the range of acceptable doses for nuclear medicine research.Taken together,these re-sults suggest that Good Manufacturing Practices produced by this immuno-positron emission tomog-raphy probe can detect CLDN18.2-overexpressing tumors.

BACKGROUND: Weather conditions are a possible contributing factor to age-related macular degeneration (AMD), a leading cause of irreversible loss of vision. The present study evaluated the joint effects of meteorological factors and fine particulate matter (PM_2.5) on AMD. METHODS: Data was extracted from a national cross-sectional survey conducted across 10 provinces in rural China. A total of 36,081 participants aged 40 and older were recruited. AMD was diagnosed clinically by slit-lamp ophthalmoscopy, fundus photography, and spectral domain optical coherence tomography (OCT). Meteorological data were calculated by European Centre for Medium-Range Weather Forecasts (ECMWF) reanalysis and were matched to participants' home addresses by latitude and longitude. Participants' individual PM_2.5 exposure concentrations were calculated by a satellite-based model at a 1-km resolution level. Multivariable-adjusted logistic regression models paired with interaction analysis were performed to investigate the joint effects of meteorological factors and PM_2.5 on AMD. RESULTS: The prevalence of AMD in the study population was 2.6% (95% CI 2.42-2.76%). The average annual PM_2.5 level during the study period was 63.1 ± 15.3 µg/m³. A significant positive association was detected between AMD and PM_2.5 level, temperature (T), and relative humidity (RH), in both the independent and the combined effect models. For PM_2.5, compared with the lowest quartile, the odds ratios (ORs) with 95% confidence intervals (CIs) across increasing quartiles were 0.828 (0.674,1.018), 1.105 (0.799,1.528), and 2.602 (1.516,4.468). Positive associations were observed between AMD and temperature, with ORs (95% CI) of 1.625 (1.059,2.494), 1.619 (1.026,2.553), and 3.276 (1.841,5.830), across increasing quartiles. In the interaction analysis, the estimated relative excess risk due to interaction (RERI) and the attributable proportion (AP) for combined atmospheric pressure and PM_2.5 was 0.864 (0.586,1.141) and 1.180 (0.768,1.592), respectively, indicating a synergistic effect between PM_2.5 and atmospheric pressure. CONCLUSIONS This study is among the first to characterize the coordinated effects of meteorological factors and PM_2.5 on AMD. The findings warrant further investigation to elucidate the relationship between ambient environment and AMD.
Humans ; Adult ; Middle Aged ; Cross-Sectional Studies ; Air Pollutants/analysis* ; Particulate Matter/analysis* ; China/epidemiology* ; Macular Degeneration/etiology* ; Meteorological Concepts

Activating metabolite glutamate receptor 8 (mGluR8) has anti-hyperpathia effect in central nervous system, however, studies of effects in gastrointestinal tract are rare. Visceral hypersensitivity is one of the pathogenesis factors of irritable bowel syndrome (IBS). Aims: To investigate the effect and potential mechanism of activating mGluR8 on visceral hypersensitivity in neonatal maternally separated (NMS) rats. Methods: Twenty-four male newborn SD rats were randomly divided into normal control (NC) group, NMS group and mGluR8 agonist (S)-3, 4-DCPG group (3, 10 mg/kg). Newborn rats were subjected to 3 hours daily maternal separation on postnatal day 2-14 to establish the NMS model; in (S)-3, 4-DCPG group, (S)-3, 4-DCPG (3 or 10 mg/kg) were administered 1 hour prior to the visceral sensitivity test in NMS rats. Abdominal withdrawal reflex (AWR) score and abdominal electromyography (EMG) activity were used to measure visceral sensitivity. mGluR8 mRNA and protein expressions in colon mucosa were measured by RT-PCR and Western blotting, respectively; TNF-α, IL-1β and IL-6 mRNA expressions in colon mucosa were measured by RT-PCR. The protein expression of myeloperoxidase (MPO) was measured by immunohistochemistry. Results: AWR score and EMG activity in NMS group were significantly higher than those in NC group under different colorectal distension (CRD) pressure. AWR score and EMG activity were significantly decreased in (S)-3, 4-DCPG group. mGluR8 mRNA and protein expressions in NMS group were significantly higher than those in NC group (P<0.05). Compared with NMS group, TNF-α mRNA expression was significantly decreased in 3 mg/kg (S)-3, 4-DCPG group (P<0.05), and MPO protein expression was significantly decreased in 10 mg/kg (S)-3, 4-DCPG group (P<0.05). Conclusions: Activating mGluR8 attenuates visceral hypersensitivity in NMS rats, the mechanism may be related to decrease of pro-inflammatory cytokine TNF-α.

The clinical data of a case of paroxysmal extreme pain disorder(PEPD) in Guangdong 999 Brain Hospital were retrospectively analyzed.The male patient, age of first examination was 7 months, began to have recurrent tonic accompanied by facial redness or cyanosis at 5 months after birth.The patient was diagnosed with epilepsy.The oral solution of sodium valproate and Levetiracetam were not effective.The video electroencephalogram examination displayed that, when the patient had tonic and bradycardia, the synchro electroencephalogram did not show epileptic discharge, so the patient was considered to have non-epileptic tonic.Genetic examination suggested that SCN9A gene mutation of c. 5240T >C resulted in amino acid changes: Val1747Ala.Combined with the skin changes, the patient was diagnosed as PEPD caused by SCN9A gene mutation.After the treatment with Carbamazepine, the patient′s abnormal skin changed and his-epileptic tonic disappeared, and his condition improved significantly.The early stage of PEPD can be mainly manifested as non-epileptic tonic.It is easy to be misdiagnosed as epilepsy, so the patient′s characteristic skin changes should be noticed, and genetic examination is also helpful in the diagnosis of the disease.

Objective:To analyze the characteristics and quantitative evaluation of Brucella spondylitis patients by magnetic resonance T2 mapping. Methods:A prospective clinical study was conducted to analyze the MRI data of 23 patients with brucellosis spondylitis diagnosed in the First Affiliated Hospital of Xinjiang Medical University from January 2016 to September 2018, and 25 healthy volunteers were selected as the control group. MRI was used to examine the vertebral bodies of the subjects, and T2 mapping map was automatically generated. Regions of interest (ROI) were selected on the T2 mapping map to generate T2 mapping values automatically. The T2 mapping values of diseased vertebrae, adjacent unaffected vertebrae, paravertebral abscess and healthy volunteers were analyzed.Results:Among 48 MRI examinees, 23 cases were Brucella spondylitis, including 17 males and 6 females, aged (38.5 ± 13.4) years; 25 healthy volunteers, including 15 males and 10 females, aged (35.1 ± 12.7) years. In 23 patients with Brucella spondylitis, 5 thoracic vertebrae, 40 lumbar vertebrae and 7 sacral vertebrae were involved, with a total of 52 vertebral bodies. Among them, 11 (21.2%) vertebral bodies showed bone marrow edema on MRI, 41 (78.8%) vertebral bodies showed bone marrow edema and vertebral bone destruction. T2 mapping values of the diseased vertebrae, adjacent unaffected vertebrae and paravertebral abscess in Brucella spondylitis patients and normal vertebrae in healthy volunteers were (115.62 ± 11.37), (75.21 ± 5.57), (240.26 ± 30.67) and (77.29 ± 4.19) ms, respectively. There were significant differences between the diseased vertebrae in Brucella spondylitis and adjacent unaffected vertebrae in Brucella spondylitis, and there were significant differences between the diseased vertebrae in Brucella spondylitis and normal vertebrae in healthy volunteers ( t = 26.78, 19.42, P < 0.05). Conclusion:Magnetic resonance T2 mapping can be used to evaluate the pathological tissues in Brucella spondylitis patients, and it has certain guiding significance for the quantitative description and qualitative diagnosis.

Objective: To detect the expression of New York esophageal squamous cell carcinoma antigen 1 (NY-ESO-1) in common types of mesenchymal myxoid tumors, and to investigate its significance in the diagnosis and differential diagnosis of myxoid liposarcoma. Methods: A total of 43 formalin-fixed paraffin-embedded samples of mesenchymal myxoid tumors from the Affiliated Hospital of Qingdao University and Qingdao Municipal Hospital ranging between 2010 and 2017 were selected. NY-ESO-1 expression was detected by immunohistochemical staining. DDIT3 gene status was detected by fluorescence in situ hybridization (FISH). NY-ESO-1 mRNA was detected by reverse transcription-PCR (RT-PCR). Results: Histopathology and FISH results confirmed that there were 11 cases of myxoid liposarcoma and 32 other types (including 7 cases of well-differentiated liposarcoma, 1 dedifferentiated liposarcoma, 3 lipomas, 2 lipoblastomas and 19 non-adipocytic tumors). Immunohistochemical staining showed that the positive expression propotion of NY-ESO-1 in myxoid liposarcoma was 11/11, and the positive location was the cytoplasm and nucleus of lipoblast cells. The expression intensity is higher in regions with round cell differentiation. Among the 32 cases of other mesenchymal myxoid tumors, only one well-differentiated liposarcoma showed positive immunoreactivity for NY-ESO-1. RT-PCR confirmed that 7 cases of myxoid liposarcoma (7/11) and one well-differentiated liposarcoma (1/7) had NY-ESO-1 mRNA expression. Conclusions NY-ESO-1 is positively expressed in myxoid liposarcoma. It can be served as a useful marker for the diagnosis and differential diagnosis of myxoid liposarcoma.

Objective To detect the expression of New York esophageal squamous cell carcinoma antigen 1 (NY?ESO?1) in common types of mesenchymal myxoid tumors, and to investigate its significance in the diagnosis and differential diagnosis of myxoid liposarcoma. Methods A total of 43 formalin?fixed paraffin?embedded samples of mesenchymal myxoid tumors from the Affiliated Hospital of Qingdao University and Qingdao Municipal Hospital ranging between 2010 and 2017 were selected. NY?ESO?1 expression was detected by immunohistochemical staining. DDIT3 gene status was detected by fluorescence in situ hybridization (FISH). NY?ESO?1 mRNA was detected by reverse transcription?PCR (RT?PCR). Results Histopathology and FISH results confirmed that there were 11 cases of myxoid liposarcoma and 32 other types (including 7 cases of well?differentiated liposarcoma, 1 dedifferentiated liposarcoma, 3 lipomas, 2 lipoblastomas and 19 non?adipocytic tumors). Immunohistochemical staining showed that the positive expression propotion of NY?ESO?1 in myxoid liposarcoma was 11/11, and the positive location was the cytoplasm and nucleus of lipoblast cells. The expression intensity is higher in regions with round cell differentiation. Among the 32 cases of other mesenchymal myxoid tumors, only one well?differentiated liposarcoma showed positive immunoreactivity for NY?ESO?1. RT?PCR confirmed that 7 cases of myxoid liposarcoma (7/11) and one well?differentiated liposarcoma (1/7) had NY?ESO?1 mRNA expression. Conclusions NY?ESO?1 is positively expressed in myxoid liposarcoma. It can be served as a useful marker for the diagnosis and differential diagnosis of myxoid liposarcoma.

Objective To explore the clinical differences between patients with early-onset myasthenia gravis (EOMG)and those with late-onset myasthenia gravis(LOMG).Methods This was a retrospective study enrolling 157 MG patients.Based on the age of onset,patients were divided into the EOMG group(n=85)and the LOMG group(n =72).The groups were compared on clinical characteristics,including clinical manifestations,MG classification,electrophysiological findings on repetitive nerve stimulation(RNS),single fiber electromyography(SFEMG),levels of antibody against acetylcholine receptors(Ach-R Ab),antibody to muscle-specific kinase(MuSK Ab),titin antibody(Titin Ab),ryanodine receptor antibody(RyR Ab),thyroid function,thymectomy,thymus pathology and responses to treatment.Results The mean ages of onset were markedly different [(40.9 ± 9.7) years vs.(62.0 ± 12.2) years,P＜ 0.05] between the EOMG and LOMG groups.The LOMG group was associated with a significantly higher rate of the ocular form(50.0 ％,n=36 vs.32.9％,n=28,P＜0.05),a lower rate of the general form(50.0％,n=36 vs.67.1％,n=57,P＜0.05),and an increased risk of bulbar involvement(41.7％ n=30 vs.23.5％,n=20,P＜0.05)than those in the EOMG group.There was no significant difference in positive rates of RNAS and SFEMG,and levels of AChR Ab,MuSK Ab and double serum negative(DSN)MG between the groups (P＞0.05).Moreover,patients in the EOMG group were more likely to have abnormal thyroid function and higher percentages of receiving steroids,tacrolimus,plasma exchange therapy,and thymectomy (P＜ 0.05).Conclusions The clinical profiles of LOMG are different from those of EOMG in clinical manifestations,thyroid function,thymectomy frequency,striational antibody levels and disease-modifying drug options.

Objective To study the correlation between vitamin D receptor (VDR) gene polymorphism and the risk of colorectal cancer.Methods Three hundred and fifty patients with colorectal cancer treated in our hospital from May 2013 to August 2016 were randomly selected as the study group,and 350 healthy subjects were recruited in this study.The genomic DNA was extracted from peripheral blood of all subjects.Twenty-nine VDR single nucleotide polymorphisms (SNPs) were selected and genotyped,and the plasma vitamin D concentration was measured.Logistic regression model was used to evaluate the odds ratio (OR) and 95％ confidence interval (CI) of colorectal cancer.Results Rs2254210,rs1540339,rs2107301,rs11168267,rs11574113,rs731236,rs3847987 and rs11574143 VDR SNPs were associated with the risk of colorectal cancer (P ＜ 0.05),and the risk of colorectal cancer was significantly higher than that of colorectal cancer (P ＜ 0.05).The SNPs of rs11574113,rs3847987 and rs11574143 were more correlated with the risk of colorectal cancer in people with higher plasma vitamin D concentrations.There was a significant difference in the proportion of patients with genotype at different levels of plasma vitamin D in the rs7968585 locus (P ＜ 0.05).Conclusion The polymorphism of vitamin D receptor gene has a certain correlation with the risk of colorectal cancer,and the detection of vitamin D gene polymorphism has a certain significance for predicting the occurrence of colorectal cancer and guiding clinical medicine.