Objective To investigate differential expressed protein in the intestinal mucosa of patients with inflammatory bowel disease (IBD) with antibody chips,and to explore the possible role of the screened proteins in pathogenesis of IBD.Methods The mucosa tissues of nine patients with ulcerative colitis (UC),nine patients with Crohn's disease (CD) and nine control individuals were collected.After total protein of each group was extracted,the differential expressed protein of each group was analyzed by Raybiotech L-series human cytokine antibody chips.The mucose tissues of other nine patients with UC,nine patients with CD and nine control individuals were collected,and were used to verify the greatly differential expressed proteins by Western blot.The t-test was performed to compare two groups.Results Compared with the control group,there was significantly difference in 263 cytokines of UC group,and 414 cytokines of CD group.And then the higher expressions of herpes virus entry mediator,leukemia inhibitory factor and platelet factor 4 in the mucosa tissues of IBD patients were confirmed by Western blot and the differences were statistically significant (UC:t=23.85,9.53,18.88; CD:t=13.54,16.65,13.67,all P＜0.01).Conclusion The screened differential expressed cytokines in the mucosa tissues of IBD patients by cytokine antibody chips could be helpful to reveal the pathogenesis of IBD and discover new molecular biomarkers.

Objective The purpose of this paper is to understand the advantages and disadvantages of the bone marrow smears and bone marrow biopsy in multiple myeloma diagnosis and efficacy judgment,explicit the value of bone marrow smears and bone marrow biopsy synchronous check in the diagnosis and treatment observation of multiple myeloma.Methods With two step-suction two biopsy specimens assay,obtained specimens of bone marrow smears and bone marrow biopsy,retrospective-ly analysed results of 283 multiple myeloma patients bone marrow smear and biopsy,and made a comparative study on the degree of bone marrow hyperplasia,myeloma cell morphology,the degree of tumor cell infiltration,proliferation pattern,bone marrow stromal pathological changes,and fibrosis cases.Results The degree of proliferation of bone marrow biopsy sections and infiltration of plasma cells was significantly higher than that of bone marrow smears,statistically there was a significant difference (P <0.01).Multiple myeloma diagnostic sensitivity by bone marrow biopsy sections was significantly higher than by the bone marrow smears,the difference was statistically significant (P < 0.05).Plasma cells in bone marrow biopsy tumor proliferation modes:clusterpiece nodular type 33 cases (11.66%),interstitial-type 86 cases (30.39%),among nodular interstitial type 112 cases (39.58%),diffuse cypriot real 52 cases (18.37%).Plasma cells in bone marrow smears tumor morphology:small mature plasma cell type 77 cases (27.21%),immature plasma cell type 148 cases (52.30%),protoplas-mic cell type 36 cases (12.72%),reticular plasma cell type 22 cases (7.77%).Conclusion Marrow biopsy can accurately reflect the degree of bone marrow hyperplasia,plasma cell tumor proliferation mode and infiltration degree,myelofibrosis sit-uation;bone marrow smears Wright-Giemsa staining,plasma cell tumor morphology was clear,typicalfeatured,and easily i-dentifiable.Bone marrow smear and biopsy synchronous check can improve the sensitivity and accuracy for multiple myeloma diagnosis,which has very important significance for multiple myeloma diagnosis and treatment observation.

Objective To investigate the correlation of multidrug resistance gene 1 (MDR1),NR3C1 gene polymorphisms and clinical risk factors with efficacy,dependence,and resistance of glucocorticoid (GC) in patients with inflammatory bowel disease (IBD).Methods Anti coagulation blood samples of 196 healthy controls and 105 IBD patients received GC therapy were collected.There were 62 ulcerative colitis (UC) and 43 Crohn's disease (CD) in the IBD patients.The number of GC sensitive,GC dependent and GC resistant of UC patients were 36,13 and 13,respectively,and those of CD patients were 24,11 and eight.GC refractoriness included GC dependence and resistance.The genotype of MDR1 C3435T and NR3C1 Bcl Ⅰ of all the subjects was detected by the restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR).The correlation between each genotype frequency,clinical features of patients with IBD and the efficacy of GC treatment was analyzed by Chisquare test,Fisher exact probability method or t test.Results Among UC patients,the disease course of GC refractory group and GC resistant group was longer than that of GC sensitive group ((6.660±1.523)years,(6.500±1.111) yearsvs (3.350±0.697) years,t=2.211,P=0.031; t=2.930,P=0.005).The serum level of C reaction protein (CRP) of GC refractory group was higher than that of GC sensitive group ((47.628±13.913) mg/Lvs (16.854±4.121) mg/L,t=2.121,P=0.047).The chronic relapse type was more common in GC refractory UC patients (Fisher exact probability method,P=0.035),and severe patients were more common in UC with GC resistance (Fisher exact probability method,P=0.021).The white blood cell count of GC resistant and GC refractory CD patient was lower than that of GC sensitive CD patients ((5.710 ± 0.604) ×109/L,(5.878±0.405) × 109/L vs (7.814 ±0.670) × 109/L,t=2.334,P=0.028; t=2.045,P=0.018).Patients with extraqntestinal manifestations was more common in CD with GC resistance (Fisher exact probability method,P=0.035).There was no statistically significant difference in the frequencies of MDR1 C3435T,NR3C1 Bcl Ⅰ genotypes,allelic genes and gene carrier among control group and GC sensitive dependent and resistant group of IBD patients.However,the frequency of MDR1 C3435T gene carrier was significantly different between GC sensitive group and GC refractory group,especially between GC sensitive group and GC resistance group (68.33％ vs 48.89％,x2 =4.051,P=0.044; 68.33％ vs 42.86％,x2 =4.274,P =0.039).Conclusions GC sensitivity of IBD patients with MDR1 C3435T loci T gene carrier was higher than that of IBD patients without T gene carrier.NR3C1 gene polymorphisms was not related with GC resistance and GC dependence.Compared with GC sensitive IBD patients,in GC resistant and GC dependent IBD pantient UC patients with long disease course,chronic relapse type,severe type,high level of CRP and CD patients with low white blood cell count and extra-intestinal manifestations were more common.

Objective To explore the abnormal karyotype characteristics of myelodysplastic syndrome (MDS)patients and their correlation with clinical prognosis.Methods Analyzed the karyotypes of 281 MDS patients by use of G-banding tech-nique.Results Through analysis of the karyotypes of 281 MDS patients,found that the percentage of abnormal karyotypes was 48.75% (137/281),among 137 patients with abnormal karyotypes,43.07% (59 cases)presented with numerical aber-ration,31.39% (43 cases)with structural aberration,and 25.54% (35 cases)with both numerical and structural abnormali-ties.As for MDS subtypes,the occurrence rate of abnormal karyotype was 63.41% (26/41)in RAEB-2,58.73% (37/63)in RAEB-1,39.2% (49/125)in RCMD,15.38% (2/13)in RAS and 22.58% (7/31)in RA.The rates of abnormal karyotype in RAEB-1 and RAEB-2 were significantly higher than that in RA and RAS(P<0.01),and in RCMD (P <0.05).The fre-quent abnormal karyotypes were as follows:+8,-7/7q-,-20/20q-,complex karyotypes chromosomal translocation,i(17),-Y and +21.The follow-up study of 159 MDS patients indicated that the median survival time was 39 months for 68 patients with normal karyotypes and 21 months for 91 patients with abnormal karyotypes,the former was significantly prolonged than the latter (P < 0.05).As far as the leukemia transition rate was concerned,the patients with aberrant karyotypes (35.5%)were significantly higher than that with normal karyotypes (10.3%)(P < 0.01),among them,the cases with complex karyotypes and-7/7q-more easily transit into leukemia.Conclusion MDS was one kind of clonal hematological ma-lignancy with high heterogeneity.Chromosomal karyotype test plays an important role in the correct diagnosis,typing and prognosis evaluation of MDS.

Lead-time bias and length bias were common systematic errors in observational screening studies, which might be a common cause of overstating or distorting the true screening effects. One of key concerns in observational screening studies was how to estimate the screening effects based on the consideration of these two biases. This paper illustrated how to identify and correct the lead-time bias using the tumor volume doubling time and the non-homogeneous Poisson process, and how to correct the length bias using a weighted method. The application conditions of each method were also discussed to present several useful toolboxes to correct the lead-time bias and length bias appropriately and evaluate the effectiveness of the cancer screening program accurately.

The neurotrophin-tyrosine receptor kinase B (TrkB) signaling pathway plays an important role in regulating the balance of excitation and inhibition in the primary visual cortex (V1). Previous studies have revealed its mechanism of regulating the level of cortical excitability by increasing the efficiency of excitatory transmission, but it has not been elucidated how TrkB receptors regulate the balance of excitation and inhibition through the inhibitory system, which in turn affects visual cortex function. Therefore, the objective of this study was to investigate how the TrkB signaling pathway specifically regulates the most important inhibitory neuron-PV neurons affects the visual cortex function of mice. The expression of TrkB receptor on PV neurons in the V1 region was specifically reduced by the virus, the functional changes of inhibitory and excitatory neurons in the primary visual cortex were recorded by multi-channel electrophysiological in vivo. The orientation discrimination ability of mice was tested by behavioral experiments, and altered orientation discrimination ability of mice was tested by behavioral experiments. The results showed that reduced expression of TrkB receptors on PV inhibitory neurons in primary visual cortex significantly increased the response intensity of excitatory neurons, reduced the orientation discrimination ability of inhibitory and excitatory neurons, and increased the signal-to-noise ratio, but the orientation discrimination ability at the individual level in mice showed a decrease. These results suggest that the TrkB signaling pathway does not modulate the function of PV neurons solely by increasing excitatory transmission targeting PV neurons, and its effect on neuronal signal-to-noise ratio is not due to enhancement of the inhibitory system.
Mice ; Animals ; Receptor, trkB/metabolism* ; Neurons/metabolism* ; Signal Transduction

Background Environmental pollutants can affect N⁶-methyladenosine (m⁶A) level in the body, but the change of m⁶A level in kidney after being exposed to cadmium (Cd) and the molecular mechanism of renal injury need to be further studied. Objective To analyze the associations of m⁶A modification and methyltransferases/demethylases with microRNA-21 (miR-21) and transforming growth factor- β1 (TGF - β1) in kidney of rats exposed to Cd. Methods Twenty-four SPF male SD rats were divided into 4 groups, with 6 rats in each group, and were exposed to Cd by subcutaneous injection of 2.0, 1.0, and 0.5 mg·kg⁻¹ cadmium chloride (CdCl₂) and equal volume of normal saline for 2 weeks, 7 d a week, respectively. The levels of N-acetyl-β-D-glucosidase (UNAG) and albumin (UALB) in urine, and the levels of m⁶A methylation and TGF-β1 in kidney were detected by enzyme-linked immunosorbent assay (ELISA). The level of blood urea nitrogen (BUN) was measured by urease method. The levels of renal oxidative stress indicators such as malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were detected by total bile acid method, water-soluble tetrazolium asssay, and colorimetric method respectively. The relative levels of TGF-β1, methyltransferases, and demethylases in kidney were measured by reverse transcription-polymerase chain reaction. The expression of miR-21 in kidney was detected by fluorescent quantitative polymerase chain reaction. Results After 2 weeks of exposure to Cd, the body weights of rats in the 2.0 and 1.0 mg·kg⁻¹ cadmium chloride groups decreased, and the ratio of kidney/body weight and the levels of BUN, UNAG, and TGF-β1 mRNA and protein increased in the 2.0 mg·kg⁻¹ cadmium chloride group (P<0.05). The expression levels of m⁶A modification, methyltransferases METTL3, METTL14, Wilms’ tumor 1-associated protein (WTAP), and miR-21 were increased both in the 2.0 and 1.0 mg·kg⁻¹ cadmium chloride groups, with significant differences compared with the control group (P<0.05). The results of correlation analysis showed that the m⁶A modification level was negatively correlated with SOD (r=−0.4489, P<0.05) and GSH-Px (r=−0.4874, P<0.05), METTL3 was negatively correlated with MDA (r=−0.5158, P<0.05), while there was a positive correlation between FTO and GSH-Px (r=0.4802, P<0.05). In addition, miR-21 was positively correlated with METTL3 (r=0.7491), METTL14 (r=0.6157), and WTAP (r=0.6660) (P<0.05), TGF-β1 was positively correlated with METTL3 (r=0.5025, P<0.05) but negatively correlated with FTO (r=−0.5634, P<0.05) . Conclusion Cd can induce m⁶A methylation and up-regulation of METTL3, METTL14, WTAP, and miR-21 expression levels in rat kidney tissues, indicating that m⁶A and miR-21 may be associated with Cd-induced renal fibrosis.

BACKGROUND: Family clustering of esophageal cancer (EC) has been found in high-risk areas of China. However, the relationships between cancer family history and esophageal cancer and precancerous lesions (ECPL) have not been comprehensively reported in recent years. This study aimed to provide evidence for identification of high-risk populations. METHODS: This study was conducted in five high-risk areas in China from 2017 to 2019, based on the National Cohort of Esophageal Cancer. The permanent residents aged 40 to 69 years were examined by endoscopy, and pathological examination was performed for suspicious lesions. Information on demographic characteristics, environmental factors, and cancer family history was collected. Unconditional logistic regression was applied to evaluate odds ratios between family history related factors and ECPL. RESULTS: Among 33,008 participants, 6143 (18.61%) reported positive family history of EC. The proportion of positive family history varied significantly among high-risk areas. After adjusting for risk factors, participants with a family history of positive cancer, gastric and esophageal cancer or EC had 1.49-fold (95% confidence interval [CI]: 1.36-1.62), 1.52-fold (95% CI: 1.38-1.67), or 1.66-fold (95% CI: 1.50-1.84) higher risks of ECPL, respectively. Participants with single or multiple first-degree relatives (FDR) of positive EC history had 1.65-fold (95% CI: 1.47-1.84) or 1.93-fold (95% CI: 1.46-2.54) higher risks of ECPL. Participants with FDRs who developed EC before 35, 45, and 50 years of age had 4.05-fold (95% CI: 1.30-12.65), 2.11-fold (95% CI: 1.37-3.25), and 1.91-fold (95% CI: 1.44-2.54) higher risks of ECPL, respectively. CONCLUSIONS: Participants with positive family history of EC had significantly higher risk of ECPL. This risk increased with the number of EC positive FDRs and EC family history of early onset. Distinctive genetic risk factors of the population in high-risk areas of China require further investigation. TRIAL REGISTRATION ChiCTR-EOC-17010553.
Case-Control Studies ; China/epidemiology* ; Esophageal Neoplasms/pathology* ; Humans ; Precancerous Conditions/pathology* ; Risk Factors ; Stomach Neoplasms

Humans ; Esophageal Squamous Cell Carcinoma/pathology* ; Esophageal Neoplasms/pathology* ; Carcinoma, Squamous Cell/pathology* ; Precancerous Conditions/pathology* ; Early Diagnosis

Objective To describe the outcomes of extracorporeal membrane oxygenation (ECMO) for patients after aortic surgery and to summarize the experience. Methods The clinical data of patients who received ECMO support after aortic surgery in Fuwai Hospital from 2009 to 2020 were retrospectively analyzed. The patients who received an aortic dissection surgery were allocated into a dissection group, and the other patients were allocated into a non-dissection group. The in-hospital and follow-up survival rates were compared between the two groups, and the causes of death were analyzed. Results A total of 22 patients were enrolled, including 17 patients in the dissection group [13 males and 4 females, with a median age of 54 (46, 61) years] and 5 patients in the non-dissection group [3 males and 2 females, with a median age of 51 (41, 65) years]. There was no statistical difference in the age and gender between the two groups (P>0.05). The in-hospital survival rate (11.8% vs. 100.0%, P=0.001) and follow-up survival rate (11.8% vs. 80.0%, P=0.009) of the patients in the dissection group were significantly lower than those in the non-dissection group. The causes of death in the dissection group included massive bleeding and disseminated intravascular coagulation (3 patients), ventricular thrombosis (1 patient), irreversible brain injury (2 patients), visceral malperfusion syndrome (4 patients) and irreversible heart failure (5 patients). Conclusion ECMO after aortic dissection surgery is associated with high mortality, which is related to the pathological features of aortic dissection and severely disrupted coagulation system after the surgery. For these patients, strict indication selection and optimal management strategy are important.