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Objective:To investigate the influencing of inferior mediastinum and esophageal hiatus lymph node metastasis by submucosal different venous divisions of esophagogastric junction (EGJ) invaded in Siewert type Ⅱ adenocarcinoma of esophagogastric junction (AEG).Methods:The retrospective case-control study was conducted. The clinicopathological data of 547 patients with Siewert type Ⅱ AEG who were admitted to Shanxi Cancer Hospital from January 2018 to December 2021 were collected. There were 461 males and 86 females, aged 61 (range, 33?75)years. Observa-tion indicators: (1) lymph node metastasis rate in different groups; (2) influencing factors of inferior mediastinum lymph node metastasis in Siewert type Ⅱ AEG; (3) influencing factors of esophageal hiatus lymph node metastasis in Siewert type Ⅱ AEG. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range) or M( Q1, Q3), and com-parison between groups was conducted using the Mann-Whitney U test. Count data were described as percentages or absolute numbers, and comparison between groups was conducted using the chi-square test. The univariate analysis was conducted using the corresponding statistical methods based on data type. The Logistic regression model was used for multivariate analysis. Results:(1) Lymph node metastasis rate in different groups. The lymph node metastasis rate in No. 1, 2, 3, 4sa, 4sb, 7, 8a, 9, 11,20, 108, 110 of the 547 patients was 17.37%(95/547), 6.76%(37/547), 46.44%(254/547), 1.65%(9/547), 1.10%(6/547), 23.22%(127/547), 4.39%(24/547), 3.11%(17/547), 3.47%(19/547), 3.66%(20/547), 0.55%(3/547), 4.20%(23/547), respectively. Of the 547 patients, there were 456 cases with proximal of AEG invading submucosal palisade venous of EGJ including 4 cases with inferior mediastinum lymph node metastasis and no case with media mediastinum or up media-stinum lymph node metastasis. There were 91 cases with proximal of AEG invading submucosal perforator venous of EGJ including 18 cases with inferior mediastinum lymph node metastasis, 3 cases with media mediastinum lymph node metastasis and no case with up mediastinum lymph node metastasis. (2) Influencing factors of inferior mediastinum lymph node metastasis in Siewert type Ⅱ AEG. Results of multivariate analysis showed that age, tumor invading submucosal perforator venous of EGJ and histological classification were independent influencing factors for inferior media-stinum lymph node metastasis of Siewert type Ⅱ AEG ( odds ratio=0.93, 23.33, 0.31, 95% confidence interval as 0.87?0.99, 4.18?130.28, 0.12?0.78, P<0.05). (3) Influencing factors of esophageal hiatus lymph node metastasis in Siewert type Ⅱ AEG. Tumor invading submucosal perforator venous of EGJ was an independent influencing factor for esophageal hiatus lymph node metastasis of Siewert type Ⅱ AEG ( odds ratio=14.95, 95% confidence interval as 2.46?90.76, P<0.05). Conclusion:Age, tumor invading submucosal perforator venous of EGJ and histological classification are independent influencing factors for inferior mediastinum lymph node metastasis of Siewert type Ⅱ AEG, and tumor invading submucosal perforator venous of EGJ is an independent influencing factor for esophageal hiatus lymph node metastasis.
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Objective:To investigate the expression of monoubiquitination histone H2B (H2Bub) in esophageal cancer tissues and its correlation with the prognosis of patients.Methods:A total of 75 patients who underwent thoracic esophagectomy in Shanxi Province Cancer Hospital from May 2010 to December 2015 were selected. The expression of H2Bub protein in esophageal carcinoma and para-carcinoma tissues was detected by using immunohistochemical method. The relationship between H2Bub expression level and the clinicopathological characteristics was analyzed, Kaplan-Meier method was used to analyze the relationship H2Bub expression level and the survival.Results:H2Bub was positively expressed in esophageal carcinoma and para-carcinoma tissues, and weakly positive expressed H2Bub was found in para-carcinoma tissues, while not found in esophageal carcinoma tissues. The strongly positive expression rate of H2Bub in esophageal carcinoma tissues was higher than that in para-carcinoma tissues [84.0% (63/75) vs. 22.7% (17/75), χ2 = 34.68, P < 0.001]. Compared with para-carcinoma tissues, 64.0% (48/75) of H2Bub expression level in carcinoma tissues was up-regulated, and 2.7% (2/75) of H2Bub expression level was down-regulated. The up-regulated expression of H2Bub in esophageal carcinoma tissues compared with para-carcinoma tissues was not related with the gender, age, tumor diameter, lymph node metastasis and T staging (all P > 0.05). The proportion of patients with up-regulated expression of H2Bub in poorly differentiated carcinoma tissues was lower than that in moderately and highly differentiated carcinoma tissues [43.8% (7/16) vs. 66.7% (34/51), 87.5% (7/8), P = 0.037]. The median overall survival time was 70 months (95% CI 45-95 months) and 68 months (95% CI 54-82 months), respectively in 12 esophageal carcinoma patients with moderately positive expressed H2Bub and 63 esophageal carcinoma patients with strongly positive expressed H2Bub, and the difference was statistically significant ( P = 0.606). Among 48 patients with up-regulated expression of H2Bub in esophageal carcinoma tissues compared with para-carcinoma tissues, the median overall survival time of poorly differentiated esophageal carcinoma group (7 cases) was shorter than that of highly differentiated (7 cases) and moderately differentiated (34 cases) esophageal carcinoma group [36 months (95% CI 24-37 months) vs. 68 months (95% CI 38-98 months), 68 months (95% CI 44-91 months)], and the differences were statistically significant (all P < 0.05). Conclusions:The expression level of H2Bub in esophageal carcinoma tissues is up-regulated compared with that in para-carcinoma tissues. The up-regulated H2Bub expression level of patients with poorly differentiated esophageal carcinoma with poor prognosis is obvious.
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OBJECTIVE@#To explore the genetic basis for a child manifesting with intellectual disability, language delay and autism spectrum disorder.@*METHODS@#Genomic DNA was extracted from peripheral blood samples of the child and his family members, and subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing and interpreted according to the guidelines of the American College of Medical Genetics and Genomics.@*RESULTS@#The child was found to harbor a heterozygous c.568C>T (p.Q190X) nonsense variant of the ADNP gene, which was not detected in either parent by Sanger sequencing.@*CONCLUSION@#The clinical and genetic testing both suggested that the child has Helsmoortel-van der Aa syndrome due to ADNP gene mutation, which is extremely rare in China.
Subject(s)
Child , Humans , Abnormalities, Multiple/genetics , Autism Spectrum Disorder/genetics , Autistic Disorder/genetics , Heterozygote , Homeodomain Proteins/genetics , Intellectual Disability/genetics , Mutation , Nerve Tissue Proteins/genetics , Rare DiseasesABSTRACT
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes coronavirus disease-2019 (COVID-19), interacts with the host cell receptor angiotensin-converting enzyme 2 (hACE2) via its spike 1 protein for infection. After the virus sequence was published, we identified two potent antibodies against SARS-CoV-2 RBD from antibody libraries using a phage-to-yeast (PtY) display platform in only 10 days. Our lead antibody JMB2002, now in a phase I clinical trial, showed broad-spectrum in vitro blocking activity against hACE2 binding to the RBD of multiple SARS-CoV-2 variants including B.1.351 that was reportedly much more resistant to neutralization by convalescent plasma, vaccine sera and some clinical stage neutralizing antibodies. Furthermore, JMB2002 has demonstrated complete prophylactic and potent therapeutic efficacy in a rhesus macaque disease model. Prophylactic and therapeutic countermeasure intervention of SARS-CoV-2 using JMB2002 would likely slow down the transmission of currently emerged SARS-CoV-2 variants and result in more efficient control of the COVID-19 pandemic.
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Objective:To analyze the correlation between 21-gene recurrence score (RS) and clinicopathological characteristics of patients with Lumina type breast cancer, and to explore its significance in individualized treatment.Methods:The clinicopathological data of 59 patients with surgical resection and pathological diagnosis of Lumina type breast cancer in Shanxi Provincial Cancer Hospital from May 2018 to May 2019 were retrospectively analyzed. Real-time fluorescence quantitative polymerase chain reaction was used to detect the expression of 21 gene and RS was calculated. According to the 21-gene RS, the patients were divided into low recurrence risk group (RS < 18 points), intermediate recurrence risk group (RS 18-31 points) and high recurrence risk group (RS > 31 points). Univariate and multivariate logistic regression analyses were made to evaluate the correlations between different recurrence risk and clinicopathological characteristics of patients and their influence on the choice of adjuvant chemotherapy.Results:Based on the 21-gene RS, 29 patients were in low recurrence risk group, 22 cases were in intermediate recurrence risk group, and 8 cases were in high recurrence risk group. Single-factor analysis showed that age ( P = 0.012), maximum mass diameter ( P = 0.031), histological grade ( P = 0.036), progesterone receptor (PR) level ( P = 0.015), Ki-67 positive index ( P = 0.049) and molecular typing ( P = 0.010) were influencing factors of 21-gene RS recurrence risk. Multivariate logistic regression analysis showed that the age and Ki-67 positive index were negatively correlated with 21-gene RS recurrence risk (both P < 0.05). After grouping according to the 21-gene RS, 17 patients in the intermediate recurrence risk group (according to the traditional postoperative recurrence risk grouping method for breast cancer) were classified as low recurrence risk group, and 4 patients in the low recurrence risk group were classified as intermediate recurrence risk group ( χ2 = 4.535, P = 0.033). After grouping based on 21-gene RS, the number of patients who needed chemotherapy in individualized treatment decreased. Of the 17 cases, 11 cases did not undergo postoperative chemotherapy, and the remaining patients received chemotherapy. The postoperative follow-up period was 11-22 months. As of March 2020, there was no recurrence or disease progress. Conclusion:The 21-gene RS can provide objective basis for the individualized precise treatment and prognosis prediction for patients with early-stage Lumina type breast cancer.
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Objective:To investigate changes in the expression of Cosmc and T-synthase in peripheral B lymphocytes and in serum levels of galactose-deficient IgA1 (Gd-IgA1) in patients with Henoch-Sch?nlein purpura (HSP) .Methods:From January to August 2014, 56 patients with HSP were collected from outpatient or inpatient department of dermatology and venereology in the Second Hospital of Hebei Medical University, and were divided into 4 groups, including skin type group (22 cases) , joint type group (9 cases) , abdominal type group (12 cases) and renal type group (13 cases) . Twenty healthy volunteers served as healthy controls. Real-time fluorescence-based quantitative PCR was performed to determine the mRNA expression of Cosmc and T-synthase in peripheral B lymphocytes, and a lectin-based enzyme-linked immunosorbent assay (ELISA) to detect the serum level of Gd-IgA1. Comparisons among multiple groups were performed using one-way analysis of variance or Kruskal-Wallis H test, multiple comparisons were performed using least significant difference (LSD) - t test or Nemenyi test, and correlation analysis was performed using Spearman rank correlation analysis. Results:There was a significant difference in the duration from disease onset to the clinic visit ( χ2= 26.19, P < 0.05) among the skin type group (6.27 ± 3.09 d) , joint type group (5.56 ± 3.05 d) , abdominal type group (6.75 ± 3.75 d) , and renal type group (26.23 ± 14.12 d) , and the duration from disease onset to the clinic visit was significantly longer in the renal type group than in the other 3 groups (all P < 0.05) . The Cosmc mRNA expression significantly differed among the skin type group, joint type group, abdominal type group, renal type group and healthy control group (0.849 ± 0.239, 0.767 ± 0.181, 0.719 ± 0.183, 0.459 ± 0.121, 1.146 ± 0.232, F= 23.37, P < 0.05) , was significantly lower in the 4 patient groups than in the healthy control group ( P < 0.01) , and lower in the renal type group than in the other 3 patient groups (all P < 0.01) . There was no significant difference in the T-synthase mRNA expression in peripheral B lymphocytes among the patient groups and healthy control group ( F= 1.05, P > 0.05) . The serum level of Gd-IgA1 significantly differed among the skin type group, joint type group, abdominal type group, renal type group and healthy control group ( F= 7.06, P < 0.05) . Moreover, the Gd-IgA1 level was significantly higher in the patient groups than in the healthy control group (all P < 0.05) , and higher in the renal type group than in the other 3 patient groups (all P < 0.05) . The serum level of Gd-IgA1 in the HSP patients was significantly and negatively correlated with the mRNA expression of Cosmc ( rs=-0.50, P < 0.01) . Conclusion:Decreased mRNA expression of Cosmc and increased serum levels of Gd-IgA1 were observed in patients with HSP, and there was a negative correlation between the two indices.
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Objective To understand the changes of serum tumor necrosis factor-α (TNF-α) among adults with Kaschin-Beck disease (KBD) in Qinghai,and to provide scientific data for KBD prevention and control.Methods A case-control study was used,according to "Diagnosis of Kaschin-Beck disease",104 cases of KBD patients [aged (47.61 ± 12.72) years old;50 males,54 females] and 95 cases of internal healthy controls [aged (48.28 ±14.87) years old;35 males,60 females],which were from KBD areas in Xinghai and Guide counties of Hainan Tibetan Autonomous Prefecture,Qinghai Province,and 73 cases of external healthy controls [aged (51.88 ± 13.93)years old;35 males,38 females] from non-KBD region of Xunhua County were included in July 2017.Serum TNF-α was determined via the enzyme linked immunosorbent assay (ELISA) method.Results Totally 272 persons were studied and divided into three groups,there was no statistical significant difference of ages among the three groups (F =2.236,P > 0.05),meanwhile,there was no statistical significant difference of genders among the three groups (x2 =3.135,P > 0.05).The serum TNF-α levels of KBD patients,internal and external healthy controls were (25.14 ± 10.29),(21.84 ± 9.37),and (24.98 ± 8.98) ng/L,respectively,which were statistically significantly different among the three groups (F =3.486,P < 0.05).The serum TNF-α levels in the KBD group and the external healthy control were higher than that in internal healthy control (P < 0.05).There was no significant difference between the KBD group and the external healthy control (P > 0.05).Conclusion There may exist inflammatory changes among KBD patients in KBD areas of Qinghai Province.
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Objective To analyze the change of intrahepatic regulatory T cells (Treg )/helper thymphorytes (Th)17 balance in patients with different phases of chronic hepatitis B virus (HBV ) infection ,and to explore the role of Treg/Th17 balance in maintaining immune tolerance and inducing immune clearance ,and its influence on disease progression .Methods Sixty-eight patients with chronic HBV infection who underwent liver biopsy in Tianjin Second People′s Hospital were included .The 68 patients included 20 cases in immune tolerant (IT) phase ,36 cases in immune clearance (IC) phase and 12 cases in inactive phase .Eight healthy liver transplant donors were collected as healthy controls .The intrahepatic Treg/Th17 levels were detected by immuno-histochemical method . The changes of Treg/Th17 balance in patients with different phases of chronic HBV infection ,and the relationship between Treg/Th17 balance and the decreases of hepatitis B surface antigen (HBsAg ) , hepatitis B antigen (HBeAg) and HBV DNA levels in the peripheral blood were analyzed in patients with IC phase at two weeks of admission .Results The intrahepatic Treg and Th17 levels in IC phase group were the highest , then and they were higher in inactive phase group were higher than those in IT phase group ,And they were the lowest in control group .The Treg level in IC phase group increased significantly compared with the other three groups (all P< 0 .01) ,and there were no significant differences among the other three groups (all P> 0 .05) .The Th17 level between IT phase group and inactive phase group was not significantly different (P> 0 .05) ,while the differences were not significant in other groups (all P>0 .05) .Treg/Th17 ratio of IT phase group was the highest ,then the ratio of control group was higher than that of inactive phase group ,and IC phase group was the lowest ratio .The differences between IC phase group ,control group and IT phase group were significant (all P< 0 .05) ,and the difference between inactive phase group and IT phase group was also significant (all P<0 .05);and there was no significant difference among other groups (all P>0 .05) .The decreases of HBsAg ,HBeAg and HBV DNA levels in the peripheral blood at two weeks admission were negatively correlated with the intrahepatic Treg cell level in patients in IC phase of chronic HBV infection ( r= -0 .941 ,-0 .869 ,and -0 .883 ,respectively ,both P<0 .01) .The Treg ,Th17 levels and their ratio in IC phase group with different degree of inflammation and fibrosis had significant differences :G4 group > G3 group > G2 group ,S3 group > S2 group > S1 group (all P<0 .05) .Conclusions There is no change of the Treg/Th17 balance in IT phase ,and Treg has no influence on maintaining immune tolerance in chronic HBV infection .T he imbalance of Treg/Th17 is observed in IC phase .Th17 may actively participate in the immune-mediated liver injury and the development of hepatic fibrosis in CHB patients .Treg may inhibit inflammation and reduce liver injury via the negative feedback regulation mechanism ,and may impede the eradication of HBV simultaneously .
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Objective To explore the effect of chloroquine on death receptor 5 (DR5) expression of hepatocellular carcinoma Huh7 cells and cell proliferation and apoptosis induced by tumor necrosis factor related apoptosis-inducing ligand (TRAIL).Methods Huh7 cells were divided into four groups:the control group (1∶1 000 dimethyl sulfoxide),TRAIL group (50 μg/L),chloroquine group (10 μmol/L) and TRAIL +chloroquine group (TRAIL 50 μg/L + chloroquine 10 μmol/L).Thiazolyl blue tetrazolium bromide (MTT) assay was used to determine the proliferation activity of cells,immunofluorescence was used to detect the expression of DR5,4',6-diamidino-2-phenylindole (DAPI) staining was used to observe cell apoptosis and Western blot was used to detect the expression of cleaved poly ADP-ribose polymerase (PARP).Results TRAIL treatment could decrease Huh7 cells proliferation activity;when compared with the cell viability in the control group,the cell proliferation inhibition rate of chloroquine group,TRAIL group and TRAIL+ chloroquine group was (89±8) %,(53±10) % and (27±7) %,respectively;compared with TRAIL group alone,cell proliferation activity was decreased in TRAIL+ chloroquine group (t =3.922,P =0.017).The expression of DR5 was upregulated in chloroquine group,and the cell apoptosis signaling was activated in TRAIL + chloroquine group.The cell apoptosis rate of TRAIL group and TRAIL + chloroquine group was (10.0±2.3) % and (20.4±4.0) %,respectively,and there was a statistical difference (t =3.894,P =0.018).Conclusion Chloroquine can enhance the cell chemosensitivity to TRAIL treatment by upregulating the expression of DR5 in Huh7 cells.
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Chemical disinfectants are generally used for virus inactivation and environment disinfection in biosafety laboratory, and the efficacy and evaluation of the disinfection are critical to ensure the laboratory biosafety.However, there is a current lack of applied standard to evaluate the virucidal efficacy of chemical disinfectants in our country.In this paper, a European Union standard“Method and Requirements of Virucidal Quantitative Suspension Test Method for Chemical Disinfectants Used in Human Medicine” was analyzed and a standard transformation scheme has been proposed.It is suggested that the model viruses should be increased from 3 to 6, including the surrogate viruses to substitute highly pathogenic viruses, and that the method to remove the residual chemical disinfectant and the calculation of 95%confidence interval should be incorporated into the standard.The suggestion will improve the scientific and operational standards related to disinfection and sterilization in biosafety laboratory in China.
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Objective To explore the role and relationship of N-terminal pro-brain natriuretic peptide (NT-proBNP) and matrix metalloproteinase-9 (MMP-9 ) in risk stratification and prognosis assessment of non-ST elevation acute coronary syndrome (NSTE-ACS).Methods We recruited 114 patients with NSTE-ACS and classified them into three groups according to the GRACE risk stratification:high-risk,intermediate-risk and low-risk groups.Another 5 8 patients were recruited as controls.Arterial blood was collected before angiography for the measurement of serum NT-proBNP and MMP-9 .Gensini score was used to evaluate the degree of coronary artery stenosis.All the patients were followed up for 6 months and MACE was observed and recorded.Results ① The levels of lg NT-proBNP and MMP-9 significantly differed between the groups (P<0.05).② ROC curve analysis showed that lg NT-proBNP could predict MACE of NSTE-ACS;area under the curve was 0.795,the cutoff value was 2 .0 6 9 ,corresponding to the NT-proBNP value of 1 1 6 .5 6 ng/L.MMP-9 could predict MACE of NSTE-ACS;area under the curve was 0 .6 9 6 ,the cutoff value was 3 2 .4 9 ng/ml;both of the abnormal indexes could predict MACE with the sensitivity of 80.41%,specificity of 82.19%,and Youden’s index of 0.63.③ Cox regression analysis showed that abnormal MMP-9 and NT-proBNP levels were independently related to the incidence of MACE by the value of OR as 3.751.Conclusion MMP-9 and NT-proBNP may be used as serological indicators in risk stratification of NSTE-ACS. The combined use of NT-proBNP and MMP-9 increases the power of predicting MACE.
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Objective To study the method of preparation and blood sugar lowering effect of oral chitosan-insulin nanoparticles (INS-NPs) in streptozotocin-induced diabetic Wistar rats. Methods The INS-NPs were prepared by an ionic gelation method. The changes in the morphology and size of the INS-NPs were observed with transmission electron microscope and Zetasizer 3000HS, respectively. The blood sugar lowering effect of the INS-NPs was evaluated by monitoring the blood glucose levels in healthy and streptozotocin-induced diabetic rats. Results INS-NPs were spherical in shape with a mean size of 220.6±15.9nm. Entrapment efficiency of INS-NPs was 75.4%±3.2% and the loading efficiency of INS-NPs was 19.5%±2.6%. In vivo blood sugar lowering study showed that the levels of blood glucose of healthy Wistar rats were significantly reduced from 6h to 12h after oral administration of INS-NPs(25U/kg). The blood glucose level of diabetic rats were significantly reduced at 6h after oral administration of INS-NPs (25U/kg), and this effect was maintained for more than 9h, and the levels of blood glucose were kept in normal range for 7h. Conclusion The INS-NPs prepared by ionic gelation method has the blood glucose lowering effect in streptozotocin-induced diabetic Wistar rats.
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Objective To study the gait footprint parameters of the normal children and the cerebral palsy (CP) children, and to explore its clinical value. Methods A total of 2 800 normal children aged 3 to 10 years and 139 spastic CP children aged 3 to 5 years were recruited in this study. The normal children were divided into seven groups with one year interval, and were measured with regard to the length of foot and step, step width and foot angle of footprint of every age group with self made oil printed carpet. The footprint of the CP children were measured and compared with that of the normal children at the same age. Results It was revealed that there was significant difference between the normal and the CP children ( P
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Objective:To study the effect of CsA on CD4+CD25+T cells from DO11.10 mice after immunization with OVA.Methods:The amount of spleen CD4+CD25+T cells and Foxp3+T cells was detected by means of flow cytometry (FCM).Results:After immunization with OVA,the ratios of CD4+CD25+T cells to CD4+T cells and Foxp3+T cells to CD4+CD25+T cells elevated in spleen,but CsA significantly decreased the percentage of CD4+CD25+T cells and CD4+CD25+Foxp3+T cells under either naive state or immune reaction state.Conclusion:CsA inhibits immune responses,while it also suppresses immune tolerance.