Objective:To investigate the expression relationship of Survivin,Bad,Bax and Bcl-2 genes in esophageal squamous cell carcinoma patients and to explore their correlation with clinicopathological markers,moreover,compare with GEPIA cancer database.Methods:48 ESCC specimens were taken from patients and used in the study.Matched adjacent normal tissues were used as controls.The expression of Survivin,Bad,Bax,and Bcl-2 genes were detected by RT-PCR.Meanwile,genes expressions were analyzed with clinicopathological factors,including tumor differentiation degree,TNM classification,clinical stage and lymph node metastasis.GEPIA analyzes the correlation between Survivin,Bad,Bax and Bcl-2 online.Results:In 48 cases of cancer tissues,Survivin expression was detected in 85.4％(41/48)of cancer tissues and in 62.5％(30/48)of adjacent normal tissues,and Bad was 45.8％(22/48)and 25％(12/48)respectively.Survivin and Bad were both highly expressed in cancer tissues,and the difference was statistically significant(P＜0.05),but Bax and Bcl-2 genes had no statical significance(P＞0.05).The mRNA expression rates of Bad,Bax,and Bcl-2 increased with higher differentiation degree(P＜0.05),while the high expression rate of Survivin mRNA was correlated with lymph node metastasis(P＜0.05).However,none of these markers showed associations with TNM staging or clinical stage.The expression of Bad had a negative correlation with the expression of Survivin(r=-0.449,P＜0.05),but a positive correlation with the expression of Bcl-2(r=0.348,P＜0.05).The expressions of Bax,Bcl-2 and survivin were positively correlated(r=0.552,0.331,respectively,both P＜0.05).The results of the GEPIA cancer database show that Survivin was highly expressed in cancer tissues(P＜0.05),and the expressions of Bad,Bax and Survivin were negatively correlated(r=-0.19,-0.16,respectively,both P＜0.01).Conclusions:Survivin and Bad may synergistically promote esophageal squamous cell carcinogenesis,while Bad,Bax,and Bcl-2 are implicated in malignant transformation.

Objective:To investigate the expression relationship of Survivin,Bad,Bax and Bcl-2 genes in esophageal squamous cell carcinoma patients and to explore their correlation with clinicopathological markers,moreover,compare with GEPIA cancer database.Methods:48 ESCC specimens were taken from patients and used in the study.Matched adjacent normal tissues were used as controls.The expression of Survivin,Bad,Bax,and Bcl-2 genes were detected by RT-PCR.Meanwile,genes expressions were analyzed with clinicopathological factors,including tumor differentiation degree,TNM classification,clinical stage and lymph node metastasis.GEPIA analyzes the correlation between Survivin,Bad,Bax and Bcl-2 online.Results:In 48 cases of cancer tissues,Survivin expression was detected in 85.4％(41/48)of cancer tissues and in 62.5％(30/48)of adjacent normal tissues,and Bad was 45.8％(22/48)and 25％(12/48)respectively.Survivin and Bad were both highly expressed in cancer tissues,and the difference was statistically significant(P＜0.05),but Bax and Bcl-2 genes had no statical significance(P＞0.05).The mRNA expression rates of Bad,Bax,and Bcl-2 increased with higher differentiation degree(P＜0.05),while the high expression rate of Survivin mRNA was correlated with lymph node metastasis(P＜0.05).However,none of these markers showed associations with TNM staging or clinical stage.The expression of Bad had a negative correlation with the expression of Survivin(r=-0.449,P＜0.05),but a positive correlation with the expression of Bcl-2(r=0.348,P＜0.05).The expressions of Bax,Bcl-2 and survivin were positively correlated(r=0.552,0.331,respectively,both P＜0.05).The results of the GEPIA cancer database show that Survivin was highly expressed in cancer tissues(P＜0.05),and the expressions of Bad,Bax and Survivin were negatively correlated(r=-0.19,-0.16,respectively,both P＜0.01).Conclusions:Survivin and Bad may synergistically promote esophageal squamous cell carcinogenesis,while Bad,Bax,and Bcl-2 are implicated in malignant transformation.

Multiple sclerosis (MS) is a neuroinflammatory demyelinating disease, mediated by pathogenic T helper 17 (Th17) cells. However, the therapeutic effect is accompanied by the fluctuation of the proportion and function of Th17 cells, which prompted us to find the key regulator of Th17 differentiation in MS. Here, we demonstrated that the triggering receptor expressed on myeloid cells 2 (TREM-2), a modulator of pattern recognition receptors on innate immune cells, was highly expressed on pathogenic CD4-positive T lymphocyte (CD4⁺ T) cells in both patients with MS and experimental autoimmune encephalomyelitis (EAE) mouse models. Conditional knockout of Trem-2 in CD4⁺ T cells significantly alleviated the disease activity and reduced Th17 cell infiltration, activation, differentiation, and inflammatory cytokine production and secretion in EAE mice. Furthermore, with Trem-2 knockout in vivo experiments and in vitro inhibitor assays, the TREM-2/zeta-chain associated protein kinase 70 (ZAP70)/signal transducer and activator of transcription 3 (STAT3) signal axis was essential for Th17 activation and differentiation in EAE progression. In conclusion, TREM-2 is a key regulator of pathogenic Th17 in EAE mice, and this sheds new light on the potential of this therapeutic target for MS.
Animals ; Humans ; Mice ; CD4-Positive T-Lymphocytes/pathology* ; Cell Differentiation ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Mice, Inbred C57BL ; Multiple Sclerosis ; Th1 Cells/pathology*

Objective To analyze the sensitivity of ARHGAP8 in predicting the efficacy of neoadjuvant chemotherapy in the patients with locally advanced mid-low colorectal cancer and provide accurate evidence for the treatment of advanced colorectal cancer.Methods The differentially expressed gene ARHGAP8 was screened out by bioinformatics analysis.Cancer tissue and rectal tissue of 68 patients with primary rectal cancer were select-ed.The rectal cancer tissue samples and the rectal tissue samples were collected for clinical validation of ARH-GAP8 expression by quantitative real-time PCR,Western blotting,and immunohistochemistry.The clinical and pathological features such as gender,age,tumor stage,differentiation degree,and pathological type of the pa-tients were collected for functional validation.Forty-four patients with locally advanced mid-low rectal cancer who received neoadjuvant chemotherapy were selected for immunohistochemical examination of ARHGAP8 expres-sion.The expression level of ARHGAP8 was compared between before and after chemotherapy and among different efficacy groups.Results The bioinformatics analysis revealed differences in the expression level of ARHGAP8 between the cancer tissue and rectal tissue(P＜0.001).The expression level of ARHGAP8 was correlated with tumor stage(P=0.024),lymph node metastasis(P=0.007),and age(P=0.005).Quantitative real-time PCR results showed that the mRNA level of ARHGAP8 in the cancer tissue was higher than that in the rectal tis-sue(P＜0.001).Western blotting and immunohistochemistry results demonstrated that the protein level of ARH-GAP8 in the cancer tissue was higher than that in the rectal tissue(P=0.011).The expression of ARHGAP8 was correlated with tumor size(P=0.010)and pathological stage(P=0.005),while it showed no significant association with tumor differentiation degree,lymph node metastasis,liver metastasis,Ki-67,or microsatellite instability expression level.The 44 patients receiving neoadjuvant chemotherapy included 13,8,8,and 15 pa-tients of tumor regression grades 0,1,2,and 3,respectively.Among them,65.91％(29/44)patients showed responses to the treatment.After neoadjuvant chemotherapy,the expression of ARHGAP8 in the cancer tissue was down-regulated in the patients who responded to the chemotherapy(P＜0.001).The response rate in the patients with low protein level of ARHGAP8 was 92.86％,which was higher than that(53.33％)in the patients with high pro-tein level of ARHGAP8(P=0.033).Conclusions ARHGAP8 is highly expressed in the rectal cancer tissue.The pa-tients with locally advanced mid-low rectal cancer and low ARHGAP8 expression are more sensitive to neoadjuvant chemotherapy with the XELOX protocol.ARHGAP8 can serve as a potential biomarker for the occurrence and develop-ment of rectal cancer and an important index for evaluating the efficacy of neoadjuvant chemotherapy with the XELOX protocol in the patients with locally advanced mid-low rectal cancer.

Humans ; Blast Crisis/genetics* ; Leukemia, Promyelocytic, Acute/genetics* ; Oncogene Proteins, Fusion/genetics* ; Tretinoin

Objective: To analyze the clinical characteristics of children with Burkitt lymphoma (BL) and to summarize the mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen. Methods: Clinical features of 436 BL patients who were ≤18 years old and treated with the CNCL-B-NHL-2017 regimen from May 2017 to April 2021 were analyzed retrospectively. Clinical characteristics of patients at disease onset were analyzed and the therapeutic effects of patients with different clinical stages and risk groups were compared. Survival analysis was performed by Kaplan-Meier method, and Cox regression was used to identify the prognostic factors. Results: Among 436 patients, there were 368 (84.4%) males and 68 (15.6%) females, the age of disease onset was 6.0 (4.0, 9.0) years old. According to the St. Jude staging system, there were 4 patients (0.9%) with stage Ⅰ, 30 patients (6.9%) with stage Ⅱ, 217 patients (49.8%) with stage Ⅲ, and 185 patients (42.4%) with stage Ⅳ. All patients were stratified into following risk groups: group A (n=1, 0.2%), group B1 (n=46, 10.6%), group B2 (n=19, 4.4%), group C1 (n=285, 65.4%), group C2 (n=85, 19.5%). Sixty-three patients (14.4%) were treated with chemotherapy only and 373 patients (85.6%) were treated with chemotherapy combined with rituximab. Twenty-one patients (4.8%) suffered from progressive disease, 3 patients (0.7%) relapsed, and 13 patients (3.0%) died of treatment-related complications. The follow-up time of all patients was 24.0 (13.0, 35.0) months, the 2-year event free survival (EFS) rate of all patients was (90.9±1.4) %. The 2-year EFS rates of group A, B1, B2, C1 and C2 were 100.0%, 100.0%, (94.7±5.1) %, (90.7±1.7) % and (85.9±4.0) %, respectively. The 2-year EFS rates was higher in group A, B1, and B2 than those in group C1 (χ²=4.16, P=0.041) and group C2 (χ²=7.21, P=0.007). The 2-year EFS rates of the patients treated with chemotherapy alone and those treated with chemotherapy combined with rituximab were (79.3±5.1)% and (92.9±1.4)% (χ²=14.23, P<0.001) respectively. Multivariate analysis showed that stage Ⅳ (including leukemia stage), serum lactate dehydrogenase (LDH)>4-fold normal value, and with residual tumor in the mid-term evaluation were risk factors for poor prognosis (HR=1.38,1.23,8.52,95%CI 1.05-1.82,1.05-1.43,3.96-18.30). Conclusions: The CNCL-B-NHL-2017 regimen show significant effect in the treatment of pediatric BL. The combination of rituximab improve the efficacy further.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Burkitt Lymphoma/drug therapy* ; Child ; Disease-Free Survival ; Female ; Humans ; Lactate Dehydrogenases ; Lymphoma, B-Cell/drug therapy* ; Male ; Prognosis ; Retrospective Studies ; Rituximab/therapeutic use* ; Treatment Outcome

Objective:To explore the possible mechanism of electroacupuncture to improve detrusor hyperreflex after suprasacral spinal cord injury. Methods:A total of 60 female Sprague-Dawley rats were included. According to the random number table, twelve were selected as the blank group, twelve as the sham operation group, and the remaining 36 were made neurogenic bladder models using modified T₁₀ spinal cord transection. After that, twelve of them were randomly selected as the model group and twelve were as the electroacupuncture group from the model rats that met the requirements. On the 19th day after modelling, Ciliao (BL32), Zhongji (RN3) and Sanyinjiao (SP6) were taken for electroacupuncture. After seven days of continuous treatment, urodynamic testing was performed, content of cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) in detrusor was determined by ELISA, and the level of phosphorylation of myosin light chain kinase (p-MLCK) of detrusor was determined by Western blotting. Results:Compared with the blank group and the sham operation group, the maximum bladder capacity and bladder compliance significantly reduced (P < 0.01), and the base pressure and leakage point pressure of bladder significantly increased (P < 0.01); the content of cAMP and PKA in detrusor reduced (P < 0.01), p-MLCK in detrusor reduced (P < 0.05) in the model group. Compared with the model group, the maximum bladder capacity and bladder compliance increased (P < 0.01), the base pressure of the bladder and the pressure at the leak point decreased (P < 0.05); the contents of cAMP and PKA protein in detrusor increased (P < 0.05), the p-MLCK in detrusor increased (P < 0.05) in the electroacupuncture group. Conclusion:Electroacupuncture at Ciliao, Zhongji and Sanyinjiao points could improve the bladder function of rats with detrusor hyperreflex after complete spinal cord injury, and its mechanism may be related to up-regulating the expression of cAMP and PKA, phosphorylating and inactivating p-MLCK, which promote relaxation of detrusor.

【Objective】 To explore the regulation and mechanism of mannose(Man) on inflammatory response, so as to provide the basis for application of Man in inflammatory diseases. 【Methods】 RAW264.7 macrophages were treated with different concentrations of Man for 24 h or 48 h, and the proliferation was detected by cell count. RAW264.7 cells were pretreated with low concentration(2 mmol/L) and high concentration(20 mmol/L) of Man for 12 h, followed by treatment with lipopolysaccharide(LPS) for 8 h or 24 h more. mRNA, protein and culture supernatant were collected, and the inflammation related cytokines, proteins and mannose receptor(CD206) were detected by Q-PCR, Western blot, and ELISA. 【Results】 The cell proliferation was increased with the increase of Man concentration under 5 mmol/L, while it was decreased with the increase of Man concentration over 5 mmol/L. Compared with LPS treatment, 2 mmol/L mannose(Man2) plus LPS increased the mRNA levels of IL-1β, IL-12 and TNF-α and the protein levels(all P<0.05), while Man20 + LPS treatment significantly decreased the mRNA levels of IL-1β, IL-12, TNF-α, IL-6, and CCL2 and the protein levels (all P<0.05). The potential targets of network pharmacology for Man and its metabolites were 20 proteins, including AKT and STAT3. Furthermore, the phosphorylation levels of AKT and STAT3(all P<0.05) were increased in Man2 + LPS group and the phosphorylation levels of AKT, p65 and ERK(all P<0.05) were decreased in Man20 + LPS group compared with LPS group. The phosphorylation levels of AKT, p65 and STAT3(all P<0.05) were decreased in Man20 group compared with control group. 【Conclusions】 Different concentrations of mannose have various effects on inflammatory response. Low concentration mannose promotes macrophage inflammatory response induced by LPS, while high concentration mannose inhibits LPS-induced inflammatory response. And this mechanism is related to the regulation of AKT, STAT3, p65, and ERK activities.

The aim of this study was to explore the neuroprotective effect and mechanism of XingNaoJing injections (XNJ) on cerebral ischemia injury and blood-brain barrier (BBB) disruption. Middle cerebral artery occlusion (MCAO) method was applicated to establish the model of cerebral ischemia/reperfusion (I/R) injury in rats. BBB permeability after I/R injury was assessed with the leaking amount of Evans Blue and the expression of occludin and ZO-1. The expression of NOD-like receptor family, pyrin domain containing (NLRP3) was checked to explore the inhibition of inflammation by XNJ. The results showed that XNJ could significantly increase the survival percent, decrease the infarct area and ameliorate neurological deficits and brain damage after I/R injury. Leaking amount of Evans Blue was reduced by XNJ, and the expression of tight junction protein, occludin and ZO-1 was also up-regulated by XNJ, which showed a role of protection on BBB disruption. The expression of NLRP3 was inhibited after exposure of XNJ, which was associated with inhibition of the inflammatory response. In summary, XNJ could suppress NLRP3 inflammasomes and improve BBB disruption and brain damage in rats after cerebral I/R injury, which provided a beneficial insight to further explore XNJ.

China ; Cross-Cultural Comparison ; Environmental Exposure ; standards ; Hearing ; Humans ; Noise ; adverse effects ; United States