ABSTRACT
Objective To study the evaluation value of lung injury score(LIS)and advanced glycation end products(AGEs)expression levels on the prognosis of elderly patients with sepsis-related acute lung injury/acute respiratory distress syndrome(ALI/ARDS).Methods A total of 98 elderly patients with sepsis-related ALI/ARDS admitted to First Branch of the First Affiliated Hospital of Chongqing Medical University from March 2019 to April 2021 were selected as the research group,and the patients were divided into two sub-groups according to their survival within 30 d after admission:the survival group(55 cases)and the death group(43 cases).Another 51 elderly patients with non-ALI/ARDS sepsis admitted to First Branch of the First Affiliated Hospital of Chongqing Medical University in the same period were selected as the control group.After admission,the clinical data of patients were recorded,and the levels of serum creatinine,troponin I,B-type brain natriuretic peptide(BNP),serum C-reactive protein(CRP)and procalcitonin(PCT)were de-tected.Enzyme-linked immunosorbent assay was used to determine the levels of AGEs in patients'serum.The LIS score was evaluated by LIS scale.With clinical factors as independent variables and prognosis as dependent variables,Logistic regression curve was used to analyze the death factors of elderly sepsis-related ALI/ARDS patients.Results AGEs levels,LIS scores,acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)scores decreased sequentially in the death group,survival group,and control group(all P<0.05).The levels of lactic acid,blood glucose,troponin I,PCT,BNP and CRP in arterial blood of patients in the death group were significantly higher than those in the survival group and the control group(P<0.05).The results showed that arterial lactate,blood glucose,troponin I,PCT,BNP,CRP,AGEs,APACHE Ⅱ score,and LIS score were all independent risk factors for mortality in elderly sepsis-related ALI/ARDS patients(P<0.05).The area under the curve(AUC)of LIS score predicting prognosis in elderly sepsis-related ALI/ARDS pa-tients was 0.857(95%CI:0.821-0.911),and AUC of serum AGEs was 0.861(95%CI:0.809-0.908).LIS score and AGEs level had certain predictive value for the prognosis of elderly sepsis-related ALI/ARDS pa-tients.Conclusion The LIS score and AGEs level of the elderly patients with sepsis-related ALI/ARDS are independent risk factors of death,which have important predictive value for prognosis.
ABSTRACT
Objective@#To investigate the longitudinal association of plasma Irisin concentrations with changes in blood pressure (BP) levels among children,and to assess the moderating effect of physical activity (PA) or sedentary behavior (SB) on the relationship between Irisin levels and BP.@*Methods@#Based on a cohort study, a cluster sampling method was used to select 3 651 school aged children from five schools in Guangzhou in 2017 at the baseline survey and follow up in 2019. Both at baseline and during follow up, PA and SB were assessed by validated questionnaires, and BP levels were measured by an electronic sphygmomanometer. A final sample of 521 children were enrolled based on the PA and SB at baseline. Plasma Irisin concentrations were measured by ELISA at baseline. Logistic regression analysis was recruited for exploring the associations of plasma Irisin concentrations with changes in BP. Moderating effects of PA and SB on the relationship between Irisin concentrations and BP were estimated using stratified analysis.@*Results@#Logistic regression analysis indicated that there was no significant association between Irisin concentrations and changes in BP levels among children ( OR =0.98, P >0.05). After stratification for SB, Irisin levels in the low SB subgroup were inversely associated with changes in diastolic blood pressure ( OR=0.87, 95%CI=0.77-0.98, P =0.02). In addition, SB level had a moderating effect on the relationship between Irisin levels and the DBP changes ( P =0.01).@*Conclusion@#Increased Irisin concentration is associated with the decrease of DBP level among low SB children. Furthermore, SB level shows moderating role in the relationship between Irisin concentrations and changes in DBP levels.
ABSTRACT
Objective: To investigate the clinicopathological features and molecular genetics of diffuse large B-cell lymphomas (DLBCL) with concurrent or secondary to nodal T-follicular helper cell lymphoma, angioimmunoblastic-type (nTFHL-AI). Methods: The clinicopathological features and molecular genetics of DLBCL associated with nTFHL-AI diagnosed between January 2015 and October 2022 at the First Affiliated Hospital of Zhengzhou University were analyzed using histology, immunohistochemistry, PCR, EBV-encoded RNA in situ hybridization and fluorescence in situ hybridization (FISH). Clinical information was collected and analyzed. Results: A total of 6 cases including 3 nTFHL-AI with secondary DLBCL and 3 composite lymphomas were reviewed. There were 4 male and 2 female patients, whose ages ranged from 40 to 74 years (median 57 years). All patients presented with nodal lesions at an advanced Ann Arbor stage Ⅲ/Ⅳ (6/6). Bone marrow involvement was detected in 4 patients. All cases showed typical histologic and immunophenotypic characteristics of nTFHL-AI. Among them, 5 cases of DLBCL with concurrent nTFHL-AI exhibited numerous large atypical lymphoid cells and the tumor cells were CD20 and CD79α positive. The only case of DLBCL secondary to nTFHL-AI showed plasma cell differentiation and reduced expression of CD20. All of cases were activated B-cell (ABC)/non-germinal center B-cell (non-GCB) subtype. Three of the 6 cases were EBV positive with>100 positive cells/high power field, meeting the diagnostic criteria of EBV+DLBCL. The expression of MYC and CD30 protein in the DLBCL region was higher than that in the nTFHL-AI region (n=5). C-MYC, bcl-6 and bcl-2 translocations were not detected in the 4 cases that were subject to FISH. Four of the 6 patients received chemotherapy after diagnosis. For the DLBCL cases of nTFHL-AI with secondary DLBCL, the interval was between 2-20 months. During the follow-up period ranging from 3-29 months, 3 of the 6 patients died of the disease. Conclusions: DLBCL associated with nTFHL-AI is very rare. The expansion of EBV-infected B cells in nTFHL-AI may progress to secondary EBV+DLBCL. However, EBV-negative cases have also been reported, suggesting possible other mechanisms. The up-regulation of MYC expression in these cases suggests a possible role in B-cell lymphomagenesis. Clinicians should be aware that another biopsy is still necessary to rule out concurrent or secondary DLBCL when nodal and extranodal lesions are noted after nTFHL-AI treatment.
Subject(s)
Female , Male , Humans , In Situ Hybridization, Fluorescence , Lymphoma, Large B-Cell, Diffuse , B-Lymphocytes , Biopsy , T-Lymphocytes, Helper-InducerABSTRACT
Objective: To investigate the clinicopathological features, diagnosis and differential diagnosis of breast myofibroblastoma. Methods: The clinicopathological data and prognostic information of 15 patients with breast myofibroblastoma diagnosed at the Department of Pathology of the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China from 2014 to 2022 were collected. Their clinical characteristics, histological subtypes, immunophenotypes and molecular characteristics were analyzed. Results: There were 12 female and 3 male patients, ranging in age from 18 to 78 years, with a median and average age of 52 years. There were 6 cases in the left breast and 9 cases in the right breast, including 12 cases in outer upper quadrant, 2 cases in inner upper quadrant and 1 case in outer lower quadrant. Most of the cases showed a well-defined nodule grossly, including pushing growth under the microscope in 13 cases, being completely separated from the surrounding breast tissue in 1 case, and infiltrating growth in 1 case. Among them, 12 cases were classic subtype and composed of occasional spindle cells with varying intervals of collagen fiber bundles; eight cases had a small amount of fat; one case had focal cartilage differentiation; one case was epithelioid subtype, in which epithelioid tumor cells were scattered in single filing or small clusters; one case was schwannoma-like subtype, and the tumor cells were arranged in a significant palisade shape, resembling schwannoma, and one case was invasive leiomyoma-like subtype, in which the tumor cells had eosinophilic cytoplasm and were arranged in bundles, and infiltrating into the surrounding mammary lobules like leiomyoma. Immunohistochemical studies showed that the tumor cells expressed desmin (14/15) and CD34 (14/15), as well as ER (15/15) and PR (15/15). Three cases with histologic subtypes of epithelioid subtype, schwannoma-like subtype and infiltrating leiomyoma-like subtype showed RB1 negative immunohistochemistry. Then FISH was performed to detect RB1/13q14 gene deletion, and identified RB1 gene deletion in all three cases. Fifteen cases were followed up for 2-100 months, and no recurrence was noted. Conclusions: Myofibroblastoma is a rare benign mesenchymal tumor of the breast. In addition to the classic type, there are many histological variants, among which the epithelioid subtype is easily confused with invasive lobular carcinoma. The schwannoma-like subtype is similar to schwannoma, while the invasive subtype is easily misdiagnosed as fibromatosis-like or spindle cell metaplastic carcinoma. Therefore, it is important to recognize the various histological subtypes and clinicopathological features of the tumor for making correct pathological diagnosis and rational clinical treatment.
Subject(s)
Female , Humans , Male , Adolescent , Young Adult , Adult , Middle Aged , Aged , Antigens, CD34 , Biomarkers, Tumor/analysis , Leiomyoma/pathology , Neoplasms, Muscle Tissue/pathology , NeurilemmomaABSTRACT
The phenylpropanoid pathway is one of the important pathways for synthesizing plant secondary metabolites, which can produce lignin, flavonoid, and sinapoylmalate. These compounds can not only affect the plant growth, development, and stress response, but also be used to produce perfume, pesticide, dye, medicine, feed, and biomass energy. R2R3-MYBs play important roles in regulating plant secondary metabolism, organ development, and in responding to environmental stresses. Wheat (Triticum aestivum L.) is an important food crop, but lots of straw will be produced accompanied by grain yields. Therefore, elucidating the function and regulatory mechanism of R2R3 MYBs of wheat is crucial for the effective utilization of the wheat straw. RT-PCR results showed that TaMYB1A was highly expressed in the wheat stems, and the GFP-TaMYB1A fusion protein was mainly localized in the nucleus of the N. benthamiana epidermal cells. TaMYB1A has transcriptional repressive activity in yeast cells. In this study, TaMYB1A-overexpressed transgenic Arabidopsis lines were generated to elucidate the effect of overexpression of TaMYB1A on the biosynthesis of lignin and flavonoid. Our results suggested that overexpression of TaMYB1A inhibited the plant height (P < 0. 05) and decreased the lignin (P < 0. 05) and flavonoid (P < 0. 05) biosynthesis of the transgenic Arabidopsis plants significantly. TaMYB1A could bind to the promoters of the Arabidopsis At4CL1, AtC4H, AtC3H, and AtCHS as well as the wheat Ta4CL1 and TaC4H1 revealed by yeast one-hybrid (Y1H) assasy, the transcriptional repressive effect of TaMYB1A on At4CL1, AtC4H, AtC3H, and AtCHS was confirmed by dual-luciferase reporter systems and also on Ta4CL1 and TaC4H1 by a genetic approach. Gene chip and quantitative RT-PCR (qRT-PCR) results showed that overexpression of TaMYB1A down-regulated the expression of most of the key genes involved in the phenylpropanoid metabolism and decreased the 4CL activity (P < 0. 05) of the transgenic Arabidopsis plants significantly. As suggested above, the wheat TaMYB1A belongs to the subgroup 4 R2R3 MYB transcription factors. TaMYB1A could bind to the promoters of the key genes involved in phenylpropanoid metabolism, repress their expression and negatively regulate the phenylpropanoid metabolism pathway and plant height.
ABSTRACT
Objective:To investigate the effects of hydroxysafflor yellow A (HSYA) on depressive-like behavior and expression of type A γ-aminobutyric acid receptor(GABAAR)in hippocampus of chronic restraint stress model mice.Methods:The SPF grade male C57BL/6C mice were divided into Control group, HSYA group, Model group, Model + HSYA group and Model + fluoxetine group according to random number table method, with 12 mice in each group.Mice model of depression was established by chronic restraint stress.Mice in HSYA group and Model+ HSYA group were intraperitoneally injected with HSYA(20 mg/kg), mice in Model+ fluoxetine group were injected intraperitoneally with fluoxetine (10 mg/kg), and mice in Control group and Model group administered with 0.9% sodium chloride solution intraperitoneally once a day for 14 days.Then, the forced swimming test (FST) and tail suspension test (TST) were performed to evaluate the depressive-like behavior of mice, and the protein expression levels of different subtypes of GABAAR in the hippocampus of mice were determined by Western blot.SPSS 19.0 and GraphPad Prism 8.0 software were used for data statistical analysis and mapping.One-way ANOVA was used for comparison among groups, and Tukey-HSD test was used for further pairwise comparison.Results:(1) In the behavioral tests, there were significant differences in swimming immobility time of FST and tail suspension immobility time of TST among the five groups ( F=21.59, 20.81, both P<0.05). The swimming immobility time ((143.91±9.97) s) and tail suspension immobility time (( 107.00±6.54) s) in Model group were higher than those in Control group ((52.92±6.70) s, ( 43.50±5.96) s, both P<0.05). There were no significant difference in swimming immobility time and tail suspension immobility time between Model+ HSYA group ((26.17±7.69)s, ( 20.17±7.89)s) and Model+ fluoxetine group ((61.60±16.22)s, (34.14±10.74)s)(both P>0.05), but the swimming immobility time and tail suspension immobility time in these two groups were lower than those in Model group (both P<0.05). (2) The Western blot results showed that there were significant differences in the expression of GABAARβ1 and GABAARβ2 protein in hippocampus among the four groups ( F=12.21, 11.40, both P<0.05). The expression levels of GABAARβ1(45.60±10.76) and GABAARβ2 (46.27±4.82) protein in hippocampus of Model group were lower than those in Control group ((100.00±3.44), (100.00±3.26), both P<0.05). Compared to Model group, the expression of GABAARβ1 (79.91±5.00) and GABAARβ2 (79.08±5.53) protein in hippocampus of Model+ HSYA group were higher (both P<0.05). In addition, the expression of GABAARα1 and GABAARγ1 proteins in hippocampus were not significantly different among the four groups( F=0.23, 0.10, both P>0.05). Conclusion:HSYA can effectively alleviate depressive-like behavior in depression model mice, which may be related with the upregulation of GABAARβ1 and GABAARβ2 of hippocampus tissue.
ABSTRACT
Objective: To study the clinicopathological characteristics, and further understand primary central nervous system T-cell lymphoma (PCNSTCL) in children and adolescents. Methods: Five cases of PCNSTCL in children and adolescents were collected from December 2016 to December 2021 at the First Affiliated Hospital of Zhengzhou University. The clinicopathological characteristics, immunophenotypic, and molecular pathologic features were analyzed, and relevant literatures reviewed. Results: There were two male and three female patients with a median age of 14 years (range 11 to 18 years). There were two peripheral T-cell lymphomas, not otherwise specified, two anaplastic large cell lymphoma, ALK-positive and one NK/T cell lymphoma. Pathologically, the tumor cells showed a variable histomorphologic spectrum, including small, medium and large cells with diffuse growth pattern and perivascular accentuation. Immunohistochemistry and in situ hybridization showed CD3 expression in four cases, and CD3 was lost in one case. CD5 expression was lost in four cases and retained in one case. ALK and CD30 were expressed in two cases. One tumor expressed CD56 and Epstein-Barr virus-encoded RNA. All cases showed a cytotoxic phenotype with expression of TIA1 and granzyme B. Three cases had a high Ki-67 index (>50%). T-cell receptor (TCR) gene rearrangement was clonal in two cases. Conclusions: PCNSTCL is rare, especially in children and adolescents. The morphology of PCNSTCL is diverse. Immunohistochemistry and TCR gene rearrangement play important roles in the diagnosis.
Subject(s)
Female , Humans , Male , Child , Adolescent , Central Nervous System/pathology , Central Nervous System Neoplasms/pathology , Epstein-Barr Virus Infections , Herpesvirus 4, Human , Lymphoma, T-Cell/pathology , Lymphoma, T-Cell, Peripheral/genetics , Receptor Protein-Tyrosine Kinases/genetics , Receptors, Antigen, T-CellABSTRACT
In recent years, the clinical treatment of colorectal cancer(CRC) has made great progress, but chemoresistance is still one of the main reasons for reducing the survival rate of patients with colorectal cancer. Therefore, ameliorating chemotherapy resis-tance is an urgent problem to be solved. The purpose of this study was to investigate the regulatory role and related molecular mechanisms of hydroxysafflor yellow A(HSYA) in colorectal cancer cell proliferation, migration, and 5-fluorouracil(5-FU) chemoresistance. In this study, HCT116 and HT-29 cells were used as research subjects. Firstly, methyl thiazolyl tetrazolium(MTT) assay and colony formation assay were used to detect and analyze the effect of HSYA on the proliferation of CRC cells. Secondly, the effect of HSYA on the cell cycle in CRC cells was analyzed by cell cycle assay. Furthermore, the effect of HSYA on the migration of CRC cells was analyzed by wound-healing assay and Transwell assay. Based on the above, the influences of HSYA on 5-FU chemoresistance of CRC cells and related molecular mechanisms were explored and analyzed. The results showed that HSYA significantly inhibited the proliferation and migration of CRC cells, and arrested the cell cycle in G_0/G_1 phase. In addition, HSYA significantly ameliorated the chemoresistance of CRC cells to 5-FU. The results of acridine orange staining and Western blot showed that the autophagy activity of CRC cells in the HSYA and 5-FU combined treatment group was significantly higher than that in the 5-FU single drug treatment group. As compared with the 5-FU single drug treatment group, the phosphorylation levels of protein kinase B(Akt) and mammalian target of rapamycin(mTOR) in the HSYA and 5-FU combined treatment group were significantly reduced, indicating that the Akt/mTOR signaling pathway in the combined treatment group was down-regulated in CRC cells. In conclusion, HSYA may upregulate autophagy activity through the Akt/mTOR signaling pathway, thereby inhibiting the proliferation and migration of CRC cells and ameliorating the chemoresistance to 5-FU.
Subject(s)
Humans , Proto-Oncogene Proteins c-akt/metabolism , Drug Resistance, Neoplasm , Cell Line, Tumor , TOR Serine-Threonine Kinases/metabolism , Fluorouracil/pharmacology , Cell Proliferation , Autophagy , Colorectal Neoplasms/drug therapyABSTRACT
To study the residue and dietary risk of propiconazole in Panax notoginseng and the effects on physiological and bioche-mical properties of P. notoginseng, we conducted foliar spraying of propiconazole on P. notoginseng in pot experiments. The physiolo-gical and biochemical properties studied included leaf damage, osmoregulatory substance content, antioxidant enzyme system, non-enzymatic system, and saponin content in the main root. The results showed that at the same application concentration, the residual amount of propiconazole in each part of P. notoginseng increased with the increase in the times of application and decreased with the extension of harvest interval. After one-time application of propiconazole according to the recommended dose(132 g·hm~(-2)) for P. ginseng, the half-life was 11.37-13.67 days. After 1-2 times of application in P. notoginseng, propiconazole had a low risk of dietary intake and safety threat to the population. The propiconazole treatment at the recommended concentration and above significantly increased the malondialdehyde(MDA) content, relative conductivity, and osmoregulatory substances and caused the accumulation of reactive oxygen species in P. notoginseng leaves. The propiconazole treatment at half(66 g·hm~(-2)) of the recommended dose for P. ginseng significantly increased the activities of superoxide dismutase(SOD), peroxidase(POD), and catalase(CAT) in P. notoginseng leaves. The propiconazole treatment at 132 g·hm~(-2) above inhibited the activities of glutathione reductase(GR) and glutathione S-transferase(GST), thereby reducing glutathione(GSH) content. Proconazole treatment changed the proportion of 5 main saponins in the main root of P. notoginseng. The treatment with 66 g·hm~(-2) propiconazole promoted the accumulation of saponins, while that with 132 g·hm~(-2) and above propiconazole significantly inhibited the accumulation of saponins. In summary, using propiconazole at 132 g·hm~(-2) to prevent and treat P. notoginseng diseases will cause stress on P. notoginseng, while propiconazole treatment at 66 g·hm~(-2) will not cause stress on P. notoginseng but promote the accumulation of saponins. The effect of propiconazole on P. notoginseng diseases remains to be studied.
Subject(s)
Panax notoginseng/chemistry , Panax , Antioxidants/pharmacology , Saponins/pharmacology , Glutathione , Risk AssessmentABSTRACT
This study aimed to investigate the mechanism of resveratrol(RES) combined with irinotecan(IRI) in the treatment of colorectal cancer(CRC). The targets of RES, IRI, and CRC were obtained from databases, and the targets of RES combined with IRI in the treatment of CRC were acquired by Venn diagram. The protein functional cluster analysis, GO and KEGG enrichment analyses were performed. In addition, the protein-protein interaction(PPI) network was constructed. The core target genes were screened out and the target-signaling pathway network was set up. IGEMDOCK was used to dock the core target gene molecules. Besides, the relationship between the expression level of key target genes and the prognosis and immune infiltration of CRC was analyzed. Based on the in vitro cell experiment, the molecular mechanism of RES combined with IRI in the treatment of CRC was explored and analyzed. According to the results, 63 potential targets of RES combined with IRI were obtained for CRC treatment. Furthermore, cluster analysis revealed that protein functions included 23% transmembrane signal receptors, 22% protein modifying enzymes, and 14% metabolite converting enzymes. GO analysis indicated that BPs were mainly concentrated in protein autophosphorylation, CCs in receptor complex and plasma membrane, and MFs in transmembrane receptor protein tyrosine kinase activity. Moreover, KEGG signaling pathways were mainly enriched in central carbon metabolism in cancer. The key targets of RES combined with IRI in the treatment of CRC were PIK3CA, EGFR, and IGF1R, all of which were significantly positively correlated with the immune infiltration of CRC. As shown by the molecular docking results, PIK3CA had the most stable binding with RES and IRI. Compared with the results in the control group, the proliferation ability and EGFR protein expression of CRC cells in the RES-treated group, the IRI-treated group, and the RES+IRI treated group significantly decreased. Moreover, the cell proliferation ability and EGFR protein expression level of CRC cells in the RES+IRI treated group were remarkably lower than those in the IRI-treated group. In conclusion, PIK3CA, EGFR, and IGF1R are the key targets of RES combined with IRI in CRC treatment. In addition, RES can inhibit the proliferation of CRC cells and improve IRI chemoresistance by downregulating the EGFR signaling pathway.
Subject(s)
Humans , Irinotecan , Colorectal Neoplasms/genetics , Resveratrol , Molecular Docking Simulation , ErbB Receptors/geneticsABSTRACT
Objective: To study the clinicopathological and genetic features of natural killer (NK)-cell enteropathy for better understanding of this rare disease and prevention of its misdiagnosis. Methods: Two cases of NK-cell enteropathy were diagnosed in the First Affiliated Hospital of Zhengzhou University, China from October 2017 to February 2021. The clinical characteristics, morphology, immunohistochemistry, Epstein-Barr virus-encoded RNA (EBER) in situ hybridization and T cell receptor gene rearrangement were analyzed. The patients were followed up by a telephone interview. Results: The patients were both male, aged 40 and 28 years, respectively. Both patients were admitted to the hospital for an annual checkup without obvious gastrointestinal symptoms. The endoscopy showed that the gastric body of case 1 had a mucosal bulge, small area of congestion and erosion, while the rectum of case 2 had congestion and erosion. Microscopically, the lesions of the 2 cases were relatively limited. Many lymphoid cells infiltrated within the lamina propria of the mucosa and into the muscularis mucosa in case 2. In case 1, the glands were reduced in the lesion, and the glandular cavity was slightly compressed and deformed. There was no infiltration or destruction of the glands in either case. Lymphoid cells were atypical, with medium-to-large cell sizes. Their cytoplasm was medium-to-slightly abundant and appeared eosinophilic or translucent. In case 2, characteristic eosinophilic granules were seen in the cytoplasm of a few cells. The nuclei in both cases were round, oval and irregular, with fine chromatin, inconspicuous nucleoli, and no mitotic figures were noted. Necrosis was seen in case 1 while both cases had no central growth or destruction of blood vessels. Immunophenotyping showed that CD56, granzyme B and TIA-1 were positive in both cases, part of the cells was CD3-positive, and some cells were weakly CD4-positive in case 2. The CD5, CD8, CD30, ALK and B-lineage markers (CD20, CD79α) were all negative. The Ki-67 proliferation index was about 60% and 30%, respectively. Both cases were EBER negative. TCR gene rearrangement was polyclonal. Follow-up showed that none of the 2 patients had any special treatments and stayed well. Conclusions: NK-cell enteropathy is rare, with biological behaviors similar to benign tumors, and occasional recurrence. Its histology and immunophenotype are easily confused with NK/T cell-derived lymphomas. Combination of its unique endoscopic features, EBER negativity, polyclonal TCR gene rearrangement and good prognosis can confirm the diagnosis and avoid misdiagnosis and overtreatment.
Subject(s)
Humans , Male , Epstein-Barr Virus Infections , Herpesvirus 4, Human/genetics , Immunophenotyping , Killer Cells, Natural , Lymphoproliferative DisordersABSTRACT
Objective: To investigate the clinicopathological features and molecular genetics of cyclin D1-negative mantle cell lymphoma (MCL). Methods: The clinicopathological features and molecular genetics of CyclinD1-negative MCL diagnosed between January 2016 and July 2021 at the First Affiliated Hospital of Zhengzhou University were analyzed using immunohistochemistry and fluorescence in situ hybridization. Clinical information was collected and analyzed. Results: A total of five Cyclin D1-negative MCL cases from all 212 MCL patients (5/212, 2.4%)were included. There were three male and two female patients,age ranged from 59 to 70 years (median 64 years). All patients presented with nodal lesions. None of the patients had B symptoms but four had bone marrow involvement. Histopathologically, four cases were classic MCL and one case was pleomorphic variant type. All five cases were negative for Cyclin D1 but SOX-11 were positive in all cases. CD5 was positive in four cases and one case was weakly positive for CD23. CD10 and bcl-6 were negative in all cases. CCND1 translocation was identified in three cases and CCND2 translocation in one case by FISH analysis. However,CCND3 translocations were not found in the five cases. Conclusions: Cyclin D1-negative MCL are uncommon, its accurate diagnosis needs combined analysis with morphologic and immunophenotypic characteristics and genetic changes. It may be particularly difficult to distinguish from other small cell type B cell lymphomas. FISH analyses for CCND1/CCND2/CCND3 translocations and immunohistochemistry for SOX-11 are helpful to resolve such a difficult distinction.
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Cyclin D1/genetics , Immunohistochemistry , In Situ Hybridization, Fluorescence , Lymphoma, Mantle-Cell/pathology , Molecular BiologyABSTRACT
Objective: To investigate the role of minimally invasive crenel lateral lumbar interbody fusion (CLIF) in the decision of fusion level in posterior correction for severe adult degenerative scoliosis. Methods: This is a prospective study.Patients with level Ⅴ and Ⅵ of Lenke-Silva classification who were treated at Department of Orthopedics,the Second Affiliated Hospital, School of Medicine, Zhejiang University from June 2016 to March 2019 were included.First,the enrolled patients completed the preoperative clinical and imaging examination,the Lenke-Silva classification was evaluated,the surgical segments in first-stage CLIF was determined and the fusion segments required for single-stage posterior correction was predicted.After the first-stage CLIF,patients received reassessment of Lenke-Silva classification and global coronal and sagittal balance.Patients were divided into two groups:the effective group (level of Lenke-Silva classification decreased) and the ineffective group (level of Lenke-Silva classification unchanged).Second-stage posterior surgery was performed based on the results of reassessments.The fusion segment,Cobb angle,parameters of global coronal and sagittal plane,visual analogue pain score (VAS) and Oswestry disability index (ODI) were compared between the two groups preoperatively,after first-stage CLIF,second-stage posterior fixation and at the final follow-up.The potential factors associated with the decrease of the level of Lenke-Silva classification were recorded and compared between the two groups.Independent sample t test,repeated measure analysis of variance,rank sum test,χ2 test or Fisher exact method were used to compare the difference among groups. Results: Fifty-four patients were enrolled,including 8 males and 46 females,aged (68.8±5.8) years (range:56 to 77 years).Preoperatively,26 patients were classified as level Ⅴ by Lenke-Silva classification,28 cases were grade Ⅵ.CLIF was performed in 194 segments,with 114 segments(58.8%) receiving anterior column realignment (ACR) and 15 segments(7.7%) using hyperlordotic cages.After first-stage CLIF,22 patients with level Ⅴ and 10 patients with Ⅵ of Lenke-Silva classification decreased and were classified into effective group.The level of the remaining 4 patients with level Ⅴ and 18 patients with grade Ⅵ unchanged and were classified into ineffective group.Preoperatively,the apical vertebrae was below L1 in all 32 patients of effective group and 18 (81.8%,18/22) patients of ineffective group.The difference was statistically significant (P=0.023).There were 7 (31.8%,7/22) patients had continuous osteophyte in front of the intervertebral space in ineffective group,while none patient had continuous osteophyte in front of the intervertebral space in effective group,and the difference was statistically significant (P=0.001).In first-stage CLIF,more intraoperative ACR(71.2% vs.39.5%,χ²=20.660,P<0.01)and hyperlordotic cage (12.7% vs.0,P=0.001) were used in the effective group,while there was less severe cage subsidence after the operation (5.9% vs.15.8%,χ²=4.793,P=0.029) in effective group.After first-stage CLIF,there was no difference in the Cobb angle between the two groups.While,lumbar lordosis (LL) in effective group (34.0±8.3)° was greater than that of the ineffective group (25.5±9.7)° (t=3.478,P=0.001),and the difference between the pelvic incidence (PI) and LL in effective group (15.7±4.6)°was significantly smaller than ineffective group(20.0±10.8)° (t=-2.129,P=0.038).The posterior fusion levels was less,the rate of fusion to thoracic spine region and the actual fusion segment was less than that of single-stage posterior correction in effective group (all P<0.01).All patients were follow-up for 24 to 45 months.There was no significant difference in radiological and clinical results between the two groups after first-,second-stage surgery and at the final follow-up (all P>0.05). Conclusions: First-stage CLIF decreased the Lenke-Silva classification of some patients with severe degenerative scoliosis.Combined with the reassessment of Lenke-Silva classification and global coronal and sagittal plane,it helps to accurately determine the fusion segment.Decrease of Lenke-Silva classification is associated with the preoperative level of apical vertebrae,continuous osteophytes in front of the intervertebral space,intraoperative use of ACR and hyperlordotic cage and the degree of cage subsidence postoperatively.
Subject(s)
Adult , Aged , Animals , Female , Humans , Male , Middle Aged , Lumbar Vertebrae/surgery , Prospective Studies , Retrospective Studies , Scoliosis/surgery , Spinal Fusion , Treatment OutcomeABSTRACT
Objective: To analyze the clinical phenotype and screen the genetic mutations of hereditary deafness in three deaf families to clarify their molecular biology etiology. Methods: From January 2019 to January 2020, three deaf children and family members were collected for medical history, physical examination, audiology evaluation, electrocardiogram and cardiac color Doppler ultrasound, temporal bone CT examination, and peripheral blood DNA was obtained for high-throughput sequencing of deafness genes. Sanger sequencing was performed to verify the variant sites among family members. The pathogenicity of the variants was evaluated according to the American College of Medical Genetics and Genomics. Results: The probands in the three families had deafness phenotypes. In family 1, proband had multiple lentigines, special facial features, growth retardation, pectus carinatum, abnormal skin elasticity, cryptorchidism and other manifestations. In family 2, proband had special facial features, growth retardation and abnormal heart, and the proband in family 3 had growth retardation and abnormal electrocardiogram. Genetic testing of three families detected three heterozygous mutations in the PTPN11 gene: c.1391G>C (p.Gly464Ala), c.1510A>G (p.Met504Val), c.1502G>A (p.Arg501Lys). All three sites were missense mutations, and the mutation sites were highly conserved among multiple homologous species. Based on clinical manifestations and genetic test results, proband 1 was diagnosed with multiple lentigines Noonan syndrome, and probands 2 and 3 were diagnosed with Noonan syndrome. Conclusion: Missense mutations in the PTPN11 gene may be the cause of the disease in the three deaf families. This study enriches the clinical phenotype and mutation spectrum of the PTPN11 gene in the Chinese population.
Subject(s)
Humans , Male , Deafness/genetics , Genetic Testing , Hearing Loss/genetics , Mutation , Phenotype , Protein Tyrosine Phosphatase, Non-Receptor Type 11/geneticsABSTRACT
ObjectiveTo explore the mechanism of Liu Junzitang in preventing and treating muscle atrophy in mice with lung cancer cachexia based on the signal transducer and activator of transcription 3(STAT3)/ubiquitin proteasome pathway in vivo. MethodForty C57BL/6 mice aged six weeks were randomly divided into a blank group, a model group, a Liu Junzitang group, an inhibitor group (stattic group),and a Liu Junzitang + inhibitor group (combination group), with eight mice in each group. The cachectic muscle atrophy model was induced by subcutaneous inoculation of Lewis lung cancer cell line under the right anterior armpit in mice except those in the blank group. On the 8th day after subcutaneous inoculation, the mice in the corresponding groups received Liu Junzitang (9.56 g·kg-1·d-1) by gavage and intraperitoneal injection of stattic [25 mg·kg-1·(2 d)-1]. After three weeks of drug intervention, the body weight and gastrocnemius muscle weight were recorded. Hematoxylin-eosin (HE) staining was used to observe the pathological changes and cross-sectional area of gastrocnemius muscle fibers in mice. Western blot was used to detect the expression of phosphorylated-STAT3 (p-STAT3), STAT3, muscle atrophy F-box (MAFbx), and muscle RING finger protein 1 (MuRF1) in the gastrocnemius muscle. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of STAT3, MAFbx, and MuRF1 in the gastrocnemius muscle. ResultCompared with the blank group, the model group showed lightened body and the gastrocnemius muscle, reduced cross-sectional area of gastrocnemius muscle fibers, and increased protein expression of p-STAT3, STAT3, MAFbx, and MuRF1 and mRNA expression of STAT3, MuRF1, and MAFbx in the gastrocnemius muscle (P<0.05). Compared with the model group, the Liu Junzitang group showed increased body weight, gastrocnemius muscle weight, and cross-sectional area of gastrocnemius muscle fibers (P<0.05), and decreased protein expression of p-STAT3, STAT3, MuRF1, MAFbx, and mRNA expression of STAT3 and MAFbx in gastrocnemius muscle (P<0.05). Compared with the model group, the inhibitor group showed increased body weight and cross-sectional area of gastrocnemius muscle fibers (P<0.05), and reduced protein expression of p-STAT3, STAT3, MuRF1, MAFbx, and mRNA expression of STAT3 and MAFbx in gastrocnemius muscle (P<0.05). Compared with the model group, the combination group showed increased body weight and gastrocnemius muscle weight (P<0.05),and decreased protein expression of p-STAT3, STAT3, MuRF1, and mRNA expression of STAT3 and MAFbx in the gastrocnemius muscle (P<0.05). Compared with the Liu Junzitang group, the stattic group and the combination group showed reduced expression of p-STAT3 protein in the gastrocnemius muscle (P<0.05). ConclusionLiu Junzitang can prevent and treat muscle atrophy in mice with lung cancer cachexia, and its mechanism may be associated with the protein and mRNA expression related to the STAT3-mediated ubiquitin proteasome pathway.
ABSTRACT
Objective:To investigate the protective effect of intermittent fasting on radiation-induced cognitive impairment and the possible underlying mechanism.Methods:A total of 36 male 7-week old c57BL/6J mice were divided into Sham-irradiation and ad libitum (Sham-AL) group, irradiation and ad libitum (IR-AL) group, and irradiation add intermittent fasting (IR-IF) group according to the random number table method, with 12 mice in each group. The cognitive function of mice was assessed by novel object recognition task. The expressions of autophagy gene 5 (ATG5), microtubulesas sociated protein light chain II (LC3II), voltage dependent anion channel protein 1 (VDAC1), interleukin-1β (IL-1β), synaptophysin (SYP), synapsin I (SYN-1), and postsynaptic density 95 (PSD95) were tested by Western blot. The location of VDAC1 in mice hippocampus was detected by immunofluorescence.Results:The discrimination index (-22.45 ± 16.76) of IR-AL group was significantly ( t=3.032, P<0.05) lower than that of Sham-AL group (30.02 ± 9.05). Compared to Sham-AL group, IR-AL group had a decreased expressions of autophagy-related proteins (ATG5 and LC3II), mitochondrial marker (VDAC1), inflammatory factors (IL-1β) as well as synapse-associated proteins SYP, SYN-1 and PSD95 ( t=2.49, 2.19, 2.40, 3.47, 2.87, 2.25, 2.17, 2.31, P<0.05). Compared to IR-AL group, IR-IF group had an increased discrimination index (21.22 ± 5.62) and the increased expressions of ATG5, LC3II, VDAC1, IL-1β, SYP, SYN-1, and PSD95 ( t=2.70, 2.88, 2.71, 3.18, 3.18, 3.11, 3.30, 3.35, 2.53, P<0.05). The immunofluorescence assay revealed that VDAC1 was co-expressed with the markers of astrocytes (GFAP) and microglia (IBA-1), but not with neurons (NEUN). Conclusions:Intermittent fasting could greatly improve the cognitive function of irradiated mice possibly by upregulating VDAC1 expression, induce autophagy, and inhibit the release of inflammatory factors and protecting the synapticplasticity in the hippocampus.
ABSTRACT
@#Objectives , , To analyze occupational stress depressive symptoms anxiety symptoms and related influencing factors Methods among bus drivers in Urumqi. A total of 709 bus drivers in Urumqi were selected as the research subjects using - , - - judgment sampling method. The Effort Reward Imbalance Questionnaire Zung 's Self rating Depression Scale and Zung 's Self - ( ) , rating Anxiety Scale were used to investigate the occupational stress in the effort reward imbalance ERI mode depression and Results , anxiety symptoms of bus drivers. The detection rates of ERI mode occupational stress symptoms of depression and ( ), ( ) ( ), anxiety were 62.2% 441/709 30.2% 214/709 and 18.2% 129/709 respectively. The results of binary logistic regression , , analysis showed that education level length of service physical exercise and drinking were independent influencing factors of ( P ) occupational stress in ERI mode all <0.05 . Personal monthly income and physical exercise were the influencing factors ( P ), (P ) of depression symptoms all <0.05 and physical exercise was the influencing factor of anxiety symptoms <0.05 . Conclusion , The occupational stress depression and anxiety symptoms of bus drivers in Urumqi are serious. Attention should , , , be paid to people with higher education long working age low personal monthly income no physical exercise habits and drinking behavior to prevent occupational stress and mental health problems.
ABSTRACT
Aim To develop a liquid chromatography electrospray-ionization tandem mass spectrometry (LC- MS/MS) method for simultaneous determination of bentysrepinine (Y101) and its metabolites M8 and M9 in rat plasma and to investigate the effect of verapamil, an inhibitor of P-glycoprotein (P-gp) , on the pharma¬cokinetics of Y101, a substrate of P-gp, in rats. Methods SD rats were divided randomly into two groups; ( 1) Y101 only as a control group, received an oral dose of 60 mg • kg"1 Y101; (2) Verapamil plus Y101 as an experimental group, received an oral dose of 60 mg • kg"1 Y101 in combination of 25 mg • kg"1 verapamil. The plasma concentrations of Y101 and its metabolites were determined by LC-MS/MS method af¬ter intragastric administration, and the pharmacokinetic parameters were calculated using non-compartmental a- nalysis. Results We successfully developed and fully validated a LC-MS/MS method, which simultaneously determined the concentration of Y101 and its metabo¬lites in rat plasma. The AUC0_t for Y101 and M9 in experimental group increased to 1.71-fold and 1.58- fold in comparison of control group. At the same time, the plasma clearance of Y101 and M9 decreased to 60% of control. However, we did not find any differ¬ence in AUC0_l and plasma clearance for M8 between two groups. Conclusions The validated LC-MS/MS method is sensitive and rapid for the determination of Y101 and its metabolites in rat plasma and was suc¬cessfully applied to the pharmacokinetic study in rats. Verapamil, a P-gp inhibitor, significantly increases the exposure of Y101 and its metabolites in vivo, indicating the adjustment of Y101 dosage for combined adminis¬tration is needed in clinical practice.
ABSTRACT
Aim To investigate the curative effects of resveratrol on OVA induced allergic rhinitis in mice and the underlying immune mechanisms. Methods Balb/c mice (female, 6 weeks) were divided randomly into normal control ( NC) group, allergic rhinitis (AR) group, high dose resveratrol treatment group (RH), low dose resveratrol treatment group (RL), and dexamethasone treatment group ( Dex). RL, RH and Dex group were oral administered with resveratrol 30 mg • kg"1, resveratrol 100 mg • kg"1 and dexamethasone 10 mg • kg"1, respectively. After the treat-ment , the sneezing and nasal rubbing behaviors of mice in all the group were recorded and HE was performed to assess the inflammatory cell infiltration in nasal tissues. The sera levels of allergic cytokines were determined with ELISA assay. The percentage of CD4+ GA- TA3 + T cells in spleen of each group was further recorded by flow cytometry. Results Compared with AR group, treatment with resveratrol (100 mg - kg"1) reduced the sneezing and nasal rubbing behaviors signifi-cantly and improved inflammatory cell infiltration in nasal tissues. The up-regulated sera levels of IL-4, IL- 13 and OVA-sIgE in AR group were reversed by RH, and ratios CD4+ GATA3 + Th2 cells in spleen of RH were also down-regulated parallelly. Conclusions RH treatment could improve the allergic related symptoms of OVA-induced allergic rhinitis, which is associated with down-regulated sera levels of IL-4, IL-13 and OVA-sIgE and ratios of CD4+ GATA3 + Th2 cells in spleen of mouse model.
ABSTRACT
Aim To set up leukemic K562/ADM cells with stable tolerance to 15 fimol • L_1 ADM induced in vitro by long-term and continuous stepwise increment of adriamycin (ADM) concentration, to observe the sensitivity to other chemotherapy drugs and the relationship between autophagy and drug resistance.Methods MTT assay was used to detect the sensitivity of cells to chemotherapy drugs.The morphological changes of autophagy were observed by transmission electron microscope and fluorescence microscopy.Cell apoptosis analysis was performed using Annexin-V/PI double staining and flow cytometry ( FCM ).The expressions of autophagy and drug resistance associated proteins were tested by Western blot.Results K562/ADM cells were cross-resistance to the other chemotherapeu-tics besides adriamyciri, such as pirarubicin, daunoru- bicin, 5-flurouracil, vincristine but not arsenic triox- ide.The number of autophagosomes, the fluorescence intensity of monodansylcadaverine (MDC) and the expression of LC3-H ,Beclin-l in K562/ADM cells were significantly higher than those in K562 cells.The inhibition of autophagy by 3-MA significantly increased the sensitivity of K562/ADM cells to ADM, and 3-MA also effectively inhibited the expressions of drug resistance related proteins P-gp, MRP1 and BCRP in K562/ADM cells.Conclusions The K562/ADM cells resistant to adriamycin occur multidrug resistance, and the drug resistanceis closely related to the level of autophagy.