Semen samples collected from 28 male partners of infertile couples were divided into three equal aliquots and prepared with three selected media,such as PureSperm (Nidacon,Gothenburg,Sweden),Sil-Select Plus^TM (Fer...Semen samples collected from 28 male partners of infertile couples were divided into three equal aliquots and prepared with three selected media,such as PureSperm (Nidacon,Gothenburg,Sweden),Sil-Select Plus^TM (Fertipro,Beemem,Belgium) and SpermGrad^TM(Vitrolife,Gothenburg,Sweden). The differences in mean percentages of semen parameters were assessed by repeated measures analysis. Correlations of sperm DNA damage,as measured by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay,and of protamine deficiency,as measured by chromomycin A3 (CMA3) staining with sperm parameters,were determined by Pearson's correlation. After preparation with all three media,sperm concentrations decreased (P〈0.05) while percentages of sperm with normal morphology increased (P〈0.05). Percentages of sperm motility,rapid motility and progressive motile concentration (PMC) increased (P〈0.05) for each ofthese parameters,PureSperm preparation gave the best results (P〈0.05). The percentage of DNA damage decreased in the PureSperm and Sil-Select Plus preparations (17.9% and 31.3%,respectively,P〈0.05) and increased in the SpermGrad preparation (56.3%,P〈0.05). Protamine deficiency also decreased in all three kinds of media,59.3%,47.7% and 40.3% for PureSperm,Sil-Select Plus and SpermGrad preparations,respectively (P〈0.05). The percentage of DNA-damaged sperm was negatively correlated with the percentages of sperm motility,rapid motility and PMC,but was positively correlated with static motility (P〈0.05). This comparative study and correlation analysis revealed that PureSperm preparation yielded sperm with the best motility and the lowest percentage of protamine deficiency. The Sil-Select Plus preparation yielded sperm with the lowest amount of DNA damage. The SpermGrad preparation had a high percentage of sperm with normal morphology,but also had the highest percentage of sperm with DNA damage. Sperm DNA damage was correlated with percentages of sperm motility,rapid motility,static motility and PMC.展开更多
BACKGROUNDβ-ketothiolase deficiency(β-KTD)is an inherited disease,and insufficient attention has been paid to imageology due to its lower morbidity.Therefore,few lesions outside the basal ganglia have been found bef...BACKGROUNDβ-ketothiolase deficiency(β-KTD)is an inherited disease,and insufficient attention has been paid to imageology due to its lower morbidity.Therefore,few lesions outside the basal ganglia have been found before,and the persistent pathological changes have rarely been reported.CASE SUMMARY A 10-mo-old Chinese female patient with a free previous medical history but with poor physical and athletic development had received the haemophilus influenzae vaccine and then developed a low fever 2 d prior.She was initially diagnosed with severe brain injury,central respiratory failure,metabolic acidosis complicated with respiratory alkalosis,hyper-IgE,etc.With further examination,a definite diagnosis ofβ-KTD was made.Symptomatic treatment was adopted.Ten days later,the dyspnea was improved evidently and the ventilator was removed,but there were still obvious abnormalities on magnetic resonance imaging(MRI).The lesions mainly invaded the corpus striatum but were not limited to the basal ganglia.Then,the patient’s disease improved and discharged approximately 1 mo later,and the abnormal lesions on MRI had partially improved.However,for about 1 year,the residual irreversible lesions were observed on MRI,the mental and physical development of the patient was obviously regressive,and extra rehabilitation training was needed.CONCLUSION The case highlights the critical importance of one view that the range of lesions in some patients may be more extensive than previously thought in someβ-KTD patients.In addition to biochemical tests,genetic tests and magnetic resonance imaging are not only conducive to quickly diagnosingβ-KTD but also to partially evaluating the short-and long-term outcomes.Moreover,more attention should be paid to the two mutations(c.478 C>G;c.951 C>T)that may be associated with severeβ-KTD.展开更多
Objective:To observe the effect of Yiqi Jianpi plus anticancer herbs on spleen deficiency in colorectal cancer and its anti-tumor role.Methods:Human intestinal cancer cell HT29 xenograft of nude mice model was establi...Objective:To observe the effect of Yiqi Jianpi plus anticancer herbs on spleen deficiency in colorectal cancer and its anti-tumor role.Methods:Human intestinal cancer cell HT29 xenograft of nude mice model was established.The expression of ECF,VEGF,gastric cancer tumor growth in mice were observed.Results:Protein kinase C expression in in the Yiqi Jianpi group and Yiqi Jianpi anti-tumor group was significantly better than the model group(P<0.01,P<0.05).There was significantly more apoptotic cells in Yiqi Jianpi anti-tumor group than Yiqi Jianpi group and model group(P<0.01).Epidermal growth factor and vascular endothelial growth factor expression in Yiqi Jianpi group was significantly lower than Yiqi Jianpi group and model group(P<0.05).Conclusions:Tumor can inhibit the expression of PKC inhibition.Yiqi Jianpi and anticancer treatment can reduce this inhibition.Besides this treatment can also inhibit expression of tumor related genes such as epidermal growth factor and vascular endothelial growth factor.展开更多
DNA hypermethylation of tumor suppressor genes has been frequently observed in cancer patients, and therefore, may provide a valuable biomarker for cancer prevention and treatment. DNA hypermethylation may also provid...DNA hypermethylation of tumor suppressor genes has been frequently observed in cancer patients, and therefore, may provide a valuable biomarker for cancer prevention and treatment. DNA hypermethylation may also provide an important mechanism in cancer progression. Lung cancer is strongly associated with exposure to environmental carcinogens, especially tobacco smoke. DNA damage generated by tobacco smoke is believed to play an important role in lung cancer development. XPC is a DNA damage recognition protein required for DNA repair and other DNA damage responses and attenuated XPC protein levels have been detected in many lung cancer patients. We studied the role of XPC protein deficiency in tobacco smoke-caused DNA hypermethylation of important tumor suppressor genes. Using both normal human fibroblasts (NF) and XPC-deficient hu man fibroblasts (XPC), our DNA methylation studies demonstrated that the XPC deficiency caused elevated levels of DNA hypermethylation in both Brca1 and Mlh1 tumor suppressor genes following exposure to tobacco smoke condensate (TSC). The results of our ChIP studies revealed that the XPC deficiency led to an increased binding of DNA methyltransferase 3A (DNMT3A) at the promoter region CpG island-containing sequences of these genes under the TSC treatment;however, this increase was partially diminished with prior treatment with caffeine. The results of our immuno-precipitation (IP) studies demonstrated a protein-protein interaction of the ATR with DNMT3A. Our western blots revealed that the XPC deficiency caused an increase in TSC-induced ATR phosphorylation at serine 428, an indicator of ATR activation. All these results suggest that XPC deficiency causes an accelerated DNA hypermethylation in important tumor suppressor genes under tobacco smoke exposure and activation of the ATR signaling pathway is involved in this DNA hypermethylation process.展开更多
Objective:DNA damage response(DDR)genes have low mutation rates,which may restrict their clinical applications in predicting the outcomes of immune checkpoint inhibitor(ICI)treatment.Thus,a systemic analysis of multip...Objective:DNA damage response(DDR)genes have low mutation rates,which may restrict their clinical applications in predicting the outcomes of immune checkpoint inhibitor(ICI)treatment.Thus,a systemic analysis of multiple DDR genes is needed to identify potential biomarkers of ICI efficacy.Methods:A total of 39,631 patients with mutation data were selected from the cBioPortal database.A total of 155 patients with mutation data were obtained from the Fudan University Shanghai Cancer Center(FUSCC).A total of 1,660 patients from the MSK-IMPACT cohort who underwent ICI treatment were selected for survival analysis.A total of 249 patients who underwent ICI treatment from the Dana-Farber Cancer Institute(DFCI)cohort were obtained from a published dataset.The Cancer Genome Atlas(TCGA)level 3 RNA-Seq version 2 RSEM data for gastric cancer were downloaded from cBioPortal.Results:Six MMR and 30 DDR genes were included in this study.Six MMR and 20 DDR gene mutations were found to predict the therapeutic efficacy of ICI,and most of them predicted the therapeutic efficacy of ICI,in a manner dependent on TMB,except for 4 combined DDR gene mutations,which were associated with the therapeutic efficacy of ICI independently of the TMB.Single MMR/DDR genes showed low mutation rates;however,the mutation rate of all the MMR/DDR genes associated with the therapeutic efficacy of ICI was relatively high,reaching 10%–30%in several cancer types.Conclusions:Coanalysis of multiple MMR/DDR mutations aids in selecting patients who are potential candidates for immunotherapy.展开更多
Protein ubiquitination plays an important role in DNA damage repair.To clarify the role of RAD6B,identified as an important ubiquitin conjugating enzyme,in neuronal genome integrity and survival,we first silenced RAD6...Protein ubiquitination plays an important role in DNA damage repair.To clarify the role of RAD6B,identified as an important ubiquitin conjugating enzyme,in neuronal genome integrity and survival,we first silenced RAD6B gene in RPE1 and found that RAD6B deficiency resulted in increased genomic instability.While in brains of RAD6B knockout mouse generated by homologous recom bination,we found that RAD6B deficiency caused a significant reduction of H2B ubiquitination and impaird DNA damage repair compared with wild type mouse brains.The accumulation of unrepaired DNA damage often leads to apoptosis or senescence,even tumor formation.Furthermore,we evaluated the effect of RAD6B deficiency on the survival of neurons,and noticed that RAD6B-deficient mice exhibited marked neuronal senescence,neurodegeneration and reduced neuronal numbers.We also observed learning and memory impairment in neuron-specific RAD6B-deficient mice.In conclusion,RAD6B is involved in DNA damage repair of neurons,and is essential to maintain neuronal genome stability.展开更多
Objective: To find some objective criteria for Syndrome Differentiation of Kidney Deficiency by analysing the relationship between Kidney and hearing as well as serum trace elements. Methods: The hearing and serum tra...Objective: To find some objective criteria for Syndrome Differentiation of Kidney Deficiency by analysing the relationship between Kidney and hearing as well as serum trace elements. Methods: The hearing and serum trace element of 73 cases of chronic nephropathy were measured. Results: The incidence of hearing damage in high frequency was 68. 5% with a mean hypoacusis of 35. 1 ±6. 1 dB, while in the 55 patients of Kidney deficiency type, the incidence of hearing damage in high frequency was 83. 6%, which was significantly higher than that in patients without Kidney Deficiency. The serum levels of trace elements (iron and zinc) in patients with Kidney Deficiency were lower than the normal level and that in patients without Kidney Deficiency, and the decrease of serum iron was directly proPOrtional to the degree of hearing damage. Conclusion: There was close relationship between Kidney Deficiency and hearing damage as well as the serum levels of iron and zinc.展开更多
文摘Semen samples collected from 28 male partners of infertile couples were divided into three equal aliquots and prepared with three selected media,such as PureSperm (Nidacon,Gothenburg,Sweden),Sil-Select Plus^TM (Fertipro,Beemem,Belgium) and SpermGrad^TM(Vitrolife,Gothenburg,Sweden). The differences in mean percentages of semen parameters were assessed by repeated measures analysis. Correlations of sperm DNA damage,as measured by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay,and of protamine deficiency,as measured by chromomycin A3 (CMA3) staining with sperm parameters,were determined by Pearson's correlation. After preparation with all three media,sperm concentrations decreased (P〈0.05) while percentages of sperm with normal morphology increased (P〈0.05). Percentages of sperm motility,rapid motility and progressive motile concentration (PMC) increased (P〈0.05) for each ofthese parameters,PureSperm preparation gave the best results (P〈0.05). The percentage of DNA damage decreased in the PureSperm and Sil-Select Plus preparations (17.9% and 31.3%,respectively,P〈0.05) and increased in the SpermGrad preparation (56.3%,P〈0.05). Protamine deficiency also decreased in all three kinds of media,59.3%,47.7% and 40.3% for PureSperm,Sil-Select Plus and SpermGrad preparations,respectively (P〈0.05). The percentage of DNA-damaged sperm was negatively correlated with the percentages of sperm motility,rapid motility and PMC,but was positively correlated with static motility (P〈0.05). This comparative study and correlation analysis revealed that PureSperm preparation yielded sperm with the best motility and the lowest percentage of protamine deficiency. The Sil-Select Plus preparation yielded sperm with the lowest amount of DNA damage. The SpermGrad preparation had a high percentage of sperm with normal morphology,but also had the highest percentage of sperm with DNA damage. Sperm DNA damage was correlated with percentages of sperm motility,rapid motility,static motility and PMC.
文摘BACKGROUNDβ-ketothiolase deficiency(β-KTD)is an inherited disease,and insufficient attention has been paid to imageology due to its lower morbidity.Therefore,few lesions outside the basal ganglia have been found before,and the persistent pathological changes have rarely been reported.CASE SUMMARY A 10-mo-old Chinese female patient with a free previous medical history but with poor physical and athletic development had received the haemophilus influenzae vaccine and then developed a low fever 2 d prior.She was initially diagnosed with severe brain injury,central respiratory failure,metabolic acidosis complicated with respiratory alkalosis,hyper-IgE,etc.With further examination,a definite diagnosis ofβ-KTD was made.Symptomatic treatment was adopted.Ten days later,the dyspnea was improved evidently and the ventilator was removed,but there were still obvious abnormalities on magnetic resonance imaging(MRI).The lesions mainly invaded the corpus striatum but were not limited to the basal ganglia.Then,the patient’s disease improved and discharged approximately 1 mo later,and the abnormal lesions on MRI had partially improved.However,for about 1 year,the residual irreversible lesions were observed on MRI,the mental and physical development of the patient was obviously regressive,and extra rehabilitation training was needed.CONCLUSION The case highlights the critical importance of one view that the range of lesions in some patients may be more extensive than previously thought in someβ-KTD patients.In addition to biochemical tests,genetic tests and magnetic resonance imaging are not only conducive to quickly diagnosingβ-KTD but also to partially evaluating the short-and long-term outcomes.Moreover,more attention should be paid to the two mutations(c.478 C>G;c.951 C>T)that may be associated with severeβ-KTD.
基金supported by Fund of Administration Bureau of TCM(2012727632)
文摘Objective:To observe the effect of Yiqi Jianpi plus anticancer herbs on spleen deficiency in colorectal cancer and its anti-tumor role.Methods:Human intestinal cancer cell HT29 xenograft of nude mice model was established.The expression of ECF,VEGF,gastric cancer tumor growth in mice were observed.Results:Protein kinase C expression in in the Yiqi Jianpi group and Yiqi Jianpi anti-tumor group was significantly better than the model group(P<0.01,P<0.05).There was significantly more apoptotic cells in Yiqi Jianpi anti-tumor group than Yiqi Jianpi group and model group(P<0.01).Epidermal growth factor and vascular endothelial growth factor expression in Yiqi Jianpi group was significantly lower than Yiqi Jianpi group and model group(P<0.05).Conclusions:Tumor can inhibit the expression of PKC inhibition.Yiqi Jianpi and anticancer treatment can reduce this inhibition.Besides this treatment can also inhibit expression of tumor related genes such as epidermal growth factor and vascular endothelial growth factor.
文摘DNA hypermethylation of tumor suppressor genes has been frequently observed in cancer patients, and therefore, may provide a valuable biomarker for cancer prevention and treatment. DNA hypermethylation may also provide an important mechanism in cancer progression. Lung cancer is strongly associated with exposure to environmental carcinogens, especially tobacco smoke. DNA damage generated by tobacco smoke is believed to play an important role in lung cancer development. XPC is a DNA damage recognition protein required for DNA repair and other DNA damage responses and attenuated XPC protein levels have been detected in many lung cancer patients. We studied the role of XPC protein deficiency in tobacco smoke-caused DNA hypermethylation of important tumor suppressor genes. Using both normal human fibroblasts (NF) and XPC-deficient hu man fibroblasts (XPC), our DNA methylation studies demonstrated that the XPC deficiency caused elevated levels of DNA hypermethylation in both Brca1 and Mlh1 tumor suppressor genes following exposure to tobacco smoke condensate (TSC). The results of our ChIP studies revealed that the XPC deficiency led to an increased binding of DNA methyltransferase 3A (DNMT3A) at the promoter region CpG island-containing sequences of these genes under the TSC treatment;however, this increase was partially diminished with prior treatment with caffeine. The results of our immuno-precipitation (IP) studies demonstrated a protein-protein interaction of the ATR with DNMT3A. Our western blots revealed that the XPC deficiency caused an increase in TSC-induced ATR phosphorylation at serine 428, an indicator of ATR activation. All these results suggest that XPC deficiency causes an accelerated DNA hypermethylation in important tumor suppressor genes under tobacco smoke exposure and activation of the ATR signaling pathway is involved in this DNA hypermethylation process.
基金This work was supported by the National Key R&D Program of China(Grant No.2018YFC1313300)the National Natural Science Foundation of China(Grant No.81572331).
文摘Objective:DNA damage response(DDR)genes have low mutation rates,which may restrict their clinical applications in predicting the outcomes of immune checkpoint inhibitor(ICI)treatment.Thus,a systemic analysis of multiple DDR genes is needed to identify potential biomarkers of ICI efficacy.Methods:A total of 39,631 patients with mutation data were selected from the cBioPortal database.A total of 155 patients with mutation data were obtained from the Fudan University Shanghai Cancer Center(FUSCC).A total of 1,660 patients from the MSK-IMPACT cohort who underwent ICI treatment were selected for survival analysis.A total of 249 patients who underwent ICI treatment from the Dana-Farber Cancer Institute(DFCI)cohort were obtained from a published dataset.The Cancer Genome Atlas(TCGA)level 3 RNA-Seq version 2 RSEM data for gastric cancer were downloaded from cBioPortal.Results:Six MMR and 30 DDR genes were included in this study.Six MMR and 20 DDR gene mutations were found to predict the therapeutic efficacy of ICI,and most of them predicted the therapeutic efficacy of ICI,in a manner dependent on TMB,except for 4 combined DDR gene mutations,which were associated with the therapeutic efficacy of ICI independently of the TMB.Single MMR/DDR genes showed low mutation rates;however,the mutation rate of all the MMR/DDR genes associated with the therapeutic efficacy of ICI was relatively high,reaching 10%–30%in several cancer types.Conclusions:Coanalysis of multiple MMR/DDR mutations aids in selecting patients who are potential candidates for immunotherapy.
文摘Protein ubiquitination plays an important role in DNA damage repair.To clarify the role of RAD6B,identified as an important ubiquitin conjugating enzyme,in neuronal genome integrity and survival,we first silenced RAD6B gene in RPE1 and found that RAD6B deficiency resulted in increased genomic instability.While in brains of RAD6B knockout mouse generated by homologous recom bination,we found that RAD6B deficiency caused a significant reduction of H2B ubiquitination and impaird DNA damage repair compared with wild type mouse brains.The accumulation of unrepaired DNA damage often leads to apoptosis or senescence,even tumor formation.Furthermore,we evaluated the effect of RAD6B deficiency on the survival of neurons,and noticed that RAD6B-deficient mice exhibited marked neuronal senescence,neurodegeneration and reduced neuronal numbers.We also observed learning and memory impairment in neuron-specific RAD6B-deficient mice.In conclusion,RAD6B is involved in DNA damage repair of neurons,and is essential to maintain neuronal genome stability.
文摘Objective: To find some objective criteria for Syndrome Differentiation of Kidney Deficiency by analysing the relationship between Kidney and hearing as well as serum trace elements. Methods: The hearing and serum trace element of 73 cases of chronic nephropathy were measured. Results: The incidence of hearing damage in high frequency was 68. 5% with a mean hypoacusis of 35. 1 ±6. 1 dB, while in the 55 patients of Kidney deficiency type, the incidence of hearing damage in high frequency was 83. 6%, which was significantly higher than that in patients without Kidney Deficiency. The serum levels of trace elements (iron and zinc) in patients with Kidney Deficiency were lower than the normal level and that in patients without Kidney Deficiency, and the decrease of serum iron was directly proPOrtional to the degree of hearing damage. Conclusion: There was close relationship between Kidney Deficiency and hearing damage as well as the serum levels of iron and zinc.