Background Sustained yet intractable immunosuppression is commonly observed in septic patients,resulting in aggravated clinical outcomes.However,due to the substantial heterogeneity within septic patients,precise indi...Background Sustained yet intractable immunosuppression is commonly observed in septic patients,resulting in aggravated clinical outcomes.However,due to the substantial heterogeneity within septic patients,precise indicators in deciphering clinical trajectories and immunological alterations for septic patients remain largely lacking.Methods We adopted cross-species,single-cell RNA sequencing(scRNA-seq)analysis based on two published datasets containing circulating immune cell profile of septic patients as well as immune cell atlas of murine model of sepsis.Flow cytometry,laser scanning confocal microscopy(LSCM)imaging and Western blotting were applied to identify the presence of S100A9^(+)monocytes at protein level.To interrogate the immunosuppressive function of this subset,splenic monocytes isolated from septic wild-type or S100a9^(–/–)mice were co-cultured with naive CD4^(+)T cells,followed by proliferative assay.Pharmacological inhibition of S100A9 was implemented using Paquinimod via oral gavage.Results scRNA-seq analysis of human sepsis revealed substantial heterogeneity in monocyte compartments following the onset of sepsis,for which distinct monocyte subsets were enriched in disparate subclusters of septic patients.We identified a unique monocyte subset characterized by high expression of S100A family genes and low expression of human leukocyte antigen DR(HLA-DR),which were prominently enriched in septic patients and might exert immunosuppressive function.By combining single-cell transcriptomics of murine model of sepsis with in vivo experiments,we uncovered a similar subtype of monocyte significantly associated with late sepsis and immunocompromised status of septic mice,corresponding to HLA-DR^(low)S100A^(high)monocytes in human sepsis.Moreover,we found that S100A9^(+)monocytes exhibited profound immunosuppressive function on CD4^(+)T cell immune response and blockade of S100A9 using Paquinimod could partially reverse sepsis-induced immunosuppression.Conclusions This study identifies HLA-DR^(low)S100A^(high)monocytes correlated with immunosuppressive state upon septic challenge,inhibition of which can markedly mitigate sepsis-induced immune depression,thereby providing a novel therapeutic strategy for the management of sepsis.展开更多
40 thyroid specimens from Tru-cut needle biopsy and surgerywere analyzed by APAAP immunohistochemical technique.It was shown thatthe expression of HLA-DR antigen on thyroid follicular cells (TFC) wasinvolved in almost...40 thyroid specimens from Tru-cut needle biopsy and surgerywere analyzed by APAAP immunohistochemical technique.It was shown thatthe expression of HLA-DR antigen on thyroid follicular cells (TFC) wasinvolved in almost every patient.The degree of DR expression was signifi-cantly higher in autoimmune thyroiditis (AIT) than in Graves’ disease (GD)and in nontoxic goiter (NTG),The level of DR expression on TFC not onlycorrelated markedly with degree of MNC infiltration,but more so with degreeof DR expression on intrathyroidal infiltrates,suggesting that aberrant DR ex-pression in vivo may be related to the activation of intrathyroidal T cells.展开更多
AIM To analyze the association of HLA-DRBl with autoimmune hepatitis (AIH) in patients from China.``METHODS In .32 patients and 45 healthy controls,polymerase chain reaction amplification with sequencespecific primers...AIM To analyze the association of HLA-DRBl with autoimmune hepatitis (AIH) in patients from China.``METHODS In .32 patients and 45 healthy controls,polymerase chain reaction amplification with sequencespecific primers (PCR-SSP) was performed to examine the association of certain alleles or polymorphic sequences of HLA-DRB1 with AIH.``RESULTS HLA-DRB1 typing by PCFLSSP showed that DR4had a significantly increased frequency among patients with AIH versus healthy control (46.9% versus 20.8%;relative risk 3.35, P=0.014). In subtypes of DR4, there was a trend of increase in the gene frequency of DRB10405 in patients with AIH versus healthy controls (21.9%vs 6.3%, P=0.04, but Pc 0.08). In addition, asignificant increase was found in the alleles frequency encoding QRRAA from the third hyperpolymorphic region of DR4 in the patients with AIH (86.7% of DR4 positive patients vs 40.0% in DR4 positive controls, P 0.016, Pc =0.028. RR 9.75).``CONCLUSION AIH in Chinese is associated with HLADR4. There is a relationship between QRRAA sequence within the third hyperpolymorphic region of the DRB allele and AIH in Chinese.展开更多
Introduction: Despite the presence of many prognostic and predictive factors, overtreatment remains a major problem in patients with breast cancer. The aim of this study is to investigate the effects of CD74 and HLA-D...Introduction: Despite the presence of many prognostic and predictive factors, overtreatment remains a major problem in patients with breast cancer. The aim of this study is to investigate the effects of CD74 and HLA-DR expressions on the prognosis of patients who have had a mastectomy for the treatment of breast cancer. Materials and Methods: A retrospective search of medical records was carried out for patients who had surgery for breast cancer at the Department of General Surgery, Akdeniz University School of Medicine, between March 1984 and November 1999. Patients with regular follow-up and necessary data for the study (i.e. patients’ demographics, pathology results, and treatment characteristics) were included in the study. Paraffin blocks of tumor specimens were re-examined with immunohistochemical methods in March 2010 to determine the extent of CD74 and HLA-DR expression and the level of tumor infiltrating lymphocyte (TILs). Results: The mean age and the median duration of follow-up for the 41 participants were 48.29 ± 11.86 years and 125 months (range 115 to 135 months), respectively. Disease-free survival (DFS) in CD74 negative subjects was better than in CD74 positive patients, but the difference was not statistically significant (p = 0.75). Similarly, HLA-DR negative and HLA-DR positive groups showed no statistically significant differences in terms of DFS (p = 0.81). Conclusion: There were positive but insignificant correlations with increased expression of CD74, decreased expression of HLA-DR, and TILs levels. Further studies involving larger sample sizes may provide more insight into these associations.展开更多
【目的】探讨分析冠状动脉粥样硬化性心脏病（CHD）患者血清胱抑素C（CysC）、CA125和骨保护素（OPG）的水平变化及临床意义。【方法】选取本院158例经冠状动脉造影确诊的 CHD 患者作为观察组（CHD组），另选95例健康人作为健康对照组...【目的】探讨分析冠状动脉粥样硬化性心脏病（CHD）患者血清胱抑素C（CysC）、CA125和骨保护素（OPG）的水平变化及临床意义。【方法】选取本院158例经冠状动脉造影确诊的 CHD 患者作为观察组（CHD组），另选95例健康人作为健康对照组。分别应用免疫比浊法、化学免疫发光法和ELISA法比较不同组别和不同病变支数患者的CysC、CA125、OPG 水平。【结果】与健康对照组比较，CHD组CysC、CA125、OPG水平明显升高（ P ＜0．05或 P ＜0．01）；单支、双支、多支病变组3组血清CysC、CA125、OPG 水平逐渐升高，左室射血分数（LVEF）逐渐下降，且差异均有显著性（ P ＜0．05或 P ＜0．01）；NYHAⅠ级、Ⅱ级、Ⅲ级、Ⅳ级组血清CysC、CA125、OPG水平逐渐升高，LVEF逐渐下降，且差异均有显著性（ P＜0．05或 P＜0．01）。CysC、CA125、OPG 水平均与冠脉病变支数、心功能级别呈正相关（ P ＜0．01），与 LVEF呈负相关（ P ＜0．01）。【结论】联合检测血浆CysC、BMG、OPG 水平不仅能评价心功能受损程度，而且有助于早期发现CHD和有助于冠脉病变严重程度的判断及预后判断。展开更多
基金supported by the Key Project of National Natural Science Foundation of China(82130062,82241062 and 81930057)the National Key Research and Development Program of China(2022YFA1104604)+1 种基金the Key Project of Military Medical Innovation Program of Chinese PLA(18CXZ026 and BLJ18J006)the CAMS Innovation Fund for Medical Sciences(2019-I2M-5-076)。
文摘Background Sustained yet intractable immunosuppression is commonly observed in septic patients,resulting in aggravated clinical outcomes.However,due to the substantial heterogeneity within septic patients,precise indicators in deciphering clinical trajectories and immunological alterations for septic patients remain largely lacking.Methods We adopted cross-species,single-cell RNA sequencing(scRNA-seq)analysis based on two published datasets containing circulating immune cell profile of septic patients as well as immune cell atlas of murine model of sepsis.Flow cytometry,laser scanning confocal microscopy(LSCM)imaging and Western blotting were applied to identify the presence of S100A9^(+)monocytes at protein level.To interrogate the immunosuppressive function of this subset,splenic monocytes isolated from septic wild-type or S100a9^(–/–)mice were co-cultured with naive CD4^(+)T cells,followed by proliferative assay.Pharmacological inhibition of S100A9 was implemented using Paquinimod via oral gavage.Results scRNA-seq analysis of human sepsis revealed substantial heterogeneity in monocyte compartments following the onset of sepsis,for which distinct monocyte subsets were enriched in disparate subclusters of septic patients.We identified a unique monocyte subset characterized by high expression of S100A family genes and low expression of human leukocyte antigen DR(HLA-DR),which were prominently enriched in septic patients and might exert immunosuppressive function.By combining single-cell transcriptomics of murine model of sepsis with in vivo experiments,we uncovered a similar subtype of monocyte significantly associated with late sepsis and immunocompromised status of septic mice,corresponding to HLA-DR^(low)S100A^(high)monocytes in human sepsis.Moreover,we found that S100A9^(+)monocytes exhibited profound immunosuppressive function on CD4^(+)T cell immune response and blockade of S100A9 using Paquinimod could partially reverse sepsis-induced immunosuppression.Conclusions This study identifies HLA-DR^(low)S100A^(high)monocytes correlated with immunosuppressive state upon septic challenge,inhibition of which can markedly mitigate sepsis-induced immune depression,thereby providing a novel therapeutic strategy for the management of sepsis.
文摘40 thyroid specimens from Tru-cut needle biopsy and surgerywere analyzed by APAAP immunohistochemical technique.It was shown thatthe expression of HLA-DR antigen on thyroid follicular cells (TFC) wasinvolved in almost every patient.The degree of DR expression was signifi-cantly higher in autoimmune thyroiditis (AIT) than in Graves’ disease (GD)and in nontoxic goiter (NTG),The level of DR expression on TFC not onlycorrelated markedly with degree of MNC infiltration,but more so with degreeof DR expression on intrathyroidal infiltrates,suggesting that aberrant DR ex-pression in vivo may be related to the activation of intrathyroidal T cells.
文摘AIM To analyze the association of HLA-DRBl with autoimmune hepatitis (AIH) in patients from China.``METHODS In .32 patients and 45 healthy controls,polymerase chain reaction amplification with sequencespecific primers (PCR-SSP) was performed to examine the association of certain alleles or polymorphic sequences of HLA-DRB1 with AIH.``RESULTS HLA-DRB1 typing by PCFLSSP showed that DR4had a significantly increased frequency among patients with AIH versus healthy control (46.9% versus 20.8%;relative risk 3.35, P=0.014). In subtypes of DR4, there was a trend of increase in the gene frequency of DRB10405 in patients with AIH versus healthy controls (21.9%vs 6.3%, P=0.04, but Pc 0.08). In addition, asignificant increase was found in the alleles frequency encoding QRRAA from the third hyperpolymorphic region of DR4 in the patients with AIH (86.7% of DR4 positive patients vs 40.0% in DR4 positive controls, P 0.016, Pc =0.028. RR 9.75).``CONCLUSION AIH in Chinese is associated with HLADR4. There is a relationship between QRRAA sequence within the third hyperpolymorphic region of the DRB allele and AIH in Chinese.
文摘Introduction: Despite the presence of many prognostic and predictive factors, overtreatment remains a major problem in patients with breast cancer. The aim of this study is to investigate the effects of CD74 and HLA-DR expressions on the prognosis of patients who have had a mastectomy for the treatment of breast cancer. Materials and Methods: A retrospective search of medical records was carried out for patients who had surgery for breast cancer at the Department of General Surgery, Akdeniz University School of Medicine, between March 1984 and November 1999. Patients with regular follow-up and necessary data for the study (i.e. patients’ demographics, pathology results, and treatment characteristics) were included in the study. Paraffin blocks of tumor specimens were re-examined with immunohistochemical methods in March 2010 to determine the extent of CD74 and HLA-DR expression and the level of tumor infiltrating lymphocyte (TILs). Results: The mean age and the median duration of follow-up for the 41 participants were 48.29 ± 11.86 years and 125 months (range 115 to 135 months), respectively. Disease-free survival (DFS) in CD74 negative subjects was better than in CD74 positive patients, but the difference was not statistically significant (p = 0.75). Similarly, HLA-DR negative and HLA-DR positive groups showed no statistically significant differences in terms of DFS (p = 0.81). Conclusion: There were positive but insignificant correlations with increased expression of CD74, decreased expression of HLA-DR, and TILs levels. Further studies involving larger sample sizes may provide more insight into these associations.
文摘【目的】探讨分析冠状动脉粥样硬化性心脏病（CHD）患者血清胱抑素C（CysC）、CA125和骨保护素（OPG）的水平变化及临床意义。【方法】选取本院158例经冠状动脉造影确诊的 CHD 患者作为观察组（CHD组），另选95例健康人作为健康对照组。分别应用免疫比浊法、化学免疫发光法和ELISA法比较不同组别和不同病变支数患者的CysC、CA125、OPG 水平。【结果】与健康对照组比较，CHD组CysC、CA125、OPG水平明显升高（ P ＜0．05或 P ＜0．01）；单支、双支、多支病变组3组血清CysC、CA125、OPG 水平逐渐升高，左室射血分数（LVEF）逐渐下降，且差异均有显著性（ P ＜0．05或 P ＜0．01）；NYHAⅠ级、Ⅱ级、Ⅲ级、Ⅳ级组血清CysC、CA125、OPG水平逐渐升高，LVEF逐渐下降，且差异均有显著性（ P＜0．05或 P＜0．01）。CysC、CA125、OPG 水平均与冠脉病变支数、心功能级别呈正相关（ P ＜0．01），与 LVEF呈负相关（ P ＜0．01）。【结论】联合检测血浆CysC、BMG、OPG 水平不仅能评价心功能受损程度，而且有助于早期发现CHD和有助于冠脉病变严重程度的判断及预后判断。
