Tumor cell lysate with low content of HMGB1 enhances immune response of dendritic cells against lung cancer in mice / 南方医科大学学报

OBJECTIVE@#To assess the effect of tumor cell lysate (TCL) with low high-mobility group B1 (HMGB1) content for enhancing immune responses of dendritic cells (DCs) against lung cancer.@*METHODS@#TCLs with low HMGB1 content (LH-TCL) and normal HMGB1 content (NH-TCL) were prepared using Lewis lung cancer (LLC) cells in which HMGB1 was inhibited with 30 nmol/L glycyrrhizic acid (GA) and using LLC cells without GA treatment, respectively. Cultured mouse DCs were exposed to different doses of NH-TCL and LH-TCL, using PBS as the control. Flow cytometry was used to detect the expressions of CD11b, CD11c and CD86 and apoptosis of the stimulated DCs, and IL-12 levels in the cell cultures were detected by ELISA. Mouse spleen cells were co-cultured with the stimulated DCs, and the activation of the spleen cells was assessed by detecting CD69 expression using flow cytometry; TNF-β production in the spleen cells was detected with ELISA. The spleen cells were then co-cultured with LLC cells at the effector: target ratios of 5:1, 10:1 and 20:1 to observe the tumor cell killing. In the animal experiment, C57/BL6 mouse models bearing subcutaneous LLC xenograft received multiple injections with the stimulated DCs, and the tumor growth was observed.@*RESULTS@#The content of HMGB1 in the TCL prepared using GA-treated LLC cells was significantly reduced (P < 0.01). Compared with NH-TCL, LH-TCL showed a stronger ability to reduce apoptosis (P < 0.001) and promote activation and IL- 12 production in the DCs. Compared with those with NH-TCL stimulation, the DCs stimulated with LH-TCL more effectively induced activation of splenic lymphocytes and enhanced their anti-tumor immunity (P < 0.05). In the cell co-cultures, the spleen lymphocytes activated by LH-TCL-stimulated DCs showed significantly enhanced LLC cell killing activity (P < 0.01). In the tumor-bearing mice, injections of LH-TCL-stimulated DCs effectively activated host anti-tumor immunity and inhibited the growth of the tumor xenografts (P < 0.05).@*CONCLUSION@#Stimulation of the DCs with LH-TCL enhances the anti-tumor immune activity of the DCs and improve the efficacy of DCbased immunotherapy for LLC in mice.

Clinical Characteristics and Prognosis of Patients with Hematological Malignancies Superimposed with Solid Tumors / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical characteristics and prognosis of hematological malignancies superimposed patients with solid tumors.@*METHODS@#The clinical data of 30 patients with more than two kinds of malignancy (the second is hematological malignancy) from October 2011 to October 2020 in Department of Hematology, Jiangning Hospital Affiliated to Nanjing Medical University were collected and analyzed retrospectively. The overall survival time was used as the prognostic evaluation standard, and the survival of patients were analyzed by KaplanMeier method. Logrank test and Cox regression model were used to carry out univariate and multivariate retrospective analysis on clinical and laboratory parameters of 30 patients.@*RESULTS@#Among 30 cases, 20 were male, 10 were female, the median age of onset of the second tumor was 70 years old. The common types of the secondary hematological malignancies to solid tumors are myelodysplastic syndrome, acute myeloid leukemia, multiple myeloma. Univariate analysis showed that patients' gender, age, type of solid tumors, the onset of interval between two kinds of tumor, chromosome karyotype were not related to do with the patients' overall survival time. Type of hematologic disease, ECOG score were associated with patients' overall survival time, and the multivariate analysis showed that the type of hematologic disease and ECOG score were independent risk factors for patients with poor prognosis.@*CONCLUSION@#Patients superimposed with solid tumors complicated with myelodysplastic syndrome or acute leukemia and ECOG score ≥3 have poor prognosis and shorter overall survival time, which are independent risk factors influencing the prognosis. Bone marrow injury, immune dysfunction and genetic susceptibility after chemoradiotherapy may be the main causes of these diseases.

Self-assembling, pH-responsive nanoflowers for inhibiting PAD4 and neutrophil extracellular trap formation and improving the tumor immune microenvironment

Self-assembling carrier-free nanodrugs are attractive agents because they accumulate at tumor by an enhanced permeability and retention (EPR) effect without introduction of inactive substances, and some nanodrugs can alter the immune environment. We synthesized a peptidyl arginine deiminase 4 (PAD4) molecular inhibitor, ZD-E-1M. It could self-assembled into nanodrug ZD-E-1. Using confocal laser scanning microscopy, we observed its cellular colocalization, PAD4 activity and neutrophil extracellular traps (NETs) formation. The populations of immune cells and expression of immune-related proteins were determined by single-cell mass cytometry. ZD-E-1 formed nanoflowers in an acidic environment, whereas it formed nanospheres at pH 7.4. Accumulation of ZD-E-1 at tumor was pH-responsive because of its pH-dependent differences in the size and shape. It could enter the nucleus and bind to PAD4 to prolong the intracellular retention time. In mice, ZD-E-1 inhibited tumor growth and metastasis by inhibiting PAD4 activity and NETs formation. Besides, ZD-E-1 could regulate the ratio of immune cells in LLC tumor-bearing mice. Immunosuppressive proteins like LAG3 were suppressed, while IFN-γ and TNF-α as stimulators of tumor immune response were upregulated. Overall, ZD-E-1 is a self-assembling carrier-free nanodrug that responds to pH, inhibits PAD4 activity, blocks neutrophil extracellular traps formation, and improves the tumor immune microenvironment.

The role of adenosine deaminase acting on RNA in the remission of aggression behavior in socially isolated mice and the mechanism of 5-serotonin-2C receptor / 中华行为医学与脑科学杂志

Objective:To investigate the effect of adenosine deaminase acting on RNA 1 (ADAR1) on 5-serotonin-2c receptor in alleviating aggression in socially isolated mice.Methods:Sixty healthy male BALB / c mice aged 21 days were randomly divided into six groups: social isolation group, social control group, ADAR1 inducer social isolation group, ADAR1 inhibitor social isolation group, ADAR1 inducer social control group and ADAR1 inhibitor control group.The mice fed in single cage for 4 weeks were used as social isolation model while the mice fed in group were used as control group.ADAR1 inducer (5.0×10 4 U/kg) and inhibitor (10 mg/kg) were given intraperitoneally to mice in the ADAR1 inducer social isolation group and the ADAR1 inhibitor social isolation group respectively.The aggressive behavior of mice was evaluated by resident-intruder test.The expression of ADAR1 and 5-serotonin-2c receptors in the brain of mice was detected by immunohistochemistry and Western blot. Results:The attack latency of social isolation group was significantly lower than that of social control group ((43.15±6.99) s, (542.40±30.50) s; t=15.906, P<0.01), and the latency of attack ((256.70±29.49) s) in the ADAR1 inducer social isolation group was significantly higher than that in the social isolation group ( t=7.046, P<0.01). The latency of attack ((15.25±2.18)s) in the ADAR1 inhibitor social isolation group was significantly lower than that in the social isolation group ( t=3.809, P<0.01). The optical density of ADAR1 immunoreactive cells in the amygdala of the social isolation group mice was significantly lower than that in the corresponding brain area of the social control group (BLA: (0.038±0.002), (0.074±0.004); LaDL: (0.033±0.002), (0.060±0.002); LaVM: (0.045±0.003), (0.073±0.004); Lavl area: (0.044±0.003), (0.070±0.003); t=8.428, 9.037, 6.462, 5.698, all P<0.01). The optical density of ADAR1 immunoreactive positive cells in the amygdala (BLA: (0.060±0.003), LaDL: (0.042±0.002), LaVM: (0.056±0.004), Lavl: (0.054±0.003) in the ADAR1 inducer social isolation group was significantly higher than those in the corresponding brain area of the social isolation group mice ( t=6.055, 2.876, 2.312, 2.492; all P<0.05). The expression of ADAR1 protein and 5-serotonin-2c receptor protein in amygdala of social isolation group were significantly lower than those of social isolation group ( t=11.37, 12.65; P<0.01). The expression of ADAR1 protein and 5-serotonin-2c receptor protein in the amygdala of the ADAR1 inducer social isolation group were significantly higher than those of the social isolation group ( t=3.02, 4.401; P<0.05). Conclusion:ADAR1 inducer alleviates the aggressive behavior of social isolated BALB / c mice by enhancing the protein expression of 5-serotonin-2c receptor in the amygdala of social isolated BALB/c mice.

Clinical observation of acupuncture plus repetitive transcranial magnetic stimulation in thetreatment of post-stroke insomnia / 针灸推拿医学（英文版）

Objective: To evaluate the clinical efficacy of the Governor Vessel-unblocking and mind-regulating acupuncture method plus repetitive transcranial magnetic stimulation (rTMS) in the treatment of post-stroke insomnia. Methods: A total of 72 patients with post-stroke insomnia were randomly divided into 2 groups, with 36 cases in each group. The control group received rTMS treatment with a frequency of 1 Hz and a motion threshold value of 90％. The observation group received acupuncture with Governor Vessel-unblocking and mind-regulating method based on the rTMS treatment of the control group. The points were Baihui (GV 20), Shenting (GV 24), Yintang (GV 29), Fengfu (GV 16), Sishencong (EX-HN 1), Shenmen (HT 7), Sanyinjiao (SP 6), Shenmai (BL 62) and Zhaohai (KI 6). The treatment was performed once a day for 5 d a week followed by 2 d of rest for 4 weeks. The improvements of Pittsburgh sleep quality index (PSQI), self-rating anxiety scale (SAS) and self-rating depression scale (SDS) scores were observed after treatment, and the clinical efficacy was compared between the two groups. Results: After 4 weeks of treatment, the PSQI, SAS, and SDS scores of the two groups were all reduced, and the intra-group differences were statistically significant (all P<0.001). After treatment, the three scores in the observation group were all lower than those in the control group, and the differences between the two groups were statistically significant (P<0.05, P<0.05, P<0.001). There was a statistically significant difference between the observation group and the control group comparing the clinical efficacy (P<0.05). Conclusion: The therapeutic effect of the Governor Vessel-unblocking and mind-regulating acupuncture method plus rTMS in treating post-stroke insomnia is better than rTMS alone, and it can better improve the anxiety and depression of patients.

Analysis of Non-genetic Factors Influencing the Overall Survival of Multiple Myeloma Patients / 中国实验血液学杂志

OBJECTIVE@#To explore the non-genetic factors of overall survival in patients with multiple myeloma (MM).@*METHODS@#Kaplan-Meier survival curve, Log-rank test and Cox regression model were used to carry out univariate and multivariate retrospective analysis on clinical and laboratory parameters of 51 patients who were newly diagnosed with MM and had complete follow-up data in the Department of Hematology, the Affiliated Jiangning Hospital of Nanjing Medical University from November 2011 to October 2019.@*RESULTS@#Fifty-one patients included 29 males and 22 females. Followed up to December 2019, 21 cases died and 30 cases survived. The univariate analysis showed that the overall survival time of the patients was influenced by age, disease stage, standard treatment, new drugs, maintenance treatment, hypercalcemia, globulin, albumin, and hemoglobin. The overall survival time of patients with age <65 years old, ISS stage I and II, standardized treatment, new drugs, normal or below normal blood calcium, normal or below normal globulin, albumin ≥35 g/L or hemoglobin ≥100 g/L was prolonged significantly (P<0.05). The multivariate analysis showed that maintenance treatment, hypercalcemia (≥2.6 mmol/L), and hemoglobin (<100 g/L) were independent risk factors influencing the prognosis of MM patients.@*CONCLUSION@#Patients with blood calcium ≥2.6 mmol/L, hemoglobin <100 g/L, and who do not undergo regular maintenance therapy show a poor prognosis.

A retrospective analysis of real-world outcomes of elderly Chinese patients with diffuse large B-cell lymphoma / 中华医学杂志(英文版)

Background@#Elderly patients with diffuse large B-cell lymphoma (DLBCL) have a worse prognosis than younger patients, and the optimal treatment strategy for this group remains controversial. We conducted a retrospective analysis to investigate the clinical features and outcomes of elderly patients (>60 years) and to assess the impact of clinical and molecular factors on outcome in this age group.@*Methods@#From April 2006 to December 2012, a total of 349 elderly patients with DLBCL from the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College were included in this analysis. Patients were further divided into two age groups (61–69 years and ≥70 years). We compared clinical characteristics and outcomes between groups.@*Results@#Of 349 total patients, 204 (58.5%) were aged 61 to 69 years, and 145 (41.5%) patients were aged 70 years or older. Except for the Eastern Cooperative Oncology Group performance status, clinical characteristics were comparable between the two groups. With a median follow-up of 82 (range, 1–129) months, the 5-year overall survival (OS) and progression-free survival (PFS) rates were 51.9% and 45.8%, respectively. The 5-year OS rates for patients aged 61 to 69 years and those over 70 years were 58.3% and 42.8% (P = 0.007), respectively, and the 5-year PFS rates were 51.0% and 38.6% (P = 0.034). Treatment regimens including rituximab provided a higher 5-year OS rate (63.1% vs. 37.1%, P < 0.001) and PFS rate (56.6% vs. 31.8%, P < 0.001) than chemotherapy alone. For patients aged 61 to 69 years, chemotherapy plus rituximab resulted in a higher 5-year OS rate (66.7% vs. 46.4%, P = 0.002) and PFS rate (60.0% vs. 38.1%, P = 0.002) than chemotherapy alone. For patients aged ≥70 years, there was a marked survival advantage in patients who received chemotherapy plus rituximab (5-year OS rate: 57.7% vs. 25.4%, P < 0.001; 5-year PFS rate: 51.3% vs. 23.9%, P < 0.001) compared with that seen in those who received chemotherapy alone. Multivariate analysis established that stage III/IV disease, elevated lactate dehydrogenase (LDH), initial treatment, and chemotherapy with rituximab were independent risk factors for 5-year OS, and stage III/IV disease, elevated LDH, and chemotherapy with rituximab were independent risk factors for 5-year PFS for elderly patients with DLBCL.@*Conclusions@#In comparison to patients aged 61 to 69 years, those aged ≥70 years have poorer survival. Prolonged survival is obtainable with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)-like in elderly Chinese patients in all age groups, indicating that the R-CHOP-like regimen should be considered for this population, even for those aged 70 years or older.

Moxibustion at acpoints of governor vessel on regulating PI3K/Akt/mTOR signaling pathway and enhancing autophagy process in APP/PS1 double-transgenic Alzheimer's disease mice / 中国针灸

OBJECTIVE@#To observe the eliminating effects of moxibustion at "Baihui" (GV 20), "Fengfu" (GV 16) and "Dazhui" (GV 14) on amyloid β-peptide (Aβ) in brain of the amyloid precursor protein/presenili1 (APP/PS1) double-transgenic mice with Alzheimer's disease (AD) by regulating the phosphoinositide 3-kinases/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway.@*METHODS@#A total of 60 APP/PS1 double-transgenic mice with AD were randomly divided into a model group, a moxibustion group, a rapamycin group and a combination group (treated with moxibustion and inhibitor), 15 mice in each group, another 15 male C57BL/6J mice with same age and background were selected as the control group. In the moxibustion group, pressing moxibustion was applied at "Baihui" (GV 20) while the mild moxibustion was applied at "Fengfu" (GV 16) and "Dazhui" (GV 14). The treatment was manipulated for 20 min each time, once a day for 2 weeks. In the rapamycin group, rapamycin (2 mg/kg) was given by intraperitoneal injection once a day for 2 weeks. On the basis of the treatment in the moxibustion group, 3-methyladenine (1.5 mg/kg) was given by intraperitoneal injection once a day for 2 weeks. The mice in the control and the model group received normal diet and no intervention was given for 2 weeks. Immunohistochemica method was used to measure the levels of Aβ in the cerebral cortex and hippocampal, transmission electron microscopy was used to observe the formation of autophagosome in hippocampus, and Western blot method was used to observe the levels of PI3K, Akt, p-Akt, mTOR and p-mTOR in hippocampus.@*RESULTS@#Compared with the control group, the levels of Aβ in the cerebral cortex and hippocampal were increased in the model group (0.05）. Compared with the rapamycin group, the levels of Aβ in the cerebral cortex and hippocampal were increased in the combination group (<0.01). In the model group, the cytoplasmic utophagic vacuoles and organelles of neuron were reduced. In the moxibustion group, the utophagic vacuoles were increased, and the organelles showed deformation and atrophy. In the rapamycin group, the utophagic vacuoles were widely disturbed and few deformed organelles were found. In the combination group, few utophagic vacuoles were found and additional organelles showed deformation and atrophy. Compared with the control group, the levels of PI3K、Akt、p-Akt、mTOR and p-mTOR were increased in the model group (all <0.01). Compared with the model group, the levels of PI3K、Akt、p-Akt、mTOR and p-mTOR were reduced in the moxibustion group, the rapamycin group and the combination group (all <0.01). Compared with the moxibustion group, the levels of PI3K、Akt、and p-mTOR were increased in the rapamycin group and the levels of PI3K、Akt、p-Akt、mTOR and p-mTOR were increased in the combination group (all <0.01). Compared with the rapamycin group, the levels of PI3K、Akt、p-Akt、mTOR and p-mTOR were increased in the combination group (<0.01).@*CONCLUSION@#Moxibustion at acupoints of governor vessel can enhance the autophagy process on Aβ in brain of the APP/PS1 double-transgenic AD mice, which may be associated with its effects on inhibiting the abnormal activation of PI3K/Akt/mTOR signaling pathway.

A retrospective analysis of real-world outcomes of elderly Chinese patients with diffuse large B-cell lymphoma / 中华医学杂志(英文版)

BACKGROUND@#Elderly patients with diffuse large B-cell lymphoma (DLBCL) have a worse prognosis than younger patients, and the optimal treatment strategy for this group remains controversial. We conducted a retrospective analysis to investigate the clinical features and outcomes of elderly patients (>60 years) and to assess the impact of clinical and molecular factors on outcome in this age group.@*METHODS@#From April 2006 to December 2012, a total of 349 elderly patients with DLBCL from the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College were included in this analysis. Patients were further divided into two age groups (61-69 years and ≥70 years). We compared clinical characteristics and outcomes between groups.@*RESULTS@#Of 349 total patients, 204 (58.5%) were aged 61 to 69 years, and 145 (41.5%) patients were aged 70 years or older. Except for the Eastern Cooperative Oncology Group performance status, clinical characteristics were comparable between the two groups. With a median follow-up of 82 (range, 1-129) months, the 5-year overall survival (OS) and progression-free survival (PFS) rates were 51.9% and 45.8%, respectively. The 5-year OS rates for patients aged 61 to 69 years and those over 70 years were 58.3% and 42.8% (P = 0.007), respectively, and the 5-year PFS rates were 51.0% and 38.6% (P = 0.034). Treatment regimens including rituximab provided a higher 5-year OS rate (63.1% vs. 37.1%, P < 0.001) and PFS rate (56.6% vs. 31.8%, P < 0.001) than chemotherapy alone. For patients aged 61 to 69 years, chemotherapy plus rituximab resulted in a higher 5-year OS rate (66.7% vs. 46.4%, P = 0.002) and PFS rate (60.0% vs. 38.1%, P = 0.002) than chemotherapy alone. For patients aged ≥70 years, there was a marked survival advantage in patients who received chemotherapy plus rituximab (5-year OS rate: 57.7% vs. 25.4%, P < 0.001; 5-year PFS rate: 51.3% vs. 23.9%, P < 0.001) compared with that seen in those who received chemotherapy alone. Multivariate analysis established that stage III/IV disease, elevated lactate dehydrogenase (LDH), initial treatment, and chemotherapy with rituximab were independent risk factors for 5-year OS, and stage III/IV disease, elevated LDH, and chemotherapy with rituximab were independent risk factors for 5-year PFS for elderly patients with DLBCL.@*CONCLUSIONS@#In comparison to patients aged 61 to 69 years, those aged ≥70 years have poorer survival. Prolonged survival is obtainable with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)-like in elderly Chinese patients in all age groups, indicating that the R-CHOP-like regimen should be considered for this population, even for those aged 70 years or older.

Retrospective analysis of the clinical features and prognostic factors of 370 patients with advanced-stage diffuse large B-cell lymphoma / 中华肿瘤杂志

Objective@#The clinical features and prognosis of diffuse large B-cell lymphoma (DLBCL) were analyzed to optimize the treatment.@*Methods@#We retrospectively collected the clinical data of patients with advanced-stage DLBCL from January 2006 to December 2012 in National Cancer Center/Cancer Hospital. The demographic characteristics, clinical stage, histological diagnosis, treatment and prognostic characteristics of these patients were analyzed.@*Results@#A total of 370 patients with median age of 55 years old were recruited in the study. The male-to-female ratio was 1.3∶1. Among the 361 patients who underwent therapy, 280 cases received chemotherapy alone, 65 cases received chemoradiotherapy, and 16 cases received chemotherapy combined with autologous hematopoietic stem cell transplantation (AHSCT). The median follow-up period was 89 months, the 5-year overall survival (OS) rate of the entire cohort was 42.9%. The 5-year OS rate of chemotherapy alone, chemoradiotherapy and chemotherapy combined with AHSCT were 36.8%, 58.5%, 87.5%, respectively. The 5-year OS rate were significantly different between chemoradiotherapy and chemotherapy alone (P=0.001), and between chemotherapy combined with AHSCT and chemoradiotherapy (P=0.040). Univariate analysis showed that the age, Eastern Cooperative Oncology Group performance status (ECOG PS) score, Ann Arbor stage, B symptom, bulky disease, number of extranodal sites, Ki-67 index, lactate dehydrogenase (LDH), β2-microglobulin (β2-MG), international prognostic index (IPI), therapeutic manner and chemotherapy combined with rituximab were significantly associated with the prognosis of advanced DLBCL patients (all P<0.05). Multivariate analysis demonstrated that the age >60 years, Ann Arbor stage IV, with B symptom, with bulky disease, ECOG PS≥1, Ki-67 index > 90%, CD5 expression, up-regulation of serum LDH and β2-MG, and chemotherapy without rituximab were related with the poor prognosis of patients with advanced-stage DLBCL (all P<0.05).@*Conclusions@#Chemotherapy combined with rituximab can improve the outcome of patients with advanced-stage DLBCL. The age, stage, B symptom, bulky disease, ECOG PS score, Ki-67 index, CD5 expression, LDH, β2-MG and chemotherapy combined with rituximab are associated with the prognosis of these patients.

Effects of Shuwei Decoction on the expressions of Beclin-1, mTOR, Cx43 Protein and mRNA in gastrointestinal smooth muscle of rats with functional dyspepsia due to liver depression and spleen deficiency / 中成药

AIM To investigate the therapeutic action and mechanism of Shuwei Decoction (Bupleuri Radix,Cyperi Rhizoma,Atractylodis macrocephalae Rhizoma,etc.) on functional dyspepsia (FD) from the perspectives of autophagy and intercellular gap junction pathway through its impact on the expressions of Beclin-1,mTOR,Cx43 protein and mRNA in gastric antrum pyloric smooth muscle cells of FD model rats.METHODS Sixty Wistar rats were randomly divided into control (blank) group,model group,mosapride group (1.37 mg/kg),low,medium and high dose Shuwei Decoction groups (7.67 g/kg,15.34 g/kg,30.68 g/kg,respectively).FD model rats were prepared according to compound etiological modeling method for 21 days.On the first day after modeling,the rats in each group were given the corresponding medicine for intragastric administration once a day for 14 days.Two hours after the last administration,we procured gastric antrum and pyloric tissues from the sacrificed rats.The expressions of Beclin-1,mTOR and Cx43 protein were detected by Western blot,and so were the expressions of Beclin-1,mTOR and Cx43 mRNA by quantitative real-time PCR (RT-qPCR).RESULTS We observed decreased expression of Beclin-1 protein in low,medium and high dose Shuwei Decoction groups (P ＜ 0.01),and an increased expression of Cx43 protein in high dose Shuwei Decoction group (P ＜ 0.05).In medium and high dose Shuwei Decoction groups,decreased expression of Beclin-1 mRNA (P ＜ 0.01),and increased expression of mTOR and Cx43 mRNA (P ＜ 0.01) were detected as well.CONCLUSION Shuwei Decoction can improve FD by suppressing cell autophagy and enhancing the function of gap junction through up-regulating the expression of mTOR mRNA and Cx43 protein and mRNA,and down-regulating the expression of Beclin-1 protein and mRNA.

Effects of ADAR1 inducer / inhibitor on cognitive impairment and the expression of ADAR1 protein of social isolation mice / 中华行为医学与脑科学杂志

Objective To explore the effects of ADAR1 inducer and inhibitor on cognition and ADAR1 expression of isolated BALB/c mice.Methods Sixty healthy BALB/c mice were divided into 6 groups according to randomized design with 10 animals each group,the gregarious control group (GH),social isolation model group (SI),ADAR1 inducer treated gregarious group (GH+IFN-γ),ADAR1 inhibitor treated gregarious group (GH+EHNA),ADAR1 inducer treated isolation group (SI+IFN-γ) and ADAR1 inhibitor treated isolation group (SI+EHNA).Mice in drug treatment groups were treated with ADAR1 inducer (5.0? 104 U/kg,20 ml/kg,ip) and inhibitor (10 mg/kg,20 ml/kg,ip).Objection recognition test was used to measure cognition.Immunohistochenmistry was used to measure ADARI immunoreactivity and Western blotwas used to measure ADAR1 protein expression.Results In the objection recognition test,the non-spatial discrimination index of mice in SI group (-0.16±0.09) was significantly lower than that of GH group (0.41 ±0.17,P＜0.01),the non-spatial discrimination index of mice in SI+IFN-γ group (0.20±0.09) and in SI+ EHNA group (-0.29±0.12) was higher (P＜0.01) and lower (P＜0.05) than that of the SI group respectively.The immunohistochemistry results showed that the ADAR1 immunoreactivity in hippocampus of mice in SI group (Hilus:(0.013±0.003),CAI:(0.021±0.005)) decreased significantly compared to those of GH group(Hilus:(0.021 ±0.002),(0.047±0.004);both P＜0.05).And GH+IFN-γgroup mice showed increased ADAR1 immunoreactivity obviously in Hilus ((0.013±0.003) vs (0.023±0.004),P＜0.01) and in CA1 ((0.021±0.005) vs (0.040±0.005),P＜0.01) compared with that of SI group,ADAR1 inducer recovered the above abnornal ADAR1 immunoreactivity.Western blot results showed that the ADAR1 protein expression of mice in SI group (0.48 ±0.07) in hippocampus was significantly decreased (P＜0.01) compared to that of GH group (1.00 ±0.00).The level of ADAR1 protein in SI+IFN-γgroup(0.82 ±0.04) increased compared with that of SI group.Conclusions Four weeks of social isolation can reduce the non-spatial cognitive ability of BALB/c mice and decrease the expression of ADAR1 in the hippocampus.The ADAR1 inducers and inhibitors can reverse and aggravate the cognitive impairment caused by social isolation respectively.The related mechanisms may be related to the expression of ADAR1.

Relationship between clinical features and peripheral blood test indicators and curative effect in patients with acquired hemophagocytic syndrome / 白血病·淋巴瘤

Objective To explore relationship between clinical features and peripheral blood test indicators and curative effect in adult patients with acquired hemophagocytic syndrome (HPS). Methods A total of 61 adult patients with acquired HPS who were admitted to the First Affiliated Hospital with Nanjing Medical University and the Affiliated Jiangning Hospital of Nanjing Medical University from April 2014 to March 2017 were enrolled, including 38 males and 23 females, with a median age of 48 years (17-86 years). The retrospective analyses of their clinical data and laboratory examination results were made in this study. Results There was no significant difference in the therapeutic effective rate of 61 HPS patients caused by different inducements after treatment (P ＝0.184). The prothrombin time (PT) before treatment was higher than that after treatment [(12.90±1.97) s vs. (12.35±1.78) s, P＝ 0.046]; the level of lactate dehydrogenase (LDH) before treatment was higher than that after treatment (median: 476 U/L vs. 231 U/L, P ＝ 0.000); the level of D-dimer (D-D) before treatment was higher than that after treatment (median: 1.46 mg/L vs. 0.51 mg/L, P ＝ 0.007); the level of aspartate aminotransferase (AST) before treatment was higher than that after treatment (median: 54.9 U/L vs. 26.0 U/L, P＝ 0.000); the level of serum calcium before treatment was lower than that after treatment [(2.07±0.20) mmol/L vs. (2.18±0.23) mmol/L, P ＝ 0.043]. The peripheral blood platelet counts (Plt) in the effective group (32 cases) before treatment was higher than that in the ineffective group (29 cases) (median: 104.0×109/L vs. 63.5×109/L, P ＝0.007), the level of albumin (ALB) in the effective group was higher than that in the ineffective group [(35.50 ±6.17) mmol/L vs. (31.93 ±6.54) mmol/L, P ＝ 0.033], the level of serum calcium in the effective group was higher than those in the ineffective group [(2.18±0.18) mmol/L vs. (2.08±0.20) mmol/L, P ＝ 0.047], the level of prothrombin time (PT) in the effective group was lower than that in the ineffective group [(12.40±1.76) s vs. (13.43±2.06) s, P ＝ 0.041], and the level of LDH in the effective group was lower than that in the ineffective group (median: 415.0 U/L vs. 593.5 U/L, P＝ 0.032). Conclusion The lower expressions of Plt, ALB and serum calcium, and the higher expressions of PT and LDH may indicate the poor prognosis of adult acquired HPS, and there fore these patients need to be paid attention.

Research progress of lncRNAs in diabetic neuropathy and vascular disease / 中国药理学通报

Long noncoding RNA is a functional RNA fragment that is not involved in translation of proteins. Many reports showed that lncRNA was closely related to diabetes. This review summarizes the pathogenesis and the role of lncRNAs in diabetic neuropathy and vascular disease,so as to provide the basis for prevention and treatment of diabetes.

The diagnostic value of four serum tumor markers for gastric cancer based on pattern recognition techniques* / 重庆医学

Objective To evaluate the diagnostic value of serum tumors CA72-4,CA242,CA19-9 and carcino-embryonic antigen(CEA)in patients with gastric cancer based on pattern recognition techniques.Methods Data of serum concentrations of CA72-4,CA242,CA19-9 and CEA of 212 patients with gastric cancer,116 patients with benign gastric disease and 117 healthy subjects were retrospectively analyzed;and the diagnostic performance of each tumor marker,four tumor markers based principle component analysis(PCA),decision tree,PCA-decision tree and the fisher discriminant analysis models were established.Results CA242 had the best diagnostic effect on gastric cancer,and the area under the ROC curve(AUC)was 0.841(95％CI:0.804-0.877).PCA model showed that the serum levels of four tumor markers in patients with gastric cancer were significantly different from those in benign and healthy patients,and obvious metabolic disorders of serum with four tumor markers were found among the patients with gastric cancer.The diagnosis accuracy of the decision tree,PCA-decision tree and the Fisher discriminant analysis models for gastric cancer patients was 58.6％,65.5％and 58.6％respectively,and for non-gastric cancer patients(benign gastric diseases and healthy controls)was 94.7％,99.4％and 97.6％.And the prediction accuracy of the decision tree,PCA-decision tree and the fisher discriminant analysis models for gastric cancer patients was 65.7％,77.6％and 73.1％,and for non-gastric cancer patients was 87.5％,96.9％and 96.9％,respectively.Conclusion The PCA-decision tree model of serum CA72-4,CA242,CA19-9 and CEA might be helpful for the diagnosis and prediction of patients with gastric cancer.

Diagnostic Value of Serum CA72-4,CA242,CA19-9 and CEA for Gastric Cancer Based on PCA-Decision Tree Model / 现代检验医学杂志

Objective To evaluate the diagnostic value of serum tumors CA72-4,CA242,CA19-9 and carcino-embryonic anti-gen (CEA)for patients with gastric cancer based on principle component analysis (PCA)-decision tree analysis.Methods Serum levels of CA72-4,CA242,CA19-9 and CEA in 193 patients with gastric cancer,106 patients with benign gastric disea-ses and 86 nornal controls were measured by electrochemiluminescence assay,and data were analyzed by the receiver operat-ing characteristic (ROC)curve,PCA and PCA-decision tree analysis.Results The area under the ROC curve of CA72-4, CA242,CA19-9 and CEA was 0.741[95% confidence interval (95%CI),0.692~0.791],0.863 (95%CI,0.827~0.898), 0.783 (95%CI,0.737~0.828)and 0.827 (95%CI,0.785~0.869),respectively.The combined four serum tumor markers in the PCA-AUC model was 0.935 (95%CI,0.912~0.958)at the cutoff value (PC score)of 44.13 with 78.2% of sensi-tivity and 94.8% of specificity.The accuracy of serum CA72-4,CA242,CA19-9 and CEA for the diagnosis of gastric cancer group and nongastric cancer group (benign gastric diseases and nornal controls)in the decision tree model were 76.2% and 94.8%,56.5% and 96.5% for prediction,respectively.The combined four serum tumors for the diagnosis of gastric cancer group and nongastric cancer group in PCA-decision tree model were 90.3% and 100%,72.4% and 92.2% for prediction,re-spectively.Conclusion The PCA-decision tree model based on serum CA72-4,CA242,CA19-9 and CEA were helpful for the diagnosis of gastric cancer.

Current status of anti-viral treatment in children with acquired immune deficiency syndrome in acquired immune deficiency syndrome care center, Yunnan / 中华传染病杂志

Objective To analyze the effect of long-term anti-viral treatment in children with acquired immune deficiency syndrome (AIDS) and investigate the factors affecting the treatment efficacy and growth and development of the children, so as to provide reference for improving the efficacy of antiviral drugs.Methods Children with AIDS receiving anti-retroviral treatment during 2004 to 2016 were retrospectively enrolled.The height, weight and CD4+ T cell counts were recorded every half year and the measurement of HIV RNA load was recorded on an annual basis.The CD4+ T cell counts and viral inhibition rates for the children who were under the treatment in the first year, 1~0.05);and viral inhibition rates were 92.9% and 97.6%, respectively with no statistical significance (χ2=1.071, P>0.05).The viral inhibition rate for the children receiving the treatment for 1 year was 85.7%, while that for whose treatment lasted for more than 10 years was 100.0%.A total of 5 cases developed drug-resistance (2 cases treated for 1 to 5 years and 3 cases for 5 to 10 years), and the virus replication was completely inhibited after switching to Lopinavir/ritonavir (LPV/r).The drug compliance was more than 95.0%.64.8% of children met the standard height, while 68.5% met the standard body mass.The baseline and last measured CD4+ T cell counts showed no significant differences between family-raised and social organization-raised children (Z=-1.159 and -0.523, respectively, both P>0.05).The children from high-income families had no significant differences compared with those from low-income ones in terms of the baseline and last measured CD4+ T cell counts (Z=-0.019 and -0.776, respectively, both P>0.05).Conclusions The long-term anti-retroviral treatment can effectively elevate the CD4+ T cell counts, inhibit viral replication and ensure drug compliance, which may promote the growth and development of children.However, approximately 30% children are still lower than the normal standards in terms of height and body mass.The drug-taking observer plays a central role on treatment effect.Most of the children′s family suffer from poor economic conditions.

Clinical effect of 1-desamino-8-D-Arginine Vasopressin different withdrawal ways in primary monosymptomatic nocturnal enuresis / 中国综合临床

Objective To explore the effect and compare the relapse rates of 1-desamino-8-D-Arginine Vasopressin(DDAVP) different withdrawal ways after initial 3 months in primary monosymptomatic nocturnal enuresis(PMNE) patients,in order to provide some evidences and references to use DDAVP to cure PMNE preferably.Methods Two hundred and fifty-six cases PMNE patients who were treated in Hubei Maternal and Child Health Hospital from November 2014 to June 2016 were selected and randomly divided into group A (DDAVP immediate withdrawal group,65 cases),group B(DDAVP day reduction group,58 cases) and group C (DDAVP step reduction group,60 cases).All patients were given DDAVP tables for 3 months.After 3 months for DDAVP,patients who were effective (full respond and partial respond) to DDAVP continued to undergo a withdrawal stage,those in group A underwent immediate cessation,those in group B continued to receive the effective dose every other day for 2 months and those in group C were step by step tapered by 0.05-0.10 mg every 2-4 weeks until completely stopped,the period was not more than 3 months.All patients had a follow-up visit for 3 months after cessation of DDAVP.Results A total of 183 patients completed the study finally,there were 65 patients in group A,58 patients in group B and 60 patients in group C.Initial 3 months the effective rates of group A,B and C were respectively 89.23％ (58/65),89.66％ (52/58) and 86.67％ (52/60),there were not statistically significant difference(x2 =0.309,P =0.857).There were 58 patients in group A,52 patients in group B and 52 patients in group C continued to undergo the withdrawal stage.One month after cessation of DDAVP,the effective rates of group B (88.46％,46/52) and group C (92.31％,48/52) were significantly higher than group A(67.24％,39/58) (x2 =7.030,P=0.008;x2 =10.417,P=0.001),while the relapse rates of group B(19.23％,10/52) and group C(17.31％,9/52) were significantly less than group A(36.21％,21/58) (x2=3.904,P=0.048;x2=4.937,P =0.026).Three months after cessation of DDAVP,the effective rates of group C (78.85％,41/52) were significantly higher than group A (50.00％,29/58) and group B (57.69％,30/52) (x2 =9.859,P=0.002;x2 =5.371,P=0.020),and the relapse rates of group C(32.69％,17/52) were significantly less than group A (55.17％,32/58) and group B (51.92％,27/52) (x2 =5.609,P =0.018;x2 =3.939,P =0.047),while the effective rates and relapse rates were not statistically significant difference between group A and group B(x2 =0.652,P =0.419;x2 =0.116,P =0.733).Severe adverse events related to DDAVP were not observed in any patients.Conclusion Gradual withdrawal after initial 3 months of DDAVP may improve the effect and reduce the relapse rates,the short-term and long-term curative effects of step-by-step withdrawal treatment are both well,while long-term curative effects of every other day withdrawal treatment is not obviously well.

Decreased Prognostic Value of International Prognostic Score in Chinese Advanced Hodgkin Lymphoma Patients Treated in the Contemporary Era / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The International Prognostic Score (IPS) was developed based on the data of Western advanced Hodgkin lymphoma (HL) patients treated before 1992. Only a few studies ever evaluated the application value of IPS in Chinese population or in patients treated in the contemporary era whose outcomes has improved significantly than before.</p><p><b>METHODS</b>We conducted a retrospective study involving 208 previously untreated Chinese advanced HL patients, who were admitted to Cancer Hospital Chinese Academy of Medical Sciences from January 1, 1999 to April 30, 2015 and received uniform first-line treatment. The prognostic value of both IPS and the seven IPS factors for freedom-from progression (FFP) and overall survival (OS) was assessed in this population. The statistical methods included Kaplan-Meier methodology, log-rank testing, and Cox proportional hazard regression analysis.</p><p><b>RESULTS</b>With a median follow-up time of 79 months (range, 15-210 months), the 5-year FFP and OS were 78.8% and 86.0% respectively, which improved obviously compared with the original IPS study. The IPS remained prognostic for both FFP (P = 0.041) and OS (P = 0.013), but the range narrowed obviously, with 5-year FFP ranging from 87.2% to 61.5%, 5-year OS ranging from 94.1% to 69.2%, and the separation of survival curves was not as good as before. Only two of the seven IPS factors showed a significant independent prognostic value in the multivariate analysis: Stage IV (for FFP, hazard ratio [HR] = 2.219, 95% confidence interval [CI]: 1.148-3.948, P = 0.016; for OS, HR = 2.491, 95% CI: 1.159-5.355, P = 0.019) and hemoglobin <105 g/L (for FFP, HR = 2.136, 95% CI: 1.123-4.060, P = 0.021; for OS, HR = 2.345, 95% CI: 1.099-5.042, P = 0.028). A simple prognostic score calculated by adding one point each for any of the two factors was prognostic both for FFP (P < 0.001) and OS (P < 0.001) with the survival curves separating very well, but the range still narrowed.</p><p><b>CONCLUSIONS</b>The IPS has decreased the prognostic value in Chinese advanced HL patients treated in the contemporary era. More prognostic factors are needed to supplement this original scoring system so as to identify different risk populations more accurately.</p>

Retrospective analysis of the clinical features and prognostic factors of 126 patients with primary gastric diffuse large B-cell lymphoma / 中国肿瘤临床

Objective:Primary gastric diffuse large B-cell lymphoma (PGLBCL) is a highly common subtype of extranodal non-Hodgkin lymphoma. We analyzed the disease's clinical features and prognosis to guide better treatment. Methods:We retrospectively collect-ed data from PGLBCL cases seen from January 1999 to March 2012 in one cancer center. We then analyzed the demographic character-istics, clinical stage, histological diagnosis, complications, treatment, and prognostic characteristics of such patients. Results:A total of 126 patients with median age of 49 years old (range:16-81 years) were included in the study. The male-to-female ratio was 68:58. A to-tal of 96 patients were pathologically diagnosed with pure diffuse large B-cell lymphoma (DLBCL), 27 with mucosa-assouated lymphoid (MALT) component, and 3 with plasmacytoid differentiation. Meanwhile, 90%of the patients were in the early stage of the disease. For the early-stage patients, treatment strategy included surgery+chemotherapy ± radiotherapy for 38 cases, chemoradiotherapy for 39 cases, chemotherapy alone for 37 cases, and surgery alone for 1 case. Under a median follow up of 48 months, the 4-year progres-sion free survival (PFS) and overall ourvival (OS) rate of the whole group were 75.6%and 82.7%, respectively. PFS rates for early and advanced stage patients were 77%and 41.7%(P=0.005), respectively. For the early-stage patients treated with chemotherapy alone, chemoradiotherapy, and surgery with therapy, the PFS rates were 67.3%, 77.8%, and 77.8%(P=0.588), respectively. The patients with international prognostic index (IPI) score of 0, 1, and>1 achieved PFS of 85.4%, 74.4%, and 55.6%(P=0.011), respectively. The PFS rates were 81.2%and 66.1%(P=0.018) for stagesⅠandⅡ, respectively, and 86.6%and 63.3%(P=0.006) for the normal and elevated LDH levels, respectively. The pathological type of pure DLBCL or a MALT component, GCB or non-GCB origin, and age more than 60 years old were not associated with prognosis. Conclusion:The majority of the PGLBCL patients were in the early stage of disease, but the outcome of early-stage disease was favorable. Surgery did not improve outcomes. Univariate analysis demonstrated that IPI score>1, stageⅡdisease, and elevated LDH levels were associated with poor prognosis in the early-stage patient.