Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

Background Aluminum activates signal transducer and activator of transcription 3 (STAT3), causing microglial nucleotide-binding and oligomerization domain-like receptors protein 3 (NLRP3) inflammasome activation and inflammatory responses and producing neurotoxicity. Objective To explore the role of STAT3 regulated NLRP3 inflammasomes in the inflammatory response of mouse microglia cell line (BV2) cells induced by maltol aluminum [Al(mal)₃]. Methods BV2 cells were assigned to five groups: one control group, three Al(mal)₃ exposure groups (low, medium, and high doses at 40, 80, and 160 μmol·L⁻¹ Al(mal)₃ respectively), and one C188-9 (STAT3 antagonist) intervention group [10 μmol·L⁻¹ C188-9 +160 μmol·L⁻¹ Al(mal)₃]. Cell viability was detected by CCK8. The expression of M1/M2 type markers, i.e. CD68/CD206, STAT3, p-STAT3, NLRP3, cleaved-casepase-1, and apoptosis-associated speck-like protein (ASC) in BV2 cells were detected by Western blotting, and proinflammatory cytokines interleukin (IL)-1β and IL-18, and anti-inflammatory cytokine IL-10 were determined by ELISA. Results The results of cell viability assay showed that cell viability gradually decreased with the increase of Al(mal)₃ dose. Compared with the control group, the cell viability of the Al(mal)₃ high-dose group was decreased by 18% (P<0.05); compared with the Al(mal)₃ high-dose group, the cell viability of the C188-9 intervention group was significantly elevated by 14% (P<0.05). Compared with the control group, the expression levels of CD68 in the Al(mal)₃ low-, medium-, and high-dose groups were elevated by 19%, 20%, and 21%, respectively (P<0.05); the expression level of CD206 in the Al(mal)₃ high-dose group was decreased by 25% (P<0.05). Compared with the Al(mal)₃ high-dose group, the expression level of CD68 in the C188-9 intervention group was reduced by 9% (P<0.05), whereas the expression level of CD206 was elevated by 22% (P<0.05). Compared with the control group, the p-STAT3 protein expression and the p-STAT3/STAT3 ratio in the Al(mal)₃ high-dose group increased by 129% and 127%, respectively (P<0.05). Compared with the Al(mal)₃ high-dose group, the p-STAT3 protein expression and the p-STAT3/STAT3 ratio in the C188-9 intervention group were decreased by 55% and 54%, respectively (P>0.05). Compared with the control group, the expression level of NLRP3 protein increased by 75% in the Al(mal)₃ high-dose group (P<0.05), the expression levels of cleaved-casepase-1 protein increased by 28% and 35% in the Al(mal)₃ medium- and high-dose groups (P<0.05), and the expression levels of ASC increased by 22%, 25%, and 53% in the Al(mal)₃ low-, medium- and high-dose groups (P<0.05), respectively. Compared with the Al(mal)₃ high-dose group, the expression levels of NLRP3, cleaved-casepase-1, and ASC proteins in the C188-9 intervention group decreased by 30%, 19%, and 32%, respectively (P<0.05). Compared with the control group, the levels of IL-1β in the Al(mal)₃ medium- and high-dose groups increased by 18% and 21%, respectively (P<0.05), and the level of IL-18 in the Al(mal)₃ high-dose group increased by 10% (P<0.05). Compared with the Al(mal)₃ high-dose group, the IL-18 levels were reduced by 23% in the C188-9 intervention group (P<0.05). The content of anti-inflammatory factor IL-10 did not differ significantly between groups (P>0.05). Conclusion Aluminum can induce inflammatory responses in BV2 microglia and is predominantly pro-inflammatory, and the mechanism may involve STAT3 regulation of NLRP3 inflammasome secretion of inflammatory factors.

The humoral immune response of B cells is the key to the protection of specific immunity, and immune aging reshapes its production and function. The decreased B cell immune function is an indicator of immune senescence. The impaired humoral immune function mediated by antibody secreted by B cells leads to a decline in the response of elderly individuals to the vaccine. These people are therefore more susceptible to infection and deterioration, and have a higher incidence of tumors and metabolic diseases. Activation-induced cytidine deaminase (AID) is an enzyme that triggers immunoglobulin class conversion recombination (CSR) and somatic high frequency mutation (SHM). It decreases during immune senescence and is considered to be a biomarker of decreased B cell function in aging mice and humans. Understanding the inherent defects of B-cell immune senescence and the regulation mechanism of AID in the aging process can provide new research ideas for the susceptibility, prevention and treatment of diseases in the elderly.
Animals ; Humans ; Mice ; Aging/metabolism* ; B-Lymphocytes/metabolism* ; Cytidine Deaminase/metabolism* ; Somatic Hypermutation, Immunoglobulin

Background Occupational aluminum exposure may associate with cognitive impairment in workers. At present, brain functional imaging data are not available for evaluating cognitive dysfunction in workers with occupational exposure to aluminum. The role of brain functional connectivity in cognitive decline associated with occupational aluminum exposure is not clear yet. Objective To explore potential mediating effect of brain functional connectivity value on cognitive decline induced by occupational aluminum exposure, to assess the relationship between cognitive impairment and brain functional connectivity, and to identify appropriate imaging evidence of early cognitive changes induced by occupational aluminum exposure. Methods This study used a subset data from a previous cross-sectional survey. Based on the data of aluminum-exposed workers, over 40 years old, aluminum-exposed working years >1 year, Montreal International Cognitive Assessment (MoCA) (Beijing version) score <26 points, 20 workers were selected as the case group, and 40 healthy workers with the same basic conditions (age, smoking, drinking, etc.) in non-aluminum production were selected as the control group with a 1∶2 matching ratio. The basic information of the subjects was collected, plasma aluminum level and cognitive function level were evaluated, and different brain functional connectivity values of default mode network (DMN) were measured by magnetic resonance imaging. The mediating effect analysis was conducted to examine the role of brain functional connectivity in the relationship between aluminum exposure and cognitive function. Results The plasma aluminum concentration of the case group was 1.76 times higher than that of the control group [(33.04±12.02) µg·L⁻¹ vs (18.74±8.95) µg·L⁻¹, P<0.05]; the MoCA score was 9.5 points lower [(18.35±2.64) vs (27.85±0.92), P<0.05]. The mean functional connection values of DMN1 and DMN2 in the case group were lower than those in the control group (P<0.05). The mean functional connection values of the left precuneus, left middle cingulate cortex, left superior medial gyrus, left precentral gyrus, and left cerebellum also decreased in the case group compared with the control group (P<0.05). Plasma aluminum concentration was negatively correlated with DMN1 functional connectivity value and MoCA scores (b=−0.004, 95%CI: −0.008–−0.001; b=−0.15, 95%CI: −0.233–−0.067; P<0.05). The mean functional connection values of DMN1 and DMN2 were positively correlated with MoCA scores (b=10.945, 95%CI: 5.574–16.316; b=10.107, 95%CI: 2.457–17.758; P<0.05). With the increase of plasma aluminum concentration, MoCA score decreased, but when the plasma aluminum concentration exceeded 19.50 µg·L⁻¹, MoCA score decreased slowly. With the increase of the mean functional connectivity value of DMN1, MoCA score increased, but when the mean functional connectivity value of DMN1 exceeded 1.05 and continued to increase, the increase of MoCA score slowed down. The results of mediating effect analysis showed that the functional connectivity value of DMN1 partially mediated the relationship between plasma aluminum concentration and MoCA score, and the mediating effect was 25.80%. Conclusion Cognitive impairment in occupational aluminum-exposed workers is closely related to brain resting-state functional connectivity. There is a dose-response relationship of plasma aluminum concentration with DMN1 functional connectivity value and MoCA scores, and DMN1 functional connectivity value partially mediates the relationship between plasma aluminum concentration and MoCA scores. The brain functional connectivity value can be used as meaningful imaging data to study the cognitive decline induced by chronic aluminum exposure.

Background Occupational aluminum exposure is closely related to cognitive impairment, and alcohol consumption is also closely related to cognitive dysfunction. Objective To explore the effects of types of alcohol consumption on cognitive function of occupational aluminum exposed workers. Methods A total of 181 workers aged from 23 to 56 years were selected by cluster sampling method in an electrolytic aluminum workshop of an aluminum plant in a region and in a maintenance workshop of another plant in the same region from July to August, 2019. Venous blood was collected, and plasma aluminum concentration was determined by inductively coupled plasma mass spectrometry. The study subjects were divided into low and high exposure groups based on the median blood aluminum level and type of work. Their basic information was collected by occupational health examination. Workers' cognitive function was assessed using the Montreal Cognitive Assessment Scale-Beijing Edition. Logistic regression was used to analyze the association between plasma aluminum concentration and cognitive impairment, and between the types of alcohol consumption (including Baijiu, red wine, and beer) and cognitive impairment, Unconditional logistic regression was used to fit multiplicative interaction model as well as additive interaction model of plasma aluminum concentration and the types of alcohol consumption, and to calculate the relative excess relative risk due to interaction (RERI) and attributable proportion due to interaction (AP). Results The M (P₂₅, P₇₅) concentrations of plasma aluminum were 40.01 (25.05, 60.56) µg·L⁻¹ in the total study subjects, 25.16 (17.13, 34.78) µg·L⁻¹ in the low exposure group and 60.56 (47.40, 68.53) µg·L⁻¹ in the high exposure group. After adjusting the type of alcohol consumption, drinking, age, duration of exposure to aluminum, education, marital status, and smoking, the odds ratios for impairments of attention, language expression, and overall cognitive function in the high exposure group were 4.295 (95%CI: 1.912-9.648), 5.687 (95%CI: 1.355-23.867), and 2.720 (95%CI: 1.225-6.040) times of the low exposure group respectively. Besides, after adjusting blood aluminum concentration, total alcohol consumption, age, duration of exposure to aluminum, education, marital status, and smoking, the risk of attention impairment of the Baijiu drinkers was 2.613 (95%CI: 1.054 to 6.837) times of the non-Baijiu drinkers; the risks of impairment of visuospatial abilities and execution functions, language expression, delayed recall, and overall cognitive function of the beer drinkers were 3.165 (95%CI: 1.285-7.797), 17.898 (95%CI: 1.590-201.480), 3.118 (95%CI: 1.215-8.003), and 3.824 (95%CI: 1.736-8.423) times of the non-beer drinkers. There were both additive [RERI (95%CI): 1.745 (1.394-2.097), AP (95%CI): 0.415 (0.201-0.630)] and multiplicative (OR=3.591, 95%CI: 1.393-9.255) interactions between Baijiu intake and plasma aluminum concentration levels on the attention domain. The cognitive impairment attributed to the interactive effects of drinking Baijiu and plasma aluminum concentration in individuals with attention impairment accounted for 41.5%. There were both additive [RERI (95%CI): 5.955 (0.562-11.328), AP (95%CI): 0.829 (0.577-1.081)] and multiplicative (OR=42.174, 95%CI: 5.469-325.252) interactions between beer drinking and plasma aluminum concentration on the overall cognitive function. Among the individuals with overall cognitive impairment, the cognitive impairment caused by the interaction of beer drinking and plasma aluminum concentration accounted for 82.9%. Conclusion Occupation aluminum exposed workers' attention, language expression, and overall cognitive function are closely related to their plasma aluminum concentration. Plasma aluminum concentrations have interactions with Baijiu and beer consumption on cognitive impairment of workers.

Objective　To investigate the changes of serum α-synuclein and white matter structure in Parkinson’s disease patients with different status of cognitive impairment,and to explore the relationship between α-synuclein,changes of white matter structure and cognitive impairment in Parkinson’s disease.Methods 　Sixty patients with Parkinson’s disease were selected and divided into 3 groups according to their cognitive function:the normal cognitive group (PD-N),mild cognitive impairment group (PD-MCI) and dementia group (PDD).Patients with cognitive impairment were assessed with the MMSE and the MoCA.All cases were scanned with routine MRI sequence and diffusion tensor imaging (DTI) sequence.Fractional anisotropy (FA) were measured.The serum levels of α-synuclein were measured by ELISA.Results　The FA values of right temporal lobe,right cingulate posterior bundle,the genu of corpus callosum in PD-M CI group were lower than that in PD-N group (all P<0.05),the same findings were found regarding the FA values of left occipital lobe,left cingulate anterior bundle and the splenium of corpus callosum in the PDD group (all P<0.05).Analysis of logistic regression equation revealed that the genu of corpus callosum might be specific for the brain white matter;and so did left cingulate anterior bundle.The Spearman correlation analysis showed that there was a negative correlation between FA values of left frontal lobe and MoCA total score in PD patients,as well as right temporal lobe,left occipital lobe,left cingulate anterior bundle,right cingulate anterior bundle and the splenium of corpus callosum (all P<0.05),positively correlated between serum α-synuclein concentration and MoCA total score in PD patients (P<0.05).Conclusion　Diffusion tensor imaging might be valuable for the diagnosis of cognitive dysfunction in PD;and there might be a certain relationship between serum α-synuclein and cognitive impairment in Parkinson’s disease.

Objective: To observe the feasibility and clinical curative effect of anatomical reduction and fixation of lesser trochanter through posterior-lateral approach for the treatment of comminuted femoral intertrochanteric fractures in elderly patients. Methods: A total of 19 cases with comminuted femoral intertrochanteric fracture, aged 60 to 84 years were enrolled in this study.According to Evans-Jensen classification, 13 cases had type Ⅱ B and 6 cases had type Ⅲ femoral fracture.Through the posterior-lateral approach, the lesser trochanter was fully exposed, reduced and fixed by screw.The proximal and distal femur were well fixed with dynamic hip screw(DHS)or proximal femoral locking plate(PFLP). The lesser trochanter reduction was observed by intraoperative vision and postoperative X-ray.The function evaluation after hip surgery was performed by using Sanders hip function score. Results: All 19 patients obtained the anatomic reattachment in the lesser trochanter.All patients were followed up for an average of 18 months.After treatment, the Sanders hip function score were excellent in 7 patients(36.8%), fine in 12 cases(63.2%). And curative efficacy was good in all cases(100%). There was no significant difference in the curative effect between patients with different classification and gender. Conclusions Through the posterior-lateral approach, the surrounding structures of the lesser trochanter can be fully exposed, and the lesser trochanter can be anatomically repositioned.The posterior-lateral approach to anatomical reduction and fixation of lesser trochanter is an effective and feasible method for the treatment of comminuted intertrochanteric fracture in the elderly.

Objective To evaluate the incidence, prognosis and influencing factors of lower cranial nerve palsy after microvascular decompression (MVD) in patients with hemifacial spasm (HFS). Methods Clinical data of 1033 patients with HFS, admitted to our hospital from May 2014 to August 2016, were retrospectively analyzed. The incidence of lower cranial nerve palsy after procedure and prognosis of these patients were summarized; and influencing factors were analyzed by statistical method. Results In 1033 patients with HFS, 10 patients (0.97％) had lower cranial nerve palsy after procedure: 6 patients suffered hoarseness, 2 patients suffered dysphasia, and 2 patients were with both symptoms; the symptoms in 6 patients completely recovered within one month, 2 patients within one-3 months, and 2 patients within 3-6 months. No permanent low cranial nerve palsy occurred. There were no statistical significances in age, gender, clinical course, sides, or the types of offending vessels between the lower cranial nerve palsy patients (n=10) and the non-palsy patients (n=1023)(P>0.05). Conclusion Lower cranial nerve palsy is a rare complication after MVD, and type of responsible vessels is not a influencing factor in this complication

Objective To investigate the effect of Dl-3-n-butylphthalide on acute cerebral infarction.Methods In Department of Neurology in the Fifth Hospital of Wuhan from March 2013 to June 2014,100 cases of patients with first onset of acute cerebral infarction were recruited.The participants were divided into 2 groups (control group and treatment group) randomly,with 50 participants in each group.Besides general treatment,the patients of treatment group received intravenous injection of Dl-3-n-butylphthalide in acute phase and orally took soft capsule of Dl-3-n-butylphthalide in recovery phase.All the patients were followed up for 24 weeks.Neurological function and general cognition were assessed separately by national institute of health stroke scale (NIHSS),and mini mental state examination (MMSE) was applied to assess overall cognitive function.Results NHISS score was gradually decreased and MMSE score was increased in both groups.As compared with the control group,NIHSS score and MMSE score were changed significantly in the treatment group.From first onset to 24 weeks after treatment,NHISS score was decreased by 30％ in the control group and 44％ in the treatment group;MMSE score was increased by 17％ in the control group and 32％ in the treatment group.Conclusion Sequential therapy with Dl-3-n-butylphthalide improves neurological function and general cognition faster and more significant for patients with acute cerebral infarction.

Objective To test the reliability and validity of Meaningful Life Measure-Chinese Revised (MLM-CR) in Chinese college students. Methods A total of 1035 college students were evaluated with MLM-CR, Satisfaction with Life Scale (SWLS), Purpose in Life (PIL) and Patient Health Questionnaire-2 (PHQ-2), and 120 of the students were examined with PIL-SF twice. Result All the items in MLM-CR had good discrimination indexes (r=0.753-0.838, P<0.001). Confirmatory factor analysis confirmed the hypothesized five-factor model of MLM-CR (χ2/df=3.4, GFI=0.946, AGFI=0.924, RMR=0.069, NFI=0.953, CFI=0.966, RMSEA=0.048). The total internal consistency reliability of MLM-CR was 0.942, and the alpha coefficients of the 5 dimensions ranged from 0.782 to 0.877;the total split-half reliability was 0.920, and the split-half reliability of the 5 dimensions ranged from 0.752 to 0.830;the total test-retest reliability was 0.871, and the test-retest reliability of the 5 dimensions ranged from 0.783 to 0.805. The criterion validity of MLM-CR in correlation with SWLS, PIL and PHQ-2 was 0.66, 0.755 and-0.388, respectively (P<0.01). The Average score of MLM-CR of the college students was 5.20 ± 0.90, and the scores were significantly higher in female students than in the male students (P<0.001). Conclusion MLM-CR has good psychometric properties for application in comprehensive evaluation of personal meaning in life.