Parkinson′s disease is a common neurodegenerative disorder, and cognitive impairment is a frequent non-motor symptom of the disease. The pathogenesis of cognitive impairment in Parkinson′s disease remains unclear, and effective treatment methods are still under investigation. Idebenone exhibits multiple protective effects, including scavenging free radicals, antioxidative stress, mitochondrial protection, anti-inflammation, and enhancing autophagy. It has shown preliminary efficacy in treating cognitive impairment associated with Parkinson′s disease. This article explores the potential of idebenone in treating cognitive impairment in Parkinson′s disease by examining the underlying pathogenic mechanisms and the specific properties of idebenone, providing a reference for clinical practice.

Parkinson′s disease is a common neurodegenerative disorder, and cognitive impairment is a frequent non-motor symptom of the disease. The pathogenesis of cognitive impairment in Parkinson′s disease remains unclear, and effective treatment methods are still under investigation. Idebenone exhibits multiple protective effects, including scavenging free radicals, antioxidative stress, mitochondrial protection, anti-inflammation, and enhancing autophagy. It has shown preliminary efficacy in treating cognitive impairment associated with Parkinson′s disease. This article explores the potential of idebenone in treating cognitive impairment in Parkinson′s disease by examining the underlying pathogenic mechanisms and the specific properties of idebenone, providing a reference for clinical practice.

Objective:To explore the correlation between high cholinergic pathway signaling and cognitive function in patients with Parkinson disease(PD) accompanied with sleep disorder.Methods:PD patients admitted from 2017 to 2022 were divided into PD with sleep disorder group (PD-SD group) ( n=56) and PD without sleep disorder group (PD-NSD group) ( n=41) according to the Parkinson's disease sleep scale (PDSS) score. All participants underwent magnetic resonance imaging examination.All patients were evaluated by the PDSS, Hoehn-Yahr (H-Y), Montreal cognitive assessment scale (MoCA), and cholinergic pathways hyper intensities scale (CHIPS). The difference of cognitive function between the two groups and the correlation between CHIPS and cognitive function were analyzed.Independent sample t-test, Spearman correlation analysis, and binary Logistic regression analysis were performed on the data by SPSS 26.0 statistical software. Results:(1)The MoCA score of the PD-SD group (22.00 (5.00)) was lower than that of the PD-NSD group (26.00 (5.00)) ( Z=-3.830, P<0.05). The total and all aspects scores of CHIPS in PD-SD group were higher than those in PD-NSD group(the total score of the low external capsule: 12.00(8.00), 0(8.00), the total score of the high external capsule: 12.00(2.00), 6.00(9.00), the total score of the radial crown: 8.00(0), 4.00(4.00), the total score of the centrum semiovale: 3.00(4.00), 0(2.00), the total score of the right side: 16.00(9.00), 5.00(10.00), the total score of the left side: 17.00(6.00), 7.00(9.00), the total score of CHIPS: 32.00(14.00), 14.00(20.00))( Z=-5.081, -5.873, -4.933, -3.211, -5.562, -6.232, -5.995, all P<0.05). (2)The correlation analysis between the score of CHIPS and cognitive function in the PD-SD group showed that, the total score of the low external capsule ( r=-0.286), the total score of the centrum semiovale ( r=-0.307), the total score of the right side ( r=-0.376), the total score of the left side ( r=-0.284) and the total score of CHIPS ( r=-0.349) were negatively correlated with MoCA(all P<0.05). (3)Binary Logistic regression analysis showed that white matter lesions in centrum semiovale, low inner capsule, right and left leukodystrophy were not influence factors for cognitive impairment (all P>0.05). Conclusion:PD patients with sleep disorders have lower cognitive function scores, higher CHIPS scores, and significant changes in white matter lesions compared to those without sleep disorders. In PD patients with sleep disorders, the higher the CHIPS score, the lower the cognitive function score, and the more significant the rate of cognitive impairment occurrence and development.

Objective:To evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection in the treatment of peripheral T-cell lymphoma (PTCL) in a real-world setting.Methods:This was a real-world ambispective cohort study (MOMENT study) (Chinese clinical trial registry number: ChiCTR2200062067). Clinical data were collected from 198 patients who received mitoxantrone hydrochloride liposome injection as monotherapy or combination therapy at 37 hospitals from January 2022 to January 2023, including 166 patients in the retrospective cohort and 32 patients in the prospective cohort; 10 patients in the treatment-na?ve group and 188 patients in the relapsed/refractory group. Clinical characteristics, efficacy and adverse events were summarized, and the overall survival (OS) and progression-free survival (PFS) were analyzed.Results:All 198 patients were treated with mitoxantrone hydrochloride liposome injection for a median of 3 cycles (range 1-7 cycles); 28 cases were treated with mitoxantrone hydrochloride liposome injection as monotherapy, and 170 cases were treated with the combination regimen. Among 188 relapsed/refractory patients, 45 cases (23.9%) were in complete remission (CR), 82 cases (43.6%) were in partial remission (PR), and 28 cases (14.9%) were in disease stabilization (SD), and 33 cases (17.6%) were in disease progression (PD), with an objective remission rate (ORR) of 67.6% (127/188). Among 10 treatment-na?ve patients, 4 cases (40.0%) were in CR, 5 cases (50.0%) were in PR, and 1 case (10.0%) was in PD, with an ORR of 90.0% (9/10). The median follow-up time was 2.9 months (95% CI 2.4-3.7 months), and the median PFS and OS of patients in relapsed/refractory and treatment-na?ve groups were not reached. In relapsed/refractory patients, the difference in ORR between patients with different number of treatment lines of mitoxantrone hydrochloride liposome injection [ORR of the second-line, the third-line and ≥the forth-line treatment was 74.4% (67/90), 73.9% (34/46) and 50.0% (26/52)] was statistically significant ( P = 0.008). Of the 198 PTCL patients, 182 cases (91.9%) experienced at least 1 time of treatment-related adverse events, and the incidence rate of ≥grade 3 adverse events was 66.7% (132/198), which was mainly characterized by hematologic adverse events. The ≥ grade 3 hematologic adverse events mainly included decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and anemia; non-hematologic adverse events were mostly grade 1-2, mainly including pigmentation disorders and upper respiratory tract infection. Conclusions:The use of mitoxantrone hydrochloride liposome injection-containing regimen in the treatment of PTCL has definite efficacy and is well tolerated, and it is a new therapeutic option for PTCL patients.

BACKGROUND: Measuring the health of the population is of great significance to the development of a region. We aimed to estimate the population, probability of death, and quality of life in western China. METHODS: We calculated the age-specific mortality rate and prevalence rate of diseases and injuries using the Full Population Database and the Home Page of Inpatient Medical Record. We used multiple interpolation methods to insert missing information from the death data and the model of Kannisto to adjust the mortality rate for elderly individuals. The age-specific prevalence rate of diseases and injuries was adjusted according to the standard ratio of age and methods of equal proportional allocation. Life expectancy was calculated by a life table, and the quality of life was estimated using the Sullivan method. RESULTS: The total population continued to increase in 2015 to 2019 in the Shaanxi Province, China. The mortality rate of children under five has improved, and the mortality rate of people over 65 is decreasing year by year. Life expectancy increased from 74.66 years in 2015 to 77.19 years in 2019. Even with the total risk of disease and injury, the health-adjusted life expectancy increased by 1.90 years within 5 years, and the number of unhealthy years significantly improved. Health-adjusted life expectancy increased by 1.75 years when only considered the ten major disease systems (tumors; endocrinology, nutrition and metabolism; mental and behavioral disorders; nervous system; sensory diseases; circulatory system; respiratory system; digestive system; genitourinary system; musculoskeletal system and connective tissue), and the number of unhealthy years increased slightly. CONCLUSIONS In the past five years, Shaanxi Province has made progress in improving life expectancy and controlling the development of chronic diseases. It is necessary to take specific preventive measures and improve the quality of basic public health services.
Child ; Humans ; Aged ; Cross-Sectional Studies ; Quality of Life ; Life Expectancy ; China/epidemiology* ; Prevalence

Objective:To compare the pharmacokinetics and safety of single intravenous injection of the generic bevacizumab injection WBP264 and the original bevacizumab injection Avastin ? in healthy male volunteers. Methods:The study was designed as a randomized, double-blind, single dose, parallel, and controlled phase I clinical trial. Healthy male volunteers who were recruited publicly were randomized into the trial group (intravenous infusion of WBP264) and the control group (intravenous infusion of Avastin ?), and the dose was 3 mg/kg. Peripheral venous blood was collected within 30 minutes before administration, 45 minutes after onset of the administration, immediately after finishing the administration, 2.5, 3.5, 5.5, 9.5, 13.5, 24, 48 hours and on the 5th, 8th, 15th, 22nd, 29th, 36th, 43rd, 57th, 71st, 85th, and 99th days after the administration. The plasma concentration was measured by enzyme-linked immunosorbent assay, the plasma concentration-time curve and its semilogarithmic plot were plotted, and the pharmacokinetic parameters such as the area under the plasma concentration-time curve [including AUC from time zero to the time of the last quantifiable concentration (AUC 0-t) and AUC from time zero to infinity (AUC 0-∞)], peak concentration ( Cmax), time to peak ( Tmax), plasma elimination half-life ( t1/2), clearance rate (CL), and apparent volume of distribution (Vd) were calculated. When the 90% confidence intervals ( CI) of the geometric mean ratio of AUC 0-t, AUC 0-∞, and Cmax between the trial group and the control group were between 0.80-1.25, it indicated that pharmacokinetics of WBP264 and Avastin ? were similar. The physical examination, vital signs detection, electrocardiogram, and laboratory tests were performed on the subjects, the occurrence of adverse events (AEs) and the severity classification were recorded, and correlation between the AEs and the trial drug was evaluated. The anti-drug antibody and its neutralizing antibody were detected before administration and on the 8th, 15th, 29th, 43rd, 71st, and 99th days after administration to evaluate the immunogenicity of the drug. Results:A total of 78 subjects were recruited, 39 in the trial group and 39 in the control group. In the trial group, 2 cases withdrew from the trial (1 case did not take the drug and 1 case withdrew for personal reason after taking the drug). Seventy-seven cases were in the safety analysis set and 76 cases in the pharmacokinetic analysis set. The differences in age, height, weight, and body mass index between the 2 groups were not significant (all P>0.05). The plasma concentration-time curves of bevacizumab between the trial group and the control group were similar. The geometric mean ratios (90% CI) of AUC 0-t, AUC 0-∞, and Cmax were 1.04 (0.98-1.10), 1.03 (0.98-1.10), and 1.09 (1.03-1.14), respectively. The differences in the incidence of overall AEs [89.5% (34/38) vs. 87.2% (34/39)] and the incidence of AEs possibly related to the trial drug [86.8% (33/38) vs. 79.5% (31/39)] between the trial group and the control group were not significant (all P>0.05). Only one case of AE in the trial group was grade 3 in severity and was assessed as being not related to the drug, and the rest were grade 1-2, with grade 1 AEs accounting for the vast majority. The difference in the positive rate of anti-drug antibody between the trial group and the control group was not significant [10.5% (4/38) vs. 10.3% (4/39), P>0.05]. The neutralizing antibody test was negative in the patients with positive anti-drug antibody. Conclusion:The pharmacokinetics and safety of WBP264 and Avastin ? are similar.

Objective:To investigate the clinical characteristics and prognosis of patients with RUNX1-RUNX1T1 fusion gene-positive acute myeloid leukemia (AML) with ASXL2 gene mutation.Methods:The clinical data of 145 newly diagnosed RUNX1-RUNX1T1 fusion gene-positive AML patients treated at the Second Hospital Center of Shanxi Medical University from October 2010 to March 2021 were retrospectively analyzed. Sanger sequencing was used to detect the gene mutation. According to the presence or absence of ASXL2 gene mutation, the patients were divided into mutation group and non-mutation group. The clinical characteristics, gene mutations and prognosis were compared among the two groups.Results:Among 145 AML patients with positive RUNX1-RUNX1T1 fusion gene, we identified recurrent mutations of c-kit, ASXL2, N/KRAS, FLT3, ASXL1, TET2, NPM1 and DNMT3A genes, with mutation rates of 40.7% (59/145), 20.7% (30/145), 15.9% (23/145), 12.4% (18/145), 11.7% (17/145), 11.0% (16/145), 5.5% (8/145), and 2.1% (3/145), respectively. A total of 18 mutation sites were detected in 30 patients with ASXL2 gene mutations including 5 point mutations and 13 frameshift mutations, which mainly occured in the exons 12 and 13. Lactate dehydrogenase (LDH) at initial diagnosis of 30 AML patients with ASXL2 mutation was lower than that of those with ASXL2 non-mutation ( Z = 2.34, P = 0.020), while prothrombin time (PT) of AML patients with ASXL2 mutation was longer than that of those with ASXL2 non-mutation ( Z = 1.99, P = 0.047). A total of 21 (21/30, 70%) patients simultaneously had other gene mutations. The incidence of RAS mutations in patients with ASXL2 mutation was higher than that those with ASXL2 non-mutation, and the difference was statistically significant [30.0% (9/30) vs. 12.1% (14/115), χ2 = 4.41, P = 0.036]. There were no statistically significant differences in complete remission rate [86.7% (26/30) vs. 74.8% (86/115)] and recurrence rate [43.3% (13/30) vs.31.3% (36/115)] of patients with ASXL2 mutation and ASXL2 non-mutation ( χ2 = 0.39, P = 0.534; χ2 = 0.54, P = 0.432). The median overall survival (OS) time was 26 months (1-135 months) and 30 months (1-120 months), respectively in patients with ASXL2 mutation and ASXL2 non-mutation; the median disease-free survival (DFS) time was 14 months (0-60 months) and 13 months (0-94 months), respectively in patients with ASXL2 mutation and ASXL2 non-mutation; and the differences in OS and DFS were not statistically significant of both groups ( χ2 = 0.05, P = 0.822; χ2 = 0.34, P = 0.562). Compared with ASXL1 mutant patients, cases with ASXL2 mutation had higher OS and DFS rates, and the differences were statistically significant ( P = 0.003, P = 0.007). The differences in OS and DFS between patients with ASXL2 mutations and those with positive mutations of c-kit, RAS, FLT3, TET2, NPM1, DNMT3A were not statistically significant (all P > 0.05). Conclusions:RUNX1-RUNX1T1 positive AML patients with ASXL2 mutation tend to have low LDH and high PT, and often coexist with RAS mutations, and their prognosis is better than that in patients with ASXL1 positive mutation.

Objective:To compare the pharmacokinetics and safety of single intravenous injection of the generic bevacizumab injection WBP264 and the original bevacizumab injection Avastin ? in healthy male volunteers. Methods:The study was designed as a randomized, double-blind, single dose, parallel, and controlled phase I clinical trial. Healthy male volunteers who were recruited publicly were randomized into the trial group (intravenous infusion of WBP264) and the control group (intravenous infusion of Avastin ?), and the dose was 3 mg/kg. Peripheral venous blood was collected within 30 minutes before administration, 45 minutes after onset of the administration, immediately after finishing the administration, 2.5, 3.5, 5.5, 9.5, 13.5, 24, 48 hours and on the 5th, 8th, 15th, 22nd, 29th, 36th, 43rd, 57th, 71st, 85th, and 99th days after the administration. The plasma concentration was measured by enzyme-linked immunosorbent assay, the plasma concentration-time curve and its semilogarithmic plot were plotted, and the pharmacokinetic parameters such as the area under the plasma concentration-time curve [including AUC from time zero to the time of the last quantifiable concentration (AUC 0-t) and AUC from time zero to infinity (AUC 0-∞)], peak concentration ( Cmax), time to peak ( Tmax), plasma elimination half-life ( t1/2), clearance rate (CL), and apparent volume of distribution (Vd) were calculated. When the 90% confidence intervals ( CI) of the geometric mean ratio of AUC 0-t, AUC 0-∞, and Cmax between the trial group and the control group were between 0.80-1.25, it indicated that pharmacokinetics of WBP264 and Avastin ? were similar. The physical examination, vital signs detection, electrocardiogram, and laboratory tests were performed on the subjects, the occurrence of adverse events (AEs) and the severity classification were recorded, and correlation between the AEs and the trial drug was evaluated. The anti-drug antibody and its neutralizing antibody were detected before administration and on the 8th, 15th, 29th, 43rd, 71st, and 99th days after administration to evaluate the immunogenicity of the drug. Results:A total of 78 subjects were recruited, 39 in the trial group and 39 in the control group. In the trial group, 2 cases withdrew from the trial (1 case did not take the drug and 1 case withdrew for personal reason after taking the drug). Seventy-seven cases were in the safety analysis set and 76 cases in the pharmacokinetic analysis set. The differences in age, height, weight, and body mass index between the 2 groups were not significant (all P>0.05). The plasma concentration-time curves of bevacizumab between the trial group and the control group were similar. The geometric mean ratios (90% CI) of AUC 0-t, AUC 0-∞, and Cmax were 1.04 (0.98-1.10), 1.03 (0.98-1.10), and 1.09 (1.03-1.14), respectively. The differences in the incidence of overall AEs [89.5% (34/38) vs. 87.2% (34/39)] and the incidence of AEs possibly related to the trial drug [86.8% (33/38) vs. 79.5% (31/39)] between the trial group and the control group were not significant (all P>0.05). Only one case of AE in the trial group was grade 3 in severity and was assessed as being not related to the drug, and the rest were grade 1-2, with grade 1 AEs accounting for the vast majority. The difference in the positive rate of anti-drug antibody between the trial group and the control group was not significant [10.5% (4/38) vs. 10.3% (4/39), P>0.05]. The neutralizing antibody test was negative in the patients with positive anti-drug antibody. Conclusion:The pharmacokinetics and safety of WBP264 and Avastin ? are similar.

Chimeric antigen receptor T-cell (CAR-T) therapy is effective in treating lymphoma and leukemia. A large number of basic and clinical studies have led to the rapid development of CAR-T therapy. This paper reviews the concept of CAR-T therapy, the application of CAR-T in hematologic diseases, and the problems and solutions of CAR-T.

Objective:To evaluate the early diagnostic value of tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein-7 (IGFBP-7) in acute kidney injury induced by sepsis.Methods:A total of 85 sepsis patients admitted to the EICU and GICU in Shanghai East Hospital from September 2017 to June 2019 were divided into theAKI group ( n=37) and the non-AKI group ( n=48) according to KIDGO diagnostic criteria, and 20 healthy volunteers were served as the control group. The clinical data were recorded and samples of urine were collected at 0 h, 6 h, 12 h, 1 d, 3 d and 7 d post sepsis. The levels of TIMP-2 and IGFBP-7 in the urine were analyzed with ELISA at different time points. Based on the receiver operating characteristic curve (ROC) and the area under the curve (AUC), the early diagnostic value of urinary TIMP-2 and IGFBP-7 in sepsis-induced AKI patients was determined. Results:Compared with the control group, the levels of TIMP-2 and IGFBP-7 of the AKI group were significantly higher at the above time points ( P<0.05), while those of the non-AKI group showed no significant differences. The levels of TIMP-2 and IGFBP-7 of the AKI group were significantly higher than the those of the non-AKI group ( P<0.05). ROC analysis showed that when the AUC of urine TIMP-2 peaked at 1 d, the sensitivity and specificity reached 97.5% and 81.2%, separately with the cutoff value of 151.23 ng/mL. Furthermore, when the AUC of urine IGFBP-7 peaked at 12 h, the sensitivity and specificity reached 100% and 72.8%, separately with the cutoff value of 14.91 ng/mL. Interestingly, when the AUC of combined TIMP-2×IGFBP-7 peaked at 12 h, the sensitivity reached 98.0% and specificity reached 91.5% with the cutoff value of 2.09 [(ng/mL) 2/1 000]. There was no significant correlation between the levels of TIMP-2 and IGFBP-7 with SOFA and APACHEⅡ score at 1 d, 3 d and 7 d post sepsis in the AKI group ( P>0.05). Conclusions:Urine TIMP-2 and IGFBP-7 have early diagnostic value in sepsis-induced AKI. Besides, the combination of the two biomarkers have superior predictive value than each single of them.