Enzymatic cascade catalysis has emerged as an effective means to enhance the sensitivity of biosensors due to its remarkable amplification effect on electrochemical signals.However,the most used natural enzymes have high specificity and high catalytic activity,but are susceptible to environmental factors,easy denaturation and inactivation,and high cost,which limit their practical applications.Additionally,the majority of nanozymes with excellent catalytic activity cannot be directly used as redox probes.The redox signal can only be required under high potentials in strong acid/alkali solutions,or functionalized with electroactive substances.To tackle this problem,herein,AuNPs(glucose oxidase-like activity)and Mn,Zr dual-doped CeO2 nanozymes(Mn,Zr-CeO2,peroxidase-like activity)were used as model enzymes to construct a high-performance nanozymes cascade catalytic system.Owing to high Ce4+/Ce3+ratio and a considerable number of oxygen vacancies,Mn,Zr-CeO2 nanozymes exhibited excellent peroxidase-like activity and could generate amplified electrochemical signals in neutral medium at low potentials.Furthermore,the porous structure of Mn,Zr-CeO2 nanozymes could accelerate the mass transfer of intermediate H2O2,thereby enhancing the efficiency of enzymatic cascade catalysis.As a result,a label-free electrochemical biosensor was constructed for sensitive detection of the cancer marker miRNA-21 at physiological pH,with a detection limit as low as 32.5 fmol/L.This strategy offered a novel approach for the development of a new generation of high-performance nanozymes cascade platforms,which could be widely applied in the fields such as biotechnology,bioanalysis,and disease diagnosis.

OBJECTIVE: To retrospectively analyze the clinical data of newly diagnosed acute myeloid leukemia (AML) patients treated with venetoclax combined with azacitidine (Ven/Aza) or standard "3+7" regimen and similar regimens, collect real-world study data, compare the treatment response and adverse events between the two regimens, as well as perform survival analysis. METHODS: To retrospectively analyze the efficacy, survival, and adverse reactions of newly diagnosed AML patients treated with Ven/Aza (24 cases) and "3+7" regimens (117 cases ) in our hospital from September 2009 to March 2023, as well as factors influencing outcomes. A propensity score matching (PSM) was performed on age and Eastern Cooperative Oncology Group performance status (ECOG PS) to obtain a 1:1 matched cohort of 20 pairs, and the efficacy and survival before and after the matching were compared. RESULTS: The median age of patients in the Ven/Aza group was 69 years, while that in the "3+7" group was 56 years (P <0.001). Objective remission rate (ORR) was 62.5% in Ven/Aza group and 74.8% in "3+7" group (P >0.05). The median overall survival (OS) in the Ven/Aza group was 522 days, while that in the "3+7" group was 1 002 days (P >0.05). After controlling the two variables of age and ECOG PS, a PSM cohort of 20 pairs was obtained, in which the ORR was 65% in Ven/Aza group and 60% in "3+7" group (P >0.05). The median OS was 522 days and 629 days, and median progression-free survival (PFS) was 531 days and 198 days between the two groups, respectively. There were no statistically significant differences in OS and PFS between the two groups (both P >0.05). Additionally, the incidence of adverse events in the Ven/Aza group was significantly reduced. CONCLUSION The overall cohort shows that the "3+7" regimen has advantages in efficacy and survival, but Ven/Aza regimen is relatively safer. After performing PSM on age and ECOG PS, the Ven/Aza group showed improved efficacy, and a longer median PFS compared to "3+7" group.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Retrospective Studies ; Sulfonamides/administration & dosage* ; Azacitidine/administration & dosage* ; Bridged Bicyclo Compounds, Heterocyclic/administration & dosage* ; Aged ; Middle Aged ; Male ; Female ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Treatment Outcome

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

[This corrects the article DOI: 10.1016/j.apsb.2022.03.002.].

OBJECTIVE: To compare the effects of different chest compression rates (60-140 times/min) on hemodynamic parameters, return of spontaneous circulation (ROSC), resuscitation success, and survival in a porcine model of cardiac arrest (CA) followed by cardiopulmonary resuscitation (CPR). METHODS: Forty healthy male domestic pigs were randomly divided into five groups based on chest compression rate: 60, 80, 100, 120, and 140 times/min (n = 8). All animals underwent standard anesthesia and tracheal intubation. A catheter was inserted via the left femoral artery into the thoracic aorta to monitor aortic pressure (AOP), and another via the right external jugular vein into the right atrium to monitor right atrial pressure (RAP). In each group, animals were implanted with a stimulating electrode via the right external jugular vein to the endocardium, and ventricular fibrillation (VF) was induced by delivering alternating current stimulation, resulting in CA. After a 1-minute, manual chest compressions were performed at the assigned rate with a compression depth of 5 cm. The first defibrillation was delivered after 2 minutes of CPR. No epinephrine or other pharmacologic agents were administered during the entire resuscitation process. From 1 minute before VF induction to 10 minutes after ROSC, dynamic monitoring of AOP, coronary perfusion pressure (CPP), and partial pressure of end-tidal carbon dioxide (P_ETCO₂). Cortical ultrastructure was examined 24 hours post-ROSC using transmission electron microscopy. RESULTS: With increasing compression rates, both the total number of defibrillations and cumulative defibrillation energy significantly decreased, reaching their lowest levels in the 120 times/min group. The number of defibrillations decreased from (4.88±0.83) times in the 60 times/min group to (2.25±0.71) times in the 120 compressions/min group, and energy from (975.00±166.90)J to (450.00±141.42)J. However, both parameters increased again in the 140 times/min group [(4.75±1.04)times, (950.00±207.02)J], the differences among the groups were statistically significant (both P < 0.01). As compression frequency increased, P_ETCO₂, pre-defibrillation AOP and CPP significantly improved, peaking in the 120 times/min group [compared with the 60 times/min group, P_ETCO₂ (mmHg, 1 mmHg≈0.133 kPa): 18.69±1.98 vs. 8.67±1.30, AOP (mmHg): 95.13±7.06 vs. 71.00±6.41, CPP (mmHg): 14.88±6.92 vs. 8.57±3.42]. However, in the 140 times/min group, these values declined significantly again [P_ETCO₂, AOP, and CPP were (10.59±1.40), (72.38±11.49), and (10.36±4.57) mmHg, respectively], the differences among the groups were statistically significant (all P < 0.01). The number of animals achieving ROSC, successful resuscitation, and 24-hour survival increased with higher compression rates, reaching a peak in the 120 times/min group (compared with the 60 times/min group, ROSC: 7 vs. 2, successful resuscitation: 7 vs. 2, 24-hour survival: 7 vs.1), then decreased again in the 140 times/min group (the animals that ROSC, successfully recovered and survived for 24 hours were 3, 3, and 2, respectively). Transmission electron microscopy revealed that in the 60, 80, and 140 times/min groups, nuclear membranes in cerebral tissue were irregular and incomplete, nucleoli were indistinct, and mitochondria were swollen with reduced cristae and abnormal morphology. In contrast, the 100 times/min and 120 times/min groups exhibited significantly attenuated ultrastructural damage. CONCLUSIONS Among the tested chest compression rates of 60-140 times/min, a chest compressions frequency of 120 times/min is the most favorable hemodynamic profile and outcomes during CPR in a porcine CA model. However, due to the wide spacing between groups, further investigation is needed to determine the optimal compression rate range more precisely.
Animals ; Cardiopulmonary Resuscitation/methods* ; Swine ; Male ; Heart Arrest/therapy* ; Heart Massage/methods* ; Hemodynamics

Objective To explore the influence of Da Vinci robot-assisted different approaches of laparoscopic partial nephrectomy(LPN)on the renal function and intestinal function recovery in the treatment of central renal tumors.Methods Totally 100 patients with central renal tumors who received Da Vinci robot-assisted LPN in the Central Hospital of Enshi Tujia and Miao Autonomous Prefecture were selected from November 2022 to March 2024.According to the consent of the patients,they were divided into transperitoneal group and retroperitoneal group by envelope drawing method,with 50 cases in each group.The transperitoneal group adopted transperitoneal approach,while the retroperitoneal group received retroperitoneal approach.The surgical status and postoperative recovery status,renal function[serum creatinine(Scr),glomerular filtration rate(GFR)and blood urea nitrogen(BUN)],intestinal function recovery status[restore exhaust time,plasma diamine oxidase(DAO),D-lactic acid and urinary lactulose/mannose(L/M)]and complications were compared between groups.Results The surgical time,intraoperative blood loss,renal warm ischemia time,restore exhaust time,urinary catheter indwelling time and hospitalization time with(126.76±23.89)h,(115.86±6.93)ml,(25.41±6.57)min,(2.29±0.56)d,(4.89±0.93)d and(11.08±1.92)d in transperitoneal group were longer or more than the retroperitoneal group[(111.58±21.86)h,(86.27±6.71)ml,(17.08±5.16)min,(1.73±0.43)d,(3.16±0.62)d and(9.29±2.07)d,all P＜0.05].1 month after surgery,the SCr level in transperitoneal group with(83.04±10.13)μmol/L was lower than(88.55±9.16)μmol/L in retroperitoneal group while the GFR value with(58.27±6.19)ml/min was higher than(54.36±6.05)ml/min in retroperitoneal group(P＜0.05).The levels of DAO,D-lactic acid and the value of urine L/M with(3.39±0.57)mg/L,(2.09±0.31)mg/L and(0.08±0.02)in transperitoneal group at 24 hours after surgery,which were higher than the retroperitoneal group[(3.07±0.46)mg/L,(1.72±0.25)mg/L and(0.05±0.02),P＜0.05].The total incidence rates of postoperative complications in transperitoneal group and retroperitoneal group were 12.00％and 8.00％(P＞0.05).Conclusion The two approaches of LPN assisted by Da Vinci robot have their own advantages in the treatment of central renal tumors.Transperitoneal approach is more conducive to improving renal function,but retroperitoneal approach is more conducive to shortening the postoperative recovery time and promoting the intestinal function recovery and has lower incidence rates of complications.

The glymphatic system is a recently discovered essential waste-clearance pathway in the central nervous system that plays a pivotal role in maintaining brain homeostasis.Growing evidence suggests that dysfunction of this system is closely associated with the pathogenesis of various neurodegenerative disorders;however,its precise mechanistic involvement in Parkinson's disease is poorly understood.This review systematically summarizes the structural and functional characteristics of the glymphatic system,provides an in-depth exploration of its potential role in Parkinson's disease pathophysiology,and synthesizes current research evidence on glymphatic system-targeted therapeutic strategies,with the aim of establishing a theoretical foundation for advancing the understanding of PD pathogenesis and developing novel diagnostic and therapeutic approaches.

Objective To investigate the influence of the liver failing to convey and disperse on space navigation aging.Methods High and low neuroticism subjects screened by Eysenck personality questionnaire were included in liver failing to convey and disperse group and liver controlling conveyance and dispersion group,respectively.The two groups were then divided into youth and elderly groups based on age.Finally,spatial navigation task was conducted to record and analyze behavioral(reaction time and accuracy)and EEG data(amplitude and latency of P2 and N2 components)of all the four groups(30 subjects each group).Results Compared with liver controlling conveyance and dispersion group,the accuracy in subjects with liver failing to convey and disperse decreased significantly(P<0.001)and reaction time was prolonged significantly(P<0.05).The interaction effect between age and liver regulation status showed a marginal significant difference(P=0.078).The accuracy of elderly people was lower than that of youth people(P=0.002)for liver failing to convey and disperse subjects,while there was no significant difference between the two groups for subjects with liver controlling conveyance and dispersion.The P2 amplitude in the elderly group was significantly smaller than that in the youth group(P=0.027).The amplitude of P2 in group of liver failing to convey and disperse was significantly smaller than that in group of liver controlling conveyance and dispersion(P=0.042).The interaction effect of P2 amplitude between age and liver regulation status showed a marginal significance(P=0.073).For youth subjects,the P2 amplitude in group of liver controlling conveyance and dispersion was significantly larger than that in group of liver failing to convey and disperse(P=0.007),while there was no significant difference in P2 amplitude between the two groups for the elderly subjects.The N2 amplitude for tasks of allocentric frames of reference was significantly greater than that of egocentric frames of reference(P=0.024).Conclusion Liver failing to convey and disperse caused by long-term emotional disturbance accelerates spatial navigation aging,and selective attention feature inhibition disorder may be the underlying ERPs neuroelectrophysiological mechanism.

Objective To investigate the influence of the and mechanism of liver failing to convey and disperse on age-related changes in attentional search based on ERPs.Methods oddball attention search task was administrated to record and analyze behavioral and EEG data(N2pc、SPCN、N2pc-Ptc components)of 120 subjects.Results Compared with liver controlling conveyance and dispersion group,the accuracy in subjects with liver failing to convey and disperse decreased significantly(P<0.05).The elderly group had a lower accuracy(P<0.001)and a longer reaction time(P<0.001)compared to the young group.The N2pc amplitude in subjects with liver failing to convey and disperse was significantly greater than that in subjects with liver controlling conveyance and dispersion(P<0.05).The interaction effect of SPCN amplitude between age and liver failing to convey and disperse status was significant(P=0.024).And in the elderly group,SPCN amplitude in subjects with liver dysregulation was significantly smaller than that of liver controlling conveyance and dispersion(P=0.042).The N2pc-Ptc peak to peak amplitude interaction effect between age and liver regulation status was marginal significant(P=0.087),and in liver failing to convey and disperse group,N2pc-Ptc peak to peak amplitude of the elderly was significantly smaller than that of the young(P=0.008).Conclusion Attention search ability is impaired in the elderly with liver failing to convey and disperse,and the electrophysiological abnormalities,such as directed attention allocation,spatiotemporal dynamic cohesion and short-term memory maintenance,may be part of the mechanism.