Objectives Our previous study has demonstrated that hydrogen sulfide (H 2 S), a novel gasotransmitter, attenuates excessive autophagy and depressive-like behaviors in chronic restraint stress (CRS)-exposed rats, but the underlying molecular mechanism remains to be elucidated. Silent information regulator 1 (SIRT1), a deacetylase at the consumption of NAD+ plays an important regulatory role in depression. Hence, this study aimed to investigate whether SIRT1 mediates the protective effect of H 2 S on CRS-induced depressive-like behaviors by regulating hippocampal autophagy. Methods Adult male Sprague-Dawley (SD) rats were subjected to CRS (6 h × 28 days) to induce depression-like behavior. Rats were injected with sodium hydrosulfate (NaHS, 100 μmol/kg/d, i.p.), as a donor of H 2 S, alone or in combination with Sirtinol (a SIRT1 inhibitor; 10 nmol, i.c.v.) during CRS process. The depression-like characteristics of rats were assessed by the novelty-suppressed feeding test (NSFT), tail suspension test (TST), forced swimming test (FST) and open field test (OFT). The number of hippocampal autophagosomes was detected by transmission electron microscopy. The expressions of hippocampal autophagy-related proteins were measured by western blotting analysis. Results Sirtinol blocked the inhibitory effect of H 2 S on depressive-like behaviors in CRS-exposed rats according to NSFT, TST, FST and OFT. In addition, sirtinol reversed the protective response of H 2 S to CRS-induced excessive autophagy, as proved by the increases in the number of autophagosomes and the expression of Beclin-1 as well as a decrease in the expression of P62 in the hippocampus. Conclusion These results indicated that SIRT1 contributes to the antidepressant-like function of H 2 S during CRS via reducing hippocampal autophagy.
Objective
To explore the therapeutic effect of group cognitive-behavioral therapy (GCBT) for obsessive-compulsive disorder (OCD).
Methods
This study used a randomized controlled trial design to compare GCBT with routine medication treatment. Unmedicated ninety-four patients who met the inclusion criteria were recruited and randomly allocated to GCBT group (n=47) and drug treatment group (n=47) by a simple random grouping method using the RAND function in Excel software which generated a table of random numbers to form a random grouping sequence. Both groups were treated for 12 weeks. The average reduction rate and value of Y-BOCS, HAMA14 and HAMD24 were compared between the two groups, t-test,chi-square (χ2) test and variance analysis (ANOVA) were condulted to analyze data.
Results
(1) There was no significant difference between two groups in Y-BOCS and HAMA14 scores at baseline (t=0.281,P=0.779; t=0.795,P=0.429), but HAMD24 scores were significantly different (t=2.316, P<0.05). Sixteen patients in GCBT group and sixteen in drug treatment group dropped out of treatment, resulted a total drop-out rate of 34%. There was no significant difference in the drop-out rate between the two groups. (2) After 12-week treatment, the Y-BOCS scores decreased compared to pre-treatment in both groups. There was no statistical difference in the mean reduction rate ((37.0±27.4)% vs. (45.5±22.9)%) and score (9.0±6.3 vs.11.0±5.8) of Y-BOCS (F(1,62)=0.069, P=0.794; F(1,62)=0.001, P=0.975) before and after treatment between the two groups. There was no statistical difference in the effective and cure rate between the two groups (χ2=1.653, P=0.199; χ2=0.088, P=0.767) . (3) There was no significant difference in the mean reduction rate and score of HAMA14 (t=-0.922, P=0.362; t=1.082, P=0.286). (4) No significant difference was found regarding the mean reduction rate of HAMD24 between the two groups, but the mean reduction scores of HAMD24 in the medication group were significantly higher than those in GCBT group (t=2.239, P=0.029).
Conclusion
GCBT is equivalent to conventional medication treatment for obsessive-compulsive and anxiety symptoms for OCD patients, and medication treatment is superior to GCBT in depressive symptoms.
Key words:
Obsessive-compulsive disorder; Cognitive therapy; Group structure; Randomized controlled trials
e16183 Background: Hepatocellular carcinoma (HCC) patients with macrovascular invasion (MVI) are considered to be at an advanced stage of disease with limited treatment options. The combination therapy of atezolizumab (atezo) plus bevacizumab (bev) has become a global standard of care for those patients and made conversion resection possible. The Chinese TALENTop study (NCT04649489) is aiming to clarify whether hepatic resection may provide additional benefit in HCC patients with MVI responding to atezo/bev. For patients without opportunity to receive hepatic resection, subsequent treatment outcomes will be reported. Methods: Potentially resectable HCC patients with MVI and without extrahepatic metastasis are eligible for this study. Eligible patients receive 3 cycles of atezo/bev and 1 cycle of atezo as primary systemic therapy (induction phase). Patients assessed as partial response (PR) or stable disease (SD) per RECIST v1.1 and considered suitable for R0 hepatic resection are randomized in a 1:1 ratio to either Arm A, hepatic resection followed by atezo/bev for 1 year, or Arm B, continuing atezo/bev therapy. The primary endpoint is the time to treatment failure. Patients failed to be randomized will enter the survival follow-up phase. After 296 patients entered induction phase, the patient profile, subsequent treatments per local standard of care and survival of patients who failed to be randomized were analyzed. Results: From Apr 2021 to Jun 2023, 296 patients were enrolled and entered induction phase and 175 patients failed to be randomized and were followed up until Sept 2023. The main reasons for failure to be randomized were disease progression (64.6%), investigator assessment of unsuitability for R0 hepatic resection (14.3%), and others. The 175 patients were characterized with a median age of 52 (26-76), and 166 (95%) had HBV infection. Among them, 165 (94%) had combined PVTT, 24 (14%) had combined HVTT and 5 (3%) had combined IVCTT. At a median follow-up time of 10.9 months (9.7-13.1), the median overall survival (mOS) is 13.8 months (8.9-15.8), 6- and 12-month survival rate were 71% and 53%, respectively. As the result of best response during induction phase, 3 patients (1.7%) achieved PR, 92 patients (52.6%) achieved SD and 65 patients (37.1%) were PD. 123 patients (70%) received subsequent therapy. The mOS of patients received different subsequent therapies was showed below. Conclusions: This study provides data on HCC patients with MVI after receiving atezo/bev. The result shows favorable survival even in patients failed to randomization to receive conversion resection, and subsequent treatment strategy may differ survival outcomes. Clinical trial information: NCT04649489 . [Table: see text]
The understanding of the organization of postsynaptic signaling systems at excitatory synapses has been aided by the identification of proteins in the postsynaptic density (PSD) fraction, a subcellular fraction enriched in structures with the morphology of PSDs. Here we described an efficient way to isolate the crude synaptosome, presynaptic fraction, and PSD fraction. It helps to identify the location of synaptic protein and find the potential synaptic complex.
Effects of solution and aging treatment on microstructure and mechanical properties of rolled AM50+xCa alloys(x=0, 1, 2 wt. %) were studied. The results indicated that, with increasing solution time i, the secondary phase Mg17Al12 was dissolved into the Mg matrix and Al2Ca became thinner and shorter, then gradually broken and spheroidized.With an increase of aging time, Mg17Al12 precipitated from the Mg matrix in the form of particles and Al2Ca changed a little. After solution treatment, hardness and tensile properties of the alloy’s decreased. After the aging treatment, the alloy’s hardness increased first and decreased later while the tensile properties increased little. The solution and aging treatment can increase the ductility of AM50 and AM50+1Ca alloys. For AM50+2Ca alloy, the ductility increased after solid solution treatment and decreased after aging treatment.
Hepatic arterial infusion chemotherapy (HAIC) with the FOLFOX regimen has demonstrated efficacy in patients with unresectable hepatocellular carcinoma (HCC). The combined targeted and immunotherapy has emerged as a first-line treatment for liver cancer. In this study, we investigated the clinical efficacy and safety of FOLFOX-HAIC in combination with targeted immunotherapy in patients with untreated, unresectable HCC.
Experiments were conducted both to evaluate the potential for grain refinement, the subsequent mechanical properties at room temperature in samples of AZ31 Mg alloy and also to investigate the relationship between one-step and two-step high ratio extrusion (HRE). The one-step HRE was undertaken using a high extrusion ratio of 70:1 at 250, 300 and 350°C. And the two-step HRE was conducted with an extrusion ratio of 7 for the first step at 250, 300 and 350°C, followed by a second-step extrusion with an extrusion ratio of 10 at 250, 300 and 350°C. The initial grain size in the AZ31 ingot was 100μm and that after one-step HRE became similar to 5μm, after two-step HRE at 250, 300 and 350°C were 2, 4, 7μm, respectively, resulting in superior mechanical properties at ambient temperature. The microstructure of two-step HRE was finer and uniformer than that of one-step HRE and the strength of one-step and two-step HRE were similar, moreover, the elongation of one-step HRE was improved markedly than that of two-step HRE. Dynamic recrystallization and adjacent grain broking during HRE is introduced to explain the effects of one-step and two-step HRE on the microstructure and mechanical properties of AZ31 Mg alloy. The current results imply that the simple HRE method might be a feasible processing method for industry applications, and the multiply steps extrusion are effective to fabricate high strength of fine grained hcp metals.
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