OBJECTIVE To investigate the protective effect of 2-dodecyl-6-methoxy-2，5-diene-1，4-cyclohexanedione （DMDD）， an active component from Averrhoa carambola root， on myocardial injury in diabetic mice based on the nuclear receptor coactivator 4/ferritin heavy chain 1/autophagy-related protein 8 （NCOA4/FTH1/ATG8） axis. METHODS The successfully modeled diabetic mice were randomly divided into model group and DMDD low-， medium-， and high-dose （12.5， 25， 50 mg/kg） groups， while an additional non-modeled control group was established， with 6 mice in each group. Each group received the corresponding drug solution or an equal volume of normal saline intragastically once daily for 21 consecutive days. After the administration， the levels of fasting blood glucose （FBG）， serum lactate dehydrogenase （LDH）， and creatine kinase isoenzyme MB （CK-MB） were measured. Myocardial pathological changes， degree of fibrosis， and myocardial cell ultrastructure were observed. Myocardial cell death index and NCOA4 protein positive index were detected. The protein expression levels of NCOA4， FTH1， ATG8， solute carrier family 7 member 11 （SLC7A11）， and glutathione peroxidase 4 （GPX4） in cardiac tissue were measured. RESULTS Compared with model group， each DMDD group showed significant alleviation of cardiac pathological injury and varying degrees of improvement in the myocardial cell ultrastructure. The FBG and serum LDH and CK-MB levels， the myocardial cell death index and NCOA4 protein positive index，the protein expression levels of NCOA4， FTH1， and ATG8 in cardiac tissue were significantly decreased （ P ＜0.001）， while the protein expression levels of SLC7A11 and GPX4 were significantly increased （ P ＜0.001）. CONCLUSIONS DMDD can reduce blood glucose levels， alleviate myocardial histopathological injury， and inhibit cell death in diabetic mice. The mechanism is associated with inhibiting excessive activation of the NCOA4/FTH1/ATG8 axis and reducing ferritinophagy.

This study retrospectively analyzed 12 patients with transfusion-dependent, non-severe aplastic anemia (TD-NSAA) refractory to cyclosporine A (CsA) , who were treated with lusutrombopag monotherapy. These patients either had a variety of chronic comorbidities or medication-related risks, or they were unresponsive to or intolerant of other thrombopoietin receptor agonists (TPO-RA) . The median treatment duration with lusutrombopag was 4 months (range: 3-11 months) , while the median follow-up period was 8 months (range: 6-11 months) . The overall response (OR) rates at months 3, 6, and the end of follow-up were 50.0%, 58.3%, and 50.0%, respectively, with a median time to OR of 2 months (range: 1-4 months) . Complete response (CR) rates were 8.3%, 16.7%, and 16.7% at the same time points, with a median time to CR of 4 months (range: 2-5 months) . Adverse events were all Grade 1, with an incidence rate of 25.0%. During follow-up, one patient experienced a loss of OR after discontinuing treatment, with a relapse rate of 14.3%; no clonal evolution or mortality was observed. These findings suggest that lusutrombopag is both effective and well-tolerated in CsA-refractory TD-NSAA patients and represents a promising therapeutic option for those with poor treatment tolerability.

OBJECTIVES: To investigate the regulatory role of astrocytes in the dorsomedial hypothalamus (DMH) during sevoflurane anesthesia emergence. METHODS: Forty-two male C57BL/6 mice were randomized into 6 groups (n=7) for assessing astrocyte activation in the dorsomedial hypothalamus (DMH) under sevoflurane anesthesia. Two groups of mice received microinjection of agfaABC1D promoter-driven AAV2 vector into the DMH for GCaMP6 overexpression, and the changes in astrocyte activity during sevoflurane or air inhalation were recorded using calcium imaging. For assessing optogenetic activation of astrocytes, another two groups of mice received microinjection of an optogenetic virus or a control vector into the DMH with optic fiber implantation, and sevoflurane anesthesia emergence was compared using behavioral experiments. In the remaining two groups, electroencephalogram (EEG) recording during sevoflurane anesthesia emergence was conducted after injection of the hChR2-expressing and control vectors. Anesthesia induction and recovery were assessed by observing the righting reflex. EEG data were recorded under 2.0% sevoflurane to calculate the burst suppression ratio (BSR) and under 1.5% sevoflurane for power spectrum analysis. Immunofluorescence staining was performed to visualize the colocalization of GFAP-positive astrocytes with viral protein signals. RESULTS: Astrocyte activity in the DMH decreased progressively as sevoflurane concentration increased. During 2.0% sevoflurane anesthesia, the mice injected with the ChR2-expressing virus exhibited a significantly shortened wake-up time (P<0.05), and optogenetic activation of the DMH astrocytes led to a marked reduction in BSR (P<0.001). Under 1.5% sevoflurane anesthesia, optogenetic activation resulted in a significant increase in EEG gamma power and a significant decrease in delta power in ChR2 group (P<0.01). CONCLUSIONS Optogenetic activation of DMH astrocytes facilitates sevoflurane anesthesia emergence but does not significantly influence anesthesia induction. These findings offer new insights into the mechanisms underlying anesthesia emergence and may provide a potential target for accelerating postoperative recovery and managing anesthesia-related complications.
Animals ; Astrocytes/physiology* ; Sevoflurane ; Mice, Inbred C57BL ; Mice ; Male ; Electroencephalography ; Anesthetics, Inhalation/pharmacology* ; Hypothalamus/cytology* ; Anesthesia Recovery Period ; Methyl Ethers/pharmacology*

OBJECTIVES: To assess the therapeutic effect of aucubin in mice with knee osteoarthritis (KOA) and investigate the underlying mechanism. METHODS: Sixty C57BL/6J mice were randomized equally into sham operation group, KOA model group, glucosamine (positive control) treatment group, and low-, medium-, and high-dose aucubin treatment groups (2, 4, and 8 mg/kg, respectively). KOA mouse models were established by transection of the anterior cruciate ligament (ACL), and the treatment was initiated on day 1 postoperatively and administered weekly for 8 weeks. Safranin O-fast green staining, immunohistochemistry, and microCT were used to evaluate the changes in cartilage pathology, inflammatory protein expression, and subchondral bone volume fraction (BV/TV). The expression levesl of COL2, SOX9, p-P65, IL-1β and MMP13 proteins in the cartilage tissues were detected using Western blotting. In a chondrocyte model with IL-1β treatment for mimicking KOA, the effect of aucubin on chondrogenic differentiation was observed with Alcian blue and Safranin O staining, and cellular COL2, SOX9 and TNF‑α mRNA expressions were detected with RT-qPCR. RESULTS: Compared with those in the model group, the mouse models receiving aucubin treatment showed significantly upregulated COL2 and SOX9 protein levels and downregulated p-P65, IL-1β and MMP13 expressions in the cartilage tissues. In the IL-1β-induced chondrocyte model, aucubin treatment significantly upregulated the mRNA expressions of SOX9 and COL2 but lowered the mRNA expression of TNF-α. Alcian blue and Safranin O staining confirmed that aucubin promoted the synthesis of cartilage extracellular matrix and enhanced chondrogenic differentiation of the cells. CONCLUSIONS Aucubin can effectively alleviate KOA in mice by inhibiting NF‑κB-mediated cartilage inflammation, promoting cartilage matrix synthesis, and improving subchondral bone microstructure.
Animals ; Mice, Inbred C57BL ; Mice ; Osteoarthritis, Knee/drug therapy* ; Signal Transduction/drug effects* ; NF-kappa B/metabolism* ; Iridoid Glucosides/therapeutic use* ; SOX9 Transcription Factor/metabolism* ; Chondrocytes/drug effects* ; Male ; Interleukin-1beta/metabolism* ; Matrix Metalloproteinase 13/metabolism* ; Collagen Type II/metabolism* ; Disease Models, Animal

As a unique type of job burnout,caregiving burnout not only reduces the quality of care,but also significant impacts the physical and mental health of both caregivers and care recipinets,extending its affects to families and society at large.This paper reviews the concept,measurement tools,and theoretical models of caregiv-ing burnout;and examines its antecedent and consequential variables.Future research should focus on distinguishing between formal and informal caregiving burnout,improving measurement methods,and developing effective inter-vention strategy tailoered to Chinese culture context.

As a unique type of job burnout,caregiving burnout not only reduces the quality of care,but also significant impacts the physical and mental health of both caregivers and care recipinets,extending its affects to families and society at large.This paper reviews the concept,measurement tools,and theoretical models of caregiv-ing burnout;and examines its antecedent and consequential variables.Future research should focus on distinguishing between formal and informal caregiving burnout,improving measurement methods,and developing effective inter-vention strategy tailoered to Chinese culture context.

This study retrospectively analyzed 12 patients with transfusion-dependent, non-severe aplastic anemia (TD-NSAA) refractory to cyclosporine A (CsA) , who were treated with lusutrombopag monotherapy. These patients either had a variety of chronic comorbidities or medication-related risks, or they were unresponsive to or intolerant of other thrombopoietin receptor agonists (TPO-RA) . The median treatment duration with lusutrombopag was 4 months (range: 3-11 months) , while the median follow-up period was 8 months (range: 6-11 months) . The overall response (OR) rates at months 3, 6, and the end of follow-up were 50.0%, 58.3%, and 50.0%, respectively, with a median time to OR of 2 months (range: 1-4 months) . Complete response (CR) rates were 8.3%, 16.7%, and 16.7% at the same time points, with a median time to CR of 4 months (range: 2-5 months) . Adverse events were all Grade 1, with an incidence rate of 25.0%. During follow-up, one patient experienced a loss of OR after discontinuing treatment, with a relapse rate of 14.3%; no clonal evolution or mortality was observed. These findings suggest that lusutrombopag is both effective and well-tolerated in CsA-refractory TD-NSAA patients and represents a promising therapeutic option for those with poor treatment tolerability.

In recent years， NOD-like receptor protein 3 （NLRP3） inflammasome in tumors has become a research hotspot， especially in melanoma， colorectal cancer， lung cancer， and breast cancer， and more and more evidence has shown that inflammation plays a role in the development， progression， angiogenesis， and invasion of cancer. Hepatocellular carcinoma （HCC） is the most common type of primary liver cancer， and there are still controversies over the role of NLRP3 inflammasome in the development and progression of HCC. Therefore， this article reviews the potential impact of NLRP3 inflammasome in the progression of HCC and its mechanism of action in anticancer therapy， and it is believed that NLRP3 inflammasome can be used as an effective therapeutic target for HCC patients.

Objective To explore the risk factors for acute thrombosis of arteriovenous fistulae(AF)in maintenance hemodialysis(MHD)patients and the construction of a Nomogram prediction model.Methods A total of 418 patients who underwent MHD treatment in the outpatient clinic of the Third Affiliated Hospital of Xinxiang Medical University from December 2020 to December 2022 were selected for the study.The patients were divided into the acute thrombosis group(n=32)and non-acute thrombosis group(n=386)according to whether acute thrombosis of AF was formed or not.The influencing factors affecting acute thrombosis of AF in MHD patients were analyzed using univariate and multivariate analysis.A Nomogram predic-tion model was established based on their independent risk factors,and Bootstrap was used to validate the efficacy of the Nomo-gram model.Results The complicated diabetes,complicated hypotension,puncture failure on dialysis,calcium-phosphorus product,hypersensitive C-reactive protein(hs-CRP),total cholesterol(TC),and low density lipoprotein-cholesterol(LDL-C)levels in patients in the acute thrombosis group were significantly higher than those in the non-acute thrombosis group(P＜0.05);logistic regression analysis showed that diabetes,hypotension,puncture failure on dialysis,calcium-phosphorus product elevation,high hs-CRP and high LDL-C level were the independent risk factors affecting acute thrombosis of AF in patients undergoing MHD(P＜0.05);the Nomogram model was constructed based on the 6 independent risk factors,and the consistency index(C-index)of the model was 0.893(95％confidence interval:0.833-0.928);in addition,its calibration curve and the standard curve were well fitted,the area under the curve was 0.918.Conclusion Diabetes,hypotension,puncture failure during dialysis,calcium-phosphorus product elevation,and high levels of hs-CRP and LDL-C are the risk factors for acute thrombosis of AF in patients undergoing MHD,and the Nomogram model constructed based on the independent risk factors has excellent predictive ability in predicting the occurrence of acute thrombosis of AF in patients undergoing MHD,which can help in the early screening of patients with high risk of clinical acute thrombosis.

Objective To evaluate the acceptability and effectiveness of different doses of midazolam oral solution in sedating infants during echocardiographic studies.Methods Two hundred and fourty patients aged 1 to 3 years who underwent echocardiographic study in sedation in our hospital were enrolled in this study.After recording the baseline data of all infants,they were randomly divided into four groups:0.3 mg·kg-1 midazolam oral solution group(M1 group),0.5 mg·kg-1 midazolam oral solution group(M2 group),0.7 mg·kg-1 midazolam oral solution group(M3 group)and 0.5 mL·kg-1 10%chloral hydrate administrated rectally group(C group),60 case per group,and the sedation was performed in the corresponding method of each group.The 5-point facial hedonic and Ramsay scales were used to evaluate acceptability and effectiveness in sedation.The onset time and duration time of sedation were recorded.Results Compared with the C group,the 5-point facial hedonic scale scores in M1,M2,and M3 groups increased during sedation(F=17.50,P<0.017).The onset time of sedation in the M1 and M2 groups was longer than that in the C group(P<0.017),and the duration time of sedation in the M1 and M2 groups was shorter than that in the C group(P<0.017).There was no significant difference in the onset time(P=0.85)and duration time(P=0.50)of sedation between the M3 and C groups.The onset time of sedation in the M1and M2groups was longer than that in the M3 group(P<0.017),and the duration time of sedation in the M1 and M2 groups were shorter than that in the M3 group(P<0.017).Conclusions The acceptability of infants with midazolam oral solution sedation under echocardiographic study was better than that of 10%chloral hydrate administrated rectally.There were fewer adverse reactions with the midazolam oral solution.The 0.7 mg·kg-1 midazolam oral solution had a rapid onset of sedation and definite effect.