Licochalcone E is a chalcone isolated from Glycyrrhiza uralensis and G. inflata Batal. This study explored the effect of licochalcone E on improving hepatic steatosis in obese mice and evaluated the role of licochalcone E in regulating lipid accumulation in hepatocytes. In vitro, oleic acid–induced hepatocytes were treated with licochalcone E to investigate its effect on lipid metabolic pathways. In animal experiments, male C57BL/6 mice were fed with a high-fat diet (HFD) and treated with licochalcone E by intraperitoneal injection for 12 weeks to assess its effects on biochemical indexes and hepatic steatosis. Furthermore, mice were fed a methionine/choline-deficient (MCD) diet and administered licochalcone E, followed by evaluation of liver fibrosis. Licochalcone E effectively reduced body weight, epididymal and inguinal fat weight, and adipocyte size in HFD-induced obese mice. Licochalcone E treatment of obese mice also reduced hepatic lipid accumulation and improved hepatocyte steatosis. Licochalcone E regulated the expression of lipogenesis- and lipolysis-related genes in the livers of obese mice and increased AMPK phosphorylation and Sirt1 expression in the liver. Licochalcone E also attenuated hepatic inflammation and oxidative stress in obese mice. Furthermore, treatment of MCD-induced mice with licochalcone E reduced the number of lipid vacuoles and the extent of fibrosis and inhibited liver inflammation. In FL83B hepatocytes, licochalcone E could regulate lipogenesis and lipolysis, and increase the phosphorylation of AMPK and ACC. These findings provide new insights into the role of licochalcone E in regulating lipid metabolism and preventing hepatic steatosis.

19 cinnamamide/ester-triazole compounds were designed, synthesized and evaluated for their anti-Alzheimer's disease (AD) activity. Among them, compound 4f displayed excellent anti-β-amyloid protein (Aβ)-mediated cytotoxicity (EC₅₀ = 2.03 ± 2.45 μmol·L^-1) in APPswe cells and acetylcholinesterase inhibiton (IC₅₀ = 4.88 ± 4.70 μmol·L^-1). Further study indicated that, at dosages of (1, 5 and 25 mg·kg^-1), compound 4f was effective in improving spatial learning and memory deficits in Aβ_1-42-impaired mice, which was achieved by promoting the nonamyloidogenic signaling and inhibiting the amyloidogenic pathway, along with the suppression of Aβ-induced Tau phosphorylation. All animal experiments in this study were approved by the Experimental Animal Care and Use Committee of the Institute of Medicinal Biotechnology (IMB-20220908D701). In conclusion, compound 4f holds promise as a lead candidate for AD treatment, and the present study lays the foundation for its subsequent development.

Objectives: . Endotype-based interventions have shown promise in the treatment of patients with obstructive sleep apnea, and upper airway surgery is a key therapeutic option. However, responses to surgery vary among patients with obstructive sleep apnea. This study aims to examine changes in endotypic traits following upper airway surgery and to explore their association with surgical outcomes. Methods: . We prospectively recruited 25 patients with obstructive sleep apnea who visited a single sleep center for upper airway surgery. These patients underwent polysomnographic studies both before and after surgical intervention. During non-rapid eye movement and rapid eye movement sleep, we estimated endotypic traits—including collapsibility (Vpassive), arousal threshold, loop gain, and upper airway compensation—with the phenotyping using polysomnography method. Based on improvements in the apnea-hypopnea index, patients were classified as either responders or non-responders. We compared the preoperative endotypic traits between these groups using Mann-Whitney tests. Additionally, we compared changes in endotypic traits pre- and post-surgery between responders and non-responders using generalized linear mixed models. Results: . We identified 12 responders and 13 non-responders. Compared to non-responders, responders exhibited improved collapsibility during rapid eye movement sleep (22.3 vs. −8.2%eupnea in Vpassive, P=0.01), and their arousal threshold decreased during non-rapid eye movement sleep (−22.4%eupnea, P=0.02). No endotypic trait predicted surgical response; however, the apnea-hypopnea index during rapid eye movement sleep was higher among responders than non-responders (51.8/hr vs. 34.4/hr, P=0.05). Conclusion . Upper airway surgery significantly reduced collapsibility during rapid eye movement sleep in responders. The target pathology for upper airway surgery is a compromised upper airway during rapid eye movement sleep.

Background: Delivering a poor prognosis to patients and their families is critically challenging in pediatric populations. The application of palliative care (PC) provides a bridge between accepting the occurrence of mortality and offering lifelong support.However, little is known about the specifics of PC. This study aims to explore the unmet need for PC in pediatric populations. Methods: We retrospectively reviewed the medical records of mortality cases in the Department of Pediatric Hematology and Oncology at Chang Gung Memorial Hospital. Statistical tests, including Chi-square and Student’s t-tests, were applied to determine the differences between early and late intervention groups in terms of the timing of PC introduction. Results: During the study period, 41 patients were included. Their median age was 11.8 years (IQR, 7.6-15.9). The majority of the disease statuses were refractory or relapsing (R/R). The incidence of memento application was significantly higher in the early intervention group (47.6% vs. 10%, P=0.0081). Vital signs variations tended to be end-of-life (EoL) indicators in this study. Conclusion The early introduction of PC encourages families to accompany their beloved child. EoL signs in the pediatric population include vital sign variations. With the presence of relevant EoL signs, clinical physicians can apply PC earlier to meet the needs.

Background: Delivering a poor prognosis to patients and their families is critically challenging in pediatric populations. The application of palliative care (PC) provides a bridge between accepting the occurrence of mortality and offering lifelong support.However, little is known about the specifics of PC. This study aims to explore the unmet need for PC in pediatric populations. Methods: We retrospectively reviewed the medical records of mortality cases in the Department of Pediatric Hematology and Oncology at Chang Gung Memorial Hospital. Statistical tests, including Chi-square and Student’s t-tests, were applied to determine the differences between early and late intervention groups in terms of the timing of PC introduction. Results: During the study period, 41 patients were included. Their median age was 11.8 years (IQR, 7.6-15.9). The majority of the disease statuses were refractory or relapsing (R/R). The incidence of memento application was significantly higher in the early intervention group (47.6% vs. 10%, P=0.0081). Vital signs variations tended to be end-of-life (EoL) indicators in this study. Conclusion The early introduction of PC encourages families to accompany their beloved child. EoL signs in the pediatric population include vital sign variations. With the presence of relevant EoL signs, clinical physicians can apply PC earlier to meet the needs.

Background: Delivering a poor prognosis to patients and their families is critically challenging in pediatric populations. The application of palliative care (PC) provides a bridge between accepting the occurrence of mortality and offering lifelong support.However, little is known about the specifics of PC. This study aims to explore the unmet need for PC in pediatric populations. Methods: We retrospectively reviewed the medical records of mortality cases in the Department of Pediatric Hematology and Oncology at Chang Gung Memorial Hospital. Statistical tests, including Chi-square and Student’s t-tests, were applied to determine the differences between early and late intervention groups in terms of the timing of PC introduction. Results: During the study period, 41 patients were included. Their median age was 11.8 years (IQR, 7.6-15.9). The majority of the disease statuses were refractory or relapsing (R/R). The incidence of memento application was significantly higher in the early intervention group (47.6% vs. 10%, P=0.0081). Vital signs variations tended to be end-of-life (EoL) indicators in this study. Conclusion The early introduction of PC encourages families to accompany their beloved child. EoL signs in the pediatric population include vital sign variations. With the presence of relevant EoL signs, clinical physicians can apply PC earlier to meet the needs.

Objectives: . Endotype-based interventions have shown promise in the treatment of patients with obstructive sleep apnea, and upper airway surgery is a key therapeutic option. However, responses to surgery vary among patients with obstructive sleep apnea. This study aims to examine changes in endotypic traits following upper airway surgery and to explore their association with surgical outcomes. Methods: . We prospectively recruited 25 patients with obstructive sleep apnea who visited a single sleep center for upper airway surgery. These patients underwent polysomnographic studies both before and after surgical intervention. During non-rapid eye movement and rapid eye movement sleep, we estimated endotypic traits—including collapsibility (Vpassive), arousal threshold, loop gain, and upper airway compensation—with the phenotyping using polysomnography method. Based on improvements in the apnea-hypopnea index, patients were classified as either responders or non-responders. We compared the preoperative endotypic traits between these groups using Mann-Whitney tests. Additionally, we compared changes in endotypic traits pre- and post-surgery between responders and non-responders using generalized linear mixed models. Results: . We identified 12 responders and 13 non-responders. Compared to non-responders, responders exhibited improved collapsibility during rapid eye movement sleep (22.3 vs. −8.2%eupnea in Vpassive, P=0.01), and their arousal threshold decreased during non-rapid eye movement sleep (−22.4%eupnea, P=0.02). No endotypic trait predicted surgical response; however, the apnea-hypopnea index during rapid eye movement sleep was higher among responders than non-responders (51.8/hr vs. 34.4/hr, P=0.05). Conclusion . Upper airway surgery significantly reduced collapsibility during rapid eye movement sleep in responders. The target pathology for upper airway surgery is a compromised upper airway during rapid eye movement sleep.

Objective:To explore the clinical efficacy of Wenshen Chushi Decoction combined with low intensity pulsed ultra-sound(LIPUS)on erectile dysfunction(ED)caused by renal deficiency and phlegm-dampness syndrome.Methods:One hundred and twenty ED patients were included from the Department of Andrology in the First Hospital of Hunan University of Traditional Chinese Medicine.The patients in control group were treated with Wenshen Chushi Decoction.While the patients in observation group were trea-ted with Wenshen Chushi Decoction combined with LIPUS for 8 consecutive weeks.After the treatment,the efficacy was evaluated using the International Index of Erectile Function-5(IIEF-5)score,Penile Flow Index(PFI),Traditional Chinese Medicine Syndrome Score,Self-Rating Depression Scale(SDS)score,and Self-Rating Anxiety Scale(SAS)score.Safety was also observed.And the ef-ficacy was followed up 4 weeks after the end of treatment.Results:Fifty-seven cases were enrolled into control group finally with 55 cases in the treatment group.After the treatment,all the patients in both of groups showed an improvement in IIEF-5 scores(P＜0.01).Compared with the control group(19.09±2.22),the IIEF-5 score in observation group(20.42±2.39)increased signifi-cantly(P＜0.01).After the treatment,the scores of PFI,TCM syndrome and SDS in both groups decreased(P＜0.01,P＜0.05,P＜0.01).Compared with the control group([3.77±1.21],[9.91±1.71]and[39.88±2.63]points),the observation group([2.92±1.08],[4.78±1.45],and[34.51±2.09]points)showed a more significant decrease(P＜0.01).There was no significant difference in total effective rate between the two groups(P＞0.05).During follow-up,the IIEF-5 scores of both groups of patients were higher than those before(P＜0.05,P＜0.01),and the observation group score was higher than that in the control group([17.15±3.37]vs[13.63±1.96],P＜0.01).No adverse reaction and abnormality of indicators occurred in both of two groups.Conclusion:Wenshen Chushi Decoction has a significant therapeutic effect on ED caused by renal deficiency and phlegm-dampness syndrome.It can not only improve the quality of erection,but also improve the physical and mental symptoms associated with ED,which makes therapeutic effect lasting longer.

Objective:To investigate the selection preference and heterogeneity of intervention measures for high-risk population of Cardiovascular Disease in rural areas,and to provide new empirical evidence and path reference for evidence-based CVD intervention strategies.Methods:Using cluster sampling method,a discrete choice experiment was designed to conduct an offline survey on 345 CVD high-risk subjects in one of the CVD high-risk screening sites in Hubei Province.Mixed logit model was used for data analysis.Results:The attributes of"Primary medical staff+County-level medical staff+Experts above county-level","Monthly or longer","Non-drug intervention","Drug intervention+non-drug intervention","One hour",all significantly increased the probability of high-risk population to choose the project,and"Online"mode and"Personalized service package"will significantly reduce the probability of respondents to choose a solution,there were significant differences in the selection preferences of high-risk population with different gender,age,education level,income level and health status.Conclusion:The rural CVD high-risk population obviously prefer the intervention model with high level of service subject,off-line implementation,low frequency,medium intensity,non-drug intervention or combined with drug intervention,and free basic service content.It is necessary to explore a more efficient and suitable intervention scheme for CVD in rural high-risk population according to the demand-side preference and its heterogeneity.

Kv1.3,a voltage-gated potassium channel,is highly expressed in T lymphocytes,the nervous system,and vascular smooth muscle cells.It plays a critical role in membrane excitability and electrical signal transduction,serving as an important target for studying T-cell function and providing a promising direction for developing therapeutics against autoimmune and inflammatory diseases.Therefore,the de-velopment of specific inhibitors of Kv1.3 channel has emerged as a novel therapeutic strategy for these disorders.In this study,we isolated and purified a novel Kv1.3-inhibitory peptide toxin,LmKTx13,from the venom of the scorpion Lychas mucronatus using reversed-phase high-performance liquid chroma-tography(RP-HPLC).LmKTx13 consists of 38 amino acid residues,including six cysteines that form three disulfide bonds.Whole-cell patch-clamp recordings revealed that LmKTx13 potently inhibited Kv1.3 with an IC50 of 7.92±3.0 nmol/L.Selectivity analysis showed that 2 μmol/L LmKTx13 also in-hibited Kv1.2 and Kv1.7,but exhibited no significant effects on other potassium channel subtypes or voltage-gated sodium channels.Further investigation into the mechanism demonstrated that LmKTx13 acts as a pore-blocking inhibitor of Kv1.3.By analyzing the effects of LmKTx13 on Kv1.3 channel gating ki-netics and performing sequence alignment of the pore regions of Kv1.3 and Kv1.5,we constructed site-directed mutants and identified the pore region of Kv1.3 as the critical binding site for LmKTx13.Key residues involved in the interaction included T425,G427,and H451.In summary,we discovered a no-vel pore-blocking Kv1.3 inhibitor,LmKTx13,from L.mucronatus venom,which exhibits high affinity and selectivity for Kv1.3.These findings highlight its potential as a potential lead molecule for developing Kv1.3-targeted therapeutics.