ObjectiveTo explore the potential categories and characteristics of the public hospice care demand in Hainan Province， and analyze different potential types of influencing factors， so as to provide reference for relevant departments to improve the public awareness and demand of hospice care. MethodsUsing convenience sampling method， select 6484 cities of the public as the survey object， using the general data questionnaire， the hospice care demand questionnaire of the potential profile analysis， and analyze the influencing factors of the public hospice care demand category. ResultsThe characteristics of the hospice care demand in Hainan Province were divided into three potential categories： low demand group （14.19%）， medium demand group （49.99%） and high demand group （35.82%）. Multivariate analysis showed that gender， age， education level， cultural belief， and life-death education experience were the main influencing factors of public hospice care demand （p<0.05）. Males， those aged 41-60 years， and those with high school education or below had relatively lower hospice care demand， while those with life-death education experience had relatively higher demand. ConclusionRelevant departments should focus on hospice care knowledge popularization and demand enhancement for males， middle-aged groups， and people with low education levels， while strengthening universal life-death education through stratified and classified publicity strategies and educational interventions to improve different populations’ awareness and acceptance of hospice care.

BACKGROUND: To evaluate the efficacy and safety of the first cohort of people in China treated with a responsive neurostimulation system (Epilcure TM , GenLight MedTech, Hangzhou, China) for focal drug-resistant epilepsy in this study. METHODS: This multicenter, before-and-after self-controlled study was conducted across 8 centers from March 2022 to June 2023, involving patients with drug-resistant epilepsy who were undergoing responsive neurostimulation (RNS). The study was based on an ongoing multi-center, single-blind, randomized controlled study. Efficacy was assessed through metrics including median seizure count, seizure frequency reduction (SFR), and response rate. Multivariable linear regression analysis was conducted to explore the relationships of basic clinical factors and intracranial electrophysiological characteristics with SFR. The postoperative quality of life, cognitive function, depression, and anxiety were evaluated as well. RESULTS: The follow-up period for the 19 participants was 10.7 ± 3.4 months. Seizure counts decreased significantly 6 months after device activation, with median SFR of 48% at the 6th month (M6) and 58% at M12 ( P  <0.05). The average response rate after 13 months of treatment was 42%, with 21% ( n  = 4) of the participants achieving seizure freedom. Patients who have previously undergone resective surgery appear to achieve better therapeutic outcomes at M11, M12 and M13 ( β  <0, P  <0.05). No statistically significant differences were observed in patients' scores of quality of life, cognition, depression and anxiety following stimulation when compared to baseline measurements. No serious adverse events related to the devices were observed. CONCLUSIONS: The preliminary findings suggest that Epilcure TM exhibits promising therapeutic potential in reducing the frequency of epileptic seizures. However, to further validate its efficacy, larger-scale randomized controlled trials are required. REGISTRATION Chinese Clinical Trial Registry (No. ChiCTR2200055247).
Humans ; Female ; Male ; Drug Resistant Epilepsy/therapy* ; Adult ; Young Adult ; Middle Aged ; China ; Adolescent ; Treatment Outcome ; Quality of Life ; Single-Blind Method ; Seizures ; Electric Stimulation Therapy/methods*

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

Traditional development of small protein scaffolds has relied on display technologies and mutation-based engineering, which limit sequence and functional diversity, thereby constraining their therapeutic and application potential. Protein design tools have significantly advanced the creation of novel protein sequences, structures, and functions. However, further improvements in design strategies are still needed to more efficiently optimize the functional performance of protein-based drugs and enhance their druggability. Here, we extended an evolution-based design protocol to create a novel minibinder, BindHer, against the human epidermal growth factor receptor 2 (HER2). It not only exhibits super stability and binding selectivity but also demonstrates remarkable properties in tissue specificity. Radiolabeling experiments with ^99mTc, ⁶⁸Ga, and ¹⁸F revealed that BindHer efficiently targets tumors in HER2-positive breast cancer mouse models, with minimal nonspecific liver absorption, outperforming scaffolds designed through traditional engineering. These findings highlight a new rational approach to automated protein design, offering significant potential for large-scale applications in therapeutic mini-protein development.

Objective To compare the efficacy and safety of great saphenous vein(GSV)trunk closure combined with local ablation and local sclerotherapy for treating varicose veins of lower limb.Methods Totally 78 patients with unilateral varicose veins of lower limb were retrospectively enrolled and divided into GSV trunk closure combined with local ablation group(group A,n=36)and local sclerotherapy group(group B,n=42).The venous clinical severity score(VCSS),Aberdeen varicose vein questionnaire(AVVQ)score before and 6 months after treatment,as well as the incidence of adverse reactions within 6 months after treatment were compared between groups.Results Six months after treatment,the main trunk closure rate of GSV was 100%in both groups,while VCSS and AVVQ scores were significantly lower than those before treatment(all P＜0.05).No significant difference of VCSS nor AVVQ score before and after treatment was found between groups(all P＞0.05).The incidence of thrombosis,skin paresthesia and subcutaneous induration in group B were all higher than those in group A,while of residual varicose veins in group B was lower than that in group A(all P＜0.05).Conclusion Both GSV trunk closure combined with local ablation and local sclerotherapy could be used to effectively treat varicose veins of lower limb,and the former had fewer adverse reactions.

Objective To compare the efficacy and safety of great saphenous vein(GSV)trunk closure combined with local ablation and local sclerotherapy for treating varicose veins of lower limb.Methods Totally 78 patients with unilateral varicose veins of lower limb were retrospectively enrolled and divided into GSV trunk closure combined with local ablation group(group A,n=36)and local sclerotherapy group(group B,n=42).The venous clinical severity score(VCSS),Aberdeen varicose vein questionnaire(AVVQ)score before and 6 months after treatment,as well as the incidence of adverse reactions within 6 months after treatment were compared between groups.Results Six months after treatment,the main trunk closure rate of GSV was 100%in both groups,while VCSS and AVVQ scores were significantly lower than those before treatment(all P＜0.05).No significant difference of VCSS nor AVVQ score before and after treatment was found between groups(all P＞0.05).The incidence of thrombosis,skin paresthesia and subcutaneous induration in group B were all higher than those in group A,while of residual varicose veins in group B was lower than that in group A(all P＜0.05).Conclusion Both GSV trunk closure combined with local ablation and local sclerotherapy could be used to effectively treat varicose veins of lower limb,and the former had fewer adverse reactions.

Objective:To construct a prognostic model for ovarian cancer based on programmed cell death receptor-1(PD-1)and B lymphocyte infiltration.Methods:A total of 102 patients with ovarian cancer admitted to the First Affiliated Hospital of Gannan Medical College from February 2019 to February 2022 were selected.PD-1 expression and CD20+B cell infiltration degree in cancer tissues were detected,relationship between them and pathological characteristics were analyzed,and correlation between PD-1 expres-sion with B lymphocyte infiltration degree and survival rate of patients were analyzed.Independent influencing factors of poor prognosis of ovarian cancer patients were analyzed,prediction model was built and validated according to independent factors.Results:PD-1 expression and CD20+B cell infiltration degree were closely related to tumor size,FIGO stage,tumor differentiation and lymph node metastasis(P<0.05).PD-1 expression was negatively correlated with B-lymphocyte infiltration degree(P<0.05).Patients with high PD-1 expression and low B-lymphocyte infiltration had higher mortality(P<0.05).FIGO stage,lymph node metastasis,PD-1 expres-sion and CD20+B cell infiltration were independent factors affecting poor prognosis of ovarian cancer patients.Prediction model was constructed by independent influencing factors,which had good differentiation and accuracy.Conclusion:PD-1 expression is closely related to CD20+B cell infiltration degree.There is a close relationship between PD-1 and CD20+B cell infiltration with clinico-pathological characteristics and prognosis of ovarian cancer patients,which are independent influencing factors for poor prognosis of ovarian cancer patients.

Objective:To construct a prognostic model for ovarian cancer based on programmed cell death receptor-1(PD-1)and B lymphocyte infiltration.Methods:A total of 102 patients with ovarian cancer admitted to the First Affiliated Hospital of Gannan Medical College from February 2019 to February 2022 were selected.PD-1 expression and CD20+B cell infiltration degree in cancer tissues were detected,relationship between them and pathological characteristics were analyzed,and correlation between PD-1 expres-sion with B lymphocyte infiltration degree and survival rate of patients were analyzed.Independent influencing factors of poor prognosis of ovarian cancer patients were analyzed,prediction model was built and validated according to independent factors.Results:PD-1 expression and CD20+B cell infiltration degree were closely related to tumor size,FIGO stage,tumor differentiation and lymph node metastasis(P<0.05).PD-1 expression was negatively correlated with B-lymphocyte infiltration degree(P<0.05).Patients with high PD-1 expression and low B-lymphocyte infiltration had higher mortality(P<0.05).FIGO stage,lymph node metastasis,PD-1 expres-sion and CD20+B cell infiltration were independent factors affecting poor prognosis of ovarian cancer patients.Prediction model was constructed by independent influencing factors,which had good differentiation and accuracy.Conclusion:PD-1 expression is closely related to CD20+B cell infiltration degree.There is a close relationship between PD-1 and CD20+B cell infiltration with clinico-pathological characteristics and prognosis of ovarian cancer patients,which are independent influencing factors for poor prognosis of ovarian cancer patients.