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.

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.

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*

Objective:To investigate the clinical efficacy and safety of a baby smoothing and special caring cream in reducing the recurrence of atopic dermatitis (AD) in infancy.Methods:A randomized controlled trial was conducted. Children with moderate AD (with overall investigator's global assessment [IGA] scores of 3 - < 4) were enrolled from Shunyi Maternal and Children′s Hospital of Beijing Children′s Hospital from April 2021 to June 2024. During the induction period, all children were topically treated with 0.1% hydrocortisone butyrate cream twice daily on the lesional skin, as well as with a baby smoothing and special caring cream at least twice daily throughout the body; at the 2-week visit, patients with an IGA score of ≤ 1 point entered the maintenance phase, while those with an IGA score of > 1 point continued the treatment for another 2 weeks; at the 4-week visit, patients with an IGA score of ≤ 1 point entered the maintenance phase, while those still with an IGA score of > 1 point were withdrawn from the study, and received conventional treatment. Patients who entered the maintenance period were randomly divided into the test group and the control group in a 1∶1 ratio using a random number table. In the test group, the hydrocortisone butyrate cream was discontinued, while the baby smoothing and special caring cream was continued twice daily for 8 consecutive weeks; in the control group, both the hydrocortisone butyrate cream and the baby smoothing and special caring cream were discontinued. IGA and Scoring AD (SCORAD) scores were assessed by clinicians at weeks 4 and 8 in the maintenance phase, while the patient-oriented eczema measure (POEM) score was evaluated weekly by patients' parents. The Kaplan-Meier survival analysis and Breslow test were used to compare recurrence rates in the two groups (the primary efficacy outcome), and a generalized estimating equation model was used to evaluate the changes in IGA, SCORAD, and POEM scores in the two groups (the secondary efficacy outcomes). Adverse reactions were monitored throughout the study to evaluate safety.Results:A total of 68 children with moderate AD aged from 3 months to 2 years were included. There were 38 females and 30 males, aged 11.72 ± 6.03 months. Fifty-two patients entered the maintenance phase; 2 were lost to follow-up, and 50 were included in the per-protocol set, with 28 in the test group and 22 in the control group. The recurrence rate during the maintenance phase was 7.14% (2/28) in the test group and 31.82% (7/22) in the control group, showing a significant difference between the two groups ( χ 2 = 5.08, P = 0.032). At weeks 4 and 8 in the maintenance phase, the IGA scores were significantly lower in the test group than in the control group (Wald χ 2 = 5.06, P = 0.024), whereas the SCORAD scores showed no significant differences between the two groups (Wald χ 2 = 2.92, P = 0.087). During weeks 1 - 8 in the maintenance phase, the POEM scores showed no significant differences between the two groups or over time (both P > 0.05), while the two groups showed different change trends in POEM scores over time (Wald χ 2interaction = 55.37, Pinteraction < 0.001). Throughout the entire study period, no adverse reactions were observed among all 68 subjects. Conclusion:With a high safety profile, the baby smoothing and special caring cream could reduce the recurrence rate during the maintenance phase, showing promise as an adjuvant therapy for the maintenance treatment of AD in infancy, and is worthy of clinical application.

Objective To investigate the correlation between serum uric acid(SUA),total bilirubin(TBil),monocyte/high-density lipoprotein cholesterol ratio(MHR)and carotid intima-media thickness(CIMT)in patients with type 2 diabetes mellitus(T2DM).Methods 212 T2DM patients treated from May 2020 to June 2023 were selected and divided into thickening(Thic,n=98)group and a simple T2DM(T2DM,n=114)group according to whether CIMT thickens.The general and clinical data of the two groups were compared.logistic regression was used to analyze the main factors affecting CIMT thickening.ROC was used to analyze the efficacy of SUA,TBil and MHR in diagnosing CIMT.Results The age,DM duration,SBP,DBP,FPG,HbA1c,HOMA-IR,TG,LDL-C,serum creatine,SUA,M,MHR and CIMT in Thic group were higher than those in T2DM group(P<0.05),while FIns and TBil were lower than those in T2DM group(P<0.05).Age,DM duration,SBP,DBP,FPG,HbA1c,HOMA-IR,LDL-C,SUA,M and MHR were positively correlated with CIMT(P<0.05).FIns,TBil were negatively correlated with CIMT(P<0.05).Logistic regression analysis showed that age,DM duration,SBP,HbA1c,SUA,TBil and MHR were the main factors affecting CIMT thickening.ROC analysis showed that the area under the curve values of SUA,TBil and MHR independently and jointly predicted CIMT thickening were 0.684,0.674,0.741 and 0.846.Conclusions SUA,TBil and MHR levels are independent risk factors for CIMT thickening in T2DM patients.The combined detection of SUA,TBiL and MHR has high efficacy in predicting CIMT thickening.

Objective:To investigate the impact of frailty on post-stroke depression (PSD) in patients with acute ischemic stroke and to identify risk factors for PSD in order to construct a risk prediction model.Methods:A convenience sampling method was used to recruit a total of 450 patients with acute ischemic stroke who were treated in the Department of Neurology at the Affiliated Hospital of Jining Medical University from March 2023 to April 2024. Data were collected using the Edmonton Frail Scale, Hamilton Depression Rating Scale, Barthel Index (Activities of Daily Living, ADL), Pittsburgh Sleep Quality Index, and Morse Fall Scale. Binary logistic regression analysis was performed to explore the impact of frailty on PSD and to identify other risk factors. Based on the results, a predictive model was developed.Results:A total of 450 questionnaires were distributed, with 412 valid responses returned, yielding a valid response rate of 91.56%. The incidence of PSD among the 412 patients was 45.63% (188/412). Binary Logistic regression analysis showed that frailty, sleep disturbance, C-reactive protein (CRP), and ADL score were the influencing factors for PSD in patients with acute ischemic stroke ( P<0.05). These factors were incorporated into the predictive model, and a risk nomogram was constructed. The area under the curve of the model was 0.764 [95% CI (0.716, 0.811) ], indicating good discriminative ability. Internal validation of the nomogram using the Hosmer-Lemeshow goodness-of-fit test showed χ 2=5.883, P=0.66 ( P>0.05), suggesting good calibration of the model. Conclusions:Frailty increases the risk of post-stroke depression in patients with acute ischemic stroke. Sleep disturbance, CRP level, and ADL score are important screening indicators for PSD risk. Targeted assessment and early intervention are recommended to reduce the likelihood of PSD.

Objective:To investigate the clinical efficacy and safety of a baby smoothing and special caring cream in reducing the recurrence of atopic dermatitis (AD) in infancy.Methods:A randomized controlled trial was conducted. Children with moderate AD (with overall investigator's global assessment [IGA] scores of 3 - < 4) were enrolled from Shunyi Maternal and Children′s Hospital of Beijing Children′s Hospital from April 2021 to June 2024. During the induction period, all children were topically treated with 0.1% hydrocortisone butyrate cream twice daily on the lesional skin, as well as with a baby smoothing and special caring cream at least twice daily throughout the body; at the 2-week visit, patients with an IGA score of ≤ 1 point entered the maintenance phase, while those with an IGA score of > 1 point continued the treatment for another 2 weeks; at the 4-week visit, patients with an IGA score of ≤ 1 point entered the maintenance phase, while those still with an IGA score of > 1 point were withdrawn from the study, and received conventional treatment. Patients who entered the maintenance period were randomly divided into the test group and the control group in a 1∶1 ratio using a random number table. In the test group, the hydrocortisone butyrate cream was discontinued, while the baby smoothing and special caring cream was continued twice daily for 8 consecutive weeks; in the control group, both the hydrocortisone butyrate cream and the baby smoothing and special caring cream were discontinued. IGA and Scoring AD (SCORAD) scores were assessed by clinicians at weeks 4 and 8 in the maintenance phase, while the patient-oriented eczema measure (POEM) score was evaluated weekly by patients' parents. The Kaplan-Meier survival analysis and Breslow test were used to compare recurrence rates in the two groups (the primary efficacy outcome), and a generalized estimating equation model was used to evaluate the changes in IGA, SCORAD, and POEM scores in the two groups (the secondary efficacy outcomes). Adverse reactions were monitored throughout the study to evaluate safety.Results:A total of 68 children with moderate AD aged from 3 months to 2 years were included. There were 38 females and 30 males, aged 11.72 ± 6.03 months. Fifty-two patients entered the maintenance phase; 2 were lost to follow-up, and 50 were included in the per-protocol set, with 28 in the test group and 22 in the control group. The recurrence rate during the maintenance phase was 7.14% (2/28) in the test group and 31.82% (7/22) in the control group, showing a significant difference between the two groups ( χ 2 = 5.08, P = 0.032). At weeks 4 and 8 in the maintenance phase, the IGA scores were significantly lower in the test group than in the control group (Wald χ 2 = 5.06, P = 0.024), whereas the SCORAD scores showed no significant differences between the two groups (Wald χ 2 = 2.92, P = 0.087). During weeks 1 - 8 in the maintenance phase, the POEM scores showed no significant differences between the two groups or over time (both P > 0.05), while the two groups showed different change trends in POEM scores over time (Wald χ 2interaction = 55.37, Pinteraction < 0.001). Throughout the entire study period, no adverse reactions were observed among all 68 subjects. Conclusion:With a high safety profile, the baby smoothing and special caring cream could reduce the recurrence rate during the maintenance phase, showing promise as an adjuvant therapy for the maintenance treatment of AD in infancy, and is worthy of clinical application.

Objective To investigate the correlation between serum uric acid(SUA),total bilirubin(TBil),monocyte/high-density lipoprotein cholesterol ratio(MHR)and carotid intima-media thickness(CIMT)in patients with type 2 diabetes mellitus(T2DM).Methods 212 T2DM patients treated from May 2020 to June 2023 were selected and divided into thickening(Thic,n=98)group and a simple T2DM(T2DM,n=114)group according to whether CIMT thickens.The general and clinical data of the two groups were compared.logistic regression was used to analyze the main factors affecting CIMT thickening.ROC was used to analyze the efficacy of SUA,TBil and MHR in diagnosing CIMT.Results The age,DM duration,SBP,DBP,FPG,HbA1c,HOMA-IR,TG,LDL-C,serum creatine,SUA,M,MHR and CIMT in Thic group were higher than those in T2DM group(P<0.05),while FIns and TBil were lower than those in T2DM group(P<0.05).Age,DM duration,SBP,DBP,FPG,HbA1c,HOMA-IR,LDL-C,SUA,M and MHR were positively correlated with CIMT(P<0.05).FIns,TBil were negatively correlated with CIMT(P<0.05).Logistic regression analysis showed that age,DM duration,SBP,HbA1c,SUA,TBil and MHR were the main factors affecting CIMT thickening.ROC analysis showed that the area under the curve values of SUA,TBil and MHR independently and jointly predicted CIMT thickening were 0.684,0.674,0.741 and 0.846.Conclusions SUA,TBil and MHR levels are independent risk factors for CIMT thickening in T2DM patients.The combined detection of SUA,TBiL and MHR has high efficacy in predicting CIMT thickening.

Objective:To investigate the impact of frailty on post-stroke depression (PSD) in patients with acute ischemic stroke and to identify risk factors for PSD in order to construct a risk prediction model.Methods:A convenience sampling method was used to recruit a total of 450 patients with acute ischemic stroke who were treated in the Department of Neurology at the Affiliated Hospital of Jining Medical University from March 2023 to April 2024. Data were collected using the Edmonton Frail Scale, Hamilton Depression Rating Scale, Barthel Index (Activities of Daily Living, ADL), Pittsburgh Sleep Quality Index, and Morse Fall Scale. Binary logistic regression analysis was performed to explore the impact of frailty on PSD and to identify other risk factors. Based on the results, a predictive model was developed.Results:A total of 450 questionnaires were distributed, with 412 valid responses returned, yielding a valid response rate of 91.56%. The incidence of PSD among the 412 patients was 45.63% (188/412). Binary Logistic regression analysis showed that frailty, sleep disturbance, C-reactive protein (CRP), and ADL score were the influencing factors for PSD in patients with acute ischemic stroke ( P<0.05). These factors were incorporated into the predictive model, and a risk nomogram was constructed. The area under the curve of the model was 0.764 [95% CI (0.716, 0.811) ], indicating good discriminative ability. Internal validation of the nomogram using the Hosmer-Lemeshow goodness-of-fit test showed χ 2=5.883, P=0.66 ( P>0.05), suggesting good calibration of the model. Conclusions:Frailty increases the risk of post-stroke depression in patients with acute ischemic stroke. Sleep disturbance, CRP level, and ADL score are important screening indicators for PSD risk. Targeted assessment and early intervention are recommended to reduce the likelihood of PSD.

Objective:We genetically modified our non-replicating vaccinia virus NTV to improve its immunogenicity.Methods:We constructed NTV-modified strain NTV-ΔF1L-C7L by homologous recombination of vaccinia virus based on CRISPR-Cas9 technology by inserting the C7L gene while deleting the F1L gene. The recombinant virus NTV-ΔF1L-C7L was then immunized with 10 7 PFU in BALB/c mice, and the levels of humoral and cellular immunity induced by NTV-ΔF1L-C7L were detected by ELISA and ELISpot method, respectively, and the levels of neutralizing antibodies were determined by the phage-reduced neutralization assay. Results:The PCR and western- blot identification proved that the F1L gene of the constructed NTV-modified strain NTV-ΔF1L-C7L was missing, while the C7L gene was inserted back in the region, and the C7L gene could be expressed normally, indicating that the recombinant virus was constructed correctly. After immunization of mice with NTV-ΔF1L-C7L, ELISA result showed that the recombinant virus NTV-ΔF1L-C7L induced a higher level of IgG antibody than NTV; ELISpot result also showed that the recombinant virus was able to induce a higher level of IFN-γ; and the result of plaque reduction neutralization test showed that the recombinant virus was able to induce a higher level of IFN-γ antibody than that of NTV.Conclusions:We correctly constructed the NTV gene-modified strain NTV-ΔF1L-C7L, which induced stronger humoral and cellular immunity compared with NTV, and provided reference data for the research and development of replacement products for smallpox or monkeypox vaccines.