Palliative care is recognized as an effective measure to improve the quality of life for patients with end-stage diseases， and the significance and role of such patients participating in clinical trials to conquer major diseases has also become a broad consensus. However， due to the special physical， psychological， and social conditions of terminal trial participants， the ethical problems encountered in the trial process are more serious and complex. Drawing on ethical practice experience， these seemingly common phenomena and issues were deeply analyzed. Combined with the palliative care philosophy for end-stage patients， this paper proposed a series of improvement suggestions throughout the entire life cycle of clinical trials， hoping to promote the quality improvement of clinical research in which end-stage patients participate as subjects， while effectively protecting the safety and rights of the subjects and ensuring they receive appropriate palliative care during their participation in clinical trials or clinical-related scientific research.

Cholangiocarcinoma (CCA) is a fatal malignancy with steadily increasing incidence and poor prognosis. Since most CCA cases are diagnosed at an advanced stage, systemic therapies, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy, play a crucial role in the management of unresectable CCA. The recent advances in targeted therapies and immunotherapies brought more options in the clinical management of unresectable CCA. This review depicts the advances of targeted therapies and immunotherapies for unresectable CCA, summarizes crucial clinical trials, and describes the efficacy and safety of different drugs, which may help further develop precision and individualization in the clinical treatment of unresectable CCA.
Humans ; Cholangiocarcinoma/drug therapy* ; Immunotherapy/methods* ; Bile Duct Neoplasms/drug therapy* ; Molecular Targeted Therapy/methods*

Metastasis is the leading cause of death from cutaneous melanoma. Identifying metastasis-related targets and developing corresponding therapeutic strategies are major areas of focus. While functional genomics strategies provide powerful tools for target discovery, investigations at the protein level can directly decode the bioactive epitopes on functional proteins. Aptamers present a promising avenue as they can explore membrane proteomes and have the potential to interfere with cell function. Herein, we developed a target and epitope discovery platform, termed functional aptamer evolution-enabled target identification (FAETI), by integrating affinity aptamer acquisition with phenotype screening and target protein identification. Utilizing the aptamer XH3C, which was screened for its migration-inhibitory function, we identified the Chondroitin Sulfate Proteoglycan 4 (CSPG4), as a potential target involved in melanoma migration. Further evidence demonstrated that XH3C induces cytoskeletal rearrangement by blocking the interaction between the bioactive epitope of CSPG4 and integrin α4. Taken together, our study demonstrates the robustness of aptamer-based molecular tools for target and epitope discovery. Additionally, XH3C is an affinity and functional molecule that selectively binds to a unique epitope on CSPG4, enabling the development of innovative therapeutic strategies.

ObjectiveTo investigate the effect and potential mechanism of caffeic acid （CA） on severe acute pancreatitis （SAP） induced by caerulein combined with lipopolysaccharide （LPS）， and to provide a basis for the research on novel drugs for the treatment of SAP. MethodsC57BL/6J mice， aged 6 weeks， were divided into control group， model group， CA group， and octreotide acetate （OA） group， with 6 mice in each group. The mice in the control group were given injection of normal saline， and those in the other groups were given intraperitoneal injection of caerulein combined with LPS to establish a mouse model of SAP. At 1 hour after the first injection of caerulein， the mice in the CA group and the OA group were given intraperitoneal injection of CA or subcutaneous injection of OA at an interval of 8 hours. The general status of the mice was observed after 24 hours of modeling， and serum， pancreas， lung， and colon samples were collected. HE staining was used to observe the histopathological changes of the pancreas and lungs， and the serum levels of α-amylase， lipase， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， alanine aminotransferase， aspartate aminotransferase， and creatinine were measured. RT-PCR was used to measure the expression of proinflammatory factors in the pancreas and lungs； myeloperoxidase （MPO） immunohistochemistry was used to observe the degree of neutrophil infiltration； Western blot was used to measure the activation of nuclear factor-kappa B （NF-κB） and the level of citrullinated histone H3 （CitH3）， a marker for the formation of neutrophil extracellular traps （NETs）， in the pancreas and lungs， as well as the expression level of ZO-1 in colon tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the Dunnett’s t-test was used for further comparison between two groups. ResultsCompared with the control group， the model group had severe injury in the pancreas and lungs and significant increases in the activity of serum α- amylase and lipase and the levels of the proinflammatory cytokines IL-6， interleukin-1β （IL-1β）， and TNF-α in serum and lung tissue （all P<0.05）， as well as significant increases in NF-κB activation， neutrophil infiltration， and the formation of NETs in the pancreas and lungs （all P<0.05）. Compared with the model group， the CA group had alleviated pathological injury of the pancreas and lungs and significant reductions in the activity of serum α-amylase and the levels of the proinflammatory cytokines IL-6， IL-1β， and TNF-α in serum and lung tissue （all P<0.05）， as well as significant reductions in NF-κB activation， neutrophil infiltration， and the formation of NETs in the pancreas and lungs （all P<0.05）. ConclusionCA can alleviate SAP induced by caerulein combined with LPS in mice， possibly by inhibiting neutrophil recruitment and the formation of NETs.

Objective To investigate the status of perceived uncertainty in the process of re-pregnancy in patients with recurrent abortion,and to systematically explore the influencing factors based on the health ecology model,to inform a reduction in the level of perceived uncertainty about their re-pregnancy and improve their quality of life.Methods A convenience sampling method was used to investigate 260 patients with recurrent spontaneous abortion during re-pregnancy from 2 reproductive clinics of a tertiary A hospital in Suzhou,from December 2023 to June 2024,and they were investigated by a self-designed general data questionnaire,Intolerance of Uncertainty Scale-12,Generalized Anxiety Disorder Scale and Simple Coping Style Questionnaire.The single factor analysis and multiple linear regression methods were used to analyze the influences factors of perceived uncertainty in patients with recurrent spontaneous abortion during re-pregnancy.Results A total of 256 valid questionnaires were collected,with a recovery rate of 98.5％.The score of intolerance of uncertainty in patients with recurrent spontaneous abortion during re-pregnancy was(35.18±9.23).Multiple linear regression analysis found that average monthly family income,residence,history with assisted reproductive therapy,anxiety and coping were the factors influencing the feeling of perceived uncertainty in patients with recurrent spontaneous abortion during re-pregnancy(P＜0.05).Conclusion The level of perceived uncertainty in patients with recurrent spontaneous abortion during re-pregnancy is at a medium level.Medical workers should pay attention to the early identification of the perceived uncertainty in patients,enhance the psychological support for patients,and improve their mental health.

Objective To observe the value of machine learning(ML)models based on ultrasound radiomics for preoperatively distinguishing atypical parathyroid tumor(APT)/parathyroid carcinoma(PC)and parathyroid adenoma(PA).Methods Totally 330 primary hyperparathyroidism patients who underwent surgical treatments were retrospectively enrolled and categorized into APT/PC group(n=78)and PA group(n=252)according to surgical pathology and clinical follow-up results,also divided into training set(n=231)and test set(n=99)at the ratio of 7∶3.Based on preoperative ultrasound,545 radiomics features were extracted,and recursive feature elimination(RFE),Kruskal-Wallis or analysis of variance methods were used to screen the features,respectively.Support vector machine(SVM),linear discriminant analysis(LDA),least absolute shrinkage and selection operator logistic regression(LRLASSO),also random forest(RF)and decision tree(DT)algorithms were adopted to construct ML models for differentiating APT/PC and PA,respectively.Then the models were trained in training set,their performance were verified in test set,and a 5-fold cross-validation was adopted to screen out the better combinations.Results Compared with Kruskal-Wallis and analysis of variance methods,the distinguishing efficacy of SVM,LDA,LRLASSO,RF and DT models constructed based on features screened out using RFE method in training set(area under the curve[AUC]=0.870,0.878,0.850,0.847,1.000)and test set(AUC=0.856,0.842,0.827,0.847 and 0.704)were all relatively higher.In test set,the AUC of SVM,LDA,LRLASSO and RF models constructed based on the features screened out using RFE method(included 25,23,17 and 23 features)were all higher than that of DT model(8 features)(all P＜0.001).No significant difference of AUC was found between SVM,LRLASSO or RF models and LDA model(all P＞0.05).The AUC of SVM and RF models were higher than that of LRLASSO model(both P＜0.05),while of SVM and RF models were not significantly different(P＞0.05),indicating that SVM,LDA and RF models were better ones.Conclusion SVM,LDA,LRLASSO,RF and DT models based on ultrasound radiomics could effectively distinguish APT/PC and PA preoperatively,among which SVM,LDA and RF models had better diagnostic efficacy.

Objective To explore the effect of remote ischemic conditioning(RIC)combined with binaural beat music(BBM)train-ing in patients with cognitive dysfunction after cerebral infarction.Methods From June,2024 to January,2025,200 patients with cognitive dysfunction after cerebral infarction in the Affil-iated Hospital of North China University of Science and Technology were randomly divided into control group(n=50),RIC group(n=50),BBM group(n=50)and combined group(n=50).All the groups received stan-dardized routine training,RIC group received RIC,BBM group received BBM,and the combined group received RIC+BBM,for 14 days.They were assessed with Montreal Cognitive Assessment(MoCA)and Stroke-Specific Quality of Life Scale(SS-QOL)at baseline,day 14,and day 90.Results Two cases in the control group,four in RIC group,three in BBM group and three in the combined group dropped out.For MoCA scores,the inter-group effect,intra-group effect and interaction effect were all significant(F>13.463,P<0.001).After intervention,on both day 14 and day 90,the score of MoCA was higher in each in-tervention group than in the control group(P<0.05),and was higher in the combined group than in both BBM and RIC groups(P<0.05);and on day 90,it was higher in RIC group than in BBM group(P<0.05).For SS-QOL,the score increased with time in all the groups(χ2>75.182,P<0.001).After intervention,there was signif-icant difference at each time point among four groups(H>18.260,P<0.001).On day 14 and day 90,the score of SS-QOL was higher in the combined group than in the control and BBM groups(|Z|>3.149,P<0.05);on day 90,the score was higher in RIC group than in the control group(|Z|=3.590,P<0.05),and it was higher in the combined group than in RIC group(|Z|=3.186,P<0.05).Conclusion RIC,BBM and their combination all improved cognitive function after cerebral infarction.RIC was superior to BBM,and the combined intervention yielded the greatest benefit.Both RIC and the combined intervention im-proved quality of life,with the combined approach being the most effective.

Objective:To construct a continuity of care plan for adolescent fixed orthodontic patients based on the theory of timing, and provide systematic and standardized nursing interventions for adolescent fixed orthodontic patients.Methods:Guided by the theory of timing, preliminary plan items were formulated through literature review and questionnaire survey. Using the Delphi method, 15 experts were consulted for two rounds to determine the continuity of care plan for adolescent fixed orthodontic patients from October to December, 2023.Results:The effective response rates of the two rounds of questionnaires were 15/15, respectively. The expert authority levels were 0.93 and 0.94, and the Kendall harmony coefficients were 0.28 and 0.38, respectively. The differences were statistically significant (both P<0.001). The final established plan included 5 primary indicators, 23 secondary indicators, and 47 tertiary indicators. Conclusions:The continuity of care plan for adolescent fixed orthodontic patients based on the timing theory is reliable and scientific, and can meet the continuity of care needs of patients at different stages, providing reliable clinical basis for carrying out continuity of care.

Objective:To investigate the current situation of nursing information ability of head nurses in different grades of hospitals in Jiaozuo City, and analyze its influencing variables based on the random forest model, so as to provide evidence-based basis for the construction of nursing information ability improvement strategies and training programs for head nurses.Methods:From August to September 2024, the head nurses of 20 hospitals of different grades were selected by cluster sampling method in Jiaozuo City as the research subjects. General Data Questionnaire and Nursing Information Ability Scale of Head Nurses were used to conduct a cross-sectional survey. Random forest model was used to evaluate the importance of variables, lasso regression analysis was applied to complete the variable screening, and the influencing factors of nursing information ability of head nurses were explored through stepwise multiple linear regression analysis.Results:A total of 305 questionnaires were ultimately collected, of which 297 were valid, the effective rate was 97.38%. Out of 297 head nurses, 6 were male and 291 were female; 49 individuals aged 20-29 years old, 127 individuals aged 30-39 years old, 92 individuals aged 40-49 years old, and 29 individuals aged ≥ 50 years old. The total score of nursing information ability was (139.06 ± 24.62). Random forest model and lasso regression analysis showed that the top 6 variables in terms of importance were the number of years serving as head nurses, participation in information function development, number of academic conferences in the past three years, hospital grade, participating in information training, and chairing or participating in scientific research in the past three years. Stepwise multiple linear regression analysis showed that the number of years serving as head nurses, participating in information training, participating in information function development and number of academic conferences in the past three years had significant effects on nursing information ability of head nurses (t values were -4.66 to 3.81, all P<0.05). Conclusions:The nursing information ability of head nurses in Jiaozuo city is in the middle level, and the nursing information ability of head nurses in different grades of hospitals is different. It is suggested to construct a stepped information ability continuing education framework and a research-information ability coupling development mechanism, and incorporate nursing information ability into the necessary conditions for the appointment of nursing management posts, so as to realize the balanced development of nursing information management ability and the continuous iteration of nursing manager information ability.

Objective:To explore the mediating role of dietary health beliefs in the relationship between family functioning and the frequency of sugar-containing food intake among adolescents with dental caries, in order to clarify the underlying mechanism through which dietary health beliefs influence caries-related dietary behaviors via family factors.Methods:Using convenience sampling method, we selected adolescents patients diagnosed with dental caries and their parents who visited the Affiliated Stomatological Hospital of Nanjing Medical University from July to September 2023 as the research subjects. Conducted a cross-sectional survey using a general information questionnaire, Family Functioning Scale, Adolescent Dietary Health Belief Scale, and Sugar-Sweetened Diet Intake Frequency Scale. Mediation analysis was conducted.Results:A total of 475 questionnaires were distributed, and 460 valid responses were obtained, yielding a valid response rate of 96.84%. Among the 460 adolescent patients, 306 were female and 154 were male, with a mean age of (13.42 ± 1.17) years old. The mother's age was (40.28 ± 4.24) years old, and the father's age was (42.12 ± 4.48) years old. The score for the frequency of sugar-containing food intake was 15.95 ± 5.34, the dietary health belief score was 75.57 ± 18.62, and the family functioning score was 174.24 ± 25.39. Family functioning was positively correlated with dietary health beliefs ( r = 0.428, P<0.05), and negatively correlated with the frequency of sugar-containing food intake ( r = -0.225, P<0.05). Dietary health beliefs were negatively correlated with the frequency of sugar-containing food intake ( r = -0.332, P<0.05). The mediating effect of dietary health beliefs on the relationship between family functioning and sugar-containing food intake frequency was -0.332, accounting for 43.92% of the total effect. Conclusions:Dietary health beliefs play a partial mediating role between family function and the frequency of sugary diet intake. It is suggested that family function construction should be strengthened to improve adolescents' health beliefs and reduce the incidence of dental caries.