Acute liver injury (ALI) serves as a critical precursor and major etiological factor in the progression and ultimate manifestation of various hepatic disorders. The prevention and treatment of ALI is still a serious global challenge. Given the limited therapeutic options for ALI, exploring novel targeted therapeutic agents becomes imperative. The potential therapeutic efficacy of inhibiting RIPK2 is highlighted, as it may provide significant benefits by attenuating the MAPK pathway and NF-κB signaling. Herein, we propose a CMD-OPT model, a two-stage molecular optimization tool for the rapid discovery of RIPK2 inhibitors with optimal properties. Compound RP20, which targets the ATP binding site, demonstrated excellent kinase specificity, ideal oral pharmacokinetics, and superior therapeutic effects in a model of APAP-induced ALI, positioning RP20 as a promising preclinical candidate. This marks the first application of RIPK2 inhibitors in ALI treatment, opening a novel therapeutic pathway for clinical applications. These results highlight the efficacy of the CMD-OPT model in producing lead compounds from known active molecules, showcasing its significant potential in drug discovery.

Objective:To apply the Timed Up and Go Test(TUGT)to investigate the correlation between motor function, emotional state, cognitive function, and sleep quality among elderly individuals in the Chinese community.Methods:A cross-sectional study was conducted, involving 739 subjects aged 60 to 90 years, who were randomly recruited from December 2021 to August 2023 across Beijing, Tianjin, Zhejiang, Guangdong, and Hainan Provinces in China.Basic demographic information was collected, and the TUGT was utilized to assess motor function.Based on the TUGT time(t), the subjects were divided into three groups: normal motor function group, mild motor abnormality group, and significant motor abnormality group.Cognitive function was evaluated using the Chinese Revised Mini-Mental State Examination(MMSE), while the Patient Health Questionnaire Depression Scale(PHQ-9)was employed to measure the degree of depression.Additionally, the Epworth Sleepiness Scale(ESS)was used to assess excessive daytime sleepiness.The correlation between subjects' motor function and their cognitive abilities, mood, and sleep was subsequently analyzed.Results:Systolic blood pressure, heart rate, PHQ-9, MMSE, and ESS scores were identified as significant factors influencing TUGT time.Specifically, TUGT time was positively correlated with PHQ-9 and ESS scores, while exhibiting negative correlations with systolic blood pressure, heart rate, and MMSE scores.Additionally, TUGT time was negatively correlated with the MMSE subcomponents of orientation, immediate memory, and verbal ability.All observed differences were statistically significant(all P<0.05).Logistic regression analysis indicated that an increase in the PHQ-9 score was associated with an odds ratio( OR)of 1.099(95% CI: 1.045-1.155, P<0.001)(mild motor abnormality group)and 1.150(95% CI: 1.066-1.242, P<0.001)(Significant motor abnormality group).Additionally, a reduction in the MMSE score was observed, with an OR of 0.939(95% CI: 0.886-0.995, P<0.001)(mild motor abnormality group)and 0.793(95% CI: 0.729-0.862, P<0.001)(Significant motor abnormality group).Furthermore, an increase in the ESS score was noted, with ORs of 1.139(95% CI: 1.094-1.186, P<0.001)(mild motor abnormality group)and 1.203(95% CI: 1.132-1.279, P<0.001)(Significant motor abnormality group).These findings suggest that these variables are independently related to decreased motor function. Conclusions:Depression, cognitive impairment, and excessive daytime sleepiness are independent risk factors for motor dysfunction among elderly individuals in community settings.The Timed Up and Go Test TUGT can be utilized for the early screening of motor function decline in this population.

Objective This study aims to observe the impact of warm moxibustion on menstrual pain in college students with primary dysmenorrhea and explore its potential mechanism.Methods College students with primary dysmenorrhea were recruited and treated with warm moxibustion at Shenque acupoint for three consecutive menstrual cycles.Healthy subjects were also recruited for comparison.Pain scale,uterine artery hemodynamics,and related inflammatory factors were assessed before and after treatment.Results ①The results of scale study showed that the severity and duration of dysmenorrhea were gradually alleviated with the prolongation of treatment time through the analysis of variance of repeated measurements of the total scores of McGill pain inquiry scale and CMSS dysmenorrhea symptom scale before and after 3 treatments.The results of variance analysis and pairwise comparison of repeated measurements of PRI,VAS and PPI of McGill pain inquiry scale before and after 3 times treatment in warm moxibustion group also showed that each index decreased gradually with the prolongation of treatment time.The comparison of the scores of each item of CMSS scale showed that the severity and duration of low back before treatment were significantly different from those in the healthy group(P<0.001),but the difference was weakened after the third treatment.The severity of vomiting,the duration of vomiting,the severity of diarrhea and the duration of diarrhea were significantly different from those in the healthy group before treatment(P<0.001),but they were still higher than those in the healthy group after the third treatment.but the difference was not statistically significant.②Prior to treatment,PD college students exhibited significantly higher S/D and PI values on both sides compared to healthy subjects,with a statistically significant difference observed for PI on the left side(P<0.001).Following treatment,all aforementioned indexes decreased significantly,particularly PI on the left side which showed a significant difference from pre-treatment levels(P<0.001).③Before treatment,the levels of serum IL-1β,TNF-α,and CRP in PD college students were significantly higher compared to those in the healthy group.The difference in IL-1β level was statistically significant(P<0.001).After treatment,there was a noticeable decrease in the levels of IL-1β,TNF-α,and CRP.Specifically,IL-1β showed a significant reduction(P<0.01),and this time the comparison with the healthy group did not reveal any significant difference in IL-1β levels.Conclusion The application of warm moxibustion at the Shenque acupoint demonstrates a significant improvement in both the dysmenorrhea pain rating index and severity among college students with primary dysmenorrhea,while also alleviating the severity and duration of associated symptoms.These positive effects may be attributed to warm moxibustion's ability to enhance uterine microcirculation in individuals with primary dysmenorrhea,and ameliorating inflammatory conditions.

Objective:To compare the efficacy and safety of crisaborole ointment 2% versus pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged 2 years or older.Methods:A multicenter, randomized, open-label, controlled clinical trial was conducted. A total of 120 pediatric patients aged 2 - 17 years with mild to moderate atopic dermatitis were enrolled from departments of dermatology of 8 hospitals in China between March 2022 and February 2023. The participants were randomly assigned in a 1∶1 ratio to the crisaborole group and the pimecrolimus group, and received the treatment with crisaborole ointment 2% and pimecrolimus cream 1% respectively, twice a day for 4 weeks. Visits were scheduled at baseline/on day 1, as well as on days 8, 15, and 29. The primary efficacy outcome was the percentage of patients achieving the Investigator's Static Global Assessment (ISGA) success (defined as clear [0] or almost clear [1] on the ISGA scale, combined with ≥ 2‐grade improvement from baseline) on day 29. The secondary efficacy outcomes included changes in the Eczema Area and Severity Index (EASI) total scores from baseline to day 29, percentages of patients achieving ISGA improvement (defined as clear [0] or almost clear [1] on the ISGA scale), as well as changes in the Peak Pruritus Numerical Rating Scale (NRS) scores, Dermatology Life Quality Index (DLQI) /Infants' Dermatology Life Quality Index (IDLQI) /Children's Dermatology Life Quality Index (CDLQI) scores, and in the Dermatitis Family Impact (DFI) scores. Drug safety was evaluated according to the incidence of adverse events. Categorical data were compared using the chi-square test. Since measurement data did not follow a normal distribution, the rank sum test was used for comparisons of measurement data between groups.Results:A total of 106 children with mild to moderate atopic dermatitis were included in the per-protocol analysis set, with 52 in the crisaborole group (26 males and 26 females) and 54 in the pimecrolimus group (27 males and 27 females). There were no significant differences in age, disease duration, ISGA and EASI scores at baseline between the two groups (all P > 0.05). On day 29, 22 patients (42.31%) in the crisaborole group and 25 (46.30%) in the pimecrolimus group achieved ISGA success, with no significant difference between the two groups ( χ2 = 0.17, P = 0.68) ; 35 patients (67.31%) in the crisaborole group and 45 (83.33%) in the pimecrolimus group achieved ISGA improvement, also with no significant difference between the two groups ( χ2 = 3.68, P = 0.06) ; additionally, there were no significant differences in the EASI, pruritus NRS, DLQI/IDLQI/CDLQI, or DFI scores between the two groups (all P > 0.05). Adverse reactions to the two topical agents were mainly local reactions such as mild to moderate pain, itching, or worsening of itching, and no obvious systemic adverse reactions occurred. The incidence of drug-related adverse reactions was 46.15% (24 cases) in the crisaborole group and 37.04% (20 cases) in the pimecrolimus group, with no significant difference between the two groups ( χ2 = 0.91, P = 0.34) . Conclusion:The efficacy of crisaborole ointment 2% was comparable to that of pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged ≥ 2 years, and it yielded early and rapid improvement in the quality of life of patients and their families, with good safety and tolerability profiles.

The 2025 American Society of Clinical Oncology(ASCO)Annual Meeting was held in Chicago from May 30 to June 3,2025.As one of the largest and most influential academic events in global oncology,the ASCO meeting brought together numerous world-class oncology experts.It focused on the unmet clinical needs in gastrointestinal malignancies such as hepatocellular carcinoma,cholangiocarcinoma,and pancreatic cancer,and presented a wealth of cutting-edge research findings and therapeutic innovations.These advances provide important evidence-based support for the diagnosis and treatment of hepatobiliary and pancreatic cancers.Based on the latest achievements presented at ASCO 2025,this article discusses the hot topics and future directions in the management of hepatobiliary and pancreatic tumors.

Objective:To compare the efficacy and safety of crisaborole ointment 2% versus pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged 2 years or older.Methods:A multicenter, randomized, open-label, controlled clinical trial was conducted. A total of 120 pediatric patients aged 2 - 17 years with mild to moderate atopic dermatitis were enrolled from departments of dermatology of 8 hospitals in China between March 2022 and February 2023. The participants were randomly assigned in a 1∶1 ratio to the crisaborole group and the pimecrolimus group, and received the treatment with crisaborole ointment 2% and pimecrolimus cream 1% respectively, twice a day for 4 weeks. Visits were scheduled at baseline/on day 1, as well as on days 8, 15, and 29. The primary efficacy outcome was the percentage of patients achieving the Investigator's Static Global Assessment (ISGA) success (defined as clear [0] or almost clear [1] on the ISGA scale, combined with ≥ 2‐grade improvement from baseline) on day 29. The secondary efficacy outcomes included changes in the Eczema Area and Severity Index (EASI) total scores from baseline to day 29, percentages of patients achieving ISGA improvement (defined as clear [0] or almost clear [1] on the ISGA scale), as well as changes in the Peak Pruritus Numerical Rating Scale (NRS) scores, Dermatology Life Quality Index (DLQI) /Infants' Dermatology Life Quality Index (IDLQI) /Children's Dermatology Life Quality Index (CDLQI) scores, and in the Dermatitis Family Impact (DFI) scores. Drug safety was evaluated according to the incidence of adverse events. Categorical data were compared using the chi-square test. Since measurement data did not follow a normal distribution, the rank sum test was used for comparisons of measurement data between groups.Results:A total of 106 children with mild to moderate atopic dermatitis were included in the per-protocol analysis set, with 52 in the crisaborole group (26 males and 26 females) and 54 in the pimecrolimus group (27 males and 27 females). There were no significant differences in age, disease duration, ISGA and EASI scores at baseline between the two groups (all P > 0.05). On day 29, 22 patients (42.31%) in the crisaborole group and 25 (46.30%) in the pimecrolimus group achieved ISGA success, with no significant difference between the two groups ( χ2 = 0.17, P = 0.68) ; 35 patients (67.31%) in the crisaborole group and 45 (83.33%) in the pimecrolimus group achieved ISGA improvement, also with no significant difference between the two groups ( χ2 = 3.68, P = 0.06) ; additionally, there were no significant differences in the EASI, pruritus NRS, DLQI/IDLQI/CDLQI, or DFI scores between the two groups (all P > 0.05). Adverse reactions to the two topical agents were mainly local reactions such as mild to moderate pain, itching, or worsening of itching, and no obvious systemic adverse reactions occurred. The incidence of drug-related adverse reactions was 46.15% (24 cases) in the crisaborole group and 37.04% (20 cases) in the pimecrolimus group, with no significant difference between the two groups ( χ2 = 0.91, P = 0.34) . Conclusion:The efficacy of crisaborole ointment 2% was comparable to that of pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged ≥ 2 years, and it yielded early and rapid improvement in the quality of life of patients and their families, with good safety and tolerability profiles.

Objective:To construct a humanistic care nursing program for adult ICU patients, providing guidance for the clinical practice of humanistic care in ICUs.Methods:Based on a literature review and clinical practice experience, a preliminary humanistic care nursing program for adult ICU patients was drafted. From August to September 2024, the Delphi method was used to conduct two rounds of expert consultation with 16 experts to revise the content of each item and the overall program, resulting in the final version of the humanistic care nursing program for ICU adult patients. The experts' engagement was measured by the effective response rate of the questionnaires, their authority by the expert authority coefficient, and the coordination of expert opinions by the Kendall's coefficient of concordance.Results:The effective response rate for the Delphi expert consultation questionnaires was 100.00% (16/16) in both rounds. The expert authority coefficients were 0.872 and 0.875, respectively. After the second round of consultation, the Kendall's coefficients for the importance, applicability, and feasibility of each level of item ranged from 0.119 to 0.313 ( P<0.05). The final humanistic care nursing program for adult ICU patients included three first-level items, 12 second-level items, and 55 third-level items. Conclusions:The humanistic care nursing program for adult ICU patients constructed in this study is scientific, targeted, and feasible, providing guidance for the clinical practice of humanistic care in ICU settings.

Objective:To explore the current status and influencing factors of non-verbal communication needs in mechanically ventilated patients in ICU using an interpretive sequential mixed research design to inform the future development of targeted non-verbal communication strategies for mechanically ventilated patients in the ICU.Methods:Convenience sampling was used to select 262 mechanically ventilated patients from the general ICUs of two Class Ⅲ Grade A hospitals in Shanghai, from January to June 2023 for the study. Patients were surveyed using the General Information Questionnaire and the Surgical ICU Tracheal Intubation Patient Communication Needs Scale. Multiple linear regression was used to analyze the factors influencing the non-verbal communication needs of mechanically ventilated patients in the ICU. A total of 262 questionnaires were distributed in the quantitative study, and 256 valid questionnaires were recovered, with a valid recovery rate of 97.71% (256/262) . Purposive sampling was used to select 16 ICU mechanically ventilated patients for semi-structured in-depth interviews. The information was analyzed using the Colaizzi 7-step analysis method.Results:In 256 mechanically ventilated patients, the total non-verbal communication needs score was (144.33±12.82) , and the items average scores of physiological needs, safety needs, love and belongingness needs, and self-esteem needs were (3.39±1.83) , (3.35±0.98) , (3.32±1.21) , and (3.29±1.32) , respectively. Multiple linear regression analysis showed that the duration of mechanical ventilation, history of intubation, and education level were the factors influencing the non-verbal communication needs of mechanically ventilated patients in the ICU ( P<0.05) . Five themes were distilled from the qualitative study, including communication needs for shared decision-making about disease trajectories, communication needs for accurate management of disease symptoms, communication needs for psychological stress adjustment, communication needs for social system support, and communication needs for dignity preservation. Integrating and analyzing the quantitative and qualitative results revealed that they complemented each other in explaining and validating ideas in elaborating the current status and intrinsic relationship of non-verbal communication needs of mechanically ventilated patients in ICU. Conclusions:The non-verbal communication needs of mechanically ventilated patients in the ICU are prevalent and influenced by a variety of factors. It is recommended that hospital administrators construct an effective non-verbal communication support system based on the status quo of patients' non-verbal communication needs in order to promote the whole process and multidimensional health management services for ICU mechanically ventilated patients and to improve patients' quality of life.

The 2025 American Society of Clinical Oncology(ASCO)Annual Meeting was held in Chicago from May 30 to June 3,2025.As one of the largest and most influential academic events in global oncology,the ASCO meeting brought together numerous world-class oncology experts.It focused on the unmet clinical needs in gastrointestinal malignancies such as hepatocellular carcinoma,cholangiocarcinoma,and pancreatic cancer,and presented a wealth of cutting-edge research findings and therapeutic innovations.These advances provide important evidence-based support for the diagnosis and treatment of hepatobiliary and pancreatic cancers.Based on the latest achievements presented at ASCO 2025,this article discusses the hot topics and future directions in the management of hepatobiliary and pancreatic tumors.

Objective This study aims to observe the impact of warm moxibustion on menstrual pain in college students with primary dysmenorrhea and explore its potential mechanism.Methods College students with primary dysmenorrhea were recruited and treated with warm moxibustion at Shenque acupoint for three consecutive menstrual cycles.Healthy subjects were also recruited for comparison.Pain scale,uterine artery hemodynamics,and related inflammatory factors were assessed before and after treatment.Results ①The results of scale study showed that the severity and duration of dysmenorrhea were gradually alleviated with the prolongation of treatment time through the analysis of variance of repeated measurements of the total scores of McGill pain inquiry scale and CMSS dysmenorrhea symptom scale before and after 3 treatments.The results of variance analysis and pairwise comparison of repeated measurements of PRI,VAS and PPI of McGill pain inquiry scale before and after 3 times treatment in warm moxibustion group also showed that each index decreased gradually with the prolongation of treatment time.The comparison of the scores of each item of CMSS scale showed that the severity and duration of low back before treatment were significantly different from those in the healthy group(P<0.001),but the difference was weakened after the third treatment.The severity of vomiting,the duration of vomiting,the severity of diarrhea and the duration of diarrhea were significantly different from those in the healthy group before treatment(P<0.001),but they were still higher than those in the healthy group after the third treatment.but the difference was not statistically significant.②Prior to treatment,PD college students exhibited significantly higher S/D and PI values on both sides compared to healthy subjects,with a statistically significant difference observed for PI on the left side(P<0.001).Following treatment,all aforementioned indexes decreased significantly,particularly PI on the left side which showed a significant difference from pre-treatment levels(P<0.001).③Before treatment,the levels of serum IL-1β,TNF-α,and CRP in PD college students were significantly higher compared to those in the healthy group.The difference in IL-1β level was statistically significant(P<0.001).After treatment,there was a noticeable decrease in the levels of IL-1β,TNF-α,and CRP.Specifically,IL-1β showed a significant reduction(P<0.01),and this time the comparison with the healthy group did not reveal any significant difference in IL-1β levels.Conclusion The application of warm moxibustion at the Shenque acupoint demonstrates a significant improvement in both the dysmenorrhea pain rating index and severity among college students with primary dysmenorrhea,while also alleviating the severity and duration of associated symptoms.These positive effects may be attributed to warm moxibustion's ability to enhance uterine microcirculation in individuals with primary dysmenorrhea,and ameliorating inflammatory conditions.