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 investigate the clinical efficacy of five-element music therapy in the treatment of bipolar disorder.Methods:Eighty patients with bipolar disorder admitted to Shandong Mental Health Center from January 2018 to December 2019 were included in this study. They were randomly divided into a study group and a control group ( n = 40/group). The control group was treated with conventional drug treatment. The study group was treated with five-element music therapy based on conventional drug treatment. Before, during and after treatment, mania and depression were evaluated. Symptom self-evaluation scale and the Traditional Chinese Medicine Five State Emotion Questionnaire were completed to evaluate the curative effect. Patients were followed up by telephone call. Recurrence at 3, 6 and 12 months was recorded. Results:Before treatment, there were no significant differences in the scores of the Bech-Rafaelsen Mania Rating Scale (BRMs), Hamilton Depression Rating Scale (HAMD), Traditional Chinese Medicine Five State Emotion Questionnaire, Symptom Checklist-90 (SCL-90) between the two groups (all P > 0.05). During and after treatment, BRMs, HAMD, Traditional Chinese Medicine Five State Emotion Questionnaire, and SCL-90 scores were significantly decreased in each group compared with before treatment [Control group: BRMs score during and after treatment: (11.52 ± 1.57) points, (9.43 ± 1.05) points; HAMD score during and after treatment: (16.75 ± 3.05) points, (13.61 ± 2.51) points; Traditional Chinese Medicine Five State Emotion Questionnaire: emotional vocabulary (67.25 ± 5.7) points, (56.38 ± 4.97) points, physical symptoms (29.52 ± 3.94) points, (24.19 ± 3.05) points, SCL-90 score: (100.52 ± 10.26) points, (68.85 ± 7.33) points. Study group: BRMs score during and after treatment: (9.33 ± 1.09) points, (7.85 ± 0.82) points; HAMD score: (13.74 ± 2.54) points, (10.17 ± 1.97) points; Traditional Chinese Medicine Five State Emotion Questionnaire: emotional vocabulary: (58.19 ± 5.06) points, (46.85 ± 4.06) points, physical symptoms (25.14 ± 3.54) points, (20.11 ± 2.57) points; SCL-90 scores: (90.85 ± 8.97) points, (56.87 ± 5.81) points]. During and after treatment, scores of BRMs, HAMD, Traditional Chinese Medicine Five State Emotion Questionnaire and SCL-90 in the study group were significantly lower than those in the control group ( t = 3.77, 7.01, 4.48, 6.99, 8.78, 4.89, 6.05, 4.19, 7.57, all P < 0.05). Total response rate in the study group was significantly higher than that in the control group (90.0% vs. 72.5%, χ2 = 4.02, P < 0.05). At 3, 6 and 12 months after treatment, recurrence rate in the study group was 2.5%, 15.0% and 30.0%, respectively, which were significantly lower than 17.5%, 35.0%, and 52.5% in the control group ( χ2 = 5.00, 4.26, 4.17, all P < 0.05). Conclusion:Five-element music therapy for the treatment of bipolar disorder can markedly alleviate depression and mania, restore patient's emotional state, improve clinical efficacy, and decrease recurrence rate.

Objective:This study aims to investigate the prevalence and distribution characteristics of mental disorders among people aged 18 and above in Shandong Province.Methods:In 2015, an epidemiological survey was carried out to investigate the patterns of mental disorders in 49 counties of Shandong Province. A total of 28 000 individuals aged 18 years or older were selected using the multistage stratified cluster sampling method. All these participants were classified as at a high or low risk of mental disorders according to the assessment results of the revised version of the General Health Questionnaire (GHQ). The diagnosis of mental disorders was confirmed using the Structured Clinical Interview for Diagnostic and Statistical Manual, Forth edition (DSM-Ⅳ) axis I or MMSE. All participants at high risk of mental disorders were evaluated using DSM-Ⅳ or MMSE to confirm the psychiatric diagnoses, while 10% of participants at low risk of mental disorders were randomly selected to be evaluated. The prevalence and its 95% confidence interval of mental disorders were adjusted according to study design and sociodemographic characteristics of the sample. The between-group differences of prevalence were compared using chi-square tests or Fisher′s exact tests as appropriately.Results:A total of 27 489 individuals completed survey. The adjusted prevalence of any mental disorder was 17.46% (95 %CI 17.02%-17.89%). The five most prevalent mental disorder spectrums were substance use disorders (5.29%), mood disorders (4.47%), anxiety disorders (4.46%), intellectual and mental disorders due to physical or substance (1.91%), and psychotic disorders (1.12%). The most common mental disorders were alcohol use disorder (5.27%) and major depressive disorder (2.14%). The prevalence of mental disorders in men was higher than that in women (23.37% vs. 13.89%; χ 2=408.91, P<0.01). There was no significant difference in the prevalence of mental disorders between rural residents and urban residents (17.69% vs. 17.20%; χ2=1.05, P=0.305). Of participants with mental disorders, 26.12% (1 047/4 008) had moderate to severe functional impairment and 10.98% (428/3 898) have sought professional help. Conclusion:The prevalence of mental disorders among people aged 18 and above in Shandong Province is basically consistent with the results of similar domestic studies. The prevalence of mental disorder was higher in men than in women and was not differ in participants living in urban and rural areas. Alcohol use disorder, major depressive disorder, non-specific anxiety disorder and non-specific depressive disorder are most common mental disorders.

Objective:This study aims to investigate the prevalence and distribution characteristics of mental disorders among people aged 18 and above in Shandong Province.Methods:In 2015, an epidemiological survey was carried out to investigate the patterns of mental disorders in 49 counties of Shandong Province. A total of 28 000 individuals aged 18 years or older were selected using the multistage stratified cluster sampling method. All these participants were classified as at a high or low risk of mental disorders according to the assessment results of the revised version of the General Health Questionnaire (GHQ). The diagnosis of mental disorders was confirmed using the Structured Clinical Interview for Diagnostic and Statistical Manual, Forth edition (DSM-Ⅳ) axis I or MMSE. All participants at high risk of mental disorders were evaluated using DSM-Ⅳ or MMSE to confirm the psychiatric diagnoses, while 10% of participants at low risk of mental disorders were randomly selected to be evaluated. The prevalence and its 95% confidence interval of mental disorders were adjusted according to study design and sociodemographic characteristics of the sample. The between-group differences of prevalence were compared using chi-square tests or Fisher′s exact tests as appropriately.Results:A total of 27 489 individuals completed survey. The adjusted prevalence of any mental disorder was 17.46% (95 %CI 17.02%-17.89%). The five most prevalent mental disorder spectrums were substance use disorders (5.29%), mood disorders (4.47%), anxiety disorders (4.46%), intellectual and mental disorders due to physical or substance (1.91%), and psychotic disorders (1.12%). The most common mental disorders were alcohol use disorder (5.27%) and major depressive disorder (2.14%). The prevalence of mental disorders in men was higher than that in women (23.37% vs. 13.89%; χ 2=408.91, P<0.01). There was no significant difference in the prevalence of mental disorders between rural residents and urban residents (17.69% vs. 17.20%; χ2=1.05, P=0.305). Of participants with mental disorders, 26.12% (1 047/4 008) had moderate to severe functional impairment and 10.98% (428/3 898) have sought professional help. Conclusion:The prevalence of mental disorders among people aged 18 and above in Shandong Province is basically consistent with the results of similar domestic studies. The prevalence of mental disorder was higher in men than in women and was not differ in participants living in urban and rural areas. Alcohol use disorder, major depressive disorder, non-specific anxiety disorder and non-specific depressive disorder are most common mental disorders.