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 construct large medical model named by "Huaxi HongYi"and explore its application effectiveness in assisting medical record generation. Methods By the way of a full-chain medical large model construction paradigm of "data annotation - model training - scenario incubation", through strategies such as multimodal data fusion, domain adaptation training, and localization of hardware adaptation, "Huaxi HongYi" with 72 billion parameters was constructed. Combined with technologies such as speech recognition, knowledge graphs, and reinforcement learning, an application system for assisting in the generation of medical records was developed. Results Taking the assisted generation of discharge records as an example, in the pilot department, after using the application system, the average completion times of writing a medical records shortened (21 min vs. 5 min) with efficiency increased by 3.2 time, the accuracy rate of the model output reached 92.4%. Conclusion It is feasible for medical institutions to build independently controllable medical large models and incubate various applications based on these models, providing a reference pathway for artificial intelligence development in similar institutions.

Objective To investigate the effects of aloperine(ALO)on bone metabolism in osteoporosis(OP)mice via Wnt/β-catenin signaling pathway-mediated autophagy and apoptosis.Methods Sixty mice were randomly allocated into six groups(n=10 per group):Sham group(sham-operated mice),OP group(osteoporosis model induced by bilateral ovariectomy),L-ALO group(OP mice intraperitoneally injected with 10 mg/kg aloper-ine),M-ALO group(OP mice intraperitoneally injected with 20 mg/kg aloperine),H-ALO group(OP mice intra-peritoneally injected with 30 mg/kg aloperine),and EV group(OP mice administered 0.09 mg/kg estradiol valerate).Bone mineral density and microstructure of the tibia were assessed.Hematoxylin and eosin(HE)staining was per-formed to examine the morphology of tibial bone tissue.Serum levels of OCN,OPG,ALP,Ca,and P were measured using ELISA.Protein expression levels of LC3-Ⅱ,LC3-Ⅰ,Beclin-1,P62,Caspase-3,Caspase-9,Bax,Wnt3a,β-catenin,and C-Myc were analyzed by Western blot.Autophagosomes were visualized using immunofluorescence.Results Compared with the Sham group,the bone mineral density(BMD)and trabecular thickness in the OP group were significantly reduced,while trabecular separation,bone surface area,and volume were significantly increased(P<0.05).The levels of OPG,OCN,Ca,and P were significantly downregulated,whereas ALP levels were significantly upregulated(P<0.05).Additionally,the LC3-Ⅱ/LC3-Ⅰ ratio and expression levels of Beclin-1,Wnt3a,β-catenin,and C-Myc proteins were significantly decreased,while the expression levels of P62,Caspase-3,Caspase-9,and Bax proteins were significantly increased(P<0.05).Compared with the OP group,the L-ALO,M-ALO,and H-ALO groups exhibited significant increases in BMD and trabecular thickness,along with significant decreases in trabecular separation,bone surface area,and volume(P<0.05).The levels of OPG,OCN,Ca,and P were significantly upregulated,while ALP levels were significantly downregulated(P<0.05).Furthermore,the LC3-Ⅱ/LC3-Ⅰ ratio and expression levels of Beclin-1,Wnt3a,β-catenin,and C-Myc proteins were significantly increased,while the expression levels of P62,Caspase-3,Caspase-9,and Bax proteins were significantly decreased(P<0.05).In contrast,compared with the OP group,the EV group showed significant increases in BMD and trabecular thickness,as well as significant decreases in trabecular separation,bone surface area to volume ratio(P<0.05).The levels of OPG,OCN,Ca,and P were significantly upregulated,while ALP levels were significantly downregulated(P<0.05).Moreover,the LC3-Ⅱ/LC3-Ⅰ ratio and expression levels of Beclin-1,Wnt3a,β-catenin,and C-Myc proteins were significantly increased,while the expression levels of P62,Caspase-3,Caspase-9,and Bax proteins were significantly decreased(P<0.05).Conclusions Peanine may promote autophagy in osteoblasts and inhibit their apoptosis,thereby improving bone metabolism in OP mice.This effect may be mediated through the activation of the Wnt/β-catenin signaling pathway.

Objective:It aims to investigate the impact of enhancing the outpatient total cost for urban and rural residents on total outpatient costs and medication expenses,providing policy recommendations for improving outpatient coverage under city-level coordination.Methods:Using Pilot County as a case study and outpatient medical record data,the PSM-DID method is employed to evaluate the effect of raising the Outpatient Medical Insurance level on total outpatient costs and medication expenses per case.Results:After improving the Outpatient Medical Insurance level,total outpatient costs per case increased significantly by 3.87%(P＜0.05),while medication expenses per case decreased significantly by 10.90%(P＜0.001).For the elderly,total outpatient costs per case rose significantly by 6.08%(P＜0.05),while there is a increase for non-elderly patients(P＞0.05).Medication expenses per case for the elderly decreased significantly by 11.32%(P＜0.001),while non-elderly patients saw a 7.85%decrease(P＞0.05).Conclusion:The improvement in the outpatient coordinated hierarchy significantly increased the total cost for urban and rural residents while significantly reducing medication expenses.The impact on outpatient costs was more pronounced among the elderly.It is recommended that policy design for enhancing the general outpatient coordination level for urban and rural residents consider both equity and efficiency.

Objective To explore the differences in terahertz(THz)signal characteristics between normal and ischemic liver tissues of New Zealand rabbits using THz time-domain spectroscopy(THz-TDS),thereby providing a novel detection technique for the pathological detection of liver tissues.Methods Liver ischemia models were established in New Zealand rabbits.The THz scanning signal maps of normal and ischemic liver tissues were obtained using a reflective THz-TDS system,and the acquired signals were subjected to principal component analysis.Results Both normal and ischemic liver tissues displayed two distinct peaks in their THz signals.However,the amplitude of the THz signal in ischemic liver tissue was higher than that in normal liver tissue,with significant differences also observed in their signal morphologies.Principal component analysis results revealed a clear clustered distribution between the signals of normal and ischemic liver tissues,indicating that THz-TDS could effectively distinguish between the two tissue types.Conclusion THz-TDS can be applied to the detection of ischemic liver tissue,providing experimental evidence to support further research on the early diagnosis of liver ischemia and exhibiting broad prospects for clinical application.

Sleep disorders is one of the most frequent and severe complications in patients with tinnitus and is highly correlated with the severity of tinnitus.Sleep disorders and tinnitus influence each other,forming a vicious circle.While in-terventions have been developed to alleviate tinnitus distress,these interventions are usually not effective in improving sleep in patients with tinnitus and sleep disorders.Helping tinnitus patients to resolve sleep disorders is the key to breaking the cycle and improving their quality of life.In this narrative review,we studyed the current state of research on sleep disorders in patients with tinnitus through three aspects:epidemiology,physiological and psychological mechanisms,and existing psychological,physical,and pharmacological interventions,and to provide a basis for further research on the relationship between tinnitus and sleep disorders and the precise treatment of tinnitus.

Objective:It aims to investigate the impact of enhancing the outpatient total cost for urban and rural residents on total outpatient costs and medication expenses,providing policy recommendations for improving outpatient coverage under city-level coordination.Methods:Using Pilot County as a case study and outpatient medical record data,the PSM-DID method is employed to evaluate the effect of raising the Outpatient Medical Insurance level on total outpatient costs and medication expenses per case.Results:After improving the Outpatient Medical Insurance level,total outpatient costs per case increased significantly by 3.87%(P＜0.05),while medication expenses per case decreased significantly by 10.90%(P＜0.001).For the elderly,total outpatient costs per case rose significantly by 6.08%(P＜0.05),while there is a increase for non-elderly patients(P＞0.05).Medication expenses per case for the elderly decreased significantly by 11.32%(P＜0.001),while non-elderly patients saw a 7.85%decrease(P＞0.05).Conclusion:The improvement in the outpatient coordinated hierarchy significantly increased the total cost for urban and rural residents while significantly reducing medication expenses.The impact on outpatient costs was more pronounced among the elderly.It is recommended that policy design for enhancing the general outpatient coordination level for urban and rural residents consider both equity and efficiency.

Objective To explore the differences in terahertz(THz)signal characteristics between normal and ischemic liver tissues of New Zealand rabbits using THz time-domain spectroscopy(THz-TDS),thereby providing a novel detection technique for the pathological detection of liver tissues.Methods Liver ischemia models were established in New Zealand rabbits.The THz scanning signal maps of normal and ischemic liver tissues were obtained using a reflective THz-TDS system,and the acquired signals were subjected to principal component analysis.Results Both normal and ischemic liver tissues displayed two distinct peaks in their THz signals.However,the amplitude of the THz signal in ischemic liver tissue was higher than that in normal liver tissue,with significant differences also observed in their signal morphologies.Principal component analysis results revealed a clear clustered distribution between the signals of normal and ischemic liver tissues,indicating that THz-TDS could effectively distinguish between the two tissue types.Conclusion THz-TDS can be applied to the detection of ischemic liver tissue,providing experimental evidence to support further research on the early diagnosis of liver ischemia and exhibiting broad prospects for clinical application.

Sleep disorders is one of the most frequent and severe complications in patients with tinnitus and is highly correlated with the severity of tinnitus.Sleep disorders and tinnitus influence each other,forming a vicious circle.While in-terventions have been developed to alleviate tinnitus distress,these interventions are usually not effective in improving sleep in patients with tinnitus and sleep disorders.Helping tinnitus patients to resolve sleep disorders is the key to breaking the cycle and improving their quality of life.In this narrative review,we studyed the current state of research on sleep disorders in patients with tinnitus through three aspects:epidemiology,physiological and psychological mechanisms,and existing psychological,physical,and pharmacological interventions,and to provide a basis for further research on the relationship between tinnitus and sleep disorders and the precise treatment of tinnitus.

Objective To investigate the effects of aloperine(ALO)on bone metabolism in osteoporosis(OP)mice via Wnt/β-catenin signaling pathway-mediated autophagy and apoptosis.Methods Sixty mice were randomly allocated into six groups(n=10 per group):Sham group(sham-operated mice),OP group(osteoporosis model induced by bilateral ovariectomy),L-ALO group(OP mice intraperitoneally injected with 10 mg/kg aloper-ine),M-ALO group(OP mice intraperitoneally injected with 20 mg/kg aloperine),H-ALO group(OP mice intra-peritoneally injected with 30 mg/kg aloperine),and EV group(OP mice administered 0.09 mg/kg estradiol valerate).Bone mineral density and microstructure of the tibia were assessed.Hematoxylin and eosin(HE)staining was per-formed to examine the morphology of tibial bone tissue.Serum levels of OCN,OPG,ALP,Ca,and P were measured using ELISA.Protein expression levels of LC3-Ⅱ,LC3-Ⅰ,Beclin-1,P62,Caspase-3,Caspase-9,Bax,Wnt3a,β-catenin,and C-Myc were analyzed by Western blot.Autophagosomes were visualized using immunofluorescence.Results Compared with the Sham group,the bone mineral density(BMD)and trabecular thickness in the OP group were significantly reduced,while trabecular separation,bone surface area,and volume were significantly increased(P<0.05).The levels of OPG,OCN,Ca,and P were significantly downregulated,whereas ALP levels were significantly upregulated(P<0.05).Additionally,the LC3-Ⅱ/LC3-Ⅰ ratio and expression levels of Beclin-1,Wnt3a,β-catenin,and C-Myc proteins were significantly decreased,while the expression levels of P62,Caspase-3,Caspase-9,and Bax proteins were significantly increased(P<0.05).Compared with the OP group,the L-ALO,M-ALO,and H-ALO groups exhibited significant increases in BMD and trabecular thickness,along with significant decreases in trabecular separation,bone surface area,and volume(P<0.05).The levels of OPG,OCN,Ca,and P were significantly upregulated,while ALP levels were significantly downregulated(P<0.05).Furthermore,the LC3-Ⅱ/LC3-Ⅰ ratio and expression levels of Beclin-1,Wnt3a,β-catenin,and C-Myc proteins were significantly increased,while the expression levels of P62,Caspase-3,Caspase-9,and Bax proteins were significantly decreased(P<0.05).In contrast,compared with the OP group,the EV group showed significant increases in BMD and trabecular thickness,as well as significant decreases in trabecular separation,bone surface area to volume ratio(P<0.05).The levels of OPG,OCN,Ca,and P were significantly upregulated,while ALP levels were significantly downregulated(P<0.05).Moreover,the LC3-Ⅱ/LC3-Ⅰ ratio and expression levels of Beclin-1,Wnt3a,β-catenin,and C-Myc proteins were significantly increased,while the expression levels of P62,Caspase-3,Caspase-9,and Bax proteins were significantly decreased(P<0.05).Conclusions Peanine may promote autophagy in osteoblasts and inhibit their apoptosis,thereby improving bone metabolism in OP mice.This effect may be mediated through the activation of the Wnt/β-catenin signaling pathway.