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 relationship between the expression of serum microRNA-326(miR-326)and microRNA-623(miR-623)in non-small cell lung cancer(NSCLC)patients and their clinical pathological characteristics and prognosis.Methods A total of 114 NSCLC patients diagnosed in our hospital from March 2019 to June 2020 were collected as study subjects as case group,123 healthy individuals who underwent physical examination were as the control group.According to the 3-year prognosis,patients were separated into a survival group of 71 cases and a death group of 43 cases.Patient related clinical data were collected,real-time fluorescence quantitative PCR method was applied to detect the expression levels of miR-326 and miR-623 in various serum samples;Kaplan-Meier method was applied to analyze the relationship between the expression levels of serum miR-326 and miR-623 in NSCLC patients and their 3-year prognosis;Cox proportional risk regression model was applied to analyze the influencing factors of 3-year prognosis in NSCLC patients.Results The expression levels of serum miR-326 in the case group and control group were 0.64±0.15 and 1.02±0.23,respectively,and the expression levels of miR-623 were 0.56±0.10 and 0.98±0.15,respectively.The difference between the two groups was statistically significant(P＜0.05).The proportions of patients with low expression of miR-326 and miR-623 in low differentiation,TNM stage Ⅲ+Ⅳ,and lymph node metastasis were higher than those in high differentiation,TNM stage Ⅰ and Ⅱ,and no lymph node metastasis(P＜0.05).The 3-year survival rates of patients with low expression of miR-326(20/55,36.36％)and miR-623(27/61,44.26％)in the serum of NSCLC patients were lower than those of patients with high expression of miR-326(51/59,86.44％)and miR-623(44/53,83.02％)(Log Rank x2=32.060,22.812,P＜0.05).Serum miR-326[(0.55±0.09)vs.(0.69±0.11)]and miR-623 levels[(0.48±0.08)vs.(0.61±0.10)]of patients in the death group were significantly lower than those in the survival group(P＜0.05).The area under the curve(AUC)for poor prognosis of serum miR-326 and miR-623 alone and in combination in patients diagnosed with NSCLC were 0.828(95％CI:0.754 to 0.901),0.763(95％CI:0.671 to 0.855),and 0.903(95％CI:0.849 to 0.958),respectively.The proportions of patients with TNM stage Ⅲ+Ⅳ,lymph node metastasis,low expression of miR-326 and low expression of miR-623in the death group were higher than those in the survival group(P＜0.05).MiR-326 and miR-623 were protective factors affecting 3-year mortality in NSCLC patients,while TNM staging and lymph node metastasis were independent risk factors affecting 3-year mortality in NSCLC patients(P＜0.05).Conclusion The low expression of miR-326 and miR-623 may be involved in the occurrence and development of lung cancer,which is closely related to the clinical pathological characteristics and poor prognosis of patients.

Objective:To explore the clinical effects of free anterolateral thigh perforator flaps in repairing diabetic foot ulcers (DFUs) under a multi-disciplinary team (MDT) cooperation model.Methods:The study was a retrospective observational study. From June 2018 to December 2022, 49 DFU patients who met the inclusion criteria were admitted to the Department of Hand and Foot Microscopy and Wound Repair Surgery of Henan Provincial People's Hospital (People's Hospital of Zhengzhou University), including 28 males and 21 females, aged from 47 to 68 years, with type 2 diabetes history period ranging from 6 months to 21 years. Under a MDT cooperation model, the physicians from department of endocrinology comprehensively assessed the patients, stabilized the patients' general condition, and controlled their complications, the surgeons from department of vascular surgery assessed and improved the patients' lower limb blood supply, the physicians from department of infectious diseases provided anti-infection treatment plans, the physicians from department of anesthesiology and perioperative medicine assessed the patients' perioperative risk and ensured their perioperative safety, and according to the patients' condition, the physicians from departments such as cardiology, neurology, nutrition, and rehabilitation actively and timely participated in the treatment. The surgeons from department of hand and foot microscopy and wound repair surgery prepared the wound base and used free anterolateral thigh perforator flaps to repair the wounds. After once or multiple debridement in the first stage, the wound area ranged from 5.0 cm×4.5 cm to 17.0 cm×10.0 cm. After once or twice vacuum sealing drainage treatment, the free anterolateral thigh perforator flaps were used to repair the wounds with incision area of 6 cm×5 cm to 18 cm×11 cm in the second stage. The descending branches of lateral circumflex femoral artery and the accompanying veins of flaps were anastomosed to the arteries and veins in the recipient sites, respectively. The wounds in the flap donor sites were sutured directly. After surgery, whether the patient's perioperative period was stable, the survival of flaps, the healing of wounds in the flap donor and recipient sites were observed. During the follow-up, the texture and appearance of flaps, whether there was a new ulcer, and the patient's walking ability were observed.Results:All the patients had stable perioperative period. Among them, the flaps in 46 patients survived successfully; the flaps in 2 patients developed complete necrosis, including 1 case whose ulcer was healed after repair of pedicled flap from the lower leg, and 1 case who underwent amputation of the lower leg; the flap in 1 patient developed partial necrosis, which was healed after dressing change and skin grafting. The wounds in the flap donor and recipient sites healed well. During the postoperative follow-up of 6-24 months, the flaps had good texture and appearance with no new ulcers, and the patients had no obvious impairment in daily walk.Conclusions:The MDT cooperation model can sufficiently ensure the perioperative safety of DFU patients. The free anterolateral thigh perforator flaps can repair the DFU wounds achieving good clinical effects with high flap survival rate and decreased amputation rate.

Malignant tumors have surpassed stroke and coronary heart disease to become the main cause of death before the age of 70 in the world. The incidence of malignant tumors is increasing year by year， which seriously affects the living standards and social and economic development of Chinese people. Surgery， radiotherapy， chemotherapy， targeted therapy， and immunotherapy are the main means of Western medicine to intervene in tumors， which are of great significance for prolonging the survival time of patients. However， there are many disadvantages such as adverse reactions and drug resistance. Traditional Chinese medicine has become a research hotspot in recent years because of its definite curative effect and wide application in tumor treatment. Xiao Chaihutang is derived from the Treatise on Febrile and Miscellaneous Diseases. It is composed of Bupleuri Radix， Scutellariae Radix， Ginseng Radix， Pinelliae Rhizoma， Glycyrrhizae Preparata Radix， Ginger， and Jujube. It has the effects of reconciling Shaoyang， reconciling cold and heat Yin and Yang， soothing the liver， and relieving depression. This prescription and the prescriptions based on it are widely used in various stages of tumors. This study summarized the Chinese and foreign research of Xiao Chaihutang in the field of tumors in the past 10 years and explored the role and mechanism of Xiao Chaihutang in blocking precancerous lesions， controlling the development of malignant tumors， reducing the occurrence of adverse reactions after intervention， and alleviating common complications， with a view to expanding the clinical medication ideas.

Objective To observe the influence of different energy windows of the medium-energy general-purpose(MEGP)collimator on image quality,so as to optimize the energy window of yttrium-90(90Y)bremsstrahlung SPECT imaging.Methods 90Y bremsstrahlung spectrum was acquired,and the sensitivity,percentage of the source counts in useful field of view(S/FOV%)and signal-to-background ratio(S/B)of 90Y bremsstrahlung SPECT imaging at MEGP under different energy windows were compared.Results The energy spectrum of 90Y bremsstrahlung was a continuous curve,with the peak of 76.2 keV with MEGP collimator.The images obtained with MEGP collimator were clear,and no significant differences of S/FOV%nor S/B was found between 10%and 20%window width groups(both P＞0.05),but the sensitivities of the latter was higher than the former(P＜0.05).The sensitivity of 70-90 keV images was relatively high,while the S/FOV%and S/B had decreased.The S/FOV%and S/B of images ranging from 40-60 keV were high,but the sensitivity was low.Images acquired with 100 keV±20%showed fairly high sensitivity,S/FOV%and S/B,which was 69.73%,0.62 and 1.64,respectively.Conclusion When performing 90Y bremsstrahlung SPECT with MEGP collimator,the image quality at 20%window width was better than at 10%window width,and 100 keV±20%showed fairly high sensitivity and not significantly decreased S/FOV%and S/B.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

OBJECTIVE To explore the safety and efficacy of tocilizumab in the treatment of refractory anti-N-methyl-D-aspartate receptor encephalitis in children, and to provide reference for the treatment of this disease. METHODS The clinical manifestations, diagnosis and treatment, safety and efficacy of tocilizumab in a case of refractory anti-NMDAR encephalitis in Children’s Hospital, Zhejiang University School of Medicine were analyzed retrospectively, and the relevant literature was reviewed. RESULTS The clinical symptoms of the patient were not improved after 2 doses of methylprednisolone, immunoglobulin and 6 doses of rituximab. After 6 doses of tocilizumab, the modified Rankin scale(mRS) score was improved without adverse reactions. CONCLUSION Tocilizumab, as a escalation second-line immunotherapy, is effective and well tolerated in the treatment of refractory anti-NMDAR encephalitis. It is one of the potential therapeutic means.

Atopic dermatitis(AD) is a chronic skin disease characterized by eczema and itching, and is one of the most common skin diseases in children. The treatment of AD is currently mainly based on drug therapy, but the treatment needs of children, especially those with moderate to severe AD, have not been fully met, safe and effective long-term treatment plans still need to be explored and practiced. Targeted drugs represented by biological agents and small molecule inhibitors are emerging drugs for the treatment of moderate to severe atopic dermatitis. Referring to relevant literature both domestically and internationally in recent years, this review focuses on two aspects: biological targeting agents and small molecule inhibitors, providing a foundation for the further development and application of targeted drugs for children with moderate to severe atopic dermatitis.

To explore the clinical and genetic features of Aicardi-Goutières syndrome (AGS) caused by IFIH1 gene mutation.

As artificial intelligence technology rapidly advances, its deployment within the medical sector presents substantial ethical challenges. Consequently, it becomes crucial to create a standardized, transparent, and secure framework for processing medical data. This includes setting the ethical boundaries for medical artificial intelligence and safeguarding both patient rights and data integrity. This consensus governs every facet of medical data handling through artificial intelligence, encompassing data gathering, processing, storage, transmission, utilization, and sharing. Its purpose is to ensure the management of medical data adheres to ethical standards and legal requirements, while safeguarding patient privacy and data security. Concurrently, the principles of compliance with the law, patient privacy respect, patient interest protection, and safety and reliability are underscored. Key issues such as informed consent, data usage, intellectual property protection, conflict of interest, and benefit sharing are examined in depth. The enactment of this expert consensus is intended to foster the profound integration and sustainable advancement of artificial intelligence within the medical domain, while simultaneously ensuring that artificial intelligence adheres strictly to the relevant ethical norms and legal frameworks during the processing of medical data.
Artificial Intelligence/legislation & jurisprudence* ; Humans ; Consensus ; Computer Security/standards* ; Confidentiality/ethics* ; Informed Consent/ethics*