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.

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.

Signal transduction and activator of transcription factor 1(STAT1), one of the important members of the STAT family, is a key cytoplasmic transcription factor and an important component of the JAK-STAT signaling pathway. Gain-of-function mutations in STAT1 (STAT1-GOF) impaired the dephosphorylation of STAT1 protein, mediated the enhancement of cell signaling pathways such as type Ⅰ, Ⅱ, and Ⅲ interferon(IFN) and interleukins-27 (IL-27), IL-6, IL-10, and IL-17, and inhibited Th17 cells. The clinical manifestations of STAT1-GOF are diverse, including chronic mucocutaneous candidiasis and autoimmune diseases. For the treatment of STAT1-GOF, such as targeted therapy with ruxolitinib for STAT1 hyperphosphorylation, immunomodulatory therapy and hematopoietic stem cell transplantation for different self-immune systems, certain curative effects can be obtained. With the understanding of disease mechanisms and the discovery of new clinical phenotypes, this review focuses on the diseases caused by gain-of-function mutations of STAT1, and introduces the clinical manifestations and treatment progress of STAT1-GOF to promote the understanding of such diseases and their future diagnosis, treatment and research works.

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

Objective To develop and evaluate the equivalence of the Mandarin test material for tracking of noise tolerance(TNT)test.Methods Six different speech materials were developed(themes including daily life,entertainment,family,festivals,outdoors,and school).Four-minute TNT tests were measured in 21 normal hear-ing subjects using six different test materials.For each session,the tolerable noise level(TNL)and TNT scores were acquired and calculated for 3 time windows(31～240 s,31～120 s,151～240 s).Results Statistic analysis showed significant differences in the TNL(F=43.611,P＜0.05)among the normal hearing listeners.There were statistically significant differences in standardize z-scored TNT scores of the six different materials in the three time windows(P＜0.05).Post-hoc comparisons revealed that all significant differences involved the family and daily life themes.Conclusion Entertainment,festival,outdoors and school themed test materials can serve as the materials of Mandarin tracking of noise tolerance test and can be appied in research and clinical testing.

A case of limb girdle muscular dystrophy type 2S (LGMD2S) caused by maternal uniparental disomy on chromosome 4 at the First Affiliated Hospital of Henan University of Chinese Medicine in March 2020 was reported.The female child, aged 9 months and 4 days, presented with developmental delay after bacterial meningitis in early infancy, decreased muscle strength in infancy and increased muscle and liver enzymes.Family genetic analysis showed that the child′s monodiploid in chromosome 4 was maternal origin, and the homozygous c. 1066T > G (p.Y356D) of TRAPPC11 gene may had pathogenic variation, which came from the child′s mother.The final diagnosis of LGMD2S was made according to the clinical manifestations and gene test results.LGMD2S is a rare autosomal recessive disease caused by the pathogenic variation of TRAPPC11 gene.Its clinical characteristics include proximal limb weakness, motor and intellectual retardation, seizures, motor disorders, elevated serum creatine kinase and muscular dystrophy like pathological changes in children.

Precision medicine aims at using target therapy on specific diseases by studying the pathogenesis and finding biomarkers. Inborn errors of immunity (IEI) are caused by single gene mutations, providing the perfect human models to study immunology. The technology rapidly developes recently, so scientists have a deeper understandings of the phenotypes, genotypes, and the biological targets, so that doctors are able to use precision medicine on IEIs with many successful cases. The precision medicine have advantages in the treatment of pathogenesis of diseases. This article summarizes successful cases of using precision medicine for IEI recently.

Chronic granulomatous disease (CGD) is a heterogeneous primary immunodeficiency characterized by severe bacterial and fungal infections and tissue granuloma formation early in life. Diagnosis of CGD involves the granulocyte function assays and gene mutation analysis. X-linked CGD (XL-CGD) caused by gene defects of CYBB is the most prevalent type of CGD. The clinical data and gene characteristics of a rare female X-chromosome mosaicism leading to inheritance of XL-CGD were reported here. The patient is a 7-year-old boy manifested as recurrent lower respiratory tract infection and failed to thrive. The patient had a history of osteo- myelitis and perianal abscess, with Bacille Calmette-Guérin (BCG) vaccine complications. Respiratory burst of neutrophils was measured with DHR oxidation assay and the histogram showing no significant change in neutrophil fluorescence after stimulation of the patient and the mother's histogram had a pattern of 2 peaks after stimulation. A heterozygous mutation in the CYBB gene (c.866G > A, p.W289X) was identified through inheritance from the patient's mother. Genetic analysis from blood and cheek mucosal cells indicated the female was a mosaicism in CYBB with mutation was present in about 19.5% of her leukocytes. We reported the clinical data and gene characteristics of a rare female X-chromosome mosaicism leading to inheritance of XL-CGD for the first time in China to enrich the understanding of XL-CGD and provide new sights for the hereditary counseling.

Objective:To apply the best evidence of phaseⅠ cardiac rehabilitation after coronary artery bypass grafting (CABG) into clinical practice and evaluate its effects.Methods:Following the Australian Jonna Briggs Institute (JBI) clinical evidence program and evidence transformational practice application system, the evidence of phaseⅠ cardiac rehabilitation exercise after CABG was retrieved, screened and evaluated, and the review indicators were formulated. From September 2019 to February 2020, 41 nurses and 109 CABG patients from the Cardiovascular Surgery Ward of the Affiliated Hospital of Qingdao University were selected. The data of 56 patients were collected before the application of the best evidence, and those of 53 patients were collected after the application of the best evidence. The implementation rate of the review indicators, the degree of knowledge of the best evidence among nurses and patients, the Six Minute Walk Test (6MWT) distance and the left ventricular ejection fraction (LVEF) before and after the application of the best evidence were compared.Results:After the application of the evidence, the nurses' implementation rate of the 13 review indicators of phaseⅠ cardiac rehabilitation exercises was improved, and the difference was statistically significant ( P<0.05) ; the nurses' exercise knowledge score increased from (53.66±14.01) points to (71.59±14.93) points; the patients' exercise knowledge score increased from (26.22±17.46) points to (60.49±15.52) points, and the differences were statistically significant ( t=-5.61, -9.40; P<0.01) . After the application of the evidence, the patients' 6MWT distance increased from (241.82±72.05) m to (246.25±69.26) m, and the difference was statistically significant ( t=-2.238, P<0.05) ; however, there was no statistically significant difference in LVEF before and after the application of the evidence ( P>0.05) . Conclusions:The clinical application of the best evidence for phase I cardiac rehabilitation exercises in CABG patients can standardize nurses' behaviors, improve nurses and patients' knowledge of evidence, and increase the 6MWT distance of CABG patients.

Objective To examine the impact of vacuum sealing drainage on clinical outcomes of patients with post-sternotomy mediastinitis after cardiac surgery. Methods A systematic search were performed in Cochrane Library, Pubmed, Embase, China Biology Medicine(CBM), WanFang, VIP database. The quality of articles was critically appraised and data were extracted by 2 reviewers independently. Meta-analysis were conducted for the eligible researches. Results Fourteen cohort studies were inclued finally. Patients treated with VSD had significantly lower in-hospital mortalityand lower re-infection compared to those treated without VSD. While there had no significant defferences in length of ICU stay(days) and in-hospital stay (days) between VSD group and control group. Conclusions VSD therapy was associated with lower re-infection and in-hospital mortality than other conventional methods in patients with post-sternotomy mediastinitis after cardiac surgery and those results should be further tested in future research and practice.