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 protective effect of Gynostemma pentaphyllum on memory of individuals rapidly ascending to high altitudes.Methods Twenty-one healthy subjects were randomly divided into a G.pentaphyllum food group(n=12)and a control group(n=9).The first group consumed G.pentaphyllum food for seven consecutive days while the control group received placebos.Both groups ascended from the plains to an altitude of 3600 m.Memory function was assessed using the matching memory and sequential memory tests of a cognitive evaluation system on day 1 and day 7 on the plains,and at 24 and 48 h after ascending to the high altitude.Scores of acute mountain sickness symptoms were also recorded.Results After 24 h of stay at the high altitude,the score of headache of the G.pentaphyllum food group was significantly lower than that of the control group(P＜0.05).Cognitive test results showed that the matching memory accuracy and sequential memory accuracy of the control group at 24 and 48 h were significantly lower than those on the plains(P＜0.05).In contrast,the G.pentaphyllum food group performed significantly better than the control group in these metrics(P＜0.05).Conclusion Regular consumption of G.pentaphyllum food can effectively alleviate headache symptoms in individuals rapidly ascending to high altitudes and mitigate the decline in working memory,short-term memory,and memory spans caused by acute hypoxic exposure.

ObjectiveTo examine the relationship between metabolic syndrome (MS) and its key components in granulomatous mastitis (GM), we explored potential pathological mechanisms through the lens of traditional Chinese medicine (TCM), particularly the concept of intermingled phlegm-blood stasis.MethodsIn this retrospective study, we enrolled 172 patients with GM and 164 patients with non-inflammatory benign breast masses. Metabolic indicators (waist circumference [WC], blood lipids, etc.), inflammatory markers (C-reactive protein, interleukin-6, tumor necrosis factor-α), and adipose tissue CD68 expression were measured. Logistic regression was used to analyze risk factors and receiver operating characteristic curves were used to evaluate diagnostic efficacy. The correlation between TCM pathogenesis and biomarkers was also examined.ResultsMS prevalence was significantly higher in the GM group than in the controls (26.16% vs. 6.10%, P .001). Multivariate analysis identified abdominal obesity (WC ≥ 80 cm, odds ratio [OR] = 1.065) and low levels of high-density lipoprotein cholesterol (HDL-C; 1.29 mmol/L, OR = 0.066) as independent risk factors for GM (P .001 for both). Among patients with GM, HDL-C levels were inversely correlated with inflammatory markers (r = −0.341 to −0.440), whereas patients with concurrent MS demonstrated greater CD68 macrophage infiltration (P .001). According to TCM, abdominal obesity corresponds to “spleen deficiency with phlegm-dampness accumulation,” and low HDL-C reflects “deficiency of vital qi,” which collectively lead to phlegm-blood stasis obstruction in the mammary collaterals; this aligns with the key MS driving mechanisms of chronic inflammation and immune dysregulation.ConclusionMS promotes GM development through chronic inflammation and immune dysregulation, with abdominal obesity and low HDL-C levels serving as core risk factors. The TCM theory of intermingled phlegm-blood stasis provides a novel interpretation of the metabolic-inflammatory mechanisms underlying GM. Accordingly, we propose phlegm-resolving and blood-activating strategies as potential therapeutic approaches for metabolic–immune axis regulation.

ObjectiveTo evaluate the efficacy and safety of spleen-strengthening therapy in the treatment of postoperative colorectal adenoma. MethodRandomized controlled trials （RCTs） of spleen-strengthening therapy for postoperative colorectal adenoma published in the databases of China National Knowledge Infrastructure （CNKI）， Wanfang Data， VIP， SinoMed， PubMed， Cochrane Library， Embase， Web of Science， and Clinical Trials registry center from database inception to February， 2024 were retrieved and selected based on inclusion and exclusion criteria. The included RCTs were subjected to Meta-analysis using RevMan 5.3 software. ResultA total of 29 articles were included， involving 2 935 patients， with 1 462 in the experimental group and 1，473 in the control group. The Meta-analysis results showed that compared with conventional Western medical treatment alone， the experimental group that combined the spleen-strengthening therapy with conventional Western treatment had a significantly lower recurrence rate at six months post-surgery ［relative risk （RR）=0.45， 95% confidence interval （CI） ［0.37， 0.53］， P<0.000 01］， and at one year post-surgery （RR=0.54， 95%CI ［0.47， 0.63］， P<0.000 01）. Additionally， the experimental group showed significant improvement in clinical symptoms （RR=1.28，95%CI ［1.17，1.40］， P<0.000 01） and more pronounced effects in suppressing inflammatory factors， with no serious adverse reactions observed. The differences were all statistically significant. The analysis of the Chinese medicines used in the included articles revealed 28 prescriptions with 99 different drugs used 369 times in total. The most frequently used drug was Atractylodis Macrocephalae Rhizoma， followed by Codonopsis Radix， Poria， Glycyrrhizae Radix et Rhizoma， and Citri Reticulatae Pericarpium. Furthermore， correlation analysis showed that spleen-strengthening drugs were often used in combination with heat-clearing and toxin-removing drugs， qi-regulating drugs， and blood-activating drugs such as Hedyotidis Diffusae Herba， Citri Reticulatae Pericarpium， and Curcumae Rhizoma. ConclusionThe spleen-strengthening therapy demonstrates good clinical efficacy and high safety for patients with postoperative colorectal adenoma. However， due to the limitations in the quantity and quality of the included RCTs， more high-quality clinical trials are needed to verify these conclusions.

Epimedin B(EB)is one of the main flavonoid ingredients present in Epimedium brevicornum Maxim.,a traditional herb widely used in China.Our previous study showed that EB was a stronger inducer of melanogenesis and an activator of tyrosinase(TYR).However,the role of EB in melanogenesis and the mechanism underlying the regulation remain unclear.Herein,as an extension to our previous investi-gation,we provide comprehensive evidence of EB-induced pigmentation in vivo and in vitro and eluci-date the melanogenesis mechanism by assessing its effects on the TYR family of proteins(TYRs)in terms of expression,activity,and stability.The results showed that EB increased TYRs expression through microphthalmia-associated transcription factor-mediated p-Akt(referred to as protein kinase B(PKB))/glycogen synthase kinase 3β(GSK3β)/β-catenin,p-p70 S6 kinase cascades,and protein 38(p38)/mitogen-activated protein(MAP)kinase(MAPK)and extracellular regulated protein kinases(ERK)/MAPK pathways,after which EB increased the number of melanosomes and promoted their maturation for melanogenesis in melanoma cells and human primary melanocytes/skin tissues.Furthermore,EB exerted repigmentation by stimulating TYR activity in hydroquinone-and N-phenylthiourea-induced TYR inhibitive models,including melanoma cells,zebrafish,and mice.Finally,EB ameliorated monobenzone-induced depigmentation in vitro and in vivo through the enhancement of TYRs stability by inhibiting TYR misfolding,TYR-related protein 1 formation,and retention in the endoplasmic reticulum and then by downregulating the ubiquitination and proteolysis processes.These data conclude that EB can target TYRs and alter their expression,activity,and stability,thus stimulating their pigmentation function,which might provide a novel rational strategy for hypopigmentation treatment in the pharmaceutical and cosmetic industries.

Objective To provide the evidence for the development of personalized health education courses for twin pregnant women.We explored the health education and psychosocial demand of twin pregnant women from the perspective of social ecosystem theory.Methods By purposive sampling,18 twin pregnant women hospitalized in the twin medical center of a tertiary A hospital in Shenyang from January to March 2023 to conduct for semi-structured interviews,and Colaizzi's 7-step analysis method was used to sort out and analyze the data.Results 3 themes were extracted from the health education and psychosocial needs of twin pregnant women.Microsystem:the content needs of twin pregnant women's health education(the guidance needs of nutrition intake and weight growth;the needs for fetus health monitoring guidance;the cognitive needs of twin pregnancy complications;the needs for health education knowledge related to puerperium and the diversification of the choice of teaching methods).Mesosystem:the emotional support needs of twin pregnant women during prenatal and puetperal(the needs of family support and peer education support).Macrosystem:seeking social support and network information support(the demand of community support;the needs of information related to twin pregnant women's hierarchical management system and maternal fetal medical referral process and the needs for network health education information).Conclusion The women with twin pregnancy have different needs for health education content in each stage of pregnancy and puerperium,and there are urgent needs for emotional support and social support.Clinical nurses should construct health education courses according to the needs of twin women,and innovate in content and form,so as to improve the self-care ability of twin pregnant women and the knowledge level of family caregivers,and improve the pregnancy outcome.

Objective:To investigate the risk factors for postsurgical gastroparesis syndrome (PGS) after laparoscopic complete mesocolic excision (CME) for right colon cancer.Methods:The clinical data of 358 patients who underwent laparoscopic CME for right colon cancer were retrospectively analyzed. Univariate and multivariate logistics regression were used to analyze the independent risk factors for PGS.Results:PGS occurred in 19 patients (4.8%). Logistic regression analysis showed that preoperative anxiety score (PAS-7)≥14 ( OR=6.450, P=0.039), preoperative serum albumin<35 g/L ( OR=9.302, P=0.011), colon cancer at hepatic flexura ( OR=9.782, P=0.007), No.206 group lymph node dissection ( OR=8.317, P=0.004), and intra-abdominal infection ( OR=5.755, P=0.043) were independent risk factors for PGS. Conclusion:Patient's preoperative health status, tumor location, scope of lymph node dissection and postoperative intra-abdominal infection are all risk factors related to PGS after CME for right colon cancer.

G-protein signaling modulator 2 is a member of the GPSM family, with emerging significance in various diseases including Chadley-McCullough syndrome, rheumatoid arthritis, and systemic lupus erythematosus. Furthermore, its involvement extends to tumor pathogenesis, encompassing non-small-cell lung cancer, breast cancer, hepatocellular carcinoma, pancreatic carcinoma, serous ovarian cancer, Ewing's sarcoma, and osteosarcoma, influencing proliferation, invasion, and metastasis. There is no relevant review on the mechanism of GPSM2 in tumor progression. This paper will summarize the research progress on GPSM2 in tumors in recent years, focusing on its role and mechanism, with the aim of providing references and guidance for further research.

Objective To establish a nomogram model for efficiently predicting overall survival(OS)and cancer-specific survival(CSS)in patients with CRCHBM.Method 2239 patients from 2010 to 2019 were retrospectively analyzed from the Surveillance,Epidemiology,and End Results Program(SEER)databases and Wuhan Union Hospital Cancer Center.SEER is randomly assigned to the training and internal validation cohorts,and the Wuhan database serves as the external validation.Cox regression analyses were used to determine the independent clinicopathological prognosis factors affecting OS and CSS,and a nomogram was constructed to predict OS and CSS.The clinical utility of columnar plots was assessed using calibration curves,area under the curve(AUC),and decision curve analysis(DCA).Result OS column line graphs were constructed based on nine independent predictors:age,tumor location,degree of differentiation,tumor size,TNM stage,chemotherapy,primary focus surgery,number of lymph nodes sampled,and serum carcinoembryonic antigen(CEA)level.The C-index of the nomogram to predict the 1-,3-,and 5-year OS were 0.764,0.790,and 0.805 in the training group,0.754,0.760,and 0.801 in the internal validation group,and 0.822,0.874,and 0.906 in the external validation group.CSS column line graphs were constructed based on 3 independent predictors of TNM staging,radiotherapy and chemotherapy.The 1-,3-,and 5-year CSS AUROC values of the training group were 0.791,0.757,and 0.782,respectively.0.682,0.709,0.625 in the internal validation group and 0.759,0.702,0.755 in the external validation group,respectively.The results of receiver operating characteristic curve(ROC),ROC and DCA showed that the use of our model was more effective in predicting OS and CSS than other single clinicopathological features.Conclusion In summary,the nomogram based on significant clinicopathological features can be conveniently used to predict OS and CSS individually in patients with CRCHBM.