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.

Psoriasis is a chronic inflammatory skin disease, and its pathogenesis is largely modulated by abnormal angiogenesis. Previous research has indicated that AlkB homolog 5 (ALKBH5), an important demethylase affecting N⁶-methyladenosine (m⁶A) modification, plays a role in regulating angiogenesis in cardiovascular and eye diseases. Our present study found that ALKBH5 was upregulated and co-localized with cluster of differentiation 31 (CD31) in the skin of IMQ group compared with control group. ALKBH5-deficient mice decreased IMQ-induced psoriatic dermatitis and exhibited histological improvements, including decreased epidermal thickness, hyperkeratosis, numbers of dermal capillary vessels and inflammatory cell infiltration. ALKBH5-KO mice alleviated angiogenesis in psoriatic lesions by downregulating the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. Additionally, the expression of ALKBH5 was significantly upregulated in IL-17A-induced human umbilical vein endothelial cells (HUVECs), which further promoted the expression of angiogenesis-related cytokines and endothelial cell proliferation. Cell proliferation and angiogenesis were suppressed in ALKBH5 knockdown group, whereas ALKBH5 overexpression promoted these processes. The regulation of angiogenesis in HUVECs by ALKBH5 was facilitated through the AKT-mTOR pathway. Collectively, ALKBH5 plays a pivotal role in psoriatic dermatitis and angiogenesis, which may offer a new potential targets for treating psoriasis.
Animals ; Psoriasis/chemically induced* ; Mice ; Humans ; Neovascularization, Pathologic/genetics* ; Human Umbilical Vein Endothelial Cells/metabolism* ; AlkB Homolog 5, RNA Demethylase/genetics* ; Proto-Oncogene Proteins c-akt/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; Cell Proliferation ; Mice, Knockout ; Disease Models, Animal ; Signal Transduction ; Male ; Skin/blood supply* ; Mice, Inbred C57BL ; Angiogenesis

Objective To construct,implement and evaluate the effectiveness of the virtual simulation technology-based prenatal health education course.Methods The curriculum included 4 parts:"warm delivery room and easy delivery","medicated analgesic delivery","non-medicated analgesic delivery"and"early maternal and infant health care".From May to September 2022,100 primiparas in an obstetrics and gynecology hospital in Zhejiang Province were investigated by convenient sampling method.Random number table method was used to divide the participants into an experimental group and a control group,with 50 participants per group.The control group received conventional health education,while the experimental group received an augmented virtual reality technology-based prenatal health education course during the late stages of pregnancy on this basis.We conducted a post-intervention comparative analysis of antenatal anxiety levels,fear of childbirth,and birth outcomes between the 2 groups.Furthermore,a post-intervention satisfaction survey was administered to the experimental group.Results After intervention,the antenatal anxiety of the experimental group was lower than that of the control group(x2=4.943,P=0.026),and the decrease in fear of childbirth scores was higher than that of the control group(t=3.200,P=0.002).The experimental group was highly satisfied with all of the 4 dimensions of the course,and the overall evaluation was(31.8±3.23)points.However,there were no significant differences in vaginal delivery rate,postpartum bleeding volume,postpartum hemorrhage incidence,perineal injury degree and duration of each labor stage between the 2 groups(P＞0.05).Conclusion The virtual reality technology-based prenatal health education course was effective in improving the antenatal anxiety and fear of childbirth of primipara,and the use satisfaction is high.

Objective:To investigate any anti-aging effect of repeated transcranial magnetic stimulation (rTMS) and explore the relationship between the effect and relief of clinical symptoms in patients with Parkinson′s disease (PD).Methods:A total of 108 PD patients were randomly divided into an rTMS group and a control group, each of 54, while another 54 healthy counterparts were selected to form a normal group. In addition to anti-PD drug therapy, the rTMS group was given daily rTMS treatment, 5 days a week for 4 weeks, while the control group received sham rTMS treatment, with no treatment of the normal group. Before the treatment and after 4 weeks of treatment as well as and 1 month after the ending of the treatment, the subjects′ clinical exercise symptoms were evaluated using the Unified Parkinson′s Disease Rating Scale (UPDRS), a timed exercise test and the 10m re-entry exercise test. Non-exercise symptoms were assessed using the Hamilton Depression Scale (HAMD), the Hamilton Anxiety Scale (HAMA) and the Mini-mental State Examination (MMSE). Fasting venous blood samples were analyzed to quantify the serum levels of tumor necrosis factor (TNF), interleukin-6 (IL-6), interleukin-1β (IL-1β) and matrix metalloproteinase-3 (MMP-3).Results:Four weeks and 1 month after the treatment, the average UPDRS scores, exercise test times and 10m re-entry exercise test results of the rTMS group were significantly better than those before treatment and significantly better than those of the control group at the same time point. The rTMS group′s average HAMA, HAMD and MMSE scores, as well as its average P300 latency and amplitude were also significantly better than those of the control group at the same time point and significantly better than those before treatment. After 4 weeks, the average MMP-3 content in the rTMS group was significantly lower than the control group′s average, and after a month the average levels of TNF, IL-6, IL-1β and MMP-3 of the rTMS group were all significantly different from those before treatment and those of the control group. The TNF, IL-6, IL-1β and MMP-3 levels were all positively correlated with the average UPDRS total score.Conclusion:High-frequency rTMS therapy can change the phenotypes related to cell senescence, and thus has good therapeutic effect on motor and non-motor symptoms of PD.

Objective:To better promote the standardization of public health management in China, and provide evidence for the development and improvement of the standardization strategy and management system in public health field in China.Methods:This paper summarizes and analyzes the information about the standardized management mechanism collected from international organizations related with standardization in public health.Results:The standards in public health varied in different management systems of the international organizations, and there were great differences in organization nature, standard types, application, release, organization structure, standard development principles, advantages, transformation, promotion and implementation, and evaluation.Conclusion:China can benefit from the studying of the working mechanism of the international organization related with standardization in public health to facilitate its own standardization in public health.

Objectives: To examine the effect of VAE and open surgery on the postoperativelocal recurrence of benign phyllodes tumors of breast and to investigate the clinical efficacy of VAE in the treatment of benign phyllodes tumors. Methods: The clinical data of 128 patients with benign phyllodes tumors of breast admitted to the Guangdong Women and Children Hospital from January 2013 to January 2018 were retrospectively analyzed. All patients were female, aged (37.7±9.1) years (range: 16 to 56 years). Eighty patients underwent ultrasound-guided VAE (minimally invasive group) and 48 patients underwent open surgery (open group). The t-test, χ² test or Fisher exact probability method were used to compare the clinical characteristics of the two groups of patients. Logistic regression was used to analyze the prognostic factors of postoperative local recurrence. Results: The maximum diameter of tumor in the minimally invasive group was smaller than that in the open group ((20.6±7.4) mm vs. (42.0±2.0) mm, t=-7.173, P=0.000). The follow-up time was (36.4±1.8) months (range: 12 to 71 months). There were 7 cases of local recurrences during the follow-up period. The local recurrence rates in the minimally invasive and open groups were 5.0% (4/80) and 6.3% (3/48). The results of multivariate analysis showed that the maximum tumor diameter of 25 mm was an independent prognosis factor for postoperativelocal recurrence (OR=0.122, 95%CI: 0.016 to 0.901, P=0.039). While surgical procedure, age, menopausal status and history of fibroadenomas in the ipsilateral breast is not an independent prognostic factor for postoperative local recurrence. In the minimally invasive surgery group, the local recurrence rates were 2.9% (2/69) and 2/11 in patients with tumor maximum diameters<25 mm and ≥25 mm, respectively. Conclusions Local recurrence of breast benign phyllodes tumors is closely related to the tumor size. For patients with tumor diameter<25 mm, the postoperative local recurrence rate of VAE is low, which can be used in clinical practice. Intraoperative complete resection to achieve a negative surgical margin should be guaranteed to avoid local recurrence.

Adipose tissue is the energy storage organ of the body, and excess energy is stored in adipocytes in the form of lipid droplets. The homeostasis of adipose tissue is the basis for the body to maintain normal metabolic activity. Prostaglandin E (PGE) is an important lipid mediator in the body. It is synthesized in almost all tissues and participates in the regulation of many physiological processes such as blood pressure, glucose and lipid metabolism, and inflammation. PGE is abundant in white adipose tissue, where it is involved in the regulation of fat metabolism. PGE plays its biological role through binding to four G protein coupled receptors (prostaglandin E receptors), including EP-1, -2, -3, and -4. The EP4 subtype has been proved to play an important role in adipogenesis and adipose metabolism: it could inhibit adipogenesis while it was activated, whereas its knockout could promote lipolysis. This review summarized the relationship between EP4 and adipose metabolism, hoping to identify new targets of drug development for metabolic disorders.
Adipocytes ; Adipogenesis ; Adipose Tissue ; metabolism ; Humans ; Receptors, Prostaglandin E, EP4 Subtype ; physiology

Objective: To investigate the efficacy and safety of cuboid stereotactic aspiration of necrotic brain tissue for treating malignant middle cerebral artery infarction in the elderly patients. Methods: Sixteen elderly patients with malignant middle cerebral artery infarction were selected from June 2017 to January 2019 in our hospital. Patients were followed up for 6 months to evaluate the efficacy of stereotactic aspiration of necrotic brain tissue using the modified Rankin Scale (mRS). Results: The 30-day mortality was 18.75%. Among the 16 elderly patients, 6 (37.5%) had an mRS score of 3 (defined as moderate disability), 6 (37.5%) had an mRS score of 4 (defined as moderate to severe disability), 1 (6.25%) had an mRS score of 5 (defined as severe disability), and 3 (18.75%) had an mRS score of 6. The probability of 6-month favorable outcome, defined as an mRS score of ≤3, was 37.5%, and the 6-month mortality was 18.75%. Conclusions It is a simple, minimally invasive, effective and safe method to treat malignant middle cerebral artery infarction in the elderly patients with cuboid stereotactic aspiration of necrotic brain tissue, which needs to be confirmed by further randomized controlled studies.

OBJECTIVE:To explore the effects of extracts from Siegesbeckiae herba (HS) on doxorubicin (DOX)-induced chronic myocardial injury in mice. METHODS:48 mice were randomly divided into 3 groups. Mice in blank control(Con)group received distilled water once every day,ig,and normal saline(2 mL/100 g)once every day,ip,for 8 weeks;mice in DOX mice received distilled water(2 mL/100 g)once every day,ig,and DOX(3 mg/kg)once every week,ip,for 8 weeks;mice in DOX+HS group received HS(340 mg/kg)once every day,ig,and DOX(3 mg/kg)once every week,ip,for 8 weeks. After administra-tion,body mass,heart coefficient,cardiac function changes,serum biochemical index levels [alanine aminotransferase(ALT),as-partate aminotransferase (AST), creatine phosphokinase (CK), creatine kinase isoenzyme (CK-MB), lactate dehydrogenase (LDH)and total cholesterol(TC)] of mice were determined. RESULTS:Compared with Con group,body mass of mice in DOX group was decreased(P<0.01);heart coefficient was increased(P<0.05);heart rate slowed down,R-wave was increased(P<0.05 or P<0.01);serum biochemical indexed were increased,there was significant difference in AST(P<0.01). Compared with DOX group,heart coefficient of mice in DOX+HS group was decreased (P<0.01);heart rate was increased (P<0.01);serum biochemical indexes were decreased,there was significant differences in CK,LDH,TC(P<0.01). CONCLUSIONS:HS has cer-tain protective effects on DOX-induced chronic myocardial injury in mice.

Objective To assess the therapeutic effect of high-frequency repetitive transcranial magnetic stimulation (rTMS) combined with neuromuscular electrical stimulation (NMES) on poststroke dysphagia.Methods A total of 90 patients with poststroke dysphagia were enrolled.They were randomly divided into either a NMES + rTMS group or a NMES + sham rTMS group (n =45 in each group).The Kuhota water drinking test and Standardized Swallowing Assessment (SSA) were used to assess the swallowing function.Results The scores of Kuhota water drinking test (F=82.001,P＜0.001) and the SSA (F =33.743,P ＜0.001) before treatment,treatment of one course,treatment of two courses,and at 3 months after treatment in the NMES + rTMS group had significant differences.Compared with before treatment,they were improved significantly for treatment of one course (P ＜0.01 and P ＜0.05,respectively),two courses (all P＜0.01),and at 3 months (all P＜0.01) after treatment.The scores of Kuhota water drinking test (F =53.647,P＜0.001) and the SSA (F=19.178,P＜0.001) in the NMES + sham rTMS group also had significant difference.Compared with before treatment,they had significant improvement for treatment of one course (all P ＜0.05),two courses (P ＜0.05 and P ＜0.01,respectively) and at 3 months (all P＜0.01)after treatment.The scores of Kuhota water drinking test for treatment of one course,two courses,and at 3 months after treatment (treatment of one course:t=2.217,P=0.02;treatment of two courses:t =2.406,P =0.019;at 3 months after treatment:t =2.128,P =0.037) and the SSA (treatment of one course:t =2.196,P =0.030,treatment of two courses:t =2.425,P =0.016;at 3 months after treatment:t =2.512,P=0.013) in the NMES + rTMS group were significantly better than those in the NMES + sham rTMS group.Conclusions High-frequency rTMS combined with NMES may significantly improve the swallowing function in patients with stroke.Its efficacy is superior to NMES.