AIM: To investigate the feasibility to inhibit the expression of MHCⅡ by special siRNA targeting class Ⅱ major histocompatibility complex (MHC Ⅱ) transactivator (CⅡTA), which might regulate MHC Ⅱexpression for suppressing immune rejection. METHODS: Five different siRNA were designed, synthesized and transfected into freshly isolated rat corneal keratocytes. At 24 hours posttransfection, the changes of MHC Ⅱexpression were detected by flowcytometry, and the mRNA abundance of CⅡTA and MHC Ⅱ was measured by FQ-PCR after inducing with recombinant rat interferon-gamma (IFN-?). RESULTS: Different siRNA showed different reduction in MHC Ⅱ and CⅡTA expression compared with the control (P

Streptococcal superantigens play an important role in many human diseases.In this paper,we mainly discuss the progress in the researches on streptococcal superantigens in such aspects as their structures,biological and pathophysiological properties,expression regulation,and their significance in the management of tumors.

Objective: To better understand surrogate technology,so as to enable surrogacy to be used more or-derly,rationally and legitimately in Chinese society as one of human assisted reproductive technologies.Methods:Through literature retrieval and other methods,this paper analyzed the possible risks of surrogate behavior at various stages.Results: China explicitly prohibited surrogacy,but surrogacy existed objectively.The risk of surrogacy ex-isted in the entire process of surrogacy,and the risks varied in different stages.There lacked perfect legal protec-tion for the rights and interests of all parties.Conclusion: It is not effective to ban surrogacy negatively in order to avoid ethical and legal disputes,and surrogacy is often illegal for many times.It should only formulate the authori-tative laws actively to respond to surrogacy issues,standardize the ethical principles of surrogacy,access condi-tions,and illegal punishment,and fundamentally deal with possible risks so as to effectively protect the rights and interests of all parties of surrogacy.Therefore,the introduction of the legislative regulation on surrogacy should not be delayed.

Mechanical stimulation in micro-environment ( such as matrix stiffness, surface topography, cyclical stretch) can be perceived by macrophages through receptors on cell membrane, transmitted to the nucleus along the adhesion protein molecular chain and cytoskeleton, and also converted into biochemical signal to stimulate gene transcription. Mechanical stimulation drives various biological functions in macrophages, such as adhesion, proliferation, migration, and polarization, thereby playing a corresponding role in disease progression and tissue regeneration. This study demonstrates the role of micro-environment mechanics in macrophages polarization and function, and elucidates the related mechanism of mechanotransduction pathway in macrophages, so as to provide molecular biomechanics insights into the development of macrophage-targeting immunomodulatorybiomaterials.

Keloids are a common type of pathological scar as a result of skin healing, which are extremely difficult to prevent and treat without recurrence. The pathological mechanism of keloids is the excessive proliferation of fibroblasts, which synthesize more extracellular matrices (ECMs), including type I/III collagen (COL-1/3), mucopolysaccharides, connective tissue growth factor (CTGF, also known as cellular communication network factor 2 (CCN2)), and fibronectin (FN) in scar tissue, mostly through the abnormal activation of transforming growth factor-‍β (TGF-‍β)/Smads pathway (Finnson et al., 2013; Song et al., 2018). Genetic factors, including race and skin tone, are considered to contribute to keloid formation. The reported incidence of keloids in black people is as high as 16%, whereas white people are less affected. The prevalence ratio of colored people to white people is 5:1‍‍-‍‍15:1 (Rockwell et al., 1989; LaRanger et al., 2019). In addition, keloids have not been reported in albinism patients of any race, and those with darker skin in the same race are more likely to develop this disease (LaRanger et al., 2019). Skin melanocyte activity is significantly different among people with different skin tones. The more active the melanocyte function, the more melanin is produced and the darker the skin. Similarly, in the same individual, the incidence of keloids increases during periods when melanocytes are active, such as adolescence and pregnancy. Keloids rarely appear in areas where melanocytes synthesize less melanin, such as in the palms and soles. Thus, the formation of keloids seems to be closely related to melanocyte activity.
Adolescent ; Cells, Cultured ; Exosomes/metabolism* ; Fibroblasts/metabolism* ; Humans ; Keloid/pathology* ; Melanins/metabolism* ; Melanocytes/pathology* ; Pilot Projects ; Skin/metabolism* ; Transforming Growth Factor beta/metabolism*

To sort out the requirements for enhancing the capacity and informatization construction of CDC laboratories in the context of high-quality development of disease prevention and control. To investigate and analyze the current situation, problems faced and development needs for laboratory informatization construction of disease prevention and control institutions in Shanghai, so as to provide an evidence for putting forward targeted suggestions. In addition, it will provide ideas for comprehensively improving the informatization construction of laboratories in disease prevention and control institutions and constructing a smart and accurate modern disease prevention and control system under the new context.

Epidermal growth factor receptor-tyrosine kinase inhibitor （EGFR-TKI） represent a class of small-molecule targeted therapeutics for oncology treatment， and serve as first-line therapy for advanced non-small cell lung cancer （NSCLC） with EGFR- sensitive mutations， with representative agents including gefitinib， dacomitinib， and osimertinib. In clinical practice， dose adjustment of EGFR-TKI may be required for cancer patients under special circumstances such as drug combinations or hepatic/ renal impairment. Physiologically-based pharmacokinetic （PBPK） model， capable of predicting pharmacokinetic （PK） processes in humans， has emerged as a vital tool for clinical dose optimization. This article sorts the modeling methodologies， workflows， and commonly used software tools for PBPK model， and summarizes the current applications of PBPK model in EGFR-TKI precision therapy as of June 30， 2024. Findings demonstrate that PBPK modeling methods commonly employ the “bottom-up” approach and the middle-out approach. The process typically involves four steps： parameter collection， compartment selection， model validation， and model application. Commonly used software for modeling includes Simcyp， GastroPlus， and open-source software such as PK- Sim. PBPK model can be utilized for predicting drug-drug interactions of EGFR-TKI co-administered with metabolic enzyme inducers or inhibitors， acid-suppressive drugs， or traditional Chinese and Western medicines. It can also adjust dosages in conjunction with genomics， predict PK processes in special populations （such as patients with liver or kidney dysfunction， pediatric patients）， evaluate the efficacy and safety of drugs， and extrapolate PK predictions from animal models to humans.