ObjectiveTo investigate the efficacy of Xingpi capsules （XPC） in treating diarrhea-predominant irritable bowel syndrome （IBS-D） with spleen deficiency and elucidate its potential molecular mechanisms. MethodsA rat model of IBS-D with spleen deficiency was established by administering senna leaf in combination with restrained stress and swimming fatigue for 14 d. Ten specific pathogen free （SPF）-grade healthy rats were used as the normal control group. After successful modeling， SPF-grade rats were randomly divided into a model group， a pinaverium bromide group （1.5 mg·kg^-1）， and low- and high-dose XPC groups （0.135 and 0.54 g·kg^-1）， with 10 rats in each group. Rats in the normal control group and the model group were given distilled water by gavage， while the remaining groups were administered corresponding drug solutions by gavage once a day for 14 consecutive days. The rat body weights and fecal condition were observed every day， and the Bristol score was recorded. Enzyme-linked immunosorbent assay （ELISA） was used to determine the levels of 5-hydroxytryptamine （5-HT） in serum and colon tissue. Transmission electron microscopy was used to observe the microvilli and tight junctions in the colon. The integrity of the colonic barrier， intestinal motility， and expression of related pathway proteins were evaluated by hematoxylin-eosin （HE） staining， immunohistochemistry， and Western blot. ResultsCompared with those in the normal control group， rats in the model group showed a significantly decreased body weight and increased diarrhea rate， diarrhea grade， and Bristol score （P<0.01）. HE staining revealed incomplete colonic mucosa in the model group， with evident congestion and edema observed. Electron microscopy results indicated decreased density and integrity of the colonic barrier， shedding and disappearance of microvilli， and significant widening of tight junctions. The expression levels of colonic tight junction proteins Occludin and Claudin-5 were downregulated （P<0.01）， and the levels of 5-HT in serum and colon tissue were elevated （P<0.01）. The small intestine propulsion rate significantly increased （P<0.01）， and the expression of contractile proteins Ras homolog family member A （RhoA） and Rho-associated coiled-coil containing protein kinase 2 （ROCK2） in colon and phosphorylation of myosin light chain （MLC₂₀） were upregulated （P<0.01）. Compared with the model group， the treatment groups showed alleviated diarrhea， diarrhea-associated symptoms， and pathological manifestations of colon tissue to varying degrees. Specifically， high-dose XPC exhibited effectively relieved diarrhea， promoted recovery of colonic mucosal structure， significantly reduced congestion and edema， upregulated expression of Occludin and Claudin-5 （P<0.01）， decreased levels of 5-HT in serum and colon tissue （P<0.05，P<0.01）， significantly slowed small intestine propulsion rate （P<0.01）， and significantly downregulated expression of contractile proteins RhoA and ROCK2 in colon and phosphorylation of MLC₂₀ （P<0.05，P<0.01）. ConclusionXPC effectively alleviates symptoms of spleen deficiency and diarrhea and regulates the secretion of brain-gut peptide. The characteristics of XPC are mainly manifested in alleviating IBS-D with spleen deficiency from the aspects of protecting intestinal mucosa and inhibiting smooth muscle contraction， and the mechanism is closely related to the regulation of the 5-HT-RhoA/ROCK2 pathway expression.

Objective: To investigate the potential protective effect of Shexiang Tongxin dropping pills (STDP) on ischemia-reperfusion injury and its underlying mechanisms in improving endothelial cell function in coronary microvascular disease (CMVD). Methods: A rat model of myocardial ischemia-reperfusion injury with CMVD was established using ligation and reperfusion of the left anterior descending artery. The effect of STDP (21.6 mg/kg) on cardiac function was evaluated using echocardiography, hematoxylin-eosin staining, and Evans blue staining. The effects of STDP on the microvascular endothelial barrier were assessed based on nitric oxide production, endothelial nitric oxide synthase expression, structural variety of tight junctions (TJs), and the expression of zonula occludens-1 (ZO-1), claudin-5, occludin, and vascular endothelial (VE)-cadherin proteins. The mechanisms of STDP (50 and 100 ng/mL) were evaluated by examining the expression of sphingosine 1-phosphate receptor 2 (S1PR2), Ras Homolog family member A (RhoA), and Rho-associated coiled-coil-containing protein kinase (ROCK) proteins and the distribution of ZO-1, VE-cadherin, and F-actin proteins in an oxygen and glucose deprivation/reoxygenation model. Results: The administration of STDP on CMVD rat model significantly improved cardiac and microvascular endothelial cell barrier functions (all P < .05). STDP enhanced the structural integrity of coronary microvascular positioning and distribution by clarifying and completing TJs and increasing the expression of ZO-1, occludin, claudin-5, and VE-cadherin in vivo (all P < .05). The S1PR2/RhoA/ROCK pathway was inhibited by STDP in vitro, leading to the regulation of endothelial cell TJs, adhesion junctions, and cytoskeletal morphology. Conclusion STDP showed protective effects on cardiac impairment and microvascular endothelial barrier injury in CMVD model rats induced by myocardial ischemia-reperfusion injury through the modulation of the S1PR2/RhoA/ROCK pathway.

Myocardial fibrosis (MF) is a common pathological hallmark of cardiovascular diseases, reflecting shared mechanisms in their progression. However, the lack of reliable MF models that accurately mimic its pathogenesis has hindered drug discovery, highlighting the urgent need for more effective therapeutic agents. Herein, a novel contractile three-dimensional (3D) myocardial tissue model integrating cardiomyocytes, cardiac-fibroblasts, and bone marrow-derived macrophages in collagen hydrogel was developed to simulate the fibrotic changes of cardiovascular disease, and facilitate the screening of anti-MF compounds. The 3D myocardial tissue model exhibited precise, visualizable, and quantifiable contractile characteristics under hypoxia and drug interventions. 76 compounds extracted from the resins of Toxicodendron vernicifluum, a traditional Chinese medicine with clear clinical benefits for fibrotic diseases, were screened for anti-fibrotic activity. Using an in vitro 3D oxygen-glucose deprivation (OGD)-treated myocardial tissue model instead of a two-dimensional transforming growth factor-β treated cardiac-fibroblasts model, two candidates including LQ-40 and SQ-3 exert impressive anti-MF activity, which was further validated in left anterior descending coronary artery ligation-induced MF mouse model. The current results demonstrate the feasibility and advantage of the novel contractile 3D tissue model with multi-cell types in discovering candidates for MF, further stressing the great potential of regulating macrophages in the treatment of MF.

The activation proteins released by fibroblasts in the tumor microenvironment regulate tumor growth, migration, and treatment response, thereby influencing tumor progression and therapeutic outcomes. Owing to the proliferation and metastasis of tumors, fibroblast activation protein (FAP) is typically highly expressed in the tumor stroma, whereas it is nearly absent in adult normal tissues and benign lesions, making it an attractive target for precision medicine. Radiolabeled agents targeting FAP have the potential for targeted cancer diagnosis and therapy. This comprehensive review aims to describe the evolution of FAPI-based radiopharmaceuticals and their structural optimization. Within its scope, this review summarizes the advances in the use of radiolabeled small molecule inhibitors for tumor imaging and therapy as well as the modification strategies for FAPIs, combined with insights from structure-activity relationships and clinical studies, providing a valuable perspective for radiopharmaceutical clinical development and application.

Drug development remains a critical issue in the field of biomedicine. With the rapid advancement of information technologies such as artificial intelligence (AI) and the advent of the big data era, AI-assisted drug development has become a new trend, particularly in predicting drug-target associations. To address the challenge of drug-target prediction, AI-driven models have emerged as powerful tools, offering innovative solutions by effectively extracting features from complex biological data, accurately modeling molecular interactions, and precisely predicting potential drug-target outcomes. Traditional machine learning (ML), network-based, and advanced deep learning architectures such as convolutional neural networks (CNNs), graph convolutional networks (GCNs), and transformers play a pivotal role. This review systematically compiles and evaluates AI algorithms for drug- and drug combination-target predictions, highlighting their theoretical frameworks, strengths, and limitations. CNNs effectively identify spatial patterns and molecular features critical for drug-target interactions. GCNs provide deep insights into molecular interactions via relational data, whereas transformers increase prediction accuracy by capturing complex dependencies within biological sequences. Network-based models offer a systematic perspective by integrating diverse data sources, and traditional ML efficiently handles large datasets to improve overall predictive accuracy. Collectively, these AI-driven methods are transforming drug-target predictions and advancing the development of personalized therapy. This review summarizes the application of AI in drug development, particularly in drug-target prediction, and offers recommendations on models and algorithms for researchers engaged in biomedical research. It also provides typical cases to better illustrate how AI can further accelerate development in the fields of biomedicine and drug discovery.

Objective To investigate the reliability and validity of the assessment tools of Brief ICF Core Sets for Arthroplasty of Knee Osteoarthritis in Perioperative Period(ICSAKOPP). Methods From May,2022 to April,2023,320 patients undergoing knee arthroplasty were selected in Peking University Third Hospital,China-Japan Friendship Hospital,Peking University First Hospital and Chinese PLA General Hospital.Trained assessors used Brief ICSAKOPP to evaluate all enrolled patients before arthroplasty,three days(±one day)after arthroplasty,three weeks(±one week)after arthroplasty,and three months(±one month)after ar-throplasty.Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)scores were recorded at the same time.Five professionals were asked to score all the items of Brief ICSAKOPP,and the content validity index(CVI)was caculated. Results A total of 64 cases were dropped down.CVI of all the items of the Brief ICSAKOPP were above 0.8,with a av-erage CVI of the scale of 0.938.The Cronbach's α coefficient of the Brief ICSAKOPP was 0.813.There was a moderate correlation(r=0.681,P<0.001)between the overall Brief ICSAKOPP and WOMAC scores,as well as body functional dimension score(r=0.668,P<0.001)and activities and participation dimension score(r=0.657,P<0.001). Conclusion Brief ICSAKOPP is good in content validity,internal consistency reliability and criterion validity.

Background Organic phosphate flame retardants are emerging environmental pollutants. While there have been multiple toxicities reported following organic phosphate flame retardants exposure, few studies focus on their potential developmental toxicities. It is necessary to elucidate these developmental toxicological effects and underlying mechanisms to improve risk assessments and better protect sensitive populations. Objective To evaluate potential developmental toxicities in early chicken embryos following exposure to triphenyl phosphate (TPhP) or cresyl diphenyl phosphate (CDP), to reveal TPhP and CDP’s capabilities to activate peroxisome proliferator-activated receptor γ (PPARγ) in vivo in an established chicken embryo gene reporter system, and to investigate the roles of PPARγ in TPhP/CDP-induced developmental toxicities with lentivirus-mediated in vivo gene silencing. Methods Firstly, diverse doses of TPhP and CDP were injected into the air sacs of fertilized eggs to assess the development of chicken embryos after 6 d of incubation, and an optimal dose was chosen for subsequent experiments. Subsequently, the report gene system was employed to evaluate the intraembryonic activation of PPARγ by TPhP and CDP. Eventually, PPARγ was silenced using lentivirus, and the embryos were co-treated with TPhP and CDP to further disclose the roles of PPARγ in the observed developmental toxicity. Results Following developmental exposure to TPhP or CDP, significantly lower chicken embryo weights (normalized with egg weights) were observed in the 6 d embryos (10, 30 mg·kg⁻¹ TPhP and 3, 10, 30 mg·kg⁻¹ CDP), indicating that both chemicals have general developmental toxicities and CDP is more potent. Additionally, exposure to CDP also resulted in remarkably increased sagittal brain area (normalized to embryo weights) and decreased sagittal eye area (normalized to embryo weights) (P<0.05), suggesting that CDP has specific developmental neurotoxicity and ocular toxicity. The PPARγ reporter gene experiment results revealed that rosiglitazone (positive control), TPhP, and CDP all significantly activated PPARγ relative to control (P<0.05). The potency order was rosiglitazone > CDP > TPhP. The lentivirus microinjection successfully achieved in vivo silencing of PPARγ in developing chicken embryos, and the estimated silencing efficacy was approximately 55% according to the real-time quantitative polymerase chain reaction (qRT-PCR) results. The in vivo silencing of PPARγ effectively alleviated TPhP or CDP-induced decrease of embryo weights (P<0.05), as well as CDP-induced increase of brain areas and decrease of eye areas (P<0.05). Conclusions Both TPhP and CDP can induce general developmental toxicities in early chicken embryos, and CDP is more potent than TPhP. Meanwhile, CDP can induce specific enlarged brain area and decreased eye area. The observed toxicities are associated with in vivo activation of PPARγ.

Breast augmentation using polyacrylamide hydrogel (PAHG) was widely used in China. We present the first case of delayed breast inflammation after 2019 novel coronavirus(2019-nCoV) infection in a patient who recieved breast augmentation with PAHG 20 years ago, without any other predispositions. The 45-year-old female patient complained of severe breast swelling and pain three weeks after 2019-nCoV infection. The swelling extended from the upper clavicle to the upper abdomen. Delayed inflammation reaction was diagnosed, followed by emergency surgery. During the surgery, the injected material was observed to gush out in a form of greenish and thin paste, with a foul odor. The wound had extensive diffuse oozing and hemoglobin decreased significantly. The patient was discharged one week after surgery. During a three-month follow-up, she experienced weakness and fatigue with no complications. There are still many unknown areas of the impact of 2019-nCoV on human foreign bodies and immune system, which is diverse and complex. Reporting various possible symptoms and mechanisms is conducive to improving the level of awareness and intervention of plastic surgeons.

Breast augmentation using polyacrylamide hydrogel (PAHG) was widely used in China. We present the first case of delayed breast inflammation after 2019 novel coronavirus(2019-nCoV) infection in a patient who recieved breast augmentation with PAHG 20 years ago, without any other predispositions. The 45-year-old female patient complained of severe breast swelling and pain three weeks after 2019-nCoV infection. The swelling extended from the upper clavicle to the upper abdomen. Delayed inflammation reaction was diagnosed, followed by emergency surgery. During the surgery, the injected material was observed to gush out in a form of greenish and thin paste, with a foul odor. The wound had extensive diffuse oozing and hemoglobin decreased significantly. The patient was discharged one week after surgery. During a three-month follow-up, she experienced weakness and fatigue with no complications. There are still many unknown areas of the impact of 2019-nCoV on human foreign bodies and immune system, which is diverse and complex. Reporting various possible symptoms and mechanisms is conducive to improving the level of awareness and intervention of plastic surgeons.

Cognitive reserve referred to the cumulative flexibility of an individual's cognitive processes,whereas accurately assessing an individual's cognitive reserve and intervening was important for preventing the occurrence of cognitive dysfunction as well as promoting cognitive health.This article reviewed the main contents and applications of cognitive reserve assessment tools,and compared the characteristics and limitations of each assessment tool.The purpose was to provide ideas for the development of cognitive reserve assessment tools suitable for China's cultural background and population characteristics,and to provide a basis for accurately assessing the current status of China's cognitive reserve and formulating targeted cognitive reserve enhancement programs.