OBJECTIVES: To investigate pharmacologically active components of Yiqi Zishen Formula (YZF) and their mechanisms for alleviating airway inflammation in mice with chronic obstructive pulmonary disease (COPD). METHODS: Ultra-high-performance liquid chromatography coupled with quadrupole-orbitrap mass spectrometry was employed to characterize the chemical components in YZF and YZF-medicated rat serum. A compound-disease target network was constructed based on serum components of YZF to screen the key pathways and targets using enrichment analysis. A mouse model of cigarette smoke-induced COPD was used to evaluate the anti-inflammatory effect of YZF and validate the expression of key proteins in network pharmacology-enriched pathways. Fifty male C57BL/6J mice were randomized equally into control group, COPD model group, high- and low-dose YZF treatment groups, and N-acetylcysteine treatment group. Pulmonary function of the mice was assessed using whole-body plethysmography, and lung histopathology, alveolar structure, and airway remodeling were analyzed using HE staining. The levels of IL-1β, IL-6, and TNF‑α in bronchoalveolar lavage fluid (BALF) were determined with ELISA, and pulmonary expressions of PI3K, Akt, phosphorylated Akt (p-Akt), p65, and phosphorylated p65 (p-p65) were detected using immunohistochemistry. RESULTS: We identified a total of 156 chemical components (including 26 flavonoids or flavonoid glycosides, 27 alkaloids, and 11 saponins) in YZF and 43 prototype components in medicated rat serum. Network pharmacology revealed 704 YZF-related targets and 1199 COPD-associated targets. Integrated analysis suggested that the anti-COPD effects of YZF were associated with the PI3K-Akt signaling pathway. In mouse models of COPD, YZF treatment significantly increased mean alveolar number and peak expiratory flow (P<0.05), reduced mean linear intercept, bronchial wall thickness, lung coefficient, and BALF cytokine levels, and suppressed the expressions of PI3K, Akt, p-Akt, p65, and p-p65 in the lung tissues. CONCLUSIONS YZF alleviates COPD symptoms and airway inflammation in mice possibly by inhibiting the PI3K/Akt/NF‑κB pathway through its multiple components that interact with multiple targets.
Animals ; Pulmonary Disease, Chronic Obstructive/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Signal Transduction/drug effects* ; Male ; Mice, Inbred C57BL ; Mice ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; NF-kappa B/metabolism* ; Inflammation/drug therapy* ; Rats

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a severe dose-limiting adverse event of chemotherapy. Presently, the mechanism underlying the induction of CIPN remains unclear, and no effective treatment is available. In this study, through metabolomics analyses, we found that nab-paclitaxel therapy markedly increased serum serotonin [5-hydroxtryptamine (5-HT)] levels in both cancer patients and mice compared to the respective controls. Furthermore, nab-paclitaxel-treated enterochromaffin (EC) cells showed increased 5-HT synthesis, and serotonin-treated Schwann cells showed damage, as indicated by the activation of CREB3L3/MMP3/FAS signaling. Venlafaxine, an inhibitor of serotonin and norepinephrine reuptake, was found to protect against nerve injury by suppressing the activation of CREB3L3/MMP3/FAS signaling in Schwann cells. Remarkably, venlafaxine was found to significantly alleviate nab-paclitaxel-induced CIPN in patients without affecting the clinical efficacy of chemotherapy. In summary, our study reveals that EC cell-derived 5-HT plays a critical role in nab-paclitaxel-related neurotoxic lesions, and venlafaxine co-administration represents a novel approach to treating chronic cumulative neurotoxicity commonly reported in nab-paclitaxel-based chemotherapy.
Paclitaxel/toxicity* ; Animals ; Albumins/adverse effects* ; Serotonin/metabolism* ; Mice ; Humans ; Male ; Female ; Venlafaxine Hydrochloride/therapeutic use* ; Neurotoxicity Syndromes/metabolism* ; Middle Aged ; Schwann Cells/metabolism* ; Peripheral Nervous System Diseases/drug therapy* ; Antineoplastic Agents

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

The hyperactivation of the PI3K/AKT/mTOR signal pathway caused by PIK3CA mutation is associated with a category of overgrowth syndromes that are defined as PIK3CA-related overgrowth spectrum (PROS). The clinical features of PROS are highly heterogeneous and typically present with vascular malformations, bone and soft tissue overgrowth, neurological and visceral abnormalities. Detection of gene mutation are necessary for diagnosis and provide the basis for the genetic targeted therapy of PROS. Drugs that inhibits PI3K pathway have offered an alternative choice to conventional therapies. This article reviews the current knowledge of PROS and summarizes the latest progress for precise treatment.

The hyperactivation of the PI3K/AKT/mTOR signal pathway caused by PIK3CA mutation is associated with a category of overgrowth syndromes that are defined as PIK3CA-related overgrowth spectrum (PROS). The clinical features of PROS are highly heterogeneous and typically present with vascular malformations, bone and soft tissue overgrowth, neurological and visceral abnormalities. Detection of gene mutation are necessary for diagnosis and provide the basis for the genetic targeted therapy of PROS. Drugs that inhibits PI3K pathway have offered an alternative choice to conventional therapies. This article reviews the current knowledge of PROS and summarizes the latest progress for precise treatment.

Parkinson disease is a common neurodegenerative disease.At present,the main therapeutic drugs have problems such as adverse reactions,lack of targeting,and low bioavailability.The development of new drugs is an important direction for research related to Parkinson disease.TCM flavonoids have various pharmacological activities and are widely used in anti-tumor and cardiovascular disease treatment,but there is relatively little research on their intervention in neurological diseases.This article elaborated on the mechanism of intervention of TCM flavonoids in Parkinson disease and summarized treatment strategies from six categories:flavonoids,flavonols,isoflavones,flavonoid glycosides,dihydroflavonols,and others,with the purpose to provide reference for the research and clinical application of TCM flavonoids.

Cancer stem cells(CSCs)are a small group of cells found in tumors that have same self-renewing properties as nor-mal stem cells.In recent years,with continuous development of science and technology in various aspects,people's research on tumor diseases has been deepened.CSCs has been defined as a key factor in promoting tumor development,especially participating in pro-moting tumor recurrence,metastasis,chemotherapy resistance,etc.Currently,CD133 has become one of popular CSCs markers,and can be highly expressed in a variety of CSCs.CD133 is closely related to diagnosis of cancer diseases,and plays an important role in dignosis and drug targeting for gastric cancer,lung cancer,brain tumor,liver cancer,ovarian cancer and colorectal cancer.This article reviews structure,function,immune mechanism escape of CD133,signal pathway of CD133 in tumorigenesis,and correlation of CD133 with various tumors as well.

In order to meet the needs of the comprehensive development of life sciences and medicine,and fulfill the coher-ence and intersectionality of undergraduate experimental courses,it is necessary to break the teaching contents of conventional single experiment courses,and carry out the teaching reform of tumor comprehensive experimental course.Molecular biology and immuno-logy are two basic subjects which are closely related to the scientific research of life science,basic medicine and clinical medicine.Meantime,they are important sources for students to acquire skill training and scientific thinking as well.In this study,we try to inte-grate the experimental courses about the analysis and intervention of tumor-related genes based on the molecular biology and immunology technologies,facilitating to establish a new tumor comprehensive experimental course system.The course focuses on the development of students'logical thinking,and simulates the scientific research process through database screening,experimental operation,experi-mental report and paper writing,so as to significantly improve undergraduates'interest in scientific research and their ability to com-bine theory with practice,and cultivate students'rigorous scientific and innovative thinking ability as well as their ability to compre-hensively analyze and solve problems.It lays a solid foundation for future postgraduate related scientific research.At the same time,it is helpful to train teachers with multi-disciplinary knowledge reserves,and promote the coordinated development of scientific research through teaching.

Objective To expore the effect of fibroblast exosomes from diabetic rats on wound healing.Methods Male SD rats were randomly divided into diabetes mellitus group(DM group,n=12)and normal control group(NC group,n=15).Fibroblast exosomes were extracted and identified.After digestion of human epidermal keratinocyte line(HEK-a)and human epidermal microvascular endothelial cell line(HMEC-1),the cells were divided into diabetes exosomes group(DM-EOXa group),normal exosomes group(N-EXOa group)and normal control group(NCa group).CCK8 was used todetect the proliferation of fibroblast.fifteen male SD rats were randomly divided into diabetes exosomes group(DM-EXOb group),normal exosomes group(N-EXOb group)and normal control group(NCb group),with 5 rats in each group.Full-thickness wounds were created on rats back,and fibroblast exosomes were used to intervene wound healing.The wound healing was compared on 3th,7th,10th,and 14th day in each group.Results The proliferation of HEK-a and HMEC-1 was higher in N-EXOa and DM-EXOa groups than in NCa group(P<0.05).On the 7th,10th and 14th day,the average wound rate was lower in N-EXOb group than in NCb and DM-EXOb groups(P<0.05 or P<0.01).On the 10th day,the average wound rate was lower in NCb group than in DM-EXOb group(P<0.05).Conclusions Normal fibroblast exosomes can promote wound healing,while diabetic fibroblast exosomes from diabetic rats have no effect on wound healing,and even inhibit wound healing.

This article reported a prenatally diagnosed case of complete ring chromosome 15. A 38-year-old woman who conceived by in vitro fertilization and frozen embryo transfer underwent amniocentesis for prenatal diagnosis at 18 +5 weeks of gestation due to advanced maternal age. The result of G-banding karyotyping was mos 46,XX,r(15)[88]/45,X,-15[11]/46,XX,r(15;15)[1]. No numerical abnormalities of chromosomes or definite pathogenic copy number variations (CNVs) were detected by chromosomal microarray analysis. Amniocentesis was performed again at 31 +6 weeks of gestation. The result of genome copy number variation sequencing indicated no pathogenic CNV and fluorescence in situ hybridization on cultured amniocytes revealed nuc ish(15q)×1[15]/(15q)×3[5]/(15q)×2[80]. Based on all the prenatal diagnosis results, it was suggested that the fetus carried a complete ring chromosome 15. As the peripheral blood chromosomes of the couple were normal and no obvious abnormalities were detected by the prenatal ultrasound either in our hospital or another hospital, the pregnant woman decided to continue the pregnancy after genetic counseling and delivered a baby girl at 41 weeks of gestation. The girl showed no physical abnormalities during a seven-month follow-up.