This study investigates the reproductive protective effect and potential mechanism of Cistanches Herba extract(CHE) on a rat model of kidney-Yang deficiency induced by adenine. Rats were randomly divided into five groups: normal, model, low-dose CHE(0.6 g·kg~(-1)·d~(-1)), high-dose CHE(1.2 g·kg~(-1)·d~(-1)), and L-carnitine(100 mg·kg~(-1)·d~(-1)). The rats were administered adenine(200 mg·kg~(-1)·d~(-1)) by gavage for the first 14 days to induce kidney-Yang deficiency, while simultaneously receiving drug treatment. After 14 days, the modeling was discontinued, but drug treatment continued to 49 days. The content of components in CHE was analyzed by high-performance liquid chromatography. The adenine-induced kidney-Yang deficiency model was assessed through symptom characterization and measurement of testosterone(T) levels using an enzyme-linked immunosorbent assay kit. Pathological damage to the testis and epididymis was evaluated based on the wet weight and performing hematoxylin-eosin staining. Sperm density and motility were measured using computer-aided sperm analysis, and sperm viability was assessed using live/dead sperm staining kits, and sperm morphology was evaluated using eosin staining, thereby determining rat sperm quality. Metabolomics was used to analyze changes in serum metabolites, enrich related metabolic pathways, and explore the mechanism of CHE in improving reproductive function damage in rats with kidney-Yang deficiency syndrome. Compared to the normal group, the model group exhibited significant kidney-Yang deficiency symptoms, reduced T levels, decreased testicular and epididymal wet weights, and significant pathological damage to the testis and epididymis. The sperm density, motility, and viability decreased, with an increased rate of sperm abnormalities. In contrast, rats treated with CHE showed marked improvements in kidney-Yang deficiency symptoms, restored T levels, alleviated pathological damage to the testis and epididymis, and improved various sperm parameters. Metabolomics results revealed 286 differential metabolites between the normal and model groups(191 upregulated and 95 downregulated). Seventy-five differential metabolites were identified between the model and low-dose CHE groups(21 upregulated and 54 downregulated). A total of 24 common differential metabolites were identified across the three groups, with 22 of these metabolites exhibiting opposite regulation trends between the two comparison groups. These metabolites were primarily involved in linoleic acid metabolism, ether lipid metabolism, and pantothenic acid and coenzyme A biosynthesis, as well as metabolites including 13-hydroperoxylinoleic acid, lysophosphatidylcholine, and pantethine. CHE can improve kidney-Yang deficiency symptoms in rats, alleviate reproductive organ damage, and enhance sperm quality. The regulation of lipid metabolism may be a potential mechanism through which CHE improves reproductive function in rats with kidney-Yang deficiency. The potential bioactive compounds of CHE include echinacoside, verbascoside, salidroside, betaine, and cistanoside A.
Animals ; Male ; Rats ; Yang Deficiency/physiopathology* ; Metabolomics ; Kidney/physiopathology* ; Rats, Sprague-Dawley ; Drugs, Chinese Herbal/administration & dosage* ; Cistanche/chemistry* ; Kidney Diseases/metabolism* ; Testis/metabolism* ; Humans ; Reproduction/drug effects* ; Testosterone/blood*

Based on the interleukin-17(IL-17) signaling pathway, this study explores the effect and mechanism of Bufei Decoction on Klebsiella pneumoniae pneumonia in rats. SD rats were randomly divided into the control group, model group, Bufei Decoction low-dose group(6.68 g·kg~(-1)·d~(-1)), Bufei Decoction high-dose group(13.36 g·kg~(-1)·d~(-1)), and dexamethasone group(1.04 mg·kg~(-1)·d~(-1)), with 10 rats in each group. A pneumonia model was established by tracheal drip injection of K. pneumoniae. After successful model establishment, the improvement in lung tissue damage was observed following drug administration. Core targets and signaling pathways were screened using transcriptomics techniques. Real-time fluorescence quantitative polymerase chain reaction was used to detect the mRNA expression of core targets interleukin-6(IL-6), interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and chemokine CXC ligand 6(CXCL6). Western blot was used to assess key proteins in the IL-17 signaling pathway, including interleukin-17A(IL-17A), nuclear transcription factor-κB activator 1(Act1), tumor necrosis factor receptor-associated factor 6(TRAF6), and downstream phosphorylated p38 mitogen-activated protein kinase(p-p38 MAPK), and phosphorylated nuclear factor-κB p65(p-NF-κB p65). Apoptosis of lung tissue cells was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling(TUNEL). The results showed that, compared with the control group, the model group exhibited significant pathological damage in lung tissue. The mRNA expression of IL-6, IL-1β, TNF-α, and CXCL6, as well as the protein levels of IL-17A, Act1, TRAF6, p-p38 MAPK/p38 MAPK, and p-NF-κB p65/NF-κB p65, were significantly increased, and the number of apoptotic cells was notably higher, indicating successful model establishment. Compared with the model group, both low-and high-dose groups of Bufei Decoction showed reduced pathological damage in lung tissue. The mRNA expression levels of IL-6, IL-1β, TNF-α, and CXCL6, and the protein levels of IL-17A, Act1, TRAF6, p-p38 MAPK/p38 MAPK, and p-NF-κB p65/NF-κB p65, were significantly decreased, with a significant reduction in apoptotic cells in the high-dose group. In conclusion, Bufei Decoction can effectively improve lung tissue damage and reduce inflammation in rats with K. pneumoniae. The mechanism may involve the regulation of the IL-17 signaling pathway and the reduction of apoptosis.
Animals ; Interleukin-17/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; Rats ; Male ; Klebsiella pneumoniae/physiology* ; Klebsiella Infections/immunology* ; Humans ; Lung/drug effects*

OBJECTIVE: To investigate the safety and efficacy of avatrombopag（AVA） combined with rhIL-11 in treating thrombocytopenia induced by chemotherapy in acute myeloid leukemia. METHODS: The clinical information of 8 patients in the real world who received avatrombopag combined with rhIL-11 in cancer treatment-induced thrombocytopenia(CTIT) after AML chemotherapy were retrospectively analyzed, and at the same time, 8 patients who received rhIL-11 only in CTIT after AML chemotherapy served as the control group, A preliminary observation was to summarize and compare the therapeutic efficacy and adverse effects between the two groups. RESULTS: D3 and D7 platelet counts were not significantly different between the observation group and the control group after treatment. The platelet counts in the observation group was significantly higher than those of the control group on the 10th day after treatment (P < 0.01). The adverse reactions, such as weakness, abdominal pain, fatigue, nausea and edema after treatment were mild in the observation group and the control group. Except for one patient in the observation group who had a history of cerebral infarction before the onset of the disease and was routinely taking antiplatelet drugs, no thrombosis events occurred in the patients in the observation and control groups during the period of administration of the drug, and the total incidence rate of adverse reactions was not significantly different between the two groups. CONCLUSION The combination of AVA and rhIL-11 can enhance platelet recovery in CTIT of AML patients after chemotherapy. Compared with the rhIL-11 alone group, the platelet recovery time in AVA+rhIL-11 group was significantly shorter, the platelet count on the 10th day after drug administration was significantly higher. No statistically significant difference in the total incidence rate of adverse reactions was observed between rhIL-11 alone group and AVA+rhIL-11 group.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Thrombocytopenia/chemically induced* ; Interleukin-11/therapeutic use* ; Retrospective Studies ; Adult ; Thiophenes/therapeutic use* ; Platelet Count ; Female ; Male ; Middle Aged ; Thiazoles

Adipose tissue is a critical energy reservoir in animals and humans, with multifaceted roles in endocrine regulation, immune response, and providing mechanical protection. Based on anatomical location and functional characteristics, adipose tissue can be categorized into distinct types, including white adipose tissue (WAT), brown adipose tissue (BAT), beige adipose tissue, and pink adipose tissue. Traditionally, adipose tissue research has centered on its morphological and functional properties as a whole. However, with the advent of single-cell transcriptomics, a new level of complexity in adipose tissue has been unveiled, showing that even under identical conditions, cells of the same type may exhibit significant variation in morphology, structure, function, and gene expression——phenomena collectively referred to as cellular heterogeneity. Single-cell transcriptomics, including techniques like single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA sequencing (snRNA-seq), enables in-depth analysis of the diversity and heterogeneity of adipocytes at the single-cell level. This high-resolution approach has not only deepened our understanding of adipocyte functionality but also facilitated the discovery of previously unidentified cell types and gene expression patterns that may play key roles in adipose tissue function. This review delves into the latest advances in the application of single-cell transcriptomics in elucidating the heterogeneity and diversity within adipose tissue, highlighting how these findings have redefined the understanding of cell subpopulations within different adipose depots. Moreover, the review explores how single-cell transcriptomic technologies have enabled the study of cellular communication pathways and differentiation trajectories among adipose cell subgroups. By mapping these interactions and differentiation processes, researchers gain insights into how distinct cellular subpopulations coordinate within adipose tissues, which is crucial for maintaining tissue homeostasis and function. Understanding these mechanisms is essential, as dysregulation in adipose cell interactions and differentiation underlies a range of metabolic disorders, including obesity and diabetes mellitus type 2. Furthermore, single-cell transcriptomics holds promising implications for identifying therapeutic targets; by pinpointing specific cell types and gene pathways involved in adipose tissue dysfunction, these technologies pave the way for developing targeted interventions aimed at modulating specific adipose subpopulations. In summary, this review provides a comprehensive analysis of the role of single-cell transcriptomic technologies in uncovering the heterogeneity and functional diversity of adipose tissues.

Objective:To explore the clinicopathologic features differences between tall cell variant of papillary thyroid cancer (TCV-PTC) and PTC with tall cell features (PTC-TCF) and the factors influencing efficacy of 131I therapy in patients with TCV-PTC and PTC-TCF. Methods:A retrospective analysis was conducted on 84 patients (28 males, 56 females, age 43.5(35.0, 55.0) years) with pathologically confirmed TCV-PTC or PTC-TCF and who were treated with 131I therapy from January 2018 to June 2023 in the Department of Nuclear Medicine, the Affiliated Hospital of Qingdao University. The patients were divided into structural incomplete response (SIR) group and non-SIR group according to 131I treatment response. Data differences were analyzed by Wilcoxon rank sum test, Fisher exact test, or Mann-Whitney U test. Variables with P<0.1 were enrolled in logistic multivariate regression analysis. The ROC curve was used to obtain the cut-off value of stimulated thyroglobulin (sTg). Results:A total of 37 patients with non-SIR and 6 patients with SIR were found in TCV-PTC group ( n=43), and 33 non-SIR and 8 SIR cases were found in PTC-TCF group ( n=41). Univariate analysis revealed that sTg differed significantly between non-SIR patients and SIR patients in TCV-PTC group ( Z=-2.81, P=0.003), while no significant differences observed for sex, age, multifocality, capsular invasion, T stage, N stage, B-Raf proto-oncogene, serine/threonine-protein kinase (BRAF) V600E mutation, initial recurrence risk, number of metastatic lymph nodes, maximum tumor diameter ( Z values: from -0.74 to -0.11, all P>0.05). In TCV-PTC group, sTg also differed significantly between non-SIR patients and SIR patients ( Z=-4.40, P<0.001), while the other clinical factors above and the proportion of tall cells showed no significant difference ( Z values: from -1.90 to -0.22, all P>0.05). The logistic regression analysis confirmed sTg as an independent risk factor of SIR in both TCV-PTC group (odds ratio ( OR) = 25.156, 95% CI: 2.245-281.812, P=0.009) and PTC-TCF group ( OR=19.214, 95% CI: 2.537-145.502, P=0.004). The ROC curve indicated that the cut-off value of sTg for predicting SIR was 20.75μg/L in TCV-PTC group and 18.55μg/L in PTC-TCF group. Conclusions:sTg is the independent risk factor for predicting the poor prognosis of patients with TCV-PTC (sTg≥20.75μg/L) and PTC-TCF (sTg≥18.55μg/L). However, other clinical characteristics show no statistical difference between TCV-PTC group and PTC-TCF group, suggesting that the invasiveness of PTC-TCF may not be lower than that of TCV-PTC, which close attention should be paid to in clinical practice.

Objective To investigate the protective effect and its mechanism of low-dose interleukin-2(IL-2)against hepatocyte injury in Concanavalin A(Con A)-induced autoimmune hepatitis(AIH)mice.Methods Eighteen SPF female C57BL/6 mice were randomly divided into normal group,model group and treatment group,each group with 6 mice.Mice in the treatment group were subcutaneously injected with 300 μl 10,000 U IL-2 for 12 d,once a day.2 h after the last dose,Con A(15 mg/kg)was injected through the tail vein in the model group and treatment group.After 8 h of modeling,the histopathological changes in the mouse liver were observed using HE staining,and the serum levels of aspartate aminotransferase(AST),alanine aminotransferase(ALT),tumor necrosis factor-α(TNF-α),and interferon-γ(IFN-γ)were detected using ELISA method;the expression of apoptotic protein caspase 8/9/3 was detected by Western blotting;and the percentages of Treg and Th1 cells were observed by flow cytometry.Results Compared with normal group,the liver index,spleen index,the percentage of necrotic area of liver tissue,the serum levels of ALT,AST,TNF-α and IFN-γ,and the expression of apoptosis protein caspase 8/9/3 significantly increased in the model group(P<0.05 or P<0.01);Compared with model group,the liver index,spleen index,the percentage of necrotic area of liver tissue,the serum levels of ALT,TNF-α and IFN-γ,and the expression of apoptosis protein caspase 8/9/3 significantly decreased in the treatment group(P<0.05 or P<0.01).The flow cytometry results showed that compared with normal group,the percentages of Treg and Th1 cells and Th1/Treg ratio increased in the model group(P<0.05 or P<0.01);Compared with the model group,the percentage of Treg cells further increased(P<0.01),Th1/Treg ratio decreased significantly in the treatment group(P<0.05),but there was no significant difference in the percentage of Th1 cells between two groups(P>0.05).Conclusion Low-dose of IL-2 can effectively improve liver injury in AIH mice,and the mechanism of action may be related to inducible Treg cell activation.

Objective:To systematically evaluate the impact of common disinfection methods on key human milk bioactive components [lactoferrin, lysozyme, immunoglobulin A (IgA), lipase, milk fat globule structure] and their sterilization efficacy.Methods:We searched eight databases (CNKI, Wanfang, VIP, Yiigle, PubMed, Web of Science, Cochrane Library, CINAHL) from inception to January 22, 2024, including 25 controlled studies. Network meta-analysis was performed using Stata 17.0, with surface under the cumulative ranking curve (SUCRA) values ranking seven methods: holder pasteurization (HoP), high-temperature short-time pasteurization (HTST), freezing, high-pressure processing (HPP), high hydrostatic pressure (HHP), ultraviolet-C (UV-C), and thermal ultrasound (TUS). Primary outcomes included bioactive component retention rates, milk fat globule integrity, and sterilization efficacy against representative pathogens [ Staphylococcus aureus, cytomegalovirus (CMV)]. Results:Bioactive component retention varied significantly: HPP demonstrated optimal lactoferrin preservation (SUCRA=98.2%, retention rate=92.4%±3.1%); HHP showed superior lysozyme retention (SUCRA=91.0%, retention rate=88.6%±2.5%); HTST maximized IgA preservation (SUCRA=75.5%, retention rate=72.3%±4.2%); UV-C achieved highest lipase retention (SUCRA=92.7%, retention rate=90.1%±1.9%). HPP maintained larger milk fat globules versus HoP. All methods achieved≥6-log pathogen reduction. HPP surpassed HoP/HTST in eliminating S. aureus (6-log vs. 4-log at 5-6 log CFU/ml initial load); HHP reduced CMV from 5.0 to 3.7 log PFU/ml (30 min), outperforming HoP (4.1 log). Non-thermal techniques (HPP/HHP/UV-C) better suppressed pathogen versus HoP. Conclusions:Bioactive component preservation is method-specific clinical protocols should therefore be optimized according to target component: HPP is recommended for lactoferrin/milk fat globule integrity; HHP for lysozyme; HTST for IgA; UV-C for lipase. While all methods meet safety standards, non-thermal technologies offer superior long-term pathogen suppression, providing optimized options for milk banks and clinical breastfeeding support.

Objective To develop and validate a transgenic mouse model enabling specific and inducible optogenetic activation of oligodendrocyte precursor cells(OPCs).Methods A conditional allele for the photosensitive opsin chicken opsin 5(cOpn5)(Rosa26-LSL-cOpn5)was generated using CRISPR/Cas9 technology.These mice were subsequently crossed with NG2-CreERT transgenic mice to produce NG2-CreERT;cOpn5 animals.In this model,tamoxifen administration induces Cre-mediated recombination,leading to specific expression of cOpn5 in NG2-positive OPCs.The specificity and efficiency of cOpn5 expression in OPCs were confirmed by immunofluorescent staining.Functional validation of light-induced OPC activation was performed by using calcium imaging in acute brain slices after stimulation with 470 nm blue light.Results Immunofluorescence analysis confirmed robust and specific expression of cOpn5 within NG2-positive OPCs in the brains of tamoxifen-treated NG2-CreERT;cOpn5 mice.Crucially,calcium imaging of acute brain slices from these mice demonstrated a significant increase in intracellular calcium levels in cOpn5-expressing OPCs upon stimulation with 470 nm blue light,indicating successful optogenetic activation.Conclusion We have successfully generated and validated a novel transgenic mouse model(NG2-CreERT;cOpn5)that permits specific and inducible optogenetic activation of OPCs.This model provides a novel tool for subsequent in vivo studies of the role and regulating mechanisms of OPCs in the central nervous system.

Breast cancer is the leading cause of cancer-related mortality among women worldwide and has drawn extensive research attention.Owing to its molecular heterogeneity,drug resistance,and low therapeutic response,single-modality treatments often fail to achieve satisfactory efficacy or broad applicability.Combination therapy,designed based on the pathophysiological characteristics,related signaling pathways,and biomarkers of breast cancer,has emerged as a promising approach for improving therapeutic outcomes.With the advancement of research on combination strategies,the understanding of their molecular mechanisms—particularly key signaling pathways and biomarkers—has become increasingly important.However,comprehensive reviews addressing these molecular mechanisms and synergistic strategies remain scarce.This article summarizes recent advances in combination therapy for breast cancer,providing a comprehensive review of recent combination therapies for breast cancer and their underlying molecular mechanisms,and focusing on key signaling pathways involved in combination therapy and synergistic strategies,thereby providing theoretical insights and reference for researchers,graduate students,and clinicians engaged in the development of novel combination therapeutic strategies for breast cancer and related malignancies.

Objective To develop and validate a transgenic mouse model enabling specific and inducible optogenetic activation of oligodendrocyte precursor cells(OPCs).Methods A conditional allele for the photosensitive opsin chicken opsin 5(cOpn5)(Rosa26-LSL-cOpn5)was generated using CRISPR/Cas9 technology.These mice were subsequently crossed with NG2-CreERT transgenic mice to produce NG2-CreERT;cOpn5 animals.In this model,tamoxifen administration induces Cre-mediated recombination,leading to specific expression of cOpn5 in NG2-positive OPCs.The specificity and efficiency of cOpn5 expression in OPCs were confirmed by immunofluorescent staining.Functional validation of light-induced OPC activation was performed by using calcium imaging in acute brain slices after stimulation with 470 nm blue light.Results Immunofluorescence analysis confirmed robust and specific expression of cOpn5 within NG2-positive OPCs in the brains of tamoxifen-treated NG2-CreERT;cOpn5 mice.Crucially,calcium imaging of acute brain slices from these mice demonstrated a significant increase in intracellular calcium levels in cOpn5-expressing OPCs upon stimulation with 470 nm blue light,indicating successful optogenetic activation.Conclusion We have successfully generated and validated a novel transgenic mouse model(NG2-CreERT;cOpn5)that permits specific and inducible optogenetic activation of OPCs.This model provides a novel tool for subsequent in vivo studies of the role and regulating mechanisms of OPCs in the central nervous system.