ObjectiveTo analyse the efficacy and mechanism of Guizhi Fulingwan in regulating sex hormone disorders in rats with benign prostatic hyperplasia （BPH）. MethodsThirty male SD rats were randomly divided into a sham group， a model group， a finasteride group （0.45 mg·kg^-1·d^-1）， and low-dose and high-dose groups of Guizhi Fulingwan （0.135， 0.337 5 g∙kg^-1∙d^-1）， with six in each group. The BPH model was prepared by subcutaneous injection of 3.5 mg∙kg^-1∙d^-1 testosterone propionate after debridement surgery in all groups except the sham group. The rats in the sham group and the model group were administered with an equal volume of saline by gavage， and the rest of the groups were administered with the corresponding medicinal solution by gavage for 35 days. Histopathology in rats was evaluated by prostate wet weight， volume， index， and hematoxylin-eosin （HE） staining. The serum sex hormone levels of testosterone （T）， dihydrotestosterone （DHT）， and estradiol （E₂） were determined by enzyme-linked immunosorbent assay. The protein expression of the androgen receptor （AR） was detected by immunohistochemistry. The serum metabolism profiles of rats in the sham group， the model group， and the high-dose group of Guizhi Fulingwan were compared by ultra-high performance liquid chromatography tandem Fourier transform mass spectrometry （UHPLCQ Exactive） to screen for metabolic markers and to obtain relevant metabolic pathways. ResultsCompared with those in the sham group， the wet weight， volume， index， serum sex hormone level， and AR protein expression of the prostate in the model group were all elevated （P<0.05， P<0.01）， and the histomorphology showed pathological changes. Compared with those in the model group， the wet weight， volume， index， serum sex hormone level， and AR protein expression of the prostate in the intervention groups showed a decreasing trend （P<0.05， P<0.01）， and histopathology was improved. Serum metabolomics analysis obtained a total of 40 metabolic markers related to the intervention effect of Guizhi Fulingwan， such as dehydrosafynol， hyoscyamine， and lumichrome， which were involved in the pathways of autophagy， riboflavin metabolism， and retrograde endocannabinoid signaling. ConclusionGuizhi Fulingwan can effectively regulate sex hormone disorders in BPH rats， and its mechanism may be related to autophagy， riboflavin metabolism， and retrograde endocannabinoid signaling.

BACKGROUND: The transcription factor POU2F1 regulates the expression levels of microRNAs in neoplasia. However, the miR-29b1/a cluster modulated by POU2F1 in gastric cancer (GC) remains unknown. METHODS: Gene expression in GC cells was evaluated using reverse-transcription polymerase chain reaction (PCR), western blotting, immunohistochemistry, and RNA in situ hybridization. Co-immunoprecipitation was performed to evaluate protein interactions. Transwell migration and invasion assays were performed to investigate the biological behavior of GC cells. MiR-29b1/a cluster promoter analysis and luciferase activity assay for the 3'-UTR study were performed in GC cells. In vivo tumor metastasis was evaluated in nude mice. RESULTS: POU2F1 is overexpressed in GC cell lines and binds to the miR-29b1/a cluster promoter. POU2F1 is upregulated, whereas mature miR-29b-3p and miR-29a-3p are downregulated in GC tissues. POU2F1 promotes GC metastasis by inhibiting miR-29b-3p or miR-29a-3p expression in vitro and in vivo . Furthermore, PIK3R1 and/or PIK3R3 are direct targets of miR-29b-3p and/or miR-29a-3p , and the ectopic expression of PIK3R1 or PIK3R3 reverses the suppressive effect of mature miR-29b-3p and/or miR-29a-3p on GC cell metastasis and invasion. Additionally, the interaction of PIK3R1 with PIK3R3 promotes migration and invasion, and miR-29b-3p , miR-29a-3p , PIK3R1 , and PIK3R3 regulate migration and invasion via the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in GC cells. In addition, POU2F1 , PIK3R1 , and PIK3R3 expression levels negatively correlated with miR-29b-3p and miR-29a-3p expression levels in GC tissue samples. CONCLUSIONS The POU2F1 - miR-29b-3p / miR-29a-3p-PIK3R1 / PIK3R1 signaling axis regulates tumor progression and may be a promising therapeutic target for GC.
MicroRNAs/metabolism* ; Humans ; Stomach Neoplasms/pathology* ; Cell Line, Tumor ; Cell Movement/physiology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Animals ; Mice ; Octamer Transcription Factor-1/metabolism* ; Mice, Nude ; Class Ia Phosphatidylinositol 3-Kinase/metabolism* ; Neoplasm Invasiveness ; Gene Expression Regulation, Neoplastic/genetics* ; Male ; Immunohistochemistry ; Female

The NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, a high-molecular-weight protein complex in the cytoplasm, is composed of three core components: the sensor protein NLRP3, the adaptor protein apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) and the effector protein caspase-1. It plays a critical role in regulating host immune and inflammatory responses. Studies have shown that the NLRP3 inflammasome has increasingly become a focal point in tumor molecular biology field. A growing body of evidence indicates that the increased expression and activation of the NLRP3 inflammasome is closely associated with the pathogenesis of head and neck squamous cell carcinoma (HNSCC) and the tumor microenvironment (TME). It may promote tumor proliferation, invasion, migration, and other biological behaviors through various regulatory mechanisms while influencing tumor immune evasion and therapy resistance, which holds promise as a prognostic biomarker for patients. This review explores the current effect and mechanism of the NLRP3 inflammasome and its signaling pathways in head and neck cancer, providing insights into clinical targeted drug development and molecular immunotherapy.
Humans ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Inflammasomes/metabolism* ; Head and Neck Neoplasms/pathology* ; Squamous Cell Carcinoma of Head and Neck/metabolism* ; Tumor Microenvironment ; Signal Transduction ; Animals

OBJECTIVES: To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application. Methods and. RESULTS: Recommendations were formulated based on literature review and expert group discussion, and consensus was reached following expert consultation. The consensus recommendations are comprehensive, covering the entire treatment procedures from preoperative assessment and preparation, surgical operation process, postoperative management and traditional Chinese medicine treatment to individualized treatment planning. The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain, reduced the use of opioid drugs, and significantly improved the quality of life and enhanced immune function of the patients. Postoperative follow-up suggested good treatment tolerance among the patients without serious complications. CONCLUSIONS The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy. The combined treatment has a high clinical value with a good safety profile for management of cancer pain.
Humans ; Medicine, Chinese Traditional ; Cancer Pain/therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Drug Delivery Systems ; Pain Management/methods* ; China

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Sepsis is a life-threatening organ dysfunction syndrome caused by a dysregulated host response to infection. Septic acute kidney injury (SAKI) is one of the most common complications of sepsis, and the occurrence of acute kidney injury (AKI) indicates that the patient's condition is critical with a poor prognosis. The traditional view holds that the main mechanism of SAKI is the reduction of renal blood flow, inadequate renal perfusion, inflammatory response, and microcirculatory dysfunction caused by sepsis, which subsequently leads to ischemia and necrosis of renal tubular cells. Recent research findings indicate that processes such as autophagy and other forms of programmed cell death play an increasingly important role. Autophagy is a programmed intracellular degradation process and is a form of programmed cell death. Cells degrade their cytoplasmic components via lysosomes, breaking down and recycling intracellular constituents to meet their metabolic needs, maintain intracellular homeostasis, and renew organelles. During SAKI, autophagy plays a crucial protective role through various mechanisms, including regulating inflammation and immune responses, clearing damaged organelles, and maintaining stability in the intracellular environment. In recent years, the role of autophagy in the pathogenesis and treatment of SAKI has received widespread attention. Research has confirmed that various intracellular signaling pathways and signaling molecules targeting autophagy [such as mammalian target of rapamycin (mTOR) signaling pathway, AMP-activated protein kinase (AMPK) signaling pathway, nuclear factor-κB (NF-κB) signaling pathway, and Sirtuins (SIRT), autophagy associated factor Beclin-1, and Toll-like receptor (TLR)] are involved in the development of SAKI. Due to the complex pathogenesis of SAKI, current treatment strategies include fluid management, infection control, maintenance of internal environment balance, and renal replacement therapy; however, the mortality remains high. In recent years, it has been found that autophagy plays a critical protective role in sepsis-mediated AKI. As a result, an increasing number of drugs are being developed to alleviate SAKI by regulating autophagy. This article reviews the latest advances in the role of autophagy in the pathogenesis and treatment of SAKI, with the aim of providing insights for the development of new drugs for SAKI patients.
Humans ; Acute Kidney Injury/etiology* ; Autophagy ; Sepsis/complications* ; Signal Transduction

ObjectiveTo assess the microstructural involvement of gray matter in recovered COVID-19 patients using Synthetic MRI. MethodsThis study was conducted in 29 recovered COVID-19 patients， including severe group （SG， n=11） and ordinary group （OG， n=18）. Healthy volunteers matched by age， sex， BMI and years of education were selected as a healthy control group （HC=23 cases）. Each subject underwent synthetic MRI to generate quantitative T₁ and T₂ maps， and the T₁ and T₂ maps were segmented into 90 regions of interest （ROIs） using automatic anatomical labeling （AAL） mapping. T₁ and T₂ values for each ROI were obtained by averaging all voxels within the ROIs. The T₁ and T₂ values of the 90 brain regions between the three groups were compared. ResultsRelative to HC， the SG had significantly higher T2 values in bilateral orbital superior frontal gyrus， bilateral parahippocampal gyrus， bilateral putamen， bilateral middle temporal gyrus， bilateral Inferior temporal gyrus， left orbital superior frontal gyrus， left orbital inferior frontal gyrus， left gyrus rectus， left anterior cingulate and paracingulate gyri， right median cingulate and paracingulate gyri， left posterior cingulate gyrus， and left supramarginal gyrus （P＜0.05）； Relative to OG， SG showed significantly increased T₂ values in the left rectus gyrus， left parahippocampal gyrus， bilateral middle temporal gyrus， and bilateral inferior temporal gyrus （P＜0.05）. Relative to HC， the T₁ values of SG were significantly increased in bilateral orbital superior frontal gyrus， left rectus gyrus， left anterior cingulate and paracingulate gyri， right posterior cingulate gyrus， left parahippocampal gyrus， left lingual gyrus， left putamen， left thalamus（P＜0.05）； Relative to OG， the T₁ values of SG were significantly higher in the right posterior cingulate gyrus， right calcarine fissure and surrounding cortex， and left putamen （P＜0.05）. ConclusionsEven after recovering from COVID-19， patients may still have persistent or delayed damage to their brain gray matter structure， which is correlated with the severity of the condition. SyMRI can serve as a sensitive tool to assess the extent of microstructural damage to the central nervous system， aiding in early diagnosis of the disease.

[摘 要] 目的：探讨使用同种异体Vγ9Vδ2 T细胞回输治疗晚期肝细胞癌（HCC）患者的安全性及治疗后患者免疫功能的变化。方法：选择2021年10月至2022年10月珠海市人民医院收治的4例晚期HCC患者，从健康供体获取外周血单个核细胞（PBMC）后经刺激扩增培养获得Vγ9Vδ2 T细胞，经质控放行后予以回输治疗，回输细胞剂量为5×108个/次，每两周一次，回输次数9次以上，治疗后检测患者αβT细胞、B细胞、NK细胞、γδT细胞各亚群比例，转氨酶、肌酐、肌酸激酶等肝、肾、心功能生化标志物，以及血常规三系（白细胞系统、红细胞系统和血小板系统）细胞数量的变化。结果：4例患者在回输治疗后均显示出对异体Vγ9Vδ2 T细胞良好的耐受性；转氨酶、肌酐、肌酸激酶等肝、肾、心功能生化标志物以及血常规三系细胞数量在回输前后均无明显变化；患者的Tfh1、Tc1、CD127+TEM、HLADR+CD8+ T细胞、CD27- B细胞比例有升高趋势，提示特异性免疫功能的增强。结论：同种异体Vγ9Vδ2 T细胞治疗晚期HCC有较好的安全性并可在一定程度上改善患者的免疫功能。

Alzheimer's disease is a common central neurodegenerative disease， mainly manifested by cognitive impairment and non-cognitive neuropsychiatric symptoms that severely affect patients' daily life and behavioral functioning. The pathogenesis of Alzheimer's disease is still unclear， and the western medicine currently used to treat Alzheimer's disease is only symptomatic， with a single pathway， limited efficacy， and many side effects. In recent years， with the deepening of research on Alzheimer's disease， the study and application of traditional Chinese medicine （TCM） in the treatment of Alzheimer's disease have gradually increased. Several studies have shown that TCM and its effective components can exert anti-Alzheimer's disease effects by regulating molecular mechanisms such as pathological protein production and aggregation， oxidative stress， neuroinflammation， ferroptosis， mitochondrial dysfunction， neurogenesis and neurotransmission， and brain-gut axis. This paper summarized the research progress of TCM in the treatment of Alzheimer's disease in recent years， so as to provide a reference for further study of the specific mechanism of TCM in the prevention and treatment of Alzheimer's disease and the discovery of effective components of TCM.

Microglia, originating from primitive macrophages in the yolk sac, serves as both immune system defenders and regulators of homeostasis. These cells exhibit two primary polarization states: conventionally activated(M1)and alternatively activated(M2). The polarization of microglia plays a crucial role in influencing inflammatory disorders, metabolic imbalances, and neural degeneration. This process is implicated in various aspects of ocular diseases, especially age-related macular degeneration(AMD), including inflammation, oxidative stress and pathological angiogenesis. The distinct functional phenotypes of microglia impact disease progression and prognosis. Thus, regulating the polarization or functional phenotype of microglia at different stages of AMD holds promise for personalized therapeutic approaches. This comprehensive review outlines the involvement of microglia polarization in both physiological and pathological conditions, emphasizing its relevance in AMD. The discussion underscores the potential of polarization as a foundation for personalized treatment strategies for AMD.