OBJECTIVE To study the protective effect and potential mechanism of chikusetsu saponin Ⅳ a （chsⅣ） on renal function in diabetic nephropathy （DN） model rats. METHODS DN rat model was established by high-fat diet combined with streptozotocin injection. Thirty-six model rats were randomly divided into model group （i.g. administration of normal saline， high-fat diet）， chsⅣ low-dose and high-dose groups （i.g. administration of 90， 180 mg/kg chsⅣ， high-fat diet）， with 12 rats in each group. Additionally， 10 normal rats were set as the control group （i.g. administration of normal saline， regular diet）. From the 5th to the 12th week after streptozotocin injection， they were given intragastric administration of relevant drug or normal saline， once a day. After the last medication， the levels of fasting blood glucose， fasting insulin， blood urea nitrogen， serum creatinine and urine protein as well as the levels of reduced glutathione （GSH）， superoxide dismutase （SOD） and malondialdehyde （MDA） in renal tissues were measured. Additionally， the insulin resistance index was calculated. Hematoxylin-eosin， periodic acid-Schiff， and Masson staining techniques were employed to examine the histopathological alterations in the renal tissue. The expressions of Notch signaling pathway-related proteins in renal tissue were detected by immunohistochemical staining and Western blot methods. RESULTS Compared with model group， the histomorphological of renal tissues in the chsⅣ low- and high-dose groups were significantly improved， with significant decreases in renal histological scores， mesangial expansion index， and glomerulosclerosis scores （ P ＜0.05）； the levels of fasting blood glucose， fasting insulin， blood urea nitrogen， serum creatinine， urine protein and homeostasis model assessment for insulin resistance， as well as MDA content， the expression levels of Notch1， Notch intracellular domain， hairy and enhancer of Split 1 and Delta-like protein 1 in renal tissue were all significantly decreased （ P ＜0.05）. The levels of GSH and SOD in renal tissue were significantly elevated （ P ＜0.05）. Moreover， the improvement in these indicators was significantly more pronounced in the chsⅣ high-dose group compared to the chsⅣ low-dose group （ P ＜0.05）. CONCLUSIONS ChsⅣ can ameliorate renal pathological damage and functional impairment in DN rats. Its underlying mechanisms include restoration of glucose homeostasis and insulin sensitivity， attenuation of renal oxidative stress， and suppression of aberrant Notch signaling pathway activation.

ObjectiveTo investigate the effect of interfering with long noncoding RNA （LncRNA） small nucleolar RNA host gene16 （SNHG16） on improving angiogenesis of ectopic endometrial stromal cells （EScs） in adenomyosis （AM） by targeting upregulation of miRNA （miR）-141-3p and inhibition of high mobility group box-1 protein （HMGB1）. MethodsThe expression levels of SNHG16， miR-141-3p and HMGB1 mRNA in endometrial tissues of 52 patients with adenomyosis （AM group） and 52 patients who needed hysterectomy due to cervical cancer or ovarian cancer （control group） were detected by quantitative reverse transcription polymerase chain reaction （qRT-PCR）. Y14 cells were divided into small hairpin RNA （shRNA） NC group， shRNA SNHG16 group， shRNA SNHG16+miR-141-3p inhibitor （inhibitor） group， shRNA SNHG16+inhibitor NC group and blank group. The targeting relationship between miR-141-3p and SNHG16 as well as HMGB1 was verified. The expression levels of SNHG16， miR-141-3p and HMGB1 mRNA in Y14 cells were detected by qRT-PCR. CCK-8 and Transwell assay were used to detect cell proliferation， invasion and migration. Microvascular density （MVD） was determined by immunofluorescence. The expressions of hypoxia-inducing factor α （HIF-1α）， cyclooxygenase-2 （Cox-2）， vascular endothelial growth factor （VEGF） and HMGB1 were detected by Western blot. ResultsThe expression of SNHG16 and HMGB1 mRNA in AM group was higher than that in control group， but the expression of miR-141-3p was lower than that in control group （P0.05）. The expression of SNHG16， HMGB1 mRNA， proliferation rate， migration， invasion number， MVD， expression of VEGF， HIF-1 α， Cox-2， and HMGB1 proteins in the shRNA SNHG16 group were lower than those in the blank group and shRNA NC group， while the expression of miR-141-3p was higher than that in the blank group and shRNA NC group （P0.05）. Inhibition of miR-141-3p reversed the improvement of EScs angiogenesis by interfering with SNHG16. ConclusionInterference with LncRNA SNHG16 improves EScs angiogenesis and inhibits proliferation， migration， and invasion of EScs by targeting upregulation of miR-141-3p and inhibition of HMGB1.

Objective To analyze the clinical efficacy and safety of transurethral blue laser vaporization of prostate (BVP) in the treatment of benign prostatic hyperplasia (BPH), and to explore the feasibility of its promotion in primary hospitals. Methods Clinical data of 30 BPH patients undergoing BVP in our hospital during Sep. and Dec. 2024 were retrospectively analyzed. The preoperative prostate volume, decrease in hemoglobin level 2 hours after operation, operation time, postoperative bladder irrigation time, catheter indwelling time, and intra-/postoperative complications were recorded. The changes of international prostate symptom score (IPSS), quality of life (QoL) score, and maximum urinary flow rate (Qmax) were compared before operation and 6 months after operation. Results The mean prostate volume was (46.9±15.7) mL. BVP was successfully completed in 28 patients. The 2 unsuccessful cases (6.7%) converted to transurethral resection of the prostate (TURP) due to intraoperative bleeding. For the 28 successful cases, the median postoperative 2-hour hemoglobin decrease was 4 (2, 11) g/L, mean operation time (59.8±13.2) min, median postoperative bladder irrigation time 21 (18, 23) h, median postoperative catheter indwelling time 5 (5, 5) d, and median postoperative hospital stay 6 (5, 6) d. After catheter removal, urinary retention with infection occurred in 1 case (3.6%), and hemorrhage in 1 case (3.6%). No severe complications occurred during the perioperative period. At 6 months postoperatively, the 28 patients showed significant improvement compared to preoperative values in IPSS[11 (10, 11) vs. 22 (21, 26), P＜0.001], QoL score[2 (2, 3) vs. 5 (5, 6), P＜0.001], and Qmax[ (17.2±5.6) mL/s vs. (7.8±1.4) mL/s, P＜0.001]. Conclusion BVP is a safe and effective treatment for BPH, offering advantages such as minimal blood loss, short operation time, and few complications. It effectively improves patients' lower urinary tract symptoms and quality of life, and is recommended for promotion in primary hospitals.

NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome mediates inflammation, induces pyroptosis, and regulates periodontal tissue remodeling through the maturation and secretion of its downstream cysteine protease 1 (Caspase-1)-dependent pro-inflammatory cytokines, interleukin (IL)-1β and IL-18. Orthodontic force mediates the aseptic inflammation of periodontal tissues and triggers adaptive alteration of periodontal tissues, thereby promoting the movement and stability of orthodontic teeth. NLRP3 inflammasome plays an important role in orthodontic tooth movement and causes periodontal tissue inflammation and orthodontic inflammatory root resorption in orthodontic patients. Literature review suggests that NLRP3 inflammasome is involved in the activation and differentiation of periodontal ligament fibroblasts, periodontal ligament stem cells, macrophages, osteoblasts, and osteoclasts in orthodontic tooth mobile tissue remodeling. Additionally, it targets the upstream nuclear factor kappa-B signaling pathway; downstream effectors, such as Caspase-1, IL-1β, and IL-18; and the NLRP3 inflammasome components for regulating tooth movement as well as treating and preventing orthodontics-associated periodontitis and orthodontic-induced inflammatory root resorption. Future studies can be focused on the specific mechanism of NLRP3 inflammasome tissue modification during orthodontic tooth movement. This article reviews the effects and regulatory mechanisms of the NLRP3 inflammasome signaling pathway on the corresponding tissue remodeling during orthodontic tooth movement.

Amyotrophic lateral sclerosis (ALS) is an irreversible, fatal neurodegenerative disorder whose incidence is positively correlated with the aging population. ALS is characterized by the progressive loss of motor neurons, leading to muscle weakness, atrophy, and ultimately respiratory failure. The pathogenesis of ALS involves multiple factors, including genetic and environmental influences, with genetic factors playing a particularly significant role. To date, several causative genes have been identified in ALS, such as the Cu/Zn superoxide dismutase 1 (Cu/Zn SOD1, also known as SOD1) gene, transactive response DNA-binding protein 43 (TDP-43) gene, fused in sarcoma (FUS) gene, and chromosome open reading frame 72 (C9orf72). Mutations in these genes have been found not only in familial ALS but also in sporadic ALS. Based on the identified ALS risk genes, various ALS animal models have been established through multiple approaches, including transgenic models, gene knockout/knock-in models, and adeno-associated virus-mediated overexpression models. These models simulate some typical pathological features of human ALS, such as motor neuron loss, ubiquitinated inclusions, and neuromuscular junction degeneration. However, these models still have limitations: (1) single-gene mutation models are insufficient to fully replicate the complex multi-factorial pathogenesis of sporadic ALS; (2) significant differences in microenvironmental regulation mechanisms and the rate of neurodegeneration between model organisms and humans may affect the accurate reproduction of disease phenotypes and the reliable evaluation of drug efficacy. To better understand the pathogenesis of ALS and promote the development of effective therapies, constructing and optimizing ALS animal models is crucial. This review aims to summarize commonly used ALS gene mutation mouse models, analyze their phenotypes and pathological characteristics, including transgenic mouse models, gene knockout/knock-in mouse models, and adeno-associated virus-mediated overexpression mouse models, and further discuss their specific applications in ALS pathogenesis research and drug development by comparing the advantages and limitations of each model.

Amyotrophic lateral sclerosis (ALS) is an irreversible, fatal neurodegenerative disorder whose incidence is positively correlated with the aging population. ALS is characterized by the progressive loss of motor neurons, leading to muscle weakness, atrophy, and ultimately respiratory failure. The pathogenesis of ALS involves multiple factors, including genetic and environmental influences, with genetic factors playing a particularly significant role. To date, several causative genes have been identified in ALS, such as the Cu/Zn superoxide dismutase 1 (Cu/Zn SOD1, also known as SOD1) gene, transactive response DNA-binding protein 43 (TDP-43) gene, fused in sarcoma (FUS) gene, and chromosome open reading frame 72 (C9orf72). Mutations in these genes have been found not only in familial ALS but also in sporadic ALS. Based on the identified ALS risk genes, various ALS animal models have been established through multiple approaches, including transgenic models, gene knockout/knock-in models, and adeno-associated virus-mediated overexpression models. These models simulate some typical pathological features of human ALS, such as motor neuron loss, ubiquitinated inclusions, and neuromuscular junction degeneration. However, these models still have limitations: (1) single-gene mutation models are insufficient to fully replicate the complex multi-factorial pathogenesis of sporadic ALS; (2) significant differences in microenvironmental regulation mechanisms and the rate of neurodegeneration between model organisms and humans may affect the accurate reproduction of disease phenotypes and the reliable evaluation of drug efficacy. To better understand the pathogenesis of ALS and promote the development of effective therapies, constructing and optimizing ALS animal models is crucial. This review aims to summarize commonly used ALS gene mutation mouse models, analyze their phenotypes and pathological characteristics, including transgenic mouse models, gene knockout/knock-in mouse models, and adeno-associated virus-mediated overexpression mouse models, and further discuss their specific applications in ALS pathogenesis research and drug development by comparing the advantages and limitations of each model.

The Master Plan on Building China into a Leading Country in Education （2024-2035） has made important arrangements for“expanding the space and battlefield for practical and online education”and“fully utilizing the educational function of red resources”. Red medicine culture is a cultural system with strong vitality and excellent genes created by the people led by the CPC in the process of creating health care undertakings. In the context of the new era， how to effectively promote the integration of red medicine culture into the ideological and political education in medical colleges and universities to enhance medical students’ sense of professional identity， responsibility， and mission has become a key issue in the current medical education reform. By analyzing the necessity and basic principles of integrating red doctor culture into ideological and political education in medical colleges and universities， a practical path based on the “three horizontal integrations and three vertical dimensions” model was proposed. Specifically， this involves horizontally promoting textbook construction， classroom teaching， and ideological and political practice， while vertically deepening pre-class preparation， classroom teaching reform， and post-class evaluation， thereby building a systematic and operational red doctor culture integration system as well as providing theoretical support and practical guidance for the cultivation of medical talents in the new era.

Direct electrical stimulation of the human cortex can produce subjective visual sensations, yet these sensations are unstable. The underlying mechanisms may stem from differences in electrophysiological activity within the distributed network outside the stimulated site. To address this problem, we recruited 69 patients who experienced visual sensations during invasive electrical stimulation while intracranial electroencephalography (iEEG) data were recorded. We found significantly flattened power spectral slopes in distributed regions involving different brain networks and decreased integrated information during elicited visual sensations compared with the non-sensation condition. Further analysis based on minimum information partitions revealed that the reconfigured network interactions primarily involved the inferior frontal cortex, posterior superior temporal sulcus, and temporoparietal junction. The flattened power spectral slope in the inferior frontal gyrus was also correlated with integrated information. Taken together, this study indicates that the altered electrophysiological signatures provide insights into the neural mechanisms underlying subjective visual sensations.
Humans ; Male ; Female ; Adult ; Visual Perception/physiology* ; Electric Stimulation ; Middle Aged ; Young Adult ; Electrocorticography ; Electroencephalography ; Brain Mapping

Epilepsy is a chronic neurological disorder affecting ~65 million individuals worldwide. Abnormal synaptic plasticity is one of the most important pathological features of this condition. We investigated how ubiquitin-specific peptidase 47 (USP47) influences synaptic plasticity and its link to epilepsy. We found that USP47 enhanced excitatory postsynaptic transmission and increased the density of total dendritic spines and the proportion of mature dendritic spines. Furthermore, USP47 inhibited the degradation of the ubiquitinated α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunit glutamate receptor 1 (GluR1), which is associated with synaptic plasticity. In addition, elevated levels of USP47 were found in epileptic mice, and USP47 knockdown reduced the frequency and duration of seizure-like events and alleviated epileptic seizures. To summarize, we present a new mechanism whereby USP47 regulates excitatory postsynaptic plasticity through the inhibition of ubiquitinated GluR1 degradation. Modulating USP47 may offer a potential approach for controlling seizures and modifying disease progression in future therapeutic strategies.
Animals ; Receptors, AMPA/metabolism* ; Neuronal Plasticity/physiology* ; Seizures/physiopathology* ; Disease Models, Animal ; Mice, Inbred C57BL ; Mice ; Ubiquitin Thiolesterase/genetics* ; Male ; Excitatory Postsynaptic Potentials/physiology* ; Ubiquitination ; Dendritic Spines/metabolism* ; Hippocampus/metabolism*

Apical microsurgery is accurate and minimally invasive, produces few complications, and has a success rate of more than 90%. However, due to the lack of awareness and understanding of apical microsurgery by dental general practitioners and even endodontists, many clinical problems remain to be overcome. The consensus has gathered well-known domestic experts to hold a series of special discussions and reached the consensus. This document specifies the indications, contraindications, preoperative preparations, operational procedures, complication prevention measures, and efficacy evaluation of apical microsurgery and is applicable to dentists who perform apical microsurgery after systematic training.
Microsurgery/standards* ; Humans ; Apicoectomy ; Contraindications, Procedure ; Tooth Apex/diagnostic imaging* ; Postoperative Complications/prevention & control* ; Consensus ; Treatment Outcome