OBJECTIVE: Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy. METHODS: Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death. RESULTS: FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism. CONCLUSION To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
Humans ; Carcinoma, Hepatocellular/diagnosis* ; Liver Neoplasms/diagnosis* ; Immunotherapy ; Fanconi Anemia Complementation Group D2 Protein/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/metabolism*

Abstract Bisphenol S is commonly utilized in the industry as a substitute for bisphenol A．However，numerous studies have indicated that bisphenol S also exhibits a wide range of toxicity．Bisphenol S has been found to cause adverse effects on the nervous system，endocrine system，reproductive system，etc．，with more extensive studies on the reproductive system．Specifically，bisphenol S exposure causes a decrease in sperm count，decreases motility and increases malformations，and decreases testosterone levels in males; on the other hand，bisphenol S exposure causes a significant reduction in ovarian volume and relative weight，affectes oocyte quality，decreases gonadotro- pins follicle-stimulating hormone，and luteinizing hormone in females．The mechanisms by which bisphenol S af- fects the body are complex and varied，involving oxidative stress，cell death，and epigenetic modifications．Nota- bly，the reproductive toxicity of bisphenol S varies in different studies．As a result，this paper reviews the reproduc- tive toxicity of bisphenol S and its underlying mechanisms．

Liver ischemia-reperfusion injury (LIRI) is a pathological process involving multiple injury factors and cell types, with different stages. Currently, protective drugs targeting a single condition are limited in efficacy, and interventions on immune cells will also be accompanied by a series of side effects. In the current bottleneck research stage, the multi-target and obvious clinical efficacy of Chinese medicine (CM) is expected to become a breakthrough point in the research and development of new drugs. In this review, we summarize the roles of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in various stages of hepatic ischemia-reperfusion and on various types of cells. Combined with the current research progress in reducing ROS/RNS with CM, new therapies and mechanisms for the treatment of hepatic ischemia-reperfusion are discussed.
Reperfusion Injury/drug therapy* ; Reactive Oxygen Species/metabolism* ; Reactive Nitrogen Species/metabolism* ; Humans ; Liver/drug effects* ; Animals ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/pharmacology*

OBJECTIVE: To elucidate the modulation mechanism of Suanzaoren Decoction (SZRD) on basolateral amygdala (BLA) neuronal activity to alleviate chronic restraint stress (CRS)-related behavioral deficits. METHODS: The male C57BL/6J mice were assigned to 4 groups using the complete randomization method, including control (CON, n=19), CRS (n=19), SZRD (n=21), and fluoxetine (Flu, n=22) groups. Mice were restrained for 6 h per day, over a 21-d period to establish CRS models. The CON group remained in their cages without food or water during the 6-h matching period. SZRD and Flu groups received intragastric administration of SZRD (4.68 g/kg) and Flu (20 mg/kg) daily, respectively, 30 min before restraint for 21 consecutive days. The therapeutic effects of SZRD were evaluated using behavioral tests including the tail suspension test, elevated plus maze test, and forced swimming test. The cellular Fletcher B. Judson murine osteosarcoma proto-oncogene (c-Fos) expression in the BLA was measured using immunofluorescence, while action potential (AP) firing and synaptic transmission in BLA pyramidal neurons were evaluated using whole-cell patch-clamp recordings. RESULTS: SZRD administration significantly increased time spent in the open arms and open-arm entries while reducing immobility time (P<0.05 or P<0.01). It downregulated CRS-induced c-Fos expression and AP firing of pyramidal neurons in the BLA (P<0.01). Additionally, SZRD selectively attenuated excitatory (P<0.01), but not inhibitory, synaptic transmission onto BLA pyramidal neurons. CONCLUSION SZRD alleviated CRS-induced anxiety- and depression-like behaviors in mice by modulating the excitability and synaptic transmission of BLA pyramidal neurons.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Depression/complications* ; Pyramidal Cells/pathology* ; Male ; Mice, Inbred C57BL ; Basolateral Nuclear Complex/pathology* ; Restraint, Physical ; Anxiety/complications* ; Behavior, Animal/drug effects* ; Stress, Psychological/physiopathology* ; Mice ; Proto-Oncogene Proteins c-fos/metabolism* ; Action Potentials/drug effects* ; Synaptic Transmission/drug effects*

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Objective: To investigate the effects of polydatin on a high-fat diet-induced non-alcoholic fatty liver disease(NAFLD) mouse model and hepatoma G2(HepG2) cell model, and to reveal its potential molecular mechanisms. Methods: Thirty 6-week-old male SPF C57BL/6J mice were randomly divided into a normal diet group and a high-fat diet group. After the NAFLD mouse model was established in the high-fat diet group, they were further divided into a model group and a polydatin treatment group. The polydatin treatment group was administered polydatin by gavage at a dose of 250 mg/(kg·d) for 10 weeks, during which body weight was monitored and oral glucose and insulin tolerance tests were performed. At the end of the experiment, a series of tests to evaluate the effects of polydatin on mouse liver weight, blood lipids, liver lipid accumulation, and liver injury markers were performed. The expression of G0/G1 switch gene 2(G0S2) and adipose triglyceride lipase(ATGL) was measured by qRT-PCR and Western blot, and gene expression was further verified using immunohistochemical staining. The effects of polydatin on HepG2 cell activity was assessed by CCK-8 assay, lipid accumulation was observed by oil red O staining, and the expression of G0S2 and ATGL was detected by qRT-PCR and Western blot. Results: Polydatin significantly reduced the body weight, liver weight, and serum and liver tissue levels of aspartate aminotransferase(AST), alanine aminotransferase(ALT), triglyceride(TG), and total cholesterol (TC) in mice (P < 0. 05) , al⁃leviated pathological liver damage , decreased G0S2 expression (P < 0. 05) , and increased ATGL expression (P <0. 05) . At the cellular level , polydatin reduced lipid droplet accumulation , improved lipid metabolism , decreased G0S2 expression ( P < 0. 05 ) , and increased ATGL expression ( P < 0. 05 ) . Even in cells with knockdown of G0S2 , polydatin still promoted fat decomposition (P < 0. 01) . Conclusion Polydatin promotes hepatic fat break⁃down by regulating the expression of G0S2 and ATGL , helping to alleviate metabolic disorders and liver damage in the NAFLD mouse model caused by a high⁃fat diet , offering a new strategy for treating NAFLD.

Periodontal bone defects, primarily caused by periodontitis, are highly prevalent in clinical settings and manifest as bone fenestration, dehiscence, or attachment loss, presenting a significant challenge to oral health. In regenerative medicine, harnessing developmental principles for tissue repair offers promising therapeutic potential. Of particular interest is the condensation of progenitor cells, an essential event in organogenesis that has inspired clinically effective cell aggregation approaches in dental regeneration. However, the precise cellular coordination mechanisms during condensation and regeneration remain elusive. Here, taking the tooth as a model organ, we employed single-cell RNA sequencing to dissect the cellular composition and heterogeneity of human dental follicle and dental papilla, revealing a distinct Platelet-derived growth factor receptor alpha (PDGFRA) mesenchymal stem/stromal cell (MSC) population with remarkable odontogenic potential. Interestingly, a reciprocal paracrine interaction between PDGFRA⁺ dental follicle stem cells (DFSCs) and CD31⁺ Endomucin⁺ endothelial cells (ECs) was mediated by Vascular endothelial growth factor A (VEGFA) and Platelet-derived growth factor subunit BB (PDGFBB). This crosstalk not only maintains the functionality of PDGFRA⁺ DFSCs but also drives specialized angiogenesis. In vivo periodontal bone regeneration experiments further reveal that communication between PDGFRA⁺ DFSC aggregates and recipient ECs is essential for effective angiogenic-osteogenic coupling and rapid tissue repair. Collectively, our results unravel the importance of MSC-EC crosstalk mediated by the VEGFA and PDGFBB-PDGFRA reciprocal signaling in orchestrating angiogenesis and osteogenesis. These findings not only establish a framework for deciphering and promoting periodontal bone regeneration in potential clinical applications but also offer insights for future therapeutic strategies in dental or broader regenerative medicine.
Receptor, Platelet-Derived Growth Factor alpha/metabolism* ; Humans ; Neovascularization, Physiologic/physiology* ; Dental Sac/cytology* ; Single-Cell Analysis ; Transcriptome ; Mesenchymal Stem Cells/metabolism* ; Bone Regeneration ; Animals ; Dental Papilla/cytology* ; Periodontium/physiology* ; Stem Cells/metabolism* ; Regeneration ; Angiogenesis

Objective To analyze the relationship between different degrees of cerebral venous sinus stenosis and the trans-stenotic pressure gradient using a 3D-printed hemodynamic simulation system for cerebral venous sinuses.Methods Based on the double elastic cavity model,a complete morphological model of the superior sagittal sinus,transverse sinus,and sigmoid sinuses was constructed using 3D printing technology.An in vitro hemodynamic simulation system incorporating pulsatile blood flow was established to simulate the hemodynamic environment of cerebral venous sinus stenosis.Using this system,both unilateral dominant drainage and bilateral balanced drainage were simulated.The degree of stenosis and the pressure upstream and downstream of the stenosis were measured.The pressure difference and pressure ratio were calculated to analyze the correlation between stenosis degree and the trans-stenotic pressure gradient.Results In the unilateral dominant drainage model,as the stenosis severity increased,the upstream pressure increased,whereas the downstream pressure remained relatively stable,leading to an increased pressure gradient between the two ends.The regression equation for stenosis degree(X)and pressure gradient(pressure difference ΔP)was:YΔP=1.962X-1.417(R=0.867,R2=0.753,P<0.001).In the bilateral balanced drainage model of cerebral venous sinuses,when the stenosis degree on one side of the model increased,the pressure gradient between the two ends changed slightly and eventually reached a stable state.The regression equation between X and ΔP was:YΔP=0.62X+1.047(R=0.98,R2=0.96,P<0.001).Conclusions Stenosis in cerebral venous sinuses with unilateral dominant drainage has a more significant impact on the pressure gradient,while unilateral stenosis in bilateral cerebral venous sinuses with balanced drainage has a smaller impact on the pressure gradient.This result suggests that for bilateral venous sinus stenosis,stent implantation can be prioritized in one side of the cerebral venous sinuses.

Objective:Time trade-off was employed to measure health state utilities associated with treatment attributes of hemophilia A patients to provide parameters for economic evaluations.Methods:Patients were recruited through patient organization and blood center of Shandong to measure health state utility values for 10 health states.Results:The utility values of preventive treatments for severe,moderate,and mild hemophilia A were 0.644,0.738,and 0.815,respectively.Compared with injections at 2-day intervals,the utility values were increased by 0.044 and 0.092 at 3-and 4-day intervals,respectively.Taking"severe hemophilia A patients injected every 2 days"as the base state,the disutility values for spontaneous bleeding and traumatic bleeding were 0.226 and 0.172.The disutility values for mild,moderate,and severe bleeding were 0.052,0.159,and 0.476,respectively,and the magnitude of the decrease gradually increased.Conclusion:Treatment attributes have an impact on patient preferences and more attention should be paid in pharmacoeconomic evaluations.

A bladder cancer patient underwent intravesical Bacillus Calmette-Guérin (BCG) instillation in Xiamen Branch, Zhongshan Hospital, Fudan University in April 2023. Following 8 instillations the patient presented with fever, cough and dyspnea, and was diagnosed as interstitial pneumonia (IP). Symptoms resolved after anti-tuberculosis and methylprednisolone treatment, with subsequent successful discharge. Using the keywords ′Bacillus Calmette-Guérin, ′ ′intravesical instillation, ′ ′pneumonia, ′ Wanfang Data, China National Knowledge Infrastructure(CNKI), Weipu(VIP), and PubMed databases were searched for relevant literature published between January 2014 and June 2024, and 20 cases of BCG instillation-induced pneumonia were retrieved, including 10 IP cases and 10 miliary pneumonia cases. Among 10 IP cases, 7 received corticosteroids combined with anti-tuberculosis therapy. Two cases unresponsive to combination therapy resulted in mortality, while others showed therapeutic efficacy. Miliary pneumonia demonstrated better prognosis, with 6 cases achieving complete remission through anti-tuberculosis monotherapy. The results indicate that severe BCG-related pneumonia generally necessitates combined anti-tuberculosis and corticosteroid therapy.