Objective: In ovarian cancer (OvCa), tumor cell high glucocorticoid receptor (GR) has been associated with poor patient prognosis. In vitro, GR activation inhibits chemotherapyinduced OvCa cell death in association with transcriptional upregulation of genes encoding anti-apoptotic proteins. A recent randomized phase II study demonstrated improvement in progression-free survival (PFS) for heavily pre-treated OvCa patients randomized to receive therapy with a selective GR modulator (SGRM) plus chemotherapy compared to chemotherapy alone. We hypothesized that SGRM therapy would improve carboplatin response in OvCa patient-derived xenograft (PDX). Methods: Six high-grade serous (HGS) OvCa PDX models expressing GR mRNA (NR3C1) and protein were treated with chemotherapy +/− SGRM. Tumor size was measured longitudinally by peritoneal transcutaneous ultrasonography. Results: One of the 6 GR-positive PDX models showed a significant improvement in PFS with the addition of a SGRM. Interestingly, the single model with an improved PFS was least carboplatin sensitive. Possible explanations for the modest SGRM activity include the high carboplatin sensitivity of 5 of the PDX tumors and the potential that SGRMs activate the tumor invasive immune cells in patients (absent from immunocompromised mice). The level of tumor GR protein expression alone appears insufficient for predicting SGRM response. Conclusion The significant improvement in PFS shown in 1 of the 6 models after treatment with a SGRM plus chemotherapy underscores the need to determine predictive biomarkers for SGRM therapy in HGS OvCa and to better identify patient subgroups that are most likely to benefit from adding GR modulation to chemotherapy.

Objective:To analyze the research hotspots and trends of phytoestrogens for menopausal syndrome based on CiteSpace.Methods:The research articles were retrieved with the search terms of"phytoestrogens""perimenopause""phytoestrogens"and"perimenopause". A total of 405 articles in PubMed database from 1996 to 2023 and 227 articles in CNKI full-text database from 2000 to 2023 were retrieved. The software CiteSpace 6.2.R6 was used to visualize the articles to explore the research hotspots and trends of phytoestrogens used in menopausal syndrome.Results:A total of 632 literatures were included, and the country with a large number of publications and a high degree of central intermediation was the United States (70 publications, 0.05 intermediation centrality). Although Chinese scholars had high publication output (12 articles), they lacked external exchanges and cooperation (0 intermediary centrality). Domestic and foreign research focused on the common source of phytoestrogens, hot flushes, sweating and other common menopausal symptoms, cardiovascular diseases, breast diseases. The research direction had gradually shifted from basic research to clinical research, and more and more natural phytoestrogens types had attracted attention. In contrast, domestic research focused more on bone health, focusing on the long-term benefits of menopausal hormone therapy for patients with low bone mass and osteoporosis.Conclusion:The study of phytoestrogens for menopausal syndrome is based on evidence-based medicine and is developing towards individualized and benefit-risk ratio maximization, but there is still a lack of high-quality randomized controlled studies.

Objective To conduct a unique and pioneering molecular epidemiological investigation of a case of Eurasian avian-like H1N1 swine influenza identified in Yunnan Province in 2022(the fourth such case in the province)and to understand its genetic characteristics so as to reveal its potential impact on human health.Methods Real-time fluorescent quantitative PCR detection technology was used for the nucleic acid testing of the case's pharyngeal swab samples,close contacts,and environmental samples from the living area.Positive samples were subjected to virus isolation using MDCK cells.Cell cultures were authenticated using erythrocyte agglutination assay with guinea pig blood and real-time fluorescence quantitative RT-PCR.Whole genome sequencing was performed using the Illumina MiseqNext-generation sequencing platform,and a phylogenetic tree was constructed using MEGA 7.0 software to analyze the genetic molecular characteristics.Results The first G5 genotype Eurasian avian-like H1N1 swine influenza virus in Yunnan Province was successfully isolated,and the whole genome sequence of the virus was obtained.This virus possessed the molecular characteristics associated with increased adaptability,virulence,or transmissibility in mammals and had a nucleotide consistency of 99.2％～99.7％with a porcine strain isolated in Jiangsu province.These findings underscored the potential threat this virus poses to human health.Conclusion The study underscores the importance of further monitoring swine influenza in preventing new influenza virus subtypes that can infect humans.

BACKGROUND:Spinal osteosarcoma is a rare and highly aggressive malignant tumor.Most existing studies are based on small sample sizes and have inconsistent results,making it difficult to provide reliable clinical guidance.Especially in China,due to the low incidence of spinal osteosarcoma and limited related research,clinicians lack effective prognostic tools during treatment.OBJECTIVE:To construct and validate a nomogram model for predicting the survival of spinal osteosarcoma patients based on the Surveillance,Epidemiology,and End Results(SEER)database,providing scientific evidence for clinical decision-making,particularly for optimizing treatment plans for Chinese patients.METHODS:This study conducted a retrospective analysis of patient data diagnosed with spinal osteosarcoma from the SEER database between 2000 and 2021.First,independent prognostic factors associated with specific mortality from spinal osteosarcoma were identified through univariate and multivariate Cox proportional hazards models.Subsequently,these independent prognostic factors were used to construct a nomogram model for predicting survival rates of spinal osteosarcoma patients using the"rms"package in RStudio.The model's discrimination was assessed using the C-index.Predictive ability was validated through receiver operating characteristic curves and area under the curve values.Calibration was evaluated by calibration plots,and clinical value was measured using decision curve analysis.Additionally,Kaplan-Meier survival analysis was performed to assess the rationality of the nomogram groupings.RESULTS AND CONCLUSION:(1)The final model included six variables:chemotherapy,tumor size,histological type,grade,race,and surgical intervention.(2)The C-indices of the model in the training and validation sets were 0.685 and 0.673,respectively,indicating good discrimination.(3)Calibration curves showed high consistency between predicted survival probabilities and actual survival probabilities.(4)Decision curve analysis indicated that the model provided significant net benefits across a wide range of mortality risks.(5)Kaplan-Meier survival analysis revealed significant differences in prognosis between high-risk and low-risk groups.(6)The constructed nomogram model accurately predicts the 1-year,2-year,and 3-year survival rates of spinal osteosarcoma patients,demonstrating high clinical applicability.This model not only provides an effective survival prediction tool for American patients but also offers important insights for optimizing treatment plans for spinal osteosarcoma patients in China.Future research should further validate the model's applicability in different populations and explore the impact of novel treatment methods on the prognosis of spinal osteosarcoma,aiming to improve the survival rates and quality of life of patients in China.

OBJECTIVE: To carry out pathological and genetic analyses on a fetus with intrauterine growth restriction and death during second trimester after induced abortion. METHODS: A fetus undergone induced abortion due to intrauterine growth restriction and death during second trimester at the the Seventh Affiliated Hospital of Sun Yat-Sen University in 2024 was selected as the study subject. Clinical data of the pregnancy were collected. DNA was extracted from tissues from the aborted fetus and peripheral blood samples from its parents. Chromosomal microarray analysis and whole exome sequencing were carried out. Candidate variants were verified by Sanger sequencing. Following abortion, routine autopsy and pathological analysis were conducted. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: KY-2025-334-01). RESULTS: The aborted fetus was a male and harbored compound heterozygous nonsense variants of the TH gene (c.457C>T/p.Arg153* and c.694C>T/p.Gln232*), for which both parents were heterozygous carriers. Autopsy and pathological analysis revealed that the fetus had pathological features including loose arrangement of myocardial fibers and congestion in the liver. CONCLUSION Biallelic null variants of the TH gene may cause heart failure by affecting the development of cardiovascular system, which in turn may lead to intrauterine death. This study has provided new clues for the molecular diagnosis of stillbirth and recurrent pregnancy loss.
Humans ; Female ; Pregnancy ; Male ; Heterozygote ; Codon, Nonsense/genetics* ; Fetal Growth Retardation/pathology* ; Adult ; Stillbirth/genetics*

Objective To compare functional differences of CD8+T cells in lung tissues between young and aged C57BL/6J mice during the contraction phase and memory immune response phase after infection with influenza A(H1N1)virus.Methods Lung tissues from young(3-month-old)and aged(24-month-old)C57BL/6J female mice without influenza virus infection were collected to prepare single-cell suspensions,which were stimulated with phorbol 12-myristate 13-acetate(PMA)/ionomycin or cluster of differentiation(CD)3/CD28 antibodies(T-cell antigen receptor/co-stimulatory signals)respectively(non-specific antigens stimulation).Flow cytometry intracellular cytokine staining(ICS)was performed on lung CD8+T cells to detect their secretion capacity of tumor necrosis factor-α(TNF-α)and interferon-γ(IFN-γ).Young and aged C57BL/6J mice were infected intranasally with 490 PFU PR8 influenza virus,and reinfected with homologous influenza virus 28 days later.Lung tissues were isolated on day 28(the contraction phase)and day 32(the memory immune response phase)after primary infection.Influenza virus-specific MHC-Ⅰ tetramer staining was used to detect the proportion of virus-specific CD8+T cells in lung tissue CD8+T cells,and ICS was used to analyze TNF-α,IFN-γ,and granzyme B expression in CD8+CD44high T cell subset.Results After non-specific antigen stimulation,TNF-α and IFN-γ secretion capacity in lung tissue CD8+T cells of aged group mice was significantly higher than that of young group(P＜0.05).After virus-specific antigen stimulation,there were no statistically significant differences in the proportion of virus-specific CD8+T cells and the expression levels of TNF-α,IFN-γ,and granzyme B between the two groups of mice during the contraction phase(P＞0.05),while during the memory immune response phase,the proportion of virus-specific CD8+T cells and the expression levels of TNF-α,IFN-γ,and granzyme B in the aged group mice were significantly lower than those in the young group(P＜0.05).Conclusion CD8+T cells in aged mice maintain normal immune-related factor expression function under non-specific antigen stimulation,but show impaired immune-related factor expression function during antigen-specific memory immune response phase,suggesting that aging leads to defects in the formation or maintenance of CD8+T cell immune memory.

Objective:To investigate expressions of LDHA,CD56 and NKG2D in liver cancer tissues,and to further explore effects and correlations of Bufalin(BF)on LDHA and NK cells in hepatocellular carcinoma.Methods:Immunohistochemistry(IHC)was used to detect differential expressions of LDHA and NK cell specific molecular markers CD56 and NKG2D in 91 postoperative paraffin pathological specimens of hepatocellular carcinoma,as well as correlation between these markers in cancer and adjacent tissues.A Hepa1-6 subcutaneous tumor bearing hepatocellular carcinoma model was constructed by C57BL/6 mice and randomly divide into Control(Ctrl)group,BF+Pyruvic acid(BF+PA)group,Oxamate(OX)group,BF group,with 5 mice per group.Growth rate and volume of subcutaneous tumors were observed;IHC was used to detect expressions of LDHA and mouse NK cell specific molecular markers NK1.1 and NKG2D in tumors of each group of mice;ELISA was used to detect concentrations of perforin,TNF-α and IFN-γ in serum of mice in each group.Results:LDHA was highly expressed in human liver cancer tissues(P<0.001),while CD56 and NKG2D were highly expressed in adjacent tissues(P<0.001);LDHA expression was negatively correlated with CD56(r=-0.529 8,P<0.000 1)and NKG2D(r=-0.320 1,P<0.001);CD56 expression was positively correlated with NKG2D(r=0.612 2,P<0.000 1).Subcutaneous tumor experiment of mouse hepatocellular carcinoma showed that compared with Ctrl group and BF+PA group,subcutaneous tumor growth rate of OX group and BF group slowed down and showed a trend of tumor reduction;IHC detection showed that compared with Control group,LDHA expression in BF group was significantly downregulated(P<0.01),NK1.1 and NKG2D expressions were significantly increased(P<0.000 1);ELISA showed that compared with Ctrl group,LDHA in serum of BF group increased perforin,TNF-α,IFN-γ expressions(P<0.000 1),and enhanced NK cell killing ability.Conclusion:BF can inhibit LDHA expression in hepatocellular carcinoma cells and increase infiltration rate of NK cells in hepatocellular carcinoma tissues,which may enhance killing ability of NK cells in tumor microenvironment and inhibit growth of hepatocellular carcinoma.

This paper summarizes Professor Gao Jiansheng's clinical experience in treating herpes simplex keratitis （HSK） based on the theory of hidden pathogens. It is believed that the core pathogenesis of HSK involves deficiency of vital qi and the internal presence of pathogenic factors. In the early stage， the pathogenesis is characterized by lung and spleen qi deficiency and invasion of external pathogens. In the middle stage， pathogenesis worsens due to latent pathogens damaging the vital qi and spleen deficiency with dampness. In the late stage， kidney yang deficiency and lingering pathogenic toxins are the root cause of recurrent attacks. In clinical practice， it is recommended to strengthen and protect the vital qi. In the early stage， the Modified Yupingfeng Powder （玉屏风散） is used. In the middle stage， the Modified Linggui Zhugan Decoction （苓桂术甘汤） is used. In the late stage， a self-formulated Modified Bushen Tuodu Fomulation （补肾托毒方） is applied. Additionally， herbs of tonifying qi and strengthening the exterior are used throughout the treatment to reduce recurrence.

Benign essential blepharospasm(BEB)is a neurological disorder characterized by involuntary contractions of periocular muscles, which can lead to functional blindness and significantly impair patients' quality of life. This article systematically reviews the epidemiology, clinical manifestations, pathogenesis, and therapeutic advances in BEB. Epidemiological data indicate that the global prevalence of BEB is approximately 1 in 200000, with a predilection for individuals over 50 years of age and a significantly higher incidence in female than in male. The exact pathogenesis of BEB remains incompletely understood, though current evidence suggests close associations with neurotransmitter dysfunction, reduced cortical inhibition, and genetic susceptibility. Therapeutic strategies primarily focus on symptomatic management. Botulinum toxin type A(BTX-A)injection remains the first-line treatment but requires repeated administrations due to transient efficacy. Other treatments, including oral drugs, surgery, and repetitive transcranial magnetic stimulation, also have major limitations. By synthesizing recent research progress from domestic and international studies, this review aims to provide novel insights for the clinical management of BEB, ultimately improving patient outcomes.