Given that ovarian stimulation is vital for assisted reproductive technology (ART) and results in elevated serum estrogen levels, exploring the impact of elevated estrogen exposure on oocytes and embryos is necessary. We investigated the effects of various ovarian stimulation treatments on oocyte and embryo morphology and gene expression using a mouse model and estrogen-treated mouse embryonic stem cells (mESCs). Female C57BL/6J mice were subjected to two types of conventional ovarian stimulation and ovarian hyperstimulation; mice treated with only normal saline served as controls. Hyperstimulation resulted in high serum estrogen levels, enlarged ovaries, an increased number of aberrant oocytes, and decreased embryo formation. The messenger RNA (mRNA)‍-sequencing of oocytes revealed the dysregulated expression of lysine-specific demethylase 6b (Kdm6b), which may be a key factor indicating hyperstimulation-induced aberrant oocytes and embryos. In vitro, Kdm6b expression was downregulated in mESCs treated with high-dose estrogen; treatment with an estrogen receptor antagonist could reverse this downregulated expression level. Furthermore, treatment with high-dose estrogen resulted in the upregulated expression of histone H3 lysine 27 trimethylation (H3K27me3) and phosphorylated H2A histone family member X (γ-H2AX). Notably, knockdown of Kdm6b and high estrogen levels hindered the formation of embryoid bodies, with a concomitant increase in the expression of H3K27me3 and γ-H2AX. Collectively, our findings revealed that hyperstimulation-induced high-dose estrogen could impair the demethylation of H3K27me3 by reducing Kdm6b expression. Accordingly, Kdm6b could be a promising marker for clinically predicting ART outcomes in patients with ovarian hyperstimulation syndrome.
Female ; Mice ; Demethylation/drug effects* ; Embryonic Stem Cells ; Estrogens/administration & dosage* ; Gene Expression/drug effects* ; Histones/metabolism* ; Jumonji Domain-Containing Histone Demethylases/metabolism* ; Mice, Inbred C57BL ; Oocytes ; Ovary/drug effects* ; Reproductive Techniques, Assisted ; Animals

Vertebral refracture following percutaneous vertebral augmentation (PVA) is commonly seen in elderly patients with osteoporotic thoracolumbar compression fractures (OTLCF). It can lead to recurrent pain, loss of vertebral height, progression of kyphosis, and even neurological dysfunction, significantly impairing patients′ quality of life. Current diagnosis and treatment face multiple challenges, including high misdiagnosis rate, difficulty in choosing between surgical and non-surgical treatment options, lack of standardized surgical protocols, interference from intralesional bone cement during procedures, inadequate stability of internal fixation in osteoporotic bone, and suboptimal compliance of anti-osteoporotic therapy. Establishing a standardized diagnostic and therapeutic framework is urgently needed. To standardize the management process and improve outcomes for vertebral refractures after PVA in elderly OTLCF patients, Spinal Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field to develop Guideline for the diagnosis and treatment of vertebral refracture after percutaneous vertebral augmentation in elderly patients with osteoporotic thoracolumbar compression fractures ( version 2025), based on current literature and clinical experience, and adhering to principles of scientific rigor and clinical applicability. A total of 11 recommendations were proposed, encompassing diagnosis, treatment, and rehabilitation of vertebral refracture after PVA in elderly patients with OTLCF, aiming to provide a foundation for a standardized management.

Objective:To explore the influencing factors of dietary habits on the progression from prediabetes to type 2 diabetes mellitus(T2DM)in elderly individuals undergoing health check-ups.Methods:In the cross-sectional study, we enrolled individuals aged 60-70 years with fasting plasma glucose (FPG)≥6.0 mmol/L who underwent health examinations at the Health Management Medical Center of Wenjiang District People's Hospital in Chengdu from 2019 to 2022.Demographic characteristics, dietary habit questionnaires, and FPG values were collected.Unconditional binary logistic regression analysis was used to identify factors influencing the natural progression from prediabetes to T2DM.A nomogram prediction model was established based on logistic regression results, and its predictive performance was evaluated by calculating the C-statistics and drawing a calibration curve.Results:A total of 13 681 elderly participants with FPG ≥6.0 mmol/L were included, comprising 4 306(31.5%)prediabetes cases(FPG 6.0-7.0 mmol/L), aged(63.54±16.49)years and 9 375(68.5%)T2DM cases(FPG>7.0 mmol/L), aged(63.09±16.21)years.Unconditional binary logistic regression analysis showed that frequent breakfast( OR=0.777, 95% CI: 0.696-0.868, P<0.001), dietary preference for light diet( OR=0.781, 95% CI: 0.710-0.858, P<0.001), salty taste( OR=0.571, 95% CI: 0.504-0.648, P<0.001), raw food( OR=0.327, 95% CI: 0.224-0.478, P<0.001)and spicy taste( OR=0.124, 95% CI: 0.112-0.137, P<0.001)were the protective factors for the conversion of prediabetes to the T2DM stage in the elderly physical examination population.While fast eating rate( OR=4.327, 95% CI: 3.978-4.772, P<0.001), dietary preference for sweets( OR=5.168, 95% CI: 4.703-5.678, P<0.001), and high-fat diet( OR=1.401, 95% CI: 1.275-1.539, P<0.001)were risk factors for conversion of prediabetes to T2DM stage.C-statistic of the Nomogram prediction model was 0.781; the goodness-of-fit test of the calibration curve was χ2=11.258, P=0.188, and the model predicted well. Conclusions:Regular breakfast, light diet, and dietary preferences for salty, raw, and spicy foods were protective factors for the transition from prediabetes to T2DM stage, whereas rapid eating rate, preference for sweets, and high-fat diets were risk factors for the transition from prediabetes to T2DM stage in the medical examination population.The constructed risk prediction model helped to find out the magnitude of the risk of T2DM in an individual, which increases the evidence for the transition from prediabetes to T2DM stage prevention evidence.

Objective:To explore the long-term survival outcomes of patients with anaplastic thyroid cancer (ATC) and analyze key factors influencing the prognosis.Methods:A retrospective analysis was conducted on the clinical and follow-up data of 77 ATC patients treated at the Sun Yat-sen University Cancer Center from March 2000 to July 2022, with tumor-specific survival as the primary endpoint. The Kaplan-Meier method was used to plot the survival curves, and univariate and multivariate Cox regression analyses were performed to identify the prognostic factors.Results:Among the 77 patients, 64 underwent surgical treatment, with 33 receiving surgery alone, 8 undergoing surgery combined with chemotherapy, 13 undergoing surgery with radiotherapy, 1 undergoing surgery with chemotherapy and radiotherapy, 2 receiving surgery combined with chemotherapy and targeted therapy, 3 receiving surgery with targeted therapy, and 4 receiving surgery with immunotherapy and targeted therapy. Among the 13 patients who did not undergo surgery, 2 received chemotherapy alone, 3 received targeted therapy alone, 1 received immunotherapy alone, 1 received chemoradiotherapy, 5 received chemotherapy combined with immunotherapy, and 1 received immunotherapy combined with targeted therapy. The median follow-up time was 8.4 months, with 58 patients (75.3%) died, and the median survival time was 6.63 months. Univariate Cox regression analysis showed that C-reactive protein, monocyte count, lymphocyte count, abnormal albumin levels, the maximum diameter of the primary tumor, BMI, and whether immunotherapy was administered were significantly associated with survival in ATC patients (all P＜0.05). Multivariate Cox regression analysis indicated that immunotherapy was an independent factor for survival in ATC patients ( HR=0.18, 95% CI: 0.05-0.62, P=0.007). Among the 40 patients admitted after 2015, the 11 patients who received immunotherapy had a median survival time of 17.2 months, which was superior to the 29 patients who did not receive this treatment (median survival time 6.2 months, P=0.03). Conclusions:ATC patients receiving immunotherapy had a better prognosis and longer survival. Additionally, elevated C-reactive protein, abnormal albumin, monocyte count, lymphocyte count, and BMI might be associated with poorer prognosis in ATC. Tailoring treatment based on the individual characteristics of ATC patients may be beneficial for their long-term survival.

Diabetes is a very complex endocrine disease whose common feature is the increase in blood glucose concentration. Persistent hyperglycemia can lead to blindness, kidney and heart disease, neurodegeneration, and many other serious complications that have a significant impact on human health and quality of life. The number of people with diabetes is increasing yearly. The global diabetes prevalence in 20-79 year olds in 2021 was estimated to be 10.5% (536.6 million), and it will rise to 12.2% (783.2 million) in 2045. The main modes of intervention for diabetes include medication, dietary management, and exercise conditioning. Medication is the mainstay of treatment. Marketed diabetes drugs such as metformin and insulin, as well as GLP-1 receptor agonists, are effective in controlling blood sugar levels to some extent, but the preventive and therapeutic effects are still unsatisfactory. Peptide drugs have many advantages such as low toxicity, high target specificity, and good biocompatibility, which opens up new avenues for the treatment of diabetes and other diseases. Currently, insulin and its analogs are by far the main life-saving drugs in clinical diabetes treatment, enabling effective control of blood glucose levels, but the risk of hypoglycemia is relatively high and treatment is limited by the route of delivery. New and oral anti-diabetic drugs have always been a market demand and research hotspot. Inhibitor cystine knot (ICK) peptides are a class of multifunctional cyclic peptides. In structure, they contain three conserved disulfide bonds (C3-C20, C7-C22, and C15-C32) form a compact “knot” structure, which can resist degradation of digestive protease. Recent studies have shown that ICK peptides derived from legume, such as PA1b, Aglycin, Vglycin, Iglycin, Dglycin, and aM₁, exhibit excellent regulatory activities on glucose and lipid metabolism at the cellular and animal levels. Mechanistically, ICK peptides promote glucose utilization by muscle and liver through activation of IR/AKT signaling pathway, which also improves insulin resistance. They can repair the damaged pancrease through activation of PI3K/AKT/Erk signaling pathway, thus lowering blood glucose. The biostability and hypoglycemic efficacy of the ICK peptides meet the requirements for commercialization of oral drugs, and in theory, they can be developed into natural oral anti-diabetes peptide drugs. In this review, the structural properties, activity and mechanism of ICK pattern peptides in regulating glucose and lipid metabolism were summaried, which provided a reference for the development of new oral peptides for diabetes.

Objective:To investigate the clinical features and multi-slice spiral computed tomography(CT)imaging features of acute appendicitis in soldiers who have been living in plateau for a long time.Methods:The clinical features and imaging data of 56 cases of acute appendicitis in soldiers who have been living in plateau for a long time confirmed by surgery from February 2022 to August 2024 were retrospectively analyzed.Results:In 56 cases with acute appendicitis in soldiers who have been living in plateau for a long time,the appendectomy position results showed:anterior ileum 4 cases(7.14％),lower ileum 10 cases(17.86％),posterior cecum 16 cases(28.57％),lower cecum 9 cases(16.07％),lateral cecum 2 cases(3.58％),posterior ileum 6 cases(10.71％),high(subhepatic)9 cases(16.07％),and left lower abdominal 0 cases,retroperitoneal appendicitis 0 cases,which was suggested that the anatomical position variation of appendicitis in soldiers with acute appendicitis who have been living at high altitude for a long time was relatively large.The direct manifestations of multi-slice spiral CT showed:appendectomy enlarged diameter＞6 mm in 49 cases(87.50％),appendicular wall thickening＞2 mm in 42 cases(75.00％),ppendiceal dilation lumen and effusion in 29 cases(51.79％),appendix indistinctness in 3 cases(5.36％),lppendix fecalith:27 cases(48.21％),gas in the appendix in 16 cases(28.57％).Indirect findings of multi-slice spiral CT showed that,periappendiceal exudation with shadow in 32 cases(57.14％),appendiceal cellulitis with peripheral abscess in 9 cases(16.07％),peritonitis and ascites in 13 cases(23.21％),ileocecal intestinal wall thickening in 22 cases(39.29％),mesenteric lymph node enlargement in 16 cases(28.57％),reflexive intestinal stasis in ileocecal region was observed in 19 cases(33.93％).Conclusion:In the officers and soldiers with acute appendicitis who lived at high altitude for a long time,multi-slice spiral CT showed the direct manifestations of appendiceal thickening,tube wall thickening,lumen dilatation,fluid accumulation,etc.,and the indirect manifestations were periappendiceal exudation with shadow,appendiceal cellulitis with peripheral abscess,ileocecal intestinal wall thickening,reflexes of small intestine and mesenteric lymph node enlargement.Multi-slice spiral CT has the advantages of clear and intuitive,high safety,high resolution and simple operation in the diagnosis of acute appendicitis.

Objective To analyze the CT manifestations of high altitude pulmonary edema(HAPE)to provide radiological evidence for its early and accurate diagnosis.Methods Totally 200 HAPE patients clinically confirmed at some hospital from April 2021 to April 2024 were enrolled into a study group,and 56 individuals undergoing health examinations at the hospital's physical examination center between January and June 2023 were included into a control group.Examinations were carried out with a United Imaging uCT528 40-slice spiral CT scanner.The patients in the study group were observed in terms of HAPE staging,the extent of pulmonary involvement,CT manifestations of different stages including location,distribution,density and morphology of pulmonary lesion.The diameters of the main pulmonary arteries and ascending aortas of the subjects in the two groups were measured,and the ratios of the two diameters were calculated.SPSS 25.0 software was used for statistical analysis.Results In the study group,there were 26 cases(13.0%)at early stage,105 ones at progression stage(52.5%),32 ones at critical outbreak stage(16.0%)and 37 ones at resolution and absorption stage(18.5%),and there were 35.5%with unilateral lung involvement and 64.5%with bilateral involvement.At early stage,HAPE chest CT manifestations included increased and thickened bilateral bronchovascular bundles,widened main pulmonary artery lumen and faint ground-glass opacity in lungs;at progression stage,HAPE chest CT manifestations revealed multiple cloud-like or patchy areas of increased density within lungs;at critical outbreak stage,CT scanning indicated diffuse patchy opacities and consolidation in lungs,white lung-like changes could be found in some severe cases,and bronchial air signs were shown within affected segments in some ones with severer signs in the right lung than in the left lung;at resolution and absorption stage the CT manifestations were similar to those at early stage,with lesions completely resolving after treatment.The study group had the diameters of the main pulmonary arteries greater while the diameters of the ascending aortas less than those of the control group,and the ratios of the diameters of the two diameters in the study group were higher than those in the control group,with the differences being statistically significant(all P<0.05).Conclusion Chest CT is an important examination method for the early diagnosis of HAPE and clarification of its clinical staging,which directly reflects the pulmonary pathological changes in HAPE patients and helps doctors fully understand the disease progression.

Objective:To explore the long-term survival outcomes of patients with anaplastic thyroid cancer (ATC) and analyze key factors influencing the prognosis.Methods:A retrospective analysis was conducted on the clinical and follow-up data of 77 ATC patients treated at the Sun Yat-sen University Cancer Center from March 2000 to July 2022, with tumor-specific survival as the primary endpoint. The Kaplan-Meier method was used to plot the survival curves, and univariate and multivariate Cox regression analyses were performed to identify the prognostic factors.Results:Among the 77 patients, 64 underwent surgical treatment, with 33 receiving surgery alone, 8 undergoing surgery combined with chemotherapy, 13 undergoing surgery with radiotherapy, 1 undergoing surgery with chemotherapy and radiotherapy, 2 receiving surgery combined with chemotherapy and targeted therapy, 3 receiving surgery with targeted therapy, and 4 receiving surgery with immunotherapy and targeted therapy. Among the 13 patients who did not undergo surgery, 2 received chemotherapy alone, 3 received targeted therapy alone, 1 received immunotherapy alone, 1 received chemoradiotherapy, 5 received chemotherapy combined with immunotherapy, and 1 received immunotherapy combined with targeted therapy. The median follow-up time was 8.4 months, with 58 patients (75.3%) died, and the median survival time was 6.63 months. Univariate Cox regression analysis showed that C-reactive protein, monocyte count, lymphocyte count, abnormal albumin levels, the maximum diameter of the primary tumor, BMI, and whether immunotherapy was administered were significantly associated with survival in ATC patients (all P＜0.05). Multivariate Cox regression analysis indicated that immunotherapy was an independent factor for survival in ATC patients ( HR=0.18, 95% CI: 0.05-0.62, P=0.007). Among the 40 patients admitted after 2015, the 11 patients who received immunotherapy had a median survival time of 17.2 months, which was superior to the 29 patients who did not receive this treatment (median survival time 6.2 months, P=0.03). Conclusions:ATC patients receiving immunotherapy had a better prognosis and longer survival. Additionally, elevated C-reactive protein, abnormal albumin, monocyte count, lymphocyte count, and BMI might be associated with poorer prognosis in ATC. Tailoring treatment based on the individual characteristics of ATC patients may be beneficial for their long-term survival.

Objective To analyze the CT manifestations of high altitude pulmonary edema(HAPE)to provide radiological evidence for its early and accurate diagnosis.Methods Totally 200 HAPE patients clinically confirmed at some hospital from April 2021 to April 2024 were enrolled into a study group,and 56 individuals undergoing health examinations at the hospital's physical examination center between January and June 2023 were included into a control group.Examinations were carried out with a United Imaging uCT528 40-slice spiral CT scanner.The patients in the study group were observed in terms of HAPE staging,the extent of pulmonary involvement,CT manifestations of different stages including location,distribution,density and morphology of pulmonary lesion.The diameters of the main pulmonary arteries and ascending aortas of the subjects in the two groups were measured,and the ratios of the two diameters were calculated.SPSS 25.0 software was used for statistical analysis.Results In the study group,there were 26 cases(13.0%)at early stage,105 ones at progression stage(52.5%),32 ones at critical outbreak stage(16.0%)and 37 ones at resolution and absorption stage(18.5%),and there were 35.5%with unilateral lung involvement and 64.5%with bilateral involvement.At early stage,HAPE chest CT manifestations included increased and thickened bilateral bronchovascular bundles,widened main pulmonary artery lumen and faint ground-glass opacity in lungs;at progression stage,HAPE chest CT manifestations revealed multiple cloud-like or patchy areas of increased density within lungs;at critical outbreak stage,CT scanning indicated diffuse patchy opacities and consolidation in lungs,white lung-like changes could be found in some severe cases,and bronchial air signs were shown within affected segments in some ones with severer signs in the right lung than in the left lung;at resolution and absorption stage the CT manifestations were similar to those at early stage,with lesions completely resolving after treatment.The study group had the diameters of the main pulmonary arteries greater while the diameters of the ascending aortas less than those of the control group,and the ratios of the diameters of the two diameters in the study group were higher than those in the control group,with the differences being statistically significant(all P<0.05).Conclusion Chest CT is an important examination method for the early diagnosis of HAPE and clarification of its clinical staging,which directly reflects the pulmonary pathological changes in HAPE patients and helps doctors fully understand the disease progression.

Objective:To investigate the clinical features and multi-slice spiral computed tomography(CT)imaging features of acute appendicitis in soldiers who have been living in plateau for a long time.Methods:The clinical features and imaging data of 56 cases of acute appendicitis in soldiers who have been living in plateau for a long time confirmed by surgery from February 2022 to August 2024 were retrospectively analyzed.Results:In 56 cases with acute appendicitis in soldiers who have been living in plateau for a long time,the appendectomy position results showed:anterior ileum 4 cases(7.14％),lower ileum 10 cases(17.86％),posterior cecum 16 cases(28.57％),lower cecum 9 cases(16.07％),lateral cecum 2 cases(3.58％),posterior ileum 6 cases(10.71％),high(subhepatic)9 cases(16.07％),and left lower abdominal 0 cases,retroperitoneal appendicitis 0 cases,which was suggested that the anatomical position variation of appendicitis in soldiers with acute appendicitis who have been living at high altitude for a long time was relatively large.The direct manifestations of multi-slice spiral CT showed:appendectomy enlarged diameter＞6 mm in 49 cases(87.50％),appendicular wall thickening＞2 mm in 42 cases(75.00％),ppendiceal dilation lumen and effusion in 29 cases(51.79％),appendix indistinctness in 3 cases(5.36％),lppendix fecalith:27 cases(48.21％),gas in the appendix in 16 cases(28.57％).Indirect findings of multi-slice spiral CT showed that,periappendiceal exudation with shadow in 32 cases(57.14％),appendiceal cellulitis with peripheral abscess in 9 cases(16.07％),peritonitis and ascites in 13 cases(23.21％),ileocecal intestinal wall thickening in 22 cases(39.29％),mesenteric lymph node enlargement in 16 cases(28.57％),reflexive intestinal stasis in ileocecal region was observed in 19 cases(33.93％).Conclusion:In the officers and soldiers with acute appendicitis who lived at high altitude for a long time,multi-slice spiral CT showed the direct manifestations of appendiceal thickening,tube wall thickening,lumen dilatation,fluid accumulation,etc.,and the indirect manifestations were periappendiceal exudation with shadow,appendiceal cellulitis with peripheral abscess,ileocecal intestinal wall thickening,reflexes of small intestine and mesenteric lymph node enlargement.Multi-slice spiral CT has the advantages of clear and intuitive,high safety,high resolution and simple operation in the diagnosis of acute appendicitis.