Hypercholesterolemia is a significant risk factor for the development of atherosclerosis. 2',3',5'-Tri-O-acetyl-N ⁶-(3-hydroxyphenyl) adenosine (IMM-H007), a novel AMPK agonist, has shown protective effects in metabolic diseases. However, its impact on cholesterol and triglyceride metabolism in hypercholesterolemia remains unclear. In this study, we aimed to elucidate the effects and specific mechanisms by which IMM-H007 regulates cholesterol and triglyceride metabolism. To achieve this goal, we used Apoe ^-/- and Ldlr ^-/- mice to establish a hypercholesterolemia/atherosclerosis model. Additionally, hepatocyte-specific Ampka1/2 knockout mice were subjected to a 5-week high-cholesterol diet to establish hypercholesterolemia, while atherosclerosis was induced via AAV-PCSK9 injection combined with a 16-week high-cholesterol diet. Our results demonstrated that IMM-H007 improved cholesterol and triglyceride metabolism in mice with hypercholesterolemia. Mechanistically, IMM-H007 modulated the AMPKα1/2-LDLR signaling pathway, increasing cholesterol uptake in the liver. Furthermore, IMM-H007 activated the AMPKα1-FXR pathway, promoting the conversion of hepatic cholesterol to bile acids. Additionally, IMM-H007 prevented hepatic steatosis by activating the AMPKα1/2-ATGL pathway. In conclusion, our study suggests that IMM-H007 is a promising therapeutic agent for improving hypercholesterolemia and atherosclerosis through the activation of AMPKα.

OBJECTIVES: To analyze the trends of disease burden of lip and oral cancers in East Asia from 1990 to 2021 and its future projections. METHODS: We used the Global Burden of Disease 2021 database to conduct a comprehensive analysis of disease burden data from China (including Taiwan Province of China), Japan, Republic of Korea, Democratic People's Republic of Korea and Mongolia. The data were stratified by age, gender and major risk factors, and a Bayesian age-period-cohort model was employed to predict the future trends. RESULTS: From 1990 to 2021, the burden of lip and oral cancers in East Asian countries exhibited a steady increase. Taiwan Province of China experienced the most significant increases in incidence, prevalence, mortality, and disability-adjusted life years (DALYs), while Mongolia saw a decline in both mortality and DALYs. In 2021, Taiwan Province of China reported the highest rates of lip and oral cancer incidence (27.50 per 100 000), prevalence (137.92 per 100 000), mortality (9.59 per 100 000), and DALYs (292.07 person-years per 100 000), particularly among male and elderly populations. Tobacco use and alcohol consumption significantly exacerbated the disease burden in Taiwan Province of China and Japan. Future projections indicate that the incidence and prevalence of lip and oral cancer in China (excluding Taiwan Province of China) will continue to rise, while their mortality rates are expected to decline in most regions, except for Taiwan Province of China and Democratic People's Republic of Korea. CONCLUSIONS By the year 2035, the disease burden of lip and oral cancers in East Asia is expected to continue to increase, especially in Taiwan Province of China. To address this challenge, it is essential to implement effective measures to control major risk factors, promote early screening, and ensure equitable distribution of healthcare resources.
Humans ; Mouth Neoplasms/epidemiology* ; Incidence ; Lip Neoplasms/epidemiology* ; Asia, Eastern/epidemiology* ; Male ; Disability-Adjusted Life Years ; Prevalence ; Female ; Forecasting ; Risk Factors ; Cost of Illness ; Middle Aged ; Global Burden of Disease ; Aged ; Bayes Theorem

Objective To investigate the effect and mechanism of melatonin in alleviating hypoxia-induced apoptosis in ovarian gra-nulosa cells.Methods Rat ovarian granulosa cells were isolated and divided into normoxic,hypoxic,and melatonin groups.Hypoxia-induced injury models were established in the hypoxic and melatonin groups,and granulosa cells in the melatonin group were treated with melatonin.A total of 24 rats were randomized into the control,model,and intervention groups(n=8 per group).Rat models of declining ovarian function induced by long-term hypoxia were established in the model and intervention groups.The rats in the intervention group were intraperitoneally injected with melatonin.Cell proliferation was measured using a CCK-8 assay,and lactate secretion and HIF-1αprotein with a specific kit,respectively.The levels of estradiol and progesterone in the cell supernatant and rat serum were detected using ELISA.Granulosa cell apoptosis was detected by flow cytometry,ovarian morphology by HE staining,and Bax and caspase-3 expression by Western blotting.Results Compared with the normoxic group,the hypoxic group exhibited decreased granulosa cell proliferation,increased apoptosis,elevated lactate and HIF-1α levels,and reduced estradiol and progesterone levels(P＜0.05).Compared with hypoxic group,these changes were significantly reversed in the molatonin group(P＜0.05).Compared with the control group,the model group showed increased lactate,HIF-1α,Bax,and caspase-3 levels,decreased estradiol and progesterone levels,and reduced follicles.Compared with the model group,all the indicators were ameliorated in the intervention group(P＜0.05).Conclusion Melatonin alleviated hypoxia-induced granulosa cell apoptosis and promoted the recovery of ovarian function.

Parkinson's disease (PD), a major neurodegenerative disease faced by an aging society worldwide, has not yet been fully elucidated in terms of its pathogenesis. Currently, clinical treatment mainly relies on symptom management and can only be relieved by medication. In recent years, many studies have shown that polysaccharides have potential in treatment of neurodegenerative diseases. Polysaccharides play a role in PD in ways such as anti-oxidative stress response, improvement of mitochondrial dysfunction, inhibition of neuroinflammation, anti-neurotoxicity, and activation of autophagy. This study discusses the mechanism of polysaccharides in PD, aiming to provide new ideas for PD prevention and treatment and new drug development in the future.

Objective To investigate the effect and mechanism of melatonin in alleviating hypoxia-induced apoptosis in ovarian gra-nulosa cells.Methods Rat ovarian granulosa cells were isolated and divided into normoxic,hypoxic,and melatonin groups.Hypoxia-induced injury models were established in the hypoxic and melatonin groups,and granulosa cells in the melatonin group were treated with melatonin.A total of 24 rats were randomized into the control,model,and intervention groups(n=8 per group).Rat models of declining ovarian function induced by long-term hypoxia were established in the model and intervention groups.The rats in the intervention group were intraperitoneally injected with melatonin.Cell proliferation was measured using a CCK-8 assay,and lactate secretion and HIF-1αprotein with a specific kit,respectively.The levels of estradiol and progesterone in the cell supernatant and rat serum were detected using ELISA.Granulosa cell apoptosis was detected by flow cytometry,ovarian morphology by HE staining,and Bax and caspase-3 expression by Western blotting.Results Compared with the normoxic group,the hypoxic group exhibited decreased granulosa cell proliferation,increased apoptosis,elevated lactate and HIF-1α levels,and reduced estradiol and progesterone levels(P＜0.05).Compared with hypoxic group,these changes were significantly reversed in the molatonin group(P＜0.05).Compared with the control group,the model group showed increased lactate,HIF-1α,Bax,and caspase-3 levels,decreased estradiol and progesterone levels,and reduced follicles.Compared with the model group,all the indicators were ameliorated in the intervention group(P＜0.05).Conclusion Melatonin alleviated hypoxia-induced granulosa cell apoptosis and promoted the recovery of ovarian function.

Parkinson's disease (PD), a major neurodegenerative disease faced by an aging society worldwide, has not yet been fully elucidated in terms of its pathogenesis. Currently, clinical treatment mainly relies on symptom management and can only be relieved by medication. In recent years, many studies have shown that polysaccharides have potential in treatment of neurodegenerative diseases. Polysaccharides play a role in PD in ways such as anti-oxidative stress response, improvement of mitochondrial dysfunction, inhibition of neuroinflammation, anti-neurotoxicity, and activation of autophagy. This study discusses the mechanism of polysaccharides in PD, aiming to provide new ideas for PD prevention and treatment and new drug development in the future.

Astrocytes are the largest glial population in the mammalian brain. However, we have a minimal understanding of astrocyte development, especially fate specification in different regions of the brain. Through lineage tracing of the progenitors of the third ventricle (3V) wall via in-utero electroporation in the embryonic mouse brain, we show the fate specification and migration pattern of astrocytes derived from radial glia along the 3V wall. Unexpectedly, radial glia located in different regions along the 3V wall of the diencephalon produce distinct cell types: radial glia in the upper region produce astrocytes and those in the lower region produce neurons in the diencephalon. With genetic fate mapping analysis, we reveal that the first population of astrocytes appears along the zona incerta in the diencephalon. Astrogenesis occurs at an early time point in the dorsal region relative to that in the ventral region of the developing diencephalon. With transcriptomic analysis of the region-specific 3V wall and lateral ventricle (LV) wall, we identified cohorts of differentially-expressed genes in the dorsal 3V wall compared to the ventral 3V wall and LV wall that may regulate astrogenesis in the dorsal diencephalon. Together, these results demonstrate that the generation of astrocytes shows a spatiotemporal pattern in the developing mouse diencephalon.
Mice ; Animals ; Astrocytes ; Neuroglia/physiology* ; Diencephalon ; Brain ; Neurons ; Mammals

Objective:To explore the current status and influencing factors of meaning in life among postoperative lung cancer patients, providing reference and guidance for the development of nursing interventions.Methods:From January to March 2023, convenience sampling was used to select 170 lung cancer patients with surgery in Department of Chest Surgery of the Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College as the study subject. The patients were surveyed using the General Information Questionnaire, Chinese version of Meaning in Life Questionnaire (C-MLQ), and the Cancer Fatigue Scale (CFS) .Results:The score of meaning in life among postoperative lung cancer patients was (45.71±5.90). Hierarchical linear regression analysis showed that living alone, educational level, and cancer-related fatigue were the influencing factors on the meaning in life among postoperative lung cancer patients ( P<0.05) . Conclusions:The meaning in life of postoperative lung cancer patients is at a moderate level. Medical and nursing staff should focus on patients who live alone and have a low level of education, and can also improve their meaning in life by alleviating cancer-related fatigue.

Objective:To investigate the risk factors associated with early hyperuricemia and gout attacks following laparoscopic sleeve gastrectomy (LSG) .Methods:This study was a retrospective observational study. Obese patients who underwent LSG surgery at Tianjin Medical University General Hospital from Jan. 2022 to Jul. 2023 were included according to inclusion and exclusion criteria. General information, body composition data, and laboratory tests were collected preoperatively and at one month postoperatively.Results:This study included a total of 300 patients. ①During the postoperative follow-up period, 216 out of 300 patients developed hyperuricemia, and 14 patients experienced gout attacks. ②Analysis of risk factors for early hyperuricemia revealed that male gender ( OR=5.32, 95% CI=1.953-14.489), postoperative creatinine ( OR=1.031, 95% CI=1.005-1.058), and preoperative uric acid levels ( OR=1.01, 95% CI=1.005-1.014) were independent risk factors for early hyperuricemia after laparoscopic sleeve gastrectomy (LSG). The area under the ROC curve (AUC) for the logistic regression model diagnosing hyperuricemia was 0.803 (95% CI=0.752-0.853), with sensitivity and specificity of 72.2% and 78.6%, respectively. ③Analysis of risk factors for early gout attacks showed that a history of gout ( OR=11.464, 95% CI=1.755-74.873), male gender ( OR=161.895, 95% CI=13.469-1946.022), postoperative fluid ratio ( OR=0.702, 95% CI=0.554-0.889), and changes in uric acid levels ( OR=1.017, 95% CI=1.006-1.028) were independent risk factors for early gout attacks after LSG. The AUC for the logistic regression model diagnosing gout was 0.921 (95% CI=0.808-1), with sensitivity and specificity of 93.4% and 92.9%, respectively. Conclusions:The incidence of early postoperative hyperuricemia is high, whereas the incidence of gout is low after LSG. Gender, preoperative uric acid, and postoperative creatinine are independent risk factors for hyperuricemia after LSG. History of gout, gender, postoperative water ratio, and change in uric acid levels are independent risk factors for gout after LSG.

Objective:To investigate the risk factors associated with early hyperuricemia and gout attacks following laparoscopic sleeve gastrectomy (LSG) .Methods:This study was a retrospective observational study. Obese patients who underwent LSG surgery at Tianjin Medical University General Hospital from Jan. 2022 to Jul. 2023 were included according to inclusion and exclusion criteria. General information, body composition data, and laboratory tests were collected preoperatively and at one month postoperatively.Results:This study included a total of 300 patients. ①During the postoperative follow-up period, 216 out of 300 patients developed hyperuricemia, and 14 patients experienced gout attacks. ②Analysis of risk factors for early hyperuricemia revealed that male gender ( OR=5.32, 95% CI=1.953-14.489), postoperative creatinine ( OR=1.031, 95% CI=1.005-1.058), and preoperative uric acid levels ( OR=1.01, 95% CI=1.005-1.014) were independent risk factors for early hyperuricemia after laparoscopic sleeve gastrectomy (LSG). The area under the ROC curve (AUC) for the logistic regression model diagnosing hyperuricemia was 0.803 (95% CI=0.752-0.853), with sensitivity and specificity of 72.2% and 78.6%, respectively. ③Analysis of risk factors for early gout attacks showed that a history of gout ( OR=11.464, 95% CI=1.755-74.873), male gender ( OR=161.895, 95% CI=13.469-1946.022), postoperative fluid ratio ( OR=0.702, 95% CI=0.554-0.889), and changes in uric acid levels ( OR=1.017, 95% CI=1.006-1.028) were independent risk factors for early gout attacks after LSG. The AUC for the logistic regression model diagnosing gout was 0.921 (95% CI=0.808-1), with sensitivity and specificity of 93.4% and 92.9%, respectively. Conclusions:The incidence of early postoperative hyperuricemia is high, whereas the incidence of gout is low after LSG. Gender, preoperative uric acid, and postoperative creatinine are independent risk factors for hyperuricemia after LSG. History of gout, gender, postoperative water ratio, and change in uric acid levels are independent risk factors for gout after LSG.