Vascular cognitive impairment (VCI), caused by cerebrovascular dysfunction, severely impacts the quality of life in the elderly population, yet effective therapeutic approaches remain limited. Mitophagy, a selective mitochondrial quality-control mechanism, has emerged as a critical focus in neurological disease research. Accumulating evidence indicates that mitophagy modulates oxidative stress, neuroinflammation, and neuronal apoptosis. Key signaling pathways associated with mitophagy—including PINK1/Parkin, BNIP3/Nix, FUNDC1, PI3K/Akt/mTOR, and AMPK—have been identified as potential therapeutic targets for VCI. This review summarizes the mechanistic roles of mitophagy in VCI pathogenesis and explores emerging therapeutic strategies targeting these pathways, aiming to provide novel insights for clinical intervention and advance the development of effective treatments for VCI.

Methods To investigate how the timing of cooling therapy affects organ injuries in rats with exertional heat stroke(EHS)and explore the possible mechanisms.Methods A total of 60 adult male Wistar rat models of EHS were randomized into model group without active cooling after modeling,immediate cooling group with cold water bath immediately after modeling,delayed cooling groups with cold water bath at 5,15 and 30 min after modeling,with another 12 mice without EHS as the normal control group.The changes in core body temperature of the mice were recorded and the cooling rate was calculated.After observation for 24 h,the mice were euthanized and blood samples were collected for detection of interleukin-1β(IL-1β),IL-2,IL-4,IL-6,IL-10,and interferon-γ,followed by pathological examination of the vital organs.The rats that died within 24 h were immediately dissected for examination.Results The number of deaths of the model rats within 24 h increased significantly with the time of delay of cooling treatment.The delay of cooling was positively correlated(r=0.996,P=0.004)while the cooling rate negatively correlated with the mortality rate(r=-0.961,P=0.009).The inflammatory cytokine levels presented with different patterns of variations among the cooling intervention groups.All the rat models of EHS had significant organ damages characterized mainly by epithelial shedding,edema,effusion,and inflammatory cell infiltration,and brain and renal injuries reached the peak level at 24 h after EHS.Conclusion EHS causes significant nonspecific pathologies of varying severities in the vital organs of rats,and the injuries worsen progressively with the delay of cooling.There is a significant heterogeneity in changes of serum inflammatory cytokines in rats with different timing of cooling intervention following EHS.

Objective To conduct the evaluation and comparison on the application effects of the 5-D Pruritus Assessment Scale and the Multidimensional Uremic Pruritus Assessment Scale in the patients with maintenance hemodialysis.Methods A total of 154 maintenance hemodialysis patients with pruritus symptom in this hospital from February to June 2023 were selected as the study subjects.The 5-D Pruritus Assessment Scale and the Multidimensional Uremic Itch Assessment Scale were used to evaluate the dimensions such as the pruritus degree,duration and itching location.After standardization treatment by aiming at the evaluation results of the two kinds of scales,the Bland-AItman method was adopted to conduct the consistency compari-son.The Spearman correlation coefficient was adopted to test the correlation between the two kinds of scales. Results The consensus limit (LoA) confidence interval of the 5-D Pruritus Assessment Scale was-0.1578 to 0.1603,the Multidimensional Uremic Pruritus Assessment Scale was-0.1592 to 0.1592.The Spearman correlation results showed that the two scales had the positive correlation (r=0.472,P<0.001).In the 5-D Pruritus Assessment Scale,the area under the curve(AUC) of the fractal dimensions such as duration,degree,development direction,disability and distribution were 0.674 (95％CI:0.557-0.790),0.799 (95％CI:0.700-0.899),0.637 (95％CI:0.528-0.747),0.951 (95％CI:0.905-0.997) and 0.786(95％CI:0.701-0.872),respectively.In the Multidimensional Uremic Pruritus Assessment Scale,AUC of the fractal dimen-sions such as symptom and sign,psychological society and sleep were 0.989 (95％CI:0.978-1.000),0.931 (95％CI:0.878-0.985),and 0.951 (95％CI:0.909-0.994),respectively.Conclusion The consistency of the two scales is good,and both scales can be used to evaluate uremia skin pruritus.The Multidimensional Uremic Pruritus Assessment Scale is more targeted in the assessment of sleep dimension,which is more suitable for the evaluation of maintenance hemodialysis patients.

Methods To investigate how the timing of cooling therapy affects organ injuries in rats with exertional heat stroke(EHS)and explore the possible mechanisms.Methods A total of 60 adult male Wistar rat models of EHS were randomized into model group without active cooling after modeling,immediate cooling group with cold water bath immediately after modeling,delayed cooling groups with cold water bath at 5,15 and 30 min after modeling,with another 12 mice without EHS as the normal control group.The changes in core body temperature of the mice were recorded and the cooling rate was calculated.After observation for 24 h,the mice were euthanized and blood samples were collected for detection of interleukin-1β(IL-1β),IL-2,IL-4,IL-6,IL-10,and interferon-γ,followed by pathological examination of the vital organs.The rats that died within 24 h were immediately dissected for examination.Results The number of deaths of the model rats within 24 h increased significantly with the time of delay of cooling treatment.The delay of cooling was positively correlated(r=0.996,P=0.004)while the cooling rate negatively correlated with the mortality rate(r=-0.961,P=0.009).The inflammatory cytokine levels presented with different patterns of variations among the cooling intervention groups.All the rat models of EHS had significant organ damages characterized mainly by epithelial shedding,edema,effusion,and inflammatory cell infiltration,and brain and renal injuries reached the peak level at 24 h after EHS.Conclusion EHS causes significant nonspecific pathologies of varying severities in the vital organs of rats,and the injuries worsen progressively with the delay of cooling.There is a significant heterogeneity in changes of serum inflammatory cytokines in rats with different timing of cooling intervention following EHS.

Objective: This study aims to assess the impact of the metabolic risk score (MRS) on time to achieve complete remission (CR) of fertility-sparing treatments for atypical endometrial hyperplasia (AEH) and early endometrial cancer (EC) patients. Methods: Univariate and multivariate cox analyses were employed to identify independent risk factors affecting the time to CR with patients at our center. These factors were subsequently incorporated into receiver operator characteristic curve analysis and decision curve analysis to assess the predictive accuracy of time to CR. Additionally, Kaplan–Meier analysis was utilized to determine the cumulative CR rate for patients. Results: The 173 patients who achieved CR following fertility preservation treatment (FPT) were categorized into three subgroups based on their time to CR (<6, 6–9, >9 months). Body mass index (hazard ratio [HR]=0.20; 95% confidence interval [CI]=0.03, 0.38; p=0.026), MRS (HR=0.31; 95% CI=0.09, 0.52; p=0.005), insulin resistance (HR=1.83; 95% CI=0.05, 3.60; p=0.045), menstruation regularity (HR=3.77; 95% CI=1.91, 5.64; p=0.001), polycystic ovary syndrome (HR=−2.16; 95% CI=−4.03, −0.28; p=0.025), and histological type (HR=0.36;95% CI=0.10, 0.62; p=0.005) were identified as risk factors for time to CR, with MRS being the independent risk factor (HR=0.29; 95% CI=0.02, 0.56; p=0.021). The inclusion of MRS significantly enhanced the predictive accuracy of time to CR (area under the curve [AUC]=0.789 for Model 1, AUC=0.862 for Model 2, p=0.032). Kaplan–Meier survival curves revealed significant differences in the cumulative CR rate among different risk groups. Conclusion MRS emerges as a novel evaluation system that substantially enhances the predictive accuracy for the time to achieve CR in AEH and early EC patients seeking fertility preservation.

Objective: This study aims to assess the impact of the metabolic risk score (MRS) on time to achieve complete remission (CR) of fertility-sparing treatments for atypical endometrial hyperplasia (AEH) and early endometrial cancer (EC) patients. Methods: Univariate and multivariate cox analyses were employed to identify independent risk factors affecting the time to CR with patients at our center. These factors were subsequently incorporated into receiver operator characteristic curve analysis and decision curve analysis to assess the predictive accuracy of time to CR. Additionally, Kaplan–Meier analysis was utilized to determine the cumulative CR rate for patients. Results: The 173 patients who achieved CR following fertility preservation treatment (FPT) were categorized into three subgroups based on their time to CR (<6, 6–9, >9 months). Body mass index (hazard ratio [HR]=0.20; 95% confidence interval [CI]=0.03, 0.38; p=0.026), MRS (HR=0.31; 95% CI=0.09, 0.52; p=0.005), insulin resistance (HR=1.83; 95% CI=0.05, 3.60; p=0.045), menstruation regularity (HR=3.77; 95% CI=1.91, 5.64; p=0.001), polycystic ovary syndrome (HR=−2.16; 95% CI=−4.03, −0.28; p=0.025), and histological type (HR=0.36;95% CI=0.10, 0.62; p=0.005) were identified as risk factors for time to CR, with MRS being the independent risk factor (HR=0.29; 95% CI=0.02, 0.56; p=0.021). The inclusion of MRS significantly enhanced the predictive accuracy of time to CR (area under the curve [AUC]=0.789 for Model 1, AUC=0.862 for Model 2, p=0.032). Kaplan–Meier survival curves revealed significant differences in the cumulative CR rate among different risk groups. Conclusion MRS emerges as a novel evaluation system that substantially enhances the predictive accuracy for the time to achieve CR in AEH and early EC patients seeking fertility preservation.

Objective: This study aims to assess the impact of the metabolic risk score (MRS) on time to achieve complete remission (CR) of fertility-sparing treatments for atypical endometrial hyperplasia (AEH) and early endometrial cancer (EC) patients. Methods: Univariate and multivariate cox analyses were employed to identify independent risk factors affecting the time to CR with patients at our center. These factors were subsequently incorporated into receiver operator characteristic curve analysis and decision curve analysis to assess the predictive accuracy of time to CR. Additionally, Kaplan–Meier analysis was utilized to determine the cumulative CR rate for patients. Results: The 173 patients who achieved CR following fertility preservation treatment (FPT) were categorized into three subgroups based on their time to CR (<6, 6–9, >9 months). Body mass index (hazard ratio [HR]=0.20; 95% confidence interval [CI]=0.03, 0.38; p=0.026), MRS (HR=0.31; 95% CI=0.09, 0.52; p=0.005), insulin resistance (HR=1.83; 95% CI=0.05, 3.60; p=0.045), menstruation regularity (HR=3.77; 95% CI=1.91, 5.64; p=0.001), polycystic ovary syndrome (HR=−2.16; 95% CI=−4.03, −0.28; p=0.025), and histological type (HR=0.36;95% CI=0.10, 0.62; p=0.005) were identified as risk factors for time to CR, with MRS being the independent risk factor (HR=0.29; 95% CI=0.02, 0.56; p=0.021). The inclusion of MRS significantly enhanced the predictive accuracy of time to CR (area under the curve [AUC]=0.789 for Model 1, AUC=0.862 for Model 2, p=0.032). Kaplan–Meier survival curves revealed significant differences in the cumulative CR rate among different risk groups. Conclusion MRS emerges as a novel evaluation system that substantially enhances the predictive accuracy for the time to achieve CR in AEH and early EC patients seeking fertility preservation.

Objective: To investigate The Cancer Genome Atlas (TCGA) molecular classification of endometrial cancer (EC) and endometrial atypical hyperplasia (AH) treated with fertility-sparing therapy. Methods: A total of 46 EC and AH patients who received fertility-sparing therapy and TCGA molecular classification tested by next generation sequencing, in Peking University People’s Hospital from June 2020 to December 2021, were retrospectively collected. We analyzed the relationship between molecular classification and clinicopathological factors and treatment outcomes. Results: Of the 46 patients, including 40 EC and 6 AH patients, 70.5% (32 patients) had complete remission (CR) after treatment, with median CR time of 8 months. The cases were distributed as no specific molecular profile (NSMP; n=34, 73.9%) subtype mainly, microsatellite instability-high (MSI-H; n=7, 15.2%), POLE ultra‑mutated (n=3, 6.5%), and copy number high (CNH; n=2, 4.3%). Patients with MSI-H subtype had lower body mass index (24.0±5.5 kg/m2), more family history of tumor (6/7), more with loss of mismatch repair protein expression by immunohistochemical (7/7), and higher Ki67 expression level (3/3). Patients in MSI-H subgroup had the lowest CR rate at 6 months (0/6, p=0.019), and survival analysis showed that such patients were less likely to achieve CR than those with NSMP subtype (p=0.022). Subgroup analysis of patients with NSMP showed that, age ≥30 years and diabetes mellitus related with longer treatment time to CR (p=0.01 and p=0.059, respectively). In addition, CR was obtained in 2 (2/3) POLE ultra‑mutated cases and 1 (2/2) CNH case, respectively. Conclusion TCGA molecular classification relates with the treatment response in patients with EC and AH treated with fertility-sparing therapy. Patients with MSI-H subtype have poor treatment efficacy.

Objective:To investigate the molecular classification of endometrial carcinoma (EC) and atypical endometrial hyperplasia (AEH) treated with fertility-sparing therapy, and to analyze its relationship with clinicopathological factors and treatment efficacy.Methods:A total of 46 EC and AEH patients who received fertility-sparing therapy and molecular classification tested by next generation sequencing in Peking University People's Hospital from June 2020 to December 2021, were retrospectively collected. The relationships between molecular classification and clinicopathological factors and treatment outcomes were analyzed.Results:(1) Of the 46 patients, including 40 EC and 6 AEH patients, 32 cases (71%, 32/45) had complete response (CR) after treatment, with median CR time of 8 months, 6 cases (13%, 6/45) had partial response, and 8 cases (25%, 8/32) had recurrence. (2) The cases were distributed as no specific molecular profile (NSMP) 34 cases (74%, 34/46) subtype mainly, high microsatellite instability (MSI-H) 7 cases (15%, 7/46), POLE ultra-mutated 3 cases (7%, 3/46), and copy number high (CNH) 2 cases (4%, 2/46). Patients with CNH had the hightest serum cancer antigen 125 (CA 125) level [(34.3±35.2) kU/L]. MSI-H subtype had more family history of tumors (6/7), more with loss of mismatch repair (MMR) protein expression by immunohistochemical (7/7), and higher nuclear antigen associated with cell proliferation (Ki-67) expression level (3/3). (3) Patients in MSI-H subgroup had the lowest CR rate at 6 months (0/6; P=0.019), and survival analysis showed that they were less likely to achieve CR than those with NSMP subtype ( P=0.022). Subgroup analysis of patients with NSMP showed that age ≥30 years related with longer treatment time to CR ( P=0.010). In addition, CR was obtained after treatment in 2/3 POLE ultra-mutated cases and 2/2 CNH, respectively. Conclusions:Molecular classification relates with the treatment response in patients with EC and AEH treated with fertility-sparing therapy. Patients with MSI-H subtype have poor treatment efficacy, and patients with NSMP need to be further studied and predict treatment benefit. However, there are few cases in POLE ultra-mutated and CNH subtypes, which need further clinical research.

Objective:To investigate the clinical features of obesity indicators in patients with endometrial atypical hyperplasia (EAH) and early endometrial cancer (EC) and analyze the relationship between these indexes and effect of fertility preservation therapy.Methods:The clinical data of patients with EAH, EC and endometrial benign lesions treated in Peking University People′s Hospital from January 1, 2018 to June 30, 2021 who required fertility-sparing treatment were collected, and obesity indicators were calculated and analyzed retrospectively.Results:(1) Obesity indicators: the obesity [body mass index (BMI) ≥28 kg/m 2] rate of patients with fertility preservation treatment was 40% (32/80), and abdominal obesity [waist circumference (WC) ≥80 cm] rate was 79% (63/80), and obesity indicators [BMI, WC, waist-hip ratio (WHR), weight height ratio (WHTR), body roundness index (BRI), lipid accumulation index (LAP), visceral adiposity index (VAI)] were higher than those with endometrial benign lesions (all P<0.001). (2) Related factors affecting the efficacy of fertility preservation treatment and their predictive value: EC, higher BMI, WC, WHR, WHTR and BRI were risk factors for lower complete remission rate after nine months′ treatment (all P<0.05). The predictive values of BRI and WHTR combined with pathological type were superior to other indicators [area under the curve (AUC)=0.716; AUC=0.714]. (3) Relation of obesity indicators and glucolipid indicators:BMI, WC, WHR, WHTR, BRI, LAP and VAI were positively correlated with homeostasis model assessment-insulin resistance index, glycosylated hemoglobin, and triacylglycerol (all P<0.05); while VAI was negatively correlated with high density lipoprotein cholesterol ( P<0.001). Conclusions:For patients with EAH and EC treated with fertility preservation therapy, abnormal obesity indexes affect the treatment effect. BRI and WHTR combined pathology have good predictive value for effect of fertility preservation treatment. In clinical practice, appropriate indicators could be selected to evaluate body shape, glucolipid metabolism and predict efficacy.