Mitochondria are the center of intracellular energy metabolism.Mitochondrial dynamics refers to the dynamic process of mitochondrial fusion and fission,which plays an important role in maintaining mitochondrial homeostasis and central nervous system function.Optic atrophy 1(OPA1)is a key factor involved in mitochondrial dynamics.OPA1 acts by regulating mitochondrial fusion and fission,reducing oxidative stress,inhibiting apoptosis,and promoting mitochondrial autophagy,to maintain the dynamic changes in mitochondrial quantity,structure,and biological function.Numerous studies have shown that OPA1-mediated mitochondrial dynamics plays an important role in ischemic stroke,Alzheimer's disease,Parkinson's disease,spinal cord injury,multiple sclerosis,and other central nervous system diseases.Here we review the regulatory mechanism of OPA1 in terms of mitochondrial dynamics and the important role of mitochondrial function mediated by OPA1 in central nervous system diseases,to provide new ideas for clinical treatment.

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.

Immune suppression in the tumor microenvironment (TME) is closely related to abnormal glycolysis. Tumor cells gain metabolic advantages and suppress immune responses through the "Warburg effect". Traditional Chinese medicine (TCM) has been shown to regulate key glycolysis enzymes (such as HK2 and PKM2), metabolic signaling pathways (such as PI3K/AKT/mTOR, HIF-1α) and non-coding RNAs at multiple targets, thus synergistically inhibiting lactate accumulation, improving vascular abnormalities, and relieving metabolic inhibition of immune cells. Studies have shown that TCM monomers and formulas can promote immune cell infiltration and functions, improve metabolic microenvironment, and with the assistance by the nano-delivery system, enhance the precision of treatment. However, the dynamic mechanism of the interaction between TCM-regulated glycolysis and TME has not been fully elucidated, for which single-cell sequencing and other technologies provide important technical support to facilitate in-depth analysis and clinical translational research. Future studies should be focused on the synergistic strategy of "metabolic reprogramming-immune activation" to provide new insights into the mechanisms of tumor immunotherapy.
Humans ; Tumor Microenvironment/immunology* ; Glycolysis/drug effects* ; Neoplasms/drug therapy* ; Medicine, Chinese Traditional ; Signal Transduction ; Drugs, Chinese Herbal/pharmacology*

Mitochondria are the center of intracellular energy metabolism.Mitochondrial dynamics refers to the dynamic process of mitochondrial fusion and fission,which plays an important role in maintaining mitochondrial homeostasis and central nervous system function.Optic atrophy 1(OPA1)is a key factor involved in mitochondrial dynamics.OPA1 acts by regulating mitochondrial fusion and fission,reducing oxidative stress,inhibiting apoptosis,and promoting mitochondrial autophagy,to maintain the dynamic changes in mitochondrial quantity,structure,and biological function.Numerous studies have shown that OPA1-mediated mitochondrial dynamics plays an important role in ischemic stroke,Alzheimer's disease,Parkinson's disease,spinal cord injury,multiple sclerosis,and other central nervous system diseases.Here we review the regulatory mechanism of OPA1 in terms of mitochondrial dynamics and the important role of mitochondrial function mediated by OPA1 in central nervous system diseases,to provide new ideas for clinical treatment.

To explore the clinical outcomes of fertility-sparing treatment (FST) in patients with POLE-mutated endometrioid carcinoma (EEC). A total of 9 EEC patients who received FST and were classified to the POLE-mutated subtype in Peking University People's Hospital from April 2020 to October 2023, were retrospectively collected. Clinical and pathological data were analyzed to describe the outcomes of FST in patients with POLE-mutated EEC.A total of 9 patients with EEC including 6 cases with well-differentiated (G1) and 3 cases with moderately-differentiated (G2). The average age was 34.8±2.1 years. POLE mutation sites were P286R (5 cases), V411L (2 cases), L424I (1 cases), and S459F (1 cases), respectively.The median follow-up time was 16 months (9–41 months). The complete response (CR) rate was 88.9% (8/9), with a median time to CR of 5.5 months (3–18 months). The partial response (PR) rate was 11.1% (1/9). The relapse rate was 50.0% (4/8), with a median recurrence time of 9.5 months (5–25 months). Of these, 75% (3/4) underwent secondary FST, with all achieving CR again (3/3). Three of 5 who were out-of-indication patients achieved CR by individual therapy. FST in patients with POLE-mutated EEC achieve a CR rate of 88.9% in this study, the largest number of retrievable reports. In certain patients who are out-ofindication, individualized treatment may also result in remission. However, unlike surgical patients, some patients experience disease recurrence and whether POLE-mutated EEC is sensitive to conventional therapy in FST is controversial given its pathogenesis.

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 evaluate the effectiveness of Roche Cobas s 201 in detecting HBV by analyzing its blood nucleic acid testing (NAT) results. 【Methods】 The results were grouped according to the enzyme-linked immunosorbent assay (ELISA) and NAT minipool test (MP), NAT individual test (ID) and repeated NAT ID test (rID), and categorized into 4 groups as ELISA+ /NAT(ID)+ , ELISA+ /NAT(rID)+ , ELISA-/NAT(ID)+ and ELISA-/NAT(rID)+ . The data were statistically analyzed to explore whether there was a difference in the detection of reactive results by repeated NAT, and the correlation between cycle threshold (Ct) and nucleic acid detection rate for NAT-reactive samples with different ELISA results. The true infection status of blood donors was further analyzed by supplementary tests, including NAT systems and chemiluminescence serological marker assays using other methodologies. 【Results】 A total of 1 691 groups of 766 293 blood donor samples were HBV NAT(MP)+ , of which 1 418 groups(83.86%) were detected with reactive results (1 418 HBV NAT+ , 7 090 NAT-), and there were still 273 groups (16.14%) that remained undetected after repeated testing[a total of 1 638 NAT-, Ct(MP): 39.49±3.62]. Of the HBV NAT+ , 881(62.13%) were ELISA+ /NAT(ID)+ , 19(1.34%) were ELISA+ /NAT(rID)+ , 451(31.81%) were ELISA-/NAT(ID)+ , and 67(4.72%) were ELISA-/NAT(rID)+ . For samples with different ELISA results, difference was found in the detection of HBV by repeated NAT (P<0.05). There was no difference in Ct(ID) values between groups ELISA+ /NAT(rID)+ and ELISA-/ NAT(ID)+ , and groups ELISA+ /NAT(rID)+ and ELISA-/ NAT(rID)+ (P>0.05), but there were significant differences between other groups compared pairwise (P<0.05). Supplementary tests were performed on 228 ELISA-/ NAT(MP)+ (ID)- samples, 56 (24.56%) were reactive by chemiluminescent detection of HBsAg+ and 7 (3.07%) by other NAT systems. Among the remaining 221 NAT- samples/donors (96.93%), 53 (23.98%) HBsAg+ donors were likely to have chronic infection, 40 (18.10%) anti-HBe+ and/or anti-HBc+ donors might have previous infections, and the remaining 128 (57.92%) donors who were non-reactive were NAT (MP) pseudo-reactive, with significant differences in anti-HBs levels \'between groups (P<0.05). 【Conclusion】 Repeated NAT has differential detection of donor samples with different reactivity categories or different serologic results, especially within a certain interval, and repeated NAT for ELISA- samples can significantly improve the detection rate. Ct values can assist in assessing the stability and accuracy of the NAT system. For ELISA-/NAT(MP)+ (ID)- donors, the combination of other highly sensitive assays can reduce the risk of viral residuals and safeguard clinical blood safety.

Objective To investigate the efficacy of oral Danning tablets for bowel preparation for colonoscopy in diabetes mellitus patients.Methods A study was conducted from November 2022 to May 2024,100 type 2 diabetic patients(aged≥30 years)admitted to endocrinology department in our hospital were selected and scheduled for colonoscopy as research subjects.These patients were randomly divided into two groups:①A control group(n=50),received 68.56 g of polyethylene glycol electrolyte powder 10 hours before the colonoscopy and an additional 137.12 g six hours before the procedure.②An experimental group(n=50),in addition to the bowel preparation regimen of the control group,orally took Danning tablets three times daily,five tablets each time,starting two days before the colonoscopy.Results The experimental group had a BBPS score of(7.44±1.03),which was higher than the control group's BBPS score of(5.58±1.98),P<0.001.In the experimental group,96%of the bowel preparations were rated as excellent or good(BBPS score≥6),significantly higher than the 58%in the control group(P<0.001).Conclusion In diabetic patients undergoing colonoscopy,oral administration of Danning tablets during bowel preparation could improve bowel cleanliness and significantly enhance the quality of bowel preparation.

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 investigate the changes of adipose tissues in mice after high-fat diet before and during pregnancy and the potential effects on adipose tissues in their offspring.Methods·C57BL/6J female mice were randomly assigned to the normal diet(CON group,n=12)or the high-fat diet(HFD group,n=12)for 5 weeks.The two groups were further subdivided according to pregnancy:a normal diet non-pregnancy group(CON-UN group),a normal diet pregnancy group(CON-P group),a high-fat diet non-pregnancy group(HFD-UN group),and a high-fat diet pregnancy group(HFD-P group).The original diet was maintained during pregnancy and lactation.White adipose tissues(WAT)and brown adipose tissues(BAT)were collected from visceral and scapula of mice after 5 weeks of feeding or E18.5d.Offspring from both dietary groups were placed on a normal diet after weaning,and their adipose tissues were collected at the 11th week.H-E staining was used to observe the changes of adipocytes.Flow cytometry was employed to detect the proportions of CD4+T cells,CD8+T cells,total T cells,CD4+T/CD8+T and NK cells in WAT.RT-PCR was used to assess the expression of IL-6 and IL-1β mRNA in WAT.Results·After 5 weeks on a high-fat diet,the body weight of female mice in the HFD group was higher than that in the CON group(P<0.05).Both WAT and BAT weights were markedly increased in the HFD groups before and during pregnancy(both P<0.05).In the WAT from HFD-UN and HFD-P groups,the number of cells within the same visual field decreased,the size of adipose cells varied,the proportion of fat droplets increased and the cell volume expanded.The proportion of lipid drop area to total visual field in the HFD-UN group and HFD-P group was compared with the CON-UN group and CON-P group,respectively,and the difference was statistically significant(all P<0.05).BAT in the HFD-UN and HFD-P groups showed a relatively chaotic arrangement and varying adipocyte sizes,although cell volume remained unchanged.The proportions of CD8+T cells and total T cells in adipose tissues were elevated in the HFD-UN and HFD-P groups,accompanied by increased mRNA levels of IL-6 and IL-1β,respectively,compared with the CON-UN and CON-P groups,and the differences were statistically significant(all P<0.05).NK cells proportions decreased at reproductive age(HFD-UN group)but increased significantly during pregnancy(HFD-P group),showing a divergent trend.Despite a return to a normal diet after weaning,offspring from the high-fat diet group had significantly higher weight of body,WAT and BAT,compared to those of normal diet(all P<0.05),and the volume of WAT was significantly enlarged.Conclusion·A high-fat diet can induce the changes of adipocyte structure and immune cell ratio,and elevate inflammation levels in adipose tissues before and during pregnancy,which also impacts the adipose structure in offspring.Adipose tissue may be a new vector mediating the intergenerational transmission of obesity.