BACKGROUND:In recent years,numerous studies have shown that autophagy and mitophagy play an important role in the regulation of bone metabolism.Under non-physiological conditions,mitophagy breaks the balance of bone metabolism and triggers metabolism disorders,which affect osteoblasts,osteoclasts,osteocytes,chondrocytes,bone marrow mesenchymal stem cells,etc. OBJECTIVE:To summarize the mechanism of mitophagy in regulating bone metabolic diseases and its application in clinical treatment. METHODS:PubMed,Web of Science,CNKI,WanFang and VIP databases were searched by computer using the keywords of"mitophagy,bone metabolism,osteoblasts,osteoclasts,osteocytes,chondrocytes,bone marrow mesenchymal stem cells"in English and Chinese.The search time was from 2008 to 2023.According to the inclusion criteria,90 articles were finally included for review and analysis. RESULTS AND CONCLUSION:Mitophagy promotes the generation of osteoblasts through SIRT1,PINK1/Parkin,FOXO3 and PI3K signaling pathways,while inhibiting osteoclast function through PINK1/Parkin and SIRT1 signaling pathways.Mitophagy leads to bone loss by increasing calcium phosphate particles and tissue protein kinase K in bone tissue.Mitophagy improves the function of chondrocytes through PINK1/Parkin,PI3K/AKT/mTOR and AMPK signaling pathways.Modulation of mitophagy shows great potential in the treatment of bone diseases,but there are still some issues to be further explored,such as different stages of drug-activated mitophagy,and the regulatory mechanisms of different signaling pathways.

OBJECTIVE To evaluate the effect of manipulation of Imipenem and cisplatin sodium （ICS） for injection on the consistency of its main drug imipenem （IPN） content， and the stability of different concentrations of ICS solution， to provide a reference for the safe and effective use of ICS in children. METHODS Three operators prepared ICS solutions according to the two commonly used dosage methods for children （10 mL or 20 mL 0.9% Sodium chloride injection to prepare the initial ICS solution and draw the required dose from the initial suspension）. The content of IPN was determined by ultra-high performance liquid chromatography-tandem mass spectrometry after parallel processing. The content consistency of solutions in each group was determined according to the coefficient of variation （CV）＜15% of the IPN content. ICS test solution X1 was prepared according to the instructions， and then test solutions X2 and X3 were prepared by diluting X1 with 0.9% Sodium chloride injection in the volume ratios of 1∶1 and 1∶2， which were stored at room temperature （[ 23.0±0.5） ℃]， in a thermostatic water bath at 30 ℃， and in a refrigerator at 2-8 ℃. The stability of the drug solution was determined by the ratio of the IPN mass concentration measured at the specified temperature and time to the initial （0 h） mass concentration （if the ratio was≥90%， it was considered that the drug solution was stable）. RESULTS CV of IPN content was ＜15% in each group of solutions prepared with two manipulation methods by each operator， indicating a small deviation in IPN content. The solutions at the three concentration levels were stable at room temperature for 6 h or refrigerated for 18 h. The test solutions X1 and X2 were also stable when placed at 30 ℃ for 6 h， but the IPN concentration in test solution X3 decreased by about 20% compared with that of 0 h. CONCLUSIONS The consistency of the content of IPN is good in the two commonly used methods for ICS manipulation in children. The stability of ICS solution is affected by concentration， temperature and time. Lower concentrations at higher temperatures resulted in decreased stability of IPN. Clinical attention should be paid to controlling the amount of solvent as well as temperature and time during preparation and use.

ObjectiveTo investigate the relationship between mitochondrial DNA copy number (mtDNAcn) and cognitive dysfunction, and its mediating role between type 2 diabetes mellitus (T2DM) and cognitive dysfunction. MethodsA case-control study was conducted from May 2019 to April 2021 at the Shanghai Yangpu District Central Hospital, China. A total of 193 subjects were recruited and divided into two groups based on the Montreal Cognitive Assessment (MoCA): normal control (NC) group (n=95) and cognitive impairment group (n=98). The prevalence of T2DM was determined on the basis of medical history, while mtDNAcn in peripheral blood samples was quantified using realtime fluorescent quantitative polymerase chain reaction. ResultsUnivariate analyses revealed that the mean mtDNAcn in the cognitive impairment group was 0.76±0.37, significantly lower than that in the NC group (1.06±0.45) (P<0.05). Logistic regression analyses showed that higher mtDNAcn was associated with a reduced risk of cognitive impairment (OR=0.315, 95%CI: 0.125‒0.795). Additionaly, a statistically significant positive correlation was observed between mtDNAcn and the total MoCA score (r=0.381, P<0.01). Morever, T2DM history (OR=2.741, 95%CI: 1.002‒7.497) and elevated glycosylated hemoglobin (HbA1c) levels (OR=1.796, 95%CI: 1.190‒2.711) were identified as risk factors for cognitive impairment. Mediation analyses indicated that mtDNAcn served as a mediator between T2DM/HbA1c and the risk of cognitive impairment, with proportions of mediating effect of 9.04% and 9.18%, respectively. ConclusionPatients with mild and moderate cognitive impairment have significantly lower mtDNAcn than those with normal cognitive function. Reduced mtDNAcn is an influencing factor for cognitive dysfunction and may play a mediating role in the association between T2DM and mild to moderate cognitive impairment.

ObjectiveEndothelial cell dysfunction being the core link. This study explores the molecular mechanism of Danshen Tongluo formula in treating coronary artery disease-dominated panvascular disease with endothelial cell changes as the core through animal experiments and single-cell transcriptome sequencing. MethodsA rat model of coronary artery disease-dominated panvascular disease was established by ligating the left anterior coronary artery. Rats were randomized into a blank group， a model group， and a Danshen Tongluo formula （28 mg·kg^-1·d^-1） group. The efficacy was evaluated by examining the cardiac ultrasound， determination of the plasma level of N-terminal pro-brain natriuretic peptide， and pathological staining. After single-cell sequencing， SingleR package， public datasets， and related literature were used for annotation of the cells. Cell chat was used for intercellular communication and ligand-receptor analysis， and scmetabolism was used for metabolic analysis of endothelial cells. ResultsAnimal experiments showed that Danshen Tongluo formula reduced the N-terminal pro-brain natriuretic peptide （ NT-proBNP ） level （P<0.05）， ameliorated myocardial cell damage and fibrosis， and increase left ventricular ejection fractions （LVEF） in the rat model of heart failure after myocardial infarction（P<0.05）. Single-cell sequencing results showed that Danshen Tongluo formula increased the proportion of arterial endothelial cells， venous endothelial cells， and capillary-arterial endothelial cells， while reducing the proportion of capillary-venous endothelial cells. In addition， this formula increased the interaction intensity of endothelial cells with cardiomyocytes and M1 macrophages and reduced the interaction intensity of endothelial cells with fibroblasts and T cells. Danshen Tongluo formula upregulated CXCL12-CXCR4 signaling in endothelium-B cells and Ptprm-Ptprm signaling in endothelial endothelial cells， while downregulating Mif-（CD74⁺CXCR44） signaling in endothelium-M1 macrophages and Mif-（CD74⁺CD44） signaling in endothelium-M2 macrophages. It reduced the citric acid cycle， oxidative phosphorylation， and glycolysis and increased the glycolysis/oxidative phosphorylation ratio in endothelial cells. GO and KEGG enrichment analysis showed that arterial endothelial cells， venous endothelial cells， and venous capillary endothelial cells can all regulate oxidative phosphorylation， cell adhesion molecules， and tyrosine metabolism. Lymphatic endothelial cells regulate immunity and vascular constriction to participate in the metabolism of various amino acids and fatty acids. ConclusionDanshen Tongluo Formula can ameliorate coronary artery disease-dominated panvascular disease by changing the composition of endothelial cells and regulating the communication between myocardial endothelial cells and non-endothelial cells.

Objective:To assess the efficacy of different fusion strategies involving the convolutional block attention module (CBAM) and Unet for automatic pancreas segmentation in enhanced CT images of patients with acute pancreatitis.Methods:A retrospective analysis was conducted on 1 158 patients with acute pancreatitis admitted to the Affiliated Hospital of North Sichuan Medical College between January 1st, 2016 and July 30th, 2021. Among them, 141 patients with first-episode acute pancreatitis were randomly categorized into mild, moderate, and severe cases. The test set comprised 5 mild and 15 severe cases, while the remaining 126 cases were used for training. Within the training set, 20% of the data was randomly allocated as the validation set. Different fusion paths of the CBAM and Unet networks were trained, utilizing the Dice similarity coefficient, Hausdorff distance (HD), and pixel accuracy (PA) as evaluation metrics. The model demonstrating the best performance on the validation set was selected and evaluated on the test set. Additionally, the Unet model was combined with the attention gate attention mechanism (AttentionUnet) in the skip connection, and the ResBlock replaced the original convolution module (ResUnet) in the Unet network. Moreover, the skip connection branch module of feature extraction was integrated with CBAM (ResUnet_CBAM) for comparison.Results:Unet_CBAM achieved better results on the test set with a Dice value of 80.06%, a HD value of 3.765 9 and a PA value of 0.992 3, all surpassing other fusion strategies. The segmentation accuracy of the pancreatic region in CT images of acute pancreatitis patients was notably enhanced compared to Unet and its related variant networks.Conclusions:The Unet network integrated into CBAM after skip connection can better perform pancreatic segmentation on enhanced CT images of patients with acute pancreatitis and can effectively improve the efficiency of relevant personnel in pancreatic segmentation on enhanced CT images of patients with acute pancreatitis.

Objective:The contaminated microorganisms in the whole production process of Yujin,mulberry leaf and cicada were investigated,and a database was established to explore the microbial key control points and control measures in the production process of traditional Chinese medicine(TCM)formula granules,in order to provide demonstration research for enterprises,provide basis for formulating standards and improving production processes,and fill the blank of the whole.Methods:The raw materials,intermediate products and final products of three kinds of TCM formula particles were analyzed according to the Chinese Pharmacopoeia 2020,and the supporting mi-croorganisms were identified by mass spectrometry technology.The degree of exogenous polluting microorganisms from raw materials to finished products of TCM formula particles and the types of microorganisms easily contamina-ted were analyzed and studied.Results:The raw materials(TCM decoction pieces)of the three TCM formulations granules had serious microbial pollution,and the thermostable bacillus of the raw materials could still be detected in the intermediate products and final products even after the process treatment,and the total number of aerobic bacte-ria in some batches exceeded the limit.Enterococcus faecium from human and animal intestines was also detected in intermediate products and finished products.Conclusion:①Strengthening the control of microbial contamination of TCM decoction pieces is conducive to reducing the microbial load of final products;②There are risks of spore microorganism contamination in the production technology of 3 kinds of formula granuleshas,and the production process parameters should be optimized to reduce the microbial load;③Pharmaceutical companies need to strength-en the whole process of product control to reduce the risk of microbial contamination.

Objective:To investigate the effect of iridin on enhancing antiviral immune effect in mice with viral myocarditis by regulating programmed death factor-1(PD-1)/programmed death factor ligand-l(PD-L1)pathway.Methods:Fifty C57BL/6 mice were inoculated intraperitoneally with Coxsackie virus B3(CVB3)to construct mouse model of viral myocarditis.Successfully modeled mice were randomly divided into model group,iridin low,medium and high doses groups and positive control group.Another 10 C57BL/6 mice were recorded as blank control group.Positive control group was given 10 000 U/g interferon by intraperitoneal injec-tion,irisin low,medium and high dosed groups were given 30,60 and 120 μg/kg iridin by intraperitoneal injection,and blank control group and positive control group were given the same amount of normal saline once a day for 2 weeks.HE staining was used to observe pathological changes of mouse myocardium.Virus titer in mouse myocardium was detected by plaque forming unit(PFU)method.Pro-portion of T lymphocyte subsets(CD4+T,CD8+T,NK cells)and CD4+T/CD8+T were detected by flow cytometry.Inflammatory cyto-kines IL-6,IL-17,TNF-α and IFN-γ levels in mouse myocardium were detected by ELISA.RT-qPCR was used to detect expression of PD-1 mRNA in T lymphocytes and expression of PD-L1 mRNA in myocardium of mouse.Western blot was used to detect expression of PD-1 protein in T lymphocytes and expression of PD-L1 protein in myocardium of mice.Results:Compared with blank control group,myocardial tissue structure of model group changed significantly,with a large number of inflammatory cell infiltration and focal necro-sis,pathological score,virus titer,levels of inflammatory cytokines IL-6,IL-17,TNF-α and IFN-γ,and PD-L1 mRNA and protein expressions in myocardial tissue were increased,proportion of peripheral blood CD8+T lymphocytes and expression of PD-1 mRNA and protein in T lymphocytes were increased,while proportion of peripheral blood CD4+T lymphocytes,NK cells and CD4+T/CD8+T were decreased,the differences were statistically significant(P<0.05).Compared with model group,pathological changes of myocardial tissue in positive control group and low,medium and high doses groups of irisin were reduced in varying degrees.Pathological score,virus titer,levels of inflammatory cytokines IL-6,IL-17,TNF-α and IFN-γ,and PD-L1 mRNA and protein expression in myocardial tissue were decreased,the proportion of peripheral blood CD8+T lymphocytes and expression of PD-1 mRNA and protein in T lymphocytes were decreased,while the proportion of peripheral blood CD4+T lymphocytes,NK cells and CD4+T/CD8+T were increased,effect of iri-din was as a dose-dependent manner,the differences were statistically significant(P<0.05).Conclusion:Iridin can enhance the anti-viral immune effect of viral myocarditis mice.It is speculated that iridin can improve the proportion imbalance of T lymphocyte subsets in peripheral blood of mice and improve the immune function of the body by inhibiting the activation of PD-1/PD-L1 pathway.

Objective:To explore the application effects of whole-process nutritional management in patients undergoing thoracoabdominal laparoscopic radical esophagectomy.Methods:A total of 144 patients who underwent thoracoabdominal laparoscopic radical esophagectomy at the Jiangsu Cancer Hospital between February 2022 and February 2024 were selected using convenience sampling method. Patients were randomly assigned to a control group ( n=72) receiving routine care and an observation group ( n=72) receiving whole-process nutritional management in addition to routine care. Nutritional status, postoperative recovery, nursing satisfaction, and weight loss were compared between the two groups. Results:On the day before surgery, the Nutritional Risk Screening (NRS-2002) score of the observation group was significantly lower than that of the control group, the difference was statistically significant ( P<0.05). The observation group had earlier times to first ambulation, bowel movement, flatus, and fewer total complications compared to the control group, the differences were statistically significant ( P<0.05). Nursing satisfaction scores in the observation group were significantly higher than in the control group, the differences were statistically significant ( P<0.05). One month postoperatively, the observation group experienced less weight loss than the control group, the difference was statistically significant ( P<0.05) . Conclusions:Whole-process nutritional management improves preoperative nutritional status scores, reduces postoperative complications and weight loss, and enhances patient satisfaction with nursing care in esophageal cancer patients undergoing thoracoabdominal laparoscopic radical esophagectomy.

Objectives:To investigate the clinical feasibility of three-dimensional(3D)high-resolution late gadolinium enhancement(LGE)MRI in accessing left atrial myocardial fibrosis in patients with atrial fibrillation(AF). Methods:A total of 34 AF patients referred for hybrid surgical ablation were retrospectively enrolled in this study.3D-LGE-MRI images were acquired by Siemens 3.0 T machine and analyzed by ADAS post-processing software by two experienced radiologists to obtain parameters such as the area and the area percentage of LGE.Regional analysis was performed by one of the two radiologists at ten left atrial segments.The Kappa test was used to assess the agreement for scoring image quality,and the interclass correlation coefficient(ICC)was used to evaluate the interobserver agreement of LGE parameters.The parameters of left atrial morphology,area(and area percentage)of LGE,and location of LGE were compared between patients with persistent AF and paroxysmal AF. Results:Images of all 34 patients were considered to have diagnostic value.The scores of the overall image quality and the clarity of the left atrial wall evaluated by two radiologists were(2.88±0.64)points and(3.26±0.75)points(radiologist 1),(2.97±0.58)points and(3.24±0.70)points(radiologist 2),respectively.The corresponding Kappa values were 0.724 and 0.859.Both the area and the area percentage of LGE showed good consistency among observers,and the ICCs were 0.969 and 0.950,respectively.The difference in the area of LGE and the area percentage of LGE between patients with paroxysmal and persistent atrial fibrillation was similar(both P＞0.05).Compared with patients with paroxysmal AF,patients with persistent AF had a higher Utah stage and more severe myocardial fibrosis in the right inferior pulmonary vein antrum and the left atrial septum(all P＜0.05). Conclusions:3D high-resolution LGE-MRI provides a non-invasive way to visualize and quantify left atrial myocardial fibrosis.The extent of left atrial fibrosis in patients with persistent AF is more severe than that in patients with paroxysmal AF,with a preferential distribution in the right inferior pulmonary vein antrum and the left atrial septum.

Purpose: The long-term fertility impact of cancer treatments is a significant concern for young breast cancer survivors. These reproductive concerns often become a persistent source of stress, negatively affecting their quality of life. This study aims to explore the reproductive concerns experienced by young breast cancer survivors post-treatment and the factors influencing their perceptions. Methods: This phenomenological study utilized semi-structured interviews to collect data. Eighteen participants were recruited from a tertiary hospital in Mainland China. The interviews were transcribed verbatim and analyzed using Colaizzi's method. Results: Data analysis revealed five themes and fourteen subthemes: (1) multiple emotional burdens interwoven with concerns about fertility; (2) concerns about risks associated with reproduction; (3) dilemma of childrearing; (4) the significance of reproduction; (5) support needs from family, peers, and professionals. Conclusion Young breast cancer survivors in China face significant challenges related to reproductive issues. Reproductive health is a crucial aspect of breast cancer survivorship care. Healthcare providers must be attentive to the reproductive concerns of survivors, recognize the importance of multidimensional support for positive adaptation, and offer tailored and ongoing interventions to manage reproductive health in young breast cancer survivors.