Diabetic retinopathy(DR)is one of the most common and severe microvascular complications in diabetic patients and has become one of the leading causes of blindness worldwide. With the continuous rise in the prevalence of diabetes, in-depth exploration of the pathogenesis of DR and effective intervention measures is of great clinical significance. The mechanistic target of rapamycin(mTOR), as a protein kinase, is widely involved in cellular processes such as growth, metabolism, and autophagy. Research indicates that the mTOR signaling pathway plays a crucial regulatory role in the pathological progression of DR, and its abnormal activity can disrupt retinal cell autophagy function, thereby accelerating cellular damage and disease progression. Autophagy, as an important regulatory mechanism for cellular homeostasis, maintains cellular functional balance by clearing damaged organelles and protein aggregates. This article provides a systematic review of the structural and functional aspects of the mTOR signaling pathway, the molecular regulatory mechanisms of autophagy, and their roles in retinal pathological changes. By summarizing current research findings, the article aims to clarify the key regulatory role of the mTOR-autophagy axis in DR, providing theoretical support for elucidating the molecular pathogenesis of DR and offering potential targets and research directions for developing novel targeted therapeutic strategies, thereby holding significant scientific and clinical value.

Diabetic retinopathy(DR)is one of the common causes of visual impairment and blindness in adults, which is caused by various pathogenesis. Although the mechanism of DR has not been elucidated yet, the destruction of blood-retinal barrier is a key process. As a highly endothelial-specific factor in promoting the growth of vascular endothelial cell, vascular endothelial growth factor(VEGF)plays a crucial role in the formation of pathological retinal neovascularization and the destruction of blood-retinal barrier. Therefore, a comprehensive understanding of the etiology and pathogenesis of blood-retinal barrier damage promoted by VEGF is critical for exploring the pathogenesis of DR. In this study, the underlying relationship between VEGF and the mechanism of blood-retinal barrier damage, including retinal vascular endothelial cell permeability, vascular inflammatory response, apoptosis, oxidative stress, mitochondrial damage and endoplasmic reticulum stress, with a view to providing a reference for the study in VEGF in the pathogenesis of blood-retinal barrier damage in DR.

Objective To discuss the clinical value of echocardiographic indicators in assessing the short-term efficacy of transcatheter aortic valve replacement(TAVR)and surgical aortic valve replacement(SAVR)in treating patients with severe aortic valve stenosis(AS).Methods The clinical data of 70 patients with severe AS,who received treatment at the Daping Hospital of Army Military Medical University of China between June 2019 and September 2022 were retrospectively analyzed.The patients were divided into SAVR group(n=40)and TAVR group(n=30).The preoperative one-week and postoperative one-month echocardiographic indicators were compared between the two groups.Results In both groups,the postoperative one-month peak aortic valve velocity(Vmax),aortic valve mean transvalvular pressure gradient(mPG),relative thickness of chamber wall(RWT),and left ventricular mass index(LVMI)were decreased when compared with preoperative values(all P＜0.05);in TAVR group the left ventricular ejection fraction(LVEF),LVMI and incidence of perivalvular leakage were remarkably higher than those in SAVR group,while the Vmax and mPG were obviously lower than those in SAVR group(all P＜0.05).In TAVR group,the mitral regurgitation decreased from preoperative 12 patients(40％)to postoperative 2 patients(6.7％)and the over-moderate tricuspid regurgitation decreased from preoperative 7 patients(23.3％)to postoperative one patient(3.3％)(all P＜0.05).In SAVR group,the mitral regurgitation decreased from preoperative 15 patients(37.5％)to postoperative 2 patients(5.0％)and the over-moderate tricuspid regurgitation decreased from preoperative 9 patients(22.5％)to postoperative one patient(2.5％)(all P＜0.05).The pulmonary artery hypertension in TAVR group decreased from preoperative 17 patients(56.7％)to postoperative 4 patients(13.3％),which in SAVR group decreased from preoperative 22 patients(55.0％)to postoperative 5 patients(12.5％)(P＜0.05),but the differences in the above indexes between the two groups were not statistically significant(all P＞0.05).Conclusion TAVR and SAVR have similar efficacy in improving secondary valve regurgitation and pulmonary artery hypertension caused by severe AS.TAVR is superior to SAVR in improving postoperative ventricular reverse remodeling and hemodynamics,although the incidence of paravalvular leakage in TAVR is higher than that in SAVR.(J Intervent Radiol,2024,33:479-482)

Objective To investigate the relationship between Notch1 and autophagy under high glucose conditions and to explore the effects of Notch1 inhibitor DAPT and autophagy inhibitor 3-MA on human retinal pigment epithelial cells cultured in high glucose conditions.Methods Via preliminary experiment,25 mmol·L-1 glucose was used as the high glucose culture medium of adult retinal pigment epithelial(ARPE)-19 cells,and 5 mmol·L-1 3-MA was adopted as the au-tophagy inhibitor.ARPE-19 cells cultured in vitro were randomly divided into four groups:control group(treated with 5 mmol·L-1 glucose for 48 h),high glucose group(treated with 25 mmol·L-1 glucose for 48 h),high glucose+DAPT group(treated with 40 μmol·L-1 DAPT for 2 h and then 25 mmol·L-1 glucose for 48 h),and high glucose+3-MA group(treated with 5 mmol·L-1 3-MA for 2 h and then 25 mmol·L-1 glucose for 48 h).A transmission electron microscope was used to observe the ultrastructure of cells in each group.Cell proliferation and migration were observed using Cell Counting Kit-8 and scratch assays.Western blot was used to detect the protein expression levels of Notch1 and autophagy-related proteins LC3 and Beclin1.Reverse transcription-polymerase chain reaction was used to measure the relative messenger ri-bonucleic acid(mRNA)expression levels of Notch1,LC3 and Beclin1 of cells in each group.Results Transmission elec-tron microscope showed that cells in the control group had normal structures,with round or oval nuclei and a few autopha-gosomes.In the high glucose group,cells exhibited slightly obvious injury,with uneven cytoplasm and numerous autolyso-somes.Compared to the control group,ARPE-19 cells in the high glucose group had increased proliferation and migration abilities,and higher mRNA and protein expression levels of Notch1,LC3 and Beclin1(all P＜0.05).Compared to the high glucose group,ARPE-19 cells in the high glucose+DAPT group showed decreased proliferation and migration abilities,and lower mRNA and protein expression levels of Notch1,LC3 and Beclin1(all P＜0.05).The high glucose+3-MA group showed reduced proliferation and migration abilities,as well as decreased mRNA and protein expression levels of LC3 and Beclin1(all P＜0.05)compared to the high glucose group.Conclusion High glucose can activate Notch1 and the auto-phagy process,promoting the proliferation of ARPE-19 cells.In the high glucose+DAPT group and high glucose+3-MA group,the autophagy process is inhibited to a certain extent,thereby restraining cell proliferation.

Objective To investigate if Lycium barbarum polysaccharide(LBP)could inhibit the high glucose-in-duced human retinal microvascular endothelial cell(HRMEC)injury by regulating the NOD-like receptor family pyrin do-main containing protein 3(NLRP3)/Caspase-1 pyroptosis pathway.Methods HRMECs cultured in vitro were randomly divided into the control group(5.5 mmol·L-1 glucose),the high glucose group(55.5 mmol·L-1 glucose),the low LBP group(55.5 mmol·L-1 glucose+100 mg·L-1 LBP),the medium LBP group(55.5 mmol·L-1 glucose+500 mg·L-1 LBP),the high LBP group(55.5 mmol·L-1 glucose+1 000 mg·L-1 LBP),the si-NC group(55.5 mmol·L-1glucose after transfection with 20 pmol·L-1 si-NC)and the si-NLRP3 group(55.5 mmol·L-1 glucose after transfection with 20μmol·L-1si-NLRP3).The Cell Counting Kit-8 was used to detect the proliferation of HRMECs in each group and flow cy-tometry was adopted to measure the pyroptosis of HRMECs in each group.The reverse transcription-polymerase chain reac-tion was used to detect the relative messenger ribonucleic acid(mRNA)expression levels of NLRP3,Caspase-1,nuclear factor(NF)-κB,Gasdermin-D(GSDMD)and vascular endothelial growth factor(VEGF)in the HRMECs of each group,Western blot was adopted to detect the relative protein expression levels of HRMEC pyroptosis-related NLRP3,Caspase-1,NF-κB,GSDMD and VEGF in each group,and enzyme-linked immunosorbent assay was used to detect the interleukin(IL)-1β and IL-18 expression levels in downstream pyroptosis in the HRMEC supernatant of each group.Results Com-pared with the control group,the proliferation rate of HRMECs decreased,the pyroptosis rate increased,the relative mR-NA and protein expression levels of NLRP3,Caspase-1,NF-κB,GSDMD and VEGF increased,and the expressions of IL-1βand IL-18 increased in the high glucose group(all P＜0.05).Compared with the high glucose group,the proliferation rate of HRMECs increased,the pyroptosis rate decreased,the relative mRNA and protein expression levels of NLRP3,Caspase-1,NF-κB,GSDMD and VEGF decreased,and the expressions of IL-1β and IL-18 decreased in the si-NLRP3 group(all P＜0.05).There were no significant differences in cell proliferation rate,pyroptosis rate,mRNA and protein expression levels of NLRP3,Caspase-1,NF-κB,GSDMD and VEGF,as well as levels of IL-1β and IL-18,in the si-NC group compared with the high glucose group(all P＞0.05).Compared with the high glucose group,the medium LBP group and high LBP group had increased proliferation rates,lower pyroptosis rates,and declined mRNA and protein expression levels of NLRP3,Caspase-1,NF-κB,GSDMD and VEGF as well as expressions of IL-1β and IL-18(all P＜0.05).Compared with the high glucose group,there was no significant difference in the proliferation rate of HRMECs and various protein expression levels in the low LBP group(all P＞0.05),and other indicators were consistent with those in the medium LBP group and high LBP group.Conclusion LBP has a protective effect on HRMEC injury induced by high glucose,can promote cell prolif-eration and inhibit pyroptosis,and its mechanism is related to inhibiting the activation of NLRP3/Caspase-1 signaling path-way and reducing the expression of related inflammatory factors.

Objective:To explore the relationship between the expression of long chain non coding ribonucleic acid (LncRNA) small nucleolar RNA host gene 1 (LncRNA SNHG1) and microRNA (miR)-143-3p in nasopharyngeal squamous cell carcinoma (HSCC) tissue and clinical pathological features and prognosis.Methods:A prospective selection was made from 97 HSCC patients admitted to the Handan Central Hospital from March 2016 to March 2018. Surgical resection of HSCC tissue and normal mucosa tissue adjacent to cancer were taken, and real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of LncRNA SNHG1 and miR-143-3p. The patient′s survival status was followed up after leaving the hospital. We compared the differences in the expression of LncRNA SNlHG1 and miR-143-3p in HSCC tissues with different clinical pathological parameters, analyzed the correlation between LncRNA SNHG1 and miR-143-3p expression, and the relationship between LncRNA SNHG1 and miR-143-3p expression and the prognosis of HSCC patients.Results:The expression of LncRNA SNHG1 in HSCC tissue was higher than that in normal mucosa tissue adjacent to cancer ( P<0.05), and the expression of miR-143-3p was lower than that in normal mucosa tissue adjacent to cancer ( P<0.05). The expression of LncRNA SNHG1 in cancer tissues of HSCC patients with tumor node metastasis (TNM) stage Ⅲ, low to medium differentiation, and lymph node metastasis was higher than that of HSCC patients with TNM stage Ⅰ-Ⅱ, high differentiation, and no lymph node metastasis (all P<0.05), and the expression of miR-143-3p was lower than that of HSCC patients with TNM stage Ⅰ-Ⅱ, high differentiation, and no lymph node metastasis (all P<0.05). The expression of LncRNA SNHG1 in HSCC tissues is negatively correlated with the expression of miR-143-3p ( r=-0.522, P<0.05). The 5-year cumulative survival rate of HSCC patients with high expression of LncRNA SNHG1 was lower than that of HSCC patients with low expression of LncRNA SNHG1 ( P<0.05), and the 5-year cumulative survival rate of HSCC patients with low expression of miR-143-3p was lower than that of HSCC patients with high expression of miR-143-3p ( P<0.05). Multivariate Cox regression analysis showed that TNM stage Ⅲ and high expression of LncRNA SNHG1 were risk factors for poor prognosis in HSCC patients (all P<0.05), while high expression of miR-143-3p was a protective factor ( P<0.05). Conclusions:The expression of LncRNA SNHG1 is upregulated and miR-143-3p is downregulated in HSCC tissues, with a negative correlation between the two, which is related to the malignant pathological characteristics and poor prognosis of HSCC.

Objective To observe the application effect of family-centered diversified extended services in treating retinopathy (ROP) of premature infants. Methods A total of 100 premature infants with ROP were selected and randomly divided into control group and observation group, with 50 cases in each group. The control group received routine nursing services, while the observation group received family-centered diversified extended services. The compliance of parents of infants, ocular parameters of infants, the 20-item Measure of Processes of Care (MPOC-20) score by parents and the Chinese version of Parenting Sense of Competence Scale (C-PSOC) score were compared between the two groups. Results The compliance of parents in the observation group was significantly better than that in the control group (P<0.05); one month after intervention, the decrease of intraocular pressure, the anterior chamber angle at 500 μm from the scleral spur (ACA500), central anterior chamber depth (CACD), and anterior chamber angle opening distance at 500 μm from the scleral spur (AOD500) in the observation group were significantly greater than those in the control group (P<0.05); after intervention, the MPOC-20 and C-PSOC scores of parents in the observation group were significantly higher than those in the control group (P<0.05). Conclusion Family-centered diversified extended services can improve the compliance of parents in participating in treatment and their satisfaction degree with nursing services, improve ocular conditions in ROP children, enhance parents′ sense of parenting competence, and have a positive effect on the prognostic recovery of ROP patients.

Objective:To explore the application value of biplane transrectal ultrasound (TRUS) combining superb microvascular imaging (SMI) in evaluating preoperative T stage of mid-low rectal cancer.Methods:From Jan 2021 to Apr 2022, 90 patients with middle and low rectal cancer undergoing surgical treatment in Da Ping Hospital, Army Medical Center of PLA were equally divided into trial group and control group . Patients in the control group received TRUS combining with color Doppler blood flow imaging (CDFI) mode, patients in the trial group received additional SMI . Preoperative ultrasound T staging was performed. Artery blood flow resistance index (RI), pulsation index (PI), peak systolic velocity (PSV), and end diastolic velocity (EDV) of tumors were measured and recorded. Receiver operating characteristics curves were drawn to evaluate the diagnostic efficacy.Results:The accuracy rate of the control group was 67% (30/45), and the consistence with the pathological stage (Kappa=0.510, P<0.05) was lower than that of 84% (38/45) and (Kappa=0.779, P<0.001) of the trial group ( χ2=3.850, P<0.05). Among different T stages, the difference of RI and PI were significant ( F=5.619, P=0.002; F=25.500, P<0.001), the difference of PSV was not significant ( F=1.464, P=0.231), and the difference of EDV was weakly correlated ( F=2.723, P=0.05). The ROC curves showed that the area under curve of RI, PI, EDV, and PSV was 0.573, 0.517, 0.527 and 0.501, respectively. With the diagnostic sensitivity rate for T1 to T4 as 70.4%, 58.8%, 93.3%, 68.8%, while the diagnostic specificity rate was 87.3%, 90.4%, 96.8%, 93.2%. Conclusion:Biplane TRUS combining SMI can improve the accuracy in preoperative ultrasound T staging of mid-low rectal cancer.

Periodontal bone regeneration is a major challenge in the treatment of periodontitis. Currently the main obstacle is the difficulty of restoring the regenerative vitality of periodontal osteoblast lineages suppressed by inflammation, via conventional treatment. CD301b⁺ macrophages were recently identified as a subpopulation that is characteristic of a regenerative environment, but their role in periodontal bone repair has not been reported. The current study indicates that CD301b⁺ macrophages may be a constituent component of periodontal bone repair, and that they are devoted to bone formation in the resolving phase of periodontitis. Transcriptome sequencing suggested that CD301b⁺ macrophages could positively regulate osteogenesis-related processes. In vitro, CD301b⁺ macrophages could be induced by interleukin 4 (IL-4) unless proinflammatory cytokines such as interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) were present. Mechanistically, CD301b⁺ macrophages promoted osteoblast differentiation via insulin-like growth factor 1 (IGF-1)/thymoma viral proto-oncogene 1 (Akt)/mammalian target of rapamycin (mTOR) signaling. An osteogenic inducible nano-capsule (OINC) consisting of a gold nanocage loaded with IL-4 as the "core" and mouse neutrophil membrane as the "shell" was designed. When injected into periodontal tissue, OINCs first absorbed proinflammatory cytokines in inflamed periodontal tissue, then released IL-4 controlled by far-red irradiation. These events collectively promoted CD301b⁺ macrophage enrichment, which further boosted periodontal bone regeneration. The current study highlights the osteoinductive role of CD301b⁺ macrophages, and suggests a CD301b⁺ macrophage-targeted induction strategy based on biomimetic nano-capsules for improved therapeutic efficacy, which may also provide a potential therapeutic target and strategy for other inflammatory bone diseases.
Animals ; Mice ; Bone Regeneration ; Cytokines/metabolism* ; Interleukin-4/therapeutic use* ; Macrophages/physiology* ; Mammals ; Osteogenesis ; Periodontitis/drug therapy*

OBJECTIVE To screen the optimal compatibility ratio of Gentiana straminea Maxim.(G.S Maxim) and Rhodiola crenulata (Hook. f. et Thoms.) H. Ohba(R. crenulata), and explore its anti-hypoxia effect and possible mechanism through in vivo and in vitro experiments and network pharmacology. METHODS PC12 cells were divided into groups, and the cell hypoxia model was established by Na2S2O4, H2O2 and physical hypoxia methods, and the compatibility ratio of G.S Maxim-R. crenulata was initially screened. Eighty SPF male Kunming mice were randomly divided into blank group, model group, positive group, and different compatibility ratio groups of G.S Maxim-R. crenulata(2:8, 3:7, 4:6, 5:5, 6:4, 7:3, 8:2), with 8 mice in each group. Gastric drug delivery in 15 d in advance, in addition to the blank group, the rest of the groups were normal pressure hypoxia experiments. Groups of mice survival time was recorded. Detected the levels of inflammatory cytokines, MDA content, and SOD activity in the lung tissues of mice in the blank group, model group, positive group, G.S Maxim-R. crenulata 4:6 group and 3:7 group. The anti-hypoxia mechanism of G.S Maxim-R. crenulata was investigated by network pharmacology and molecular docking, and verified by qPCR. RESULTS In vitro experiments showed that G.S Maxim-R. crenulata had better anti-hypoxia activity. In vivo experimental results showed that the combination ratio of G.S Maxim-R. crenulata with 4:6 and 3:7 could significantly improve the survival time of mice, reduce the contents of NF-κB, IL-6, IL-1β and MDA in lung tissue, and increase the content of IL-10 and SOD activity, and the effect of G.S Maxim-R. crenulata 3:7 group was the best. Network pharmacological studies showed that the potential active components of G.S Maxim-R. crenulata in anti-hypoxia might be ursolic acid, oleanolic acid, and ethyl gallate, etc. The core targets included SRC, PIK3CA, MAPK3, etc., and its anti-hypoxia signaling pathways mainly included PI3K-Akt, HIF-1, etc. The results of qPCR showed that G.S Maxim-R. crenulata could increase the expression of PI3K, Akt, mTOR and p62 in the lung tissue of hypoxic mice. Molecular docking verification showed that the core targets SRC, PIK3CA, and p62 had good binding activity with potential active components such as oleanolic acid, kaempferol, ethyl gallate and quercetin. CONCLUSION G.S Maxim-R. crenulata has anti-hypoxia activity, which may be related to PI3K/Akt signaling pathway through anti-inflammatory, anti-oxidative stress and regulation of autophagy.