The excessive accumulation of advanced glycosylation end products(AGEs), the end products of non-enzymatic glycosylation reactions, can be involved in the pathological processes of various ocular diseases through mechanisms such as oxidative stress, inflammatory responses and apoptosis. In this paper, we systematically reviewed the key role of AGEs in diabetic keratopathy, cataract, glaucoma, age-related macular degeneration(ARMD)and diabetic retinopathy(DR). It was found that AGEs activate signalling pathways such as NADPH oxidase, MAPK and NF-κB by binding to the receptor RAGE, leading to reactive oxygen species(ROS)generation, release of inflammatory factors, and vascular endothelial dysfunction, which in turn induces delayed corneal healing, cross-linking of lens proteins, optic nerve degeneration, formation of choroidal neovascularisation(CNV), and blood-retinal barrier(BRB)disruption. For example, in diabetic keratopathy, AGEs delay wound healing via the ROS/NLRP3 inflammatory vesicle axis; in cataract, ascorbic acid-mediated cross-linking of lens proteins due to AGEs directly impairs lens transparency; and in DR, AGEs exacerbate microvascular damage by regulating vasucular endothelial growth factor(VEGF)expression and pericyte apoptosis. In addition, this article discusses the advances and limitations of AGEs detection techniques, such as the potential application of lens AGEscan fluorescence assay in screening for diabetic complications, and the need to develop tissue-specific assays for aqueous humour and vitreous. For therapeutic strategies, the research directions of inhibiting AGEs production, blocking RAGE signalling pathway and developing anti-glycosylation drugs are proposed to emphasise their clinical value in delaying disease progression. This review not only integrates the molecular mechanisms and clinical associations of AGEs in ocular diseases, but also provides a theoretical basis for targeted interventions, which is of great significance in exploring novel diagnostic and therapeutic strategies.

Objective:To investigate the clinical application of internal mammary perforator (IMP) as recipient vessels in immediate breast reconstruction using deep inferior epigastric perforator (DIEP) flap.Methods:The clinical data of 10 patients with early breast cancer who underwent DIEP for immediate breast reconstruction using IMP as the recipient vessels from January 2022 to December 2023 were analyzed. The number, position, and diameter of IMP, diameter of DIEP, the size of the flap, the operation time, surgical complications, cosmetic effect of breast, and patients' satisfaction were summarized and analyzed.Results:The number of IMPs was 2-3, and they were distributed in the second to the fourth ribs. The diameter of the IMP artery was (1.15±0.22) mm, and the diameter of the vein was (1.35±0.19) mm. The diameter of the DIEP was (1.55±0.28) mm, and that of its accompanying vein was (1.50±0.23) mm. The sizes of the flaps ranged from 10.0 cm×8.0 cm×3.0 cm to 12.0 cm×22.0 cm×4.0 cm, with an average of 20.5 cm×11.2 cm×2.8 cm. The weight of the flap was (389.1±51.5) g. The operation time was (574.8±68.1) min. All 10 cases of flaps survived. The reconstructed breasts were natural, soft, and symmetrical to the healthy side breasts. There was no obvious operative complication. The average BREAST-Q score of the patients was 93.5. No recurrence or metastasis was found during follow-up.Conclusions:Although technically difficult, using IMP as recipient vessels in DIEP flats for immediate breast reconstruction results in a low complication rate of the injuries in the internal mammary region. Under the premise of strictly adhering to the surgical indications, satisfactory results can be achieved, and it is safe and reliable.

Objective:To investigate the effects and underlying mechanisms of Stat3 knockout in donor T cells on acute gastrointestinal graft-versus-host disease (GI-aGVHD) .Methods:BALB/c mice were exposed to lethal irradiation and transplanted with bone marrow and spleen cells from BALB/c mice (syngeneic control group), C57BL/6 mice (wild-type T cell group, WT group), or C57BL/6J-Stat3 em1cyagen mice (Stat3 gene knockout T cell group, Stat3-KO group) via tail vein injection to establish the aGVHD model. The survival rate, body weight changes, and clinical scores of mice were monitored. Cytometric bead array (CBA) was used to detect the concentrations of serum cytokines. Lymphocytes were isolated from tissues for flow cytometric analysis. H&E staining was performed to observe intestinal pathological changes. FITC-dextran assay was conducted to assess intestinal permeability. Immunohistochemistry was used to evaluate the expression of Ki67 and Muc2. Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) was employed to analyze the gene expression levels of Olfm4, Lysozyme, and Muc2 in the small intestine. Metabolomics was conducted to detect metabolites in serum and intestinal tissues. An in vitro GI-aGVHD organoid model was established by coculturing intestinal organoids with allogeneic T cells, where the number and area of small intestinal organoids were recorded. The GVL effect was assessed using luciferase-transfected ALL cells (ALL/Luc) and bioluminescent imaging. Results:Compared with the WT group, Stat3 knockout T cells alleviated body weight loss, reduced symptoms—such as hunchback and diarrhea—in mice, improved survival rate ( P<0.05), and reduced serum interleukin (IL) -2, IL-6, interferon-γ, tumor necrosis factor-α, IL-17A, and IL-10 levels (all P<0.05), intestinal inflammatory cell infiltration ( P<0.05), and intestinal mucosal permeability. Further, Muc2 and Ki67 expression levels in the small intestine of the Stat3 knockout group were markedly increased, and Olfm4, Lysozyme, and Muc2 gene expression levels were significantly increased (all P<0.05). In vitro, the Stat3 knockout group demonstrated better organoid development than the WT group. Metabolomic analyses indicated that Stat3 knockout in T cells may affect the pathways associated with bile acid secretion and unsaturated fatty acids. ALL/Luc cells in the GVL mouse model proliferated rapidly in the TCD-BM group; however, 80% of the mice in the Stat3-KO group survived tumor-free for >100 days ( P<0.05) . Conclusion:Knocking out Stat3 in graft T cells reduces T cell damage to intestinal stem cells, thereby ultimately alleviating GI-aGVHD while maintaining a stable GVL effect.

Objective To explore the clinical efficacy of Liuwei Dihuang Capsules for type 2 diabetes mellitus(T2DM)with yin deficiency syndrome and the effects on intestinal flora and inflammatory factors.Methods Totally 60 patients of T2DM with yin deficiency syndrome in Dongzhimen Hospital of Beijing University of Chinese Medicine from September 2022 to June 2023 were selected as the study objects,and were divided into control group and observation group according to the method of block randomization,with 30 cases in each group.Both groups received basic treatment.The control group was given a simulated agent of Liuwei Dihuang Capsules,while the observation group was given Liuwei Dihuang Capsules.The treatment course for both groups was 4 weeks.Clinical efficacy,blood glucose levels[fasting plasma glucose(FPG),2-hour postprandial plasma glucose(2 hPG),glycated albumin(GA)],serum insulin levels[fasting insulin(FINS)and insulin resistance index(HOMA-IR)],changes in gut microbiota,and serum inflammatory cytokine levels[interleukin(IL)-6,tumor necrosis factor(TNF)-α]of both groups were compared.Results The total effective rate of the observation group(76.67%)was better than that of the control group(50.00%)(P<0.05).Compared with before treatment,the FPG,2 hPG,GA,FINS and HOMA-IR decreased in the observation group,while the FPG,2 hPG and FINS decreased in the control group(P<0.05);after treatment,the Shannon index of the observation group increased after treatment(P<0.05),and the diversity of the microbiota increased;the abundance of the microbial communities such as Coprococcus 3,Cutibacterium,Pseudomonas,Faecalibaculum,Dubosiella and Mucispirillum significantly increased(P<0.05);the abundance of Sphingomonas,Corynebacterium 1,Ileibacterium,Ruminiclostridium and other microbiota communities significantly decreased(P<0.05).Compared with before treatment,the levels of IL-6 and TNF-α in both groups were significantly reduced after treatment(P<0.01,P<0.05).After treatment,the levels of IL-6 and TNF-α in the observation group were significantly lower than those in the control group(P<0.05).Conclusion Liuwei Dihuang Capsules can effectively reduce blood glucose levels in patients of T2DM with yin deficiency syndrome,improve insulin resistance,increase gut microbiota diversity,increase beneficial bacterial abundance,reduce harmful bacterial abundance,and alleviate inflammatory cytokine levels.

Objective:To investigate the clinical application of internal mammary perforator (IMP) as recipient vessels in immediate breast reconstruction using deep inferior epigastric perforator (DIEP) flap.Methods:The clinical data of 10 patients with early breast cancer who underwent DIEP for immediate breast reconstruction using IMP as the recipient vessels from January 2022 to December 2023 were analyzed. The number, position, and diameter of IMP, diameter of DIEP, the size of the flap, the operation time, surgical complications, cosmetic effect of breast, and patients' satisfaction were summarized and analyzed.Results:The number of IMPs was 2-3, and they were distributed in the second to the fourth ribs. The diameter of the IMP artery was (1.15±0.22) mm, and the diameter of the vein was (1.35±0.19) mm. The diameter of the DIEP was (1.55±0.28) mm, and that of its accompanying vein was (1.50±0.23) mm. The sizes of the flaps ranged from 10.0 cm×8.0 cm×3.0 cm to 12.0 cm×22.0 cm×4.0 cm, with an average of 20.5 cm×11.2 cm×2.8 cm. The weight of the flap was (389.1±51.5) g. The operation time was (574.8±68.1) min. All 10 cases of flaps survived. The reconstructed breasts were natural, soft, and symmetrical to the healthy side breasts. There was no obvious operative complication. The average BREAST-Q score of the patients was 93.5. No recurrence or metastasis was found during follow-up.Conclusions:Although technically difficult, using IMP as recipient vessels in DIEP flats for immediate breast reconstruction results in a low complication rate of the injuries in the internal mammary region. Under the premise of strictly adhering to the surgical indications, satisfactory results can be achieved, and it is safe and reliable.

Objective To explore the clinical efficacy of Liuwei Dihuang Capsules for type 2 diabetes mellitus(T2DM)with yin deficiency syndrome and the effects on intestinal flora and inflammatory factors.Methods Totally 60 patients of T2DM with yin deficiency syndrome in Dongzhimen Hospital of Beijing University of Chinese Medicine from September 2022 to June 2023 were selected as the study objects,and were divided into control group and observation group according to the method of block randomization,with 30 cases in each group.Both groups received basic treatment.The control group was given a simulated agent of Liuwei Dihuang Capsules,while the observation group was given Liuwei Dihuang Capsules.The treatment course for both groups was 4 weeks.Clinical efficacy,blood glucose levels[fasting plasma glucose(FPG),2-hour postprandial plasma glucose(2 hPG),glycated albumin(GA)],serum insulin levels[fasting insulin(FINS)and insulin resistance index(HOMA-IR)],changes in gut microbiota,and serum inflammatory cytokine levels[interleukin(IL)-6,tumor necrosis factor(TNF)-α]of both groups were compared.Results The total effective rate of the observation group(76.67%)was better than that of the control group(50.00%)(P<0.05).Compared with before treatment,the FPG,2 hPG,GA,FINS and HOMA-IR decreased in the observation group,while the FPG,2 hPG and FINS decreased in the control group(P<0.05);after treatment,the Shannon index of the observation group increased after treatment(P<0.05),and the diversity of the microbiota increased;the abundance of the microbial communities such as Coprococcus 3,Cutibacterium,Pseudomonas,Faecalibaculum,Dubosiella and Mucispirillum significantly increased(P<0.05);the abundance of Sphingomonas,Corynebacterium 1,Ileibacterium,Ruminiclostridium and other microbiota communities significantly decreased(P<0.05).Compared with before treatment,the levels of IL-6 and TNF-α in both groups were significantly reduced after treatment(P<0.01,P<0.05).After treatment,the levels of IL-6 and TNF-α in the observation group were significantly lower than those in the control group(P<0.05).Conclusion Liuwei Dihuang Capsules can effectively reduce blood glucose levels in patients of T2DM with yin deficiency syndrome,improve insulin resistance,increase gut microbiota diversity,increase beneficial bacterial abundance,reduce harmful bacterial abundance,and alleviate inflammatory cytokine levels.

Objective:To investigate the effects and underlying mechanisms of Stat3 knockout in donor T cells on acute gastrointestinal graft-versus-host disease (GI-aGVHD) .Methods:BALB/c mice were exposed to lethal irradiation and transplanted with bone marrow and spleen cells from BALB/c mice (syngeneic control group), C57BL/6 mice (wild-type T cell group, WT group), or C57BL/6J-Stat3 em1cyagen mice (Stat3 gene knockout T cell group, Stat3-KO group) via tail vein injection to establish the aGVHD model. The survival rate, body weight changes, and clinical scores of mice were monitored. Cytometric bead array (CBA) was used to detect the concentrations of serum cytokines. Lymphocytes were isolated from tissues for flow cytometric analysis. H&E staining was performed to observe intestinal pathological changes. FITC-dextran assay was conducted to assess intestinal permeability. Immunohistochemistry was used to evaluate the expression of Ki67 and Muc2. Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) was employed to analyze the gene expression levels of Olfm4, Lysozyme, and Muc2 in the small intestine. Metabolomics was conducted to detect metabolites in serum and intestinal tissues. An in vitro GI-aGVHD organoid model was established by coculturing intestinal organoids with allogeneic T cells, where the number and area of small intestinal organoids were recorded. The GVL effect was assessed using luciferase-transfected ALL cells (ALL/Luc) and bioluminescent imaging. Results:Compared with the WT group, Stat3 knockout T cells alleviated body weight loss, reduced symptoms—such as hunchback and diarrhea—in mice, improved survival rate ( P<0.05), and reduced serum interleukin (IL) -2, IL-6, interferon-γ, tumor necrosis factor-α, IL-17A, and IL-10 levels (all P<0.05), intestinal inflammatory cell infiltration ( P<0.05), and intestinal mucosal permeability. Further, Muc2 and Ki67 expression levels in the small intestine of the Stat3 knockout group were markedly increased, and Olfm4, Lysozyme, and Muc2 gene expression levels were significantly increased (all P<0.05). In vitro, the Stat3 knockout group demonstrated better organoid development than the WT group. Metabolomic analyses indicated that Stat3 knockout in T cells may affect the pathways associated with bile acid secretion and unsaturated fatty acids. ALL/Luc cells in the GVL mouse model proliferated rapidly in the TCD-BM group; however, 80% of the mice in the Stat3-KO group survived tumor-free for >100 days ( P<0.05) . Conclusion:Knocking out Stat3 in graft T cells reduces T cell damage to intestinal stem cells, thereby ultimately alleviating GI-aGVHD while maintaining a stable GVL effect.

Objective To preliminarily investigate the anti-tumor effects of phytosphingosine(PHS)and the involvement of inducing apoptosis of leukemia cells.Methods Cellular model of leukemia was established in leukemia cell lines K562 and SUP-B15.CCK-8 assay and EdU assay were used to measure the viability and DNA synthesis of K562 and SUP-B15 cells.RNA-seq was carried out to verify the differentially expressed genes(DEGs)after PHS treatment.Gene Ontology(GO)enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were applied to analyze the involved functions and signaling pathways.Comparative Toxicogenomics Database(CTD)and Discovery Studio software were employed to predict the underlying targets of PHS and molecular docking.Cell apoptosis was detected by flow cytometry,mitochondrial membrane potential was evaluated by JC-1 probe,and protein expression of key molecules was validated by Western blotting.Results PHS inhibited the proliferation of K562 and SUP-B15 cells in a time-and dose-dependent manner.The half-maximal inhibitory concentration(IC50)of K562 cells was 17.67 and 12.52 pmol/L for 24 and 48 h,respectively,and the IC50 value of SUP-B15 cells was 17.58 and 14.86 μmol/L for 24 and 48 h,respectively.PHS treatment at a dose of 20 μmol/L for 48 h resulted in significant inhibition of DNA synthesis.GO enrichment analysis of the K562 cells showed that PHS might be involved in positive regulation of apoptotic process,plasma membrane and its integral components,and protein kinase binding and activity.Reverse predictive analysis showed that BCL-2 protein was the most likely target of PHS.PHS significantly increased the apoptotic rate of leukemia cells(P＜0.05)in a dose-dependent manner,reduced the mitochondrial membrane potential,and down-regulated BCL-2 level(P＜0.05)and up-regulated the levels of Cleaved caspase-3 and Cleaved caspase-9(P＜0.05).Conclusion PHS may inhibit the proliferation of leukemia cells by inducing mitochondria-dependent apoptosis,possibly through PHS and BCL-2 interaction.

bjective　To analyze the drug resistance screening status and drug resistance influencing factors of high-risk groups of drug-resistant pulmonary tuberculosis in Qingdao, and to understand the inclusion of rifampicin patients in treatment, so as to provide a reference for the prevention and treatment of drug-resistant pulmonary tuberculosis. Methods　The medical records of 726 cases of drug-resistant pulmonary tuberculosis among high-risk populations registered in Qingdao from 2018 to 2022 were obtained from the National Health Insurance Information System of the China Center for Disease Control and Prevention. The drug resistance to five anti-tuberculosis drugs, namely isoniazid (INH), rifampicin (RFP), ethambutol (EMB), levofloxacin (Lfx), and amikacin (Am), in the high-risk populations of drug-resistant pulmonary tuberculosis was analyzed. Univariate and multivariate logistic regression were used toidentify factors influencing rifampicin resistance, and the detection and inclusion of treatment for rifampicin-resistant patients were evaluated. Results　Of the 726 subjects, 278 were drug-resistant, with a total drug resistance rate of 38.29%. The drug resistance for the five anti-tuberculosis drugs in descending order was: INH 25.90%(188/726), RFP 22.87%(166/726), Lfx 14.19%(103/726), EMB 11.29%(82/726), Am 2.48%(18/726). Analysis of the drug resistance spectrum showed that among those resistant to one drug, RFP was most common, accounting for 13.67% (38/278); among those resistant to two drugs, INH+RFP was predominant, accounting for 15.83% (44/278); among those resistant to three drugs, INH+RFP+Lfx was most frequent, at 7.19% (22/278); and among those resistant to four drugs, INH+RFP+EMB+Lfx was highest, at 6.12% (17/278). Multivariate logistic regression analysis of rifampicin resistance showed that compared with patients under 25 years of age, the risk of developing rifampicin resistance was lower in the groups aged 45 to under 65 and those aged 65 and above (OR=0.356, 95%CI: 0.181-0.700; OR=0.352, 95%CI: 0.170-0.729). Compared with migrant patients in other provinces, local patients from within the same county or district had a lower risk of developing rifampicin resistance (OR=0.599, 95%CI:0.383-0.962). Compared with patients who were smear-positive at the end of the second month of initial treatment, the risk of developing rifampicin resistance was higher in patients with relapse/return, failure of retreatment/chronic, and other categories of patients (OR=9.380, 95%CI:3.717-23.671;OR=25.749, 95%CI:8.037-82.490; OR=36.651, 95%CI:8.438-159.201). Conclusions　The situation of drug-resistant pulmonary tuberculosis in Qingdao cannot be ignored. Individuals under 25 years old, migrants from other provinces, and patients with relapse/return, failure of retreatment/chronic, and other categories are significant risk factors for developing rifampicin resistance in the high-risk groups of drug-resistant pulmonary tuberculosis.

Objective To investigate the effects of Gli2 on the proliferation,growth,migration,and invasion of oral cancer cells(Tca8113)at the cellular level,and to clarify the molecular mechanism of how Gli2 regulation affects the migration and invasion of oral cancer cells.Methods Small interfering(si)RNA was used to inhibit Gli2 expression in Tca8113 cells.The effects of Gli2 on the proliferation,growth,migration,and invasion of Tca8113 cells were examined by CCK-8,platb cloning,and transwell chamber assay.Further qRT-PCR and Western blot assays were used to explore the mechanism of how Gli2 regulation effects the malignant proliferation and metastasis of Tca8113 cells.Results The mRNA and protein expression of Gli2 in oral cancer cells(Tca8113)increased.Interference of Gli2 expression inhibited the proliferation,growth,migration,and invasion of Tca8113 cells.Further experiments showed that interfering with Gli2 expression inhibited the mRNA and protein expression of key factors in the Hedgehog(Hh)pathway.In addition,interference of Gli2 expression significantly affected the mRNA and protein expression of key factors in epithelial mesenchymal transformation(EMT)pathways.Conclusions Gli2 is abnormally activated during oral cancer,and interference of Gli2 expression significantly inhibits the proliferation,growth,migration,and invasion of oral cancer cells.Gli2 influences the migration and invasion of oral cancer cells by regulating the Hh and EMT pathways.This study has provided a new way to elucidate the pathogenesis of oral cancer and new perspectives on the clinical treatment of oral cancer.