AIM: To investigate the relationship between microvascular density in macular area and anti-vascular endothelial growth factor(VEGF)response in patients with diabetic macular edema(DME). METHODS: Retrospective case-control study. Clinical data of DME patients who received anti-VEGF treatment in the hospital from January 2021 to August 2025 were collected. All patients received intravitreal anti-VEGF treatment once a month for a total of 3 times. The patients were divided into the good response group and the poor response group based on the anti-VEGF treatment response. The vascular density of superficial capillary plexus(SCP)and deep capillary plexus(DCP)were compared between the two groups before treatment. Multivariate logistic regression models were used to analyze the factors affecting the anti-VEGF treatment response in DME patients. The receiver operating characteristic(ROC)curve was drawn to analyze the predictive value of SCP and DCP vascular density for anti-VEGF treatment response in DME patients. RESULTS: The study included a total of 315 DME patients 315 eyes, including 172 males and 143 females with the mean age of 62.06±7.38 y. After completing three treatments, there were 211 cases 211 eyes in the good response group, including 114 males and 97 females with the mean age of 61.92±7.52 y. There were 104 cases in the poor response group, including 58 males and 46 females with the mean age of 62.35±7.10 y. The course of diabetes in the poor response group was longer than that in the good response group, the central retinal thickness before treatment was greater than that in the good response group, the level of glycosylated hemoglobin(HbA1c)before treatment was higher than that in the good response group, and the proportion of patients with serous retinal detachment was higher than that in the good response group. Before treatment, the vascular density of SCP and DCP in the poor response group was lower than that in the good response group(all P<0.01). Multivariate Logistic regression analysis showed that SCP and DCP vascular density were both influencing factors of anti-VEGF treatment response in DME patients(both P<0.05). ROC curves showed that the area under the curve(AUC)of the pre-treatment SCP vascular density, pre-treatment DCP vascular density alone, and their combined model for predicting poor response to anti-VEGF therapy in DME patients were 0.812, 0.797 and 0.901, respectively, indicating high predictive value.CONCLUSION: The microvascular density in the macular area is closely related to the anti-VEGF treatment response in DME patients. The vascular density of SCP and DCP before treatment can be used as important indicators to predict treatment response, and targeted preventive and therapeutic interventions can be adopted in clinical practice.

Obesity is a significant risk factor for cancer and is associated with breast cancer metastasis. Nevertheless, the mechanism by which alterations in systemic metabolism affect tumor microenvironment (TME) and consequently influence tumor metastasis remains inadequately understood. Herein, we found that perturbations in circulating metabolites induced by obesity promote metastasis-like phenotypes in breast cancer. Oleoylcarnitine (OLCarn) concentrations were elevated in the serum of obese mice and humans. Administration of exogenous OLCarn induces metastasis-like characteristics in breast cancer cells. Mechanistically, OLCarn directly interacts with the Arg176 site of adenylate cyclase 10 (ADCY10), leading to the activation of ADCY10 and enhancement of cAMP production. Mutations at Arg176 prevent OLCarn from binding to ADCY10, disrupting the ADCY10-mediated activation of cyclic adenosine monophosphate (cAMP) signaling pathway. This activation promotes transcription factor 4 (TCF4)-dependent kinesin family member C1 (KIFC1) transcription, thereby driving breast cancer metastasis. Conversely, the neutralization of both ADCY10 and KIFC1 through knockdown or pharmacological inhibition abrogates the oncogenic effects mediated by OLCarn. Hence, obesity-induced systemic environmental changes lead to the aberrant accumulation of OLCarn within the TME, making it a potential therapeutic target and biomarker for breast cancer.

Ovarian cancer poses a significant threat to women's health, necessitating effective therapeutic strategies. Emd-D, an emodin derivative, demonstrates enhanced pharmaceutical properties and bioavailability. In this study, Cell Counting Kit 8 (CCK8) assays and Ki-67 staining revealed dose-dependent inhibition of cell proliferation by Emd-D. Migration and invasion experiments confirmed its inhibitory effects on OVHM cells, while flow cytometry analysis demonstrated Emd-D-induced apoptosis. Mechanistic investigations elucidated that Emd-D functions as an inhibitor by directly binding to the glycolysis-related enzyme PFKFB4. This was corroborated by alterations in intracellular lactate and pyruvate levels, as well as glucose transporter 1 (GLUT1) and hexokinase 2 (HK2) expression. PFKFB4 overexpression experiments further supported the dependence of Emd-D on PFKFB4-mediated glycolysis and SRC3/mTORC1 pathway-associated apoptosis. In vivo experiments exhibited reduced xenograft tumor sizes upon Emd-D treatment, accompanied by suppressed glycolysis and increased expression of Bax/Bcl-2 apoptotic proteins within the tumors. In conclusion, our findings demonstrate Emd-D's potential as an anti-ovarian cancer agent through inhibition of the PFKFB4-dependent glycolysis pathway and induction of apoptosis. These results provide a foundation for further exploration of Emd-D as a promising drug candidate for ovarian cancer treatment.
Female ; Humans ; Ovarian Neoplasms/physiopathology* ; Phosphofructokinase-2/genetics* ; Apoptosis/drug effects* ; Glycolysis/drug effects* ; Animals ; Cell Line, Tumor ; Mice ; Cell Proliferation/drug effects* ; Emodin/administration & dosage* ; Mice, Nude ; Mice, Inbred BALB C ; Hexokinase/metabolism* ; Xenograft Model Antitumor Assays

ObjectiveTo analyze the evolutionary characteristics and genetic variations of the HA (hemagglutinin) and NA (neuraminidase) genes of influenza A(H1N1) viruses in Shanghai during 2024, to investigate their transmission patterns, and to evaluate their potential impact on vaccine effectiveness. MethodsFrom January to October 2024, throat swab specimens were collected from influenza like illness (ILI) patients at 4 hospitals in Shanghai. Real-time fluorescence ploymerase chain reaction (RT-PCR) was used for virus detection and isolation of H1N1 influenza viruses. Forty influenza A(H1N1) virus strains were sequenced using Illumina NovaSeq 6000 platform, followed by phylogenetic analyses, genetic distance analysis, and amino acid variation analyses of HA and NA genes. ResultsPhylogenetic tree of the HA and NA genes revealed that the 40 influenza A(H1N1) virus strains circulating in Shanghai in 2024 exhibited no significant geographic clustering, with a broad origin of strains and complex transmission chains. Genetic distance analyses demonstrated that the average intra-group genetic distances of HA and NA genes among the Shanghai strains were 0.005 1±0.000 6 and 0.004 6±0.000 6, respectively, which were comparable to or higher than those observed in global surveillance strains. Both HA and NA genes displayed frequent mutations. Compared to the 2023‒2024 and 2024‒2025 Northern Hemisphere A(H1N1) vaccine strains (WHO-recommended), the HA proteins of 40 Shanghai strains exhibited amino acid substitutions at positions 120, 137, 142, 169, 216, 223, 260, 277, 356 and 451, with critical mutations at positions 137 and 142 located within the Ca2 antigenic determinant. Furthermore, mutations in the NA protein were observed at positions 13, 50, 200, 257, 264, 339 and 382. ConclusionThe genetic background of the 2024 Shanghai influenza A(H1N1) virus strains is complex and diverse, and antigenic variation may affect vaccine effectiveness. Therefore, it is recommended to enhance genomic surveillance of influenza viruses, evaluate vaccine suitability, and implement more targeted prevention and control strategies against imported influenza viruses.

Compared to traditional suturing, lung stapling using automatic staplers offers advantages such as smaller trauma, faster wound healing, ease of operation, and lower complication rates, making it widely used in clinical practice. However, there are significant differences in bronchial tissue thickness at different anatomical locations, and the market is flooded with various types of staplers. Currently, there is a lack of recommended stapling schemes for bronchial staplers at different anatomical locations. This article reviews the development and application of automatic staplers and summarizes some types of staplers that are currently used in clinical practice, with the aim of promoting the formation of individualized stapler selection protocols for minimally invasive thoracic surgery based on the Chinese population.

Objective To investigate the correlation between self-injurious and suicidal behavior in adolescents with depressive disorder and their non-enzymatic antioxidants and thyroid hormones.Methods A total of 93 adolescent patients with depressive disorder who were hospitalized at the Qingdao Mental Health Center from August 2023 to May 2024 were selected as the research subjects.The patients were divided into three groups:depression group(n=33),self-injurious behavior group(n=30)and a suicidal behavior.Plasma levels of non-enzymatic antioxidants and thyroid hormones were measured at admission and after 8 weeks of treatment,and their clinical symptoms were assessed by the Hamilton depression scale(HAMD)and the Hamilton anxiety scale(HAMA).Differences in plasma non-enzymatic antioxidants and thyroid function levels and scale scores were compared among three groups.Results Compared with depression group,baseline UA levels were lower in self-injurious and suicidal behavior groups.After 8 weeks of treatment,FT3 levels were higher in self-injurious group than in the suicidal behavior group,and both HAMD and HAMA scores decreased in all patients.After correction,HAMA scores were higher in suicidal behavior group than in depression group(P=0.047).Compared to baseline levels,TSH levels increased,and HAMD and HAMA scores decreased in all groups after treatment(P＜0.001).In suicidal behavior group,TBIL and FT3 levels decreased,and UA levels increased after treatment,while in depression group,FT4 levels decreased after treatment.Conclusion Non-enzymatic antioxidants may serve as potential biological markers for adolescents with depressive disorder who exhibit self-injurious and suicidal behavior.

Objective To explore the mechanism of Tongluo Baoshen Decoction in improving podocyte injury in rats with IgA nephropathy based on Gprc5b/NF-κB/NLRP3 pathway.Methods Totally 130 SPF-grade male SD rats were randomly divided into a normal group(n=20)and a modeling group(n=110).The IgA nephropathy model was established using a compound modeling method,and 100 modeling rats were randomly divided into model group,losartan potassium group(5 mg/kg),and Tongluo Baoshen Decoction low-,medium-,and high-dosage groups(5.3,10.6,21.2 g/kg),with 20 rats in each group.The administration group was given the corresponding dosage of medication by gavage,while the normal group and model group were given an equal amount of distilled water by gavage once a day.After 4 and 8 weeks of administration,urine samples were collected for 24 hours,and blood and kidney tissue specimens were collected.24-hour urinary protein quantification(24 h-UTP),urinary Nephrin,serum creatinine(SCr),blood urea nitrogen(BUN)and blood uric acid(BUA)contents were detected;RT-qPCR and Western blot were used to detect the expressions of G protein coupled receptor C-family 5b(Gprc5b),nuclear factor(NF)-κB p50,NOD like receptor protein 3(NLRP3),Caspase-1,interleukin(IL)-1β,Nephrin mRNA and protein in renal tissue,respectively;HE,PAS,PASM,Masson staining were used to observe the morphology of renal tissue,immunofluorescence was used to observe IgA deposition in the mesangial area of renal tissue,and transmission electron microscopy was used to observe the ultrastructure of podocytes.Results Compared with the normal group,the model group rats showed significantly increased contents of 24 h-UTP,urinary Nephrin and BUA(P<0.01),the mRNA and protein expressions of Gprc5b,NF-κB p50,NLRP3,Caspase-1 and IL-1β in renal tissue were significantly increased(P<0.01),while the mRNA and protein expressions of Nephrin were significantly decreased(P<0.01),with mild to moderate proliferation of mesangial cells in the glomerulus,increased mesangial matrix,and immunofluorescence showed clustered and linear deposition of IgA in the mesangial area,electron microscopy showed partial fusion of the foot processes.Compared with the model group,the 24 h-UTP and urinary Nephrin contents in different dosage groups of Tongluo Baoshen Decoction and the losartan potassium group after 4 and 8 weeks administration significantly decreased(P<0.01),with a decrease in BUA content in Tongluo Baoshen Decoction high-dosage group(P<0.05),the mRNA and protein expressions of Gprc5b,NF-κB p50,NLRP3,Caspase-1 and IL-1β in renal tissue of Tongluo Baoshen Decoction groups and losartan potassium group decreased(P<0.05,P<0.01),while the mRNA and protein expressions of Nephrin increased(P<0.05,P<0.01),with the proliferation of mesangial cells,the increase of mesangial matrix,the deposition of IgA in the mesangial area,and the fusion of foot processes in renal tissue were alleviated to varying degrees in different dosage groups of Tongluo Baoshen Decoction,with the most significant improvement observed in the high-dosage group.Compared with the 4-week administration,Tongluo Baoshen Decoction high-dose group showed further reductions in 24 h-UTP and urinary Nephrin contents after 8 weeks of administration(P<0.01),further decreases in the mRNA and protein expressions of Gprc5b,NF-κB p50,NLRP3,Caspase-1 and IL-1β in renal tissue(P<0.05,P<0.01),and further increases in the mRNA and protein expressions of Nephrin(P<0.01).Conclusion Tongluo Baoshen Decoction can reduce proteinuria,alleviate renal tissue lesions and improve podocyte injury in IgA nephropathy rats,and its mechanism may be related to the inhibition of Gprc5b/NF-κB/NLRP3 pathway in renal tissue.

ObjectiveTo investigate the inhibitory effects and mechanisms of Xiayuxue Tang （XYXT） on hepatocellular carcinoma cells through the regulation of succinate metabolism and succinylation modification. MethodsXYXT-medicated serum was prepared. The effects of different concentrations of succinate on the proliferation of HepG2 and MHCC97H cells were observed using the cell counting kit-8 （CCK-8） assay， and the experimental concentrations for subsequent tests were determined. Further CCK-8 assays were performed to evaluate the effects of XYXT-medicated serum of different concentrations （5%， 10%， and 15%） on cell proliferation. Flow cytometry， scratch test， and Transwell assay were employed to analyze the effect of 10% XYXT-medicated serum on the cell cycle， migration， invasion， and apoptosis. The changes in succinate metabolism and succinylation modification were examined based on succinate content assays， succinate dehydrogenase （SDH） activity detection， and western blot. The expressions of Yes-associated protein 1 （YAP1） and sirtuin 5 （SIRT5） were detected via Real-time PCR and western blot. Molecular docking was applied to validate the binding between XYXT’s main components and target proteins. ResultsCompared with the control group， 1-2 mmol·L^-¹ succinate significantly promoted HepG2 and MHCC97H cell proliferation （P<0.01）. XYXT-medicated serum （5%， 10%， and 15%） markedly inhibited the proliferation of both cell lines compared with the blank group （P<0.05， P<0.01）. Treatment with 10% XYXT-medicated serum arrested the cell cycle at the stage prior to DNA synthesis （G₀/G₁） （P<0.01）， suppressed migration （P<0.01） and invasion （P<0.05， P<0.01）， and promoted apoptosis of HepG2 and MHCC97H cells （P<0.01）. Co-treatment with XYXT and succinate reversed the inhibitory effects of XYXT on proliferation， migration， and invasion of HepG2 and MHCC97H cells （P<0.05， P<0.01）. The proportion of cells at G₀/G₁ phase decreased （P<0.01）， and the apoptosis rate decreased （P<0.01）. In terms of succinate metabolism， compared with the blank serum group， the 10% XYXT-medicated serum reduced succinate levels of HepG2 and MHCC97H cells （P<0.05， P<0.01）， enhanced SDH activity （P<0.01）， and downregulated succinylation modification. In terms of YAP1/SIRT5 pathway， compared with the blank serum group， the 10% XYXT-medicated serum significantly downregulated the mRNA and protein expressions of YAP1 in HepG2 and MHCC97H cells （P<0.05， P<0.01） while significantly upregulated the mRNA and protein expressions of SIRT5 （P<0.05， P<0.01）. Molecular docking confirmed that there was a good binding ability between YAP1 and SIRT5， as well as between XYXT's main active components and YAP1 and SIRT5. ConclusionXYXT suppresses hepatocellular carcinoma cells by modulating the YAP1/SIRT5 signaling axis to intervene in succinate metabolism and succinylation modification.

Objective:To investigate the role of the nuclear factor-kappa B (NF-κB) /nuclear factor E2 related factor 2 (Nrf2) pathway in the occurrence of lung tissue in the pulmonary alveolar proteinosis (PAP) model of rats induced by indium tin oxide nanoprticles (Nano-ITO) .Methods:In October 2019, 120 SD rats were divided into 3, 7, 14, 28, 56, and 84 day Nano ITO exposure groups and corresponding time point control groups, with 10 rats in each group; the exposure group was treated with 6 mg/kg·bw Nano-ITO via non exposed tracheal injection, twice a week. Time-course studies were performed to examine the pulmonary toxicity induced by Nano-ITO. At the end of the experiment, cytokines levels and oxidative stress were analyzed in the bronchoalveolar lavaged fluid (BALF). Rat lung tissues were also harvested for staining with HE, PAS, Masson, and Oil Red O. Ultrastructure of lung tissue cells was observed by transmission electron microscope. The localization and expression of NF-κB p65, IκB-α, IKK-β, Nrf2, NQO1, HO-1 were observed by immunohistochemistry, Western blot and real-time fluorescent quantitative PCR. The comparison between the two groups was analyzed by independent sample T test, and the comparison between the multiple groups was analyzed by one-way ANOVA.Results:Nano-ITO intratracheal instillation caused pulmonary toxicity by inducing acute inflammation, granuloma (nodule) formation, and alveolar proteinosis. ELISA analysis showed that, compared with the corresponding time points control groups, the levels of superoxide dismutase (SOD), total antioxidant capacity (T-AOC), malondialdehyde (MDA), interleukin (IL) -1β, IL-6, tumor necrosis factor alpha (TNF-α), IL-10, total protein (TP), and lactate dehydrogenase (LDH) in BALF of rats exposed to Nano ITO were all increased ( P<0.05) ; The protein expression of Nrf2 and NF-κB p65 was upregulated in rat lung tissue, while the protein expression of KK-β was increased ( P<0.01). Nrf2 and its downstream proteins NQO1 and HO-1 were highly expressed in Nano-ITO-induced PAP rat. Conclusion:NF-κB/Nrf2 signal pathway is involved in the process of Nano-ITO induced pulmonary alveolar proteinosis in rats.

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.