AIM: To understand the publication status, research trends, and cutting-edge and hot topics in this field by conducting a bibliometrics analysis of relevant literatures on the pathogenesis of primary open angle glaucoma(POAG)in the past 30 a.METHODS:A total of 986 relevant literatures on the pathogenesis of POAG published on the core databases of China National Knowledge Infrastructure(CNKI)and Web of Science(WOS)from 1 September 1993 to 1 September 2023 were retrieved. CiteSpace(6.2.R.4)and VOSviewer(1.6.18)software were used to conduct knowledge graph analysis on the retrieved literature, including publication volume, author, research institution, country/region, and keywords.RESULTS:The United States(243 articles)has the highest number of publications, followed by China(121 articles). The foreign institution with the highest number of publications is Harvard University(37 articles), while domestic institutions such as Zhongshan Ophthalmic Center, Sun Yat-sen University, ophthalmology department of Xuanwu Hospital of Capital Medical University, and Peking University First Hospital tied for the highest number of publications. Louis R. Pasquale(21 articles)is the most prolific English author. Wang Ningli is the most active Chinese researcher in this field. Keywords include trabecular meshwork, intraocular pressure, aqueous humor, glucocorticoid, hemorheology, etc.CONCLUSION: The research on the pathogenesis of POAG is in a period of vigorous development. The United States has the largest number of publications in this field, and Harvard University is a leading institution in this field. The research focus in the field of POAG has shifted from the structural aspect to the genetic level, and gene research and traditional Chinese medicine treatment have broad application prospects in this field.

This study utilized the CCK-8 assay to examine the effects of various concentrations of CoCl2(0,50,100,200,300,400 μmol/L)and different treatment durations(0,6,12,24,48 h)on the viability of adipocytes,in order to determine the most suitable treatment conditions.Western blot analysis was employed to investigate the impact of different concentrations of CoCl2(0,50,100,200,400 μmol/L)on the expression of hypoxia and its downstream key proteins in adipocytes.The results indicated that higher concentrations of CoCl2 led to lower adipocyte viability,with sig-nificant decreases in cell viability observed in the 300,400 μmol/L treatment groups(P＜0.01),while the 200 μmol/L group exhibited the highest cell viability.Compared to the control group,the 200 μmol/L CoCl2 treatment group showed a significant upregulation in the expression of hypoxia and its downstream signaling pathway key molecules:hypoxia-inducible factor 1-alpha(HIF-1α),glucose transporter type 4(GLUT4),vascular endothelial growth factor receptor 1(FLT-1),prolyl hydroxylase 2(PHD2),and vascular endothelial growth factor(VEGF)(P＜0.01).Addi-tionally,the 200 μmol/L CoCl2 treatment group exhibited higher levels of key lipolytic enzymes,including adipose triglyceride lipase(ATGL),perilipin 1(PLIN1),protein kinase A(PKA),and increased phosphorylation levels of hormone-sensitive lipase(HSL)in the 300 and 400 μmol/L groui ps(P＜0.01).CoCl2-mediated hypoxia in the 200 μmol/L treatment group also in-creased the protein expression of phosphatidylinositol 3-kinase(PI3K)and the phosphorylation level of protein kinase B(Akt).These findings suggest that adding 200 μmol/L CoCl2 can enhance the expression of hypoxia-related proteins,lipolytic enzymes,and insulin-related signaling proteins in primary bovine adipocytes.

Objective:To analyze the genes related to platelet activation in essential thrombocythemia (ET)based on transcriptome sequencing technology (RNA-seq ),and to explore the potential targets related to ET thrombosis. Methods:Blood samples from ET patients and healthy individuals were collected for RNA-seq,and differentially expressed lncRNAs,miRNAs,and mRNAs were selected to construct a lncRNA-miRNA-mRNA regulatory network. Differential mRNAs in the regulatory network were enriched and analyzed using Gene Ontology (GO ) and Kyoto Encyclopedia of Genes and Genomes (KEGG).The real-time PCR method was applied to validate differential mRNAs on crucial signaling pathways.Results:A total of 32 lncRNAs (3 up-regulated,29 down-regulated),16 miRNAs (8 up-regulated,8 down-regulated),and 35 mRNAs (27 up-regulated,8 down-regulated)were identified as differentially expressed.Among them,5 lncRNAs,12 miRNAs,and 19 mRNAs constituted the regulatory network.KEGG enrichment analysis showed that the differential mRNAs were related to the platelet activation signaling pathway,and there were 6 differential mRNAs related to platelet activation,namely F2R,ITGA2B,ITGB1,ITGB3,PTGS1,and GP1 BB,which were all up-regulated in their expression.RT-PCR results showed that the expression of five mRNAs including F2R,ITGA2B,ITGB1,ITGB3,and GP1BB were upregulated in ET patients compared with healthy subjects,and consistent with RNA-seq results,while PTGS1 expression was not significantly different.Conclusion:Differential mRNAs in ET patients are related to the platelet activation pathway,and F2R,ITGA2B,ITGB1,ITGB3,and GP1BB mRNAs may serve as novel targets associated with platelet activation in ET.

Objective:To summarize the clinical characteristics of patients with renal angiomyolipoma(RAML)combined with inferior vena cava(IVC)tumor thrombus,and to explore the feasibility of par-tial nephrectomy and thrombectomy in this series of patients.Methods:The clinical data of patients diagnosed with RAML combined with IVC tumor thrombus in the Department of Urology of the Peking University Third Hospital from April 2014 to March 2023 were retrospectively analyzed,and demographic and perioperative data of RAML patients with IVC tumor thrombus were recorded and collected from Elec-tronic Medical Record System,including age,gender,surgical methods,and follow-up time,etc.The clinical characteristics between classic angiomyolipoma(CAML)patients with IVC tumor thrombus and epithelioid angiomyolipoma(EAML)patients with IVC tumor thrombus were compared to determine the clinical characteristics of these patients.Results:A total of 11 patients were included in this study,in-cluding 7 patients with CAML with IVC tumor thrombus and 4 patients with EAML with IVC tumor thrombus.There were 9 females(9/11,81.8％)and 2 males(2/11,18.2％),with an average age of(44.0±17.1)years.9 patients(9/11,81.8％)experienced clinical symptoms,including local symp-toms including abdominal pain,hematuria,abdominal masses,and systemic symptoms including weight loss and fever;2 patients(2/11,18.2％)with RAML and IVC tumor thrombus did not show clinical symptoms,which were discovered by physical examination.Among the 11 patients,10 underwent radical nephrectomy with thrombectomy,of whom,3 underwent open surgery(3/10,30.0％),2 underwent laparoscopic surgery(2/10,20.0％),and 5 underwent robot-assisted laparoscopic surgery(5/10,50.0％).In addition,1 patient underwent open partial nephrectomy and thrombectomy.The patients with EAML combined with I VC tumor thrombus had a higher proportion of systemic clinical symptoms(100％vs.0％,P=0.003),more intraoperative bleeding[400(240,3 050)mL vs.50(50,300)mL,P=0.036],and a higher proportion of tumor necrosis(75％vs.0％,P=0.024)compared to the patients with CAML combined with I VC tumor thrombus.However,there was no statistically significant difference in operation time[(415.8±201.2)min vs.(226.0±87.3)min,P=0.053]between the two groups.Conclusion:Compared with the patients with CAML and IVC tumor thrombus,the patients with EAML and IVC tumor thrombus had a higher rate of systemic symptoms and tumor necrosis.In addi-tion,in the selected patients with CAML with IVC tumor thrombus,partial nephrectomy and tumor thrombectomy could be performed to better preserve renal function.

Objective To construct a culture system of endometrial organoids for infertility induced by non-immune or immune factors,and to compare the immune cytokines between them.Methods The samples were collected from infertility patients undergoing hysteroscopy in Department of Reproductive Medicine Center of The First Affiliated Hospital of Naval Medical University(Second Military Medical University).Endometrial tissues were obtained from patients with infertility caused by non-immune factors(n=3)and patients with repeated implantation failure(RIF)(n=5).The tissues were embedded in matrix glue for 3D culture after washing,digestion,re-suspension and plate attachment.The growth of endometrial organoids of the 2 groups was observed under inverted microscope;the expression of estrogen receptor,keratin and E-cadherin,which were specific endometrial markers,was detected by immunofluorescence staining;and the cytokines of the 2 groups were determined by enzyme-linked immunosorbent assay(ELISA)and the differences of cytokines between the 2 groups were observed.Results During the process of in vitro culture of endometrial organoids,the volume of organoids and the number of cells gradually increased.After 7-10 d of culture,the volume of organoids reached a stable state,and the shape gradually became a perfect circle.At the same time,the number of organoids from the infertility patients caused by non-immune factors was more than that from the infertility patients caused by RIF.Immunofluorescence staining showed the expression of endometrial related marker proteins estrogen receptor,keratin and E-cadherin,indicating the successful construction of endometrial organoids.ELISA results showed that the levels of interferon(IFN)-γ,interleukin(IL)-10,tumor necrosis factor(TNF)-α,IL-4 and TNF-α/IL-4 ratio between the 2 groups were significantly different(P＜0.05 or P＜0.01).There were no significant differences in the levels of TGF-β1 or IL-17,the ratios of IL-17/TGF-β1,IFN-γ/IL-10 or TNF-α/IL-10(all P＞0.05).Conclusion Endometrial organoids with proliferative ability from patients with non-immune infertility and RIF have been successfully cultured in vitro,which provides a new model for the basic research of immune infertility.

Objective To detect the expression changes of interleukin-10(IL-10)and transforming growth factor-β1(TGF-β1)during the development of deep vein thrombosis in mice,and to explore the application value of them in thrombus age estimation.Methods The mice in the experimental group were subjected to ligation of inferior vena cava.The mice were sacrificed by excessive anesthesia at 1 d,3 d,5 d,7 d,10 d,14 d and 21 d after ligation,respectively.The inferior vena cava segment with thrombosis was extracted below the ligation point.The mice in the control group were not ligated,and the inferior vena cava segment at the same position as the experimental group was extracted.The ex-pression changes of IL-10 and TGF-β1 were detected by immunohistochemistry(IHC),Western blot-ting and real-time qPCR.Results IHC results revealed that IL-10 was mainly expressed in monocytes in thrombosis and TGF-β1 was mainly expressed in monocytes and fibroblast-like cells in thrombosis.Western blotting and real-time qPCR showed that the relative expression levels of IL-10 and TGF-β1 in each experimental group were higher than those in the control group.The mRNA and protein levels of IL-10 reached the peak at 7 d and 10 d after ligation,respectively.The mRNA expression level at 7 d after ligation was 4.72±0.15 times that of the control group,and the protein expression level at 10 d after ligation was 7.15±0.28 times that of the control group.The mRNA and protein levels of TGF-β1 reached the peak at 10 d and 14 d after ligation,respectively.The mRNA expression level at 10 d after ligation was 2.58±0.14 times that of the control group,and the protein expression level at 14 d after ligation was 4.34±0.19 times that of the control group.Conclusion The expressions of IL-10 and TGF-β1 during the evolution of deep vein thrombosis present time-dependent sequential changes,and the expression levels of IL-10 and TGF-β1 can provide a reference basis for thrombus age estimation.

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Objective:To establish a mortality risk prediction model of severe bacterial infection in children and compare it with the pediatric early warning score (PEWS), pediatric critical illness score (PCIS) and pediatric risk of mortality score Ⅲ (PRISM Ⅲ).Methods:A total of 178 critically ill children were selected from the PICU of the Children's Hospital of Nanjing Medical University from May 2017 to June 2022. After obtaining the informed consent of the parents/guardians, basic information such as sex, age, height and weight, as well as indicators such as heart rate, systolic blood pressure and respiratory rate were collected from all children. A standard questionnaire was used to score the child 24 h after admission to the PICU. The children were divided into the survival and death groups according to their survival status at 28 d after admission. A mortality risk prediction model was constructed and nomogram was drawn. The value of the mortality risk prediction model, PEWS, PCIS and PRISM in predicting the risk of death was assessed and compared using the receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC).Results:Among the 178 critically ill children, 11 cases were excluded due to severe data deficiencies and hospitalization not exceeding 24 h. A total of 167 children were included in the analysis, including 134 in the survival group and 33 in the death group. A mortality risk prediction model for children with severe bacterial infection was constructed using pupillary changes, state of consciousness, skin color, mechanical ventilation, total cholesterol and prothrombin time. ROC curve analysis showed that the AUCs of mortality risk prediction model was 0.888 ( P<0.05). The AUCs of PEWS, PCIS and PRISM Ⅲ in predicting death in children with severe bacterial infection were 0.769 ( P< 0.05), 0.575 ( P< 0.05) and 0.759 ( P< 0.05), respectively. Hosmer-Lemeshow goodness-of-fit test showed the best agreement between risk of death and PEWS predicted morbidity and mortality and actual morbidity and mortality (χ 2 = 5.180, P = 0.738; χ 2 = 4.939, P = 0.764), and the PCIS and PRISM Ⅲ predicted mortality rates fitted reasonably well with actual mortality rates (χ 2= 9.110, P= 0333; χ 2 = 8.943, P= 0.347). Conclusions:The mortality risk prediction model for predicting the death risk has better prognostic value than PEWS, PCIS and PRISM Ⅲ for children with severe bacterial infection.

Objective:To investigate the clinical features of pertussis in children and analyze the risk factors of severe pertussis.Methods:The clinical data of 248 children with pertussis hospitalized in Hunan Children′s Hospital from March 2018 to March 2022 were analyzed retrospectively.According to the age at admission, the patients were divided into two groups: ≤3 months and > 3 months.According to the patient′s condition, they were classified into ordinary group and severe group.According to the pathogens detected, the children were divided into single infection group and mixed infection group.The independent sample t-test, chi- square test were used to analyze the clinical indexes of the infants in above groups. Results:(1)Of 248 hospitalized children with pertussis, 204 cases (82.2%) were less than 1 year old, 92 cases (37.0%) had contact with a coughing family member before, and 169 cases (68.1%) were unvaccinated.Among 248 children, 193 cases (77.8%) had an elevated white blood cell count, and 145 cases (58.4%) had mixed infections.The most common pathogen was respiratory syncytial virus [29/248(11.6%)]. About 173 cases (69.7%) had concurrent pneumonia, and 35 cases (14.1%) had pulmonary consolidation.(2)Compared with the group > 3 months of age, more patients in the group ≤3 months of age had contact with a coughing family member before, and suffered from cyanosis, dyspnea, respiratory failure, heart failure and pertussis encephalopathy ( χ2=4.612, 20.810, 7.882, 16.617, 13.740, 7.846, all P<0.05). The proportions of patients in the group ≤3 months of age required intensive care unit(ICU) hospitalization and mechanical ventilation were higher than those in the group > 3 months of age ( χ2=14.810, 21.436, all P<0.05). The mortality of the group ≤3 months of age was higher than that of the group >3 months of age ( χ2=12.016, P<0.05). Children ≤3 months of age had a higher WBC level [(27.83±27.70)×10 9/L vs.(23.34±15.28)×10 9/L, t=22.244, P<0.001], longer duration of spasmodic cough [(16.56±9.33) d vs.(15.06±6.16) d, t=10.145, P=0.002] and longer hospitalization time [(11.47±10.48) d vs.(9.48±4.80) d, t=20.050, P<0.001] than those >3 months of age.(3)Compared with the ordinary group, a higher proportion of children in the severe pertussis group were under 3 months old, and had not been vaccinated against pertussis vaccine ( χ2=14.803, 4.475, all P<0.05). The ratio of patients with dyspnea, an lymphocyte count/neutral cell(LC/NC) ratio <1, mixed infections, lung consolidation and pleural effusion in the severe pertussis group was higher than that in the ordinary group ( χ2=116.940, 43.625, 13.253, 106.370, 11.874, all P<0.05). The patients in the severe pertussis group had a higher WBC [(61.66±29.63)×10 9/L vs.(18.83±10.00)×10 9/L, t=112.580, P<0.001] and a lower LC (0.494±0.186 vs.0.676±0.132, t=13.752, P<0.001) than those in the ordinary group.(4)Compared with the single infection group, the proportions of children with fever, dyspnea, fine moist lung rales, an LC/NC ratio <1, and lung consolidation were higher in the mixed infection group ( χ2=8.909, 6.804, 7.563, 8.420, 12.458, all P<0.05). More children in the mixed infection group required ICU hospitalization and mechanical ventilation than those in the single infection group ( χ2=11.677, 7.397, all P<0.05). The mixed infection group had higher respiratory failure and death rates than the single infection group ( χ2=7.980, 4.267, all P<0.05). Compared with the single infection group, the mixed infection group had a higher WBC level [(27.73±24.13)×10 9/L vs.(21.25±14.65)×10 9/L, t=13.318, P<0.001], longer hospitalization time [(11.593±9.010) d vs.(8.339±4.047) d, t=17.283, P<0.001], and a smaller LC ratio (0.626±0.165 vs.0.684±0.132, t=7.997, P=0.005). (5) Logistic regression analysis showed that age ≤3 months, peak WBC and dyspnea were risk factors of severe pertussis. Conclusions:Hospitalized pertussis children are prone to pneumonia and pulmonary consolidation.Patients aged ≤3 months with a large WBC and dyspnea easily develop into severe pertussis.Monitoring blood routine is helpful for judging the severity of the disease.Mixed infections increase the incidence of complications and can impair the treatment effect.

NDFIP1 has been previously reported as a tumor suppressor in multiple solid tumors, but the function of NDFIP1 in NSCLC and the underlying mechanism are still unknown. Besides, the WW domain containing proteins can be recognized by NDFIP1, resulted in the loading of the target proteins into exosomes. However, whether WW domain-containing transcription regulator 1 (WWTR1, also known as TAZ) can be packaged into exosomes by NDFIP1 and if so, whether the release of this oncogenic protein via exosomes has an effect on tumor development has not been investigated to any extent. Here, we first found that NDFIP1 was low expressed in NSCLC samples and cell lines, which is associated with shorter OS. Then, we confirmed the interaction between TAZ and NDFIP1, and the existence of TAZ in exosomes, which requires NDFIP1. Critically, knockout of NDFIP1 led to TAZ accumulation with no change in its mRNA level and degradation rate. And the cellular TAZ level could be altered by exosome secretion. Furthermore, NDFIP1 inhibited proliferation in vitro and in vivo, and silencing TAZ eliminated the increase of proliferation caused by NDFIP1 knockout. Moreover, TAZ was negatively correlated with NDFIP1 in subcutaneous xenograft model and clinical samples, and the serum exosomal TAZ level was lower in NSCLC patients. In summary, our data uncover a new tumor suppressor, NDFIP1 in NSCLC, and a new exosome-related regulatory mechanism of TAZ.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Carrier Proteins/metabolism* ; Cell Line ; Cell Proliferation ; Exosomes/metabolism* ; Lung Neoplasms/genetics* ; Membrane Proteins/metabolism* ; Transcriptional Coactivator with PDZ-Binding Motif Proteins/metabolism*