ObjectiveTo investigate the protective effect and underlying mechanisms of Yishen Huayu prescription （YSHYP） on transdifferentiation of mouse renal tubular epithelial cells （TCMK-1） induced by transforming growth factor-β₁ （TGF-β₁）. MethodsA transdifferentiation model was established by treating TCMK-1 cells with 10 μg·L^-1 TGF-β₁. Experimental groups were established using 2 μmol·L^-1 silent information regulator 1 （SIRT1） inhibitor EX527. These included the blank group， model group， YSHYP group （treated with 10% YSHYP-medicated serum）， valsartan group （treated with 10% valsartan-medicated serum）， EX527+TGF-β₁ group， EX527+YSHYP group， and EX527 group. Immunofluorescence was used to detect the protein localization of α-smooth muscle actin （α-SMA）， E-cadherin， and microtubule-associated protein light chain 3 （LC3）. Western blot and Real-time polymerase chain reaction （Real-time PCR） were used to assess the expression of proteins and mRNA related to transdifferentiation， autophagy， and associated signaling pathways. ResultsThe results from Real-time PCR and Western blot indicate that compared with those in the blank group， expression levels of α-SMA， ubiquitin-binding protein p62 （p62）， and acetylated forkhead box protein O1（Ac-FoxO1） were significantly increased in the model group， EX527+TGF-β₁ group， and EX527 group （P<0.01）. Compared with that in the model group， the expression of α-SMA and p62 were significantly downregulated in the YSHYP and valsartan groups （P<0.05， P<0.01）. Ac-FoxO1 protein levels were significantly reduced in the YSHYP group （P<0.05）， while the valsartan group showed no significant changes in Ac-FoxO1 levels. Compared with the YSHYP group， the valsartan group showed significant differences in p62 mRNA， α-SMA， and p62 protein expression （P<0.05）. Compared with those in the blank group， LC3， Beclin1， SIRT1， and forkhead box protein O1 （FoxO1） expression levels were significantly decreased in the model group， EX527+TGF-β₁ group， and EX527 group （P<0.01）. In the model and EX527+TGF-β₁ groups， E-cadherin expression levels were significantly reduced （P<0.01）， while the EX527 group showed no statistically significant change. Compared with the model group， E-cadherin， LC3， Beclin1， SIRT1， and FoxO1 expression levels were significantly increased in both the YSHYP and valsartan groups （P<0.01， P<0.05）. Compared with the YSHYP group， the valsartan group exhibited significant differences in LC3， SIRT1， and FoxO1 mRNA expression （P<0.05， P<0.01）. Immunofluorescence results were consistent with those of Western blot and Real-time PCR. ConclusionYSHYP may protect TCMK-1 cells by activating the SIRT1/FoxO1 pathway， thereby promoting autophagy and restoring the autophagy flux to reduce the extent of transdifferentiation of TCMK-1 cells.

ObjectiveTo investigate the protective effect and underlying mechanisms of Yishen Huayu prescription （YSHYP） on transdifferentiation of mouse renal tubular epithelial cells （TCMK-1） induced by transforming growth factor-β₁ （TGF-β₁）. MethodsA transdifferentiation model was established by treating TCMK-1 cells with 10 μg·L^-1 TGF-β₁. Experimental groups were established using 2 μmol·L^-1 silent information regulator 1 （SIRT1） inhibitor EX527. These included the blank group， model group， YSHYP group （treated with 10% YSHYP-medicated serum）， valsartan group （treated with 10% valsartan-medicated serum）， EX527+TGF-β₁ group， EX527+YSHYP group， and EX527 group. Immunofluorescence was used to detect the protein localization of α-smooth muscle actin （α-SMA）， E-cadherin， and microtubule-associated protein light chain 3 （LC3）. Western blot and Real-time polymerase chain reaction （Real-time PCR） were used to assess the expression of proteins and mRNA related to transdifferentiation， autophagy， and associated signaling pathways. ResultsThe results from Real-time PCR and Western blot indicate that compared with those in the blank group， expression levels of α-SMA， ubiquitin-binding protein p62 （p62）， and acetylated forkhead box protein O1（Ac-FoxO1） were significantly increased in the model group， EX527+TGF-β₁ group， and EX527 group （P<0.01）. Compared with that in the model group， the expression of α-SMA and p62 were significantly downregulated in the YSHYP and valsartan groups （P<0.05， P<0.01）. Ac-FoxO1 protein levels were significantly reduced in the YSHYP group （P<0.05）， while the valsartan group showed no significant changes in Ac-FoxO1 levels. Compared with the YSHYP group， the valsartan group showed significant differences in p62 mRNA， α-SMA， and p62 protein expression （P<0.05）. Compared with those in the blank group， LC3， Beclin1， SIRT1， and forkhead box protein O1 （FoxO1） expression levels were significantly decreased in the model group， EX527+TGF-β₁ group， and EX527 group （P<0.01）. In the model and EX527+TGF-β₁ groups， E-cadherin expression levels were significantly reduced （P<0.01）， while the EX527 group showed no statistically significant change. Compared with the model group， E-cadherin， LC3， Beclin1， SIRT1， and FoxO1 expression levels were significantly increased in both the YSHYP and valsartan groups （P<0.01， P<0.05）. Compared with the YSHYP group， the valsartan group exhibited significant differences in LC3， SIRT1， and FoxO1 mRNA expression （P<0.05， P<0.01）. Immunofluorescence results were consistent with those of Western blot and Real-time PCR. ConclusionYSHYP may protect TCMK-1 cells by activating the SIRT1/FoxO1 pathway， thereby promoting autophagy and restoring the autophagy flux to reduce the extent of transdifferentiation of TCMK-1 cells.

Persistent left superior vena cava is a rare venous variant that is often combined with cardiovascular malformations. In thoracic surgery, especially mediastinal tumor resection, neglect of this variant may make the surgery difficult and risky, and careful preoperative imaging interpretation and adequate preoperative evaluation play an important role in the perioperative safety of the patient. In this paper, we reported a case of a 17-year-old female patient with a persistent left superior vena cava combined with mediastinal tumors. She was successfully discharged 5 days after thoracoscopic surgery, and after 3 years of postoperative follow-up, no tumor recurrence was observed.

ObjectiveTo investigate the mechanism of action of Xiayuxue decoction in inhibiting nonalcoholic fatty liver disease （NAFLD） induced by high-fat diet in mice by regulating nucleotide binding oligomerization domain like receptor containing pyrin domain protein 6 （NLRP6）. MethodsA total of 15 male C57BL/6 mice were randomly divided into low-fat diet （LFD） group， high-fat diet （HFD） group， and Xiayuxue decoction-HFD group （XYXD group）， with 5 mice in each group. Liver function parameters （alanine aminotransferase ［ALT］ and aspartate aminotransferase ［AST］） and blood lipid metabolic indicators （triglycerides ［TG］ and total cholesterol ［TC］） were measured； HE staining and oil red O staining were performed for liver tissue to observe histomorpholoty and lipid droplet deposition； quantitative real-time PCR was used to measure the expression levels of inflammatory factors （tumor necrosis factor-α ［TNF-α］， interleukin-1β ［IL-1β］， interleukin-18 ［IL-18］， and NLRP6） in liver tissue； Western blot was used to measure the protein expression levels of NLRP6， nuclear factor-kappa B （NF-κB）， and NF-κB p65； immunohistochemistry was used to measure the expression of NLRP6 and CD68. Mouse Raw264.7 cells were treated with palmitic acid （PA）， lipopolysaccharide， and serum containing Xiayuxue decoction to observe inflammation. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the LFD group， the HFD group had significant increases in the serum levels of ALT， AST， TC， and TG （all P<0.05）. Liver histopathological examination showed that the HFD group had marked hepatic steatosis and a signficant increase in NAS score （P<0.05）， and quantitative real-time PCR showed significant increases in the inflammatory factors such as IL1β and IL-18 and a significant reduction in the expression of NLRP6 （all P<0.05）. Immunohistochemistry showed that the expression of NLRP6 showed a similar trend as that of the macrophage marker CD68. Western blot showed that after the downregulation of NLRP6 expression， there was a significant increase in phosphorylated NF-κB p65 （P<0.05）. Compared with the HFD group， Xiayuxue decoction effectively improved liver inflammation， upregulated the expression of NLRP6， and downregulated phosphorylated NF-κB p65 in HFD mice （all P<0.05）. After Raw264.7 cells were treated with PA， NLRP6 was downregulated to promote the progression of inflammation （P<0.05）， and treatment with Xiayuxue decoction could upregulate NLRP6 and inhibit inflammation NF-κB （P<0.05）. ConclusionXiayuxue decoction can effectively improve hepatic steatosis and liver inflammation in a mouse model of NAFLD， possibly by regulating NLRP6/NF-κB to alleviate macrophage activation.

BACKGROUND:To investigate the research focus and follow-up research trend of exosomes in the diagnosis and treatment of chronic kidney disease,in order to provide a corresponding reference basis for the future research of exosomes in the diagnosis and treatment of chronic kidney disease,and promote the development of this field. OBJECTIVE:To conduct a bibliometric analysis of relevant studies in each database painstakingly until now for public publication on exosome diagnosis and treatment of chronic kidney disease,to explore the current state and trend of the field in this discipline,and to predict future research directions. METHODS:A computerized search was performed on WanFang,CNKI,CBM,VIP,Web of Science,Cochrane Library,PubMed,and Embase databases from inception to December 2022 for published literature related to the diagnosis and treatment of chronic kidney disease by exosomes.The literature transcripts were screened by NoteExpress for co-occurrence,clustering and mutational analysis among authors,institutions,and keywords through CiteSpace 6.1R4 and VOSviewer software,and the visual knowledge map was plotted. RESULTS AND CONCLUSION:(1)A total of 804 articles,including 133 in Chinese and 671 in English,were included,and the volume of publications climbed year by year with a rapid trend.We included 3 649 literature authors,including 326 Chinese authors and 3 323 English authors,and the field has formed a core team centered on scholars such as Liu Bicheng,Wang Bin,Lyu LinLi,Wang Xiaonan and Wang Haidong,and has formed a stable multicenter collaboration platform among institutions.Research focuses on the three functions of exosomes:carrier,diagnosis and therapy.(2)As a form of extracellular vesicles,exosomes have important mechanisms for carrying,transferring molecular mediators and signal transduction,and have an important role in the physiopathological development of chronic kidney disease,which can provide important health surveillance data for epidemiological studies and clinical decision-making.In recent years,the development of relevant studies on exosome-based diagnosis of chronic kidney disease has expanded dramatically,forming a development layout of collaborative cooperation among multiple institutions worldwide,led by our scientific research institutions.However,at present,the study of the specific function and mechanism of action of exosomes and contents in the disease process has not been fully validated.Their significance for the early diagnosis and prognosis evaluation of chronic kidney disease is not very clear.The intrinsic mechanism of action-related research is still relatively poor.Isolation and purification techniques still need to be improved,and high-quality evidence-based clinical trials with multicenter and large samples have not yet appeared,which still need to be verified by further studies.

BACKGROUND:The stability of the pelvis is mainly determined by the posterior pelvic ring and the sacroiliac joint.The posterior pelvic ring injury and the dislocation of the sacroiliac joint caused by high energy impacts such as car accidents increase year by year.Surgical treatment is the best method,and there are many kinds of endophytorepair methods in clinical practice,but which treatment method has the best biomechanical properties is still controversial. OBJECTIVE:To compare the biomechanical properties of three kinds of internal implants:anterior double plates,posterior bridging plate and tension nail in the repair of unilateral unstable pelvic posterior ring injury,to provide a reference for the clinical treatment and development of a new pelvic tension screw. METHODS:(1)Finite element simulation:Mimics,Wrap and SolidWorks were used to establish normal pelvic model,unilateral injured pelvis model,and three kinds of internal implant repaired models(anterior double plates,posterior bridging plate and tension nail).Ansys was used to analyze the stress and deformation of the models.(2)Biomechanical test:A total of 15 intact pelvic specimens were randomly grouped into five groups,normal pelvic model,unilateral injured pelvis model,anterior double plates,posterior bridging plate and tension nail groups.The mechanical test was performed using an Instron E10000 testing machine. RESULTS AND CONCLUSION:(1)Simulation:In the normal pelvic model,the average displacement of the sacrum was 0.174 mm,and the maximum stress of the sacral iliac bone was 10.51 MPa,and the stress distribution was uniform.The mean sacral displacement of the unilateral injured pelvis model was 0.267 mm,and the stress concentration of the model was obvious.The mean displacement of the sacrum in the three repaired models was close to that in the normal pelvic model,and the stress distribution of the sacral iliac bone in the tension nail repaired model was uniform.(2)Mechanical test:The stiffness of the normal pelvic model was(226.38±4.18)N/mm,and that of the unilateral unstable pelvic model was the smallest(130.02±2.19)N/mm.The deviation of the normal pelvic model stiffness and the three repaired models'stiffness were all within(±10%),and the repair effect was obvious.(3)The simulation results were in agreement with the experimental results.(4)The biomechanics of the tension nail repaired model was the most similar to that of the normal pelvis,and this method was the best.The repairing stiffness of the anterior double plate was too large,and the stress shielding effect was more significant.The posterior bridging plate repair could not solve the compensatory effect of the normal side soft tissue and had defects.This study provides an optimal basis for clinical surgery.(5)The new type of pelvic tension nail should be improved from the point of view of the tension nail to retain the good biomechanical properties of the tension nail,while adding other advantages,such as being used for the osteoporotic pelvis.

BACKGROUND:Autophagy and ferroptosis play important roles in the development of chronic kidney disease,but the molecular mechanisms and gene targets related to autophagy and ferroptosis in renal tissue of chronic kidney disease are still unclear. OBJECTIVE:To screen differentially expressed genes in chronic kidney disease-related datasets based on bioinformatics,and to explore potential key biomarkers suitable for screening renal function progression in patients with chronic kidney disease. METHODS:(1)The GSE137570 dataset was obtained from GEO database to screen the differentially expressed genes by Networkanalyst database analysis.Ferroptosis and autophagy related targets were obtained by OMIM,GENECARD,FerrDb and HAMdb databases.The respective data were intersected to obtain autophagy-ferroptosis related differentially expressed genes in chronic kidney disease for parallel enrichment analysis.The STRING website was used to construct the protein-protein interaction network of differentially expressed genes,which was imported into Cytoscape software and analyzed by MCODE and Cytohubba plug-in to screen potential core targets.Enrichment analysis was performed to obtain the functions of these potential core targets.(2)In the in vitro experiment,mouse renal tubular epithelial cells were divided into two groups:the control group received no intervention,while the model group was stimulated with 5 ng/mL transforming growth factor β1 for 24 hours to induce mesenchymal transformation of renal tubular epithelial cells.Flow cytometry was used to measure the levels of reactive oxygen species and changes in mitochondrial membrane potential in the cells.RT-PCR was employed to assess ferroptosis,autophagy-related markers,and the mRNA expression of potential core targets in the cells. RESULTS AND CONCLUSION:After screening the GSE137570 dataset,a total of 480 differentially expressed genes were obtained,including 104 upregulated genes and 376 downregulated genes(log2|(FC)|>1,P<0.05).There were 562 ferroptosis-related targets and 1 266 autophagy-related targets obtained from the OMIM,GENECARD,FerrDb,and HAMdb databases.Intersection of differentially expressed genes with ferroptosis-and autophagy-related targets yielded 15 ferroptosis-related targets and 18 autophagy-related targets,respectively.The enrichment analysis results indicate that ferroptosis-related differentially expressed genes are primarily involved in biological processes such as sulfur amino acid metabolism,neutrophil degranulation,and ferroptosis signaling pathways.Autophagy-related differentially expressed genes are mainly enriched in biological processes such as platelet degranulation,extracellular matrix degradation,and receptor tyrosine kinase signaling.After screened by MCODE and CytoHubba,key genes were identified in the protein-protein interaction network,including CD44,ALB,TIMP1,PLG,CCL2,and DPP4.Immune infiltration analysis results indicate that immune cells such as B cells,CD4+ T cells,NK cells,and monocytes show significant differential expression in renal tissue after chronic kidney disease,and the core targets are also significantly correlated with these immune cells(P<0.05).The results of receiver operator characteristic curve analysis further demonstrate that the pathological progression of chronic kidney disease can be effectively diagnosed by CD44,ALB,TIMP1,PLG,CCL2,and DPP4.Single-cell sequencing results show that,except for PLG,the expression of target genes in the renal tissue of mice in each model group is generally consistent with the results of this experiment.RT-PCR results demonstrate that,for the validation of autophagy and ferroptosis phenotypes,compared with the control group,the model group shows a significant decrease in mRNA expression of LC3B,Nrf2,and SLC7A11(P<0.05),and a significant increase in P62 mRNA expression(P<0.05).Regarding the validation of potential core targets,compared with the control group,the model group exhibits a significant decrease in mRNA expression of ALB and PLG(P<0.05),and a significant increase in TIMP1 and CCL2 mRNA expression(P<0.05).Overall,these findings indicate that,through bioinformatics analysis and experimental validation,CD44,ALB,TIMP1,PLG,and CCL2 are abnormally expressed in the renal tissue of patients with chronic kidney disease,closely correlated with estimated glomerular filtration rate and tubulointerstitial fibrosis,and maybe play a predictive role in the progression of chronic kidney disease.

Objective:To assess the efficacy and safety of the treat-and-extend (TAE) regimen and pro re nata (PRN) regimen of intravitreal conbercept in polypoidal choroidal vasculopathy (PCV) patients.Methods:A non-randomized controlled study was performed.Ninety-one patients (91 eyes) diagnosed with treatment-na?ve PCV from October 2016 to January 2019 at Department of Ophthalmology, Peking University People's Hospital were enrolled.All the patients received the intravitreal injection of 0.5 mg conbercept.After the initial treatment, the patients were divided into 3+ PRN group and 3+ TAE group according to their willingness.The follow-up time was one year.All the eyes underwent visual acuity test with ETDRS chart, optical coherence tomography (OCT) examination, fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA). Best corrected visual acuity (BCVA), central retinal thickness (CRT), maximum retinal thickness (MRT), pigment epithelium detachment (PED) height, the number and area of polypoidal lesions, the area of retinal hemorrhage and the area of branching vascular network (BVN) were recorded.Treatment interval and injection frequencies during the one-year follow-up were compared between the two groups.This study adhered to the Declaration of Helsinki.The study protocol was approved by Peking University People's Hospital (No.2020PHB250-01). Written informed consent was obtained from each patient.Results:One-year after treatment, the BCVA improvement in the 3+ PRN group and 3+ TAE group was 5.0(-2.0, 15.0) and 6.0(-1.0, 14.0) letters, respectively, showing no significant difference ( Z=-0.352, P=0.725). No significant differences were found in CRT, MRT and PED height between the two groups ( Z=-0.145, -0.529, -0.985, all at P>0.05). There was no significant difference in polypoidal lesions number, polypoidal lesions area, the number of eyes with different degrees of polyp regression, BVN area and retinal hemorrhage area between the two groups ( Z=-0.502, -0.300, -0.047, -0.265, -1.243, all at P>0.05). After the one-year follow-up, the mean injection frequency of 3+ PRN group was (7.6±0.9) times, which was lower than (8.4±2.0) times of 3+ TAE group, showing a significant difference ( t=2.432, P=0.019). The mean follow-up frequency was (11.3±1.5) times of 3+ PRN group, which was significantly higher than (10.1±1.7) times of 3+ TAE group ( t=3.403, P=0.001). For the 3+ TAE group, 17.1%(6/35) of patients achieved an extension interval of 12 weeks after the first 3 doses, and 48.5%(17/35) of patients achieved an extension interval of 8 weeks or more, with a mean maximum extension interval of (9.5±2.0) weeks.During the follow-up, 10 patients in 3+ PRN group and 8 patients in 3+ TAE group received photodynamic therapy as a rescue treatment. Conclusions:The 3+ PRN and 3+ TAE regimens of intravitreal injection of conbercept combined with photodynamic therapy as a rescue treatment have similar efficacy in visual and anatomical outcomes for PCV patients.3+ TAE regimen has a higher treatment frequency and fewer follow-up visits.

PPG(photoplethysmography)holds significant application value in wearable and intelligent health devices.However,during the acquisition process,PPG signals can generate motion artifacts due to inevitable coupling motion,which diminishes signal quality.In response to the challenge of real-time detection of motion artifacts in PPG signals,this study analyzed the generation and significant features of PPG signal interference.Seven features were extracted from the pulse interval data,and those exhibiting notable changes were filtered using the dual-sample Kolmogorov-Smirnov test.The real-time detection of motion artifacts in PPG signals was ultimately based on decision trees.In the experimental phase,PPG signal data from 20 college students were collected to formulate the experimental dataset.The experimental results demonstrate that the proposed method achieves an average accuracy of(94.07±1.14)%,outperforming commonly used motion artifact detection algorithms in terms of accuracy and real-time performance.

Objective:To explore the application effect of early nursing intervention based on NNN-link in social disorders of children with autism spectrum disorders (ASD) .Methods:A total of 126 hospitalized children with ASD in the Rehabilitation Center of Henan Children's Hospital from January to May 2023 were selected as research subjects by convenience sampling. They were randomly divided into an intervention group ( n=63) and a control group ( n=63) using a random number table. The control group received routine care, while the intervention group received early nursing intervention based on NNN-link in addition to routine care. The Social Disorder-related Nursing Diagnosis Outcome Scales and the Childhood Autism Rating Scale (CARS) scores were compared between the two groups before and after intervention. Results:After the early nursing intervention, the scores for family atmosphere, participation in leisure activities, participation in play, social skills, and social participation were higher in the intervention group compared to the control group, the differences were statistically significant ( P<0.05). The CARS scores of the intervention group were also lower than those of the control group, the differences were statistically significant ( P<0.05) . Conclusions:Early nursing intervention based on NNN-link can effectively improve the social disorder conditions of children with ASD, reduce their autism symptoms, and promote recovery.