BACKGROUND:Previous studies of the research group have found that icariin-containing serum can delay the progression of knee osteoarthritis,promote chondrocyte proliferation and stem cell cartilage differentiation in rats,but there is still a lack of sufficient basis for clinical application.OBJECTIVE:To investigate the repair effect of icariin-containing serum on lipopolysaccharide-induced inflammatory damage of human chondrocytes.METHODS:The effect of icariin-containing serum on chondrocyte viability was detected by cell counting kit-8 method,and the optimal volume fraction and time of icariin-containing serum were screened.The cells were then divided into blank group,lipopolysaccharide group,icariin-containing serum group and lipopolysaccharide+icariin-containing serum group.After grouping,immunofluorescence was used to detect the secretion of type Ⅱ collagen in chondrocytes in each group.Real-time PCR was used to detect the expression of related genes.RESULTS AND CONCLUSION:(1)Icariin-containing serum showed good biosafety characteristics for human chondrocytes,and the cell viability reached the highest level after 48 hours of intervention when the icariin-containing serum volume fraction was 15％,and the follow-up experiments were carried out according to the conditions.(2)Compared with the blank group,lipopolysaccharide significantly inhibited the expression of type Ⅱ collagen in chondrocytes,while icariin-containing serum showed a positive mobilization effect,which could effectively promote the secretion of type Ⅱ collagen in chondrocytes under normal and inflammatory conditions.(3)The mRNA expression of type Ⅱ collagen and Aggrecan in chondrocytes decreased significantly under lipopolysaccharide stimulation,and the mRNA expression levels of matrix metalloproteinase 13 and a disintegrin-like and metalloproteinase with thrombospondin motifs-5 increased significantly.Icariin-containing serum promoted the mRNA expression of type Ⅱ collagen in human chondrocytes under inflammatory conditions and reduced the mRNA expression of matrix metalloproteinase 13 and a disintegrin-like and metalloproteinase with thrombospondin motifs-5 in chondrocytes after lipopolysaccharide intervention.Therefore,these findings indicate that the icariin-containing serum has good safety for human chondrocytes and plays an important role in maintaining the normal physiological functions of chondrocytes,promoting the synthesis of extracellular matrix,and inhibiting the secretion of inflammatory factors.

BACKGROUND:Previous studies of the research group have found that icariin-containing serum can delay the progression of knee osteoarthritis,promote chondrocyte proliferation and stem cell cartilage differentiation in rats,but there is still a lack of sufficient basis for clinical application.OBJECTIVE:To investigate the repair effect of icariin-containing serum on lipopolysaccharide-induced inflammatory damage of human chondrocytes.METHODS:The effect of icariin-containing serum on chondrocyte viability was detected by cell counting kit-8 method,and the optimal volume fraction and time of icariin-containing serum were screened.The cells were then divided into blank group,lipopolysaccharide group,icariin-containing serum group and lipopolysaccharide+icariin-containing serum group.After grouping,immunofluorescence was used to detect the secretion of type Ⅱ collagen in chondrocytes in each group.Real-time PCR was used to detect the expression of related genes.RESULTS AND CONCLUSION:(1)Icariin-containing serum showed good biosafety characteristics for human chondrocytes,and the cell viability reached the highest level after 48 hours of intervention when the icariin-containing serum volume fraction was 15％,and the follow-up experiments were carried out according to the conditions.(2)Compared with the blank group,lipopolysaccharide significantly inhibited the expression of type Ⅱ collagen in chondrocytes,while icariin-containing serum showed a positive mobilization effect,which could effectively promote the secretion of type Ⅱ collagen in chondrocytes under normal and inflammatory conditions.(3)The mRNA expression of type Ⅱ collagen and Aggrecan in chondrocytes decreased significantly under lipopolysaccharide stimulation,and the mRNA expression levels of matrix metalloproteinase 13 and a disintegrin-like and metalloproteinase with thrombospondin motifs-5 increased significantly.Icariin-containing serum promoted the mRNA expression of type Ⅱ collagen in human chondrocytes under inflammatory conditions and reduced the mRNA expression of matrix metalloproteinase 13 and a disintegrin-like and metalloproteinase with thrombospondin motifs-5 in chondrocytes after lipopolysaccharide intervention.Therefore,these findings indicate that the icariin-containing serum has good safety for human chondrocytes and plays an important role in maintaining the normal physiological functions of chondrocytes,promoting the synthesis of extracellular matrix,and inhibiting the secretion of inflammatory factors.

Objective To explore the relationship between systemic immune-inflammation index(SⅡ)at admission and occurrence of early neurological deterioration(END)in patients with branch atheromatous disease(BAD).Methods A retrospective analysis was performed on 326 BAD patients admitted in Department of Neurology of Handan Central Hospital from October 2021 to February 2024.Based on occurrence of END or not,they were divided into END group(97 cases)and non-END group(229 cases).Clinical data of the patients were collected,and multivari-ate logistic regression analysis was used to identify the END risk variables in BAD patients.ROC curve was plotted to evaluate the value of NIHSS score,hs-CRP and SⅡ in predicting the inci-dence of END in the patients.Results Significantly advanced age,higher NIHSS score at admis-sion,and elevated hs-CRP level,neutrophil count and SⅡ,but lower platelet and lymphocyte counts were observed in the END group than the non-END group(P＜0.05,P＜0.01).Multi vari-ate logistic regression analysis indicated that NIHSS score at admission(OR=1.134,95％CI:1.050-1.226,P=0.001),hs-CRP(OR=1.131,95％CI:1.024-1.249,P=0.015),and SⅡ(OR=1.001,95％CI:1.001-1.002,P=0.003)were independent risk factors for END in BAD patients.The AUC value of SⅡ in the prediction of END was 0.660,which was significantly higher than that of NIHSS score and hs-CRP in BAD patients(P＜0.05).Conclusion SⅡ is an independent risk factor for END in BAD patients,and SⅡ at admission has a certain predictive value for the oc-currence of END in these patients.

Purpose This study aimed to investigate the expression,function,and molecular mechanisms of ZNF384 in esophageal squamous cell carcinoma(ESCC),as well as its role in tumor progression and chemoresistance.Methods The expression of ZNF384 in ESCC cell lines and tissues was assessed using RT-qPCR.Correlations with TNM stage,invasion depth,lymph node metastasis,and prognosis were evaluated.In vitro assays were performed to examine the effects of ZNF384 on ESCC cell proliferation,migration,invasion,and chemosensitivity.Dual-luciferase reporter assays were conducted to determine the interaction between ZNF384 and FZD3,and to assess the activation of the Wnt signaling pathway.Results ZNF384 expression was significantly upregulated in ESCC cell lines and tissues(P＜0.01).Elevated ZNF384 expression was associated with advanced TNM stage,greater invasion depth,lymph node metastasis,and poor prognosis(P＜0.05).Functional assays demonstrated that ZNF384 overexpression promo-ted ESCC cell proliferation,migration,and invasion(all P＜0.01),whereas ZNF384 knockdown inhibited these processes and enhanced chemosensitivity to cisplatin(all P＜0.01).Mechanistic studies showed that ZNF384 directly bound to the FZD3 promoter,upregulated FZD3 expression,and activated the Wnt signaling pathway(P＜0.05).Overexpression of FZD3 partially reversed the inhibitory effects of ZNF384 knockdown on cell malignancy and chemore-sistance(P＜0.05).Conclusion ZNF384 promotes ESCC progression and reduces chemosensitivity through activa-tion of the FZD3/Wnt signaling pathway,suggesting its potential as a therapeutic target in ESCC.

Objective To investigate the distribution patterns of TCM syndrome elements and syndrome types in Klebsiella pneumoniae pneumonia.Methods The study adopted a retrospective research method to collect the basic demographic data,pathogenic characteristics,TCM syndrome patterns,and four diagnostic examination information(including tongue and pulse manifestations)of hospitalized patients with Klebsiella pneumoniae pneumonia at Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine,from September 2022 to June 2024.Based on clustering analysis and factor analysis,the study explored the characteristics of TCM syndrome elements and the distribution patterns of TCM syndromes in Klebsiella pneumoniae pneumonia.Results A total of 365 patients(236 males,129 females)aged 23-100 years were included.Statistical analysis identified 33 core syndrome items,with cough being the most frequent(66.0%),followed by viscous phlegm(42.2%);the most common tongue characteristics were red tongue(50.4%)and greasy coating(45.8%),with slippery pulse being predominant(54.0%).Clustering analysis revealed four syndrome types:lung-kidney yin deficiency,phlegm-dampness with qi deficiency,yang deficiency with water overflow,and phlegm-heat obstructing the lung.Phlegm-heat obstructing the lung was the most prevalent(38.1%),followed by yang deficiency with water overflow(22.5%)and lung-kidney yin deficiency(22.2%).Factor analysis identified four common factors encompassing 21 variables,with a cumulative variance contribution rate of 74.888%.The results of syndrome elements were divided into phlegm,heat,qi stagnation,water retention,dampness,yang deficiency,yin deficiency,qi deficiency,and lung,kidney,heart,spleen based on pathological syndrome elements and pathological location syndrome elements.Conclusion Klebsiella pneumoniae pneumonia primarily affects the lungs,kidneys,heart,and spleen,with the lungs being the key organ.The most common TCM syndrome types are phlegm-heat obstructing the lung,lung-kidney yin deficiency,yang deficiency with water overflow,and phlegm-dampness with qi deficiency,among which phlegm-heat obstructing the lung is the most prevalent.

ObjectiveTo study the regulatory effect of the partial sequence within the 3’ untranslated region （3’UTR） of slit guidance ligand 1 （Slit1） （Slit1-3’UTR） on the fibrotic phenotypes of cardiac fibroblasts （CFs） and its potential mechanism. MethodsThe adenovirus vector was used to overexpress the 1526nt sequence of Slit1-3’UTR in ICR neonatal mouse CFs （mCFs）. The expression of fibrosis-related genes in mCFs， such as collagen type 1 alpha1（COL1A1）， collagen type 3 alpha3 （COL3A1） and alpha smooth muscle actin （α-SMA） were detected by Western blot assay. The effect of Slit1-3’UTR 1526nt on the proliferation and migration of mCFs was assessed by EdU staining and Trans-well assays. Angiotensin Ⅱ （Ang Ⅱ） was used to treat mCFs， and the impact of Slit1-3’UTR 1526nt on the fibrotic phenotypes of Ang Ⅱ-induced mCFs was evaluated. After overexpression of Slit1-3’UTR 1526nt， miR-34a-5p mimic was transfected into mCFs， followed by actinomycin D treatment to detect the mRNA stability of Slit1-3’UTR 1526nt， and the levels of miR-34a-5p and its target gene SIRT1（si-SIRT1） in mCFs were determined. The effects of miR-34a-5p and small interfering RNA targeting SIRT1 on the Slit1-3’UTR 1526nt-mediated regulation of fibrotic phenotypes were also determined. ResultsAdenovirus-mediated overexpression of Slit 1-3’UTR 1526nt was achieved in mCFs. Overexpression of Slit 1-3’UTR 1526nt markedly inhibited the expression of the fibrosis-related genes， proliferation and migration of mCFs and fibrotic phenotypes of Ang Ⅱ. The results of actinomycin D assay showed that miR-34a-5p inhibited the stability of Slit1-3’UTR 1526nt in mCFs， while the level of miR-34a-5p was reduced in mCFs with overexpression of Slit1-3’UTR 1526nt. Transfection of miR-34a-5p promoted the fibrotic phenotypes， and reversed the inhibitory effect of Slit1-3’UTR 1526nt on the fibrotic phenotypes of mCFs. Overexpression of Slit1-3’UTR 1526nt significantly increased the level of miR-34a-5p target gene SIRT1 in mCFs. Transfection of miR-34a-5p and si-SIRT1 consistently reversed the inhibitory effects of Slit1-3’UTR 1526nt on the fibrotic phenotypes of mCFs. ConclusionSlit1-3’UTR1526nt inhibits the fibrotic phenotypes of mCFs by binding to miR-34a-5p and increasing the expression of its target gene of SIRT1.

BACKGROUND:The capability of repairing articular cartilage damage is very limited,and tissue engineering technology provides new therapeutic options for repairing damaged cartilage,in which the interaction and induction between chondrocytes,bone marrow mesenchymal stem cells,and synovial mesenchymal stem cells is the basis of autologous healing of cartilage damage. OBJECTIVE:To construct the chondrocyte-bone marrow mesenchymal stem cell-synovial mesenchymal stem cell co-culture system to simulate the in vitro microenvironment of chondrocytes,and to explore the optimal cell inoculation ratio,meanwhile to observe the effects of icariin-containing serum on the proliferation of chondrocytes and the chondrogenic differentiation of stem cells in the system. METHODS:Rat knee chondrocytes,bone marrow mesenchymal stem cells and synovial mesenchymal stem cells were extracted,cultured and identified,and a chondrocyte-bone marrow mesenchymal stem cell-synovial mesenchymal stem cell non-contact co-culture system was constructed according to different cell inoculation ratios.After 72 hours of co-culturing,the chondrocyte proliferative activity and phenotypic ability were observed,and the co-culture system with the best overall effect was selected.New Zealand white rabbits were gavaged with icariin solution(0.25 mg/mL)to prepare icariin-containing serum,and cultured in conventional complete medium(high sugar DMEM culture medium containing 10%fetal bovine serum and 1%double antibody by volume)as the control group,while the experimental group was intervened by adding 10%icariin-containing serum by volume on the basis of above.The proliferative activity of chondrocytes and the expression of collagen type II were tested for the two groups after 24 and 48 hours.The differentiation of bone marrow mesenchymal stem cells and synovial mesenchymal stem cells into chondrocytes in the co-culture system was tested by immunofluorescence staining after 14 days. RESULTS AND CONCLUSION:(1)The three kinds of cells grew normally adherently to the wall in different ratios of co-culture,where chondrocytes showed the best proliferative activity and phenotypic ability in the co-culture system when chondrocytes:bone marrow mesenchymal stem cells:synovial mesenchymal stem cells=2:1:1.(2)Compared with the control group,the proliferative activity and type II collagen expression of chondrocytes in the experimental group were significantly increased after 24 hours(P<0.01),and the two groups still had difference after 48 hours(P<0.05).The two groups showed obvious chondrogenic differentiation of bone marrow mesenchymal stem cells and synovial mesenchymal stem cells after 14 days(P<0.01),and some of the cells appeared round or oval,and the cytoplasmic type II collagen immunofluorescence staining was positive.The fluorescence intensity of the experimental group was significantly higher than that of the control group(P<0.01).(3)The results showed that the chondrocyte-bone marrow mesenchymal stem cell-synovial mesenchymal stem cell co-culture system could be successfully established by the non-contact co-culture method,and the best chondrocyte proliferative activity and phenotypic ability could be obtained when the cell ratio was 2:1:1.Icariin-containing serum had the promoting effect on chondrocyte proliferation,and chondrogenic differentiation of bone marrow mesenchymal stem cells and synovial mesenchymal stem cells in the system.

Purpose This study aimed to investigate the expression,function,and molecular mechanisms of ZNF384 in esophageal squamous cell carcinoma(ESCC),as well as its role in tumor progression and chemoresistance.Methods The expression of ZNF384 in ESCC cell lines and tissues was assessed using RT-qPCR.Correlations with TNM stage,invasion depth,lymph node metastasis,and prognosis were evaluated.In vitro assays were performed to examine the effects of ZNF384 on ESCC cell proliferation,migration,invasion,and chemosensitivity.Dual-luciferase reporter assays were conducted to determine the interaction between ZNF384 and FZD3,and to assess the activation of the Wnt signaling pathway.Results ZNF384 expression was significantly upregulated in ESCC cell lines and tissues(P＜0.01).Elevated ZNF384 expression was associated with advanced TNM stage,greater invasion depth,lymph node metastasis,and poor prognosis(P＜0.05).Functional assays demonstrated that ZNF384 overexpression promo-ted ESCC cell proliferation,migration,and invasion(all P＜0.01),whereas ZNF384 knockdown inhibited these processes and enhanced chemosensitivity to cisplatin(all P＜0.01).Mechanistic studies showed that ZNF384 directly bound to the FZD3 promoter,upregulated FZD3 expression,and activated the Wnt signaling pathway(P＜0.05).Overexpression of FZD3 partially reversed the inhibitory effects of ZNF384 knockdown on cell malignancy and chemore-sistance(P＜0.05).Conclusion ZNF384 promotes ESCC progression and reduces chemosensitivity through activa-tion of the FZD3/Wnt signaling pathway,suggesting its potential as a therapeutic target in ESCC.

Objective To analyze the current status and emerging technology trends in domestic medical drainage tube patents,so as to explore possible factors for low patent conversion rates.Methods Patents associated with"drainage tube","medical drainage tube","surgical drainage tube"and related terms were retrieved from the National Intellectual Property Administration Database and the Innojoy Patent Search Engine,covering the period from 2010 to 2020.Screening and visual analysis were conducted using Excel and SPSS 27.0.Results A total of 2 895 relevant patents were identified,comprising 2 489 utility model patents,367 invention patents and 39 design patents.The number of patent applications demonstrated a year-on-year growth trend,with a higher concentration in eastern coastal regions and provinces housing numerous top-tier hospitals and medical institutions.Approximately 49.26％of the patents filed by individuals were affiliated with hospitals,universities,or enterprises.Innovation hotspots included the design,functionality,performance,and safety aspects of drainage tubes and probes.Of the patents,72.61％were invalid,and 61.73％had a survival period of three years or less.Only 5.15％were commercially utilized through transfers,pledges,or licensing.Conclusion Domestic patent applications for medical drainage tubes have seen rapid growth,with a focus on enhancing tube structures such as sleeves,balloons,drainage holes,and threaded designs.However,the unsatisfactory situation of patent conversion and operation have been mainly limited by factors such as weak core technology of patents,insufficient awareness of achievements conversion,poor operation of patent conversion mechanism,insufficient market promotion,and insufficient integration of industry,academia,and research.To address this issue,enhancing intellectual property protection,revitalizing valid patents,and expanding transformation channels would benefit patients and facilitate hospitals'high-quality development,injecting new vitality into the health industry.

Objective To explore the relationship between systemic immune-inflammation index(SⅡ)at admission and occurrence of early neurological deterioration(END)in patients with branch atheromatous disease(BAD).Methods A retrospective analysis was performed on 326 BAD patients admitted in Department of Neurology of Handan Central Hospital from October 2021 to February 2024.Based on occurrence of END or not,they were divided into END group(97 cases)and non-END group(229 cases).Clinical data of the patients were collected,and multivari-ate logistic regression analysis was used to identify the END risk variables in BAD patients.ROC curve was plotted to evaluate the value of NIHSS score,hs-CRP and SⅡ in predicting the inci-dence of END in the patients.Results Significantly advanced age,higher NIHSS score at admis-sion,and elevated hs-CRP level,neutrophil count and SⅡ,but lower platelet and lymphocyte counts were observed in the END group than the non-END group(P＜0.05,P＜0.01).Multi vari-ate logistic regression analysis indicated that NIHSS score at admission(OR=1.134,95％CI:1.050-1.226,P=0.001),hs-CRP(OR=1.131,95％CI:1.024-1.249,P=0.015),and SⅡ(OR=1.001,95％CI:1.001-1.002,P=0.003)were independent risk factors for END in BAD patients.The AUC value of SⅡ in the prediction of END was 0.660,which was significantly higher than that of NIHSS score and hs-CRP in BAD patients(P＜0.05).Conclusion SⅡ is an independent risk factor for END in BAD patients,and SⅡ at admission has a certain predictive value for the oc-currence of END in these patients.