OBJECTIVES: To explore the mechanism by which astragaloside IV (AS-IV) alleviates D-galactose (D-GAL)-induced senescence in human umbilical vein endothelial cells (HUVECs). METHODS: Cultured HUVECs were treated with D-GAL (40 g/L), AS-IV (200 μmol/L), D-GAL+AS-IV, or D-GAL+AS-IV+MTK458 (a mitochondrial autophagy agonist, 25 μmol/L) for 48 h, and the changes in cell proliferation, migration, and angiogenesis capacity were evaluated. Cell apoptosis, reactive oxygen species (ROS) levels, mitochondrial membrane potential, and expressions of autophagy-related proteins (LC3-II/LC3-I) and PINK1/Parkin pathway proteins in the treated cells were detected. RESULTS: AS-IV treatment significantly reduced the inhibitory effect of D-GAL on HUVEC viability, effectively alleviated D-GAL-induced impairment of tube-forming ability, and promoted angiogenesis and migration ability of the cells. AS-IV also significantly reduced the rate of D-GAL-induced HUVECs positive for senescence-associated β-galactosidase (SA-β-Gal) staining and inhibited the expression of senescence-related genes P21 and P53. AS-IV restored mitochondrial membrane potential and reduced intracellular ROS levels in D-GAL-induced HUVECs, and inhibited the fusion of autophagosomes and lysosomes to prevent the completion of autophagic flux. In HUVECs treated with both D-GAL and AS-IV, the application MTK458 significantly increased the number of yellow spots and enhanced the expressions of P21, P53, PINK1, Parkin, LC3, and Beclin proteins. CONCLUSIONS AS-IV alleviates D-GAL-induced endothelial cell senescence by inhibiting the PINK1/Parkin pathway to regulate mitochondrial autophagy.
Humans ; Human Umbilical Vein Endothelial Cells/drug effects* ; Cellular Senescence/drug effects* ; Autophagy/drug effects* ; Saponins/pharmacology* ; Ubiquitin-Protein Ligases/metabolism* ; Mitochondria/drug effects* ; Triterpenes/pharmacology* ; Protein Kinases/metabolism* ; Galactose/pharmacology* ; Reactive Oxygen Species/metabolism* ; Signal Transduction/drug effects* ; Cells, Cultured ; Apoptosis/drug effects* ; Membrane Potential, Mitochondrial ; Cell Proliferation/drug effects*

Objective: To investigate the efficacy, nursing characteristics, and management of different desensitization strategies before allogeneic hematopoietic stem cell transplantation (allo-HSCT) among patients with high level of human leukocyte antigen (HLA) antibodies. Methods: A retrospective analysis was conducted on 82 patients with high levels of HLA antibodies who underwent allo-HSCT at the First Affiliated Hospital of Soochow University and Suzhou Hopes Hematonosis Hospital between January 2020 to November 2023. Patients were divided into two groups based on the desensitization strategy they received: the anti-CD20 monoclonal antibody combined with therapeutic plasma exchange (TPE) group (n=50) and the anti-CD20 monoclonal antibody combined with Protein A immunoabsorption group (n=32). The differences of efficacy between the desensitization strategies were analyzed. The safety of both desensitization strategies were assessed by close monitoring of adverse events throughout the treatment. The nursing characteristics and interventions specific to these strategies were comprehensively summarized. Results: There were no significant differences in age, gender, and diagnosis between the two groups of patients receiving different desensitization strategies (P>0.05). Following desensitization in the immunoadsorption group, the mean fluorescence intensity (MFI) levels of anti-HLA Class I antibody decreased significantly compared to initial screening (P=0.048), while the decrease in MFI values of anti-HLA Class II antibody was not statistically significant (P=0.173). In the TPE group, the MFI levels for both anti-HLA Class I and II antibodies after desensitization decreased significantly compared to initial screening (P=0.025 and 0.028, respectively). Monitoring of adverse events during desensitization treatment, found that patients in the immunoadsorption group experienced mild decreases in blood pressure during the process, with two patients developing severe hypotension. No allergic reactions occurred, and no damage of liver or kidney function was observed after the immunoadsorption. In the immunoadsorption group, a total of 19 patients underwent sera immunoglobulin assays before and after immunoadsorption. Compared to the initial screening, the immunoglobulin G (IgG) levels significantly decreased after immunoadsorption (P<0.001). In TPE group, 12 patients experienced mild hypotension during the plasma exchange process, but no severe hypotension was observed. One patient developed an allergic reaction. After the TPE treatment, no damage of liver or kidney function was observed, nor any decrease of IgG levels. In terms of safety of intravenous access, neither group experienced severe complications such as catheter-related bloodstream infections or deep vein thrombosis. In the TPE group, catheter occlusion occurred during the process of plasma exchange in 2 patients, while no such incident was observed in the immunoadsorption group. Patients of both groups exhibited anxiety and depression before treatment. After psychological care, the scores for anxiety and depression significantly decreased (P<0.001). Conclusion: Both desensitization strategies significantly decreased the HLA antibodies in highly sensitized patients with high level of HLA antibodies undergoing allo-HSCT. For patients receiving immunoabsorption, nursing care should focus on preventing and managing hypotension and implementing infection-prevention measures due to IgG depletion. In contrast, for those undergoing TPE, vigilant monitoring and prompt management of potential allergic reactions are essential components of nursing practice.

Objective Stereotactic body radiotherapy(SBRT)and radiofrequency ablation(RFA)are primary treatments for hepatocellular carcinoma(HCC)at present.However,the effect of these treatments in clinical trails are rather controversial.The purpose of this paper is to conduct a meta-analysis on the clinical effect and related complications of SBRT and RFA for HCC.Methods A computerized retrieval of academic papers concerning the treatment effect of SBRT and RFA for HCC from the databases of PubMed,Embase,Cochrane Library,Scopus,Web of Science,CBM,CNKI,Wanfang database,VIP was conducted.The retrieval time period was from the establishment of the database to June 2022.Stata14.0 software was used to make meta-analysis.Results A total of 14 retrospective studies including 6 806 patients were included in this analysis.The results of combined hazard ratio(HR)based on overall survival(OS)showed that the OS rate of SBRT was lower than that of RFA(HR=1.25,95％CI=1.10-1.43,12=0％,P=0.000 9),while the results of combined HR of local control(LC)rate indicated that SBRT had a better therapeutic effect(HR=0.61,95％CI=0.47-0.78,I2=0％,P=0.000 1).Subgroup analysis revealed that the combined HR of LC rate favored the performance of SBRT for patients with tumor diameter larger than 2 cm(HR=2.64,95％CI=1.56-4.48,I=0％,P=0.000 3).No statistically significant difference in the incidence of late serious adverse reactions existed between SBRTgroup and RFA group(OR=1.01,95％CI=0.59-1.73,I2=30％,P=0.97).Conclusion SBRT is superior to RFA in controlling local HCC lesions,especially in patients whose tumor diameter is larger than 2 cm,although it does not show certain advantages in the survival benefit.(J Intervent Radiol,2023,32:1233-1241)

Objective:To explore the effects of multidisciplinary pain management in patients with cesarean scar pregnancy (CSP) undergoing uterine artery embolization (UAE) .Methods:Totally 140 CSP patients who underwent UAE in Nantong Maternity and Child Health Care Hospital, Nantong University from January 2019 to March 2021 were selected by convenient sampling and divided into the observation group and control group according to the random number table, with 70 patients in each group. Patients in the control group received routine care, while patients in the observation group underwent multidisciplinary pain management. The stress response-related indicators, complication rates, and pain control satisfaction were compared between the two groups.Results:The heart rate, systolic blood pressure, visual analog pain score, and anxiety score of the observation group were lower than those of the control group, and the Brinell comfort score was higher than that of the control group, with statistically significant differences ( P<0.05) . The total incidence of complications in the observation group was 8.57% (6/70) , which was lower than 21.43% (15/70) in the control group, and the difference was statistically significant ( P<0.05) . The total satisfaction with pain control in the observation group was 91.43% (64/70) , which was higher than 75.71% (53/70) in the control group, and the difference was statistically significant ( P<0.05) . Conclusions:The multidisciplinary pain management is beneficial to relieve the degree of stress response of patients, reduce the occurrence of complications, and improve the satisfaction with pain control.

Objective:To explore the integration path of medical resources in regional medical consortium, find out the problems affecting the process of integration, and put forward relevant suggestions.Methods:Methods According to the purposive sampling and combined with grounded theoretical research methods, semi-structured interviews were conducted with 73 government officials, heads and backbones of medical institutions in different regions of a city from August to November 2019. The data obtained from semi-structured interviews were analyzed by using grounded theory, and the path framework of medical resource integration in regional medical consortium was constructed through open coding, spindle coding and selective coding.Results:Four key links of medical resource integration in the regional medical alliance were sorted out, namely, integration prerequisites, integration strategies, support conditions, and integration methods, which together constituted the main axis of the theoretical framework. In addition, integration methods were affected by integration prerequisites, integration strategies and support conditions. The four factors and integration willingness served as influencing factors to exert impact on the integration tendency.Conclusions:The integration of medical resources in the medical alliance is a systematic project, which emphasizes the organic and overall governance of each key link, and the interaction between various elements will affect the final effect of medical resource integration.

COVID-19 has swept globally and Pakistan is no exception.To investigate the initial introductions and transmissions of the SARS-CoV-2 in Pakistan,we performed the largest genomic epidemiology study of COVID-19 in Pakistan and generated 150 complete SARS-CoV-2 genome sequences from samples collected from March 16 to June 1,2020.We identified a total of 347 mutated positions,31 of which were over-represented in Pakistan.Meanwhile,we found over 1000 intra-host single-nucleotide variants(iSNVs).Several of them occurred concurrently,indicating possible interactions among them or coevolution.Some of the high-frequency iSNVs in Pakistan were not observed in the global population,suggesting strong purifying selections.The genomic epidemiology revealed five distinctive spreading clusters.The largest cluster consisted of 74 viruses which were derived from different geographic locations of Pakistan and formed a deep hierarchical structure,indicating an extensive and persistent nation-wide transmission of the virus that was probably attributed to a signature mutation(G8371T in ORF 1ab)of this cluster.Further-more,28 putative international introductions were identified,several of which are consistent with the epidemiological investigations.In all,this study has inferred the possible pathways of introduc-tions and transmissions of SARS-CoV-2 in Pakistan,which could aid ongoing and future viral surveillance and COVID-19 control.

Objective To investigate whether platelet?derived growth factor?BB (PDGF?BB) can regulate phenotypic transformation of pulmonary artery smooth muscle cells (PASMCs) via SIRT3 affecting glycolytic pathway. Methods The PASMCs were isolated from Sprague Dawley rats. PASMCs were divided into 3 groups by using 2?deoxyglucose (2?DG), an inhibitor of the glycolytic pathway: normal control group, PDGF?BB group(30 ng/ml) and PDGF?BB (30 ng/ml)+2?DG (10 mmol/L) group. In lentivirus?mediated overexpression assay, cells were divided into control group, PDGF?BB group(30 ng/ml), PDGF?BB+deacetylase sirtuin?3 (SIRT3) overexpression group and PDGF?BB+empty vector group. The expression levels of phenotype related index such as α?smooth muscle actin (α?SMA), smooth muscle myosin heavy chain (SM?MHC), calponin, vimentin were detected by qRT?PCR and Western blot. Meanwhile, the expression of α?SMA was detected by cellular immunofluorescence staining. EDU staining was used to detect the proliferation of PASMCs. The expression of SIRT3 was detected by Western blot. The expressions of glucose transporter 1 and aerobic glycolytic enzymes were detected by qRT?PCR and Western blot in lentivirus?mediated overexpression assay. Results (1) PDGF?BB affects PASMCs phenotypic transformation through glycolytic pathway: compared with normal control group, PDGF?BB significantly decreased the expressions of contractile phenotype markers such as α?SMA, SM?MHC, calponin mRNA and protein (all P<0.05), but it increased the expressions of the synthetic phenotype marker vimentin mRNA and protein (both P<0.05). Cellular immunofluorescence assay showed that PDGF?BB significantly decreased the number of α?SMA positive cells, while 2?DG reversed the process. (2) PDGF?BB promoted cell proliferation through glycolytic pathway: the proliferation of PASMCs was significantly higher in PDGF?BB group than in control group (P<0.05), and which could be significantly reduced by 2?DG (P<0.05). (3) PDGF?BB inhibited the expression of SIRT3 protein in PASMCs: the expression of SIRT3 protein in PDGF?BB group was lower than that in control group (P<0.05). (4) PDGF?BB affected glycolytic pathway through SIRT3:compared with the control group, PDGF?BB significantly increased the expression levels of glucose transporter 1 (Glut1), hexokinase 2 (HK2) and 6?phosphfructo?2?kinase 3 (PFKFB3) mRNA (all P<0.05), which was reserved by over?expression of SIRT3. There were no significant difference in mRNA expression levels between PDGF?BB group and PDGF?BB+empty vector group (P>0.05).Compared with the control group, PDGF?BB significantly increased the expression levels of Glut1, HK2 and PFKFB3 protein(all P<0.05), which was reserved by over?expression of SIRT3. There were no significant differences in protein expression levels between PDGF?BB group and PDGF?BB+empty vector group (all P>0.05). Conclusion PDGF?BB regulates phenotypic transformation of PASMCs via SIRT3 affecting glycolytic pathway.

Objective: To investigate whether platelet-derived growth factor-BB (PDGF-BB) can regulate phenotypic transformation of pulmonary artery smooth muscle cells (PASMCs) via SIRT3 affecting glycolytic pathway. Methods: The PASMCs were isolated from Sprague Dawley rats. PASMCs were divided into 3 groups by using 2-deoxyglucose (2-DG), an inhibitor of the glycolytic pathway: normal control group, PDGF-BB group(30 ng/ml) and PDGF-BB (30 ng/ml)+2-DG (10 mmol/L) group. In lentivirus-mediated overexpression assay, cells were divided into control group, PDGF-BB group(30 ng/ml), PDGF-BB+deacetylase sirtuin-3 (SIRT3) overexpression group and PDGF-BB+empty vector group. The expression levels of phenotype related index such as α-smooth muscle actin (α-SMA), smooth muscle myosin heavy chain (SM-MHC), calponin, vimentin were detected by qRT-PCR and Western blot. Meanwhile, the expression of α-SMA was detected by cellular immunofluorescence staining. EDU staining was used to detect the proliferation of PASMCs. The expression of SIRT3 was detected by Western blot. The expressions of glucose transporter 1 and aerobic glycolytic enzymes were detected by qRT-PCR and Western blot in lentivirus-mediated overexpression assay. Results: (1) PDGF-BB affects PASMCs phenotypic transformation through glycolytic pathway: compared with normal control group, PDGF-BB significantly decreased the expressions of contractile phenotype markers such as α-SMA, SM-MHC, calponin mRNA and protein (all P<0.05), but it increased the expressions of the synthetic phenotype marker vimentin mRNA and protein (both P<0.05). Cellular immunofluorescence assay showed that PDGF-BB significantly decreased the number of α-SMA positive cells, while 2-DG reversed the process. (2) PDGF-BB promoted cell proliferation through glycolytic pathway: the proliferation of PASMCs was significantly higher in PDGF-BB group than in control group (P<0.05), and which could be significantly reduced by 2-DG (P<0.05). (3) PDGF-BB inhibited the expression of SIRT3 protein in PASMCs: the expression of SIRT3 protein in PDGF-BB group was lower than that in control group (P<0.05). (4) PDGF-BB affected glycolytic pathway through SIRT3:compared with the control group, PDGF-BB significantly increased the expression levels of glucose transporter 1 (Glut1), hexokinase 2 (HK2) and 6-phosphfructo-2-kinase 3 (PFKFB3) mRNA (all P<0.05), which was reserved by over-expression of SIRT3. There were no significant difference in mRNA expression levels between PDGF-BB group and PDGF-BB+empty vector group (P>0.05).Compared with the control group, PDGF-BB significantly increased the expression levels of Glut1, HK2 and PFKFB3 protein(all P<0.05), which was reserved by over-expression of SIRT3. There were no significant differences in protein expression levels between PDGF-BB group and PDGF-BB+empty vector group (all P>0.05). Conclusion PDGF-BB regulates phenotypic transformation of PASMCs via SIRT3 affecting glycolytic pathway.

Objective To investigate the effects of dexmedetomidine (DEX) on the mRNA expression of triggering receptor expressed on myeloid cells 1 (TREM-1) in peripheral blood mononuclear cells of rats with acute obstructive suppurative cholangitis (AOSC).Methods Sixty healthy male Wistar rat models of AOSC induced by complete common bile duct ligation and injection of E.coli into the bile duct through an intubation tube were replicated successfully.After modeling,the peripheral blood was collected and mononuclear cells were isolated and cultured.According to random number table method,the mononeuclear cells were divided into model group (no drug added in culture of mononuclear cells) and low,medium and high dose DEX groups (final concentrations 0.4,0.8,1.2 μg/L DEX were in low,medium and high DEX mononuclear cell cultures,respectively).After the mononuclear cells were cultured for 24 hours,the levels of tumor necrosis factor-α (TNF-α),interleukins (IL-1 and IL-6) in the supernatant of the cultured mononuclear cells were detected by enzyme linked immunosorbent assay (ELISA).The level of C-reactive protein (CRP) was detected by immunity transmission turbidimetry.The expression of TREM-1 mRNA in the mononuclear cells was detected by reverse trantscription-polymerase chain reaction (RT-PCR).Results Compared with the model group,the levels of TNF-α,IL-1,IL-6,CRP were decreased,the TREM-1 mRNA expressions were down-regulated in the different DEX dose groups,and the degrees of descent in medium and high dose groups were more significant than those in low dose group [TNF-oα (ng/L):95.5±8.6,88.9±5.3 vs.131.1 ± 14.2;IL-1 (ng/L):53.5±8.3,48.3 ± 6.7 vs.73.7 ± 12.8;IL-6 (ng/L):266.9±26.2,252.1 ± 17.7 vs.349.9±40.4;CRP (ng/L):4.3 ± 1.1,3.9 ±0.7 vs.5.6 ± 1.7;TREM-1 mRNA (A value):0.43 ± 0.18,0.39 ± 0.16 vs.0.65 ±0.25,all P ＜ 0.05].Conclusion DEX can down-regulate the expression of TREM-1 mRNA and inhibit the formation and secretion of inflammatory factors TNF-α,IL-1,IL-6 and CRP in peripheral blood mononuclear cells of rats with ASOC.

Objective: To investigate the efficacy and safety of the recombinant human tumor necrosis factor receptor Ⅱ-IgG Fc fusion protein (rhTNFR: Fc, etanercept) for the treatment of occupational medicamentosa-like dermatitis induced by trichloroethylene (OMLDT) . Methods: In September 2011 to February 2016, 12 patients with OMLDT were treated with etanercept 25 mg, subcutaneous injection, twice per week, doubling of first dose. The course of treatment was 6 weeks. The drug eruption area and severity index (DASI) score, the proportion of patients achieving a 50%, 75% and 90% reduction in DASI (DASI50, DASI75, DASI90) and the serum level of TNF-α were used to assess the efficacy at different times. Adverse reactions were also recorded and evaluated. The results were statistically analyzed by nonparametric Friedman test and repetitive measurement ANOVA using the software SPSS19.0. Results: After 4 weeks treatment, the DASI score decreased form 56.33±7.02 to 0.50±0.91 (P<0.01) . The DASI50, DASI75 and DASI90 were all increased to 12 (100%) . The serum level of TNF-α decreased form (43.74±41.62) pg/ml to (3.03±0.47) pg/ml (P<0.01) . Statistically significant difference was observed from the above indexes. There were no adverse reactions in clinical application. Conclusion Recombinant human tumor necrosis factor receptor Ⅱ-IgG Fc fusion protein may be a safe and effective drug in the treatment of OMLDT.