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ObjectiveTo establish an allele-specific polymerase chain reaction （PCR） method for identifying Scolopendra dispensing granules， so as to ensure the quality and therapeutic effects of Scolopendra and its preparations. MethodThe primer interval suitable for the PCR was selected based on the cytochrome c oxidase subunit 3（COX-3） gene sequence of Scolopendra， and the single nucleotide polymorphism （SNP） loci of Scolopendra and its adulterants were mined from the interval for the design of specific primers. The samples of Scolopendra and its adulterants were collected. The PCR system was established and optimized regarding the annealing temperature， cycles， Taq enzymes， DNA template amount， PCR instruments， and primer concentrations， and the specificity and applicability of this method were evaluated. ResultThe PCR system was composed of 12.5 μL 2×M5 PCR Mix， 0.4 μL forward primer （10 μmol·L-1）， 0.4 μL reverse primer （10 μmol·L-1）， 2.5 μL DNA template， and 9.2 μL sterile double distilled water. PCR parameters： Pre-denaturation at 94 ℃ for 3 min， 30 cycles （94 ℃ for 20 s， 62 ℃ for 20 s， 72 ℃ for 45 s）， and extension at 72 ℃ for 5 min. After PCR amplification with the system and parameters above， the electrophoresis revealed a bright band at about 135 bp for Scolopendra and no band for the adulterants. ConclusionThe established allele-specific PCR method can accurately identify the medicinal materials， decoction pieces， and standard decoction freeze-dried powder of Scolopendra， as well as the intermediates and final products of Scolopendra dispensing granules， which is of great significance for ensuring the quality and clinical efficacy of Scolopendra and its preparations.
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The correct pairing of disulfide bonds maintains the correct folding mode and high-level structure formation of peptides and protein drugs, which is crucial for the quality control of products. In order to ensure that the disulfide bonds are correctly paired, disulfide bond analysis is an essential part of peptides and protein drug characterization. Mass spectrometry can be used to analyze disulfide bonds. However, insulin and its analogues have two pairs of disulfide bonds without restriction enzyme cutting site. Conventional collision-induced dissociation (CID) and high-energy induced cleavage (HCD) cannot accurately locate the complex disulfide bond. In our study, three methods were used to localize the complex disulfide, including enzyme digestion combined with key peptide fragment in source decay (ISD) fragmentation method, enzyme digestion combined with partial reduction alkylation method, intact protein source ISD and electron transfer dissociation (ETD) cleavage method, The applicability of insulin aspart, insulin lispro and insulin glargine were also investigated. This study provides a new way for the quality control of disulfide bonding mode of insulin and its analogues, and also provides a reference for the disulfide bond localization of peptides or proteins containing this complex disulfide bond.
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Lung cancer is characterized by high incidence and mortality rates and invasiveness, and its occurrence and development are influenced by various factors. Mitochondria, as ubiquitous organelles in the human body, regulate cellular processes, such as metabolism, signal transduction, oxidative stress, and genomic instability, thereby affecting the initiation and progression of lung cancer. This article summarizes the recent research progress on mitochondrial-targeted drugs, mitochondrial transfer, and mitochondrial gene therapy for lung cancer treatment. This work also discusses the principles and prospects of mitochondrial therapy to provide new insights for lung cancer treatment.
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Combining domestic and international studies, an overview of the development of human papilloma virus (HPV) vaccine in the world and China is presented. The current situation of HPV vaccination for adolescents in China is analysed in the light of the latest policies in China, and rationalized recommendations are made to improve the HPV vaccination rate for adolescents in China.
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Objective:To analyze the potential therapeutic targets of Huangqin Tang in treatment of colorectal cancer(CRC)by network pharmacology and molecular docking techniques,and to clarify the related molecular mechanism.Methods:The active component and target dataset for Huangqin Tang were constructed based on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP);the CRC-disease related target dataset was built by Databases such as GeneCards,Online Mendelian Inheritance in Man(OMIM),and pharmacogenetics and Pharmacogenomics Knowledge Base(PharmGKB).Drug-disease target intersect,Huangqin Tang herbal formula network,and protein-protein interaction(PPI)networks were built by R software,Cytoscape software,and STRING Database;Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis were conducted by R software and Metascape platform;molecular docking validation was performed with AutoDock and PyMOL software to assess the ligand-receptor binding.Results:A total of 136 effective active components of Huangqin Tang were screened,and 242 potential targets were identified for treatment of CRC,including 18 core targets.Five core key targets closely related to CRC,identified through signaling pathway analysis,were protein kinase B1(AKT1),mitogen-activated protein kinase 3(MAPK3),proto-oncogene FOS,tumor protein p53(TP53),and proto-oncogene MYC.The GO functional enrichment analysis results mainly involved various biological processes related to cellular stress responses.The KEGG signaling pathway enrichment analysis results showed that potential targets were highly enriched in the cancer pathway;further analysis on CRC core targets via KEGG signaling pathway revealed involvement primarily in pathways related to endocrine resistance,apoptosis,and epidermal growth factor receptor-tyrosine kinase inhibitor(EGFR-TKI)resistance.The molecular docking results showed that the active components of Huangqin Tang,including quercetin,kaempferol,baicalein,7-methoxy-2-methyl isoflavone,and naringenin,were stably docked with AKT1,MAPK3,FOS,TP53,and MYC,and quercetin exhibited the best binding with AKT1.Conclusion:The active components of Huangqin Tang can treat CRC through multi-target and multi-pathway.The core ligand quercetin and AKT1 may exert the therapeutic effect in CRC by regulating the phosphatidylinositol 3-kinase(PI3K)/AKT and mammalian target of rapamycin(mTOR)signaling pathways to influence the cell proliferation,differentiation,and apoptosis processes.
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Objective:To observe the effects of Zhulian stimulant type Ⅰ acupuncture on the expression of brain-derived neurotrophic factor (BDNF) and its receptor TrkB and tissue homogenate cyclic adenosine phosphate (cAMP) in rats with diabetic bladder (DCP); To explore the mechanism of Zhulian stimulant type Ⅰacupuncture on DCP.Methods:Totally 50 SD rats were divided into control group, model group, Western medicine group, ordinary acupuncture group, Zhulian stimulant type Ⅰ acupuncture treatment group (acupuncture treatment group) according to random number table method, with 10 rats in each group. DCP rat model was prepared by intraperitoneal injection of streptozotocin (STZ), except for the control group. The Western medicine group was given mecobalamine for gavage; acupoints of "Zhongji", "Sanyinjiao", "Liechou" and "Taichong" were selected. The ordinary acupuncture group was treated with ordinary acupuncture technique, and the acupuncture treatment group was treated with Zhulian stimulant type Ⅰ acupuncture, 1 time/d, 30 minutes/time. Samples were taken after 4 weeks of treatment. The maximum bladder volume, residual urine volume and wet weight of the bladder were detected. The morphology of rat bladder was observed by HE staining. The expression level of BDNF was detected by immunohistochemistry. The expression of cAMP was detected by Western blot. The level of TrkB was determined by ELISA. Real-time fluorescence quantitative PCR (RT-PCR) was used to detect the mRNA expressions of BDNF and cAMP.Results:Compared with model group, maximum bladder volume, residual urine volume and wet weight of bladder in Western medicine group, ordinary acupuncture group and acupuncture treatment group decreased ( P<0.01), and those in Western medicine group and acupuncture treatment group were lower than those in ordinary acupuncture group ( P<0.01). The expressions of BDNF mRNA and protein, cAMP mRNA and protein in Western medicine group, ordinary acupuncture group and acupuncture treatment group increased ( P<0.05), and the level of TrkB increased, and the Western medicine group and acupuncture treatment group were higher than that in ordinary acupuncture group ( P<0.05). Conclusions:Zhuliping stimulant type Ⅰ acupuncture has a protective effect on the bladder function of diabetic rats. The mechanism may be related to the up-regulation of BDNF and mRNA, TrkB, cAMP and mRNA expressions.
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Objective To compare the effects of CalliSpheres drug-eluting beads transcatheter arterial chemoembolization(DEB-TACE)and conventional TACE(c-TACE)on liver fibrosis and liver function in the treatment of primary hepatocellular carcinoma(HCC).Methods A total of 40 patients diagnosed with HCC at Xuzhou Municipal Cancer Hospital of China between October 2020 and October 2022 were enrolled in this study.According to therapeutic scheme,the patients were divided into DEB-TACE group(n=20)and c-TACE group(n=20).The preoperative,and postoperative 5-day and one-month hyaluronidase(HA),type Ⅲ procollagen peptide(P Ⅲ NP),type Ⅳ collagen(CⅣ)and laminin(LN),alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBil),albumin(Alb),and prothrombin time(PT)were compared between the two groups.Results The technical success rate was 100％in both groups,and tumor staining completely disappeared immediately after TACE in all patients.The postoperative 5-day levels of HA,LN,P Ⅲ NP,and CⅣ in both groups were remarkably higher than the preoperative ones(P＜0.05).One month after TACE,HA level in the DEB-TACE group was prominently higher than its preoperative value(P＜0.05);HA and LN levels in the c-TACE group were obviously higher than their preoperative values(P＜0.05);and the HA and LN levels in c-TACE group were significantly higher than those in DEB-TACE group(P＜0.05).Five days after TACE,in the DEB-TACE group the AST and PT levels were higher than their preoperative values while the Alb level was lower than its preoperative value(P＜0.05);in the c-TACE group the ALT,AST,TBiL and PT were higher than their preoperative values while the Alb level was lower than its preoperative value(P＜0.05);the ALT and AST levels in the c-TACE group were strikingly higher than those in the DEB-TACE group while Alb level was strikingly lower than that in the DEB-TACE group(P＜0.05).Conclusion Both CalliSpheres DEB-TACE and c-TACE can aggravate liver fibrosis and cause liver function damage.However,the degree of liver fibrosis and liver function damage caused by CalliSpheres DEB-TACE is less than that caused by c-TACE.(J Intervent Radiol,2024,33:259-263)
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Biological toxins are toxic molecules produced by specific microorganisms,plants or animals.Due to their wide range of sources and high toxicity,the availability of protein and non-protein toxins is becoming increasingly important,some of which are used for military purposes and developed as biotoxin warfare agents.In this paper,the classification and mechanism of action of biological toxins are discussed.In addition,the strategies for prevention and control of biological toxins as well as their therapeutic applications are reviewed.
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Objective To comapre and analyze the differences and commonalities of expression profiles of serum exosomal microRNA between patients with thyroid nodules and healthy persons at different iodine levels,and then provide evidence for screening early diag-nostic markers of thyroid nodules at different iodine levels.Methods The peripheral blood samples from 10 patients with thyroid nod-ules and healthy volunteers at different iodine levels were collected.Their serum iodine levels were measured by the arsenic cerium cat-alytic spectrophotometry.Serum exosomal microRNA were extracted and the expression levels of microRNA were determined by the high-throughput sequencing technology.The differential target genes were predicted and further performed Gene ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis.Results Compared with healthy volunteers,there were 6 downreg-ulated miRNAs in the patients with thyroid nodules at different iodine levels,namely miR-324-5p,miR-6511b-3p,miR-9903,miR-550a-3p,miR-5001-3p,and miR-3688-3p.Differentially expressed exosomal microRNA could regulate the MAPK signaling path-way,PI3K-AKT signaling pathway,VEGF signaling pathway,and NF-κB signaling pathway.Conclusion Six differentially expressed microRNAs is identified,which may serve as biological markers for the early diagnosis of thyroid nodules at different iodine levels.
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Objective To investigate the distribution of abnormal karyotypes and their associations with clinical manifestations of the infertile patients in southern Sichuan Province.Methods A total of 4 157 infertile patients who attended the Reproductive Medicine Center of our hospital from July 2018 to June 2021 were included.The chromosome karyotype in peripheral blood was detected by G-banding,and their semen analysis results,uterine development and other clinical data were collected.Results Among the 4 157 patients,chromosomal polymorphisms were found in 239 cases(5.75％),and abnormal karyotypes wee found 137 cases(3.30％).The abnormal karyotypes included 57 cases(41.61％)of sex chromosome aneuploidy,6 cases(4.38％)of Robertsonian transloca-tions,32 cases(23.36％)of balanced translocations,21 cases(15.33％)of chromosomal inversions,9 cases(6.57％)of mosai-cism,8 cases(5.84％)of marker chromosomes,3 cases(2.19％)of sex reversal and 1 case(0.73％)of sex chromosome deletion.In male patients with abnormal karyotypes,91.58％showed abnormal semen parameters,while in those with polymorphic karyotypes,55％had abnormal semen parameters.The patients with Turner syndrome had significantly smaller uterine dimensions(longitudinal,transverse,and anteroposterior)compared to the normal control group(P＜0.01).Conclusion Chromosomal abnormalities should be the important cause of infertility.Conducting karyotype analysis combining with clinical manifestations is crucial examination for the di-agnosis and reproductive guidance of infertile patients.
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Purpose To explore the clinical and pathologi-cal features and the relationships between pathological features and drugs of patients with drug-induced liver injury(DILI)based on the hepatotoxicity injury patterns.Methods The clin-ical data,laboratory indicators,drugs,and liver biopsy of 50 cases of DILI were collected,the expression of CK19 was detec-ted by immunohistochemistry EnVision two-step method,and the reticular scaffold of liver tissue was displayed by Reticular fiber staining.Results Among the 50 patients with DILI,there were 29 cases of hepatocellular DILI,11 cases of cholestatic DILI,and 10 cases of mixed DILI,respectively,with the hepatocellu-lar DILI accounting for the highest proportion(58％).7 catego-ries of drugs induced DILI,with herbal ranking first(52％).Different types of drugs could cause different types of DILI,with herbal induced 17 cases hepatocellular DILI(58.62％)and an-ti-infectious and anticancer drugs induced all 3 cases cholestatic DILI(27.27％).Different types of DILI displayed various pathological characteristics.Hepatocellular congestion,feathery degeneration,and small bile duct thrombosis primarily occur in cholestasis and mixed DILI,while bridging necrosis,sub-large and large necrosis were mainly seen in hepatocellular DILI.Conclusion Based on hepatotoxicity injury patterns,DILI ex-hibits a variety of clinical and pathological characteristics,and there is some relationship between pathological characteristics and drugs.Liver puncture pathological biopsy plays an important role in improving the diagnosis and treatment of DILI.
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Objective:To construct a risk prediction model for urinary retention in patients undergoing radical cervical cancer surgery based on machine learning, and the prediction effect of the model was internally verified and evaluated, in order to provide reference for the early prevention and treatment of urinary retention in patients undergoing radical cervical cancer surgery.Methods:A total of 981 patients who underwent radical cervical cancer surgery in the First Affiliated Hospital of Anhui Medical University from June 2017 to February 2022 were selected and divided into the training set (687 cases) and the test set (294 cases) according to a ratio of 7∶3. Through literature review and risk factor analysis, the influencing factors of urinary retention after radical treatment of cervical cancer were explored, and the risk prediction model of urinary retention was constructed by using XGBoost, random forest, support vector machine and decision tree in machine learning. The accuracy rate, recall rate, F1 value and AUC of four machine learning algorithms were calculated by using the method of 10-fold cross-validation, and the model with the highest predictive efficiency was selected.Results:Among the 981 patients included, the incidence of urinary retention after radical cervical cancer surgery was 18.86% (185/981). The median age of urinary retention group was 51 years old, and that of non urinary retention group was 50 years old. Statistically significant variables in the univariate analysis and influencing factors summarized by literature review were featured, including patient age, intraoperative blood loss, body mass index (BMI), cancer stage, surgical method, surgical resection scope, whether pelvic lymph node dissection was performed, comorbidities and residual urine. Among the four model building methods of machine learning, the random forest model has the best effect, its training set F1 value was 0.94, the test set F1 value was 0.77, the ROC was plotted and the AUC was calculated to be 0.73. Age, intraoperative blood loss, BMI, cancer stage and surgical method contributed significantly to the classification of random forest model.Conclusions:The prediction model of urinary retention risk after radical cervical cancer surgery based on random forest method has the best efficacy. It is useful to help nursing personnel evaluate the risk of the uroschesis for a patient and then take targeted nursing interventions to actively prevent postoperative urinary retention.
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Objective:To develop a risk assessment tool for chemotherapy induced nausea and vomiting after transcatheter arterial chemoembolization in patients with primary liver cancer, and to verify its predictive efficiency, so as to provide reference for risk assessment and nursing intervention of nausea and vomiting in patients with primary liver cancer.Methods:A cross-sectional survey was used. The risk assessment tool was compiled by using literature analysis, Delphi expert consultation and analytic hierarchy process. 153 patients with primary liver cancer who underwent transcatheter arterial chemoembolization in the Department of Intervention, Jiangsu Cancer Hospital from May 2022 to April 2023 were selected for assessment by using convenience sampling method. Receiver operating characteristic curve, sensitivity, specificity and Youden index were used to test the prediction efficiency of risk assessment tools.Results:Among 153 patients, there were 78 males, 75 females, aged (48.44 ± 7.76) years old. The expert positive coefficient of the three rounds of inquiry letters was all 100%, the expert authority coefficient was 0.936, 0.950 and 0.960 respectively, and the Kendall harmony coefficient was 0.490, 0.327 and 0.414 respectively (all P<0.01). The risk assessment tool for chemotherapy induced nausea and vomiting after transcatheter arterial chemoembolization in patients with primary liver cancer included 14 items. The results of prediction efficiency analysis showed that the area under the receiver operating characteristic curve was 0.938 (95% CI 0.903-0.974, P<0.01). When the cut-off score was 56.2, the sensitivity, specificity and Youden index of the risk assessment tool were 0.926, 0.881 and 0.807, which had the best prediction efficiency. Conclusions:The risk assessment tool for chemotherapy induced nausea and vomiting after transcatheter arterial chemoembolization in patients with primary liver cancer has high scientificity, predictive efficiency and practicability, and is suitable for the risk assessment for chemotherapy induced nausea and vomiting after transcatheter arterial chemoembolization in patients with primary liver cancer in China.
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BACKGROUND:Previous research by the research team found that domestically produced porous tantalum is beneficial for early adhesion and proliferation of MG63 cells,and can be used as a scaffold material for bone tissue engineering. OBJECTIVE:To investigate the effect of domestic porous tantalum modified by osteogenic induction factor slow-release system on the adhesion,proliferation,and differentiation of MG63 cells. METHODS:Osteogenic induction factor slow-release system was constructed by adding 15%volume fraction of osteogenic factor solution to poly(lactic-co-glycolic-acid)gel.The passage 3 MG63 cells were inoculated on a porous tantalum surface(control group),porous tantalum surface coated with poly(lactic-co-glycolic-acid)copolymer gel(gel group),and porous tantalum surface coated with osteoblastic induction factor slow-release system(slow-release system group),and co-cultured for 5 days.The surface cytoskeleton of the material was observed by phalloidine staining.Cell proliferation was detected by flow cytometry.Western blot assay and RT-qPCR were used to detect the protein and mRNA expressions of type Ⅰ collagen,osteopontin,and RUNX-2 on the surface cells of the material. RESULTS AND CONCLUSION:(1)Phalloidine staining showed that MG63 cells adhered to and grew on the surface and inside of the three groups of porous tantalum,and the matrix secreted by the cells covered the surface of the material.(2)Flow cytometry showed that the cell proliferation in the slow-release system group was faster than that in the control group and the gel group(P<0.05).(3)Western blot assay and RT-qPCR showed that the protein and mRNA expressions of type Ⅰ collagen,osteopontin,and RUNX-2 in the slow-release system group were higher than those in the control group and gel group(P<0.05).(4)The results showed that the domestic porous tantalum modified by the osteogenic induction factor slow-release system was beneficial to the adhesion,proliferation,and differentiation of MG63 osteoblasts.
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BACKGROUND:Orthopedic robots have been widely used in clinical practice,and relevant reports have shown that they have many advantages such as minimal trauma and short surgical time.However,there is currently no clear report on how accurate they are. OBJECTIVE:To evaluate the accuracy of robot-assisted sacroiliac screw insertion. METHODS:A total of 131 patients with sacroiliac joint fracture and dislocation and sacral fracture admitted to the Department of Trauma Surgery,Gansu Provincial Hospital from January 2020 to April 2023 were retrospectively collected,including 131 S1 screws and 46 S2 screws,totaling 177 screws.They were divided into two groups based on whether robot-assisted navigation was performed.There were 63 cases of sacroiliac screws inserted under robot-assisted navigation(observation group),with 36 males and 27 females,aged 19-72 years,with a mean age of(45.3±17.6)years.Among them,39 cases were fixed with only S1 screws,while 24 cases were fixed with S1S2 screws,resulting in a total of 87 sacroiliac screws.Under C-arm fluoroscopy,68 cases of sacroiliac screws were inserted with bare hands(control group),including 41 males and 27 females,aged 23-67 years,with a mean age of(42.6±21.3)years.Among them,46 cases were fixed with simple S1 screws,while 22 cases were fixed with S1S2 screws,resulting in a total of 90 sacroiliac screws.A postoperative CT scan was performed to evaluate the number of S1 screws,S2 screws,total screw level,and calculate accuracy based on the method introduced by SMITH et al. RESULTS AND CONCLUSION:(1)In the observation group,62 S1 screws were accurately placed(62/63),with an accuracy rate of 98%.24 S2 screws were accurately placed(24/24),with an accuracy rate of 100%.The total number of screws accurately placed was 86(86/87),with an accuracy rate of 99%.(2)In the control group,58 S1 screws were accurately inserted(58/68),with an accuracy rate of 85%.19 S2 screws were accurately inserted(19/22),with an accuracy rate of 86%.The total number of screws accurately inserted was 77(77/90),with an accuracy rate of 86%.(3)There was a statistically significant difference in the accuracy of the S1 screw,S2 screw,and total screw between the two groups(P<0.05).It is suggested that the placement of sacroiliac screws under robot navigation has higher accuracy compared to manual placement under C-arm fluoroscopy,but still has a lower error rate in placement.
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BACKGROUND:Intervertebral disc degeneration is a condition caused by the combined effects of various factors,such as cellular apoptosis,oxidative stress,and inflammatory responses.Currently,it is believed that the core of this condition lies in the degeneration and apoptosis of nucleus pulposus cells(NPCs).However,the specific pathological mechanisms remain unclear. OBJECTIVE:By investigating the expression of the phosphatidylinositol-3 kinase(PI3K)/protein kinase B(Akt)/hypoxia-inducible factor 1-alpha(HIF-1α)signaling pathway and the apoptosis of NPCs under different oxygen concentrations,to clarify the biological characteristics of NPCs under varying oxygen levels,and to explore the mechanisms of intervertebral disc degeneration. METHODS:Normal and degenerated NPCs were collected.The second-generation cells were used for imaging identification.The third-generation cells were cultured in the following conditions:37℃,air,100%humidity.Leibovitz's medium containing 100 μmol/L CoCl2 and 10%fetal bovine serum medium containing 100 μmol/L H2O2 were used to create distinct oxygen concentration environments for the third-generation cells,allowing for the investigation of cellular responses and behaviors under normal,low oxygen,and oxidative stress conditions.The third-generation cells were divided into six groups:normal NPCs+hypoxia,normal NPCs+normoxia,normal NPCs+oxidative stress,degenerated NPCs+hypoxia,degenerated NPCs+normoxia,and degenerated NPCs+oxidative stress groups.Cell viability and proliferation were assessed using the cell counting kit-8 method.Cell apoptosis was detected using flow cytometry.RT-PCR and western blot assay were utilized to examine the protein and mRNA expression levels of PI3K,AKT,and HIF-1α. RESULTS AND CONCLUSION:At different oxygen concentrations,the cell proliferation rate of both normal and degenerated NPCs decreased as the oxygen concentration increased.Conversely,the apoptosis rate increased as the oxygen concentration rose(P<0.05).With the normal NPCs+hypoxia group as the control group,the effect of degenerated NPCs on the apoptosis rate was highly significant(P<0.001).Oxygen concentration had a highly significant impact on both NPC proliferation rate and apoptosis rate(P<0.001).The interaction between cell degeneration and oxygen concentration significantly affected both NPC proliferation and apoptosis rates(P<0.05).At different oxygen concentrations,the protein and mRNA expression levels of PI3K,AKT,and HIF-1α in normal NPCs were highest under low oxygen concentration,followed by oxidative stress environment,and lowest under normoxia.In degenerated NPCs,the protein and mRNA expression levels of PI3K,AKT,and HIF-1α decreasd as the oxygen concentration increased.The protein and mRNA expression levels of PI3K and Akt in normal NPCs were significantly higher than those in degenerated NPCs(P<0.05).With the normal NPCs+hypoxia group as the control group,the effects of normal or degenerated NPCs,as well as oxygen concentration,on the protein and mRNA expression of PI3K,AKT,and HIF-1α were highly significant.The interaction between cell degeneration and oxygen concentration also had an extremely significant effect on the protein and mRNA expression of PI3K,AKT,and HIF-1α(P<0.001).To conclude,there is a close correlation between the proliferation and apoptosis of NPCs and both oxygen concentration and the cellular functional state.The PI3K/Akt/HIF-1α signaling pathway exhibits antagonistic regulatory effects under various cellular functional states and different oxygen concentration environments.The mechanism may be associated with the activation of the PI3K/Akt signaling pathway,which consequently transcribes HIF-1α,thus maintaining the balance of reactive oxygen species metabolism.This pathway plays a significant role in inhibiting oxidative stress,antagonizing NPCs apoptosis,and consequently delaying intervertebral disc degeneration.
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BACKGROUND:Previous studies have successfully constructed erythropoietin-overexpressed umbilical cord mesenchymal stem cells.It was found that the apoptosis of ischemic and hypoxic human neuroblastoma cell line(SH-SY5Y)was significantly reduced by erythropoietin-overexpressed umbilical cord mesenchymal stem cells. OBJECTIVE:To explore the possible neuroprotective mechanisms of erythropoietin-overexpressed umbilical cord mesenchymal stem cells against ischemic-hypoxic SH-SY5Y and their associated epigenetic mechanisms. METHODS:Oxygen-glucose deprivation was applied to ischemia-hypoxia-induced SH-SY5Y cell injury,and multifactorial assays were applied to detect the expression levels of inflammatory factors in the cells before and after hypoxia and co-culture,respectively,with mesenchymal stem cells,as well as lentiviral-transfected null-loaded plasmids of the negative control mesenchymal stem cells and erythropoietin-overexpressed umbilical cord mesenchymal stem cells.The expression levels of supernatant inflammatory factors were detected by multifactor assay after co-culture.Proteomics was used to detect the differentially expressed proteins of negative control mesenchymal stem cells and erythropoietin-overexpressed umbilical cord mesenchymal stem cells.Cleavage under targets and tagmentation sequencing was applied to detect genomic H3K4me2 modification,and joint analysis was conducted with RNA-sequencing.Lentiviral vector infection was applied to construct the stable knockdown of REST in SH-SY5Y cells.qRT-PCR and western blot assay were performed to detect the expression level of REST.The apoptosis was detected by flow cytometry after co-culture of oxygen-glucose deprivation treatment with erythropoietin-overexpressed umbilical cord mesenchymal stem cells.The expression difference of H3K36me3 group proteins was detected by western blot assay,and transcriptome sequencing was performed to analyze the differentially expressed genes. RESULTS AND CONCLUSION:(1)Compared with the control group,monocyte chemotactic protein 1,interleukin-6,interleukin-18,and interleukin-1 beta,interferon α2,and interleukin-23 levels significantly increased in the cerebrospinal fluid supernatant of patients with ischemic-hypoxic encephalopathy(P<0.01).(2)After co-culturing SH-SY5Y cells with erythropoietin-overexpressed umbilical cord mesenchymal stem cells under ischemia and hypoxia,the expression levels of monocyte chemotactic protein 1 and interleukin-6 were significantly reduced.(3)Analysis of protein network interactions revealed significant downregulation of monocyte chemotactic protein 1,interleukin-6 related regulatory proteins CXCL1 and BGN.(4)Transcriptome sequencing analysis found that pro-inflammatory genes were down-regulated,and functional enrichment of histone modifications,and the expression of transcription factors REST and TET3 significantly up-regulated in the erythropoietin-overexpressed umbilical cord mesenchymal stem cell group compared with the negative control mesenchymal stem cell group.(5)Combined analysis of transcriptome sequencing and cleavage under targets and tagmentation revealed changes in epigenetic levels as well as significant activation of the promoter regions of transcription factors REST and TET3.(6)Stable knockdown REST in SH-SY5Y cells was successfully constructed;the transcript levels of REST mRNA and protein expression were both decreased.(7)After the REST knockdown SH-SY5Y cells were co-cultured with erythropoietin-overexpressed umbilical cord mesenchymal stem cells,apoptosis was significantly increased and H3K36me3 expression was significantly decreased.Transcriptome sequencing results showed that the expression of inflammation-related genes Aldh1l2 and Cth,as well as apoptosis-suppressor genes Mapk8ip1 and Sod2 was reduced at mRNA transcription level(P<0.01).(8)It is concluded that erythropoietin-overexpressed umbilical cord mesenchymal stem cells activated the expression of REST and TET3 by altering the kurtosis of H3K4me2 and upregulated the modification level of H3K36me3,which in turn regulated the expression of inflammation-related genes Aldh1l2 and Cth,as well as apoptosis-suppressor genes Mapk8ip1 and Sod2,and facilitated neuronal survival.
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Primary hepatic cancer is one of the major problems that need to be solved urgently in the field of public health, seriously endangering the life and health of Chinese people. Its treatment mode is multidisciplinary participation and synergy of multiple therapeutic methods. Even though there are many common clinical treatments for liver cancer in China, its therapeutic outcome is still unsatisfactory. yttrium-90 has been applied for more than 20 years, and a large amount of foreign clinical data have been accumulated. Combining the latest literature and clinical practice, the authors describe the clinical application and research progress of yttrium-90 micro-sphere selective internal radiation therapy in primary liver cancer.
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Objective:To investigate the evaluation efficacy and predictive prognostic value of alpha-fetoprotein (AFP) response in tyrosine kinase inhibitors (TKIs) in combination with PD-1 inhibitors (α-PD-1) for intermediate-to-advanced hepatocellular carcinoma (HCC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 205 patients with intermediate-to-advanced HCC who were admitted to 9 medical centers, including Mengchao Hepatobiliary Hospital of Fujian Medical University et al, from March 2020 to July 2022 were collected. There were 178 males and 27 females, aged (52±12)years. Based on AFP response at 6-8 weeks after treatment, patients were divided into the AFP response group (AFP level decreased by ≥50% compared to baseline) and the AFP no response group (AFP level decreased by <50% compared to baseline). Observation indicators: (1) AFP response evaluation of anti-tumor efficacy; (2) comparison of patient prognosis; (3) analysis of factors affecting patient prognosis. Measurement data with normal distrubution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range) and M( Q1, Q3). Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. The Kaplan-Meier method was used to draw survival curve and calculate survival rate, and the Log-Rank test was used for survival analysis. The COX proportional risk model was used for univariate analysis and the COX stepwise regression model was used for multivariate analysis. Results:(1) AFP response evaluation of anti-tumor efficacy. Before treatment, all 205 patients were positive of AFP, with a baseline AFP level of 1 560(219,3 400)μg/L. All 205 patients were treated with TKIs in combination with α-PD-1, and the AFP level was 776(66,2 000)μg/L after 6 to 8 weeks of treatment. Of the 205 patients, 88 cases were classified as AFP response and 117 cases were classified as AFP no response. According to the response evaluation criteria in solid tumors version 1.1, the objective response rate (ORR) and disease control rate (DCR) were 42.05%(37/88) and 94.32%(83/88) in patients of the AFP response group and 16.24% (19/117) and 64.10% (75/117) in patients of the AFP no response group, showing significant differences between them ( χ2=16.846, 25.950, P<0.05). According to the modified response evaluation criteria in solid tumors, the ORR and DCR were 69.32% (61/88) and 94.32% (83/88) in patients of the AFP response group and 33.33% (39/117) and 64.10% (75/117) in patients of the AFP no response group, showing significant differences between them ( χ2=26.030, 25.950, P<0.05). (2) Comparison of patient prognosis. All 205 patients were followed up for 12.4(range, 2.4-34.0)months after treatment. The median progression free survival time and total survival time were 5.5 months and 17.8 months, respectively. The 1-year, 2-year progression free survival rates were 20.8% and 7.2%, and the 1-year, 2-year overall survival rates were 68.7% and 31.5%, respectively. The median progression free survival time, 1-year and 2-year progression free survival rates were 9.7 months, 39.6% and 14.2% in patients of the AFP response group and 3.7 months, 7.8% and 2.0% in patients of the AFP no response group, showing a significant difference in progression free survival between them ( χ2=43.154, P<0.05). The median overall survival time, 1-year and 2-year overall survival rates were not reached, 85.2% and 56.3% in patients of the AFP response group and 14.6 months, 56.3% and 14.5% in patients of the AFP no response group, showing a significant difference in overall survival between them ( χ2=33.899, P<0.05). (3) Analysis of factors affecting patient prognosis. Results of multivariate analysis showed that invasion of large blood vessels, extrahepatic metastasis, combined hepatic artery intervention therapy, and AFP response were independent factors influencing progression free survival in patients with intermediate-to-advanced HCC who were treated with TKIs in combination with α-PD-1 ( hazard ratio=1.474, 1.584, 0.631, 0.367, 95% confidence interval as 1.069-2.033, 1.159-2.167, 0.446-0.893, 0.261-0.516, P<0.05), and Eastern Cooperative Oncology Group score, invasion of large blood vessels, extrahepatic metastasis, and AFP response were independent factors influencing overall survival in patients with intermediate-to-advanced HCC who were treated with TKIs in combination with α-PD-1 ( hazard ratio= 1.347, 1.914, 1.673, 0.312, 95% confidence interval as 1.041-1.742, 1.293-2.833, 1.141-2.454, 0.197-0.492, P<0.05). Conclusions:AFP response at 6-8 weeks after treatment can effectively evaluate anti-tumor efficacy of TKIs in combination with α-PD-1 for intermediate-to-advanced HCC. AFP response is the independent factor influencing progression free survival and overall survival in patients with intermediate-to-advanced HCC who were treated with TKIs in combination with α-PD-1.
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Objective:To study the clinical value of enhanced recovery after surgery(ERAS) strategy combined with early intestinal fluid reinfusion among neonates receiving jejunostomy due to intestinal obstruction.Methods:From December 2018 to December 2022, neonates with intestinal obstruction receiving jejunostomy in the Department of Neonatal Surgery of our hospital were prospectively enrolled. They were randomly assigned into ERAS group and traditional treatment (TT) group after surgery. The ERAS group was treated with ERAS strategy plus early intestinal fluid reinfusion. The TT group was treated with conventional gastrointestinal decompression, analgesia as needed and enteric fluid reinfusion according to the amount of defecation. The postoperative parenteral nutrition (PN) duration (T pn), central venous catheter (CVC) duration (T cvc), daily weight gain, duration of postoperative hospital stay (T hos), complications and readmission rate within 30 days were compared between the two groups. Results:A total of 22 cases were included in the ERAS group and 20 cases were in the TT group. T pn [(22.6±9.4) d vs. (30.7±11.3) d], T cvc [(5.9±0.8) d vs. (9.9±2.1) d] and T hos [(26.8±9.8) d vs. (33.8±11.5) d] in the ERAS group were significantly shorter than the TT group ( P<0.05). No significant difference existed in daily weight gain between the two groups ( P>0.05). The incidence of postoperative gastrointestinal mucosal bleeding in the ERAS group was significantly lower than the TT group (13.6% vs. 45.0%)( P<0.05). No significant differences existed in the following items between the two groups: feeding intolerance, PN-associated cholestasis, CVC-related bloodstream infection, intestinal fluid reinfusion-related complications, premature closure of fistula and readmission rate within 30 days (all P>0.05). Conclusions:The application of ERAS strategy plus early intestinal fluid reinfusion in neonates with enterostomy is safe and feasible, which can reduce the postoperative durations of PN, CVC and hospital stay and accelerate the recovery.