Based on copper death, this study investigates the effect and mechanism of Shenmai Injection on isoproterenol(ISO)-induced myocardial fibrosis(MF) in rats. SPF-grade male SD rats were randomly divided into a normal group, model group, captopril(5 mg·kg~(-1)) positive control group, and Shenmai Injection low(6 mL·kg~(-1)), medium(9 mL·kg~(-1)), and high(12 mL·kg~(-1)) dose groups. Except for the normal group, the rats in the other groups were subcutaneously injected with ISO(5 mg·kg~(-1)) once a day for 10 consecutive days to establish an MF model. Starting from the second day after successful modeling, intraperitoneal injections of the respective treatments were administered for 28 consecutive days. Hematoxylin-eosin(HE) and Masson staining were used to observe pathological changes and fibrosis levels in the myocardial tissue. Colorimetry was employed to detect serum Cu~(2+) concentration in rats. The levels of inflammatory cytokines interleukin-6(IL-6), interleukin-1β(IL-1β), interleukin-18(IL-18), tumor necrosis factor-α(TNF-α), as well as mitochondrial energy metabolites adenosine triphosphate(ATP), adenosine diphosphate(ADP), and adenosine monophosphate(AMP) in serum were measured using enzyme-linked immunosorbent assay(ELISA). Western blot was performed to detect the expression of collagen Ⅰ(Col-Ⅰ), collagen Ⅲ(Col-Ⅲ), and copper death-related proteins dihydrolipoamide acetyltransferase(DLAT), ferredoxin 1(FDX1), lipoic acid synthetase(LIAS), and heat shock protein 70(HSP70) in myocardial tissue. Immunofluorescence was used to detect the expression of DLAT, FDX1, and HSP70, while immunohistochemistry was conducted to examine the expressions of DLAT, FDX1, LIAS, and HSP70. The results showed that, compared to the model group, the myocardial structure disorder and collagen fiber deposition in the drug treatment groups were significantly improved, the cardiac index level was reduced, serum Cu~(2+), IL-6, IL-1β, IL-18, TNF-α, ADP, and AMP levels were significantly decreased, ATP levels were significantly increased, and the expressions of Col-Ⅰ, Col-Ⅲ, and HSP70 proteins in myocardial tissue were significantly reduced, while the expressions of DLAT, FDX1, and LIAS proteins were significantly elevated. In conclusion, Shenmai Injection effectively alleviates myocardial structure disorder and interstitial collagen fiber deposition in ISO-induced MF rats, promotes copper excretion, and reduces copper death in the ISO-induced rat MF model.
Animals ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Rats ; Myocardium/metabolism* ; Drug Combinations ; Fibrosis/metabolism* ; Copper/blood* ; Cardiomyopathies/genetics* ; Humans

OBJECTIVE: To study the efficacy of lumbar oblique manipulation in the treatment of lumbar disc herniation with different herniation locations based on MSU classification. METHODS: A total of 272 patients with lumbar disc herniation who were treated from June 2023 to December 2023 were divided into central type group, paracentral type group, and far lateral type group. Among them, there were 73 cases in the central type group, including 41 males and 32 females, with an age of (46.39±6.89) years;161 cases in the paracentral type group, including 88 males and 73 females, with an age of (37.14±5.89) years;and 38 cases in the far lateral type group, including 22 males and 16 females, with an age of (28.56±4.89) years. The visual analogue scale (VAS) and straight leg raising angle of the three groups of patients before treatment, after treatment, and at 1 and 3 months after treatment were recorded, and inter-group, intra-group, and correlation comparisons were made. RESULTS: A total of 272 patients were followed up, with a follow-up time of (3.0±0.2) months. The VAS score of central type patients after treatment was 2(2, 3) points, which was lower than 4(3, 5) points before treatment, and the difference was statistically significant (P<0.05). There was no statistically significant difference between 1 month and 3 months after treatment and before treatment (P>0.05). The VAS score of paracentral type patients after treatment 2(2, 3) points and 1 month after treatment 3(2, 4) points were lower than that before treatment 5(4, 6) points, and the differences were statistically significant (P<0.05). There was no statistically significant difference in VAS between 3 months after treatment and before treatment (P>0.05). There were no statistically significant differences in VAS scores of far lateral type patients before treatment, after treatment, and at 1 and 3 months after treatment (P>0.05). The straight leg raising angle of central type patients after treatment 64(58, 69) and 1 month after treatment 58(52, 65) were significantly different from that before treatment 44(40, 51) (P<0.05);there was no statistically significant difference between 3 months after treatment and before treatment (P>0.05). The straight leg raising angle of paracentral type patients after treatment 61(55, 67)°, 1 month after treatment 61(53, 66)°, and 3 months after treatment 47(41, 56)° were significantly different from that before treatment 44(36, 52)° (P<0.05). There were no statistically significant differences in the straight leg raising angle of far lateral type patients before treatment, after treatment, and at 1 and 3 months after treatment (P>0.05). There was a correlation between VAS and straight leg raising angle in the three groups of patients, but there was no linear relationship. CONCLUSION Lumbar oblique manipulation has a better effect in treating patients with central and paracentral lumbar disc herniation, but a poor effect in treating far lateral type;after treatment, the curative effect of paracentral type patients lasts longer than that of central type patients.
Humans ; Male ; Female ; Intervertebral Disc Displacement/physiopathology* ; Adult ; Lumbar Vertebrae/physiopathology* ; Middle Aged ; Manipulation, Spinal

OBJECTIVES: To investigate the role of long noncoding RNA (lncRNA) HClnc1 in regulating proliferation, invasion, and migration of hepatocellular carcinoma (HCC) cells and the regulatory mechanism. METHODS: HClnc1 expression levels in liver cancer tissues were analyzed using data from the TCGA database. BrdU incorporation, plate cloning, and transwell assays were employed to examine the effects of HClnc1 silencing/overexpression and/or ODC1 silencing on proliferation, invasion, and migration of liver cancer cells. The effects of HClnc1 silencing on ODC1 protein and mRNA expression in the liver cancer cells were analyzed using qRT-PCR and Western blotting. The activity of ODC1 promoter was analyzed using a dual luciferase reporter gene assay. Pull-down experiment, mass spectrometry analysis, and chromatin immunoprecipitation (ChIP) assay were used for identification of HClnc1-binding proteins and their interactions. Protein interactions with the ODC1 promoter region and their binding efficiencies were investigated using RNA interference and ChIP analysis. RESULTS: HClnc1 was significantly overexpressed in HCC tissues. In liver cancer cells, HClnc1 silencing significantly inhibited cell proliferation, invasion, and migration, while HClnc1 overexpression promoted these behaviors. ODC1 silencing also suppressed malignant behaviors of liver cancer cells, and counteracted the effects of HClnc1 overexpression. Interference of HClnc1 obviously inhibited ODC1 promoter activity. RBBP5 and KAT2B proteins were identified to bind simultaneously with HClnc1. HClnc1 overexpression upregulated ODC1 protein expression, while interference of RBBP5 or KAT2B downregulated ODC1 protein expression and blocked HClnc1-induced upregulation of ODC1 protein. Both RBBP5 and KAT2B could directly bind to ODC1 promoter region; knocking out KAT2B or RBBP5 reduced the binding efficiency, while knocking out HClnc1 reduced the binding of both RBBP5 and KAT2B to ODC1 promoter region. CONCLUSIONS By targeting the RBBP5/KAT2B epigenetic modification complex, HClnc1 increases ODC1 promoter activity to enhance ODC1 transcription and promote the proliferation and migration of liver cancer cells.
Humans ; Cell Proliferation ; RNA, Long Noncoding/genetics* ; Cell Movement ; Liver Neoplasms/metabolism* ; Cell Line, Tumor ; Carcinoma, Hepatocellular/genetics* ; Promoter Regions, Genetic ; Gene Expression Regulation, Neoplastic

Objective To explore the role of miR-429 in synovial mesenchymal stem cell-derived exosomes(SMSC-Exos)in repairing cartilage damage in temporomandibular joint osteoarthritis(TMJ OA)by extracting SMSC-Exos from human synovial tissue and screening differentially expressed microRNA(miRNA)through transcriptome sequencing.Methods Human synovial tissues were obtained from 6 patients who underwent surgery at the First Medical Center of the Chinese PLA General Hospital from June to December 2023,including 3 patients with osteoarthritis(OA group)and 3 control patients(control group),all of whom were male.SMSC-Exos were extracted from the synovial tissues for miRNA sequencing and differential expression analysis.Further,Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed on the target genes of differentially expressed miRNA to identify key functional miRNA and construct miRNA-target gene regulatory networks and protein-protein interaction(PPI)networks of target genes.An in vitro model of rabbit condylar cartilage cell inflammatory microenvironment induced by interleukin-1β(IL-1β)was established,with the control group cultured in DMEM/F12 basic medium and the inflammation-induced group cultured in DMEM/F12 basic medium containing 10 ng/ml IL-1β.RT-qPCR was used to detect the effects of overexpressed target miRNA on the mRNA expression levels of cartilage phenotype factors such as type Ⅱ collagen α1 chain(Col2a1),aggrecan(Acan),as well as inflammatory factors including a disintegrin and metalloproteinase with thrombospondin motifs 5(Adamts5)and cyclooxygenase-2(Cox-2).Results(1)SMSC-Exos were successfully isolated,cultured,and identified.(2)miRNA sequencing of SMSC-Exos from OA and control groups revealed 16 differentially expressed miRNAs(|log2FC|>2,P<0.05).Compared with control group,7 miRNAs were up-regulated and 9 were down-regulated in OA group.GO and KEGG analysis indicated that the target genes of miR-429 were mainly involved in development process,anatomical structure development,system development,cell development and differentiation,and were enriched in inflammation-related pathways such as mitogen-activated protein kinase(MAPK)and phosphatidylinositol 3-kinase-protein kinase B(PI3K-Akt).(3)Functional validation of miR-429 in the rabbit condylar cartilage cell inflammatory model showed that overexpression of miR-429 increased the mRNA expression levels of Col2a1 and Acan(P<0.05)and decreased the mRNA expression levels of Adamts5 and Cox-2(P<0.05)in the inflammation-induced group.Conclusions miRNA sequencing of SMSC-Exos isolated and identified from human synovial tissues reveals a specific miRNA expression profile in OA patients,with miR-429 significantly down-regulated.Functional validation demonstrates that overexpression of miR-429 has reparative and anti-inflammatory effects on condylar cartilage cells in an inflammatory microenvironment.

Aim To investigate the role of metabolites of eicosapentaenoic acid (EPA) in promoting the transdifferentiation of pancreatic α cells to β cells. Methods Male C57BL/6J mice were injected intraperitoneally with 60 mg/kg streptozocin (STZ) for five consecutive days to establish a type 1 diabetes (T1DM) mouse model. After two weeks, they were randomly divided into model groups and 97% EPA diet intervention group, 75% fish oil (50% EPA +25% DHA) diet intervention group, and random blood glucose was detected every week; after the model expired, the regeneration of pancreatic β cells in mouse pancreas was observed by immunofluorescence staining. The islets of mice (obtained by crossing GCG

Objective:To analyze the clinical characteristics of patients undergoing extracorporeal cardiopulmonary resuscitation (ECPR), and to explore the risk factors leading to poor prognosis.Methods:The clinical data of 95 patients with ECPR admitted to the First Affiliated Hospital of Zhengzhou University from January 2020 to May 2023 were retrospectively analyzed. According to the survival status at the time of discharge, the patients were divided into the survival group and death group. The difference of clinical data between the two groups was compared to explore the risk factors related to death and poor prognosis. Risk factors associated with death were identified by Binary Logistic regression analysis. Results:A total of 95 patients with ECPR were included in this study, 62 (65.3%) died and 33 (34.7%) survived at discharge. Patients in the death group had longer low blood flow time [40 (30, 52.5) min vs. 30 (24.5, 40) min ] and total cardiac arrest time[40 (30, 52.5) min vs. 30(24.5, 40) min], shorter total hospital stay [3 (2, 7.25) d vs. 19 (13.5, 31) d] and extracorporeal membrane oxygenation (ECMO) assisted time [26.5 (17, 50) h vs. 62 (44, 80.5) h], and more IHCA patients (56.5% vs. 33.3%) and less had spontaneous rhythm recovery before ECMO (37.1% vs. 84.8%). Initial lactate value [(14.008 ± 5.188) mmol/L vs.(11.23 ± 4.718) mmol/L], APACHEⅡ score [(30.10 ± 7.45) vs. (25.88 ± 7.68)] and SOFA score [12 (10.75, 16) vs. 10 (9.5, 13)] were higher ( P< 0.05). Conclusions:No spontaneous rhythm recovery before ECMO, high initial lactic acid and high SOFA score are independent risk factors for poor prognosis in ECPR patients.

Objective To investigate the association between four single nucleotide polymorphisms(SNP)(rs9340 in MAPK1,rs14804 in NRAS,rs712 and rs7973450 in KRAS)in the 3'UTR of ERK1/2 signaling pathway-related genes and non-small cell lung cancer(NSCLC).Methods A total of 478 NSCLC patients and 480 healthy controls were enrolled in this study.Four SNPs were genotyped by using TaqMan assays.The association between the four SNPs and NSCLC was analyzed.Results The distribution frequency difference of the allele of rs9340 was statistically significant between the control group and the non-small cell squamous cell carcinoma(SCC)group(P = 0.009),suggesting that the G allele of rs9340 may be a protective factor for non-small cell lung squamous cell carcinoma(OR = 0.67,95%CI:0.50～0.91).In addition,in the<50 years age group,the distribution frequency difference of the allele of rs9340 was statistically significant between the control group and the NSCLC group(P = 5.07×10-4),indicating that the G allele of rs9340 may be a protective factor for NSCLC(OR = 0.46,95%CI:0.29～0.72).Conclusion The SNP rs9340 in MAPK1 may be associated with the risk of NSCLC.

Objective To study the clinical characteristics of children with anti-neutrophil cytoplasmic antibody(ANCA)-associated vasculitis(AAV).Methods A retrospective analysis was conducted on the clinical data of 25 children diagnosed with AAV at the Second Xiangya Hospital of Central South University from January 2010 to June 2022.Results Among the AAV children,there were 5 males and 20 females,with a median age of onset of 11.0 years.Involvement of the urinary system was seen in 18 cases(72%);respiratory system involvement in 10 cases(40%);skin involvement in 6 cases(24%);eye,ear,and nose involvement in 5 cases(20%);joint involvement in 4 cases(16%);digestive system involvement in 2 cases(8%).Eleven cases underwent kidney biopsy,with 5 cases(46%)showing focal type,2 cases(18%)showing crescentic type,2 cases(18%)showing mixed type,and 2 cases(18%)showing sclerotic type.Immune complex deposits were present in 5 cases(45%).Seven cases reached chronic kidney disease(CKD)stage Ⅴ,with 2 cases resulting in death.Two cases underwent kidney transplantation.At the end of the follow-up period,2 cases were at CKD stage Ⅱ,and 1 case was at CKD stage Ⅲ.Of the 16 cases of microscopic polyangiitis(MPA)group,13(81%)involved the urinary system.Of the 9 cases of granulomatosis with polyangiitis(GPA),6 cases(66%)had sinusitis.Serum creatinine and uric acid levels were higher in the MPA group than in the GPA group(P<0.05),while red blood cell count and glomerular filtration rate were lower in the MPA group(P<0.05).Conclusions AAV is more common in school-age female children,with MPA being the most common clinical subtype.The onset of AAV in children is mainly characterized by renal involvement,followed by respiratory system involvement.The renal pathology often presents as focal type with possible immune complex deposits.Children with MPA often have renal involvement,while those with GPA commonly have sinusitis.The prognosis of children with AAV is poor,often accompanied by renal insufficiency.

Objective To observe the safety and effectiveness of single dose intravenous infusion of tranexamic acid(TX-A)in dual level posterior lumbar interbody fusion(PLIF),and to explore the changes and trends in perioperative white blood cell(WBC),erythrocyte sedimentation rate(ESR),and C-reactive protein(CRP).Methods Between October 2020 and September 2022,46 patients with lumbar degenerative disease were treated with dual level PLIF,including 18 males and 28 females,with an average age of(60.24±10.68)years old,from 34 to 80 years old.They were divided into observation group and control group according to different treatment methods.There were 28 patients in the observation group,including 12 males and 16 females,with an average age of(61.04±9.03)years old.There were 3 cases with lumbar disc herniation(LDH),lumbar spinal stenosis(LSS)18 cases,lumbar spondylolisthesis(LS)7 cases.TXA(1 g/100 ml)was administered intravenously 15 min before skin incision after general anesthesia.The control group consisted of 18 patients,including 6 males and 12 females,with an average age of(59.00±13.04)years old.There were 5 cases with LDH,LSS 9 cases,LS 4 cases,and TXA was not used.The operation time,intraoperative bleeding volume,postoperative drainage volume,postoperative deep vein thrombosis(DVT),postoperative hospital stay,postoperative activated partial thromboplastin time(APTT),prothrombin time(PT),thrombin time(TT),fibrinogen(FIB),platelet(PLT),red blood cell(RBC),hemoglobin(HB),hematocrit(HCT),the first day,the fourth day,the seventh day and the last tested after operation WBC,ESR and CRP were recorded.Results The postop-erative wounds of the patients healed well and there was no DVT.46 patients were followed up from 3 to 6 months.The intraop-erative blood loss was 400.0(300.0,500.0)ml and the postoperative drainage was 260.0(220.0,450.0)ml in the observation group,which were lower than the control group[600.0(400.0,1000.0)ml,395.0(300.0,450.0)ml],P＜0.05.There was no significant difference between the two groups in operation time,postoperative hospital stay,postoperative APTT,PT,TT,FIB,PLT,RBC,HB,HCT,and postoperative WBC,ESR and CRP at different times(P＞0.05).Conclusion Single dose intravenous infusion of TXA can reduce the blood loss of bi-segmental PLIF,and has no significant effect on WBC,ESR and CRP after op-eration.

Background and Aims:Accurate early pathogen diagnosis is a breakthrough for improving the prognosis of infectious pancreatic necrosis(IPN)patients.However,there is currently a lack of efficient methods for early identification of IPN in clinical settings.This study was performed to assess the application value of next-generation sequencing technology based on metagenomic capture(MetaCAP)in the pathogen diagnosis of IPN. Methods:A prospective study was conducted on 29 patients suspected of having acute necrotizing pancreatitis at Xiangya Hospital of Central South University between January and July 2024.Blood samples were tested using MetaCAP and conventional pathogen culture.The results of peritoneal fluid pathogen culture were used as the gold standard to compare the diagnostic efficacy of the two methods. Results:Due to three cases lacking peritoneal fluid culture results,a total of 26 cases were included in the final analysis.The overall mortality rate was 23.1％(6/26).During hospitalization,9 cases(34.6％)were diagnosed with IPN.The sensitivity and negative predictive value of MetaCAP for diagnosing IPN were significantly higher than those of conventional pathogen culture(77.8％vs.11.1％,P=0.031;86.7％vs.65.2％,P=0.032),while the differences in specificity(76.5％vs.88.2％,P=0.689)and positive predictive value(63.6％vs.33.3％,P=0.347)between the two methods were not statistically significant.The average detection time for MetaCAP was 33(20-49)h,while microbial culture took 125(45-142)h,with a significant difference(P＜0.001).The average cost for blood MetaCAP testing was 2 500 yuan per case,but it accounted for only 1.19％of the average hospitalization cost. Conclusion:MetaCAP has significant value in the early pathogen diagnosis of IPN,with a shorter detection time,good testing efficacy,and health-economic value,demonstrating a promising clinical application prospect.