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

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.

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 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 investigate the mechanism of DNA damage and repair in MLL-rearranged acute myeloid leukemia(MLL-r AML)cells by the combination of Chidamide and the BRD4 inhibitor(+)-JQ-1.Methods:MLL-r AML cell lines Molm-13,MV4-11 and non-MLL-r AML cell line Kasumi were divided into control group(contr),Chidamide group(chida),(+)-JQ-1 group and Combination group(combi),respectively.Cell viability of Molm-13 was measured by CCK-8 to determine optimal the concentrations of Chidamide and(+)-JQ-1.The cell cycle was detected by flow cytometry,and apoptosis-related factors Bcl-2,Bax and caspase-3 were detected by Western blot.DNA damage marker γH2AX was detected by immunofluorescence.The protein expressions of DNA damage factor γH2AX,DNA damage checkpoint kinases p-ATR,p-CHK1,p-ATM,p-CHK2 and DNA damage repair factors Rad51 and 53BP1 were detected by Western blot.The expression of DNA damage repair factors Rad51 and 53BP1 mRNA was detected by qRT-PCR.Results:Under the treatment of Chidamide(300 nmol/L)and(+)-JQ-1(400 nmol/L),the proportion of G1 phase cells in MLL-r AML cell lines Molm-13 and MV4-11 was increased in combination group compared with control group.In non-MLL-r AML cell line Kasumi,compared with control group,the proportion of G1 phase cells in combination group was increased(P＜0.05).In Molm-13 and MV4-11 cell lines,compared with control group,the expression level of DNA damage marker γH2AX in combination group was increased(P＜0.05).The expression levels of DNA damage checkpoint and damage repair factors p-ATR,p-CHK1,p-ATM,p-CHK2,Rad51,53BP1 were decreased(P＜0.05).In Kasumi cell line,compared with control group,there was no significant change in the expression of some of the above factors in combination group(P＞0.05),but the expression trend of some factors was opposite.In MLL-r AML cell lines Molm-13 and MV4-11,compared with control group,the expression levels of Bax and caspase-3 protein were increased in combination group,while the expression levels of Bcl-2 protein were decreased(P＜0.05).In non-MLL-r AML cell line Kasumi,there was no significant change in apoptotic factor protein expression in combination group compared with control group(P＞0.05).Conclusion:Chidamide combined with(+)-JQ-1 can inhibit the proliferation of MLL-r AML cells,inhibit the initiation of protective self-repair of these leukemia cells by inhibiting the DNA damage response pathway,and ultimately increase the apoptosis of these cells,but non-MLL-r AML cells have no similar results.

Objective:To analyze the construction of human resources in specialized public health institutions in China,with a view to providing reference for strengthening the construction of human resources in public health in China.Methods:Based on the data of China Health and Wellness Statistical Yearbook,descriptive statistical analysis,Gini coefficient and health resource agglomeration were used to analyze the quantity and quality of human resources in specialized public health institutions and the equity of human resource allocation in different regions of China from 2012 to 2021.Results:From 2012 to 2021,the average annual growth rate of the number of specialized public health institution personnel nationwide was 4.10%,and the average annual growth rate of the number of specialized public health institution personnel per 1 000 population was 3.71%.In 2021,the Gini coefficient of human resources in China's specialized public health institutions allocated by population was 0.1002,and the Gini coefficient of the allocation of human resources according to the geographic area was 0.6706,and 21 provinces'health resource agglomeration value were greater than 1.Conclusion:the total amount of human resources in China's specialized public health institutions has steadily increased during the decade,and the quality has been greatly improved,but there is still a gap with the expected development goal;the development of human resources in different specialized public health institutions is not balanced;demographic fairness is better than geographic fairness in the allocation of human resources in public health,and there are significant inter-provincial differences.

Aim To investigate the preventive and therapeutic effects of the mfat-1 gene therapy on exper-imental autoimmune encephalomyelitis in mice.Meth-ods mfat-1 gene therapy was used to render the host endogenous capability of producing ω-3 PUFAs,con-comitantly reduce the levels of ω-6 PUFAs,and change the proportion of ω-3/ω-6 PUFAs.Then,the levels of PUFAs in blood were analyzed by gas chromatography.The neurological deficits in mice were evaluated by neurological dysfunction score.HE staining and LFB staining of mouse spinal cord slices were used to ob-serve central nervous system inflammation infiltration and demyelinating lesions.Flow cytometry microsphere microarray technology was used to detect the content of cytokines in serum.Results The mfat-1 gene therapy could significantly raise the proportion of ω-3/ω-6 PU-FAs(P＜0.05),markedly delay the incubation period and peak period and reduce neurological dysfunction scores(P＜0.05),and improve inflammation and de-myelination of spinal cords(P＜0.05).It could also greatly increase the levels of IL-2,IFN-γ,IL-4 and IL-17 in serum(P＜0.05).Conclusion The pro-portion of ω-3/ω-6 PUFAs in blood circulation en-hanced by mfat-1 gene therapy can effectively prevent and treat experimental autoimmune encephalomyelitis in mice.

Objective To investigate the in vitro anti-inflammatory effects of Sophora davidii Hance leaves total alkaloids(SDLTAs)and possible molecular mechanisms.Methods The lipopolysaccharide(LPS)-induced inflammation model of RAW264.7 cells was used,and different concentrations of SDLTAs(50,100 and 200 μg/mL)were administered,and the effect of SDLTAs on cellular NO expression was detected by the Griess method;ELISA method was used to detect the effect of SDLTAs on the expression of IL-6,TNF-α and IL-1β;The expression of iNOS,NF-κB p65 and IκBα mRNA was detected by RT-qPCR;Western blotting was used to detecte the expres-sion of p-p38,p-p65 and p-JNK in the cells and NF-κB p65 in the nucleus.Results SDLTAs could significantly inhibit the LPS-induced inflammatory response in RAW264.7 cells.SDLTAs significantly decreased the secretion of NO,IL-6,TNF-α and IL-1β in cells(P<0.01),and significantly decreased the mRNA expressions of iNOS,NF-κB p65 and IκBα in cells(P<0.01).Significantly decreased the protein expression of p-p38,p-p65 and p-JNK in cells and NF-κB p65 in nucleus(P<0.01).Conclusion SDLTAs can exert anti-inflammatory effects by regulating the MAPK/NF-κB signalling pathway.