BACKGROUND:With the increase of age,the function of bone marrow-derived mesenchymal stem cells is gradually reduced,and delaying the aging of bone marrow-derived mesenchymal stem cells itself has become an important topic.OBJECTIVE:To explore ways to delay the aging of bone marrow-derived mesenchymal stem cells by changing the expression of telomerase Cajal body protein 1(TCAB1)gene.METHODS:Mouse bone marrow-derived mesenchymal stem cells were cultured by cell adhesion method.TCAB1 gene in bone marrow-derived mesenchymal stem cells was overexpressed and interfered by recombinant lentivirus technique.The expression of aging related genes P16,P21,P53,and P27 was detected by qPCR.The relative length of telomeres was detected by qPCR.The expression of aging proteins P16,P21,P53,and P27 was detected by western blot assay.Cell proliferation was detected by CCK-8 assay.Annexin V-PE/7-AAD apoptosis kit was used to detect the degree of cell apoptosis.RESULTS AND CONCLUSION:Bone marrow-derived mesenchymal stem cell lines overexpressing TCAB1 gene had decreased expression of senescence related genes and proteins,increased Telomere relative length,stronger cell proliferation,less apoptosis,and a youthful state.The expression of age-related genes and proteins in bone marrow mesenchymal stem cells interfering with TCAB1 gene increased,and the relative telomere length decreased;cell proliferation ability was weak;cell apoptosis was more,and cells showed senescence.These results indicate that increasing the expression of TCAB1 in an appropriate range can delay the rate of cell senescence.

BACKGROUND:Studies have shown that intradiscal injection of syringin solution can improve the structure and function of the intervertebral disc,prevent and slow down the process of intervertebral disc degeneration in rats.However,the biological half-life of syringin is short and it is difficult for it to continue to play a role in the intervertebral disc.Its bioavailability needs to be further improved.OBJECTIVE:To observe the effect of syringin-chitosan hydrogel on intervertebral disc degeneration in rats and the mechanism of syringin in the treatment of intervertebral disc degeneration.METHODS:(1)Cell experiment:Passages 2-5 rat nucleus pulposus cells were divided into four groups for treatment.The normal control group did not undergo any treatment.The degeneration group was added with interleukin-1β(to establish the intervertebral disc degeneration cell model).The drug group was added with interleukin-1β and syringing.The inhibitor group was added with interleukin-1β,syringing,and phosphatidylinositol 3-kinase(PI3K)inhibitor LY294002.After 24 hours of treatment,apoptosis,extracellular matrix,oxidative stress,and apoptosis-related proteins and PI3K/protein kinase B(AKT)signaling pathway proteins were detected respectively.(2)Animal experiment:Syringin-chitosan hydrogels were prepared,and the micromorphology and slow-release properties of the hydrogels were tested.Thirty SD rats were randomly divided into model control group,model intervention group,hydrogel group,syringin solution group,and syringin hydrogel group,with 6 rats in each group.The intervertebral disc degeneration model was established by the acupuncture method.Immediately after model establishment,the rats in model intervention group,hydrogel group,syringin solution group,and syringin hydrogel group were injected with PBS,chitosan hydrogel,syringin solution,and syringin-chitosan hydrogel,respectively.The samples were taken 8 weeks after modeling for histological detection.RESULTS AND CONCLUSION:(1)Cell experiment:Compared with the normal control group,apoptosis rate,reactive oxygen species level,and expression of BAX,cleaved caspase-9,cleaved caspase-3,and matrix metalloproteinase 13 protein were increased in the nucleus pulpocytes in the degeneration group(P＜0.05),and the expression levels of p-PI3K,p-AKT,BCL-2,and type Ⅱ collagen were decreased(P＜0.05).Superoxide dismutase activity decreased(P＜0.05).Compared with the degeneration group,apoptotic rate,reactive oxygen species level,and expression of BAX,cleaved caspase-9,cleaved caspase-3,and matrix metalloproteinase 13 protein were decreased in the syringin solution and syringin solution groups(P＜0.05),and expression levels of p-PI3K,p-AKT,BCL-2,and type Ⅱ collagen were increased(P＜0.05).Superoxide dismutase activity increased(P＜0.05).LY294002 could partially inhibit the effect of syringin.(2)Animal experiment:Syringin-chitosan hydrogel had a loose porous structure and good slow-release performance.Hematoxylin-eosin and safranin O-fast green staining showed that compared with the model control group and model intervention group,chitosan hydrogel,syringin solution and syringing-chitosan hydrogel could improve the intervertebral disc degeneration in different degrees,and the therapeutic effect of syringing-chitosan hydrogel was better than that of hydrogel and drug solution alone.(3)These findings indicate that syringin can regulate apoptosis of nucleus pulposus cells and extracellular matrix degradation induced by oxidative stress by activating PI3K/AKT signaling pathway,thus delaying disc degeneration.Compared with syringin injection alone,syringin loading in chitosan hydrogel can further delay the progression of intervertebral disc degeneration in rats.

Objective To investigate the changes of inflammatory factors in bronchoalveolar lavage fluid(BALF),lung tissue,and serum of a rat pneumonia model induced by inhalation of lipopolysaccharides(LPS).Methods Three days after modeling by LPS 4 mg/mL inhalation,15 min/d,was conducted while monitoring the particle size distribution and aerosol concentration of LPS,the degree of inflammation in lung tissues of rats in each group was observed via HE staining,and neutrophils in BALF were counted by microscope.The contents of interferon gamma(IFN-γ),interleukin-1 beta(IL-1 β),IL-4,IL-5,IL-6,IL-10,IL-13,tumor necrosis factor alpha(TNF-α),and KC/GRO in lung tissue,serum,and BALF were detected by Meso Scale Discovery.Results The lung histopathology of model rats displayed focal and diffuse alveolar epithelial necrosis with shedding and the aggregation and infiltration of inflammatory cells.The particle size distribution of atomized LPS was as follows,Dv(10)=0.6974μm,Dv(50)=3.387 μm,Dv(90)=8.836 μm.The aerosol concentration of LPS was 4.08 g/m3,and the calculated inhalation dose for rats was 47.10 mg/kg.The neutrophil count(P＜0.01)and contents of IL-1β,IL-6,and TNF-α(P＜0.05,P＜0.001,P＜0.001)in the BALF,and the contents of IL-1β,IL-6,and KC/GRO in lung tissue(P＜0.01,P＜0.05,P＜0.01),of model rats were significantly increased.No biologically significant changes were observed in inflammatory factor levels in the serum.Conclusions In the acute pneumonia model induced by inhalation of LPS,significant changes in inflammatory factors such as IL-1β,IL-6,KC/GRO,and TNF-α were observed in both lung tissue and bronchoalveolar lavage fluid(BALF),while no notable changes in these inflammatory factors were detected in serum.This indicates that the inflammation responses are primarily localized in the lungs.

Enteric human adenovirus(HAdV),a common cause of acute viral gastroenteritis in children,frequently triggers spo-radic infections,nosocomial transmissions,and outbreaks in kindergarten settings.This study was aimed at investigating the molecular characteristics and genetic evolution of enteric HAdV among patients with acute gastroenteritis younger than 5 years in China,to pro-vide foundational data for disease prevention and control.A total of 8 074 stool samples were collected from hospitalized or outpatient children younger than 5 years with acute gastroenteritis in China during 2023.HAdV screening was conducted with real-time fluores-cence PCR.Positive samples were sequenced,then subjected to bioinformatics analysis including genotyping,homology assessment,and phylogenetic analysis with GenBank,BioAider,and MEGA11.0.A total of 370 samples(4.58%)tested positive for HAdV.Two enteric HAdV genotypes were identified:HAdV-F41(which predominated,at 98.09%)and HAdV-F40(1.90%).HAdV-F41 was the dominant genotype among patients with acute gastroenteritis younger than 5 years in China.Bioinformatics analysis indicated that the predominant HAdV lineages in China were lineage 1 and 2,whereas European lineage 3 showed no influence.Systematic and long-term surveillance of HAdV should help elucidate its diversity and evolutionary patterns in China,thereby providing scientific evi-dence for developing more effective prevention strategies.

This study investigated the full-genome molecular characteristics of a rotavirus vaccine-derived strain,G1P[8]geno-type A group rotavirus RVA/Human-wt/CHN/HN1140/2021/G1P[8](referred to as HN1140).The gene fragments of the HN1140 strain were amplified with reverse transcription-polymerase chain reaction(RT-PCR)combined with whole-genome primers to obtain the full genome sequence.Genotyping was performed with the online genotyping tool RotaC 2.0,and similarity and genetic evolution analyses for each gene segment were conducted in DNAstar5.1 and MEGA11.0 software.The genotype of the HN1140 strain was deter-mined to be G1-P[8]-I2-R2-C2-M2-A3-N2-T6-E2-H3.Phylogenetic analysis demonstrated that all 11 genomic segments clus-tered closely with the RotaTeq vaccine strains,sharing 99.7%-100%nucleotide sequence similarity.Notably,VP1,VP2,VP6,and NSP2-NSP5 segments showed 100%nucleotide identity with RotaTeq strains.Comparative genomic analysis identified 13 nucleotide and 8 amino acid substitutions between HN1140 and RotaTeq strains,localized within the VP7,VP4,VP1,VP2,VP3,and NSP1 segments.The HN1140 strain exhibited the genotype G1-P[8]-A3-T6-H3,which was consistent with the typical profile of a vaccine-derived reassortant.This strain demonstrated high genetic similarity to RotaTeq vaccine strains,with nucleotide sequence identity ranging from 99.7%to 100%.These findings suggested that HN1140 evolved from RotaTeq vaccine strains through genetic reassortment.

Background and Aims:Acute pancreatitis(AP)is an acute inflammatory disease of the pancreas caused by abnormal activation of pancreatic enzymes.Although gallstones,hyperlipidemia,and alcohol use are the most common causes,a subset of patients develop AP secondary to rare etiologies that are often misdiagnosed or diagnosed late,leading to recurrence or inappropriate management.This study aims to summarize the clinical characteristics,diagnostic strategies,and treatment outcomes of four cases of AP caused by uncommon etiologies,supported by a literature review.Methods:Clinical data of 4 patients admitted to the Department of Hepatobiliary and Pancreatic Surgery,the Third Xiangya Hospital of Central South University,between November 2021 and September 2024,were retrospectively analyzed.Their etiological characteristics,diagnostic approaches,and treatment strategies were reviewed in combination with relevant literature.Results:The underlying causes of AP were intraductal papillary mucinous neoplasm,pancreatic neuroendocrine tumor,pancreatic ductal adenocarcinoma,and duodenojejunal intussusception.All cases initially presented as idiopathic AP.Three patients underwent definitive surgical treatment and recovered well,while one patient with pancreatic cancer received only palliative care due to delayed diagnosis and died three months later.Conclusion:AP secondary to rare etiologies often mimics common forms in clinical presentation but poses diagnostic challenges.For patients with recurrent or idiopathic AP,clinicians should emphasize etiological tracing and utilize advanced imaging and endoscopic modalities for early identification.Timely etiological intervention,particularly surgical management when appropriate,is essential for preventing recurrence and improving prognosis.

Background and Aims:Infected necrotizing pancreatitis(INP),particularly with diffuse distribution,is a life-threatening condition.The optimal initial intervention-minimally invasive step-up therapy vs.direct open necrosectomy-remains controversial.Moreover,the impact of necrosis morphology("wet"or"dry")and the presence of severe acute pancreatitis(SAP)on treatment selection has not been fully clarified.This study aimed to compare the efficacy and safety of these two approaches in diffuse INP and to evaluate the guiding value of CT-based necrosis type and SAP status in clinical decision-making.Methods:A retrospective analysis was conducted on 458 patients with diffuse INP admitted to the Third Xiangya Hospital of Central South University from January 2012 to March 2023.Patients were divided into a minimally invasive step-up group(n=256)and a direct open surgery group(n=202).SAP was defined according to the determinant-based classification,and necrosis was categorized as"wet"or"dry"based on CT features.The primary endpoint was a composite of death or major complications,while secondary endpoints included mortality,length of hospital stay,and incision-related complications,were compared between the two groups,with subgroup analyses performed accordingly.Results:Overall,the open surgery group had higher rates of the primary endpoint(62.4%vs.48.1%,P=0.003)and mortality(27.2%vs.16.8%,P=0.008)compared with the step-up group.Among SAP patients,the step-up approach resulted in a significantly lower primary endpoint rate(66.7%vs.97.7%,P=0.003).In non-SAP patients,the primary endpoint rates were similar,but open surgery was associated with a shorter hospital stay[(36.5±10.4)d vs.(45.6±18.6)d,P<0.001]and higher incidences of wound infection and incisional hernia(both P<0.001).Multivariate analysis identified infection onset time,effusion characteristics,gas bubbles,and necrosis location as independent predictors of prolonged hospitalization in the step-up group(all P<0.05).Patients with"wet"necrosis benefited more from the step-up approach,whereas those with"dry"necrosis experienced shorter hospitalization following open surgery.Conclusion:For diffusely distributed INP,treatment strategies should be individualized based on SAP status and necrosis liquefaction/imaging characteristics.The step-up minimally invasive approach is preferred for SAP patients and those with"wet"necrosis on CT,while direct open necrosectomy may be advantageous for"dry"necrosis(particularly with limited liquefaction)by shortening hospital stay and reducing certain major outcomes,though at the cost of increased incision infection and incision herina.CT imaging features and SAP classification can serve as valuable tools for risk stratification and guiding individualized timing and modality of intervention.

Objective To investigate the effects of parecoxib sodium on pain and Toll-like receptor 4(TLR4)/p38 mitogen activated protein kinase(p38MAPK)pathway in rats with femoral fracture.Methods Sixty rats were randomly separated into sham operation group,model group,TLR4 inhibitor(TAK-242)group(3 mg/kg),parecoxib sodium group(10 mg/kg),and parecoxib sodium+TLR4 activator lipopolysaccharide group(10 mg/kg parecoxib sodium+15 mg/kg LPS),with 12 rats in each group.Except for the sham operation group,rats in all other groups were used to establish a femoral fracture model by transverse cutting of the mid femur.After 28 days of treatment in each group,X-rays were used to detect the degree of fracture healing in rats.The mechanical pain threshold(PWMT)and thermal pain threshold(PWTL)of rats were measured.ELISA was applied to detect the levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and IL-10 in serum.Micro-CT method was applied to detect changes in femoral bone density(BMD),bone volume fraction(BV/TV),trabecular thickness(Tb.Th),and trabecular quantity(Tb.N)in rats.HE staining was applied to observe the pathological changes of bone tissue at the fracture site in rats.Western blot was applied to detect the expression of TLR4/p38MAPK pathway related proteins in bone tissue at the fracture site.Results Compared with the sham operation group,the fracture lines of rats in the model group were obvious,with a small amount of callus growth,the PWMT,PWTL,femoral BMD,BV/TV,Tb.Th,and Tb.N decreased,while the levels of serum IL-6,TNF-α,and IL-10,and the levels of TLR4 and p-p38MAPK/p38MAPK proteins in the bone tissue at the fracture site increased(P＜0.05).Compared with the model group,the fracture lines in the TAK-242 group and the parecoxib sodium group were blurred,and there was an increase in callus growth,the PWMT,PWTL,femoral BMD,BV/TV,Tb.Th,and Tb.N,the serum IL-10 level increased,while the serum IL-6,TNF-αlevels,the TLR4 and p-p38MAPK/p38MAPK protein levels in bone tissue at the fracture site decreased(P＜0.05).LPS could upregulate the phosphorylation levels of TLR4 and p38MAPK,and weaken the relieving effects on anti-inflammatory and pain of parecoxib sodium on fracture rats.Conclusion Paracoxib sodium may alleviate pain and accelerate fracture healing in rats with femoral fractures by inhibiting the TLR4/p38MAPK pathway and suppressing inflammatory responses.

Enteric human adenovirus(HAdV),a common cause of acute viral gastroenteritis in children,frequently triggers spo-radic infections,nosocomial transmissions,and outbreaks in kindergarten settings.This study was aimed at investigating the molecular characteristics and genetic evolution of enteric HAdV among patients with acute gastroenteritis younger than 5 years in China,to pro-vide foundational data for disease prevention and control.A total of 8 074 stool samples were collected from hospitalized or outpatient children younger than 5 years with acute gastroenteritis in China during 2023.HAdV screening was conducted with real-time fluores-cence PCR.Positive samples were sequenced,then subjected to bioinformatics analysis including genotyping,homology assessment,and phylogenetic analysis with GenBank,BioAider,and MEGA11.0.A total of 370 samples(4.58%)tested positive for HAdV.Two enteric HAdV genotypes were identified:HAdV-F41(which predominated,at 98.09%)and HAdV-F40(1.90%).HAdV-F41 was the dominant genotype among patients with acute gastroenteritis younger than 5 years in China.Bioinformatics analysis indicated that the predominant HAdV lineages in China were lineage 1 and 2,whereas European lineage 3 showed no influence.Systematic and long-term surveillance of HAdV should help elucidate its diversity and evolutionary patterns in China,thereby providing scientific evi-dence for developing more effective prevention strategies.

This study investigated the full-genome molecular characteristics of a rotavirus vaccine-derived strain,G1P[8]geno-type A group rotavirus RVA/Human-wt/CHN/HN1140/2021/G1P[8](referred to as HN1140).The gene fragments of the HN1140 strain were amplified with reverse transcription-polymerase chain reaction(RT-PCR)combined with whole-genome primers to obtain the full genome sequence.Genotyping was performed with the online genotyping tool RotaC 2.0,and similarity and genetic evolution analyses for each gene segment were conducted in DNAstar5.1 and MEGA11.0 software.The genotype of the HN1140 strain was deter-mined to be G1-P[8]-I2-R2-C2-M2-A3-N2-T6-E2-H3.Phylogenetic analysis demonstrated that all 11 genomic segments clus-tered closely with the RotaTeq vaccine strains,sharing 99.7%-100%nucleotide sequence similarity.Notably,VP1,VP2,VP6,and NSP2-NSP5 segments showed 100%nucleotide identity with RotaTeq strains.Comparative genomic analysis identified 13 nucleotide and 8 amino acid substitutions between HN1140 and RotaTeq strains,localized within the VP7,VP4,VP1,VP2,VP3,and NSP1 segments.The HN1140 strain exhibited the genotype G1-P[8]-A3-T6-H3,which was consistent with the typical profile of a vaccine-derived reassortant.This strain demonstrated high genetic similarity to RotaTeq vaccine strains,with nucleotide sequence identity ranging from 99.7%to 100%.These findings suggested that HN1140 evolved from RotaTeq vaccine strains through genetic reassortment.