BACKGROUND:Spleen has the functions of blood storage,hematopoiesis,and immunity.With the increase of age,the structural degeneration and functional decline of spleen lead to the impairment of immune system function,thus accelerating the aging process of the body.The treatment of spleen aging in tree shrews with highly active umbilical cord mesenchymal stem cells has not been reported. OBJECTIVE:To explore the intervention effect and mechanism of highly active umbilical cord mesenchymal stem cells on spleen aging in tree shrews. METHODS:Highly active umbilical cord mesenchymal stem cells were isolated,cultured,and obtained from the umbilical cord tissue of newborn tree shrews by caesarean section.The differentiation abilities of adipogenesis,osteogenesis,and chondrogenesis were detected by three-line differentiation kit.Cell cycle and surface markers were detected by flow cytometry.The second generation of highly active umbilical cord mesenchymal stem cells were transfected with Genechem Green Fluorescent Protein with infection complex values of 100,120,140,160,180,and 200,respectively,to screen the best transfection conditions.After transfection,the fourth generation of highly active umbilical cord mesenchymal stem cells was injected into the tail vein of tree shrews in the elderly treatment group.The young control group and the aged model group were not given special treatment.After 4 months of treatment,the spleen tissue was taken and the structure of the spleen was observed by hematoxylin-eosin staining.β-Galactosidase staining was used to detect the activity of aging-related galactosidase.Immunohistochemical staining was used to detect the expression levels of p21 and p53 proteins.Ki67 and PCNA immunofluorescence staining was used to detect cell proliferation activity.Immunofluorescence staining was used to detect the expression levels of spleen autophagy protein molecules Beclin 1 and APG5L/ATG5.Reactive oxygen species fluorescence staining was used to detect the content of reactive oxygen species in spleen tissue.CD3 immunofluorescence staining was used to detect the change of the proportion of total T lymphocytes.The secretion levels of interleukin 1β and transforming growth factor β1 in spleen were detected by enzyme linked immunosorbent assay.The distribution of highly active umbilical cord mesenchymal stem cells labeled with green fluorescent protein in spleen tissue was observed by DAPI double staining of nucleus. RESULTS AND CONCLUSION:(1)Highly active umbilical cord mesenchymal stem cells grew in a short spindle shape with fish-like growth,with a large proportion of G0/G1 phase,and had the potential to differentiate into adipogenesis,osteogenesis,and chondrogenesis.(2)Multiplicity of infection=140 and transfection for 72 hours were the best conditions for labeling tree shrews highly active umbilical cord mesenchymal stem cells with Genechem Green Fluorescent Protein.(3)Compared with the aged model group,in the aged treatment group,the spleen tissue cells of tree shrews were arranged closely,and the area of white pulp was increased(P<0.01);the boundary between red pulp and white pulp was clear;the proportion of germinal centers did not show statistically significant difference(P>0.05).The activity level of galactosidase related to spleen tissue aging was decreased(P<0.001),and the expression levels of aging protein molecules p21 and p53 were down-regulated(P<0.001).The expression levels of proliferation-related molecules Ki67 and PCNA were up-regulated(P<0.001,P<0.05);expression levels of autophagy-related molecules Beclin 1 and APG5L/ATG5 were up-regulated(P<0.001),and the content of reactive oxygen species decreased(P<0.001),and the proportion of CD3+T cells increased(P<0.05).The secretion level of interleukin 1β in the aging-related secretion phenotype decreased(P<0.001);no significant difference was found in transforming growth factor β1 level(P>0.05).Compared with the young control group,the above indexes were significantly different in the elderly treatment group(P<0.05).(4)Green fluorescent cells labeled with green fluorescent protein were observed in spleen tissue of tree shrews the elderly treatment group by frozen tissue section observation.The results show that intravenous infusion of highly active umbilical cord mesenchymal stem cells can migrate to spleen tissue,inhibit the production of reactive oxygen species,down-regulate the expression of aging-related proteins,induce autophagy,promote cell proliferation,reduce chronic inflammation,and then improve the structure and function of spleen tissue.

Traditional Chinese medicine （TCM） offers a rich theoretical foundation and clinical experience for the prevention and treatment of cardiovascular-kidney-metabolic syndrome（CKM）， demonstrating unique advantage. Building on previous work in managing diabetes， its complications， and chronic kidney disease， our team has proposed a five-phase evolution theory of "constraint， heat， deficiency， stasis， and toxin" as the core pathogenesis. These phases correspond to the pathological progression of constraint of phlegm-dampness， constraint transforming into heat， heat damaging qi and yin， stasis accumulated in the collateral vessels， and toxin induced by deficiency and stasis. In the prevention and treatment of CKM by TCM， it is emphasized to integrate the concept of "treating disease before it arises" with constitution theory， and incorporate the "2-5-8" prevention and treatment strategy， which combines prevention with treatment， tailors interventions to different phases， and employs comprehensive treatment modalities. Our goal is to leverage TCM's holistic advantages in preventing and treating CKM.

Objective:To explore the regulatory effects of long non-coding RNA H19(LncRNA H19)on the osteogenic differentia-tion of MC3T3-E1 cells under the stimulation of advanced glycation end products(AGEs).Methods:MC3T3-E1 cells were cultured under the stimulation of 10 μg/mL AGEs.The cells were observed by alkaline phosphatase(ALP)staining after 7 d and alizarin red staining after 21 d culture respectively.Cell transfection technology was used to overexpress LncRNA H19 in the cells,RT-qPCR was used to detect the mRNA expression levels of ALP,Runx-2,OCN,SP7 before and after transfection of LncRNA H19.Western blotting was used to detect the protein expression of Runx-2 and[3-catenin in the cells.Results:Under the stimulation of AGEs,the ALP stai-ning color of MC3T3-E1 cells became lighter,the formation of calcified nodules was reduced,the mRNA expression levels of ALP,Runx-2,OCN,SP7 and LncRNA H19 were decreased(P＜0.05),and the protein expression level of Runx-2 was decreased.After transfection of LncRNA H19(lv-H19),the mRNA expression of LncRNA H19 was significantly up-regulated(P＜0.05),the mRNA expression of ALP,Runx-2,OCN and SP7 genes was increased(P＜0.05),ALP staining was deeper,and the expression of β-catenin was increased.Conclusion:Under the stimulation of AGEs,LncRNA H19 may affect the osteogenic differentiation of MC3T3-E1 cells by activating the expression of WNT/[3-catenin.

Objective To explore clinical effect of vancomycin calcium sulfate combined with internal fixation on cal-caneal beak-like fracture secondary to calcaneal osteomyelitis caused by diabetic foot.Methods From April 2018 to October 2021,a retrospective analysis was performed on 5 patients with calcaneal bone osteomyelitis secondary to diabetic foot,includ-ing 2 males and 3 females,aged from 48 to 60 years old;diabetes course ranged from 5 to 13 years;the courses of diabetic foot disease ranged from 18 to 52 days;5 patients were grade Ⅲ according to Wagner classification.All patients were treated with debridement,vancomycin bone cement implantation,negative pressure aspiration at stage Ⅰ,vancomycin calcium sulfate and internal fixation at stage Ⅱ for calcaneal beak-like fracture.Surgical incision and fracture healing time were recorded,and the recurrence of osteomyelitis was observed.American Orthopedic Foot Andankle Society(AOFAS)score and exudation at 12 months after operation were evaluated.Results Five patients were successfully completed operation without lower extremity vascular occlusion,and were followed up for 16 to 36 months.The wound healing time after internal fixation ranged from 16 to 26 days,and healing time of fractures ranged from 16 to 27 weeks.AOFAS score ranged from 65 to 91 at 12 months after oper-ation,and 2 patients got excellent result,2 good and 1 fair.Among them,1 patient with skin ulcer on the back of foot caused by scalding at 5 months after operation(non-complication),was recovered after treatment;the wound leakage complication oc-curred in 2 patients,and were recovered after dressing change.No osteomyelitis or fracture occurred in all patients.Conclusion Vancomycin calcium sulfate with internal fixation in treating calcaneal osteomyelitis secondary to calcaneal osteomyelitis caused by diabetic foot could not only control infection,but also promote fracture healing,and obtain good clinical results.

Objective To analyze the seroepidemiology characteristics of Epstein-Barr virus(EBV)infection in children in Shenyang.Methods From June 2022 to May 2023,serum was collected from 12 083 children at Shengjing hospital of China Medical University.Serum capsid antigen(VCA)-IgM,VCA-IgG,EBV nuclear antigen-IgG(EBNA-IgG),and early antigen-IgG(EA-IgG)antibodies were detected using the LIAISION chemiluminescence immunoassay.EBV-DNA was detected using real-time PCR.Differences in antibody positivity rates between sexes,ages,and seasons of onset were compared.Results In 12 083 patients,the positive rates of VCA-IgM,VCA-IgG,EBNA-IgG,and EA-IgG were 9.95％(1 202/12 083),50.57％(6 110/12 083),46.03％(5 562/12 083)and 4.93％(596/12 083).The positive rates of VCA-IgM and EA-IgG were lower in male patients(9.09％and 4.44％,respectively)than in female patients(11.10％,5.60％;all P＜0.05).The differences in the positive rates for VCA-IgM,VCA-IgG,EBNA-IgG,and EA-IgG antibodies in children of different ages were statistically significant(all P＜0.05).Differences in the positive rates of VCA-IgG,EBNA-IgG,and EA-IgG antibodies were statistically significant when compared between seasons(all P＜0.05).Fourteen EBV antibody-positive combinations were detected,of which the main combination was VCA-IgG and EBNA-IgG double-positive,with a total of 4 741 cases(39.24％).Of the 3 712 children who underwent EBV-DNA detection testing,3 034(81.73％)were EBV-DNA-negative and 678(18.27％)were EBV-DNA-posi-tive.VCA-IgG and EBNA-IgG double positivity was the most common in EBV-DNA-negative and EBV-DNA-positive children,accounting for 983(26.48％)and 194 cases(5.23％),respectively.Conclusion Both VCA-IgG and EBNA-IgG antibodies are main positive in children with EBV infection in Shenyang.The positive rate of EBV antibodies is lower in boys than in girls.The positive rates of EBV anti-bodies differ in children of different ages and seasons of onset.

Male ; Humans ; Germ-Line Mutation ; Prostatic Neoplasms/genetics* ; BRCA2 Protein/genetics* ; Genetic Predisposition to Disease

Objective: To report the clinical manifestations and laboratory features of five patients with congenital thrombotic thrombocytopenic purpura (cTTP) and explore its standardized clinical diagnosis and treatment along with a review of literature. Methods: Clinical data of patients, such as age of onset, disease manifestation, personal history, family history, and misdiagnosed disease, were collected. Treatment outcomes, therapeutic effects of plasma infusion, and organ function evaluation were observed. The relationship among the clinical manifestations, treatment outcomes, and ADAMTS13 gene mutation of patients with cTTP was analyzed. Additionally, detection of ADAMTS13 activity and analysis of ADAMTS13 gene mutation were explored. Results: The age of onset of cTTP was either in childhood or adulthood except in one case, which was at the age of 1. The primary manifestations were obvious thrombocytopenia, anemia, and different degrees of nervous system involvement. Most of the patients were initially suspected of having immune thrombocytopenia. Acute cTTP was induced by pregnancy and infection in two and one case, respectively. ADAMTS13 gene mutation was detected in all cases, and there was an inherent relationship between the mutation site, clinical manifestations, and degree of organ injury. Therapeutic or prophylactic plasma transfusion was effective for treating cTTP. Conclusions: The clinical manifestations of cTTP vary among individuals, resulting in frequent misdiagnosis that delays treatment. ADAMTS13 activity detection in plasma and ADAMTS13 gene mutation analysis are important bases to diagnose cTTP. Prophylactic plasma transfusion is vital to prevent the onset of the disease.
Female ; Pregnancy ; Humans ; Adult ; Blood Component Transfusion ; Plasma ; Purpura, Thrombotic Thrombocytopenic/therapy* ; Mutation ; Purpura, Thrombocytopenic, Idiopathic ; ADAMTS13 Protein/therapeutic use*

Humans ; Factor XIII/genetics* ; Factor XIII Deficiency/genetics* ; Mutation ; Pedigree

National Comprehensive Cancer Network (NCCN) has updated and released the latest content of NCCN guidelines version 1. 2023 thymomas and thymic carcinomas (known as "guidelines"). The guideline sets standards for the diagnosis and treatment of thymoma and thymic carcinoma based on high quality clinical evidence and the latest advances in research. There have been some updates and revisions in the latest two versions of the guidelines, mainly focusing on the principles of radiotherapy, the principles of systematic therapy, multidisciplinary participation and the improvement of some footnotes, compared with the first version of the guidelines in 2022. In this paper, the contents of the new guideline will be interpreted in order to provide reference for the work of thymoma and thymic carcinoma in our country at the present stage.

Objective:To evaluate the efficacy and safety of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of pseudomyxoma peritonei (PMP).Methods:In this descriptive case series study, we retrospective analyzed the records of PMP patients treated with CRS and HIPEC between January 2013 and June 2023 at Affiliated Cancer Hospital and Institute of Guangzhou Medical University. The inclusion criteria were as follows: (1) Aged 18 to 75 years and nonpregnant women. (2) Histologically confirmed diagnosis of pseudomyxoma peritonei. (3) Karnofsky Performance Scale (KPS)>70. (4) The functions of major organs such as the heart, liver, lungs, and kidneys can tolerate major surgery for long periods of time. (5) No evidence of extra-abdominal metastasis. Patients with extensive intra-abdominal adhesions or severe infectious diseases were excluded. The main outcomes were overall survival (OS) and postoperative major complications. The postoperative major complications were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0). We used the peritoneal cancer index (PCI) score to quantitatively assess the peritoneal metastases and the completeness of cytoreduction (CCR) score at the end of surgery (CCR-0 and CCR-1 considered to be complete CRS).Results:A total of the 186 PMP patients with a median age of 56 (interquartile range extremes (IQRE), 48-64) years were included, 65 (34.9%) males and 121 (65.1%) females. The median peritoneal cancer index (PCI) score was 28 (20-34). Appendiceal origin accounted for 91.4%. Histological types were low grade in 99 patients (53.2%), high grade in 57 patients (30.6%), and 55 patients (29.6%) received complete cytoreduction (CCR-0/1). The median operative duration was 300 (211-430) minutes for all patients. Treatment-related 30-day mortality was 2.7%; 90-day mortality 4.3%; reoperation 1.6%; and severe morbidity 43.0%. Within the entire series, anemia(27.4%), electrolyte disturbance(11.6%), and hypoalbuminemia(7.5%) were the most frequent major complications (grade 3-4). The incidences of gastrointestinal anastomotic leakage, abdominal bleeding, and abdominal infection were 2.2%, 2.2%, and 4.3%, respectively. After a median follow-up of 38.1 (95%CI:31.2-45.1) months, the 5-year OS was 50.3% (95%CI: 40.7%-59.9%) with a median survival time of 66.1 (95%CI: 43.1-89.1) months. The survival analysis showed that patients with pathological low grade, low PCI, and low CCR score had better survival with statistically significant differences (all P<0.05). Further stratified into complete and incomplete CRS subgroups, the 5-year OS of the CCR-0 and CCR-1 subgroups was 88.9% (95%CI: 68.3%-100.0%) and 77.6% (95%CI: 62.7%-92.5%), respectively; and 42.0% (95%CI: 29.5%-54.5%) in the CCR-2/3 subgroup. Conclusions:CRS and HIPEC may result in a long-term survival benefit for PMP patients with acceptable perioperative morbidity and mortality. This strategy, when complete CRS is possible, could significantly prolong survival for strictly selected patients at experienced centers.