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.

Objective:To investigate the current status and challenges of pediatric life support training in China and provide references for improving training quality.Methods:A cross-sectional study was conducted to collect data from pediatric life support training centers across the country，covering basic institutional information，training capacity and training faculty，training program funding，as well as existing challenges and issues.The domestic registry of training centers in 2023 was obtained through the American Heart Association's online platform.After contacting and verifying each center，an online questionnaire was distributed，and the aggregated data were statistically analyzed.Results:A total of 42 institutions participated in the survey，including 19 children's hospitals，14 general hospitals，6 maternal and child health hospitals，2 women and children’s hospitals，and 1 training institution.The distribution of training centers showed a concentration in coastal areas，with the top three provinces/municipalities being Guangdong（7/42，16.7%），Zhejiang（6/42，14.3%），and Shanghai（4/42，9.5%）.As of December 31 2023，the 42 institutions had an annual basic life support（BLS）training volume of 8 587 individuals，the median was 120 (100,200)，and an annual pediatric advanced life support（PALS）training volume of 2 448 individuals，the median was 30 (20,50).Among the 42 institutions，there were 598 BLS instructors and 306 PALS instructors.Among the surveyed institutions，24（24/42，57.1%）reported BLS instructor teams comprising fewer than 10 members，and 33（33/42，78.6%）reported PALS instructor teams comprising fewer than 10.Only 7 centers(7/42,16.7%）reported having dedicated funding support.The top three challenges were：training sessions occupying instructors’personal time（27/42，64.3%），low instructor compensation（16/42，38.1%），and issues with the data submission system（16/42，38.1%）.Conclusion:Pediatric life support training centers in China are primarily children’s hospitals，with a geographical concentration in coastal areas，which is also reflected in the distribution of training scale and instructor resources.Most centers have relatively small training scales and limited instructor capacity，with many instructors conducting training during their personal time.These issues may hinder the implementation and effectiveness of training programs.

Objective:To investigate the current status and challenges of pediatric life support training in China and provide references for improving training quality.Methods:A cross-sectional study was conducted to collect data from pediatric life support training centers across the country，covering basic institutional information，training capacity and training faculty，training program funding，as well as existing challenges and issues.The domestic registry of training centers in 2023 was obtained through the American Heart Association's online platform.After contacting and verifying each center，an online questionnaire was distributed，and the aggregated data were statistically analyzed.Results:A total of 42 institutions participated in the survey，including 19 children's hospitals，14 general hospitals，6 maternal and child health hospitals，2 women and children’s hospitals，and 1 training institution.The distribution of training centers showed a concentration in coastal areas，with the top three provinces/municipalities being Guangdong（7/42，16.7%），Zhejiang（6/42，14.3%），and Shanghai（4/42，9.5%）.As of December 31 2023，the 42 institutions had an annual basic life support（BLS）training volume of 8 587 individuals，the median was 120 (100,200)，and an annual pediatric advanced life support（PALS）training volume of 2 448 individuals，the median was 30 (20,50).Among the 42 institutions，there were 598 BLS instructors and 306 PALS instructors.Among the surveyed institutions，24（24/42，57.1%）reported BLS instructor teams comprising fewer than 10 members，and 33（33/42，78.6%）reported PALS instructor teams comprising fewer than 10.Only 7 centers(7/42,16.7%）reported having dedicated funding support.The top three challenges were：training sessions occupying instructors’personal time（27/42，64.3%），low instructor compensation（16/42，38.1%），and issues with the data submission system（16/42，38.1%）.Conclusion:Pediatric life support training centers in China are primarily children’s hospitals，with a geographical concentration in coastal areas，which is also reflected in the distribution of training scale and instructor resources.Most centers have relatively small training scales and limited instructor capacity，with many instructors conducting training during their personal time.These issues may hinder the implementation and effectiveness of training programs.

China prospective multicenter birth cohort (Prospective Omics Health Atlas birth cohort, POHA birth cohort) study was officially launched in 2022. This study, in collaboration with 12 participating units, aims to establish a high-quality, multidimensional cohort comprising 20 000 naturally conceived families and assisted reproductive families. The study involves long-term follow-up of parents and offspring, with corresponding biological samples collected at key time points. Through multi-omics testing and analysis, the study aims to conduct multi-omics big data research across the entire maternal and infant life cycle. The goal is to identify new biomarkers for maternal and infant diseases and provide scientific evidence for risk prediction related to maternal diseases and neonatal health.

Objective To analyze the structural changes and reasons for hospitalization expenditure among patients with thyroid cancer,so as to provide a reference basis for reasonable control of medical costs,making the structure of hospitalisation costs for patients undergoing surgery for thyroid cancer more rational.Methods The degree of structural change and the grey correlation method were used to quantitatively analyze the changes in the structure of hospitalization expenses and the degree of correlation of patients with thyroid cancer surgery in a hospital in Shanxi Province from 2017 to 2022.Results From 2017 to 2022,the hospitalization expenses of thyroid cancer surgery patients in the hospital showed a decreasing trend,and drug fees and consumables fees accounted for a large proportion.Consumables fees and treatment fees showed positive contribution changes,drug fees and diagnosis fees showed negative contribution changes.Nursing fees and general medical service fees showed positive contribution changes,but were not obvious.During the 6-year period,the top two related factors affecting the hospitalization expenses of thyroid cancer patients were drug fees and consumables fees.Conclusion The structure of hospitalization expenses of per thyroid cancer patients tends to be reasonable,but there is still a large room for improvement.It is suggested to continue to strengthen the control of drugs and medical consumables,and clarify the value composition of technical labor and material consumables,so as to further optimize the structure of hospitalization expenses.

Objective:With the rapid increase in the number of real world studies, especially the use of health data in medical institutions, ethical issues such as the use of patient health data and the protection of patient′s privacy rights and the right to know have been gradually exposed. To strike a good balance between promoting data sharing and maintaining subjects′ personal privacy, the mode of informed consent appears to be crucial. This paper provided guidance for the selection of informed consent models for real world research health data utilization.Methods:The authors extensively studied the relevant laws and regulations of health data utilization worldwide, conducted extensive searches in Chinese and English databases, sorted out and analyzed various alternative informed consent models, and summarized their characteristics and applications.Results:At present, five alternative informed consent models were used to conduct real world research based on health data utilization. Researchers can choose informed consent models according to the research purpose, research design, research risk, operability of informed consent, and vulnerable groups.Conclusions:Different alternative informed consent models have varied characteristics. Researchers need to choose informed consent models based on the above factors to ensure the maximum protection of patients' privacy rights while using health data.

Cardiometabolic disease (CMD), characterized with metabolic disorder triggered cardiovascular events, is a leading cause of death and disability. Metabolic disorders trigger chronic low-grade inflammation, and actually, a new concept of metaflammation has been proposed to define the state of metabolism connected with immunological adaptations. Amongst the continuously increased list of systemic metabolites in regulation of immune system, bile acids (BAs) represent a distinct class of metabolites implicated in the whole process of CMD development because of its multifaceted roles in shaping systemic immunometabolism. BAs can directly modulate the immune system by either boosting or inhibiting inflammatory responses via diverse mechanisms. Moreover, BAs are key determinants in maintaining the dynamic communication between the host and microbiota. Importantly, BAs via targeting Farnesoid X receptor (FXR) and diverse other nuclear receptors play key roles in regulating metabolic homeostasis of lipids, glucose, and amino acids. Moreover, BAs axis per se is susceptible to inflammatory and metabolic intervention, and thereby BAs axis may constitute a reciprocal regulatory loop in metaflammation. We thus propose that BAs axis represents a core coordinator in integrating systemic immunometabolism implicated in the process of CMD. We provide an updated summary and an intensive discussion about how BAs shape both the innate and adaptive immune system, and how BAs axis function as a core coordinator in integrating metabolic disorder to chronic inflammation in conditions of CMD.

Objective: To explore the prognostic relationship between initial absolute lymphocyte count(ALC) of peripheral blood and primary immune thrombocytopenia (ITP) in children, in order to provide basis for judging the prognosis and treatment of ITP in children. Methods: Clinical data of 166 children with primary ITP in children admi-tted at the Affiliated Hospital of Guizhou Medical University from January 2014 to March 2018 were analyzed retrospectively, and they were followed up by clinic and telephone, the prognostic factors (gender, age, ethnicity, inducement, bleeding, initial ALC, platelet count and treatment) were statistically analyzed, and the relationship between ALC of peripheral blood and the prognosis of children with ITP was observed. Results: Of 166 children with ITP, 89 cases (53.6%) had remission within 3 months, 18 cases (10.8%) within 3-12 months, 20 cases (12.0%) within 1-4 years, a total of 39 cases (23.5%) were refractory (no remission in 1-10 years), the remission rate within 1 year was 64.5%, the total remission rate was 76.4%.ALC of remission cases was (4.58±2.87)×10⁹/L within 3 months, (4.47±2.04)×10⁹/L within 3-12 months, and (2.86±1.61)×10⁹/L within 1- 4 years.Thirty-nine cases (23.5%) were refractory(no remission in 1-10 years), ALC of them was (2.07±0.98)×10⁹/L, and there were significant differences among different groups (F= 12.06, P<0.01). Univariate analysis showed that age (F=27.28), pre-morbidity history of infection and vaccination history(χ²= 9.31), initial ALC (F=12.06) at initial diagnosis were related with the prognosis of children with ITP (all P<0.05). Multivariate analysis showed that the history of infection before onset, the history of vaccination(95%CI: 0.19 to 1.51, P<0.05)and initial ALC(95%CI: -0.64 to -0.23, P<0.001) at the time of initial diagnosis were independent factors affecting the prognosis of children with ITP.The receivers operating characteristic (ROC) was drawn with the development of chronic disease (course >12 months) as state variable and ALC as test variable.The area under curve(AUC) was 0.765(P<0.05), cut-off point was 3.925×10⁹/L, sensitivity was 0.542, and specificity was 0.966. Conclusions Initial ALC can be used as one of the prognosis index of ITP in children, and low ALC is the risk signal for chronic development of ITP in children.

Objective To study the clinical effects of continuous blood purification (CBP) in the treatment of newborns with severe sepsis and multiple organ dysfunction syndrome (MODS). Method From May 2013 to November 2018, the clinical data of infants with severe sepsis and MODS receiving CBP in the neonatal department of our hospital were retrospectively analysed. Changes of blood pressure, arterial partial pressure of oxygen/inhaled oxygen concentration (PaO2/FiO2), pH, serum potassium, sodium, urea nitrogen, creatinine, urine volume and maintenance dose of adrenaline at different time points before and after CBP were analysed. Result According to the inclusion and exclusion criteria, a total of 8 newborns with sepsis and MODS were enrolled in the study. One patient had the complication of perforated colon, and the other one had acute renal failure. The number of affected organs in these infants was 3～5. Six cases began CBP treatment within 1～5 days after admission, and the other two cases began CBP treatment on the 38th and 47th days after admission. The average treatment duration was (58.6±25.9) h. The effective rate of CBP in the treatment of severe sepsis with MODS was 75.0％(6/8). Blood pressure was increased at 6 h, 12 h, 24 h and 48 h after treatment and at the end of treatment. PaO2/FiO2 and blood pH were increased. The urine volume was increased at 24 h and 48 h after treatment and at the end of treatment (P<0.05). Serum potassium, urea nitrogen and creatinine were significantly decreased (P<0.05). The maintenance dose of adrenaline was also decreased significantly at 12 h after CBP (P<0.05), and withdrawn at 48 h after treatment. Only one case experienced membrane blockage during CBP. Dialysis was continued after the replacement of filtration membrane. No other complications existed. Conclusion CBP is effective in the treatment of neonatal severe sepsis with MODS. It can improve the circulation and renal function.

Objective To evaluate the differences of toxicities,therapeutic efficacy and immune function between induction chemotherapy followed by sinusoidal chrono-modulated infusion and flat intermittent infusion of cisplatin (DDP)with intensity-modulated radiotherapy (IMRT) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC).Methods Seventy patients with biopsydiagnosed stages Ⅲ and Ⅳ B NPC (according to the 2010 UICC staging system) were treated with two-cycle induction chemotherapy before chemoradiotherapy in Guizhou Cancer Hospital.The TPF chemotherapy regimen was administered as follows:The TXT and DDP with the dose of 75 mg/m2 was carried out by bolus infusing for the first day,the 5-FU with 750 mg · m-2 · d-1 was carried out by continuous intravenous pumping for the first day to fifth day(120 h).The induction chemotherapy was 21 days per cycle,for two cycles.After that all patients were randomly treated with 2-3 cycles of sinusoidal chronomodulated infusion or flat intermittent constant rate infusion of DDP with IMRT.Using a multi-channel programmed pump,the patients were given 12 h continuous infusions of DDP (100 mg/m2) for day one,repeated every 3 weeks for 2-3 cycles.DDP was administered from 10:00 am to 10:00 pm.Concurrent radiotherapy regimen was administered as follows:GTVnx 69.96-73.92 Gy/33 f,PTVnx 69.96 Gy/33 f,PTVnd 69.96 Gy/33 f,PTV1 60.06 Gy/33 f,PTV2 50.96 Gy/28 f.Results The main toxicities of chemoradiotherapy in the group of sinusoidal chrono-modulated infusion were bone marrow suppression:leukocytes,and then nausea,oral mucositis and hemoglobin.The main toxicities of chemoradiotherapy in the group of flat intermittent constant rate infusion were bone marrow suppression:hemoglobin,leukocytes,and then nausea,oral mucositis.No significant differences were observed for toxicities(P ＞ 0.05).After concurrent chemoradiotherapy,the complete response rate (CR),partial response rate (PR),stable disease rate(SD),progressive disease rate (PD) and overall response rate (ORR) were 11.4％,85.7％,2.9％,0 and 97.1％ in the group of sinusoidal chrono-modulated infusion.The CR,PR,SD,PD,ORR in the group of flat intermittent constant rate infusion were 22.9％,74.2％,2.9％,0,97.1％,respectively.However,there was no significant differences of effect in the two Arms (P ＞ 0.05).For sinusoidal ehrono-modulated infusion and flat intermittent infusion group,the 2-year overall survival(OS) were 82.9％ and 94.3％ respectively,the 2-year progression-free survival(PFS) were 77.1％,91.4％ respectively,and the 2-year distant metastasis free survival (DMFS) were 82.9％,91.4％ respectively.The value of CD3 + in the group of sinusoidal chrono-modulated infusion was higher than the group of flat intermittent constant rate infusion after therapy (Z =3.254,P ＜ 0.05).The value of CD4 +,CD8 +,CD16 + CD56 +,CD19 +,and CD4 +/CD8 + had no differences in two Arms (P ＞ 0.05).Conclusions No significance differences on the toxicities,therapeutic efficacy and survival were observed between the two groups,but immune function might be improved in the sinusoidal chrono-modulated infusion group.