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.

BACKGROUND:Periodontitis is an inflammatory and destructive disease with plaque biofilm as the main pathogenic material,which occurs in the gingiva,periodontal ligament,alveolar bone and cementum.The antigen of bacterial complex and its secreted toxin and enzyme directly lead to the destruction of periodontal tissue and trigger the host's immune response,causing indirect damage to the body tissue.Silence information regulatory factors(Sirtuins,SIRTs)play an important role in anti-aging,anti-oxidative stress,regulating inflammation,and mediating autophagy,and are closely related to the occurrence and development of periodontitis. OBJECTIVE:To review the research status of Sirtuins in periodontitis. METHODS:The first author used the computer to search the relevant research regarding the role of Sirtuins in periodontitis in PubMed,Web of Scene,CNKI and WanFang databases.The key words were"Sirtuins,Sirtuin1-7,periodontitis"in English and Chinese.After literature screening,57 articles were included for review and analysis. RESULTS AND CONCLUSION:SIRT1,SIRT2,SIRT3,and SIRT6 participate in regulating the occurrence and development of periodontitis.Inhibition of SIRT1 expression may be the target of periodontitis treatment,while overexpression of SIRT1 can inhibit periodontitis and protect periodontal tissue.The activator of SIRT1 can reduce the inflammation of periodontal tissue and improve the systemic pathological changes caused by periodontitis.SIRT2 is involved in nicotinamide phosphoribosyltransferase-mediated periodontal inflammation and plays a role in the treatment and prognosis of periodontal diseases.SIRT3 can improve age-related periodontal disease.Gastrodin promotes the osteogenic differentiation of periodontal ligament stem cells through the up-regulation of SIRT3.The activator of SIRT3 reduces the damage of periodontitis to periodontal and renal tissues by regulating the level of autophagy in the cells.SIRT6 can inhibit the inflammatory reaction of periodontal tissue and inhibit the differentiation and mineralization of cementoblasts.SIRT6 is beneficial to the prognosis of periapical periodontitis.The relationship between SIRT4,SIRT5,SIRT7 and periodontitis is rarely reported.

Lower-cost genotyping technology has promoted the generation of large genetic datasets with the evolving next-generation sequencing technology. The emergence of genome-wide association studies (GWAS) has facilitated researchers’ understanding of common complex diseases. GWAS refers to finding the sequence variations present in the human genome and screening out disease-related single nucleotide polymorphisms (SNPs). These SNPs are considered as the basis for assessing the stability of complex diseases. However, a single variation is not sufficient to assess an individual’s risk of disease. Polygenic risk score (PRS) is an emerging genetic data analysis method for quantitatively estimating an individual’s genetic risk for complex diseases by comprehensively considering multiple genetic variation sites. A single-value estimate of an individual’s genetic risk for a certain phenotype can be calculated as the cumulative impact of multiple genetic variants by building a PRS model. The finally expected risk score is weighted by the strength and direction of association of each SNP with the phenotype based on the number of alleles carried by each SNP. With the continuous development of various PRS calculation methods and the constant accumulation of genomic data, PRS has received widespread attention in the field of genetics. So far, quite a few studies at home and abroad have shown that PRS is valuable in risk prediction of different types of human traits or complex diseases, and its effectiveness has been further verified in clinical applications. At present, many studies have established PRS models based on GWAS summary statistics to quantify the genetic risk of susceptibility loci and clinical characteristics on diseases such as lung cancer, breast cancer, coronary heart disease, diabetes and Alzheimer’s disease. The disease-susceptible populations can be recognized through comparing the relative risk and absolute risk of the disease in different risk groups according to the population risk stratification results. Additionally, individual-level genotype data and omics data can also be used as data sources for PRS analysis research, especially the latter can dynamically reflect the short-term or long-term effects of environmental factors on human gene expression, and has potential application value in building early warning models to assess health risks. Since the calculation of PRS involves a large amount of genomic data analysis, there are big differences in the methods for data selection, model building and validation. Different PRS construction methods and software have different performances in disease risk prediction, and even the performance of same algorithm varies across diseases. It is worth noting that the PRS model often needs to be re-evaluated and verified for different groups of people, because PRS is affected by race and region. This review combines currently published PRS-related research and algorithms to describe the basic principles of PRS, compares their construction and verification methods, and discusses their applications and prospects. As a powerful genetic risk assessment tool, PRS has great potential in analyzing the genetic code of complex diseases and achieving precise diagnosis and personalized treatment.

Objective This paper intends to compare the efficacy and safety of high-dose dual regimens containing Vonoprazan and proton pump inhibitor in patients infected with Helicobacter pylori(H.pylori).Methods A prospective randomized controlled study was conducted.According to inclusion and exclusion criteria.,243 patients with H.pylori infection admitted to the Department of Gastroenterology,the First Hospital of Lanzhou University from February 2023 to December 2023 were enrolled as the research objects.They were randomly divided into two groups.The high-dose dual therapy containing Vonoprazan group(VPZ-HDDT group)was given Vonoprazan fumarate tablet 20mg twice daily plus amoxicillin 750 mg four times daily for 14 days and the high-dose combination group containing PPI(PPI-HDDT group)was given esomeprazole 40 mg twice daily plus amoxicillin 750 mg four times daily for 14 days.Patients were followed up and recorded by telephone or WeChat on the 7th and 14th day of starting treatment for drug intake and occurrence of adverse reactions.Patients were instructed to recheck the 13C or 14C urea breath test at least 1 month after the end of medication.Treatment by protocol(PP)analysis,modified intention to treat(mITT)and intention-to-treat(ITT)analysis were used for H.pylori eradication rates in both groups,and compliance and incidence of adverse reactions were compared between the two groups.Results The eradication rates of the VPZ-HDDT group and the PPI-HDDT group in the initial treatment were 94.0％and 88.5％(P=0.209)by PP analysis,and 91.8％and 87.5％(P=0.358)86.7％by mITT analysis,and 81.9％(P=0.377)by ITT analysis,respectively.In the retreated patients,the PP analysis and mITT analysis eradication rates in these two groups were consistent,87.0％and 84.2％(P=0.800),respectively,and 83.3％and 76.2％(P=0.550)by ITT analysis.For the refractory H.pylori patients,the PP analysis and mITT analysis eradication rates in these two groups were also consistent,71.4％and 50.0％(P=0.429),and the eradication rates of ITT analysis were 62.5％and 50.0％(P=0.640),respectively.In different stratifications,the eradication rates of the VPZ-HDDT group were higher than those of the PPI-HDDT group,but the differences were not statistically significant.The incidence of adverse reactions and compliance of the VPZ-HDDT group and the PPI-HDDT group were similar,with no statistically significant differences.Conclusion Both two combination regimens can achieve clinically acceptable eradication rates(＞85％)in the first-time treatment patients.For the retreated and refractory patients,the choice of vonoprazan is more beneficial.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To explore the effect of gastrodin(GAS)on the polarization of M2 microglia under oxygen and glucose deprivation(OGD)and the effect of p38 MAPK inhibition on the polarization status of microglia.Methods BV2 microglia was divided into the control group(Ctrl),p38 MAPK inhibitor SB203580 group(Ⅰ),OGD group(OGD),OGD+I group,gastrodin treatment group(G+OGD),and G+OGD+Ⅰ group.The expressions of p38 MAPK,phosphorylated p38 MAPK(p-p38 MAPK),M2 microglia marker arginase-1(Arg-1)and chitinase like protein 1/2(YM1/2)were detected by immunofluorescent staining and Western blotting.Results Immunofluorescent staining results showed that the pretreatment with gastrodin reduced the fluorescence expression of p-p38 MAPK in OGD induced BV2 microglia,enhanced the fluorescence expressions of Arg-1 and YM1/2.After pretreatment with SB203580,the fluorescence expressions of p-p38 MAPK further decreased,the fluorescence expressions of Arg-1 and YM1/2 further increased,both were significantly different from the G+OGD group(n=3,P＜0.05).The fluorescence expressions of p38 MAPK in each group was not statistically significant(n=3,P＞0.05).Western blotting results showed that the protein expressions of p-p38 MAPK,Arg-1 and YM1/2 in the OGD group enhanced,compared with that in the control group(n=3,P＜0.05).After the pretreatment with gastrodin,the protein expression of p-p38 MAPK was reduced significantly,the protein expressions of Arg-1 and YM1/2 was enhanced obviously,both were significantly different from the OGD group(n=3,P＜0.05).After pretreatment with SB203580,the protein expressions of p-p38 MAPK was further reduced,the protein expression of Arg-1 and YM1/2 were further enhanced,both were significantly different from the G+OGD group(n=3,P＜0.05).In addition,there was no significant change in p38 MAPK protein expression among groups(n=3,P＞0.05).Conclusion Gastrodin inhibits p38 MAPK signaling activation to promote BV2 microglial polarization towards the M2 phenotype,reducing inflammatory responses and exerting a protective effect.

Objective:To understand the current status of anemia, iron deficiency, and iron-deficiency anemia among preschool children in China.Methods:A cross-sectional study was conducted with a multi-stage stratified sampling method to select 150 streets or townships from 10 Chinese provinces, autonomous regions, or municipalities (East: Jiangsu, Zhejiang, Shandong, and Hainan; Central: Henan; West: Chongqing, Shaanxi, Guizhou, and Xinjiang; Northeast: Liaoning). From May 2022 to April 2023, a total of 21 470 children, including community-based children aged 0.5 to<3.0 years receiving child health care and kindergarten-based children aged 3.0 to<7.0 years, were surveyed. They were divided into 3 age groups: infants (0.5 to<1.0 year), toddlers (1.0 to<3.0 years), and preschoolers (3.0 to<7.0 years). Basic information such as sex and date of birth of the children was collected, and peripheral blood samples were obtained for routine blood tests and serum ferritin measurement. The prevalence rates of anemia, iron deficiency, and iron-deficiency anemia were analyzed, and the prevalence rate differences were compared among different ages, sex, urban and rural areas, and regions using the chi-square test.Results:A total of 21 460 valid responses were collected, including 10 780 boys (50.2%). The number of infants, toddlers, and preschoolers were 2 645 (12.3%), 6 244 (29.1%), and 12 571 (58.6%), respectively. The hemoglobin level was (126.7±14.8) g/L, and the serum ferritin level was 32.3 (18.5, 50.1) μg/L. The overall rates of anemia, iron deficiency, and iron-deficiency anemia were 10.4% (2 230/21 460), 28.3% (6 070/21 460), and 3.9% (845/21 460), respectively. The prevalence rate of anemia was higher for boys than for girls (10.9% (1 173/10 780) vs. 9.9% (1 057/10 680), χ2=5.58, P=0.018), with statistically significant differences in the rates for infants, toddlers and preschoolers (18.0% (475/2 645), 10.6% (662/6 244), and 8.7% (1 093/12 571), respectively, χ2=201.81, P<0.01), and the rate was significantly higher for children in rural than that in urban area (11.8% (1 516/12 883) vs. 8.3% (714/8 577), χ2=65.54, P<0.01), with statistically significant differences in the rates by region ( χ2=126.60, P<0.01), with the highest rate of 15.8% (343/2 173) for children in Central region, and the lowest rate of 5.3% (108/2 053) in Northeastern region. The prevalence rates of iron deficiency were 33.8% (895/2 645), 32.2% (2 011/6 244), and 25.2% (3 164/12 571) in infants, toddlers, and preschoolers, respectively, and 30.0% (3 229/10 780) in boys vs. 26.6% (2 841/10 680) in girls, 21.7% (1 913/8 821), 40.0% (870/2 173), 27.1% (2 283/8 413), 48.9% (1 004/2 053) in Eastern, Central, Western, and Northeastern regions, respectively, and each between-group showed a significant statistical difference ( χ2=147.71, 29.73, 773.02, all P<0.01). The prevalence rate of iron-deficiency anemia showed a significant statistical difference between urban and rural areas, 2.9% (251/8 577) vs. 4.6% (594/12 883) ( χ2=38.62, P<0.01), while the difference in iron deficiency prevalence was not significant ( χ2=0.51, P=0.476). Conclusions:There has been a notable improvement in iron deficiency and iron-deficiency anemia among preschool children in China, but the situation remains concerning. Particular attention should be paid to the prevention and control of iron deficiency and iron-deficiency anemia, especially among infants and children in the Central, Western, and Northeastern regions of China.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

The alterations of serum biological endogenous chemicals in rats with phlegm dampness accumulation syndrome of prehypertension (PHT) were interfered by Banxia Baizhu Tianma decoction (BBT), and the metabolic regulatory pathway of BBT was clarified using serum metabonomics analysis. To replicate the rat model of prehypertension phlegm dampness syndrome, blood pressure, behavioral markers, and serum biochemical markers of rats were collected. BBT's effectiveness in controlling blood pressure and blood lipids was assessed, and changes in endogenous small molecules in rat serum were determined using UPLC-Q-Orbitrap MS metabolic analysis. The results showed that BBT could regulate 9 metabolites, including arachidonic acid, cholic acid, glycodeoxycholic acid, N-adenosyltyrosine, arginine, lysophosphatidylethanolamine (20:0/0:00), lysophospholipid (P-18:0), lysophospholipid (18:0), lysophospholipid (22:5(7Z,10Z,13Z,16Z,19Z)). MetaboAnalyst was used to analyze the metabolic pathway. There were 7 metabolic pathways closely related to the change of blood pressure in rats, among which arachidonic acid metabolic pathway was the most critical. The metabolism difference foreign body in the model rats tends to return to the normal level, which provides a research basis for the mechanism of BBT from the perspective of metabonomics. This study was approved by the Experimental Animal Welfare Ethics Review Committee of Shandong University of Traditional Chinese Medicine (approval number: SDUTCM20211103001).

Sepsis is a systemic inflammatory syndrome induced by infection and other factors， with the number of patients worldwide exceeding 10 million each year. The pathophysiological mechanism is of this disease complex. Sepsis is often accompanied by endotoxin translocation， gastrointestinal dysfunction， inflammatory cytokine activation， immune dysregulation， coagulation disorder， multiple organ function impairment and many other body imbalances， as well as systemic inflammation， apoptosis， oxidative stress injury and other cell damage mechanisms. This disease causes a heavy medical burden due to the difficult diagnosis and treatment and the poor prognosis. Great progress has been achieved in the diagnosis and treatment of sepsis with traditional Chinese medicine （TCM） and western medicine. The value of western medicine in the diagnosis and treatment of sepsis is limited due to antibiotic resistance， hormone abuse， and high medical costs. Sepsis is classified as a warm disease or typhoid fever in TCM. Da Chengqitang is a classical formula in the Treatise on Typhoid Fever to deal with the excess syndrome of Yang brightness Fu-organ. Modern medicine has proved that Da Chengqitang has the effect of inhibiting oxidative stress， reducing inflammation， and delaying apoptosis by improving gastrointestinal dynamics and regulating intestinal microecology. On the basis of the previous theoretical basis and the rich experience in the medication， medical practitioners have proposed a new therapeutic concept of using Da Chengqitang in combination with western drugs from a holistic view involving both bacteria and toxicity for treating both the symptoms and the root cause， which has a wide range of application. The article reviews the classical research and latest findings of Da Chengqitang in the treatment of sepsis， with a view to clarifying the mechanism and advantages of this formula in the adjuvant treatment of sepsis， exploring its potential efficacy， and providing timely， adequate， and scientific theoretical support for the promotion of this formula in the clinical practice.