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.

The prevalence of diabetes mellitus in China has recently been increasing year by year,and spontaneous skin ulcers in diabetic patients,as one of the most serious complications,often develop on the patient's extremities represented by foot ulcers.Due to the complexity and variety of its pathogenesis,it leads to poor clinical outcomes and difficulty in healing.Thus,pa-tients often face the risk of amputation and death.Therefore,the exploration of mechanisms of the vascular pathogenesis of diabetic delayed-healing wounds and targeted screening of therapeutic agents has become a current research hotspot.Herein,in this paper,we briefly review the role of impaired angiogenesis and vascular dysfunction in diabetic skin ulcers,and the research progress of classical hypoglycemic and natural compounds against vascular lesions is preliminarily summarized to provide a theoretical basis for effective clinical treatment.

Objective To investigate the clinical effect of recombinant interferon(IFN)-α-2b and ipratropium bromide atomized inhalation in pediatric bronchiolitis.Methods A total of 112 children with bronchiolitis diagnosed and treated in Huzhou Central Hospital from April 2020 to August 2022 were selected and divided into control group and observation group according to envelope method,with 56 cases in each group.The control group was treated with atomization inhalation of ipratropium bromide,and the observation group was treated with atomization inhalation of recombinant IFN-α-2b.Both groups completed 7 days of treatment,and the lung function,interferon-γ(IFN-γ),interleukin-10(IL-10),immune function and adverse reaction were compared between two groups.Results After 7 days of intervention,the disappearance time of wheezing,cough,lung moist rales and sputum sounds in observation group were significantly shorter than those in control group(P＜0.05).The tidal volume(TV),peak tidal expiratory flow(PTEF),ratio of time to peak tidal expiratory flow to total expiratory time(TPTEF/TE),IFN-γ and IL-10 in both groups were significantly higher than those before intervention(P＜0.05).TV,PTEF,TPTEF/TE,IFN-γ and IL-10 in observation group were higher than those in control group(P＜0.05).The levels of CD3+,CD4+and CD4+/CD8+in both groups were significantly higher than before intervention,and the levels of CD8+were significantly lower than before intervention(P＜0.05).The levels of CD3+,CD4+and CD4+/CD8+in observation group were significantly higher than those in control group,and CD8+was significantly lower than that in control group(P＜0.05).There was no significant difference in the incidence of adverse reactions between two groups(x2=0.704,P=0.401).Conclusion Both recombinant IFN-α-2b and ipratropium bromide atomized inhalation can achieve good therapeutic effect in children with bronchiolitis,but the former can help shorten the time of symptom disappearance and improve the immune level of children,and is worthy of clinical application.

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.

Objective: To explore the effect of improving these traits through art therapy group meetings as a form of psychological counseling, so as to promote mental wellness among this population. Methods: A total of 74 hearing impaired students from grades 3 to 9 were surveyed with the Children s Self concept Scale (PHCSS) and Social Adaptability Scale. Eight art therapy group meetings, as a form of psychological counseling, were then held. Results: Self consciousness among hearing impaired students aged 10-12 and 13-16 years old was significantly lower than the national norm ( t =-6.51, -8.50, P <0.01). The social adaptability level of this group was very poor(2.89±8.26), and a significant positive correlation was found between self awareness and social adaptability among hearing impaired students. Further, self awareness could predict the social adaptability of these students ( F = 9.04 , P <0.05). After group psychological counseling intervention, there was significant increases in self consciousness among students from grades 3 to 9, and significant increases were also found in the social adaptability of students in grades 3, 4, 5, 6 and 8 ( P <0.05). Conclusion Self awareness shows certain influence on the social adaptability level of hearing impaired students, and group psychological counseling can promote social adaptability by improving self awareness among this population.

BACKGROUND: Microglia plays an indispensable role in the pathological process of sleep deprivation (SD). Here, the potential role of microglial CX3C-chemokine receptor 1 (CX3CR1) in modulating the cognition decline during SD was evaluated in terms of microglial neuroinflammation and synaptic pruning. In this study, we aimed to investigat whether the interference in the microglial function by the CX3CR1 knockout affects the CNS's response to SD. METHODS: Middle-aged wild-type (WT) C57BL/6 and CX3CR1-/- mice were either subjected to SD or allowed normal sleep (S) for 8 h to mimic the pathophysiological changes of middle-aged people after staying up all night. After which, behavioral and histological tests were used to explore their different changes. RESULTS: CX3CR1 deficiency prevented SD-induced cognitive impairments, unlike WT groups. Compared with the CX3CR1-/- S group, the CX3CR1-/- SD mice reported a markedly decreased microglia and cellular oncogene fos density in the dentate gyrus (DG), decreased expression of pro-inflammatory cytokines, and decreased microglial phagocytosis-related factors, whereas increased levels of anti-inflammatory cytokines in the hippocampus and a significant increase in the density of spines of the DG were also noted. CONCLUSIONS These findings suggest that CX3CR1 deficiency leads to different cerebral behaviors and responses to SD. The inflammation-attenuating activity and the related modification of synaptic pruning are possible mechanism candidates, which indicate CX3CR1 as a candidate therapeutic target for the prevention of the sleep loss-induced cognitive impairments.
Animals ; Cognitive Dysfunction ; Mice ; Mice, Inbred C57BL ; Microglia ; Neuroinflammatory Diseases ; Sleep Deprivation

OBJECTIVE: To analyze a pathogenic variant of MEFV gene in a family with autosomal dominant-familial Mediterranean fever (AD-FMF). METHODS: A 5-year-old boy presented with recurrent aseptic meningitis and his major symptoms included recurrent fever with headache and vomiting. His family members including his mother, sister and brother also had recurrent fever. A genetic disease was considered. DNAs were extracted from patient and all his family members' blood samples. Whole exome sequencing was performed to identify putative pathogenic variants that can explain this family's condition and Sanger sequencing was conducted. The impact of detected variants were predicted and validated by bioinformatics. RESULTS: A missense variant c.2229C>G (p.Phe743Leu) in MEFV gene was identified in the proband and his family members including his mother, sister and brother. This variant had not been reported in China previously, but the locus of it had already been reported in Arabic patient with AD-FMF (PS1). This variant was absent in major allele frequency databases (PM2) and had been predicted to be pathogenic based on Mutationtaster, PROVEAN and PolyPhen-2. In addition, the change of amino acid, locating in 743 locus of pyrin protein, encoding by MEFV gene, was found to cause SPRY_PRY_TRIM20 and SPRY_superfamily domain destroyed and finally influenced the fuction of pyrin protein. On the other hand, using UCSF chimera software, we find the variant c.2229C>G (p.Phe743Leu) can induce serious influence to the spatial structure of pyrin protein and loss of protein fuction (PP3). According to the ACMG variant classification guideline, the variant c.2229C>G (p.Phe743Leu) in MEFV gene was classified as likely pathogenic (PS1+PM2+PP3). CONCLUSION The condition of this AD-FMF family may be attributed to the missense variant c.2229C>G (p.Phe743Leu) in MEFV gene. The recurrent aseptic meningitis was a very rare manifestation in AD-FMF patients and had not been reported in China previously. The clinical and genetic findings of the present study are helpful for the further understanding of AD-FMF.
Child, Preschool ; Familial Mediterranean Fever/genetics* ; Gene Frequency ; Genetic Testing ; Humans ; Male ; Mutation ; Pyrin/genetics* ; Whole Exome Sequencing

RNF20, an E3 ligase critical for monoubiquitination of histone H2B at lysine 120 (H2Bub), has been implicated in the regulation of various cellar processes; however, its physiological roles in adipocytes remain poorly characterized. Here, we report that the adipocyte-specific knockout of Rnf20 (ASKO) in mice led to progressive fat loss, organomegaly and hyperinsulinemia. Despite signs of hyperinsulinemia, normal insulin sensitivity and improved glucose tolerance were observed in the young and aged CD-fed ASKO mice. In addition, high-fat diet-fed ASKO mice developed severe liver steatosis. Moreover, we observed that the ASKO mice were extremely sensitive to a cold environment due to decreased expression levels of brown adipose tissue (BAT) selective genes, including uncoupling protein 1 (Ucp1), and impaired mitochondrial functions. Significantly decreased levels of peroxisome proliferator-activated receptor gamma (Pparγ) were observed in the gonadal white adipose tissues (gWAT) from the ASKO mice, suggesting that Rnf20 regulates adipogenesis, at least in part, through Pparγ. Rosiglitazone-treated ASKO mice exhibited increased fat mass compared to that of the non-treated ASKO mice. Collectively, our results illustrate the critical role of RNF20 in control of white and brown adipose tissue development and physiological function.

Objective To investigate the clinical effect of atorvastatin combined with aspirin in the treatment of acute cerebral infarction ( ACI) .Methods 700 patients with ACI were selected ,and they were randomly divided into two groups according to the digital table ,with 350cases in each group.The control group was treated with aspirin .The observation group was given atorvastatin combined with aspirin .The neurological deficits ,daily living ability,overall treatment effect , disease related parameters and adverse reactions were compared between the two groups .Results After treatment,the NIHSS score,carotid IMT,plaque area,RI,TC,TG,LDL-C,hs-CRP,oxLDL,MDA,TNF-α, IL-6 and IL -1 levels in the observation group were (11.20 ±3.87) points,(1.04 ±0.13) mm,(0.51 ± 0.07)cm2,(63.26 ±2.56)%,(4.21 ±0.27)mmol/L,(1.32 ±0.12)mmol/L,(1.51 ±0.20)mmol/L,(1.61 ± 0.50)mg/L,(42.50 ±7.15) mg/L,(4.33 ±1.34)μmol/L,(419.65 ±51.16)μg/L,(120.04 ±22.50) ng/L, (310.45 ±44.82) ng/L,respectively,which were significantly lower than those in the control group [(14.79 ± 3.64)points,(1.20 ±0.17) mm,(0.67 ±0.12) cm2,(65.38 ±2.70)%,(4.76 ±0.36) mmol/L,(1.75 ± 0.17)mmol/L,(1.92 ±0.27) mmol/L,(2.32 ±0.67) mg/L,(60.15 ±9.15) mg/L,(6.19 ±1.40)μmol/L, (480.62 ±55.96)μg/L,(157.33 ±25.79)ng/L,(357.39 ±46.20)ng/L].The Barthel index,carotid artery lumen diameter,SV,DV,HDL-C and SOD levels in the observation group were (75.40 ±7.96),(7.57 ±0.24)mm, (0.789 ±0.18)m/s,(0.314 ±0.030)m/s,(1.69 ±0.15)mmol/L,(122.64±19.55)U/mL,respectively,which were significantly higher than those in the control group [(67.27 ±7.55),(7.23 ±0.28)mm,(0.673 ±0.125)m/s, (0.226 ±0.029)m/s,(1.42 ±0.20)mmol/L,(103.60 ±16.68)U/mL].The obvious effective rate and total effective rate of the observation group were 56.00% and 80.57%,respectively,which were significantly higher than those of the control group (39.71%and 68.00%,χ2 =18.599,14.478,all P<0.01).Conclusion Atorvastatin combined with aspirin in the treatment of patients with ACI has significant clinical effect and high safety .

Objective To investigate the clinical efficacy of piperacillin/tazobactam in the treatment of community acquired pneumonia (CAP).Methods 100 cases of CAP in Songyang People's Hospital from March 2016 to March 2017 were collected and randomly divided into two groups according to the digital table , with 50 cases in each group .The piperacillin/tazobactam group was treated with piperacillin/tazobactam , and the cefotaxime sodium group was given cefotaxime sodium .The clinical indicators ,symptoms and imaging effects ,blood indicators ,blood gas analysis and inflammatory indicators were compared between the two groups .Results The clinical symptoms disap-peared time,hospitalization time and hospitalization expenses in the piperacillin /tazobactam group were (3.77 ± 1.12)d,(8.44 ±2.47) d,(1780 ±489) CNY,respectively,which were significantly lower than those in the cefotaxime sodium group [(5.36 ±1.70)d,(11.37 ±3.68)d,(2136 ±470)CNY,t=5.523,4.675,3.711,all P<0.01].The effective rate of the piperacillin/tazobactam group was 90％,which was significantly higher than 70％ of the cefotaxime sodium group (χ2 =6.25,P <0.05).The effective rate of imaging treatment in the piperacillin /tazobactam group was 94％,which was significantly higher than 68％in the cefotaxime sodium group (χ2 =10.981, P<0.01).After treatment,the WBC and neutrophil percentage of the piperacillin/tazobactam group were (7.30 ± 1.08) ×109/L,(0.65 ±0.04),respectively,which were significantly lower than those of the cefotaxime sodium group [(8.66 ±1.25) ×109/L,(0.71 ±0.04),t=5.821,7.405,all P<0.01].The PaO2 level of the piperacillin/tazobactam group was significantly higher than that of the cefotaxime sodium group [(81.90 ±6.83)％vs.(74.20 ± 6.27)％,t=5.873,P<0.01].The levels of CRP,PCT,IL-1 and TNF-αin the piperacillin/tazobactam group