objective To examine nuclear transIocation of peroxisome proliferator-activated receptor γ(PPARγ)in rats following focal cerebral ischemia/reperfusion(I/R),and to explore the significance of altered PPARγ,nuclear translocation in ischemic brain injury.Methods Healthy adult male SD rats underwent 60-min cerebral artery occlusion followed by reperfusion of 4,8,or 24 h,respectively.The cytoplasmic-to-nuclear shuttling of PPARγ was characterized by Western blot,immunohistochemical and immunofluoreseence staining.The effects of PPARγ agonist rosiglitazone (Ros) and antagonist GW9662 on I/R-induced PPARγ nuclear translocation were also examined in the present study. Furthermore,TTC staining war adopted to determine the change in cerebral infarction volume. Results (1)Western blot analysis revealed an increase of PPARγ in the nucleus and a simultaneous reduction in the cytosol following ischemia and reperfusion for 4 h(tcytosol=9.03,tmuclear=27.19,P=0.00).Prolonged the reperfusion further enhanced this I/R induced PPARγ translocation in a time-dependent manner.Using immunohistochemistry and immunofluorescence,nuclear PPAR γ positive staining increased from 48.3%in the sham control to 80.3% following ischemia and reperfusion for 24 h.(2)Western blot analysis revealed that PPARγ agonist Ros further increased I/R-induced nuclear enrichment of PPARγ,whereas PPARγ antagonist GW9662inhibited I/R-stimulated change in PPARγ.(3)When compared to the L/R group using TTC staining,Ros treatment significantly decreased the infarction volume by 48.40%(15.46±4.94 versus 29.96±3.39,t=5.93.P=0.00),whereas GW9662 increased by 58.95%(47.62±4.93 versus 29.96±3.39,t=7.23,P=0.00).Conclusions Cerebral I/R injury induces PPARγ translocation from the cytosol to the nucleus.This change may represent an intrinsic neuroprotective response against brain I/R injury.

Objectives:To evaluate if the administration of an enteral diet supplemented with glutamine,arginine and ? 3 fatty acids modulate the inflammatory and immune responses and the outcome after surgery. Methods:A prospective,randomized,double blind and clinical trial was performed.Eighty eight patients with gastrointestinal cancer were randomly divided itnto two groups.One group was given an isocaloric and isonitrogenous standard diet and the other was fed with the supplemented diet with glutamine, arginine and ? 3 fatty acids.Feedings were started within 48 hour after operation, and continued until day 8.All variables were measured before operation and on postoperative day 1,4 and 8.Blood was drawn at different time points to assess albumin, prealbumin and transferring.Immune responses was determined by phagocytosis ability,respiratory burst of polymorphonuclear cells, total lymphocytes, lymphocyte subsets, nitric oxide,cytokine concentration,immunoglobins,and inflammatory responses by plasma levels of C reactive protein and prostaglandin E 2. Results:Tolerance of both formula diets was excellent.There were significant differences in the immunological and inflammatory responses between the two groups.In supplemented group,the serum concentrations of IgA,IgG,IgM,phagocytosis and respiratory burst after surgery were higher and C reactive protein level was lower( P

Objective To investigate the effect of ketamine on depression-like behaviors at different developmental stages of offspring rat exposed to prenatal restraint stress (PRS).MethodsPregnant SD rats were randomly divided into control group (n=6) and PRS group (n=8).The dams of PRS group received three times(45 minutes/time)restraint stress every day.The anxiety-like and depression-like behaviors of the offsprings of the two groups were tested in the stage of juvenile,adolescence and early adulthood.Then the antidepressant effect of ketamine on prenatal stress rats at different developmental stages was observed.ResultsIn the open-field test,the time in the central area of the offspring rats in PRS group at different developmental stages (juvenile(2.50±0.43)s,adolescence(9.17±1.05)s,early adulthood(8.33±0.92)s) were significantly lower than those of the control group((8.33±1.05)s,(19.17±1.06)s,(18.83±1.30)s,all P<0.05).In the forced swimming test,the immobility time in the offspring rats of PRS group at the different developmental stages (juvenile(192.50±10.82)s,adolescence(182.75±10.12)s,early adulthood(199.88±9.20) s)were significantly higher than those of control group((76.00±19.00)s,(96.30±12.91)s,(108.30±10.98)s,all P<0.05).Ketamine could quickly and strongly reduce the immobility time of the offsprings exposed to PRS in the stage of adolescence and early adulthood (P<0.01),but the effect was weaker in the juvenile offsprings (P<0.05).ConclusionPRS leads to persistent anxiety-like and depression-like behavior in offsprings and ketamine exerts a good antidepressant effect on the offspring rats in the stage of adolescence and early adulthood.

Alzheimer's disease(AD),the most common progressive neurodegenerative disease in dementia,is also a special lipid disease.From the perspective of modern medicine,cholesterol homeostasis is an important risk factor for AD.Amyloid-beta plaque deposition,neurofibrillary tangles,and large amount of lipid granule accumulation are typical pathological features of AD.From the perspective of TCM,turbidity is the key to the pathogenesis of AD.Phlegm turbid,stasis turbid and turbid toxin are the concrete derivation of turbidity,which are the standard of AD.Cholesterol is the greasy lipid which is produced from of the essence of water and food,the disturbance of cholesterol homeostasis is a typical embodiment of the pathogenesis mechanism of endogenous turbidity.Regulating cholesterol homeostasis by traditional Chinese medicine may be a new direction for the treatment of AD in the future.Focusing on the modern research of cholesterol homeostasis,taking the theory of turbidity as the starting point,this paper analyzed the correlation between the connotation of turbidity theory and the imbalance of cholesterol homeostasis as well as the pathogenesis mechanism,and further elucidated the clinical application results in the treatment of AD from the aspects of phlegm turbid,stasis turbid and turbid toxin,so as to better guide clinical practice and scientific research.

ObjectiveTo analyze the relationship of the static single-leg stance balance with ankle muscles strength and position sense in individuals with functional ankle instability (FAI). MethodsFrom March to May, 2023, 44 FAI individuals were recruited in Hebei Normal University, and the maximum isokinetic muscle strength (60°/s and 180°/s) and position sense as ankle flexion, extension, inversion and eversion were measured using isokinetic dynamometer; while the center of pressure (COP) sway distance and envelope area were measured as static single-leg stance with eyes open or closed using three-dimensional force plate. ResultsThe maximum isokinetic torque as ankle eversion at 180°/s correlated with the COP anterior-posterior sway distance with eyes closed (r = -0.378, P < 0.05). ConclusionExplosive ankle eversion strength is related with the balance in static single-leg stance, which may help to evaluate and intervent the ankle function of FAI individuals.

Objective:To observe the effects of Qifu Lizhong Enema Prescription on ulcerative colitis rats with yang deficiency of spleen and kidney syndrome; To discuss its mechanism.Methods:Totally 70 male SD rats were randomly divided into blank group, model group, mesalazine group, Qifu Lizhong Guanchang Prescription high-, medium- and low-dosage groups; blank group ( n=10), other groups ( n=12). Except for the blank group, the other groups used bitter cold purgative therapy (Dahuang Decoction) by gavage, and combined with trinitrobenzen sulfonic acid (TNBS) +55% ethanol compound method to induce UC rat model. After successful modeling, the blank group and model group were given 1 ml normal saline enema daily, Qifu Lizhong Enema Prescription groups were given Qifu Lizhong Enema Prescription 3.00, 1.50, 0.75 g/kg enema daily, and the mesalazine group was given mesalazine 0.03 g/kg enema daily, once a day for consecutive 14 days. After 14 days, Disease Activity Index (DAI) score was performed, and hematoxylin-eosin staining (HE) was used to observe the pathological tissues of the colon. The expressions of Occludin and adhesion molecules A (JAM-A) protein in colon tissue were detected by immunohistochemistry and Western blot. Results:HE results showed that the mucosal structure was damaged, inflammatory cells were infiltrated, edema and ulcer foci were observed in model group. The mucosal structure of mesalazine group and Qifu Lizhong Enema Prescription groups were intact, and inflammatory infiltration, edema and ulcer of neoepithelial were improved. Compared with model group, the DAI scores of Qifu Lizhong Enema Prescription groups decreased ( P<0.01), the expressions of Occludin and JAM-A in Qifu Lizhong Guanchang Prescription high- and medium-dosage groups significantly increased ( P<0.05). Conclusion:Qifu Lizhong Enema Prescription can significantly relieve the symptoms and pathological morphology of UC rats, and the mechanism of repairing intestinal mucosal barrier may be related to up-regulating the expressions of Occludin and JAM-A proteins.

Alzheimer's disease （AD） is a common chronic degenerative neurological disease in the elderly and is mainly manifested by the impairment of cognition， memory， and behaviors. At present， the etiology and pathogenesis of this disease have not been fully unraveled， and the research on related drugs for alleviating the disease progression is still in clinical trials. Traditional Chinese medicine （TCM） believes that the elderly have reduced visceral function. Deficiency of vital Qi and turbid phlegm obscuring orifices are the core pathogenesis of AD. Qi deficiency and phlegm obstruction run through the whole pathological process of AD， and the important role of therapeutic principles of supplementing Qi and resolving phlegm is emphasized in treatment. In recent years， the Chinese medicinal compounds effective in supplementing Qi and resolving phlegm represented by Kaixin Powder have been widely used in the clinical and basic research of AD. As reported， in addition to the improvement of the cognitive function of AD， it can also reduce β amyloid （Aβ） deposition， inhibit tau hyperphosphorylation， improve neurotransmitter activity， regulate neuronal synaptic plasticity， resist oxidant stress injury， and inhibit the central inflammatory response and neuronal apoptosis. Therefore， this article reviewed and analyzed the theoretical basis of the treatment of AD by supplementing Qi and resolving phlegm and the mechanism of Chinese medicinal compounds effective in supplementing qi and resolving phlegm against AD to provide theoretical support and a scientific basis for the clinical application of TCM in the prevention and treatment of AD.

Microneedle percutaneous immunization is achieved by puncturing the stratum corneum of the skin with microneedles so that the vaccine is efficiently recognized by antigen-presenting cells to induce a specific immune response. Due to the advantages of efficient induction of immune response, low pain and easy storage, transdermal immunization by microneedles has been widely used for immunization of various vaccines in recent years. This review summarizes the materials of microneedles, application for transcutaneous immunization, as well as the challenges that need to be addressed.
Administration, Cutaneous ; Drug Delivery Systems ; Needles ; Vaccination ; Vaccines

Although widely applied in treating hematopoietic malignancies, transplantation of hematopoietic stem/progenitor cells (HSPCs) is impeded by HSPC shortage. Whether circulating HSPCs (cHSPCs) in steady-state blood could be used as an alternative source remains largely elusive. Here we develop a three-dimensional culture system (3DCS) including arginine, glycine, aspartate, and a series of factors. Fourteen-day culture of peripheral blood mononuclear cells (PBMNCs) in 3DCS led to 125- and 70-fold increase of the frequency and number of CD34⁺ cells. Further, 3DCS-expanded cHSPCs exhibited the similar reconstitution rate compared to CD34⁺ HSPCs in bone marrow. Mechanistically, 3DCS fabricated an immunomodulatory niche, secreting cytokines as TNF to support cHSPC survival and proliferation. Finally, 3DCS could also promote the expansion of cHSPCs in patients who failed in HSPC mobilization. Our 3DCS successfully expands rare cHSPCs, providing an alternative source for the HSPC therapy, particularly for the patients/donors who have failed in HSPC mobilization.
Antigens, CD34/metabolism* ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Humans ; Leukocytes, Mononuclear/metabolism* ; Peptides/metabolism*