Objective To explore the possible causes of CAST/EiJ mouse susceptibility to multiple pathogens,the immune cell phenotypes in the peripheral blood and spleen of CAST/EiJ mice were analyzed to clarify their composition.Methods Classical dendritic cells(cDCs),natural killer(NK)cells,B lymphocytes,T lymphocytes,and their subsets in the peripheral blood and spleen of CAST/EiJ mice and C57BL/6J mice were detected by flow cytometry using the cell surface markers CD3,CD4,CD8,CD11b,CD11c,CD19,CD27,CD49b,and TCRβ.Results There was no significant difference in the proportion of cDCs between CAST/EiJ and C57BL/6J mice,but the cDC1 cell subset population was smaller in CAST/EiJ.The proportions of NK cells(mainly mature NK cell subsets)and T lymphocytes(mainly CD8+T cells)were both lower in CAST/EiJ mice than C57BL/6J mice,while the proportion of B cells was higher in CAST/EiJ mice than C57BL/6J mice.Conclusions The proportions of NK and T lymphocytes in CAST/EiJ mice were lower than those in C57BL/6J mice.

Objective: To compare the effects between second toe tibial dorsal artery flap (2-TDAF) and second toe tibial plantar proper artery flap (2-TPPAF) in repairing finger skin and soft tissue defects. Methods: A retrospective cohort study was conducted. From January 2019 to June 2020, 27 patients with skin and soft tissue defects at the fingertips with area of 1.5 cm×1.2 cm-2.6 cm×1.8 cm after debridement who met the inclusion criteria were admitted to Suzhou Ruihua Orthopaedic Hospital, including 21 males and 6 females, aged 19-59 (37±10) years. According to flap repair methods used in the defective fingers, the patients were divided into 2-TDAF group (12 cases) and 2-TPPAF group (15 cases). The area of 2-TDAF ranged from 1.5 cm×1.2 cm to 2.5 cm×1.6 cm, and the area of 2-TPPAF ranged from 1.7 cm×1.3 cm to 2.6 cm×1.8 cm. Full-thickness skin grafts from the medial side of the ipsilateral leg were grafted to the wounds in donor sites, and the wounds in donor sites of skin grafts were directly sutured. Flap arterial diameter, flap excision time, flap survival situation of patients in 2 weeks after operation, and follow-up time were recorded. At the last follow-up, the two-point discrimination distance of flap graft site, total action motion (TAM) of the finger joints, and wound healing of the flap donor site were recorded; the Vancouver scar scale (VSS) was used to score the scar in donor area of the second toe and the recipient area of fingers; the appearance and self-satisfaction subscales of the Michigan hand outcomes questionnaire (MHQ) were used to evaluate the affected finger. Data were statistically analyzed with independent sample t test or Fisher's exact probability test. Results: The flap artery diameter of patients in 2-TDAF group was 0.35-0.80 (0.56±0.14) mm and the flap cutting time was (14.0±2.7) min, which were significantly shorter than 0.80-1.35 (1.02±0.16) mm and (19.7±3.4) min in 2-TPPAF group (with t values of 7.81 and 4.79, respectively, P<0.01). The flaps of patients in the 2 groups in recipient areas survived well in 2 weeks after operation, and the wounds in donor areas of flaps of patients in the 2 groups healed well at the last follow-up. There was no statistically significant difference in the postoperative follow-up time, and two-point discrimination distance of flap graft site, TAM of the finger joints, VSS score of scar in the second toe donor site and the finger recipient site, and the appearance and self-satisfaction of MHQ scores of the affected finger at the last follow-up (P>0.05). Conclusions: Compared with 2-TPPAF, 2-TDAF has a shallower anatomical layer and shorter time for surgical flap removal, which can preserve the proper arteries and nerves at the base of the toes and reduce the damage to the donor site.
Male ; Female ; Humans ; Soft Tissue Injuries/surgery* ; Finger Injuries/surgery* ; Cicatrix/surgery* ; Plastic Surgery Procedures ; Retrospective Studies ; Treatment Outcome ; Surgical Flaps ; Skin Transplantation ; Toes/surgery* ; Arteries ; Perforator Flap

Chaperone-mediated autophagy (CMA) is a lysosome-dependent selective degradation pathway implicated in the pathogenesis of cancer and neurodegenerative diseases. However, the mechanisms that regulate CMA are not fully understood. Here, using unbiased drug screening approaches, we discover Metformin, a drug that is commonly the first medication prescribed for type 2 diabetes, can induce CMA. We delineate the mechanism of CMA induction by Metformin to be via activation of TAK1-IKKα/β signaling that leads to phosphorylation of Ser85 of the key mediator of CMA, Hsc70, and its activation. Notably, we find that amyloid-beta precursor protein (APP) is a CMA substrate and that it binds to Hsc70 in an IKKα/β-dependent manner. The inhibition of CMA-mediated degradation of APP enhances its cytotoxicity. Importantly, we find that in the APP/PS1 mouse model of Alzheimer's disease (AD), activation of CMA by Hsc70 overexpression or Metformin potently reduces the accumulated brain Aβ plaque levels and reverses the molecular and behavioral AD phenotypes. Our study elucidates a novel mechanism of CMA regulation via Metformin-TAK1-IKKα/β-Hsc70 signaling and suggests Metformin as a new activator of CMA for diseases, such as AD, where such therapeutic intervention could be beneficial.

Objective: To observe changes in the molecular expression of the NLR Family Pyrin Domain Containing Protein 3 (NLRP3) pathway in depressed rats after treatment with Xiaoyaosan, and identify the regu-latory mechanism of this compound. Methods: Male Sprague-Dawley rats were randomly divided into five groups with 12 rats in each group, including the control group, model group, Fluoxetine group, Xiaoyaosan group, and MCC950 group. A depression model was generated by chronic immobilization stress (induced by 3 h of restraint immo-bilization every day), and the drugs were administered at the same time in each group for 21 days. The effects of Xiaoyaosan on behavioral changes of depressed rats were observed through macroscopic characterization, body mass, open field experiments, and a sucrose preference test. The mRNA and protein expression of the NLRP3 signaling pathway was examined by fluorescence real-time quantitative PCR and Western blot assays. Results: The Xiaoyaosan group, Fluoxetine group, and MCC950 group rats showed improved depressive behavior and an increased weight of sucrose water consumption. The protein and mRNA expression levels of NLRP3, Caspase-1, and IL-1β were also decreased in the Fluoxetine, Xiaoyaosan, and MCC950 groups. Conclusion: NLRP3, Caspase-1, and IL-1β protein and mRNA expression levels were increased in the cortex of depressed rats, while Xiaoyaosan protected cortical tissue in these rats by decreasing NLRP3, Caspase-1, and IL-1βprotein and mRNA expression.

Objective To explore developmental states on the preterm and term neonatal brain white matter based on the co-variation of metrics derived from diffusion tensor imaging(DTI).Methods This work enrolled 66 neonates,consisting of 33 preterm(21 males and 12 females;gestational age:30.143-36.286 weeks)and 33 full-term neonates(22 males and 11 females;gestational age:37.000 -41.429 weeks).DTI derived metrics included axial diffusivity(AD),radial diffusivity(RD),and fractional anisotropy(FA).Spearman's rank correlation between metrics and postmenstrual age was analyzed in the preterm and term neonates.Developmental states were evaluated according to the method proposed by Dubois:fiber organization was associated with increased AD, decreased RD and increased FA;pre-myelination was related to decreased AD,decreased RD and unchanged/increased FA;myelination was revealed by unchanged AD,decreased RD and increased FA.Mann-Whitney U test was used to compare DTI metrics between the preterm and term neonates.Results According to the method proposed by Dubois,posterior limb of internal capsule and corpus callosum underwent myelination in the preterm-neonate period.Cerebral peduncle started myelination in the term-neonate period.Superior corona radiate,inferior fronto-occipital fasciculus and external capsule underwent pre-myelination on preterm and term neonates.FA values were higher in term neonates than those in preterm neonates in all the selected regions(P＜0.05).AD and RD values were lower in term neonates than those in preterm neonates in the selected regions except for cerebral peduncle(P＜0.05).Conclusion Changes in DTI metrics and the method of Dubois can be used to quantitatively evaluate developmental states of the neonatal brain white matter.The changes coincided with DTI variations associated with pre-myelination and myelination.White matter development is delayed in preterm neonates compared with term neonates.

Objective To study the characteristics and general regulari-ty of adverse reactions of the traditional Chinese medicine injection.Methods A total of 63 cases of adverse reaction reports were collected, reported to the national adverse drug reaction monitoring center, from January 2014 to November 2014 in the third hospital of Shijiazhuang city.The data of the patient gender, age, history of adverse reactions, combi-nation therapy, the type and quantity of drugs, involving the organ/system, the time adverse reaction occurred, route of administration and association analysis and prognosis of adverse reaction were statistically analyzed.Results Among 63 cases, 60 cases of them were administered with drugs intravenously and most of them were elderly patients (≥40 years).Clinical manifestations of adverse reactions were skin rash, itching common, followed by digestive symptoms.All the cases involved 7 categories and 15 varieties, mostly being blood circulation and detoxification drugs.Conclusion Traditional Chinese medicine injections have been widely used , with frequent adverse reactions.Adequate attention should be given, and rational drug management to ensure patient medication safety be strengthened.