Coronary Disease ; complications ; Erdheim-Chester Disease ; complications ; Humans ; Male ; Middle Aged

Adrenal Gland Neoplasms ; Adult ; Humans ; Male ; Pheochromocytoma ; Rupture, Spontaneous

Objective To evaluate the effect of mechanical ventilation on synaptic plasticity in hippocampal CA1 region of mice.Methods Thirty-six male C57BL/6 mice,aged 8-10 weeks,weighing 20-25 g,were randomly divided into 2 groups (n =18 each) using a random number table:control group (group C) and mechanical ventilation group (group M).After anesthesia,endotracheal intubation was carried out,and open reduction and internal fixation was performed after tibial fracture was induced in mice.In C group,the endotracheal tube was removed after operation,and then the mice were exposed to 1.5％ isoflurane for 6 h in a chamber.In M group,the mice were mechanically ventilated continuously for 6 h,and 1.5％ isoflurane was inhaled to maintain the level of anesthesia.At 2 h and 1 and 3 days after the end of ventilation,6 mice were chosen from each group,and fear conditioning test was performed,and the percentage of freezing time was recorded.Six mice were chosen from each group on 1 day after the end of ventilation,and novel object recognition task was carried out.The preference index was calculated at 5-min,2-h and 1-day intervals on 4 days after the end of ventilation.Three mice were chosen from each group on 1 day after the end of ventilation and sacrificed,and the hippocampi were isolated for examination of hippocampal ultrastructure (with electron microscope) and for calculation of the number of synapses.Three mice were chosen from each group on 1 day after the end of ventilation and sacrificed,and the whole brain was removed for measurement of dendritic spine density in brain tissues.Results Compared with group C,the percentage of freezing time was significantly decreased at 2 h and 1 day after operation,the preference index at different intervals was decreased,the number of synapses in hippocampal CA1 region was reduced,and the apical and basal dendritic spine densities were decreased in group M.Conclusion Mechanical ventilation can change synaptic plasticity in hippocampal CA1 region of mice.

Arachnoid ; pathology ; surgery ; Bone Neoplasms ; surgery ; Humans ; Male ; Middle Aged ; Neurilemmoma ; surgery

Objective To evaluate the role of Toll-like receptor 4 (TLR4) in mechanical ventilation-induced activation of microglias in the hippocampi of mice.Methods Forty-two healthy male TLR4 gene knocked out C57BL/10ScNJNju mice and 42 wild type C57BL/6 mice,aged 10-12 weeks,weighing 20-25 g,were used in the study.The mice of either group were divided into 2 subgroups (n =21 each) using a random number table:spontaneous breathing subgroup (subgroup SB) and mechanical ventilation subgroup (subgroup MV).In subgroup SB,the mice were exposed to isoflurane for 6 h in an anesthesia chamber.After tracheal intubation,the mice were mechanically ventilated for 6 h when anesthesia was maintained with isoflurane in subgroup MV.Twelve mice were selected from each subgroup at 1 and 3 days after ventilation,fear conditioning test was performed to assess the cognitive function,and the rate of freezing time was recorded.Three mice in each subgroup were sacrificed at 1 day after ventilation,and the brains were removed to observe the morphological changes of microglias (by double immunofluorescent staining) and to count CD11b positive cells and co-expression of TLR4 with CD11b (TLR4/CD11b) positive cells in hippocampal microglias.Six mice in each subgroup were sacrificed at 1 day after ventilation,and the hippocampi were isolated for determination of the content of tumor necrosis factor-alpha (TNF-α) in hippocampal tissues by enzyme-linked immunosorbent assay.Results Compared with subgroup SB of wild type group,the rate of freezing time was significantly decreased at 1 and 3 days after ventilation,and the number of CD1 1b positive cells and TLR4/CD1 1b positive cells were increased,and the content of TNF-α was increased in subgroup MV of wild type group (P＜0.05),and the number of CD1 1b positive cells and content of TNF-α were significantly increased in subgroup MV of geue knockout group (P＜0.05).Compared with subgroup SB of gene knockout group,the rate of freezing time was significantly decreased at 1 and 3 days after ventilation,and the number of CD1 1b positive cells and content of TNF-α were increased in subgroup MV of gene knockout group (P＜0.05).Compared with subgroup MV of wild type group,the rate of freezing time was significantly increased at 1 and 3 days after ventilation,and the number of CD11b positive cells and content of TNF-α were decreased in subgroup MV of gene knockout group (P＜0.05).Conclusion The mechanism by which mechanical ventilation induces activation of microglias in hippocampi is partially related to TLR4 in mice.

With the in-depth study of related substances and the development of consistency evaluation of generic drugs, relative correction factors are gaining increasing attention. By analyzing the domestic and foreign literature on correction factors in recent years, this paper describes the correction factor component, the current measurement method and its application. The rules and key points of use of an impurity correction factor and its determination and application are described, and some problems in its determination and application are discussed, providing a reference and basis for the standardization of research on impurity correction factors in the future.

Objective To evaluate the effect of long?time mechanical ventilation on early postoper?ative inflammatory responses in the hippocampi of mice. Methods Forty?eight healthy male C57BL∕6 mice, aged 8-10 weeks, weighing 20-25 g, were divided into 3 groups ( n=16 each) using a random number table: control group ( group C) , operation group ( group O) and long?time mechanical ventilation after operation group ( group MV) . Open reduction and internal fixation was performed after tibial fracture was induced in O and MV groups. Group O inhaled isoflurane for 6 h after operation. The mice were me?chanically ventilated for 6 h under isoflurane anesthesia in group MV. On 1 and 3 days after the end of ven?tilation, 8 mice were randomly selected, and contextual fear conditioning test was carried out to assess the cognitive function. The rate of time spent freezing was calculated. Then venous blood samples were collected and hippocampi removed for determination of the levels of interleukin?6 ( IL?6) , tumor necrosis factor?al?pha ( TNF?α) and IL?1β in plasma and hippocampal tissues by enzyme?linked immunosorbent assay. Re?sults Compared with group C, the rate of time spent freezing was significantly decreased, and the levels of IL?6, TNF?α and IL?1β in plasma and hippocampal tissues were significantly increased after the end of ventilation in group O ( P<0.01) . Compared with group O, the rate of time spent freezing was significantly decreased, and the levels of IL?6, TNF?α and IL?1β in plasma and hippocampal tissues were significantly increased after the end of ventilation in group MV ( P<0.01) . Conclusion The mechanism by which long?time mechanical ventilation leads to early postoperative cognitive dysfunction is related to induction of in?flammatory responses in the hippocampi of mice.

Objective To evaluate the relationship between inflammatory responses induced by perioperative infection and surgical stress and postoperative cognitive dysfunction in mice. Methods One hundred forty?four healthy male C57BL∕6 mice, aged 8-12 weeks, weighing 20-25 g, were divided into 4 groups ( n=36 each) using a random number table: control group ( group C) , surgery group ( group S) , infection group ( group I) , and infection+surgery group ( group I+S) . In group S, the open reduction and internal fixation was performed after tibial fracture was induced. Lipopolysaccharide ( LPS) 100 μg∕kg was injected intraperitoneally at the same time every day for 5 consecutive days starting from 1 day before surgery in group I. In group I+S, LPS 100 μg∕kg was injected intraperitoneally at the same time every day for 5 consecutive days starting from 1 day before surgery, and the open reduction and internal fixation was per?formed after tibial fracture was induced at 2 h after LPS injection on the day of surgery. Contextual fear con?ditioning test was performed on 1 and 3 days after surgery, and cognitive function was assessed. The rate of freezing time was calculated. The peripheral venous blood samples were collected for determination of plas?ma interleukin?6 ( IL?6) and IL?1β concentrations by enzyme?linked immunosorbent assay. The animals were then sacrificed, and the hippocampi were isolated for determination of IL?6, IL?1β and prostaglandin E2 ( PGE2 ) contents in hippocampal tissues by enzyme?linked immunosorbent assay. Results Compared with group C, the rate of freezing time was significantly decreased on 1 and 3 days after surgery, and the contents of IL?6, IL?1βand PGE2 in hippocampal tissues were significantly increased on 1 and 3 days after surgery in S and I+S groups, the concentrations of plasma IL?6 and IL?1βwere significantly increased on 1 day after surgery, and the concentration of plasma IL?1βwas significantly increased on 3 days after surgery in group S, the concentrations of plasma IL?6 and IL?1β were significantly increased on 1 and 3 days after surgery in I and I+S groups ( P<0?01) , and no significant change was found in the rate of freezing time on 1 and 3 days after surgery in group I ( P>0?05) . Compared with group S or group I, the rate of freezing time was significantly decreased on 1 and 3 days after surgery, and the concentrations of IL?6 and IL?1βin plasma and contents of IL?6, IL?1β and PGE2 in hippocampal tissues were significantly increased on 1 and 3 days after surgery in group I+S ( P<0?01) . Conclusion Inflammatory responses induced by periopera?tive infection and surgical stress can aggravate postoperative cognitive dysfunction in mice.

In traditional oral practice, the presystemic interactions with gut microbiota is an important mechanism underlying the holistic health benefits of Chinese herbal medicines (CHMs), making the study of CHMs distinct from the research of Western medicines of which the systemic exposure (level in blood) is the starting point and the core. Gut microbial metabolism complements host metabolism in maintaining metabolic homeostasis of many biologically important endogenous molecules and the disposition of numerous exogenous compounds. Among them, the widely distributed gut bacterial β-glucuronidases (BGUSs) coordinate with host UDP-glucuronosyltransferases (UGTs) to play a role in the occurrence and intervention of diseases by affecting the glucuronidation homeostasis and altering the intestinal local and/or systemic exposure of endogenous compounds and xenobiotics. On one hand, many ingredients of CHMs undergo enterohepatic circulation; On the other hand, CHMs can act on BGUSs directly or indirectly change the distribution and function of BGUSs through reprogramming gut microbiome. The multiple interactions between BGUSs and CHMs may play an important role in the overall therapeutic benefits of CHMs. This work firstly summarizes the latest research progress on BGUSs; then the physiological, pathological and pharmacological significance of BGUSs are exemplified with representative endogenous and exogenous compounds from the aspects of nutrient utilization, metabolic homeostasis, and therapeutic response based on the varied substrate spectra of BGUSs; finally, the scattered data in literature were integrated to summarize the multiple interactions between BGUSs and CHMs, highlighting the important role of BGUSs in the holistic actions of CHMs.

Objective To investigate the expression of osteopontin and matrix metalloproteinase-9 (MMP9),and the relationship of osteopontin and MMP9 in malignant melanoma.Methods Expression of osteopontin and MMP9 was measured by immunohistochemical SP method in 23 patients with primary cuta- neous malignant melanoma,17 patients with metastatic melanoma and 20 patients with pigmented nevus. Results Osteopontin and MMP9 were expressed respectively in 87.5% and 75.0% of 40 malignant melanoma specimens,15.0% and 10.0% of 20 pigmented nevus specimens.The expression of both osteo- pontin and MMP9 was significantly higher (both P＜0.05) in malignant melanoma than in pigmented ne- vus.There was no correlation between the expression of osteopontin and MMP9,with age,sex,lymph node metastasis or location of lesions (P＞0.05).Twenty-nine cases were positive for both osteopontin and MMP9,4 negative for either osteopontin or MMP9.Conclusion Both osteopontin and MMP9 were over- expressed in malignant melanoma,but neither was related to lymph node metastasis.