OBJECTIVES: To explore the effect of A. muciniphila gavage on intestinal microbiota and gut-brain interaction disorders (DGBIs) in gp120tg transgenic mouse models of HIV-associated neurocognitive disorder (HAND). METHODS: Intestinal microbiota was detected by 16S rRNA gene sequencing in 6-, 9-, and 12-month-old wild-type (WT) mice and gp120tg transgenic mice. The 12-month-old WT and transgenic mice were divided into 2 groups for daily treatment with PBS or A.muciniphila gavage (2×10⁸ CFU/mouse) for 6 weeks. After the treatment, immunohistochemistry, ELISA and qPCR were used to detect changes in colonic expression levels of glycosylated mucins, MBP and IL-1β, eosinophil infiltration, serum lipopolysaccharide (LPS) levels, and colonic expressions of occludin, ZO-1, IL-10, TNF-α and INF-γ mRNA. Morris water maze test and immunofluorescence assay were used to assess learning and spatial memory abilities and neuronal damage of the mice. RESULTS: Compared with WT mice, the transgenic mice exhibited significantly lowered Simpson's diversity of the intestinal microbiota with reduced abundance of Akkermansia genus, increased serum LPS levels and decreased colonic expression of glycosylated mucin. A.muciniphila gavage obviously ameliorated the reduction of glycosylated mucin in the transgenic mice without causing significant changes in body weight. The 12-month-old gp120tg mice had significantly decreased cdonic expressions of Occludin and ZO-1 with increased eosinophil infiltration and TNF-β, INF-γ and IL-1β levels and obviously lowered IL-10 level; all these changes were significantly mitigated by A.muciniphila gavage, which also improved cognitive impairment and neuronal loss in the hippocampus and cortex of the transgenic mice. CONCLUSIONS The gp120tg mice have lower intestinal microbiota richness and diversity than WT mice. The 12-month-old gp120tg mice have significantly reduced Akkermansia abundance with distinct DGBIs-related indexes, and A. muciniphila gavage can reduce intestinal barrier injury, colonic inflammation and eosinophil activation, cognitive impairment and brain neuron injury in these mice.
Animals ; Mice, Transgenic ; Gastrointestinal Microbiome ; Mice ; Brain ; HIV Envelope Protein gp120/genetics* ; Akkermansia ; Disease Models, Animal

OBJECTIVE: Salt-processed Psoraleae Fructus (SPF) is widely used as a phytoestrogen-like agent in the treatment of osteoporosis. However, due to improper clinical use or misuse, resulting in liver damage. In this study, network pharmacology was employed to analyze the mechanism of cholestatic liver damage. An adeno-associated virus overexpressing SULT1E1 (rAAV8-SULT1E1) was constructed and the hepatotoxicity of SPF, psoralen, and isopsoralen was determined. METHODS: By utilizing three databases inclding TCMSP, TCMID, and BATMAN- TCM, the targets of the three databases were summarized, and a total of 45 psoralen compounds were included. Network pharmacology analysis was then performed. The adenoviral vectors were injected into the tail vein of C57BL6 mice to elucidate the role of SULT1E1 in SPF-induced cholestasis-mediated hepatotoxicity in vivo. SPF (10 g/kg), psoralen, and isopsoralen (50 mg/kg each) were intragastrically administered to mice for 30 d. B-ultrasound and samples were collected and examined for follow-up experiments. RESULTS: A total of 854 targets were predicted for 45 active components, with 151 cholestasis-mediated hepatotoxicity-related disease targets obtained for SPF. A total of 126 pathways were enriched based on KEGG pathway analysis, with the "estrogen signaling pathway" identified as one of the top 20 pathways. In terms of pathological hepatic changes, treated mice had visually swollen hepatocytes, dilated bile ducts, and elevated serum biochemical markers, which were more prominent in mice treated with isopsoralen than in those treated with other compounds. Notably, the overexpression of SULT1E1 could reverse liver damage in each treatment group. B-ultrasound was used to observe the size of the gallbladder in vivo. The size of the gallbladder was found to significantly increase on day 30 after treatment in the SPF-, psoralen-, and isopsoralen-treated groups, especially the SPF group. Compared with the expression levels in the negative control group (rAAV8-empty + con), the expression levels of FXR, Mrp2, Bsep, SULT1E1, SULT2A1, Ntcp, and Nrf2 decreased, whereas those of CYP7a1 and IL-6 increased in the SPF-, psoralen-, and isopsoralen-treated groups. CONCLUSION The overexpression of SULT1E1 could alleviate the decreased or increased expression of indicators, indicating that SULT1E1 is an important target gene for SPF-induced liver damage. The severity of liver damage was significantly lower in the rAAV8-SULT1E1 groups than in the rAAV8-empty groups.

BACKGROUND:Bone mineral density is the clinical gold standard for determining bone strength,but bone mineral density is less sensitive to changes in bone mass,with large changes in bone mineral density only occurring when bone mass is significantly reduced,so bone mineral density has limited ability to predict changes in bone strength and fracture risk. OBJECTIVE:A model of the normal and osteoporotic hip joint was developed to analyze the stresses and deformation in the hip of normal and osteoporotic patients under single-leg standing conditions. METHODS:A healthy adult female volunteer at the age of 36 years was selected as the study subject.The CT data of the hip joint of this volunteer were obtained and saved in DICOM format.The hip joint model was reconstructed in three dimensions,and the material properties were assigned by the gray value assignment method to obtain the normal and osteoporotic hip joint models according to the empirical formula.The same boundary conditions and loads were set to simulate the stresses and deformation in the normal and osteoporotic hip joints in the single-leg standing position. RESULTS AND CONCLUSION:(1)In the finite element model of the normal and osteoporotic hip,the stress distribution was more concentrated in the medial region of the femoral neck.(2)In the hip bone,the stress distribution was mainly concentrated in the upper part of the acetabulum.(3)The stress peaks in the medial femoral neck and upper acetabulum were larger in the normal hip model than in the osteoporotic hip model,probably due to the reduced bone strength of the osteoporotic bone.(4)The peak Von Mises of both normal and osteoporotic hip models were concentrated on the medial femoral neck,and the peak Von Mises of the hip bone was smaller,indicating that the overall effect of osteoporosis on hip bone stresses was relatively small.(5)In terms of deformation in the single-leg standing position,the maximum deformation in the normal hip model was located at the acetabulum and femoral head,and the maximum deformation was located at the upper part of the greater trochanter of the femur.(6)It is suggested that the finite element analysis method to model the values of parameters related to bone tissue in osteoporosis may improve clinical prediction of bone strength changes and fracture risk.It is explained from the biomechanical view that the intertrochanteric femur and femoral neck are good sites for osteoporotic hip fractures.

Objective:To investigate the effect of 3D-printed customized flanged cup in hip revision with severe acetabular bone defects.Methods:Since February 2017, 10 cases of 3D-printed customized flanged cups were used in hip revision with severe acetabular bone defects, including 2 cases of Paprosky type IIIA and 8 cases of Paprosky type IIIB. There were 5 males and 5 females, mean age 73.6±8.1 yrs (range, 62-87 yrs), 5 left and 5 right cases. The preoperative thin-layer CT scan was preformed to reverse reconstruct digital pelvis. Five cases of one-piece flanged cups and 5 cases of decomposed flanged cups, including 3 cases of composite one-piece cups were designed by computer. The surgery was performed strictly according to the plan.Postoperative follow-up was performed to evaluate the Harris score. Operation time,intraoperative bleeding and other complications such as vascular and nerve injury, postoperative infection, and dislocation were counted. Pelvic X-ray was used to assess the height and horizontal position of the center of rotation and the stability of the prosthesis.Results:The surgical procedure was successful, with an average operative time of 147.9±48.3 min (range, 96-212 min) and an average intraoperative bleeding of 730.4±262.6 ml (range, 500-1 300 ml). The mean time of final follow-up was 40.8±18.7 months (range, 16-70 months) after surgery. At the last follow-up, the average Harris score was 83.80±6.73, with 4 cases excellent, 5 cases good, and 1 case fair. The excellent and good rate was 90%. The last Harris score was significantly higher than that before operation 28.60±8.40 ( t=16.84, P<0.001). The height of affected hip joint rotation center decreased from 46.24±7.74 mm before operation to 15.54±2.54 mm after operation with significant difference ( t=14.61, P<0.001). It was slightly higher than the opposite side (13.81±1.48 mm), which had no significant difference ( t=1.83, P=0.100). The horizontal distance of affected hip joint rotation center increased from 33.79±5.27 mm before operation to 40.53±4.50 mm after operation with significant difference ( t=3.62, P=0.006). It had no significant difference ( t=1.28, P=0.232) compared with the opposite side (38.54±3.46 mm). All incisions were healed in one stage without infection, vascular or nerve injury. During the following-up, all prostheses were in satisfied position without loosening, dislocation or screw breaks. Conclusion:Digitally assisted 3D-printed flanged cups can be used in hip revision with severe acetabular bone defect. It can not only improve hip joint function, but also restore the acetabular rotation center and the prosthesis stability, which can achieve good early and mid-term effect.

Hypertrophic scar is an abnormal fibrous proliferative disease that occurs after deep cutaneous injury, which not only affects aesthetics and function but also has negative psychological effects on the patients. However, the mechanism of hypertrophic scar formation has not been fully elucidated, and its clinical treatment is complex with a high rate of recurrence and no radicle cure. Intervention based on molecular targets will likely be the future direction for the prevention and treatment of hypertrophic scar. In this article, we review the specific roles and mechanisms of drug-targeted interventions in hypertrophic scar formation, including general drugs, cytokines, immunomodulators, herbal extracts, exosomes, and nanomaterials, in the context of advances in both basic and clinical research at home and abroad.

Objective To understand the current situation of occupational exposure and occupational safety attitudes among nursing students in Kunming Medical University, and to find effective interventions to improve nurses' occupational safety,and to reduce occupational exposure.Methods 854 students in Kunming Medical University were investigated by a questionnaire survey, including Demographic characteristics, Occupational exposure conditions, Occupational safety attitude and Gathers, quit intention . The correlations between occupational safety attitudes and occupational exposure were analyzed with Simple Linear Correlation.Results There were 94.30%female respondents,and only 5.70%male respondents.The average age of respondents was 22.52±2.90 years. The Simple Linear Correlation analysis showed that correlation between Negative attitude and occupational exposure was positive correlated, the occupational exposure and Support from managers, and Optimistic were negative correlation ( <0.05) .Conclusions Occupational safety and attitude are related to occupational exposure. Nursing students should apply standardized operation to improve the professional quality and ability. Schools should strengthen the education of occupational protection for nursing students. Hospital management should regularly organize nurses to study occupational exposure protection knowledge,give full affirmation of the nurse's achievements in the work, and offer certain reward appropriately.

Objective To study the clinicopathologic characteristics of triple-negative breast cancer (TNBC) and its value in the prediction of prognosis. Method In this study,500 cases of female breast cancers were examined immunohistochcmically for the TNBC. The clinicopathologic characteristics of the 243 TNBC cases were inspected. Results TNBC accounted for 17.6% (88/500) of the 500 breast cancers. The histological types of the TNBC included mainly infihrative ductal carcinoma, metaplastic carcinoma and medullar carcinoma. Among those, histological grade Ⅲ accounted for 72.7% (64/88) of all the TNBC and was more common than that in hormone receptor positive breast cancers (HR+ group ) and Her-2 overexpression breast cancers (Her-2 group)(P=0.000). The positive rates of CK5/6 and EGFR in the TNBC were 30.7% (27/88) and 34.1% (30/88), respectively. The positive rates of ERCC1 and KIT in the TNBC were 28.4% (25/88) and 34.1% (30/88), respectively, Both of which were higher than those in the HR + group and Her-2 group, respectively (P=0.032 and P=0.026). 3-year survival rate of the TNBC was 71.5% and it was lower than that of HR group (P=0.021) and not significantly different from that of Her-2 group (P=0.474). Conclusions TNBC is the breast cancer with high aggressive pathologic futures and poor prognosis. EGFR and ERCC1 expression were positive in a portion of TNBC cases.