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:To explore the impact of treatment duration with human urinary kallidinogenase (HUK) on the efficacy and safety of acute ischemic stroke (AIS).Methods:In this subgroup analysis of RESK study, a total of 990 AIS patients recruited from 65 centers in China between August 2015 and June 2020 were included and divided into short medication group (HUK for 8 days, n=185) or long medication group (HUK for 15 days or 21 days, n=805). The proportions of patients with modified Rankin Scale (mRS) score of 0, 0-1, 0-2 at 90 days, National Institutes of Health Stroke Scale (NIHSS) score change from baseline to 22 days, the proportions of patients with Barthel index (BI)≥95 at 90 days, and the incidences of adverse events were analyzed. Comparisons between groups were conducted using chi-square test, single factor and multivariate Logistic regression analysis, etc. Results:Multivariate regression analysis showed that the proportions of patients with 90-day mRS score of 0-2 [74.1% (137/185) vs 75.0% (604/805); OR=1.047, 95% CI 0.676-1.620, P=0.838] and 22-day NIHSS score change from baseline (4.60±2.00 vs 4.26±2.80; OR=-0.390, 95% CI -1.125-0.344, P=0.297) showed no statistically significant difference between the short medication and long medication groups; the proportions of patients with 90-day mRS score of 0-1 [48.1% (89/185) vs 59.1% (476/805); OR=0.674, 95%CI 0.463-0.983, P=0.041] and 90-day BI≥95 [43.6% (79/181) vs 55.1% (442/802); OR=0.614, 95%CI 0.420-0.897, P=0.012] were significantly lower in the short medication group than in the long medication group. There was no statistically significant difference in the incidences of adverse events between these 2 groups. Conclusions:In AIS patients, consecutive 8-day dosing of HUK improved immediate (22-day NIHSS score) and long-term outcome (90-day mRS score 0-2) and was safely tolerated. When applicable, extended duration of HUK could improve long-term disability-free rate (90-day mRS score 0-1) and quality of life (90-day BI) without increasing the risk of adverse events.

Objective To evaluate whether susceptibility weighted imaging (SWI) can be used in definition of penumbra during acute stage of cerebral infarction,compared with perfusion weighted imaging (PWI).Methods Ischemic stroke patients within 3 days after onset were included.They adopted multimodal magnetic resonance imaging examination,including regular magnetic resonance imaging sequence (T1 WI,T2 WI and T2-weight fast fluid-attenuated inversion-recovery),diffusion weighted imaging (DWI),PWI and SWI.Alberta Stroke Programme Early CT Score was done on DWI,SWI and PWI.The mismatch of SWI-DWI (minimal indensity projection (mIP)-DWI) was compared with that of PWI-DWI (mean transit time (MTT)-DWI) and analyzed statistically.The application of prominent vein (PV) on SWI as a sort of alternation of cerebral blood volume (CBV) and direct observation of thrombosis in arteries on SWI were done.Results The SWI-DWI (2.39 ± 1.42) and the MTT-DWI (2.72 ± 1.49) mismatch showed no statistically significant difference (r =0.726,P ＞ 0.05).The grade of PV was positively related with the CBV of the ipsilateral brain tissue on admission (r =0.564,P ＜ 0.05).SWI showed the similar ability with magnetic resonance angiography to judge responsible blood vessels with susceptibility vessel sign.Conclusion SWI-DWI can evaluate the ischemic penumbra.PV may reflect the increased blood volume of the lesion side of the brain tissue.SWI can reveal the thrombosis of the responsible vessels.

Objective To explore the application and management of deep hypothermic extracorporeal circulation (DHECC) in surgical procedures. Methods From Dec. 1997 to Dec. 2007, DHECC was applied in 54 patients suffered from great vessel diseases (34/54), complex congenital heart disease (10/54), giant basilar artery aneurysm (5/54), and abdominal tumor with tumor embolus intruding into right atrium or inferior vena cava (5/54) in the General Hospital of PLA. Extracorporeal circulation was performed with arterial perfusion by ascending aorta (n=25), axillary artery (n=18) and femoral artery (n=11), and venous drainage by superior vena cava and inferior vena cava (n=21), right atrium (n=25), and femoral vein (n=8). Clinical data were analyzed retrospectively including extracorporeal circulation (ECC) time, aortic clamping time, deep hypothermic circulation time, the lowest temperature, and the use of ultrafiltration. Results The ECC time was 63-414 (178.55?74.42)min. Aortic clamping time was 16-259 (123.39?52.21) min in 46 patients. Deep hypothermic circulatory arrest (DHCA) was performed in 43 patients, and the duration was 2-109 (30.00?22.37)min. The lowest nasopharyngeal temperature was 13.6-25.7 (19.61?3.40)℃, and the lowest rectal temperature was 15.2-30.5 (21.58?3.63)℃. Ultrafiltration technique was used in 49 cases. 36 of 54 cases (66.7%) self-awakened. Four cases (7.41%) died in the early post-operation period. Conclusion The DHECC can offer a clear and exsanguinated operating field, and is helpful to execute complicated or major operations which are hard to complete with common techniques.

Objective To analyze and evaluate the effect addition of albumin to the extracorporeal circulation (CPB) in patients undergoing valve replacement. Methods 62 patients under 60 years of age, with the blood level of albumin nearly normal, undergoing mitral valve replacement or aortic valve replacement were randomly divided into two groups. In 34 patients albumin was added to the priming fluid of extraporeal circulation, and in 28 patients it was not. The pre-operative and postoperative serum albumin levels, the duration of assisting ventilation, and the amount of albumin needed between the time of operation to 7 am of the first postoperative day were compared. In both groups the primary priming fluid consisted of balanced electrolyte solution, hydroxyethyl starch, 5% sodium bicarbonate, and 25% mannitol. Results All the indexes, including the preoperative level of albumin, the amount of albumin needed from operation to 7 am of the first postoperative day, and the albumin level at 7 am of the first postoperative day showed no notable differences. Conclusion For patients with no hypoalbuminemia, mitral valve replacement or aortic valve replacement is safe to withhold the addition of albumin to the priming fluid for CPB.

To summarize the experience of application of the cardiopulmonary bypass (CPB) technique in non cardiac surgery in 28 patients, including 22 cases of Budd Chiari syndrome, 2 cases of renal cell carcinoma with cancer cell emboli in the inferior vena cava, 2 cases of tracheal carcinoma, 1 case of intracranial basilar artery aneurysm, and 1 case of leiomyolipoma of the liver with excision and replantation of remaining liver. Different types of CPB were adopted as follows: 10 cases were supplemented by hypothermia and low flow perfusion, 15 cases by deep hypothermia and circulation arrest (DHCA) and 3 cases with vena vena bypass in normothermia, respectively. 2 patients died in early post operative period. It is our opinion that CPB can be used in non cardiac surgery, when it is difficult or almost impossible to carry out with routine surgical technique. The technique can make operations more convenient and safer to perform, even though there are some disadvantages, such as more trauma and higher cost.