This study aims to investigate the protective effects and mechanisms of polysaccharide extract PCP1 from Polygonatum cyrtonema in ameliorating cerebral ischemia-reperfusion(I/R) injury in rats through modulation of the Toll-like receptor 4(TLR4)/NOD-like receptor protein 3(NLRP3) signaling pathway. In vivo, SD rats were randomly divided into the sham group, model group, PCP1 group, nimodipine(NMDP) group, and TLR4 signaling inhibitor(TAK-242) group. A middle cerebral artery occlusion/reperfusion(MCAO/R) model was established, and neurological deficit scores and infarct size were evaluated 24 hours after reperfusion. Hematoxylin-eosin(HE) and Nissl staining were used to observe pathological changes in ischemic brain tissue. Transmission electron microscopy(TEM) assessed ultrastructural damage in cortical neurons. Enzyme-linked immunosorbent assay(ELISA) was used to measure the levels of interleukin-1β(IL-1β), interleukin-6(IL-6), interleukin-18(IL-18), tumor necrosis factor-α(TNF-α), interleukin-10(IL-10), and nitric oxide(NO) in serum. Immunofluorescence was used to analyze the expression of TLR4 and NLRP3 proteins. In vitro, a BV2 microglial cell oxygen-glucose deprivation/reperfusion(OGD/R) model was established, and cells were divided into the control, OGD/R, PCP1, TAK-242, and PCP1 + TLR4 activator lipopolysaccharide(LPS) groups. The CCK-8 assay evaluated BV2 cell viability, and ELISA determined NO release. Western blot was used to analyze the expression of TLR4, NLRP3, and downstream pathway-related proteins. The results indicated that, compared with the model group, PCP1 significantly reduced neurological deficit scores, infarct size, ischemic tissue pathology, cortical cell damage, and the levels of inflammatory factors IL-1β, IL-6, IL-18, TNF-α, and NO(P<0.01). It also elevated IL-10 levels(P<0.01) and decreased the expression of TLR4 and NLRP3 proteins(P<0.05, P<0.01). Moreover, in vitro results showed that, compared with the OGD/R group, PCP1 significantly improved BV2 cell viability(P<0.05, P<0.01), reduced cell NO levels induced by OGD/R(P<0.01), and inhibited the expression of TLR4-related inflammatory pathway proteins, including TLR4, myeloid differentiation factor 88(MyD88), tumor necrosis factor receptor-associated factor 6(TRAF6), phosphorylated nuclear factor-kappaB dimer RelA(p-p65)/nuclear factor-kappaB dimer RelA(p65), NLRP3, cleaved-caspase-1, apoptosis-associated speck-like protein(ASC), GSDMD-N, IL-1β, and IL-18(P<0.05, P<0.01). The protective effects of PCP1 were reversed by LPS stimulation. In conclusion, PCP1 ameliorates cerebral I/R injury by modulating the TLR4/NLRP3 signaling pathway, exerting anti-inflammatory and anti-pyroptotic effects.
Animals ; Toll-Like Receptor 4/genetics* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Rats, Sprague-Dawley ; Rats ; Reperfusion Injury/genetics* ; Male ; Signal Transduction/drug effects* ; Polysaccharides/isolation & purification* ; Polygonatum/chemistry* ; Brain Ischemia/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Humans

Aim To investigate the effect of ellagic acid (EA) on cognitive function in APP/PS 1 double- transgenic mice, and to explore the regulatory mechanism of ellagic acid on the level of oxidative stress in the hippocampus of double-transgenic mice based on the phosphatidylinositol 3-kinase/protein kinase B/glycogen synthase kinase-3 (PI3K/AKT/GSK-3 β) signaling pathway. Methods Thirty-two SPF-grade 6-month-old APP/PS 1 double transgenic mice were randomly divided into four groups, namely, APP/PS 1 group, APP/PS1 + EA group, APP/PS1 + LY294002 group, APP/PS 1 + EA + LY294002 group, with eight mice in each group, and eight SPF-grade C57BL/6J wild type mice ( Wild type) were selected as the blank control group. The APP/PS 1 + EA group was given 50 mg · kg

Objective:To compare magnetic resonance imaging (MRI)-based and computed tomography (CT)-based target volume delineation and dose coverage in partial breast irradiation (PBI) for patients with breast cancer, aiming to explore the application value of MRI localization in PBI after breast-conserving surgery.Methods:Twenty-nine patients with early breast cancer underwent simulating CT and MRI scans in a supine position. The cavity visualization score (CVS) of tumor bed (TB) was evaluated. The TB, clinical target volume (CTV), planning target volume (PTV) were delineated on CT and MRI images, and then statistically compared. Conformity indices (CI) between CT- and MRI-defined target volumes were calculated. PBI treatment plan of 40 Gy in 10 fractions was designed based on PTV-CT, and the dose coverage for PTV-MRI was evaluated.Results:The CVS on CT and MRI images was 2.97±1.40 vs. 3.10±1.40( P=0.408). The volumes of TB, CTV, PTV on MRI were significantly larger than those on CT, (24.48±16.60) cm 3vs. (38.00±19.77) cm 3, (126.76±56.81) cm 3vs. (168.42±70.54) cm 3, (216.63±81.99) cm 3vs. (279.24±101.55) cm 3, respectively, whereas the increasing percentage of CTV and PTV were significantly smaller than those of TB. The CI between CT-based and MRI-based TB, CTV, PTV were 0.43±0.13, 0.66±0.11, 0.70±0.09( P<0.001), respectively. The median percentage of PTV-MRI receiving 40 Gy dose was 81.9%(62.3% to 92.4%), significantly lower than 95.6%(95.0%~97.5%) of PTV-CT. Conclusions:The CVS between CT and MRI is not significantly different, but the MRI-based TB, CTV, PTV are significantly larger than CT-based values. The PTV-MRI is of underdose if PBI treatment plan is designed for PTV-CT. As a supplement of CT scan, MRI can enhance the accuracy of TB delineation after breast-onserving surgery.

OBJECTIVE: To investigate the mechanism of Tojapride, a Chinese herbal formula extract, on strengthening the barrier function of esophageal epithelium in rats with reflux esophagitis (RE). METHODS: Ten out of 85 SD rats were randomly selected as the sham group (n10), and 75 rats were developed a reflux esophagitis model (RE) by the esophageal and duodenal side-to-side anastomosis. Fifty successful modeling rats were divided into different medicated groups through a random number table including the model, low-, medium-, and high-dose of Tojapride as well as omeprazole groups (n10). Three doses of Tojapride [5.73, 11.46, 22.92 g/(kg•d)] and omeprazole [4.17 mg/(kg•d)] were administrated intragastrically twice daily for 3 weeks. And the rats in the sham and model groups were administered 10 mL/kg distilled water. Gastric fluid was collected and the supernatant was kept to measure for volume, pH value and acidity. Esophageal tissues were isolated to monitor the morphological changes through hematoxylin-eosin (HE) staining, and esophageal epithelial ultrastructure was observed by transmission electron microscopy. The expressions of nuclear factor kappa-light-chain-enhancer of activated B cells p65 (NF-KBp65), κB kinase beta (IKKß), occludin, and zonula occludens-1 (ZO-1) in the esophageal tissues were measured by immunohistochemistry and Western blot, respectively. RESULTS: The gastric pH value in the model group was significantly lower than the sham group (P<0.05). Compared with the model group, gastric pH value in the omeprazole and medium-dose of Tojapride groups were significantly higher (P<0.05). A large area of ulceration was found on the esophageal mucosa from the model rats, while varying degrees of congestion and partially visible erosion was observed in the remaining groups. Remarkable increase in cell gap width and decrease in desmosome count was seen in RE rats and the effect was reversed by Tojapride treatment. Compared with the sham group, the IKKß levels were significantly higher in the model group (P<0.05). However, the IKKß levels were down-regulated after treatment by all doses of Tojapride (P<0.01 or P<0.05). The occluding and ZO-1 levels decreased in the model group compared with the sham group (Ps0.01 or Ps0.05), while both indices were significantly up-regulated in the Tojapride-treated groups (P<0.01 or P<0.05). CONCLUSIONS Tojapride could improve the pathological conditions of esophageal epithelium in RE rats. The underlying mechanisms may involve in down-regulating the IKKß expression and elevating ZO-1 and occludin expression, thereby alleviating the inflammation of the esophagus and strengthening the barrier function of the esophageal epithelium.

AIM: The changes of optic disc and macular blood flow in POAG patients with different symptom types of traditional chinese medicine(TCM)were detected by OCTA, and the correlation between them and optic nerve damage was analyzed.

METHODS: Totally 103 eyes of 103 POAG patients were classified according to the different symptom types of TCM. The vascular density of optic disc, the vascular density of macular area, the thickness of peripapillary retinal nerve fiber layer(pRNFL), and the thickness of ganglia cell complex(GCC)were collected by OCTA, and then the differences among them were analyzed. The correlation between the blood flow parameters and visual field of mean deviation(MD)was also analyzed.

RESULTS: There were significant differences in best corrected visual acuity(BCVA), intraocular pressure(IOP)and course of disease among the three groups of POAG patients(F=29.671, 13.05, 108.60; all P<0.01). The differences in macular GCC thickness, pRNFL thickness, optic disc vascular density and macular vascular density in different regions among the three groups were significant(P<0.01). Linear positive correlation were found between optic disc vascular density, macular vascular density and visual field MD(r=0.591, 0.402, all P<0.001).

CONCLUSION: OCTA can be used as an evaluation index for POAG patients with different symptom types, and it can provide a strong objective theoretical basis for the treatment of POAG.

Background::Fever is the most common chief complaint of emergency patients. Early identification of patients at an increasing risk of death may avert adverse outcomes. The aim of this study was to establish an early prediction model of fatal adverse prognosis of fever patients by extracting key indicators using big data technology.Methods::A retrospective study of patients’ data was conducted using the Emergency Rescue Database of Chinese People’s Liberation Army General Hospital. Patients were divided into the fatal adverse prognosis group and the good prognosis group. The commonly used clinical indicators were compared. Recursive feature elimination method was used to determine the optimal number of the included variables. In the training model, logistic regression, random forest, adaboost, and bagging were selected. We also collected the emergency room data from December 2018 to December 2019 with the same inclusion and exclusion criterion. The performance of the model was evaluated by accuracy, F1-score, precision, sensitivity, and the areas under receiver operator characteristic curves (ROC-AUC).Results::The accuracy of logistic regression, decision tree, adaboost and bagging was 0.951, 0.928, 0.924, and 0.924, F1-scores were 0.938, 0.933, 0.930, and 0.930, the precision was 0.943, 0.938, 0.937, and 0.937, ROC-AUC were 0.808, 0.738, 0.736, and 0.885, respectively. ROC-AUC of ten-fold cross-validation in logistic and bagging models were 0.80 and 0.87, respectively. The top six coefficients and odds ratio (OR) values of the variables in the logistic regression were cardiac troponin T (CTnT) (coefficient = 0.346, OR = 1.413), temperature (T) (coefficient = 0.235, OR = 1.265), respiratory rate (RR) (coefficient= –0.206, OR = 0.814), serum kalium (K) (coefficient = 0.137, OR = 1.146), pulse oxygen saturation (SPO 2) (coefficient = –0.101, OR = 0.904), and albumin (ALB) (coefficient = –0.043, OR = 0.958). The weights of the top six variables in the bagging model were: CTnT, RR, lactate dehydrogenase, serum amylase, heart rate, and systolic blood pressure. Conclusions::The main clinical indicators of concern included CTnT, RR, SPO 2, T, ALB, and K. The bagging model and logistic regression model had better diagnostic performance comprehesively. Those may be conducive to the early identification of critical patients with fever by physicians.

Objective: To observe the effect of whole-body vibration therapy on the lower extremity the motor function of children with spastic diplegia. Methods: Fifty-six children with spastic diplegia were randomly divided into a treatment group and a control group, each of 28. Both groups were given routine rehabilitation exercise training, while the treatment group was additionally provided with 15 minutes of whole-body vibration therapy every day, 5 days a week for 12 weeks. Their GMFM-88 D (standing) and E (walking and jumping) scores were recorded before and after the treatment along with the active and passive range of motion of the ankle in dorsiflexion, and the root mean square surface electromyogram signals from the tibialis anterior and gastrocnemius muscles. Berg balance scale scores were also assigned before and after the treatment for both groups. Results: There were no significant differences between the two groups before the treatment. Afterward all of the evaluations except the signals from the tibialis anterior muscle in active ankle dorsiflexion had improved significantly. The improvements were all significantly better in the treatment group. Conclusion Whole-body vibration therapy can effectively improve the lower extremity motor function of children with spastic diplegia.

Objective To investigate the diagnostic significance of optical coherence tomography angiography (OCTA) in the detection of primary glaucoma.Methods Totally 70 patients (116 eyes) of primary glaucoma were selected as the experimental group and 20 normal subjects (36 eyes) as the control group.The changes in macular vessel density,macular retinal ganglion cell (RGC) thickness,macular thickness,and optic disc retinal pigment epithelium (RPE) opening distance were measured by OCTA,and the correlation between the parameters and the mean deviation (MD) of visual field.Results When compared with the control group,the upper macular thickness,inferior macular thickness,macular RGC thickness and macular vessel density were reduced in the experimental group (all P ＜ 0.05).There was no significant difference in optic disc RPE opening distance between the control group and the experimental group (F =2.646,P =0.051 3).Linear positive correlations were found between macular thickness,macular RGC thickness,macular vessel density and MD (all r ＞ 0.5,P ＜0.01).The area under the curve of the diagnostic ROC curve of the macular vessel density,macular RGC thickness and mactlar thickness for glaucoma were all greater than 0.7.Conelusion There are linear positive correlations between macular thickness,macular RGC thickness,macular vessel density and MD.The parameters have a high diagnostic ability for the primary glaucoma.OCTA is a valuable technique for detecting glaucoma.

AIM:To evaluate the morphological and functional changes of retinas induced by treatment of tunicamycin with optical coherence tomography (OCT) in rats.METHODS:Totally 60 SD rats were randomly divided into 3 groups (20 in each group), 0.5mg/kg (in low dose group), 1.5mg/kg (in high dose group) tunicamycin were injected into vitreous cavity and saline (9g/L NaCl) were injected in the same dose as a control group.Changes of retinas were observed by OCT on the 1,7 and 14d after treatment of tunicamycin.Then the rats were sacrificed, retinas were taken out and embedded by the paraffin, tissue sections and the HE staining were performed.RESULTS:OCT results suggested that tunicamycin played damage effects on retinal morphology and structure which appeared a time-and dose-dependent.Fundus photography results suggested that 2wk after tunicamycin treatments, with the gradually changing of tunicamycin concentration, peripheral retinal and macular region became pale color gradually, edema occurred in optic disk, retinal vessels appeared thinner in the high dose group, optic nerve came out atrophy.Fluorescein angiography confirmed that tunicamycin injection in vitreous cavity 2wk later, retinal vessels injury occurred, resulted in leaking of intravascular contrast agent from peripheral to the central part of the retinas.Electrophysiological data showed that retinal electrogram occurred disorder induced by tunicamycin, such as the amplitude of a wave, b wave decreased gradually, even closed to zero, which was very different from control significantly (P<0.05).HE staining of paraffin sections showed that retina injuries induced by tunicamycin were in dose-time dependent, which was consistent with the results of OCT.CONCLUSION: Clinical retinal diseases could be simulated by retinal damage animal model induced by tunicamycin treatment.OCT detection offered real-time images of the retinal cross-section, which provided a helpful non-invasive method for detecting and evaluating the retinal damages.

Objective To investigate the effect of FOCUS-PDCA program on pressure ulcers nursing quality management. Methods By using the 9 steps of FOCUS-PDCA program of exploring, organizing, clarifying, understanding, selecting, planning, enforcing, checking and executing, we looked into the primarily factors for pressure ulcers and modified and improved our pressure ulcer nursing management system. Then training was done to the nurses, and the pressure ulcer management system was used. The effects in implementation of pressure ulcers prevention, mastery of pressure ulcers prevention knowledge among nurses and occurrence of pressure ulcers in the high-risk patients were studied after applying the program. Results After use of FOCUS-PDCA program, the qualification rate of pressure ulcers prevention implementation and mastery of pressure ulcers prevention knowledge were both higher than before the use. The occurrence rate of pressure ulcers in the high-risk patients was lower than before the use (P<0.05). Conclusion By using the FOCUS-PDCA program in the nursing quality management for patients with pressure ulcers, we can effectively improve the implementation of pressure ulcers preventive measures, enhance the nursing staff to master knowledge on pressure ulcers and reduce the incidence of pressure ulcers.