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

Chronic obstructive pulmonary disease(COPD)is one of the most common chronic lung diseases,which is characterized by chronic irreversible airway obstruction.Chronic airflow restriction causes a decrease in oxygen supply to the brain,which inevitably leads to a series of changes in brain function and structure.In recent years,many magnetic resonance imaging(MRI)technology has been applied to explore the brain function and structure of COPD.Resting-state functional MRI,voxel-based morphometry,and diffusion tensor imaging are reviewed in this article to discuss the recent research progress of brain function and structure imaging study in COPD.

Fluorescence-guided surgery (FGS) with tumor-targeted imaging agents, particularly those using the near-infrared wavelength, has emerged as a real-time technique to highlight the tumor location and margins during a surgical procedure. For accurate visualization of prostate cancer (PCa) boundary and lymphatic metastasis, we developed a new approach involving an efficient self-quenched near-infrared fluorescence probe, Cy-KUE-OA, with dual PCa-membrane affinity. Cy-KUE-OA specifically targeted the prostate-specific membrane antigen (PSMA), anchored into the phospholipids of the cell membrane of PCa cells and consequently showed a strong Cy7-de-quenching effect. This dual-membrane-targeting probe allowed us to detect PSMA-expressing PCa cells both in vitro and in vivo and enabled clear visualization of the tumor boundary during fluorescence-guided laparoscopic surgery in PCa mouse models. Furthermore, the high PCa preference of Cy-KUE-OA was confirmed on surgically resected patient specimens of healthy tissues, PCa, and lymph node metastases. Taken together, our results serve as a bridge between preclinical and clinical research in FGS of PCa and lay a solid foundation for further clinical research.

Humans ; Temperature ; Cities/epidemiology* ; Hot Temperature ; Cardiovascular Diseases/epidemiology* ; China/epidemiology* ; Mortality

OBJECTIVE Cognitive deficit is a com-mon comorbidity in temporal lobe epilepsy(TLE)and that is not well controlled by current therapeutics.Currently,how epileptic seizure affects cognitive performance remains largely unclear.The subiculum is the major out-put of the hippocampus,which projects to entorhinal cor-tex and other more distinct brain regions.Physiologically,the subiculum codes spatial working memory and naviga-tion information including place,speed,and trajectory.Importantly,prior studies have noted the importance of the subiculum in the beginning,spreading,and generaliz-ing process of hippocampal seizure.How seizure-activated neurons in subiculum participate in cognitive impairment remains largely elusive.METHODS In this study,we sought to label the subicular seizure-activated c-fos+ neu-rons with a special promoter with enhanced synaptic activity-responsive element E-SARE in the subiculum,combined with chemogenetics and designer receptors exclusively activated by designer drugs(DREADDs),Ca2+ fiber photometry approaches,and behavioral tasks,to reveal the role of these neurons in cognitive impairment in epilepsy.RESULTS We found that chemogenetic inhibi-tion of subicular seizure-tagged c-fos+ neurons(mainly CaMK Ⅱ α+ glutamatergic neurons)alleviates seizure generalization and improves cognitive performance in the hippocampal CA3 kindling TLE model.While inhibition of seizure-labeled c-fos+ GABAergic interneuron shows no effect on seizure and cognition.As a comparison,che-mogenetic inhibition of the whole subicular CaMK Ⅱ α+ neuron impairs cognitive function in na?ve mice in basal condition.Notably,inhibition of subicular seizure-tagged c-fos+ neurons enhances the recruitment of cognition-responsive c-fos+ neurons via increasing neural excitability during cognition tasks.CONCLUSION Our results dem-onstrate that subicular seizure-activated c-fos+ neurons contribute to cognitive impairment in TLE,suggesting sei-zure-tagged c-fos+ neurons as the potential therapeutic target to alleviate cognitive impairment in TLE.

Danggui Buxue Decoction is a classic prescription of Qi and blood tonification, which is mainly applied in treating fatigue, internal damage Qi weakness, blood deficiency, and outward going of floating Yang. Modern pharmacology shows that it can promote hematopoiesis, regulate immunity, and protect heart and cerebral vessels. The prescription, often used for the treatment of anemia and other diseases in clinic, is composed of Astragali Radix and Angelicae Sinensis Radix at a dosage ratio of 5∶1. It is a modern compound prescription for invigorating Qi and generating blood. Based on the review of the chemical constituents, pharmacological effects, and clinical applications of Danggui Buxue Decoction, its Q-marker was predicted and analyzed according to the "five principles" of Chinese medicine Q-marker--quality transmissibility and traceability, ingredient specificity, component validity, component measurabi-lity, and formula compatibility environment. The results suggested that calycosin, calycosin-7-O-β-D-glucoside, formononetin, ononin, astragaloside A, ferulic acid, and ligustilide could be used as Q-markers of Danggui Buxue Decoction, which provides reference for establishing the quality system of Danggui Buxue Decoction.
Astragalus Plant ; Drugs, Chinese Herbal/pharmacology* ; Plant Roots

Objective　To study the relationship between cerebral artery stenosis and homocysteine（HCY） level and methylenetetrahydrofolate reductase（MTHFR）C677T gene polymorphism in ischemic youth stroke. Methods　50 patients with ischemic young stroke were randomly selected from department 2 of neurology，China-Japan Union Hospital of Jilin University，41 of whom met the inclusion criteria. They were divided into stenosis group（20 cases） and non-stenosis group（21 cases） according to the presence or absence of cerebrovascular stenosis. The plasma HCY level and MTHFR C677T gene polymorphism were measured and analyzed statistically. Results　In 41 patients，HCY level CC genotype（10.61±2.66）μmol/L was lower than TT genotype（19.65±14.43）μmol/L（P=0.033） and CT+TT genotype（16.65±12.48）μmol/L（P=0.015）. HCY levels in cerebral artery stenosis group and non-stenosis group were（20.44±14.70）μmol/L，（11.03±4.40）μmol/L（P=0.012） respectively（P= 0.012）. The level CC genotype 12.23±2.18 μmol/Lof HCY in stenosis group was lower than TT genotype（28.55±16.82）μmol/L（P=0.043） and CT+TT genotype（22.48±15.82）μmol/L（P=0.023）. The HCY level of CC genotype（8.46±1.40）μmol/L in non-stenosis group was lower than that of TT genotype（11.86±5.0）μmol/L（P=0.161） and CC+TT genotype（11.46±4.60）μmol/L（P=0.048）. The level of the same genotype HCY in the two groups was（28.55±16.82）μmol/L，（11.86±5.02）μmol/L（P=0.040），the CC genotype was（12.23±2.18）μmol/L，（8.46±1.40）μmol/L（P=0.049），and the CT genotype was（17.77 ±14.12）μmol/L，（11.14±4.48）μmol/L（P=0.178）. TT，CT and CT+TT genotypes of MTHFR C677T in the two groups were respectively compared with CC genotype P>0.05，and T was compared with C allele P>0.05. Logistic regression analysis showed that HCY（OR=1.168，95%CI 1.015～1.344，P=0.030） was a risk factor for cerebrovascular stenosis. Conclusion　The level of HCY is a high risk factor for cerebral artery stenosis in ischemic young stroke patients. TT genotype of MTHFR C677T is the key factor affecting plasma HCY level，but C677T genotype and allele frequency have no direct correlation with cerebral artery stenosis.

Objective: To investigate the effect of oral nutritional supplements(ONS) on body weight loss and life quality in post-discharge patients with gastric and colorectal cancer. Methods: All the enrolled post-operative gastric or colorectal cancer patients were randomly divided into ONS group and control group. Body weight loss, middle arm circumference, triceps skinfold thickness and right-hand grip strength were measured and the Karnofsky score, ECOG score and QOL score were calculated 3 months after the discharge. Results: The body weight loss of gastric cancer patients was lower in ONS group than in control group since 2 months after discharge.(2 months after discharge: 1.65±2.11vs. 2.70±1.90 kg, t=-2.385 3, P=0.019 3; 3 months after discharge: 1.95±2.75vs. 3.67±2.29 kg, t=-3.134 7, P=0.002 4), There was no difference of body weight loss between two groups in colorectal cancer patients. The middle arm circumference, triceps skinfold thicknessand right-hand grip strength showed no statistic difference between two groups both in gastric and colorectal cancer patients. The Karnofsky score(56.82±13.65%vs. 51.71±9.72%, t=2.014 8, P=0.047 2) and QOL score(41.91±6.92 vs. 38.39±8.77, t=2.059 7, P=0.042 6) were higher in ONS group than in control group in gastric cancer patients. While all 3 types of scores had no difference between two groups in colorectal cancer patients. Conclusion ONS can efficiently reduce the body weight loss and improve the performance status and life qualityin post-discharge gastric cancer patients, but not in colorectal cancer patients.

To evaluate the efficacy and safety of Choudongning (CDN)capsule in children with Tourette's syndrome of spleen deficiency and phlegm accumulation through a randomized double-blind three-arm controlled phase Ⅲ study in 588 patients from 8 hospitals. The included patients were randomly divided into test group, positive control group and placebo group at the ratio of 3∶1∶1. Patients in the test group orally took CDN capsules and simulated Tiapridal tablets; the patients in positive control group took Tiapridal tablets and simulated CDN capsules; whereas the patients in placebo group orally took the simulated agents of the above two drugs. The treatment course was 6 weeks for three groups. The global grading rates, YGTSS scores and its factor scores, the degree of social function damage, as well as traditional Chinese medicine syndrome efficacy were evaluated as the outcome measures on efficacy. The AEs/ADRs, vital signs and laboratory testing were observed as outcome measures on safety. The total effective rate of YGTSS was 75.92% in the test group, 72.65% in the positive control group, and 37.29% in the placebo group. Non inferiority test stands between the test group and the positive control group, and they were superior to placebo group in efficacy with statistical difference. Significant difference had also been found among the 3 groups in YGTSS tics score, motor tics score, vocal tics, degree of social function damage and traditional Chinese medicine syndrome efficacy. During the study, there were 5 (1.42%)ADRs in the test group, 10 (8.55%)in the positive control group and 3 (2.54%)in the placebo group. The incidence of ADRs in the test group was lower than that in the positive control group, with statistical difference. It is clear to say that CDN capsule can effectively treat the Tourette's syndrome of spleen deficiency and phlegm accumulation. Its efficacy is not inferior to the commonly used Tiapridal tablets, with even less adverse reactions, so it has clinical application value.

OBJECTIVETo evaluate the consistency between the clinical diagnostic criteria and the ascertained diagnostic criteria for diabetic peripheral neuropathy (DPN) in the Preventive and Treatment Guidelines of Diabetes in China (2013) and explore an economic, convenient, and accurate approach to DPN diagnosis.

METHODSThe patients with type 2 diabetes admitted in our department from April to June, 2014 were examined for nerve conduction velocity, 10 g nylon silk, vibration threshold value, sense of temperature and pain, and ankle reflex. The sensitivity, specificity, positive predictive value, negative predictive value, Youden index, and Kappa value were calculated to assess the diagnostic power of the two diagnostic criteria.

RESULTSOf the 151 patients enrolled, 106 (70.2%) had a diagnosis of DPN consistent with the ascertained diagnostic criteria, as compared to 86 (56.95%) who were diagnosed according to the clinical diagnostic criteria; the latter patients accounted for 81.13% of former cases. The sensitivity, specificity, positive predictive value, negative predictive value, Youden index, and Kappa value of the clinical diagnostic criteria were 80.19%, 97.78%, 98.84%, 67.69%, 77.97%, and 0.69, respectively, which were highly consistent with those of the ascertained diagnostic criteria; the sensitivity to compression showed a poor consistency between the two diagnostic criteria. In the 5 screening tests, the combined test of temperature sensation, vibration perception, and ankle reflex showed the highest AUC value among their different combinations.

CONCLUSIONThe clinical diagnostic criteria for DPN show good consistency with the ascertained diagnostic criteria, and for patients with clinical symptoms or with only one positive sign, combination of the two diagnostic criteria can achieve the maximum diagnostic power.