Objective To observe the effect of Qixian Tongluo Formula on contralateral corticospinal tract(CST)remodeling and motor functional recovery in rats with cerebral infarction,and to explore its potential molecular mechanism from the perspective of regulating factors related to never remodeling.Methods The rat middle cerebral artery occlusion(MCAO)model was established by silk thread ligation.Fifty model rats were randomly divided into model group,citicoline group(0.054 g·kg-1),Qixian Tongluo Formula low-,medium-and high-dose(7.83,15.66,31.32 g·kg-1)groups,and sham operation group,with 10 rats in each group.The intervention administration was started on the 3rd day after operation once a day for 26 consecutive days.On the 3rd,14th and 28th day after operation,the gross motor function was evaluated by Longa score,and the fine motor function was evaluated by beam-walking test(BWT)score.The contralateral motor cortex was injected with the nerve tracer biotin dextran amine(BDA)on the 14 th day after operation to anterogradely trace the CST.On the 28th day after operation,the expression of axonal growth associated protein-43(GAP-43)and BDA positive fibers in the contralateral motor cortex and cervical spinal cord were detected by immunohistochemistry.The co-localization areas of BDA positive fibers and presynaptic marker protein vesicular glutamate transporter 1(VGLUT1)in the cervical spinal cord gray matter were detected by immunofluorescence.The expressions of brain-derived neurotrophic factor(BDNF),glial cell-derived neurotrophic factor(GDNF),nerve growth factor(NGF)and nerve remodeling-associated inhibitory factor[Nogo-A,oligodendrocyte myelin glycoprotein(OMgp)and myelin-associated glycoprotein(MAG)]in the contralateral motor cortex were detected by Western Blot.Pearson correlation analysis was used to analyze the correlation between Longa score or BWT score and BDA/VGLUT1 co-localization area,respectively.Results Compared with the sham operation group,rats in the model group had obvious symptoms of motor function deficits,and the Longa scores were significantly increased(P＜0.01)and the BWT scores were significantly decreased(P＜0.05,P＜0.01)at each time point.The expression of GAP-43 in the contralateral motor cortex and cervical spinal cord was up-regulated(P＜0.05),the number of edge-crossing fibers from the posterior funiculus in cervical cord was increased(P＜0.05),the co-localization area of BDA/VGLUT1 in the gray matter of the cervical spinal cord was increased(P＜0.05),the expressions of BDNF,GDNF and NGF in the contralateral motor cortex were up-regulated(P＜0.05),while the expressions of Nogo-A,OMgp and MAG were down-regulated(P＜0.05).Compared with the model group,the Longa scores in each administration group on the 14th and 28th day after MCAO operation were significantly decreased(P＜0.01),the BWT scores were significantly increased(P＜0.01),the expression of GAP-43 in the contralateral motor cortex and cervical spinal cord was significantly up-regulated(P＜0.01).The number of edge-crossing fibers from the posterior funiculus in cervical cord was significantly increased(P＜0.01),the co-localization area of BDA/VGLUT1 in the gray matter of the cervical spinal cord was significantly increased(P＜0.01).The expressions of BDNF,GDNF and NGF in the contralateral motor cortex were significantly up-regulated(P＜0.01,P＜0.05),while the expressions of Nogo-A,OMgp and MAG were significantly down-regulated(P＜0.05),and the most significant effect was observed in the high dose group.The Longa score was negatively correlated with the co-localization area of BDA/VGLUT1(r=-0.89,P＜0.01),and the BWT score was positively correlated with the co-localization area of BDA/VGLUT1(r=0.84,P＜0.01).Conclusion Qixian Tongluo Formula can improve motor function through promoting contralateral CST remodeling in MCAO rats after cerebral infarction,and the molecular mechanism may be related to the regulation of the expression of nerve remodeling-associated factor in the contralateral motor cortex.

Objective: To explore the relationship between the ratio of dietary vitamin A (VitA) to body weight and hypertension among children, so as to provide a reference for blood pressure control through dietary nutritional interventions and childhood hypertension prevention. Methods: Utilizing the baseline survey and followup sample data from the Healthy Children Cohort established in urban and rural areas of Chongqing from 2014 to 2019, structured quantitative dietary questionnaire and selfdesigned questionnaire were used to investigate the information of dietary intake and socioeconomic characteristics of 15 279 children, as well as blood pressure, height, weight measurement. The ratio of dietary VitA to body weight was divided into four groups based on quartiles [≤P25(Q1), >P25~P50(Q2), >P50~P75(Q3), >P75(Q4)]. Generalized linear regression models and Logistic regression models were used to analyze the correlation between ratio of dietary VitA to body weight with blood pressure levels and prevalence of hypertension. Results: The results of the 2014 baseline survey indicated that, after adjusting for confounding factors such as demographic indicators and nutritional intake, significant differences were observed in systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) among different groups categorized by the ratio of dietary VitA to body weight (F=157.57, 44.71, 95.92, P<0.01). The baseline ratio of dietary VitA to body weight in children exhibited a negative correlation with DBP, SBP and MAP at baseline and in 2019[baseline: β(95%CI)=-0.65(-0.89--0.42), -0.22(-0.42--0.01), -0.36(-0.56--0.16); 2019: β(95%CI)=-0.77(-1.34--0.19), -0.62(-1.21--0.02), -0.77(-1.34--0.19), P＜0.05]. Compared to Q1 group, the risk of hypertension decreased among children in Q4 at baseline and followup in 2019 [OR(95%CI)=0.63(0.49-0.81), 0.18(0.08-0.42), P<0.01]. Conclusions The ratio of dietary VitA to body weight is significantly negatively correlated with blood pressure levels among children, and dietary VitA deficiency is an independent risk factor for hypertension among children. Measures should be taken to actively adjust childrens dietary nutrition and reduce the risk of childhood hypertension.

Objective To identify the pathogenic bacteria such as Staphylococcus aureus and Enterococcus faecalis in bloodstream infec-tions with high confidence based on three deep learning models such as GoogleNet,ResNet101,and Vgg19,compare the performance and classification ability of these models,and explore the feasibility of applying the deep learning models for the rapid identification of pathogenic bacteria in bloodstream infections.Methods The preprocessed Gram-stained bacterial images,including 1 682 images for Staphylococcus aureus and 1 723 for Enterococcus faecalis,and 688 blank control microscopic images were input into three models for training and validation,respectively.Among them,1 344 images for Staphylococcus aureus,1 376 for Enterococcus faecalis,and 544 blank control images were used for training,and the remaining images were used for validation.The model with the best performance was identified according to the classification parameters between the models.Results The ResNet101 model had the lowest cross-en-tropy loss value(0.008 710 3),the largest Epoch value(93),and the highest accuracy rate(99％)for identifying the three types of validation set images.The cross-entropy loss value,Epoch value,and accuracy rate of the GoogleNet model were 0.063 89,86 and 98.6％,respectively,for identifying the three types of validation set images.Those of the Vgg19 model were 0.035 682,86 and 97.7％,respectively.Conclusion The ResNet101 model has the best performance in the classification of three kinds of images.The deep learning model may accurately,reliably and rapidly identify the Gram-stained images of pathogenic bacteria such as Staphylococcus aureus and Enterococcus faecalis in bloodstream infections.

Objective:To explore the construction of evaluation criteria for long-term care ability of the elderly suitable for China's national conditions.Methods:The evaluation criteria were initially established through literature research and field semi-structured interviews. Through the Delphi method, 15 experts were consulted and the evaluation criteria for the long-term care ability of the elderly were finally established.Results:The effective rate of the two rounds of expert consultation questionnaires was 100%, and the expert authority coefficients were 0.91 and 0.92 respectively. The evaluation criteria for long-term care ability of the elderly were established, including two first-level indicators of self-care ability and disease severity, four second-level indicators of abilities of daily living, mental state and social participation, perception and communication, and disease severity, as well as 39 third-level indicators including recumbent status, cognitive function, level of consciousness, illness and so on.Conclusions:The evaluation criteria for long-term care ability of the elderly are scientific and reliable, which can provide a reference for the classification of long-term care services for the disabled elderly in China.

Six new ent-abietane diterpenoids, abientaphlogatones A-F (1-6), along with two undescribed ent-abietane diterpenoid glucosides, abientaphlogasides A-B (7-8) and four known analogs were isolated from the aerial parts ofPhlogacanthus curviflorus (P. curviflorus). The structures of these compounds were determined using high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), one-dimensional and two-dimensional nuclear magnetic resonance (NMR) spectroscopy, electronic circular dichroism (ECD) spectra, and quantum chemical calculations. Notably, compounds 5 and 6 represented the first reported instances of ent-norabietane diterpenoids from the genus Phlogacanthus. In the β-hematin formation inhibition assay, compounds 2, 4, 7-10, and 12 displayed antimalarial activity, with IC₅₀ values of 12.97-65.01 μmol·L^-1. Furthermore, compounds 4, 5, 8, and 10 demonstrated neuroprotective activity in PC12 cell injury models induced by H₂O₂ and MPP⁺.
Abietanes/pharmacology* ; Antimalarials ; Hydrogen Peroxide ; Biological Assay ; Plant Components, Aerial

Abstract OBJECTIVE To optimize the extraction process of Guiqi Yiyuan decoction and establish its quality control method. METHODS L9(34) orthogonal test was used to optimize the extraction process of Guiqi Yiyuan decoction by using index as comprehensive evaluation of the extraction rate, total polysaccharide content and n-butanol extract content. Thin layer chromatography(TLC) was used to identify Astragali Radix, Angelicae Sinensis Radix, Lycii Fructus and Ginseng Radix et Rhizoma in the decoction. The content of glucoside of calycosin as the main active ingredient of Astragali Radix was determined by HPLC. The differences in relative density, insoluble matter and loading amount were checked according to the Chinese Pharmacopoeia 2020 edition, and the quality control method was established. RESULTS The optimum process was 12 times water, 4 h extraction time and 2 times extraction. TLC identification results showed that the chromatograms had clear spots, good separation and strong specificity. The linear range of calycosin glucoside was 0.089 6-1.344 0 µg(r2=0.999 4), the average recovery was 99.51%, RSD was 2.59%(n=9). The relative density of decoction was 1.39, and the difference of insoluble matter and loading amount was in accordance with the provisions of Chinese Pharmacopoeia 2020 edition. CONCLUSION The optimized water extraction process is scientific and reasonable, and the quality standard is effective and controllable, which can be used for the quality control of Guiqi Yiyuan decoction.

Inflammatory bowel disease (IBD) is a non-specific inflammatory disease of the gastrointestinal (GI) tract that is generally accepted to be closely related to intestinal dysbiosis in the host. GI infections contribute a key role in the pathogenesis of IBD; however, although the results of recent clinical studies have revealed an inverse correlation between Helicobacter pylori (H. pylori) infection and IBD, the exact mechanism underlying the development of IBD remains unclear. H. pylori, as a star microorganism, has been a focus for decades, and recent preclinical and real-world studies have demonstrated that H. pylori not only affects the changes in the gastric microbiota and microenvironment but also influences the intestinal microbiota, indicating a potential correlation with IBD. Detailed analysis revealed that H. pylori infection increased the diversity of the intestinal microbiota, reduced the abundance of Bacteroidetes, augmented the abundance of Firmicutes, and produced short-chain fatty acid-producing bacteria such as Akkermansia. All these factors may decrease vulnerability to IBD. Further studies investigating the H. pylori-intestinal microbiota metabolite axis should be performed to understand the mechanism underlying the development of IBD.
Chronic Disease ; Dysbiosis/microbiology* ; Gastrointestinal Microbiome ; Helicobacter Infections ; Helicobacter pylori ; Humans ; Inflammatory Bowel Diseases/microbiology* ; Microbiota

Drug repurposing or repositioning has been well-known to refer to the therapeutic applications of a drug for another indication other than it was originally approved for. Repurposing non-oncology small-molecule drugs has been increasingly becoming an attractive approach to improve cancer therapy, with potentially lower overall costs and shorter timelines. Several non-oncology drugs approved by FDA have been recently reported to treat different types of human cancers, with the aid of some new emerging technologies, such as omics sequencing and artificial intelligence to overcome the bottleneck of drug repurposing. Therefore, in this review, we focus on summarizing the therapeutic potential of non-oncology drugs, including cardiovascular drugs, microbiological drugs, small-molecule antibiotics, anti-viral drugs, anti-inflammatory drugs, anti-neurodegenerative drugs, antipsychotic drugs, antidepressants, and other drugs in human cancers. We also discuss their novel potential targets and relevant signaling pathways of these old non-oncology drugs in cancer therapies. Taken together, these inspiring findings will shed new light on repurposing more non-oncology small-molecule drugs with their intricate molecular mechanisms for future cancer drug discovery.

Adipocytes ; Adipose Tissue ; Exosomes ; Stem Cells ; Wound Healing

Objective:To evaluate the cerebral blood flow circulation time (CCT) by contrast-enhanced ultrasound, and to explore the change rule of CCT in different degree of intracranial pressure, so as to provide a new method for non-invasive monitoring of intracranial pressure.Methods:Ten patients with hemorrhagic stroke or acute craniocerebral trauma with increased intracranial pressure were selected from Tangdu Hospital, the Air Force Military Medical University from January to December 2019. Contrast-enhanced ultrasound was performed when the invasive intracranial pressure (iICP) increased (>20 mmHg, iICP increased group) and decreased to normal (≤20 mmHg, iICP normal group), CCT was measured and analyzed. The differences of CCTs between different iICP groups were compared and the relationship between CCT and iICP was analyzed.Results:①The CCT on the lesion sides of the same patients in the iICP increased group was significantly longer than in the iICP normal group[(9.34±2.58)s vs (6.48±1.91)s, P=0.002]. ②When iICP was increased in patients with hemorrhagic stroke or acute craniocerebral trauma, the CCTs of the diseased side and the non-pathological side were not statistically significant [(9.34±2.58)s vs (9.01±3.22)s, P=0.809]. ③Pearson correlation analysis and Spearman rank correlation analysis showed that there were no correlations between patient′s breathing, heart rate, carbon dioxide partial pressure, body temperature, GCS score and CCT (all P>0.05). Age, mean arterial pressure and CCT were moderately correlated ( r=0.518, 0.463 and P=0.023, 0.046, respectively). ④Logistic regression analysis showed that CCT was an independent risk factor related to intracranial hypertension( OR=0.7, 95% CI=0.47-0.95, P=0.036). The area under ROC curve (AUC) predicted by logistic regression was 0.750(0.588~0.912). Conclusions:Contrast-enhanced ultrasound noninvasive assessment of CCT can reflect the intracranial pressure in patients with hemorrhagic stroke or acute traumatic brain injury, and CCT has a predictive value for intracranial hypertension. When the patient has limited conditions for invasive intracranial pressure monitoring, or when the invasive monitoring probe is pulled out but still needs to evaluate intracranial pressure, the change of CCT can provide an effective reference for clinical diagnosis and treatment.