Objective To investigate the improvement effect and mechanism of marmesin on cognitive impairment in Alzheimer's disease(AD)mice.Methods Fifty mice were randomly divided into five groups:blank group,model group,low-and high-dose marmesin groups and donepezil(positive drug)group,with 10 mice in each group.After 21 days of continuous administration,except for the blank group,the mice in other groups were given intraperitoneal injection of scopolamine to establish the AD model.Network pharmacology was used to construct the protein-protein interaction(PPI)network of common targets of marmesin in the treatment of AD,and gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were performed to provide further research direction.The cognitive function of AD model mice was evaluated by Morris water maze,open field test and new object recognition test.Nissl staining was used to observe the damage of hippocampal neurons.The levels of acetylcholine(Ach),acetylcholine transferase(ChAT),acetylcholinesterase(AChE),reactive oxygen species(ROS),malondialdehyde(MDA)and catalase(CAT)in hippocampus of mice were detected by kit.The protein expression levels of interleukin 6(IL-6),interleukin 1β(IL-1 β),tumor necrosis factor α(TNF-α),nuclear factor E2-related factor 2(NRF2),silent information regulator homologous protein 3(SIRT3),Kelch-like ECH-associated protein 1(KEAP1),quinone oxidoreductase 1(NQO1)and heme oxygenase 1(HO-1)in hippocampus were detected by Western Blot.Results Compared with the model group,the latency of Morris water maze test was significantly shortened in the high-dose marmesin group,the time of entering the target area in the open field new object test and the movement distance in the central area of the open field were prolonged,the number of neurons in the hippocampal CA1 and CA3 regions was significantly increased,the levels of ChAT and Ach in the hippocampus were significantly increased,AChE level was significantly decreased,CAT level was significantly increased,ROS and MDA levels were significantly decreased,TNF-α expression level was decreased,SIRT3 and HO-1 expression levels were increased,and KE AP1 protein expression level was decreased,the differences being statistically significant(P＜0.05 or P＜0.01 or P＜0.001).Conclusion Marmesin can effectively improve the learning and memory impairment of AD mice,and its mechanism may be related to the activation of NRF2/SIRT3 signaling pathway,thereby alleviating oxidative stress level and neuroinflammation,and repairing cholinergic neuron function.

The parahippocampal gyrus-orbitofrontal cortex (PHG-OFC) circuit in humans is homologous to the postrhinal cortex (POR)-ventral lateral orbitofrontal cortex (vlOFC) circuit in rodents. Both are associated with visuospatial malfunctions in Alzheimer's disease (AD). However, the underlying mechanisms remain to be elucidated. In this study, we explored the relationship between an impaired POR-vlOFC circuit and visuospatial memory deficits through retrograde tracing and in vivo local field potential recordings in 5XFAD mice, and investigated alterations of the PHG-OFC circuit by multi-domain magnetic resonance imaging (MRI) in patients on the AD spectrum. We demonstrated that an impaired glutamatergic POR-vlOFC circuit resulted in deficient visuospatial memory in 5XFAD mice. Moreover, MRI measurements of the PHG-OFC circuit had an accuracy of 77.33% for the classification of amnestic mild cognitive impairment converters versus non-converters. Thus, the PHG-OFC circuit explains the neuroanatomical basis of visuospatial memory deficits in AD, thereby providing a potential predictor for AD progression and a promising interventional approach for AD.

COVID-19 Nucleic Acid Testing/methods* ; Clinical Laboratory Techniques ; Containment of Biohazards ; Disinfection ; Environmental Monitoring ; Humans ; Nucleic Acids/isolation & purification* ; SARS-CoV-2/isolation & purification* ; Specimen Handling

In countries and regions with high vaccination coverage, several vaccine-preventable diseases have been resurged in recent years, such as measles, varicella, pertussis and mumps. Some studies have found that the clinical manifestation and epidemiological characteristics of these diseases were different from those in pre-vaccine era. This article reviewed the clinical and epidemiological features of vaccine-preventable diseases before and after wide immunization implementation, focusing on the situation in China, in order to attract the attention of clinicians, raise awareness, strengthen prevention and control, and promote in-depth research for these diseases.
Chickenpox ; China ; Humans ; Measles ; Mumps ; Vaccination ; Vaccines

Objective: To evaluate the feasibility and potential value of comprehensive geriatric assessment (CGA) in elderly (≥60 years) patients with newly diagnosed acute myeloid leukemia (AML) in China. Methods: The CGA results of 83 newly diagnosed AML (non-APL) patients from 16 hospitals in Beijing and Tianjin between March 2016 and December 2017 were prospectively collected and analyzed. The clinical data, treatment and follow-up information were also collected. Results: Of 83 newly diagnosed elderly AML patients, 81 patients (97.6%) completed all designated CGA assessment. The median number of impaired scales of the CGA assessment in the studied population was 2(0-6). Sixteen patients (19.3%) showed no impairments according to the geriatric assessment scales implem ented by this study. The distributions of impaired scales were as follows: impairment in ADL, 55.4%; IADL impairment, 42.2%; MNA-SF impairment, 48.2%; cognitive impairment, 15.7%; GDS impairment, 31.7%; HCT-CI impairment, 19.5%, respectively. In patients with "good" ECOG (n=46), the proportion of impairment for each CGA scale ranged from 6.5% to 37.0% and 32 patients (68.9%) had at least one impaired CGA scale. Survival analysis showed that the number of impaired scales of the CGA was significantly correlated with median overall survival (P=0.050). Conclusions: CGA was a tool with feasibility for the comprehensive evaluation in elderly AML patients in China. Combined with age and ECOG, CGA may be more comprehensive in assessing patients' physical condition.
Activities of Daily Living ; Aged ; China ; Geriatric Assessment ; Humans ; Leukemia, Myeloid, Acute ; Prospective Studies

Objective: To assess the diagnostic value of soluble suppression of tumorigenicity-2 (sST2) in heart failure (HF) by Meta-analysis. Methods: We searched the databases of CNKI, Wei Pu, CBMdisc,WanFang and Pubmed up to 2017-03-14 for diagnostic value of sST2 in HF patients. Corresponding references were enrolled and relevant data was extracted. Quality evaluation was conducted by quality assessment of diagnostic accuracy studies-2(QUADAS-2)method, effect of sST2 in HF diagnosis was analyzed by Stata14.0 and Revman software. Results: A total of 13 references were eligible including 5 English and 8 Chinese. Meta analysis showed that the diagnostic value of sST2 in HF had the pooled sensitivity at 79%, 95% CI (0.68-0.86);pooled specificity at 69%, 95% CI (0.58-0.79); positive like hood rate was 2.57, 95% CI(1.86-3.53), negative like hood rate was 0.31, 95%CI (0.21-0.46), diagnostic odds rate was 8.28, 95% CI (4.76-14.42); the area under ROC was 0.8. Deek's funnel plot demonstrated no publication bias in Meta-analysis. Conclusion: sST2 had moderate value in diagnosing HF; duo to the defect in methodology, large sample, scientific and reasonable random controlled trails should be conducted to confirm the diagnostic efficacy.

OBJECTIVE Bingpian is an almost pure chemical with a chemical composition of (+)-borneol and has been historically used as a topical analgesic in traditional Chinese medicine for millen-nia. However, the clinical efficacy of topical bingpian lacks stringent evidence-based clinical studies and the underlying molecular mechanisms are unclear.This study verified the analgesic efficacy of topi-cal bingpian in humans, and elucidated the underling mechanisms in animal models of pain. METH-ODS The analgesic efficacy of topical bingpian was examined in a randomized,double-blind,placebo-controlled clinical study at the Shanghai Changzheng Hospital. Capsaicin, formalin, CFA or thermal caused pain/hyperalgesia were established in different mouse models,and bingpian-induced analgesia and the underlying mechanisms were studied in these models.The molecular targets of bingpian were examined by calcium imaging, patch-clamp recording and enzymatic activity assay in mouse sensory neurons or transfected HEK 293 cells. RESULTS (1)Topical application of bingpian leads to significantly greater pain relief than placebo does in a randomized, double-blind, placebo-controlled clinical study involving 122 patients with postoperative pain.(2)TRPM8 channel is the most sensitive molecular target of bingpian and mediates topical bingpian-induced analgesia in mice. (3)A downstream glutamatergic mechanism in the spinal cord contributes to topical bingpian-induced analgesia. (4)Bingpian shows mechanistic differences and advantages as a topical analgesic when compared with menthol.

Integrative pharmacology (IP) is a discipline that studies the interaction, integration and principle of action of multiple components with the body, emphasizing the integrations of multi-level and multi-link, such as "whole and part", " and ", " process and activity evaluation". After four years of development and practice, the theory and method of IP has received extensive attention and application.In order to better promote the development of IP, this paper systematically reviews the concepts, research contents, research methods and application fields about IP.

Based on the transcriptome data, the study cloned full-length cDNA of TwGPPS1 and TwGPPS2 genes from Tripterygium wilfordii suspension cells and then analyzed the bioinformation of the sequence and protein expression. The cloned TwGPPS1 has a 1 278 bp open reading frame (ORF) encoding a polypeptide of 425 amino acids. The deduced isoelectric point (pI) was 6.68, a calculated molecular weight was about 47.189 kDa. The full-length cDNA of the TwGPPS2 contains a 1 269 bp open reading frame (ORF) encoding a polypeptide of 422 amino acids. The deduced isoelectric point (pI) was 6.71, a calculated molecular weight was about 46.774 kDa.The entire reading frame of TwGPPS1,2 was cloned into the pET-32a(+) vector and expressed in E. coli BL21 (DE3) cells to obtain the TwGPPS protein, which laid a basis for further study on the regulation of terpenoid secondary metabolism and biological synthesis.

In this study, we cloned a monoterpene synthases, TwMS from Tripterygium wilfordii suspension cells. TwMS gene contained a 1 797 bp open reading frame (ORF), encoding a polypeptide of 579 amino acids, which deduced isoelectric point (pI) was 6.10 and the calculated molecular weight was 69.75 kDa. Bioinformation analysis showed that the sequence of TwMS was consistent with the feature of monoterpene synthases. Differential expression analysis revealed that the relative expression level of TwMS increased significantly after being induced by methyl jasmonate (MeJA). The highest expression level occurred at 24 h. TwMS protein was successfully expressed in Escherichia coli BL21 (DE3), which laid the foundation for identifying the function of T. wilfordii monoterpene synthases.