ObjectiveTo explore the effect of Polygonati Odorati Rhizoma polysaccharides on hyperlipidemia in mice by modulating the gut microbiota. MethodsNinety male C57BL/6J mice were randomized into the following groups （n=15）： control， model， simvastatin， low- （100 mg·kg^-1）， medium- （200 mg·kg^-1）， and high-dose （400 mg·kg^-1） Polygonati Odorati Rhizoma polysaccharides groups. Other groups except the control group were fed with a high-fat diet for the modeling of hyperlipidemia， and drug interventions lasted for 12 weeks. Serum levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） were measured by an automatic biochemical analyzer. The pathological changes in the liver and epididymal fat were observed by hematoxylin-eosin staining， and lipid accumulation in the liver was assessed by oil red O staining. The gut microbiota was analyzed by 16S rRNA gene sequencing. ResultsCompared with the control group， the model group exhibited an increase in body weight （P<0.01）， along with marked elevations in serum levels of TC， TG， and LDL-C （P<0.05，P<0.01）. Furthermore， the model group showcased increase in the liver index and epididymal fat coefficient （P<0.05）， increased liver fat accumulation， enlargement of adipocytes in the epididymal fat， decreases in both alpha and beta diversity of the gut microbiota， and an increase in the relative abundance of Allobaculum （P<0.01）. Compared with the model group， Polygonati Odorati Rhizoma polysaccharides suppressed the increase in body weight （P<0.01）， lowered the serum levels of TC， TG， and LDL-C （P<0.05，P<0.01）， reduced the liver index and epididymal fat coefficient （P<0.05）， alleviated liver fat accumulation， and decreased the size of adipocytes in the epididymal fat. Furthermore， it enhanced the alpha and beta diversity of the gut microbiota in mice， reduced the relative abundance of Allobaculum， Erysipelotrichaceae， and Clostridium （P<0.01）， and increased the relative abundance of Akkermansia and Blautia （P<0.01）. ConclusionPolygonati Odorati Rhizoma polysaccharides can ameliorate hyperlipidemia induced by a high-fat diet in mice by regulating the diversity and composition of the gut microbiota.

Objective Exploring the behavioral changes induced by quinpirole in obsessive-compulsive disorder(OCD)mouse,investigating the activation of neurons in different brain regions,and identifying differentially expressed genes(DEGs)and enriched biological pathways through transcriptome sequencing technology to elucidate the pathogenesis of OCD.Methods Randomly assign 32 male C57BL/6J mice,aged two months,to an OCD group and a control group(n=16).Administering quinpirole(0.75 mg/kg)via subcutaneous injection to the OCD group mice every other day for a total of 19 injections,while the control group mice received an equivalent volume of saline solution.Following the completion of the model construction,open field testing,elevated plus maze testing,and marble burying tests were conducted.After the completion of behavioral studies,tissue samples were collected.Neuronal damage was assessed using Nissl staining,while the expression of c-Fos and Iba1 proteins was examined through immunofluorescence staining.Transcriptome sequencing technology was utilized to screen for differentially expressed genes and to enrich relevant signaling pathways.The expression of inflammatory cytokines,including TNF-α,NF-κB p65,phosphorylated NF-κB p65(p-NF-κB p65),and IL-6,was detected using Western Blot analysis.Results Mouse induced with OCD by quinpirole exhibit anxiety-like behaviors and compulsive-like behaviors.Neurons in the hippocampal and hypothalamic regions exhibit signs of damage.The expression of c-Fos and Iba1 proteins is increased in the cortex,striatum,hypothalamus,and other brain regions.Western Blot result indicate a significant increase in the expression of pro-inflammatory cytokines such as TNF-α,p-NF-κB p65,and IL-6.Conclusions In OCD mouse,neurons in multiple brain regions are abnormally activated,microglia exhibit dysfunction,and neuroinflammation induced by the activation of the NF-κB signaling pathway accompanies the development of OCD.

Alzheimer's disease(AD)is one of the most prevalent neurodegenerative disorders,and is increasingly becoming a global health challenge,in line with the intensification of population aging.The pathogenesis of AD is currently unclear and treatment options are limited.Currently available drugs can only alleviate the symptoms of AD to a certain extent,and cannot delay its progression.Numerous studies,however,have shown that a variety of micronutrients may play a positive role in the treatment of AD.Vitamins and trace metal elements have many functions,including anti-inflammation,anti-oxidation,and protection of mitochondria.Micronutrients can effectively reduce β-amyloid protein plaque deposition and Tau protein hyperphosphorylation to improve brain energy metabolism,thereby helping to prevent and treat AD.This article reviews and summarizes the roles of common vitamins and trace metal elements in the prevention and treatment of AD,with the goal of offering new perspectives for the clinical management and prevention of this disease.

Objective Exploring the behavioral changes induced by quinpirole in obsessive-compulsive disorder(OCD)mouse,investigating the activation of neurons in different brain regions,and identifying differentially expressed genes(DEGs)and enriched biological pathways through transcriptome sequencing technology to elucidate the pathogenesis of OCD.Methods Randomly assign 32 male C57BL/6J mice,aged two months,to an OCD group and a control group(n=16).Administering quinpirole(0.75 mg/kg)via subcutaneous injection to the OCD group mice every other day for a total of 19 injections,while the control group mice received an equivalent volume of saline solution.Following the completion of the model construction,open field testing,elevated plus maze testing,and marble burying tests were conducted.After the completion of behavioral studies,tissue samples were collected.Neuronal damage was assessed using Nissl staining,while the expression of c-Fos and Iba1 proteins was examined through immunofluorescence staining.Transcriptome sequencing technology was utilized to screen for differentially expressed genes and to enrich relevant signaling pathways.The expression of inflammatory cytokines,including TNF-α,NF-κB p65,phosphorylated NF-κB p65(p-NF-κB p65),and IL-6,was detected using Western Blot analysis.Results Mouse induced with OCD by quinpirole exhibit anxiety-like behaviors and compulsive-like behaviors.Neurons in the hippocampal and hypothalamic regions exhibit signs of damage.The expression of c-Fos and Iba1 proteins is increased in the cortex,striatum,hypothalamus,and other brain regions.Western Blot result indicate a significant increase in the expression of pro-inflammatory cytokines such as TNF-α,p-NF-κB p65,and IL-6.Conclusions In OCD mouse,neurons in multiple brain regions are abnormally activated,microglia exhibit dysfunction,and neuroinflammation induced by the activation of the NF-κB signaling pathway accompanies the development of OCD.

Alzheimer's disease(AD)is one of the most prevalent neurodegenerative disorders,and is increasingly becoming a global health challenge,in line with the intensification of population aging.The pathogenesis of AD is currently unclear and treatment options are limited.Currently available drugs can only alleviate the symptoms of AD to a certain extent,and cannot delay its progression.Numerous studies,however,have shown that a variety of micronutrients may play a positive role in the treatment of AD.Vitamins and trace metal elements have many functions,including anti-inflammation,anti-oxidation,and protection of mitochondria.Micronutrients can effectively reduce β-amyloid protein plaque deposition and Tau protein hyperphosphorylation to improve brain energy metabolism,thereby helping to prevent and treat AD.This article reviews and summarizes the roles of common vitamins and trace metal elements in the prevention and treatment of AD,with the goal of offering new perspectives for the clinical management and prevention of this disease.

Objective To explore the mechanisms of circadian rhythm disorder(CRD)on behavior and testicular spermatogenic capacity in adolescent mice.Methods Thirty SPF grade C57 mice were selected and randomly di-vided into the control and CRD groups with 15 mice in each group.The control group kept 12 h dark/12 h bright circulating light,and the CRD group kept 24 h light.The trial lasted for 61 days.The growth curves of mice in each group were counted;the elevated plus maze test and open field test were performed to detect mice behavior;neuronal morphology was visualized by Nissl staining.The distribution of ionized calcium-binding adapter molecule 1(Iba1)and neuron-specific nuclear protein(NeuN)in the hypothalamus were detected by immunofluorescence and Western blot.Expression of testosterone synthesis-related genes steroidogenic acute regulatory protein(StAR)and hydroxy-delta-5-steroid dehydrogenase,3 beta-and steroid delta-isomerase 1(HSD3B1)and spermatogenesis-related genes gametogenetin binding protein 2(GGNBP2)and deleted in azoospermia-like(DAZL)were deter-mined by RT-qPCR.Results The weight of the CRD group was significantly higher than that of control group at 61 days;in the elevated plus maze test,the time,frequency,and percentage of time in the open arm of the CRD group were significantly less than those of the control group;in the open field test,there was no significant differ-ence in movement distance between the two groups;however,the residence time of the central area in the CRD group was significantly less than that in the control group;the frequency of entering the central area in the CRD group was significantly less than that in the control group.Nissl staining results showed that the positive cells in the CRD group were significantly lower than the control group.Immunofluorescence and Western blot results showed that Iba1 protein expression was up-regulated and NeuN protein expression was down-regulated in the hypothalamus of the CRD group.In the RT-qPCR experiment,the expression of HSD3B1 in the CRD group was significantly low-er than that of the control group;the expression of GGNBP2 and DAZL in the CRD group was significantly lower than that in the control group.Conclusion The CRD treatment can not only lead to depressive behavior in adoles-cent mice but also reduce the development of reproductive system in male adolescent mice.

Objective To construct the etoposide (VP-16)combined with cisplatin (DDP) chemotherapy scheme (EP chemotherapy scheme)resistant small cell lung cancer (SCLC)cell line H446/EP and to identify the drug resistance characteristics and explore the mechanism.Methods NCI-H446 cells were treated with increasing concentrations of VP-16 and DDP to construct an H446/EP cell line.H446/EP and NCI-H446 cells were used as the research objects.The cell viability was detected by MTT assay,and the resistance index (RI)of H446/EP cells was calculated.Cell cloning assay and Incucyte cell proliferation (label-free)assay were used to detect cell proliferation ability.Transcriptome sequencing was performed to analyze the enrichment of differentially expressed genes (DEGs)in the 2 cell lines.Western blotting was applied to detect the protein expression levels of drug resistance,DNA damage repair (DDR),and autophagy markers.Results MTT assay showed that the resistance index (RI)of H446/EP cells to VP-16,DDP,and DOX were 6.14,3.43,and 1.96,respectively.The results of cell cloning assay and Incucyte cell proliferation assay indicated that the proliferation ability was significantly higher in the H446/EP cells than the NCI-H446 cells (P<0.01).Transcriptome sequencing and pathway enrichment analysis displayed that the DEGs between H446/EP and NCI-H446 cells were enriched in tumor chemoresistance,DDR,and autophagy pathways.Western blot results showed the expression levels of MRP1,BCRP,RAD51,γ-H2AX,and LC3-Ⅱ/LC3-Ⅰ were significantly increased,and that of p62 was obviously decreased in the H446/EP cells when compared with the NCI-H446 cells (P<0.05).Conclusion An EP chemotherapy-resistant H446/EP cell line is successfully constructed.Stronger proliferation ability,increased expression of efflux transporters,and enhanced DDR and autophagy may be the mechanisms of the resistance of SCLC to EP chemotherapy scheme.

Neurodegenerative diseases(NDs)are closely related to the central nervous system and characterized by morphological abnormalities and progressive loss of function in specific neuron groups.The main NDs include Alzheimer's disease,Parkinson's disease,amyotrophic lateral sclerosis,multiple sclerosis and Huntington's disease.However,no direct therapies for NDs exist.In recent years,single cell RNA-sequencing(scRNA-seq)has been widely used in various NDs.The pathogenesis of NDs is closely related to morphology of immune cells,and the pathogenesis mainly involves mitochondrial function,glucose metabolism,inflammation,and synaptic transmission.Induced pluripotent stem cells are a potential therapy for NDs.Ultimately,we review the application of scRNA-seq to various NDs and provide a reference for prevention and treatment of NDs.

Objective To explore the effects of the Chinese medicine, modified Erchen decoction, on the serum lipid spectrum of ApoE-/-mice, and to explore its possible anti-atherosclerotic mechanism.Methods Forty-four male 7-8-week old ApoE-/-mice were used in this experiment.ApoE-/-mouse models of atherosclerosis were generated by high-cholesterol diet for 4 weeks.And then, they were given simvastatin or modified Erchen decoction by gavage.The body weight of mice was recorded every week, The mice were sacrificed after treated with the drugs for 8 weeks continuously, and the plasma lipid was determined by enzymatic method.The aortic valves and arches were stained with oil red O to depict atherosclerotic plaques and liver structural changes of the mice were examined by pathology.Results Modified Erchen decoction lowered plasma lipid ( including TCHOL and LDL-C ) significantly ( P<0.01 ) .The body weight was increased in the mice of all groups, but it was more pronounced in the mice of model group than in the blank and modified Erchen decoction groups.The serum CHOL and LDL-C levels were significantly lowered in the modified Erchen decoction group (P<0.01).The area of atherosclerotic plaques in the aortic wall was significantly reduced in the mice of modified Erchen decoction group as shown by oil red O staining.The pathological changes of hepatocytes were less severe and the structure of hepatic lobules was better preserved in the mice of modified Erchen decoction group.Conclusions The Chinese medicin modified Erchen decoction can effectively reduce serum lipids, regulate lipid metabolism, and ameliorate the process of atherosclerosis in ApoE-/-mice.

Objective To evaluate the expression and clinical significance of human papillomavirus(HPV)L1 caspid protein in cytologic specimens of the cervix.Methods The HPV L1 caspid protein in cytologic specimens of the cervix was detected by using immunochemistry in 309 women treated in Shenzhen Hospital of Peking University from Jan.2008 to May 2009.According to histological biopsy,of 309 liquid-based cytologic smears,there were 33 cases of normal cervixes or chronic cervititis,168 cases of grade I of cervical intraepithelial neoplasia(CIN I),84 cases of grade Ⅱ/Ⅲof CIN,and 24 cases of squamous cell carcinomas(SCC).Results The positive expression rate of HPV L1 caspid protein was 27.3%,66.7%,25.0%,and 0 in the normal cervixes or chronic cervititis,CIN I and CIN Ⅱ/Ⅲ,and SCC respectively.There was significant difference between CIN I or SCC and the normal cervixes or chronic cervititis,between CIN I with CIN Ⅱ/Ⅲ,and between CIN I or CIN Ⅱ/m with SCC(all P<0.0 1).The positive expression rate of HPV L1 caspid protein was reduced with the lesion progression from CIN I to CINⅡ/Ⅲ to SCC.309 cases were divided into two groups by 30 and 40 years of age,and there was no significant difference in the HPV L1 caspid protein expression between different age groups(P>0.05).The positive expression rate of HPV L1 caspid protein in the over-1000 RLU/PC viral load group was significantly higher than in the under-1000 RLU/PC viral load group(P<0.05).The sensitivity,specificity,positive predictive value,negative predictive value of HPV L1 caspid protein for detecting high-grade cervical lesions were 80.6%,60.2%,52.1% and 85.2%,respectively.Conclusion The positive rate of HPV L1 caspid protein is decreased with the lesion progression from CIN I to CIN Ⅱ/Ⅲto SCC.HPV L1 caspid protein among HPV-positive women can be a helpful molecular biomarker in risk assessment and prognostic prediction.