Aim To assess the effects of Banqiao Codonopisis Pilosula(BCP)decoction on learning and memory dysfunction in AD model rats induced by high activity GSK-3β and its possible mechanism.Methods The SD rats(4 months old,♂)were divided into five groups,namely,sham-operated group(blank group),AD model group,BCP high-dose(2.16 g·kg-1·d-1)group,BCP medium-dose(1.08 g·kg-1·d-1)group,and BCP lower-dose(0.54 g·kg-1·d-1)group.Treatment group received BCP decoction by gavage once a day for 14 days,while other groups were offered drinking water by gavage once a day for 14 days.The autonomous behavior activities of all rats were observed and recorded after gavage.In the last seven days by gavage,Morris water maze test was used to test the spatial learning and memory ability of the five groups.After five days training,treatment groups and AD model group were injected wortmannin(WT,PI3K specific inhibitor)and GF-109203X(GFX,PKC specific inhibitor)(100 μmol·L-1 of each,total volume of 10 μL)into the right lateral ventricle of the rats.The blank group was only injected 2％DMSO.The spatial memory retention was detected by water maze 24 hours after lateral ventricle injection.Then,changes in the spatial learning memory of rats were observed.The level of Tau phosphorylation in SD rat hippocampus and the expression and activity changes of related protein kinase GSK-3β were detected by Western blot and immunohistochemistry.The changes of Nissl bodies in SD rat hippocampus were observed by Nissl′s staining.Results After intragastric administration of BCP,the rat autonomous behavior activities in each group all showed a declining trend,and the differences in low-dose and middle-dose groups had statistical significance compared with blank group.The Morris water maze tests showed that the latency navigation of model group was significantly longer than that of blank group(P<0.01),while that of the BCP three doses groups was shorter than that of model group(P<0.05).Compared with the same group,the latency navigation of the three groups after gavage BCP low,middle and high dose was significant shorter than that without gavage(P<0.05).Western blot results showed that the activity of GSK-3β in AD model group was up-regulated compared with the blank group.However,BCP inhibited activity of GSK-3β.Western blot and immunohistochemistry results showed the level of Tau phosphorylation in AD model group was increased compared with the blank group in the area of CA3(P<0.05).Compared with AD model group,the level of Tau phosphorylation was decreased in treatment group.Nissl′s staining results showed that dendritic spines in AD model group was significantly attenuated compared with the blank group(P<0.05).Far more dendritic spines were observed in treatment group than in AD model group.The number of Nissl′s bodies in neuron cells of hippocampus in hippocampal CA3 was obviously larger in treatment groups than in AD model group.These effect of BCP was dose-dependent.Conclusions BCP can prevent the learning and memory dysfunction in AD model rats induced by high activity of GSK-3β.The mechanism may be related to inhibiting GSK-3β activity and then reducing the level of phosphorylation of Tau and improving neural development.

Objective:To investigate the association between time in target range and risk of vertebral fracture in patients with type 2 diabetes.Methods:The clinical data of 1 032 patients with type 2 diabetes who were hospitalized in endocrine department of Henan Provincial People′s Hospital from June 2017 to July 2021 were collected. Among which 632 patients were included into final analysis. The diabetes-specific risk score for vertebral fracture was used to assess the risk of vertebral fracture. Multivariate linear regression analysis was used to test the association between time in target range and risk score of vertebral fracture. Risk score≥9 was defined as increased risk of vertebral fracture. Multivariate logistic regression was used to estimate the association between time in target range and risk of vertebral fracture. Results:Among the included patients, mean age was(55.0±12.4) years and the percent of male was 72.5%. The mean course of diabetes was(9.4±8.0) years, and mean score of risk of vertebral fracture was 5.6±4.3. Time in target range was negatively correlated with risk score of vertebral fracture( P for trend <0.001), which was independent of potential confounders and continuous glucose monitoring parameters. The included patients were divided into four groups based on quartiles of time in target range. Multivariate logistic regression indicated that the risk of vertebral fracture in the first quartile of time in target range was 4.6 times higherthanthatinthe4thquartile, and the significance remained adjusted for potential confounders, s, CV, or meanamplitudeofglycemicexcursions(MAGE), respectively. Conclusion:Timein target rangewasnegativelycorrelatedwithriskscoreofvertebralfracturein patient with type 2 diabetes. Low time in range level was an independent risk factor for increased risk of vertebral fracture.

Objective:To explore the application effect of integrated Chinese and Western medicine nursing based on the individual and family self-management theory (IFSMT) in patients with urinary incontinence after stroke, and provide reference for clinical nurses to effectively rehabilitate these patients.Methods:This was a quasi-experimental study. A total of 136 patients with urinary incontinence after stroke who were hospitalized in the Department of Encephalopathy of Shanxi Acupuncture and Moxibology Hospital from February 2022 to May 2023 were selected as the study objects by convenience sampling method. The subjects were divided into the control group and the experimental group with 68 cases in each group by random number table method. The control group received routine rehabilitation nursing, and the experimental group received integrated Chinese and western medicine nursing based on IFSMT on the basis of routine rehabilitation nursing. Urinary status, activities of daily living and quality of life of 2 groups were compared.Results:Ultimately, there were 68 cases were admitted in each group. In the control group, male 45 cases, female 23 cases, aged (62.35 ± 4.94) years old. In the experimental group, male 49 cases, female 19 cases, aged (61.94 ± 5.02) years old. There was no statistical significance in urinary status, activities of daily living and quality of life scores between the 2 groups before the intervention (all P>0.05). After the intervention, the average daily urination frequency of experimental group was (7.94 ± 1.08) times, which was lower than that of control group (9.88 ± 1.09) times; the average daily frequency of incontinence in the experimental group was (3.63 ± 1.65) times, lower than (5.03 ± 3.35)times in the control group; the average daily urine volume of experimental group was (107.34 ± 4.15) ml, higher than (89.62 ± 19.71) ml of control group, and the differences were statistically significant ( t=10.46,3.09, -7.23, all P<0.05). The scores of activities of daily living in the experimental group was (60.44 ± 3.65) points, which were higher than (46.24 ± 3.29) points in the control group; the Incontinence Quality of Life Questionnaire score of experimental group was (80.38 ± 4.65) points, which was higher than (64.62 ± 5.62) points of control group; Insomnia Severity Index-Short Form score of the experimental group was (10.94 ± 5.17) points, which was lower than (12.85 ± 4.30) points of the control group, and the differences were statistically significant ( t=23.85, -17.86, 2.34, all P<0.05). Conclusions:Integrated Chinese and western medicine nursing intervention based on IFSMT has a positive effect on patients with urinary incontinence after stroke, and can significantly improve patients' urination and daily living activities, thus improving patients' quality of life.

Objective:Explore the establishment of a fast, stable and sensitive high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for detecting the level of m6A modification in RNA and its application.Methods:The degree of m6A in RNA can be expressed as the ratio of m6A and adenosine (A) in concentration, which can be determined by ESI source positive ion multiple reaction monitoring (MRM) mode. The established method was verified by analyzing three quality control samples (m6A: 4, 40, 400 nmol/L; A: 40, 400, 4 000 nmol/L) with three different concentrations of low, medium, and high. The method was used to detect the degree of m6A in RNA from mouse spleen T cells treated in different ways. The t test was used to compare the differences between the two groups of data. Results:The established method had a good Linearity ( R2>0.99) in a range of 1-500 nmol/L for m6A and 10-5 000 nmol/L for A. The limit of detection (LOD) was 1 nmol/L for m6A and 10 nmol/L for A. The recoveries were between 98.9% and 116.5%. The intra-day ( n=5) RSDs and the inter-day ( n=15, 5 days) RSDs were 2.4%-9.5% and 4.4%-9.6%, respectively. And this method was used to detect the degree of m6A in the RNA from mouse spleen T cells cultured in different conditions. The results showed that the m6A modification level in the RNA of primary CD8 +T cell was 0.271 5±0.017 9, and the m6A modification level in the RNA of primary CD8 +T cell with IL-27 was 0.251 7±0.015 0, indicating that primary CD8 +T cells have a higher level of RNA methylation. Conclusion:This research has established a fast, simplemethylation degree in RNA with HPLC-MS/MS. This method is easy to be popularized and is suitable for the detection of large quantity of samples, and of great significance in analyzing the relationship between methylation and diseases.

Objective:Explore the establishment of a fast, stable and sensitive high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for detecting the level of m6A modification in RNA and its application.Methods:The degree of m6A in RNA can be expressed as the ratio of m6A and adenosine (A) in concentration, which can be determined by ESI source positive ion multiple reaction monitoring (MRM) mode. The established method was verified by analyzing three quality control samples (m6A: 4, 40, 400 nmol/L; A: 40, 400, 4 000 nmol/L) with three different concentrations of low, medium, and high. The method was used to detect the degree of m6A in RNA from mouse spleen T cells treated in different ways. The t test was used to compare the differences between the two groups of data. Results:The established method had a good Linearity ( R2>0.99) in a range of 1-500 nmol/L for m6A and 10-5 000 nmol/L for A. The limit of detection (LOD) was 1 nmol/L for m6A and 10 nmol/L for A. The recoveries were between 98.9% and 116.5%. The intra-day ( n=5) RSDs and the inter-day ( n=15, 5 days) RSDs were 2.4%-9.5% and 4.4%-9.6%, respectively. And this method was used to detect the degree of m6A in the RNA from mouse spleen T cells cultured in different conditions. The results showed that the m6A modification level in the RNA of primary CD8 +T cell was 0.271 5±0.017 9, and the m6A modification level in the RNA of primary CD8 +T cell with IL-27 was 0.251 7±0.015 0, indicating that primary CD8 +T cells have a higher level of RNA methylation. Conclusion:This research has established a fast, simplemethylation degree in RNA with HPLC-MS/MS. This method is easy to be popularized and is suitable for the detection of large quantity of samples, and of great significance in analyzing the relationship between methylation and diseases.

Objective: To evaluate the clinicopathologic characteristics of lung non-terminal respiratory unit (non-TRU) type adenocarcinoma. Methods: Seventy-two cases of lung non-TRU type adenocarcinoma that underwent complete resection and diagnosed at Departments of Pathology, Affiliated Suzhou Hospital of Nanjing Medical University and Nanjing General Hospital of the PLA from January 2005 to December 2016 were retrospectively studied. The histomorphological changes and precursor lesions were observed under microscope. The expression of lineage-specific markers and tumor stem cell markers was detected by immunohistochemistry (IHC). The major driver mutations of lung adenocarcinoma were tested by ARMS and directive gene sequencing. Results: Non-TRU type adenocarcinomas were more commonly found in male (65.3%, 47/72), former or current smokers (68.1%, 49/72), the elder (mean 61 years old), central adenocarcinoma (75.0%, 54/72), tumors with necrosis (61.1%, 44/72) and higher grade (73.6%, 53/72). Histologically, non-TRU type adenocarcinoma displayed complex histomorphology and was often composed of large irregular gland-like and acinar pattern accumulating extracellular mucin, necrotic tumor cell debris and neutrophils, or invasive adenocarcinoma with mucin production. The tumor cells were composed of bronchial surface epithelial cells, mucinous column cells, polygonal cells and goblet cells. Eighteen (25.0%), 23 (31.9%) and 28 (38.9%) cases exhibited ciliated columnar cell metaplasia (CCCM), mucous columnar cell change (MCCC) and bronchiolar columnar cell dysplasia (BCCD) (precursor lesion of lung adenocarcinoma). IHC showed the expression of CK7 (100.0%, 72/72), TTF1 (12.5%, 9/72), Napsin A (5.6%, 4/72), MUC5AC (81.9%, 59/72), MUC5B (87.5%, 63/72), p53 (66.7%, 48/72), CK5/6 (12.5%, 9/72), p63 (18.1%, 13/72), CK20 (19.4%, 14/72) and CDX2 (16.7%, 12/72) in the tumor cells. The expression of tumor stem cell markers was detected in 43.1% cases (31/72) for CD44, 31.9% (23/72) for CD133, 58.3% (42/72) for β-catenin, 36.1% (26/72) for ALDH1, 12.5% (9/72) for GATA6, 20.8% (15/72) for SOX2 and 29.2% (21/72) for OCT4. The driver mutations were 26.4% (19/72) for KRAS, 2.8% (2/72) for EGFR and 1.4% (1/72) for EML4-ALK, and none for BRAF and ROS1. Conclusion Non-TRU type adenocarcinoma is an uncommon subtype of lung adenocarcinoma with distinct clinicopathologic characteristics, histologic appearances, immunophenotype and molecular genetic alterations.

Diabetic kidney disease is a severe microvascular complication of diabetes characterized by complex etiology, diverse mechanisms, long course, and poor prognosis, posing a significant threat to patients′ quality of life. In recent years, research on gut microbiota has progressed deeper, and the concept of the gut-kidney axis emerges, introducing novel therapeutic concepts. This article provides an overview of the role of gut microbiota in the development of diabetic kidney disease and explores potential therapeutic strategies involving gut microbiota for the treatment of this condition.

Objective:To analyze the clinical phenotype and genetic characteristics for a child with Canavan disease.Methods:A child who was admitted to the Children's Hospital Affiliated to Shandong University on April 9, 2021 for inability to uphold his head for 2 months and increased muscle tone for one week was subjected to whole exome sequencing, and candidate variants were verified by Sanger sequencing.Results:Genetic testing revealed that the child has harbored compound heterozygous variants of the ASPA gene, including a paternally derived c. 556_559dupGTTC (p. L187Rfs*5) and a maternally derived c.919delA (p. S307Vfs*24). Based on the guidelines from the American College of Medical Genetics and Genomics, both variants were predicted to be pathogenic (PVS1+ PM2_Supporting+ PM3). Conclusion:The c. 556_559dupGTTC (p.L187Rfs*5) and c. 919delA (p.S307Vfs*24) compound heterozygous variants of the ASPA gene probably underlay the pathogenesis of Canavan disease in this child.

As a potential vectored vaccine,Newcastle disease virus(NDV)has been subject to various studies for vaccine development,while relatively little research has outlined the immunomodulatory effect of the virus in antigen presentation.To elucidate the key inhibitory factor in regulating the interaction of infected dendritic cells(DCs)and T cells,DCs were pretreated with the NDV vaccine strain LaSota as an inhibitor and stimulated with lipopolysaccharide(LPS)for further detection by enzyme-linked immunosorbent assay(ELISA),flow cytometry,immunoblotting,and quantitative real-time polymerase chain reaction(qRT-PCR).The results revealed that NDV infection resulted in the inhibition of interleukin(IL)-12p40 in DCs through a p38 mitogen-activated protein kinase(MAPK)-dependent manner,thus inhibiting the synthesis of IL-12p70,leading to the reduction in T cell proliferation and the secretion of interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),and IL-6 induced by DCs.Consequently,downregulated cytokines accelerated the infection and viral transmission from DCs to T cells.Furthermore,several other strains of NDV also exhibited inhibitory activity.The current study reveals that NDV can modulate the intensity of the innate?adaptive immune cell crosstalk critically toward viral invasion improvement,highlighting a novel mechanism of virus-induced immunosuppression and providing new perspectives on the improvement of NDV-vectored vaccine.

Abstract OBJECTIVE To clarify the resource status and diversity of endemic medicinal plants in Shaanxi province. METHODS The species specificity, species composition, faunal composition, family and genus types, medicinal value and endangerment degree of endemic medicinal plants in Shaanxi province were studied by literature review.RESULTS There were 713 species of 331 genera and 101 families endemic to Chinese medicinal plants in the study area. Fifteen species were naturally distributed only in Shaanxi province, and the remaining 698 species were also naturally distributed in other provinces of China. Among the 713 species, 233 species(69 families, 159 genera) were not collected from the fourth resource census in Shaanxi province. There were 11 species of pteridophytes in 7 families and 11 genera, 14 species of gymnosperms in 4 families and 10 genera, 627 species of dicotyledons in 82 families and 278 genera, and 59 species of monocots in 8 families and 32 genera. The endemic life forms of medicinal plants in the study area were mostly herbaceous, followed by shrubs and trees, and semi-shrubs and epiphytes accounted for the least. There were 9 families with ≥ 20 species and 4 families with ≥ 10 species in the study area. The 90 families belonging to the endemic species of medicinal plants in Shaanxi province were divided into 13 distribution types and 9 variations, and the tropical distribution(2-7 categories) had a total of 34 families. There were 5 endemic species of medicinal plants in the study area under the national class I key protection, and 14 species under the national class II key protection. There were 26 species of plants under local key protection in Shaanxi province. There were 21 plants that could be used as original plants for medicinal materials included in the Pharmacopoeia of the People's Republic of China(2020 edition). CONCLUSION The endemic species of medicinal plants in Shaanxi province are rich in resources and have good medicinal value. However, the growing environment of some plants is harsh and human damage is serious. Multiple protection measures should be taken to maintain the species diversity and sustainable development of resources in the study area.