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.

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.

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.

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.

Platycodon grandiflorum (Jacq.) A. DC. is a famous medicinal plant commonly used in East Asia. Triterpene saponins isolated from P. grandiflorum are the main biologically active compounds, among which polygalacin D (PGD) has been reported to be an anti-tumor agent. However, its anti-tumor mechanism against hepatocellular carcinoma is unknown. This study aimed to explore the inhibitory effect of PGD in hepatocellular carcinoma cells and related mechanisms of action. We found that PGD exerted significant inhibitory effect on hepatocellular carcinoma cells through apoptosis and autophagy. Analysis of the expression of apoptosis-related proteins and autophagy-related proteins revealed that this phenomenon was attributed to the mitochondrial apoptosis and mitophagy pathways. Subsequently, using specific inhibitors, we found that apoptosis and autophagy had mutually reinforcing effects. In addition, further analysis of autophagy showed that PGD induced mitophagy by increasing BCL2 interacting protein 3 like (BNIP3L) levels.In vivo experiments demonstrated that PGD significantly inhibited tumor growth and increased the levels of apoptosis and autophagy in tumors. Overall, our findings showed that PGD induced cell death of hepatocellular carcinoma cells primarily through mitochondrial apoptosis and mitophagy pathways. Therefore, PGD can be used as an apoptosis and autophagy agonist in the research and development of antitumor agents.
Humans ; Mitophagy ; Carcinoma, Hepatocellular/pathology* ; Liver Neoplasms/pathology* ; Cell Line ; Autophagy ; Apoptosis ; Membrane Proteins ; Proto-Oncogene Proteins/genetics* ; Tumor Suppressor Proteins/pharmacology*

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.

ObjectiveTo explore the mechanism of Jianpi Yishen Huazhuo prescription in the improvement of ovarian function in polycystic ovary syndrome （PCOS）. MethodSeventy female SD rats in SPF grade were randomly divided into 6 groups， 15 in the blank group and 15 in the model group， 10 in the metformin group （0.1 g·kg^-1·d^-1）， and 10 in the low （1.275 g·kg^-1·d^-1）， medium （2.55 g·kg^-1·d^-1）， and high-dose （5.10 g·kg^-1·d^-1） Jianpi Yishen Huazhuo prescription groups. The blank group was given normal saline （10 mL·kg^-1·d^-1） by gavage and ordinary feed， and the other groups were given letrozole （1 mg·kg^-1·d^-1） by gavage combined with high-fat feed for 21 days to induce the model of PCOS. After modeling， the blank group and model group were given equal volume normal saline by gavage， and each drug group was given the corresponding dose of the drug by gavage for 30 days. The changes in body mass and fasting blood glucose （FPG） of rats before and after modeling were compared. Hematoxylin eosin （HE） staining was used to observe the morphological change in the ovaries of rats in each group. The serum levels of follicle stimulating hormone （FSH）， luteinizing hormone （LH）， testosterone （T）， anti-Mullerian hormone （AMH）， and estradiol （E₂） were measured by enzyme-linked immunosorbent assay （ELISA）， and the LH/FSH ratio was calculated. Immunohistochemical staining （IHC） and Western blot were used to detect the protein expression levels of nucleoside binding oligomerization domain protein like receptor 3 （NALP3）， apoptosis-associated speck-like protein （ASC）， cysteine protease-1 （Caspase-1）， nuclear transcription factor-κB （NF-κB）， interleukin-1β （IL-1β）， interleukin-18 （IL-18）， and interleukin-6 （IL-6） in the rat ovaries. ResultAs compared with the blank group， large follicles with polycystic expansion were found in the ovaries of the model group， no dominant follicles were found， the granular layer of follicles decreased and arranged loosely， and the number of corpus luteum decreased significantly. Serum T， LH， AMH and LH/FSH increased in the model group （P<0.05， P<0.01）， while FSH and E₂ decreased （P<0.05， P<0.01）. The relative protein expression levels of NALP3， ASC， Caspase-1， NF-κB， IL-1β， IL-18， and IL-6 increased （P<0.05， P<0.01） in the ovaries of the model group. Compared with the model group， the low， medium， and high-dose Jianpi Yishen Huazhuo prescription groups and the metformin group showed growing follicles and corpus luteum at all levels， the number of cystic expanding follicles decreased， the thickness of follicular granular layer increased， the number of follicular fluid increased， mature follicles were visible， and the local morphology of oocytes was complete. Serum T， LH， AMH， and LH/FSH in these groups decreased （P<0.05， P<0.01）， while E₂ and FSH increased （P<0.05）. The relative protein expressions of NALP3， ASC， Caspase-1， NF-κB， IL-1β， IL-18， and IL-6 in the ovaries of these groups decreased （P<0.05， P<0.01）. There was no significant difference among the treatment groups. ConclusionBy inhibiting the activation of NLRP3 inflammasome， Jianpi Yishen Huazhuo prescription reduces the release of NALP3， ASC， Caspase-1， NF-κB， IL-18， IL-1β， and IL-6 inflammatory factors in ovarian tissues， regulates endocrine level， and effectively reduces PCOS inflammatory statu， so as to play a role in improving ovarian function.

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.