Objective To investigate the relationship between the degree of liver fibrosis in non-alcoholic fatty liver disease(NAFLD)and the left ventricular structure and function of the heart.Methods A total of 411 patients with NAFLD admitted to the Sec-ond Affiliated Hospital of Xinjiang Medical University from June 2022 to April 2023 were collected.NAFLD patients were stratified using the FIB-4 non-invasive liver fibrosis scoring system and divided into the progressive fibrosis group(n=138)and non-progressive fi-brosis group(n=273).A total of 151 patients with normal abdominal ultrasound examination during the same period were selected as the control group,the relationship between the severity of liver fibrosis in NAFLD patients and the left ventricular structure and function of the heart were analyzed.Results Liver fibrosis was a risk factor for cardiac diastolic function limitation in NAFLD patients(P＜0.05),and the more severe the degree of liver fibrosis,the more severe the cardiac diastolic function limitation.Conclusion The degree of liver fi-brosis in NAFLD is significantly correlated with limited left ventricular diastolic function;it may be related to changes in the left ventricu-lar structure of the heart.

Glyceryl phenylbutyrate(GPB)serves as a long-term management medication for Ornithine transcarbamylase deficiency(OTCD),effectively controlling hyperammonemia,but there is a lack of experience in using this medicine in China.This article retrospectively analyzes the case of a child diagnosed with OTCD at Shanghai Children's Medical Center,Shanghai Jiao Tong University School of Medicine,including a review of related literature.After diagnosis,the patient was treated with GPB,followed by efficacy follow-up and pharmacological monitoring.The 6-year and 6-month-old male patient exhibited poor speech development,disobedience,temper tantrums,and aggressive behavior.Blood ammonia levels peaked at 327 μmol/L;urine organic acid analysis indicated elevated uracil levels;cranial MRI showed extensive abnormal signals in both cerebral hemispheres.Genetic testing revealed de novo mutation in the OTC gene(c.241T＞C,p.S81P).Blood ammonia levels were approximately 43,80,and 56 μmol/L at 1,2,and 3 months after starting GPB treatment,respectively.During treatment,blood ammonia was well-controlled without drug-related adverse effects.The patient showed improvement in developmental delays,obedience,temperament,and absence of aggressive behavior.

Cellulose synthase (CesA), one of the key enzymes in the biosynthesis of cellulose in plants, plays an important role in plant growth and plant resistance. In this study, a total of 21 AsCesA genes from Aquilaria sinensis were systematically identified and the physico-chemical characteristics were analyzed based on genome database and bioinformatical methods. The phylogenetic tree was constructed and the gene location on chromosome, cis-acting elements in the 2 000 basepairs upstream regulatory regions and conservative motifs were analyzed. The AsCesA proteins were mainly located on the plasma membrane. The number of amino acids of the proteins ranged from 390 to 1 261. The isoelectric point distributed from 5.67 to 8.86. All of the 21 AsCesA proteins possessed the transmembrane domains, the number of which was from 6 to 8. The genes were classified into 3 groups according to the phylogenetic relationship. Obvious differences were observed in motif composition in genes from different groups. However, motif2, motif6, motif7 and motif10 were observed in all of AsCesA proteins. Analysis of cis-acting elements indicated that AsCesA genes family has cis-acting elements related to plant hormones, abiotic stresses, and biological processes. Seven AsCesA genes with differential expression were selected according to the calli transcriptome data induced by NaCl at different times and their expression levels under different abiotic stresses were analyzed by quantitative real-time PCR. The results indicated that salt, low temperature, drought, and heavy metal stresses could affect the expression level of AsCesA genes, and the abundance of AsCesA1, AsCesA3 and AsCesA20 showed a significant change, implying their potential important roles to the abiotic stresses. The accumulation pattern of cellulose content under different abiotic stresses was similar to the expression trend of AsCesA genes. Our results provide valuable insights into the role of cellulose synthase in A.sinensis in plant defense.

Objective: To explore the characteristics of plasma Epstein-Barr virus (EBV) DNA in primary infection in pediatric cases. Methods: The laboratory and clinical data of 571 children diagnosed with EBV primary infection in Children's Hospital of Fudan University during September 1^st, 2017 to September 30^th, 2018 were retrospectively analyzed. According to the results of plasma EBV DNA, they were divided into positive group and negative group. According to the EBV DNA, they were devided into high plasma virol load group and low plasma virol load group. The Chi-square test, Wilcoxon rank sum test were used to compare the differences between groups. Results: Among the 571 children with EBV primary infection, 334 were males and 237 were females. The age of first diagnosis was 3.8 (2.2, 5.7) years. There were 255 cases in positive group and 316 cases in negative group. The percentage of cases with fever,hepatomegaly and (or) splenomegaly, elevated transaminase in the positive group were higher than those in the negative group (235 cases (92.2%) vs. 255 cases (80.7%), χ²=15.22, P<0.001; 169 cases (66.3%) vs. 85 cases (26.9%), χ²=96.80, P<0.001; and 144 cases (56.5%) vs. 120 cases (38.0%), χ²=18.27, P<0.001; respectively).In the positive group, 70 cases were followed up for 46 (27, 106) days, 68 cases (97.1%) turned negative within 28 days, with the exception of 2 cases (2.9%) developed chronic active EBV infection by follow-up revision.There were 218 cases in high plasma viral DNA copies group and 37 cases in low copies group. More cases presented with elevated transaminases in the high plasma viral DNA copies group than those in the low group (75.7% (28/37) vs. 56.0%(116/207), χ²=5.00, P=0.025).Both the positive rate of EBV DNA in peripheral blood leukocytes (84.2% (266/316) vs. 44.7% (255/571), χ²=76.26, P<0.001) and the copies of EBV DNA (7.0×10⁷ (1.3×10⁷, 3.0×10⁸) vs. 3.1×10⁶ (1.6×10⁶, 6.1×10⁶) copies /L, Z=15.23, P<0.001) were higher than that of plasma. Conclusions: In immunocompetent pediatric cases diagnosed as EBV primary infection, cases with positive plasma EBV DNA were prone to have fever, hepatomegaly and (or) splenomegaly, and elevated transaminase than those with negative plasma viral DNA. The plasma EBV DNA usually turns negative within 28 days after initial diagnosis.Most cases with high viral load in plasma showed elevated aminotransferase.
Female ; Male ; Humans ; Child ; DNA, Viral ; Herpesvirus 4, Human ; Epstein-Barr Virus Infections ; Hepatomegaly ; Retrospective Studies ; Splenomegaly ; Fever ; Transaminases

Dihydroflavonol 4-reductase (DFR) plays an essential role in the biosynthesis of anthocyanin and regulation of plant flower color. Based on the transcriptome data of Cistanche tubulosa (Schenk) Wight, a full-length cDNA sequence of CtDFR gene was cloned by reverse transcription-polymerase chain reaction (RT-PCR). CtDFR contains an open reading frame (ORF) of 1 263 bp which encodes 420 amino acids with a predicted molecular weight of 47.5 kDa. The sequence analysis showed that CtDFR contains a nicotinamide adenine dinucleotide phosphate (NADPH) binding domain and a specific substrate binding domain. The expression analysis indicated that CtDFR was highly expressed in red and purple flowers, and the relative expression levels were 4.04 and 19.37 times higher than those of white flowers, respectively. The recombinant CtDFR protein was expressed in E.coli BL21 (DE3) using vector pET-28a-CtDFR and was purified. In vitro enzyme activity analysis, CtDFR could reduce three types of dihydroflavonols including dihydrokaempferol, dihydroquercetin, and dihydromyricetin to leucopelargonidin, leucocyanidin and leucodelphinidin. Subcellular localization analysis showed that CtDFR was mainly localized in the cytoplasm. These results demonstrate that CtDFR plays an important role in regulation of flower color in C. tubulosa and make a valuable contribution for the further investigation on the regulation mechanism of C. tubulosa (Schenk) Wight flower color.

Tbx18,Wt1,and Tcf21 have been identified as epicardial markers during the early embryonic stage.However,the gene markers of mature epicardial cells remain unclear.Single-cell transcriptomic analysis was performed with the Seurat,Monocle,and CellphoneDB packages in R software with standard pro-cedures.Spatial transcriptomics was performed on chilled Visium Tissue Optimization Slides(10x Genomics)and Visium Spatial Gene Expression Slides(10x Genomics).Spatial transcriptomics analysis was performed with Space Ranger software and R software.Immunofluorescence,whole-mount RNA in situ hybridization and X-gal staining were performed to validate the analysis results.Spatial transcriptomics analysis revealed distinct transcriptional profiles and functions between epicardial tissue and non-epicardial tissue.Several gene markers specific to postnatal epicardial tissue were identified,including Msln,C3,Efemp1,and Upk3b.Single-cell transcriptomic analysis revealed that cardiac cells from wildtype mouse hearts(from embryonic day 9.5 to postnatal day 9)could be categorized into six major cell types,which included epicardial cells.Throughout epicardial development,Wt1,Tbx18,and Upk3b were consistently expressed,whereas genes including Msln,C3,and Efemp1 exhibited increased expression during the mature stages of development.Pseudotime analysis further revealed two epicardial cell fates during maturation.Moreover,Upk3b,Msln,Efemp1,and C3 positive epicardial cells were enriched in extracellular matrix signaling.Our results suggested Upk3b,Efemp1,Msln,C3,and other genes were mature epicardium markers.Extracellular matrix signaling was found to play a critical role in the mature epicardium,thus suggesting potential therapeutic targets for heart regeneration in future clinical practice.

OBJECTIVE: To investigate the role of tacrolimus-binding protein 38 (FKBP38) in follicle development and the mechanism by which Fkbp38 gene deletion causes premature ovarian insufficiency (POI). METHODS: The Cre-loxp system was used to construct oocyte-specific Fkbp38 knockout transgenic mice. The genotype of the transgenic mice was identified using PCR, and the expression of FKBP38 in the oocytes was verified. The numbers of primordial follicles, primary follicles, secondary follicles and antral follicles in Fkbp38 knockout mice and non-transgenic littermate control mice were counted with HE staining under a microscope for analyzing the effect of Fkbp38 deletion on follicular development. The fertility and serum sex hormone levels of the mice were determined by reproduction experiments and ELISA to assess ovarian function. Ovarian granulosa cell apoptosis of the mice was assessed using TUNEL assay. The activity of the downstream target protein of phosphorylated ribosomal S6 (PS6) of mTOR signaling pathway was detected, and the expressions of BCL-2 and BAX proteins were determined using immunofluorescence assay for assessing oocyte development in the mice. RESULTS: The oocyte-specific Fkbp38 knockout transgenic mouse model was successfully constructed, which showed decreased fertility, disordered sex hormone levels, and significantly reduced primordial follicles, primary follicles and secondary follicles in the ovary (P < 0.05), demonstrating POI-like changes. Compared with the control mice, oocyte-specific Fkbp38 knockout caused activation of the mTOR signaling pathway, significantly increased apoptosis of the granulosa cells, and obviously increased the BAX/BCL- 2 ratio by increasing BAX expression and reducing BCL-2 expression in the oocytes (P < 0.05). CONCLUSION FKBP38 plays an important role in follicle development, and Fkbp38 gene deletion in mice causes POI possibly by activating the mTOR signaling pathway and inducing granulosa cell apoptosis.
Female ; Humans ; Mice ; Animals ; Primary Ovarian Insufficiency/genetics* ; Apoptosis ; Signal Transduction ; Proto-Oncogene Proteins c-bcl-2 ; Granulosa Cells ; Mice, Transgenic ; Mice, Knockout ; TOR Serine-Threonine Kinases

BACKGROUND: Recent cardiovascular outcome trials (CVOTs) changed the therapeutic strategy of guidelines for type 2 diabetes. We compared the characteristics of patients from real-world hospital settings with those of participants in recent pragmatic randomized trials. METHODS: This electronic medical record (EMR)-based retrospective observational study investigated the data of patients with diabetes from inpatient and outpatient settings in West China Hospital of Sichuan University from January 1, 2011, to June 30, 2019. We identified patients meeting the inclusion criteria of a pragmatic randomized trial (EMPA-REG OUTCOME) based on EMRs and compared their baseline characteristics with those of the trial participants. The cutoff for the clinical significance of each characteristic was set as its minimal clinically important difference based on expert consultation. RESULTS: We included 48,257 inpatients and 36,857 outpatients with diabetes and found that 8389 (17.4%) inpatients and 2646 (7.2%) outpatients met the inclusion criteria for the EMPA-REG OUTCOME trial. Compared with the trial population, the real-world inpatients meeting the eligibility criteria of the EMPA-REG OUTCOME had similar age, blood pressure, and lipid profiles but comprised of fewer males, metformin users, anti-hypertensive drug users, and aspirin users, and had a lower body mass index. The group of outpatients meeting the eligibility criteria had fewer males, similar age, fewer metformin users, fewer insulin users, fewer anti-hypertensive drug users, and fewer aspirin users compared with the trial population. CONCLUSIONS The trial population in EMPA-REG OUTCOME represents only a small portion of patients with diabetes from the inpatient and outpatient departments of a Chinese tertiary medical center. Evidence localization in different clinical settings and validation are essential to enabling extrapolation of the results from CVOTs in patients with diabetes to Chinese clinical practice.
Benzhydryl Compounds ; Canagliflozin ; Cardiovascular Diseases ; China ; Diabetes Mellitus, Type 2/drug therapy* ; Glucosides ; Humans ; Male ; Sodium-Glucose Transporter 2 Inhibitors ; Tertiary Care Centers

Objective To investigate the prevalence and influencing factors of intestinal protozoan infections among rural children in Henan Province. Methods A total of 104 survey sites were sampled from 35 counties (cities) in Henan Province using the stratified cluster sampling method to investigate the prevalence of intestinal protozoan infections among rural children from 2014 to 2015. The trophozoites and cysts of intestinal protozoa were identified using the iodine staining method and the physiological saline direct smear method (one detection for one stool sample). The prevalence of intestinal protozoan infections was compared among rural children with different characteristics, and the factors affecting intestinal protozoan infections among rural children were identified. Results The overall prevalence of intestinal protozoan infections was 0.60% (40/6 771) among rural children in Henan Province from 2014 to 2015. There were 7 species of intestinal protozoa identified, and there was no species-specific prevalence (χ² = 37.732, P = 0.000). No significant differences were found in prevalence of intestinal protozoan infections among rural children in terms of gender (χ² = 1.793, P = 0.181), age (χ² = 1.443, P = 0.486), occupation (χ² = 0.219, P = 0.896) or ecological region (χ² = 1.700, P = 0.637). In addition, terrain (χ² = 2.311, P = 0.510), economic level (χ² = 4.322, P = 0.229), source of drinking water (χ² = 0.731, P = 0.393), eating raw vegetables (χ² = 1.134, P = 0.287) and deworming (χ² = 1.089, P = 0.297) had no remarkable effects on the prevalence of intestinal protozoan infections among rural children in Henan Province; however, the prevalence of intestinal protozoan infections varied significantly among rural children living in regions with different coverage of non-harmless toilets (χ² = 10.050, P = 0.018). Conclusion The prevalence of intestinal protozoan infections is low among rural children in Henan Province.

Objective:To investigate the antitumor effect and the mechanism of Dunhuang Pingweiwan and its decomposed recipes based on phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway in SCG-7901 gastric cancer-mice. Method:The subcutaneous tumor bearing model of SCG-7901 gastric cancer in mice was established， and the the mice were randomized into model group， Dunhuang Pingweiwan group （14.04 g·kg^-1·d^-1）， Huoxue Jiedu group （6.50 g·kg^-1·d^-1）， Wenzhong Sanhan group （3.64 g·kg^-1·d^-1） and cisplatin group （2 mg·kg^-1·d^-1）， with 8 mice in each group. From the 8^th day of inoculation， the mice were administered for 10 consecutive days. The mice were weighed and the general conditions were observed every other day. On the next day of the last administration， the mice were sacrificed， and the tumor was removed and weighed to calculate the anti-tumor rate. The histopathological changes were observed by hematoxylin-eosin （HE） staining， and the mRNA and protein expressions of PI3K， Akt， and mTOR in tumor tissues were detected by real-time polymerase chain reaction（Real-time PCR） and immunohistochemistry （IHC）， respectively. Result:From the 10^th day of inoculation， the mice in cisplatin group were generally in poor condition and their body mass decreased. The mice in model group， Dunhuang Pingweiwan group， Huoxue Jiedu group and Wenzhong Sanhan group were generally fair， and their body mass increased without significant difference among groups. The tumor inhibition rates of Dunhuang Pingweiwan， Huoxue Jiedu， Wenzhong Sanhan and cisplatin groups were 30.74%， 24.80%， 4.19% and 63.84%， respectively. Except for Wenzhong Sanhan group， tumor weight of the other treatment groups was significantly lower than that of the model group （P<0.01）， and there was no significant difference between the Dunhuang Pingweiwan and Huoxue Jiedu group. Dunhuang Pingweiwan and Huoxue Jiedu group could significantly reduce tumor cell density and cause tumor cell necrosis. Compared with the model group， the expressions of PI3K， Akt， and mTOR mRNA and protein in the Dunhuang Pingweiwan， Huoxue Jiedu and cisplatin groups significantly decreased （P<0.05， P<0.01）， and there was no significant difference between the Dunhuang Pingweiwan group and Huoxue Jiedu group. Conclusion:Dunhuang Pingweiwan and its decomposed recipes （Huoxue Jiedu） have a certain anti-tumor effect on the SCG-7901 gastric cancer-mice， and the mechanism may be related to the down-regulation of key molecules in the PI3K/Akt/mTOR signaling pathway.