Objective:To explore the clinical characteristics and genetic etiology of a child with Spondyloocular syndrome (SOS) in order to enhance the awareness and understanding of this disease.Methods:A 3.5-year-old boy with SOS who had presented at the Department of Medical Genetics of Hunan Children′s Hospital on August 10, 2023 due to the repeated fractures for over 2 years and after binocular cataract surgery was selected as the study subject. Clinical data of his pedigree were collected, and peripheral venous blood samples were collected for the extraction of genomic DNA and subjected to trio-whole exome sequencing. Candidate variants were verified by Sanger sequencing and analyzed with bioinformatic software. This study was approved by the Medical Ethics Committee of Hunan Children′s Hospital (No. KYSQ2022-263).Results:The child had manifested repeated fractures, bilateral bowed femur, osteoporosis, cataract, atrial septal defect, and developmental delay. Ultrasonography has revealed fetal edema, peritoneal effusion, pleural effusion and polyhydramnios. Trio-whole exome sequencing and Sanger sequencing revealed that he has harbored compound heterozygous variants of the XYLT2 gene, namely c. 1103_1104delAG (p.Gln368Argfs*8) and c. 1238_1253delinsA (p.Val413_Pro418delinsGlu), which were inherited from his phenotypically normal father and mother, respectively. Neither variant was reported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG) and recommendations from the Clinical Genome Resource (ClinGen), the c. 1103_1104delAG was predicted as a pathogenic variant (PVS1+ PM2_Supporting+ PP4), whilst the c.1238_1253delinsA was predicted as a likely pathogenic variant (PM4+ PM3+ PM2_Supporting+ PP4). Conclusion:The c. 1103_1104delAG and c. 1238_1253delinsA compound heterozygous variants of the XYLT2 gene probably underlay the pathogenesis in this child. Above finding has enriched the phenotypic and mutational spectrum of SOS, and provided a basis for the clinical diagnosis, treatment, prognosis assessment and genetic counseling for this pedigree.

Objective To evaluate the ability of average nucleotide identity(ANI)and 16S rDNA technology on the identification of Salmonella.Methods The genomes and corresponding serovars of global Salmonella were downloaded in batch from the GenBank database.The classical strains of Salmonella were used as typing strains.The ANI analysis was conducted by the fastANI software according to the silent parameters.The species and serovars of Salmonella were identified by their 16S rDNA using the online software SpeciesFinder.Results Among the downloaded 2 306 genomes,1 767 strains of Salmonella had 178 serovars,with 323 strains(18.3%)of Salmonella Typhimurium and 300 strains(17.0%)of Salmonella Enteritidis being the most common.The ANI analysis showed that with a 95%threshold,only 30 strains(1.3%)of Salmonella were assigned to a specific subspecies,while the remaining 2 276 strains(98.7%)of Salmonella could be assigned to 2-5 subspecies.When the threshold was 97%,all 2 306 strains(100%)of Salmonella could be assigned to a specific subspecies.Based on the analysis of 16S rDNA,only 1 072 strains(46.5%)of Salmonella were identified,of which 95.2%(1 021/1 072)of Salmonella subspecies were completely consistent with the results of ANI(≥97%)analysis.Only 2.4%(19/784)of Salmonella strains showed consistent results with known serovars.Conclusion ANI is more suitable for the identification of Salmonella species and subspecies,and ANI≥97%can be used as the identification standard for Salmonella subspecies.The sensitivity of 16S rDNA for the identification of Salmonella still needs to be improved.

Objective To analyze the prevalence and molecular characteristics of global Salmonella Typhimurium.Method The ge-nome and the corresponding serovars as well as meta-information of global Salmonella were downloaded in batch from the National Cen-ter for Biotechnology Information(NCBI)database using the online softwares,ResFinder,PlasmidFinder,Mobile Element Finder and MLST,to analyze the distribution of antibiotic resistant genes(ARGs),plasmids,mobile genetic elements(MGEs)and the sequence types(STs)among S.Typhimurium strains.Results A total of 101 ARGs were detected in 323 strains of S.Typhimurium,among which the most common was aac(6')-Iaa(322/323,99.69％),followed by sul2(155/323,47.99％),aph(3")-Ib(128/323,39.63％),aph(6)-Id(127/323,39.32％),tet(B)(109/323,33.75％),and blaTEM-1B(106/323,32.82％).Totally,36 plasmids were identified,among which IncFⅡ(S)(110/323,34.06％)and IncFⅠB(S)(108/323,33.44％)were the most common.Moreo-ver,376 MGEs were found,including 367 insertion sequences and nine transposons,among which MITEEc1(322/323,99.69％)and ISSen1(308/323,95.36％)were the most popular.Furthermore,323 strains of S.Typhimurium were assigned into 32 different STs,a-mong which,ST19(157/323,48.61％)and ST34(105/323,32.51％)were the most common accounting for over 82％.Among 115 strains of S.Typhimurium from human,18 STs were identified including ST19(52/115,45.22％)and ST34(39/115,33.91％)which were the most common.Conclusion S.Typhimurium carried multiple types of ARGs,in addition to the wide distribution of a large number of insertion sequences and plasmids,whch provide favorable conditions for the spread of drug resistance.Therefore,the meas-ures of prevention and control against the infection from this bacterium should be strengthened.

Colorectal cancer (CRC) is a prevalent malignant tumor often leading to liver metastasis and mortality. Despite some success with PD-1/PD-L1 immunotherapy, the response rate for colon cancer patients remains relatively low. This is closely related to the immunosuppressive tumor microenvironment mediated by tumor-associated macrophages (TAMs). Our previous work identified that a phosphoglycerate mutase 1 (PGAM1) allosteric inhibitor, HKB99, exerts a range of anti-tumor activities in lung cancer. Here, we found that upregulation of PGAM1 correlates with increased levels of M2-like tumor-associated macrophages (TAMs) in human colon cancer samples, particularly in liver metastatic tissues. HKB99 suppressed tumor growth and metastasis in cell culture and syngeneic tumor models. M2-polarization, induced by colon cancer cell co-culture, was reversed by HKB99. Conversely, the increased migration of colon cancer cells by M2-TAMs was remarkably restrained by HKB99. Notably, a decrease in TAM infiltration was required for the HKB99-mediated anti-tumor effect, along with an increase in CD8⁺ T cell infiltration. Moreover, HKB99 improved the efficacy of anti-PD-1 treatment in syngeneic tumors. Overall, this study highlights HKB99's inhibitory activity in TAM-mediated colon cancer progression. Targeting PGAM1 could lead to novel therapeutic strategies and enhance the effectiveness of existing immunotherapies for colon cancer.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. Fat accumulation "sensitizes" the liver to insult and leads to nonalcoholic steatohepatitis (NASH). G protein-coupled receptor 35 (GPR35) is involved in metabolic stresses, but its role in NAFLD is unknown. We report that hepatocyte GPR35 mitigates NASH by regulating hepatic cholesterol homeostasis. Specifically, we found that GPR35 overexpression in hepatocytes protected against high-fat/cholesterol/fructose (HFCF) diet-induced steatohepatitis, whereas loss of GPR35 had the opposite effect. Administration of the GPR35 agonist kynurenic acid (Kyna) suppressed HFCF diet-induced steatohepatitis in mice. Kyna/GPR35 induced expression of StAR-related lipid transfer protein 4 (STARD4) through the ERK1/2 signaling pathway, ultimately resulting in hepatic cholesterol esterification and bile acid synthesis (BAS). The overexpression of STARD4 increased the expression of the BAS rate-limiting enzymes cytochrome P450 family 7 subfamily A member 1 (CYP7A1) and CYP8B1, promoting the conversion of cholesterol to bile acid. The protective effect induced by GPR35 overexpression in hepatocytes disappeared in hepatocyte STARD4-knockdown mice. STARD4 overexpression in hepatocytes reversed the aggravation of HFCF diet-induced steatohepatitis caused by the loss of GPR35 expression in hepatocytes in mice. Our findings indicate that the GPR35-STARD4 axis is a promising therapeutic target for NAFLD.

OBJECTIVES: To explore the molecular mechanism for thyroid cancer metastasis via analyzing the role of microRNA (miR)-21-5p and its target gene recombinant sclerostin domain containing protein 1 (SOSTDC1) in thyroid cancer. METHODS: The target miR-21-5p was screened through bioinformatics analysis and cell verification, and the thyroid cancer cell lines was transfected with miR-21-5p inhibitor. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) test, flow cytometry, and cell scratch test were used to detect the proliferation, apoptosis and migration of thyroid cancer cells in the miR-21-5p inhibitor group and the inhibitor control group, respectively. The luciferase report experiment was used to verify the relationship between miR-21-5p and SOSTDC1, Western blotting was used to detect the expression levels and phosphorylation levels of SOSTDC1,phosphatidylinositol 3 kinase (PI3K), protein kinase B (Akt) and mitogen-activated protein kinases (MAPK), extracellular regulated protein kinases (ERK) in thyroid cancer cells. RESULTS: MiR-21-5p was significantly increased in thyroid cancer cells,which was negatively correlated with SOSTDC1 ( CONCLUSIONS MiR-21-5p in thyroid cancer cells can target the expression of SOSTDC1 and affect the activities of PI3K/Akt and MAPK/ERK, thereby inhibiting the apoptosis of thyroid cancer cells and promoting cell proliferation and migration.
Adaptor Proteins, Signal Transducing ; Apoptosis/genetics* ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Humans ; MicroRNAs/genetics* ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Thyroid Neoplasms/genetics*

【Objective】 To explore the relationship between changes in the entorhinal cortex （EC） of traumatic brain injury （TBI） and cognitive function based on structural magnetic resonance imaging. 【Methods】 MRI was performed in 26 patients with clinically confirmed TBI after admission， and the Mini-mental State Examination （MMSE） was followed up 6 months later. The TBI patients were classified as mild TBI and moderate to severe TBI according to the post-traumatic Glasgow coma scale （GCS）. We compared the differences in age， gender， education level， hypertension， diabetes， TBI operation history， and follow-up MMSE between the two groups. Then the morphology， surface area， volume and thickness of the patient’s EC were evaluated using the visual score and Freesurfer software， and finally the correlation between EC parameters and MMSE was analyzed. 【Results】 The study included 12 cases of mild TBI and 14 cases of moderate to severe TBI. There were no statistical differences in age， gender， years of education， hypertension， diabetes or TBI operation history. However， the two groups differed significantly in follow-up MMSE. Visual evaluation showed statistical difference in the left EC scores. Structural MRI showed that the volume and thickness of left EC were statistically different between the two groups. The correlation analysis showed that there was a positive correlation between the thickness of left EC and MMSE （r=0.430， P<0.05）. 【Conclusion】 Entorhinal cortex atrophy after TBI is related to the severity of trauma， and it can reflect the long-term cognitive level of patients， which can be used as a noninvasive and reliable imaging marker for evaluating cognitive impairment after TBI.

With the development of China's economy and aging of the population,patient's demands for nursing are increasingly high,thus it is very important to cultivate high-end and practical nursing personnel.This paper analyzes the necessity and feasibility of the development of Nurse Practitioner in China,and explores the qualifications and management of Nurse Practitioner,the job content of Nurse Practitioner,and the training of Nurse Practitioner.

Objective To assess the value of contrast-enhanced ultrasonography(CEUS)in evaluating the therapeutic efficacy of uterine leiomyoma treated by radiofrequency ablation(RFA)and to discuss the value of its application.Methods Forty-four patients which were diagnosed as uterine leiomyomas by ultrasonic guidance needle puncture biopsy preoperation were examined by CEUS before and one week after RFA treatment respectively,and the patho-results were got again after the surgery.Routine ultrasonography was performed in 1,3,6,12 months after the treatment to compare the volume change of uterine leiomyomas with the change of the clinical symptoms.Results After the treatment,CEUS showed that the contrast agent didn't appear in thirty-five patients'uterine leiomyomas and the nonperfusion regions matched the size of the uterine leiomyomas completely.The contrast agent enhanced on the edge of the uterine leiomyomas in nine,the patho-results confirmed that the nonperfusion regions of the contrast agent were necrosis tissues and the marginal local enhancement regions were incomplete necrosis.Three month after RFA treatment,the uterine leiomyomas began to shrink,which showed obviously in 6 months after the treatment.There were significant differences in the parameters before and after the treatment(P＜0.05).Clinical symptoms improved obviously in thirty-five patients(90%)after the treatment.Conclusions RFA is an effective minimally invasive surgery of the uterine leiomyoma.CEUS can identify the treatment range and the remaining tissues.It has significant value in guiding the supplementary treatment.