Purpose To investigate whether ketogenic diet(KD)can promote cognition by regulating brain metabolism and neuroinflammation in Alzheimer's disease model mice.Materials and Methods Twenty male APP/PS1 mice were randomly assigned to either a KD group(APP/PS1+KD)or a regular diet group(APP/PS1),with 10 mice in each group.Additionally,10 wild-type C57BL/6 male mice served as the control group.The APP/PS1+KD group was fed with a ketogenic feed,the APP/PS1 group received a regular diet,and the control group was maintained on standard chow for a duration of 4 months.Blood ketone levels of mice were monitored after 4 weeks and 4 months of continuous feeding.Cognitive function was assessed via the morris water maze.18F-FDG and 18F-DPA-714 micro PET/CT were performed to evaluate the effects of KD on glucose metabolism and neuroinflammation across various brain regions in the Alzheimer's disease mice.Following PET/CT imaging,brain tissue samples were collected,and the hippocampal Cal region was selected for paraffin sectioning to detect the expression of glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1 through immunofluorescence analysis.Results In the Morris water maze in the fourth month,compared with the control group,the APP/PS1 group had a significantly longer escape latency on days 3-4(P＜0.05 or P＜0.01).Compared with the control group,the APP/PS1 group showed a significant decrease in relative 18F-FDG uptake in brain regions such as the striatum,hippocampus,dorsal thalamus,central gray matter,superior colliculus,olfactory bulb,and midbrain(P＜0.01,P＜0.05).Compared with the APP/PS1 group,the APP/PS1+KD group showed a significant increase in relative 18F-FDG uptake in the hippocampus and dorsal thalamus(P＜0.01).Compared with the control group,the APP/PS1 group showed a significant increase in relative uptake of 18F-DPA-714 in brain regions such as the striatum,hippocampus and hypothalamus(P＜0.05 or P＜0.001).Compared with the APP/PS1 group,the APP/PS1+KD group decreased the relative uptake of 18F-DPA-714 in the hippocampus(P＜0.01).Compared with the control group and APP/PS1+KD group,the fluorescence intensity of glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1 protein in the brain(hippocampus)of APP/PS1 group mice was significantly increased(both P＜0.01).Conclusion KD has the potential to ameliorate cognitive and behavioral deficits in APP/PS1 mice by enhancing brain metabolism and attenuating neuroinflammation.

GLIl-altered mesenchymal tumors are a relatively rare type of mesenchymal tumor that is common in the head and neck.It is a newly added tumor type in the World Health Organization Tumor Classification of Head and Neck(5th edition).This article reports a case of GLI1-altered mesenchymal tumor occurring at the left tongue and reviews the relevant literature to summarize the pathological morphological characteristics,immunophenotype,molecular changes,clinical manifestations,and prognosis of the disease.

Hepatic stellate cell(HSC)activation is a key link in the development of liver fibrosis.The metabolic reprogramming of activated HSC has become a hot topic in current research,especially the change of glycolysis is an important factor in regulating HSC activation.Based on the metabolic reprogramming in the process of HSC activation,this paper expounds the mechanism of regulating HSC activation and liver fibrosis through glycolysis,and reviews the research progress of traditional Chinese medicine and its active ingredients in regulating HSC glycolysis to prevent and treat liver fibrosis.Liver fibrosis is a complex pathological process involving multiple factors and pathways.From the perspective of regulating the glycolysis of activated HSC,it can provide a new idea for the development of anti-liver fibrosis drugs.

Objective:To evaluate the safety of early enteral nutrition (EEN) support in patients with severe intra-abdominal infection and intestinal fistulas.Methods:This was a retrospective cohort study. We collected relevant clinical data of 204 patients with severe intra-abdominal infection and intestinal fistulas who had been managed in the No. 1 Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University between 1 January 2017 and 1 January 2020. The patients were allocated to EEN or delayed enteral nutrition (DEN) groups depending on whether enteral nutrition had been instituted within 48 hours of admission to the intensive care unit. The primary outcome was 180-day mortality. Other outcomes included rates of intraperitoneal hemorrhage, septic shock, open abdominal cavity, bloodstream infection, mechanical ventilation, and continuous renal replacement therapy. Risk factors for mortality were analyzed by logistic regression.Results:There were no significant differences in hematological data or other baseline characteristics between the two groups at the time of admission to the intensive care unit (all P>0.05). However, septic shock (31.2% [15/48] vs. 15.4% [24/156], χ 2=4.99, P=0.025), continuous renal replacement therapy (27.1% [13/48] versus 9.0% [14/156], χ 2=8.96, P=0.003), and 180-day mortality (31.2% [15/48] vs. 7.7% [12/156], χ 2=15.75, P<0.001) were significantly more frequent in the EEN than the DEN group (all P<0.05). Multivariate regression analysis showed that older age (OR=1.082, 95%CI:1.027-1.139, P=0.003), worse Acute Physiology and Chronic Health Evaluation (APACHE) II scores (OR=1.189, 95%CI: 1.037-1.363, P=0.013), higher C-reactive protein (OR=1.013, 95%CI:1.004-1.023, P=0.007) and EEN (OR=8.844, 95%CI:1.809- 43.240, P=0.007) were independent risk factors for death in patients with severe intra-abdominal infection and intestinal fistulas. Conclusion:EEN may lead to adverse events and increase mortality in patients with both enterocutaneous fistulas and severe abdominal infection. EEN should be implemented with caution in such patients.

Objective:To evaluate the safety of early enteral nutrition (EEN) support in patients with severe intra-abdominal infection and intestinal fistulas.Methods:This was a retrospective cohort study. We collected relevant clinical data of 204 patients with severe intra-abdominal infection and intestinal fistulas who had been managed in the No. 1 Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University between 1 January 2017 and 1 January 2020. The patients were allocated to EEN or delayed enteral nutrition (DEN) groups depending on whether enteral nutrition had been instituted within 48 hours of admission to the intensive care unit. The primary outcome was 180-day mortality. Other outcomes included rates of intraperitoneal hemorrhage, septic shock, open abdominal cavity, bloodstream infection, mechanical ventilation, and continuous renal replacement therapy. Risk factors for mortality were analyzed by logistic regression.Results:There were no significant differences in hematological data or other baseline characteristics between the two groups at the time of admission to the intensive care unit (all P>0.05). However, septic shock (31.2% [15/48] vs. 15.4% [24/156], χ 2=4.99, P=0.025), continuous renal replacement therapy (27.1% [13/48] versus 9.0% [14/156], χ 2=8.96, P=0.003), and 180-day mortality (31.2% [15/48] vs. 7.7% [12/156], χ 2=15.75, P<0.001) were significantly more frequent in the EEN than the DEN group (all P<0.05). Multivariate regression analysis showed that older age (OR=1.082, 95%CI:1.027-1.139, P=0.003), worse Acute Physiology and Chronic Health Evaluation (APACHE) II scores (OR=1.189, 95%CI: 1.037-1.363, P=0.013), higher C-reactive protein (OR=1.013, 95%CI:1.004-1.023, P=0.007) and EEN (OR=8.844, 95%CI:1.809- 43.240, P=0.007) were independent risk factors for death in patients with severe intra-abdominal infection and intestinal fistulas. Conclusion:EEN may lead to adverse events and increase mortality in patients with both enterocutaneous fistulas and severe abdominal infection. EEN should be implemented with caution in such patients.

Objective:To study the expression of methyltransferase-like protein 14 (METTL14) in epithelial ovarian cancer and its clinical significance, and to explore the effect of METTL14 expression on the proliferation, invasion and migration of ovarian cancer cells.Methods:Immunohistochemistry (IHC) was used to detect METTL14 expression in tumor tissue samples, and analyze the relationships among METTL14 expression, clinicopathological factors, and prognosis in ovarian cancer. Lentiviral vectors and small interfering RNA (siRNA) were used to up-regulate and down-regulate the METTL14 expression in ovarian cancer cell lines A2780 and SKOV3, respectively. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was used to detect the N6-methyladenosine (m6A) content in ovarian cancer cells. Cell counting kit-8 (CCK-8), wound healing assay, and transwell assay were used to examine the function of METTL14 expression in the cells.Results:(1) The IHC score of METTL14 protein was 6.2±3.7 in 20 samples of ovarian cancer tissues and 3.3±2.5 in 15 samples of normal ovarian tissues, and the difference was statistically significant ( t=-2.64, P=0.012). Among the patients who suffered from ovarian cancer, there were 69 cases with high expression of METTL14 protein (IHC score≥6), accounting for 57.0% (69/121), and the cases with low expression of METTL14 protein (IHC score<6) accounting for 43.0% (52/121). Compared with the patients with low expression of METTL14, the patients with high expression of METTL14 had later stages, higher rates of lymph node metastasis, abdominal metastasis, and more ascite amount. The differences were statistically significant (all P<0.05). The overall survival rate was significantly lower in patients with high METTL14 expression than the low expression ( P=0.009). (2) LC-MS/MS data showed that the relative expression of m6A in A2780 and SKOV3 cells in the lentivirus (LV)-METTL14 group were 0.213±0.024 and 0.181±0.018, which were significantly higher than those in the LV-normal control (NC) group (0.109±0.022 and 0.128±0.020; all P<0.05). While the relative expression of m6A in A2780 and SKOV3 cells in the si-METTL14 group were 0.063±0.012 and 0.069±0.015, which were significantly lower than the expression in si-NC group of 0.108±0.014 and 0.121±0.014 (all P<0.05). CCK-8 assay showed that the absorbance values were significantly lower in the si-METTL14 group compared with the si-NC group at 36, 48, 60 hours (all P<0.05); while were significantly increased in the LV-METTL14 group compared with the LV-NC group at 48, 60 hours (all P<0.01). Scratch wound assays showed that the migration rate of the si-METTL14 group was lower than those of the si-NC group, while the LV-METTL14 group were higher than the LV-NC group by 24 hours, the differences were statistically significant (all P<0.01). Cell migration and invasion were detected by transwell migration and invasion assays. After cultivated for 24 hours, the invasion cell number and the migration cell number in the si-METTL14 group were less than those in the si-NC group. While the invasion cell number and the migration cell number in the LV-METTL14 group were more than those in the LV-NC group, respectively. The differences were statistically significant (all P<0.01). Conclusion:Patients with high METTL14 expression have a worse prognosis in ovarian cancer, which may increase the m6A modification of ovarian cancer cells and promote cells proliferation, invasion and migration.

Objective:To analyze the indications for prenatal diagnosis and summarize the pregnancy outcomes and its influencing factors of pregnant women with fetal sex chromosome aneuploidy (SCA).Methods:This study retrospectively enrolled 1 372 fetuses prenatally diagnosed with SCA in Medical Genetics Center of Guangdong Women and Children Hospital from January 2013 to December 2021. The relationship between prenatal diagnosis indications and SCA as well as between ultrasound abnormalities, pregnancy outcomes and SCA types were analyzed by Chi-square test and trend Chi-square test. Results:The most common prenatal diagnosis indication was abnormal non-invasive prenatal testing (NIPT) (61.6%, 845/1 372). The most common SCA type was 47,XXY in cases with indications of abnormal NIPT and advanced maternal age, mosaic in cases with high or borderline risk of Down syndrome, and 45,X in cases with increased nuchal translucency or cystic hygroma. Of 1 372 pregnant women with fetal SCA, 17 were lost to follow-up, seven had intrauterine fetal death, and 1 348 (98.3%) were followed up for pregnancy outcomes including 36.3% (489/1 348) continued pregnancies and 63.7% (859/1 348) terminations. Pregnancy termination rates decreased sequentially in pregnant women carrying fetuses with 45,X, 47,XXY, mosaic, 47,XXX and 47,XYY [99.2% (247/249), 74.5% (307/412), 67.8% (156/230), 36.6% (86/235) and 28.4% (63/222), χ2trend=352.76, P<0.001]. There was no significant difference in pregnancy termination rates among the cases with different mosaic mutations (all P>0.05). The pregnancy termination rate was higher in fetuses with SCA complicated by ultrasound structural abnormalities than in those without ultrasound abnormalities and those with ultrasound soft markers [91.5% (182/199) vs 57.1% (535/937) and 67.0% (142/212), χ2 were 83.68 and 36.85, both P<0.001]. Moreover, the pregnancy termination rate in fetuses with SCA complicated by ultrasound soft markers was higher than those without ultrasound abnormalities ( χ2=7.13, P<0.05). Conclusions:NIPT abnormality is the most common indication for prenatal diagnosis of SCA. The types of SCA and ultrasound findings are important factors determining whether the pregnancy would be continued or not.

Resection is one of the most important treatments for esophageal squamous cell carcinoma, and routine postoperative follow-up is an effective method for early detection and treatment of recurrent metastases, which can improve patients' quality of life and prognosis. This consensus aims to provide a reference for colleagues responsible for postoperative follow-up of esophageal squamous cell carcinoma patients in China, and further improve the standardization of the diagnosis and treatment of esophageal squamous cell carcinoma.

Genomic disorders caused by pathogenic copy number variation (pCNV) have proven to underlie a significant proportion of birth defects. With technological advance, improvement of bioinformatics analysis procedure, and accumulation of clinical data, non-invasive prenatal screening of pCNV (NIPS-pCNV) by high-throughput sequencing of maternal plasma cell-free DNA has been put to use in clinical settings. Specialized standards for clinical application of NIPS-pCNV are required. Based on the discussion, 10 pCNV-associated diseases with well-defined conditions and 5 common chromosomal aneuploidy syndromes are recommended as the target of screening in this consensus. Meanwhile, a standardized procedure for NIPS-pCNV is also provided, which may facilitate propagation of this technique in clinical settings.
Aneuploidy ; Cell-Free Nucleic Acids/genetics* ; Consensus ; DNA Copy Number Variations ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; Pregnancy ; Prenatal Diagnosis

With the rapid development and adaptation of high-throughput sequencing in clinical settings, application of exome sequencing (ES) has been gradually expanded from pediatric to prenatal diagnosis in recent years. There is an urgent need to establish criteria for clinical grade ES in order to facilitate such a complex testing. The standardization of pre- and post-test consultation, quality control for sample processing process and validation of bioinformatics data analysis, and more importantly data interpretation and reporting, as well as appropriate reporting scope, is of great importance for health care stakeholders. To achieve this, a committee composed of a wide range of healthcare professionals has proposed an ES standard for prenatal diagnosis. This has provided expert opinion on the genetic counseling and reporting standards of prenatal ES for the purpose of applying ES technology in prenatal setting.