Objective To investigate the mechanism of Yes-associated protein 1(YAP1)ameliorating aristolochic acid 1(AAI)-induced liver injury in mice based on untargeted metabolomics techniques.Methods There were 83-week-old male hepatocyte-specific Yap1 gene knockout mice(genotyped as Yap1Flox/Flox,Albumin-Cre,aka.Yap1LKO)were randomly selected as the Yap1LKO+AAI group,and 8 Yap1Flox control mice as the Yap1Flox+AAI group.Both groups were injected intraperitoneally with AAI at a dose of 2.5 mg·kg-1·d-1 for 14 consecutive days.Genotypes were identified by tail PCR;serum alanine transaminase(ALT)and aspartate transaminase(AST)activities were determined by microplate assay;histopathological changes of liver tissue were observed by HE staining;and the protein expression of YAP1 in liver tissue was determined by immunohistochemistry.The untargeted metabolomics approach was used to analyze the liver tissue differential metabolites,and the samples were analyzed by ultra performance liquid chromatography-quadrupole-electrostatic field orbit trap high-resolution mass spectrometry,and the differential metabolites were screened by principal component analysis(PCA),Partial least square-discriminant analysis(PLS-DA),and orthogonal partial least squares-discriminant analysis(OPLS-DA);using HMDB database and METLIN database to identify metabolites,and the pathway enrichment of differential metabolites was analyzed by KEGG database.Results(1)After 14 days of AAI induction,the increase of body mass in Yap1LKO mice was lower than that in Yap1Flox mice,but there was no statistical significance(P＞0.05).On day 14,compared with the Yap1Flox+AAI group,the serum ALT and AST enzyme activities in the Yap1LKO+AAI group of mice were significantly increased(P＜0.05),and the histopathological damage of the liver was significantly aggravated.The livers of the Yap1Flox mice had a positive protein expression of YAP1,whereas the Yap1LKO mice did not have a positive protein expression of YAP1.(2)A total of 139 differential metabolites with significant changes(VIP＞1 and P＜0.05)were screened by metabonomic analysis;compared with Yap1LKO+ AAI group,62 liver metabolites in Yap1Flox+AAI group were up-regulated,including choline,taurine,hypotaurine,α-linolenic acid,eleostearic acid,chenodeoxycholic acid and so on.Seventy-seven metabolites were down-regulated including glycerophosphocholine,L-phosphatidylcholine,L-glutamine,L-serine,L-glutathione,5-methionine,phenylalanine,glucose 6-phosphate,lactic acid,uric acid glycosides,etc..KEGG-enriched pathways were mainly choline metabolism,glycerophospholipid metabolism,insulin resistance,glutathione metabolism,etc..Conclusion Hepatocyte-specific Yap1 gene knockout exacerbated AAI-induced liver injury in mice,and YAP1 was involved in the regulation of choline metabolism and glycerophospholipid metabolism through the up-regulation of unsaturated fatty acids,such as choline and taurine,which ameliorated AAI-induced liver injury in mice.

【Objective】 To clarify the concept of health literacy among children and adolescents with accidental injuries through literature review and analysis. 【Methods】 A systematic search was conducted across multiple databases, including China National Knowledge Infrastructure, Wanfang database, VIP database, China Biomedical literature database, PubMed, CINAHL, and PscyINFO database. The literature was analyzed using Rodgers′ evolutionary concept analysis method. 【Results】 A total of 56 articles were included. The health literacy of children and adolescents with accidental injuries comprised three conceptual attributes:cognition, emotion and behavior. The influencing factors included children′s demographic factors, family and school related factors and social related factors. The result can be beneficial to reduce the occurrence of injury events, save family economic expenditure and alleviate the burden on social medical resources. However, there is currently a lack of specific measurement tools for assessing health literacy in this population, as the existing evaluation items are drawn from general health literacy scales. 【Conclusions】 The concept of health literacy among children and adolescents with accidental injuries is multifaceted and evolving. Future research should focus on exploring the characteristics of health literacy among children and adolescents of different ages and regions from their own perspectives. Additionally, efforts should be made to refine the concept and develop specialized measurement tools to facilitate further studies in this area.

Klebsiella pneumoniae(K.pneumoniae)is important zoonotic pathogen causing multiple local and systemic infections.At present,the drug resistance of K.pneumoniae is serious,and mul-tiple drug-resistant strains continue to emerge.Even the incidence of drug-resistant K.pneumoniae infection is increasing year by year.In this study,K.pneumoniae clinical isolate 71Y was used as the starting strain,and a phage with strong lytic activity was successfully obtained from sewage samples.The phage was named vB_KpnP_71Y(abbreviated as P71Y),the general biological char-acteristics and genome of P71Y were further studied and analyzed.P71Y can form clear plaque with a diameter of 2-5 mm and a translucent halo ring on the host bacterium 71Y lawn.Electron micros-copy observation shows that P71Y is a member of the order Autographiviridae and family Caudovi-rales.The incubation period for P71Y infected with K.pneumoniae is about 3 minutes,and one in-fection cycle lasts for about 50 minutes.Each infection of a bacterium can produce approximately 58 progeny phage virus particles.Cleavage spectra showed that the phage could lysate K20 and K57 serotypes of K.pneumoniae.The phage had good stability at 4-50 ℃ and pH values of 3-12.Genom-ic analysis revealed that P71Y contained a double-stranded DNA with a total length of 39 700 bp and a G+C content of 53％.There are a total of 53 coding genes,P71Y does not carry virulence factors and drug resistance genes,which has shown genetic safety.This study isolated a novel lytic phage that can cleave multiple serotypes of K.pneumoniae,which provided experimental materials for the study of the interaction between bacteriophages,different serotypes of K.pneumoniae,and the application of phage for the prevention and controlling of infections caused by multi-drug-re-sistant K.pneumoniae.

BACKGROUND: Preliminary studies have indicated that Shexiang Baoxin Pill (MUSKARDIA) has a coronary artery dilation effect and increases the coronary blood flow, relieving the symptoms of angina. This study aimed to evaluate the benefit of MUSKARDIA on patients with stable coronary artery disease (CAD) and diabetes mellitus (DM). METHODS: This was a subgroup analysis of a multicenter, randomized, placebo-controlled phase IV trial. CAD patients with a medical history of DM or baseline fasting blood glucose (FBG) ≥7.0 mmol/L were grouped according to the treatment (standard therapy plus MUSKARDIA or placebo). The primary outcome was major adverse cardiovascular events (MACEs), which was the composite outcome of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. The secondary outcome was the composite outcome of all-cause death, non-fatal myocardial infarction, non-fatal stroke, hospitalization for unstable angina or heart failure, and coronary angioplasty. RESULTS: MACEs occurred in 2.6% (9/340) and 4.8% (18/376) of patients in the MUSKARDIA and placebo groups, respectively ( P  = 0.192). Secondary composite outcome was significantly less frequent with MUSKARDIA than with placebo (15.3% [52/340] vs . 22.6% [85/376], P  = 0.017). Risk of MACEs (hazard ratio [HR] = 0.69, 95% confidence interval [CI]: 0.31-1.57) was comparable between two groups. In patients with uncontrolled DM (≥4 measurements of FBG ≥7 mmol/L in five times of follow-up), the risk of secondary outcome was significantly lower with MUSKARDIA (5/83, 6.0%) than with placebo (15/91, 16.5%) (HR = 0.35, 95%CI: 0.13-0.95). CONCLUSION: As an add-on to standard therapy, MUSKARDIA shows a trend of reduced MACEs in patients with stable CAD and DM. Furthermore, MUSKARDIA may reduce the frequency of all-cause death, hospitalization, and coronary angioplasty in this population, especially in those with uncontrolled DM. TRIAL REGISTRATION ChiCTR.org.cn, ChiCTR-TRC-12003513.
Humans ; Coronary Artery Disease/complications* ; Diabetes Mellitus, Type 2/drug therapy* ; Myocardial Infarction/complications* ; Stroke/epidemiology*

The effect of anti-programmed cell death 1 (anti-PD-1) immunotherapy is limited in patients with hepatocellular carcinoma (HCC). Yes-associated protein 1 (YAP1) expression increased in liver tumor cells in early HCC, and Akkermansia muciniphila abundance decreased in the colon. The response to anti-PD-1 treatment is associated with A. muciniphila abundance in many tumors. However, the interaction between A. muciniphila abundance and YAP1 expression remains unclear in HCC. Here, anti-PD-1 treatment decreased A. muciniphila abundance in the colon, but increased YAP1 expression in the tumor cells by mice with liver tumors in situ. Mechanistically, hepatocyte-specific Yap1 knockout (Yap1^LKO) maintained bile acid homeostasis in the liver, resulting in an increased abundance of A. muciniphila in the colon. Yap1 knockout enhanced anti-PD-1 efficacy. Therefore, YAP1 inhibition is a potential target for increasing A. muciniphila abundance to promote anti-PD-1 efficacy in liver tumors. Dihydroartemisinin (DHA), acting as YAP1 inhibitor, increased A. muciniphila abundance to sensitize anti-PD-1 therapy. A. muciniphila by gavage increased the number and activation of CD8⁺ T cells in liver tumor niches during DHA treatment or combination with anti-PD-1. Our findings suggested that the combination anti-PD-1 with DHA is an effective strategy for liver tumor treatment.

Objective:To explore the feasibility of deep learning technology for renal artery recognition in retroperitoneal laparoscopic renal surgery videos.Methods:From January 2020 to July 2021, the video data of 87 cases of laparoscopic retroperitoneal nephrectomy, including radical nephrectomy, partial nephrectomy, and hemiurorectomy, were retrospectively analyzed. Two urological surgeons screened video clips containing renal arteries. After frame extraction, annotation, review, and proofreading, the labeled targets were divided into training set and test set by the random number table in a ratio of 4∶1. The training set was used to train the neural network model. The test set was used to test the ability of the neural network to identify the renal artery in scenes with different difficulties, which was uniformly transmitted to the YOLOv3 convolutional neural network model for training. According to the opinion of two senior doctors, the test set was divided into high, medium, and low discrimination of renal artery and surrounding tissue. High identification means a clean renal artery and a large exposed area. For middle recognition degree, the renal artery had a certain degree of blood immersion, and the exposed area was medium. Low identification means that the exposed area of the renal artery was small, often located at the edge of the lens, and the blood immersion was severe, which may lead to lens blurring. In the surgical video, the annotator annotated the renal artery truth box frame by frame. After normalization and preprocessing, all images were input into the neural network model for training. The neural network output the renal artery prediction box, and if the overlap ratio (IOU) with the true value box was higher than the set threshold, it was judged that the prediction was correct. The neural network test results of the test set were recorded, and the sensitivity and accuracy were calculated according to IOU.Results:In the training set, 1 149 targets of 13 videos had high recognition degree, 1 891 targets of 17 videos had medium recognition degree, and 349 targets of 18 videos had low recognition degree. In the test set, 267 targets in 9 videos had high recognition degree, 519 targets in 11 videos had medium recognition degree, and 349 targets in 18 videos had low recognition degree. When the IOU threshold was 0.1, the sensitivity and accuracy were 52.78% and 82.50%, respectively. When the IOU threshold was 0.5, the sensitivity and accuracy were 37.80% and 59.10%, respectively. When the IOU threshold was 0.1, the sensitivity and accuracy of high, medium and low recognition groups were 89.14% and 87.82%, 45.86% and 78.03%, 32.95%, and 76.67%, respectively. The frame rate of the YOLOv3 algorithm in real-time surgery video was ≥15 frames/second. The false detection rate and missed detection rate of neural network for renal artery identification in laparoscopic renal surgery video were 47.22% and 17.49%, respectively (IOU=0.1). The leading causes of false detection were similar tissue and reflective light. The main reasons for missed detection were image blurring, blood dipping, dark light, fascia interference, or instrument occlusion, etc.Conclusions:Deep learning-based renal artery recognition technology is feasible. It may assist the surgeon in quickly identifying and protecting the renal artery during the operation and improving the safety of surgery.

Objective To investigate the influence of postoperative groin pressure on transabdominal preperitoneal hernioplasty (TAPP).Methods From Mar 2015 to Jul 2016 113 TAPP cases were prospectively divided into two groups,with observation group not taking any measures and intervention group using salt bag of 500 g to compress inguinal region for 12 hours.Postoperative recovery was compared between the two groups.Results After 48 hours,there was no significant difference between the two groups in pain,local complications,scrotum or labia majora swelling remission rate and urinary retention (P ＞ 0.05).However,the observation group had a less foreign body sensation (P =0.038).After 1 month,the two groups had no significant difference in terms of pain,foreign body sensation,sexual life and scrotum or labia majora swelling residual rate (P ＞ 0.05).Conclusions Groin region compression after TAPP does not help alleviate the pain,or reduce the incidence of local complications,and it does increase the foreign body sensation.

OBJECTIVETo explore the genetic cause for two familial Angelman syndrome cases and correlation between the clinical phenotypes and their genetic basis.

METHODSKaryotyping analysis and microarray assay were carried out to exclude chromosome anomalies and uniparental disomy. The UBE3A gene was analyzed for potential point mutations, deletions, insertions and splice site mutations. Reverse transcription PCR was used to evaluate splicing mutation of the RNA transcripts.

RESULTSDNA sequencing showed the proband of family 1 has carried a novel maternal UBE3A splice acceptor site mutation, resulting in a guanine-to-cytosine transversion (IVS15-1G>C). Reverse transcription PCR revealed the proband and his mother both carried heterozygous mutant transcripts with loss of 54 and 59 nucleotides in exon 16, respectively. The proband displayed severe mental retardation, ataxia, seizures and inappropriate laughter. The siblings of family 2 has carried a novel maternal missense mutation in exon 16 of the UBE3A gene (c.2540C>T). She also presented with mental retardation, absent speech, mild ataxia and inappropriate laughter.

CONCLUSIONThe novel IVS15-1G>C and c.2540 C>T mutations of the UBE3A gene probably underlie the AS in the two families. Compared with small-scale mutations, larger fragments mutations can produce more severe phenotypes.

Angelman Syndrome ; genetics ; Female ; Humans ; Karyotyping ; Male ; Mutation ; Ubiquitin-Protein Ligases ; genetics

OBJECTIVETo explore the correlation between 13q33-q34 microdeletion and clinical phenotype.

METHODSRoutine chromosomal banding was performed to analyze the karyotype, while array-based comparative genomic hybridization (aCGH array) and single nucleotide polymorphism array(SNP array) were employed to investigate the genome copy number variations.

RESULTSThe karyotype of patient 1 was 46, XY, 9qh+,13qs. Patient 2 showed 46, XX, der (13). Patient 3 showed 46, XX, r(13) (p11.2q32) [43]/45, XX, 13[4]/46, XX, r(13;13) [2]/47, XX, 2r(13;13) [1]. Patient 4 did not undergo chromosome karyotyping analysis. Array analysis showed that four patients have different microdeletions in 13q33-34 region and had common features of 13q33-q34deletion including intellectual disability, facial dysmorphism, microcephaly, hypotonia, low birth weight and genital abnormality.

CONCLUSIONThe severity of phenotypes showed no correlation with the size of deletion in 13q33-q34. The lower percentage of patients with congenital heart disease suggested a complex pathogenesis of such disease. EFNB2, LIG4 and SOX1 in 13q33-34 region are promising candidates for mental retardation. LIG4 was also a likely candidate for microcephaly.

Child, Preschool ; Chromosome Banding ; methods ; Chromosome Deletion ; Chromosomes, Human, Pair 13 ; genetics ; Female ; Genetic Testing ; methods ; Humans ; Infant ; Intellectual Disability ; genetics ; Male

Objective To estimate prenatal diagnoses strategy with abnormal results of non-invasive prenatal testing (NIPT) based on a case of mosaic for trisomy 22.Methods The pregnanct woman was recruited from Department of Prenatal Diagnosis Center of Xinhua Hospital.Ultrasound scans suggested fetal nuchal translucency was 3.5 mm.Peripheral venous blood was drawn from the pregnant woman for NIPT at 12+2 weeks gestation.For further prenatal diagnosis, amniocentesis was conducted at 16+2 weeks gestation, and karyotype analysis combination with chromosome microarray analysis (CMA) was executed to analysis amniocytes.Results NIPT results suggested that chromosome 21, 18 and 13 were normal and supplementary reports suggested that chromosome 22 were slightly above the normal range.Karyotype analyzed 35 cultured cells.Each of them revealed a normal female karyotype.However, CMA results suggested that chromosome 22 gain mosaic and its copy number was 2.26.The fetus was diagnosed as high possibility of mosaic for trisomy 22.Conclusions Combined with the NIPT results, which was slightly gain mosaic of chromosome 22, a prenatal diagnosis strategy were proposed.When NIPT results suggest chromosomal abnormities, karyotype analysis combination with CMA to diagnose were recommended.