Serum fibroblast growth factor-2 levels complement vital biomarkers for diagnosing heart failure.

BACKGROUND: Early diagnosis of atrial fibrillation is important as it is crucial for improving patient outcomes. Fibroblast growth factor-2 (FGF2) may serve as a diagnostic biomarker for heart failure due to its ability to promote cardiac fibrosis and hypertrophy; however, the relationship between FGF2 concentration and heart failure is unclear. Therefore, this study aimed to explore whether FGF2 could aid in distinguishing patients with heart failure from healthy controls and those with dyspnea without heart failure. Additionally, to evaluate the possible correlation between serum FGF2 levels and its diagnostic parameters in patients with heart failure. METHODS: Plasma FGF2 concentration was measured in 114 patients with a complaint of dyspnea (enrolled in the study between January 2022 and August 2022). Based on heart failure diagnosis, the patients were assigned to three groups, as follows: heart failure (n = 80), non-heart-failure dyspnea (n = 34), and healthy controls (n = 36), following physical examination. Possible correlations between serum FGF2 levels and other prognostic parameters in patients with heart failure were analyzed. RESULTS: Serum FGF2 levels were higher in patients with heart failure (125.60 [88.95, 183.40] pg/mL) than in those with non-heart-failure dyspnea (65.30 [28.85, 78.95] pg/mL) and healthy controls (78.90 [60.80, 87.20] pg/mL) (p < 0.001). Receiver operating characteristic curve analysis identified FGF2 concentration as a significant predictor in heart failure diagnosis, with an area under the curve of 0.8693 (p < 0.0001). Importantly, in the heart failure group, serum FGF2 concentrations correlated with key prognostic parameters for heart failure, such as reduced left ventricular ejection fraction and elevated serum levels of N-terminal pro-B-type natriuretic peptide. CONCLUSIONS: Elevated serum FGF2 level is strongly associated with an increased risk of heart failure and could serve as a useful biomarker to complement vital diagnostic parameters for heart failure.

Invited review: Good practices in genome-wide association studies to identify candidate sequence variants in dairy cattle.

Genotype data from dairy cattle selection programs have greatly facilitated GWAS to identify variants related to economic traits. Results can enhance the accuracy of genomic prediction, analyze more complex models that go beyond additive effects, elucidate the genetic architecture of a trait, and finally, decipher the underlying biology of traits. The entire process, comprising data generation, quality control, statistical analyses, interpretation of association results, and linking results to biology should be designed and executed to minimize the generation of false-positive and false-negative associations and misleading links to biological processes. This review aims to provide general guidelines for data analysis that address data quality control, association tests, adjustment for population stratification, and significance evaluation to improve the reliability of conclusions. We also provide guidance on post-GWAS strategy and the interpretation of results. These guidelines are tailored to dairy cattle, which are characterized by long-range linkage disequilibrium, large half-sib families, and routinely collected phenotypes, requiring different approaches than those applied in human GWAS. We discuss common limitations and challenges that have been overlooked in the analysis and interpretation of GWAS to identify candidate sequence variants in dairy cattle.

[Application value of whole exon sequencing and immune related indicators in the precision treatment of oral squamous cell carcinoma].

OBJECTIVE: To explore the significance and feasibility of whole exon sequencing and immune related indexes in personalized precision treatment of oral squamous cell carcinoma (OSCC). METHODS: We retrospectively screened the patients who underwent surgery for oral cancer in Peking University Hospital of Stomatology and underwent genetic and immune biomarkers tests between January 2021 and June 2022. Combined with the clinicopathological characteristics of patients, potential targeted drugs and immunotherapy drugs were screened to evaluate the possibility of gene testing benefiting OSCC. The main evaluation indicators included the number of gene mutations, combined positive score (CPS), tumor mutation burden (TMB), microsatellite sequence status and human leukocyte antigen B (HLA-B) locus. Excel was used for statistical analysis. RESULTS: A total of 10 patients were enrolled and 9 were included in this study, including 6 males and 3 females, with an average age of (55.44±9.59) years. The tumor location was buccal (5 cases), tongue (3 cases) and gingival (1 case). The results of genetic testing showed that 3 (33.3%) patients had no gene mutations in the tumor tissue, 5 (55.6%) patients had unique TP53 gene mutations, and 1 (11.1%) patient had TP53 and CHEK1 mutations. However, no drugs were available for targeted therapy of the mutated genes. The genetic tumor gene testing results showed that no genetic tumor gene was found in all the patients, suggesting that OSCC had a low possibi-lity of hereditary tumor. In terms of immune efficacy related markers, CPS test results showed that 8 patients had CPS≥1. TMB detection results showed that the median value of TMB value was 0.72 mutations/Mb, and the range was 0 to 4.32 mutations/Mb. The negative and positive control results of microsatellite sequence status were consistent, indicating that all the tumor tissues detected were microsatellite stability. The results of HLA-B detection showed that only one patient had B62 gene mutation, suggesting that the B44 and B62 related genotypes of HLA-B in OSCC tissue samples were low. CONCLUSION: The present results do not support the wide application and promotion of genetic testing and immune related indexes in OSCC.

[Category of facial symmetry perception after maxillary reconstruction using anterolateral thigh flap].

OBJECTIVE: To preliminarily establish a category of facial symmetry perception after maxillary reconstruction using anterolateral thigh flap (ALTF) by the methods of stereophotogrammetry and subjective assessment. METHODS: The patients underwent maxillectomy due to neoplasms invasion, and all the maxillary defects were reconstructed using ALTF.Three-dimensional (3D) photographs were captured from the patients with a stereophotogrammatrical camera set-up.In the Geomagic software, the mirror image was created by reflecting along an arbitrary plane outside of the face.After the registration, the postoperative side on the original 3D photograph was segmented into 6 areas.The 3D change of the facial soft-tissue was measured using surface-based color map.Twenty laypeople took part in the study as observers, and they were asked to rate the 3D photographs using 5 point Likert-type scale according to their own aesthetic standard.The soft tissue asymmetry was graded according to the score.The collected data were subjected to statistical analysis using the SPSS 24.0 software. RESULTS: In the study, 44 subjects were recruited (21 males and 23 females, age range from 19 to 79 years).The soft-tissue symmetry was graded into three levels according to the subjective scores.The grade Ⅰ was basically symmetrical.The grade Ⅱ was slightly asymmetrical.The grade Ⅲ was obviously asymmetrical.Statistically significant differences were found in the suborbital (P < 0.05) and zygomatic (P < 0.05) areas when comparing all grades of soft-tissue asymmetry, and in the buccal (P < 0.05) and superiolabial (P < 0.05) areas when comparing grades Ⅰ and Ⅲ.The extent of maxillary defect had significant impact on the symmetry of the midface soft-tissue after maxillary reconstruction. CONCLUSION: Varying extent maxillectomy would result in varying degrees of asymmetry, and cause different grades of symmetry perception even if they had been reconstructed using ALTF.The higher the grade, the worse the symmetry of facial soft-tissue.Suborbital and zygomatic areas were important aesthetic units that affected the facial symmetry perception, followed by buccal and superiolabial areas.The clinicians should pay attention to the soft-tissue support in these areas when reconstructing the maxillary defect, especially large defect with orbital floor involved.

[Application of methylene blue near-infrared fluorescence imaging for oral sentinel lymph node mapping in rats].

OBJECTIVE: To explore the concentration range and penetration depth of methylene blue near-infrared fluorescence imaging, and to clarify the role of methylene blue in oral lymphatic drainage and sentinel lymph node localization, so as to lay a foundation for the potential research and application of sentinel lymph node in oral cancer. METHODS: 10% (mass fraction) methylene blue injection was diluted into 29 different concentrations with 0.9% (mass fraction) normal saline, and the concentration range of methylene blue near-infrared fluorescence imaging was determined by near-infrared fluorescence imager. The maximum penetration depth of methylene blue near-infrared fluorescence was determined by covering pigskin with different thicknesses (1, 2, 3, 4 and 5 mm) in methylene blue solution. 0.2 mL methylene blue solution was injected into the submucosal 0.5 cm at the lateral margin of tongue on one side of the rats. The near-infrared fluorescence imager was used for continuously monitoring for 3 hours. The first near-infrared fluorescence hotspot was identified as sentinel lymph node and labeled by percutaneous observation. The rats were then sacrificed and dissected in the head and neck. Near-infrared fluorescence imaging was performed again to observe whether the fluorescent tissue was consistent with the labeled fluorescent hotspot in vitro, and the presence of lymphoid tissue was confirmed by pathological examination after resection. RESULTS: Except that no fluorescence signals were detected in the blank control groups, the fluorescence intensity of methylene blue increased first and then decreased with its solution concentration decreased. When the concentration of methylene blue was diluted to the picomole level, the fluorescence signal could still be detected. The maximum penetration depth of methylene blue fluorescence was 4 mm. Methylene blue near-infrared fluorescence could be localized in oral lymphatic drainage and sentinel lymph node. The fluorescence was sustained for more than 3 hours after methylene blue injection. Methylene blue solution concentrations of 3.34 mmol/L, 6.68 mmol/L, 13.37 mmol/L and 26.74 mmol/L were selected in the rats to map sentinel lymph node by near-infrared fluorescence. CONCLUSION: Methylene blue near-infrared fluorescence has a certain penetrating ability and can transcuta-neously map the sentinel lymph node and their associated lymphatic vessels in rats, which is expected to be further applied in the study of sentinel lymph node in oral cancer.

[Bioinformatics analysis in metagenomic next-generation sequencing of pathogenic microorganisms: current status and challenges].

The clinical application of metagenomic next-generation sequencing (mNGS) in the diagnosis of unknown pathogenic infections and critical infections has become increasingly valuable. Due to the huge volume of mNGS data and the complexity of clinical diagnosis and treatment, mNGS has difficulties in data analysis and interpretation in practical application. Therefore, in the process of clinical practice, it is crucial to grasp the key points of bioinformatics analysis and establish a standardized bioinformatics analysis process, which is an important step in the transformation of mNGS from laboratory to clinic. At present, bioinformatics analysis of mNGS has made great progress, but with the high requirements of clinical standardization of bioinformatics analysis and the development of computer technology, bioinformatics analysis of mNGS is also facing new challenges. This article mainly elaborates on quality control, and identification and visualization of pathogenic bacteria.

Mitochondrial quality control in cartilage damage and osteoarthritis: new insights and potential therapeutic targets.

Osteoarthritis (OA) is a multifactorial arthritic disease of weight-bearing joints concomitant with chronic and intolerable pain, loss of locomotion and impaired quality of life in the elderly population. Although the prevalence of OA increases with age, its specific mechanisms have not been elucidated and effective therapeutic disease-modifying drugs have not been developed. As essential organelles in chondrocytes, mitochondria supply energy and play vital roles in cellular metabolism, proliferation and apoptosis. Mitochondrial quality control (MQC) is the key mechanism to coordinate various mitochondrial biofunctions, primarily through mitochondrial biogenesis, dynamics, autophagy and the newly discovered mitocytosis. An increasing number of studies have revealed that a loss of MQC homeostasis contributes to the cartilage damage during the occurrence and development of OA. Several master MQC-associated signaling pathways and regulators exert chondroprotective roles in OA, while cartilage damage-related molecular mechanisms have been partially identified. In this review, we summarized known mechanisms mediated by dysregulated MQC in the pathogenesis of OA and latent bioactive ingredients and drugs for the prevention and treatment of OA through the maintenance of MQC.

What is an appropriate caesarean delivery rate for China: a multicentre survey.

OBJECTIVE: To assess the current status of caesarean delivery (CD) in China, propose reference CD rates for China overall, and by regions, investigate the main indications for CDs and identify possible areas for safe reduction. DESIGN: A multicentre cross-sectional study. SETTING: A total of 94 hospitals across 23 provinces in China. POPULATION: A total of 73 977 randomly selected deliveries. METHODS: We used a modified Robson classification to characterise CDs in subgroups and by regions, and the World Health Organization (WHO) C-Model to calculate reference CD rates. MAIN OUTCOME MEASURES: CD rates in China. RESULTS: In 2015-2016, the overall CD rate in China was 38.9% (95% CI 38.6-39.3%). Considering the obstetric characteristics of the population, the multivariable model-based reference CD rate was estimated at 28.5% (95% CI 28.3-28.8%). Accordingly, an absolute reduction of 10.4% (or 26.7% relative reduction) may be considered. The CD rate varied substantially by region. Previous CD was the most common indication in all regions, accounting for 38.2% of all CDs, followed by maternal request (9.8%), labour dystocia (8.3%), fetal distress (7.7%) and malpresentation (7.6%). Overall, 12.7% of women had prelabour CDs, contributing to 32.8% of the total CDs. CONCLUSIONS: Nearly 39% of births were delivered by caesarean in China but a reduction of this rate by a quarter may be considered attainable. Repeat CD contributed more than one-third of the total CDs. Given the large variation in maternal characteristics, region-specific or even hospital-specific reference CD rates are needed for precision management of CD. TWEETABLE ABSTRACT: The caesarean rate in 2015-2016 in China was 38.9%, whereas the reference rate was 28.5%.

Potential biomarkers in the fibrosis progression of nonalcoholic steatohepatitis (NASH).

PURPOSE: Fibrosis is the only histological feature reflecting the severity and prognosis of nonalcoholic steatohepatitis (NASH). We aim to explore novel genes associated with fibrosis progression in NASH. METHODS: Two human RNA-seq datasets were downloaded from the public database. Weighted gene co-expression network analysis (WGCNA) was used to identify their co-expressed modules and further bioinformatics analysis was performed to identify hub genes within the modules. Finally, based on two single-cell RNA-seq datasets from mice and one microarray dataset from human, we further observed the expression of hub genes in different cell clusters and liver tissues. RESULTS: 7 hub genes (SPP1, PROM1, SOX9, EPCAM, THY1, CD34 and MCAM) associated with fibrosis progression were identified. Single-cell RNA-seq analysis revealed that those hub genes were expressed by different cell clusters such as cholangiocytes, natural killer (NK) cells, and hepatic stellate cells (HSCs). We also found that SPP1 and CD34 serve as markers of different HSCs clusters, which are associated with inflammatory response and fibrogenesis, respectively. Further study suggested that SPP1, SOX9, MCAM and THY1 might be related to NASH-associated hepatocellular carcinoma (HCC). Receiver operating characteristic (ROC) analysis showed that the high expression of these genes could well predict the occurrence of HCC. At the same time, there were significant differences in metabolism-related pathway changes between different HCC subtypes, and SOX9 may be involved in these changes. CONCLUSIONS: The present study identified novel genes associated with NASH fibrosis and explored their effects on fibrosis from a single-cell perspective that might provide new ideas for the early diagnosis, monitoring, evaluation, and prediction of fibrosis progression in NASH.

miRNA-mRNA associations with inosine monophosphate specific deposition in the muscle of Jingyuan chicken.

1. Inosine monophosphate (IMP), is an essential component for meat flavour and microRNAs (miRNAs) play a vital role in its post-transcriptional regulation. However, the mechanism of how miRNA expression affects muscle-specific IMP deposition is unclear.2. The following study performed transcriptome sequencing and bioinformatics analysis of breast and leg muscle, which have significantly different IMP content in Jingyuan chicken. The differential miRNA-mRNAs were screened out and correlation analysis with IMP content was performed.3. A total of 39 differentially expressed miRNAs (DE miRNAs) and 666 differentially expressed mRNAs (DE mRNAs) were identified between breast muscles and leg muscles. Using miRNA-mRNA integrated analysis, 29 miRNA-target gene pairs were obtained, composed of 13 DE miRNAs and 28 DE mRNAs. Next, purine metabolism, glycolysis/gluconeogenesis, pyruvate metabolism and the biosynthesis of amino acid pathways as necessary for muscle IMP-specific deposition were identified. The differentially expressed gene PKM2, which was significantly enriched in all four pathways, is involved in IMP anabolism in the form of energy metabolism and enzyme activity regulation. The correlation analysis suggested that the gga-miR-107-3p-KLHDC2 negative interaction may be a key regulator in IMP deposition.4. This study explores the functional mechanism of IMP-specific deposition in Jingyuan chicken muscles at the miRNA and mRNA levels and highlights multiple candidate miRNAs and mRNAs for molecular-assisted breeding.

[Naringenin inhibits thoracic aortic aneurysm formation in mice with Marfan syndrome].

OBJECTIVE: To identify whether naringenin plays a protective role during thoracic aneurysm formation in Marfan syndrome. METHODS: To validate the effect of naringenin, Fbn1C1039G/+ mice, the mouse model of Marfan syndrome, were fed with naringenin, and the disease progress was evaluated. The molecular mechanism of naringenin was further investigated via in vitro studies, such as bioluminescence resonance energy transfer (BRET), atomic force microscope and radioligand receptor binding assay. RESULTS: Six-week-old Fbn1C1039G/+ mice were fed with naringenin for 20 weeks. Compared with the control group, naringenin significantly suppressed the aortic expansion [Fbn1C1039G/+ vs. Fbn1C1039G/++naringenin: (2.49±0.47) mm, n=18 vs. (1.87±0.19) mm, n=22, P < 0.05], the degradation of elastin, and the expression and activity of matrix metalloproteinase 2 (MMP2) and MMP9 in the ascending aorta of Fbn1C1039G/+ mice. Besides, treatment with naringenin for 6 weeks also attenuated the disease progress among the 20-week-old Fbn1C1039G/+ mice with established thoracic aortic aneurysms [Fbn1C1039G/+ vs. Fbn1C1039G/++naringenin: (2.24±0.23) mm, n=8 vs. (1.90±0.17) mm, n=8, P < 0.05]. To understand the underlying molecular mechanisms, we examined the effects of naringenin on angiotensin Ⅱ type 1 receptor (AT1) signaling and transforming growth factor-ß (TGF-ß) signaling respectively, which were the dominant signaling pathways contributing to aortopathy in Marfan syndrome as previously reported. The results showed that naringenin decreased angiotensin Ⅱ (Ang Ⅱ)-induced phosphorylation of protein kinase C (PKC) and extracellular regulating kinase 1/2 (ERK1/2) in HEK293A cell overexpressing AT1 receptor. Moreover, naringenin inhibited Ang Ⅱ-induced calcium mobilization and uclear factor of activated T-cells (NFAT) signaling. The internalization of AT1 receptor and its binding to ß-arrestin-2 with Ang Ⅱ induction were also suppressed by naringenin. As evidenced by atomic force microscope and radioligand receptor binding assay, naringenin inhibited Ang Ⅱ binding to AT1 receptor. In terms of TGF-ß signaling, we found that feeding the mice with naringenin decreased the phosphorylation of Smad2 and ERK1/2 as well as the expression of TGF-ß downstream genes. Besides, the serum level of TGF-ß was also decreased by naringenin in the Fbn1C1039G/+ mice. Furthermore, we detected the effect of naringenin on platelet, a rich source of TGF-ß, both in vivo and in vitro. And we found that naringenin markedly decreased the TGF-ß level by inhibiting the activation of platelet. CONCLUSION: Our study showed that naringenin has a protective effect on thoracic aortic aneurysm formation in Marfan syndrome by suppressing both AT1 and TGF-ß signaling.

[Heparin-binding hemagglutinin as a composition antigen of tuberculosis vaccine exerts protective immune effects by inducing IL-17].

To explore the protective immune effect induced by mucosal delivery heparin-binding hemagglutinin (HBHA)-a candidate vaccine antigen of Mycobacterium tuberculosis. Female C57BL/6 mice were between 6 and 8 weeks of age before experimental use. Thirty mice received different immunization strategies and were randomly divided into the control group, the early secreting antigen target-6 (ESAT-6) intranasal immunization group, the HBHA intranasal immunization group, the BCG priming PBS control group, or BCG priming HBHA boost group, 6 mice in each group. In order to analyzed the immune effect, the concentrations of plasma Interleukin-17A (IL-17A) and other cytokines were measured by ELISA. Quantitative real-time PCR analyses were performed to detect the relative quantity (RQ) mRNA of IL-17A in the lung. The lung tissue sections were stained to detect the formation of the tertiary lymphoid structures. The chemokines contributed to formation of the tertiary lymphoid structures were also measured. Flow cytometry was used to detect the frequency of Th1 and Th17 cells in the system. Sixty mice in the BCG priming PBS control group and the BCG priming HBHA boost group were sacrificed at different time points after infection to count the lung bacterial burden. The concentrations of plasma IL-17A and relative quantity of lung IL-17A mRNA were highest in the BCG priming HBHA boost group [(14.76±4.73) pg/mL,RQ (12.27±6.71)], which was significantly higher than the control group [(5.57±2.95) pg/mL,RQ (1.30±0.97)] (t=4.213, P<0.001; t=5.984, P<0.001), and also significantly higher than the BCG priming PBS control group [(6.81±2.18) pg/mL,RQ (1.44±1.16)] (t=3.646 P=0.001; t=6.185 P<0.001). Compared with the BCG priming PBS control group (0.38±0.38)% the frequency of spleen Th17 cells were also significantly increased (t=-0.280, P=0.048) in the BCG-primary HBHA boost group (1.02±0.34)%. In addition, HBHA boosting could promote better formation of the tertiary lymphoid structures in the lung, and decrease the bacterial load on the early stage after BCG challenge. Collectively, mucosal delivery of HBHA can effectively enhance the protective effect after BCG vaccination, and it is a potential candidate vaccine component.

[Risk factors of newly developed nonalcoholic fatty liver disease after pancreaticoduodenectomy].

Objective: To identify the risk factors of newly developed nonalcoholic fatty liver disease(NAFLD) after pancreaticoduodenectomy(PD). Methods: The clinical data of 130 patients who had undergone PD at Department of Hepatopancreatobiliary Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Medical School of Nanjing University from June 2018 to December 2020 were collected retrospectively. There were 74 males and 56 females, with age(M(IQR)) of 62(16) years (range: 22 to 84 years). Twenty-nine patients who developed NAFLD were divided into NAFLD group and 101 patients who did not suffer NAFLD were divided into no NAFLD group. Observation indications included:(1)preoperative demographics,intraoperative and postoperative characteristics; (2)the risk factors of newly developed NAFLD after PD. Count data were analyzed using χ2 test or Fisher's exact test. Measurement data were analyzed by student t test or Mann-Whitney U test. Multivariate analysis was performed using Logistic regression model with a stepwise forward approach. Results: All 130 patients successfully underwent PD and 29 cases(22.3%) developed NAFLD in 6 months after PD. The results of univariate analysis showed that gender,diabetic mellitus,the level of triglyceride preoperatively,and pancreatic ductal adenocarcinoma were the related factors of the development of NAFLD after PD(t=-2.655, χ²=4.563,U=-2.192,χ²=7.044;all P<0.05).Multivariate analysis revealed that gender,body mass index and pancreatic ductal adenocarcinoma were independent risk factors for the development of NAFLD after PD(OR=2.849,1.214,4.165,all P<0.05). Conclusion: Gender, body mass index and pancreatic ductal adenocarcinoma were independent risk factors for the development of NAFLD after PD.

[Impact of adjuvant chemotherapy on prognosis in intrahepatic cholangiocarcinoma patients underwent radical resection].

Objectives: To investigate the clinical value of adjuvant chemotherapy(ACT) in patients with intrahepatic cholangiocarcinoma(ICC) who underwent radical resection and to explore the optimal population that can benefit from ACT. Methods: A retrospective cohort study method was adopted. The clinical and pathological data of 685 patients with ICC who underwent curative intent resection in 10 Chinese hepatobiliary surgery centers from January 2010 to December 2018 were collected;There were 355 males and 330 females. The age(M(IQR)) was 58(14) years (range: 22 to 83 years). Propensity score matching(PSM) was applied to balance the differences between the adjuvant and non-adjuvant chemotherapy groups. Log-rank test was used to compare the prognosis of the two groups of patients. A Bayesian network recurrence-free survival(RFS) prediction model was constructed using the median RFS time (14 months) as the target variable, and the importance of the relevant prognostic factors was ranked according to the multistate Birnbaum importance calculation. A survival prognostic prediction table was established to analyze the population benefiting from adjuvant chemotherapy. Results: Among 685 patients,214 received ACT and 471 did not receive ACT. A total of 124 pairs of patients were included after PSM, and patients in the ACT group had better overall survival (OS) and RFS than those in the non-ACT group(OS: 32.2 months vs. 18.0 months,P=0.003;RFS:18.0 months vs. 10.0 months,P=0.001). The area under the curve of the Bayesian network RFS prediction model was 0.7124. The results of the prognostic factors in order of importance were microvascular invasion (0.158 2),perineural invasion (0.158 2),N stage (0.155 8),T stage (0.120 9), hepatic envelope invasion (0.090 3),adjuvant chemotherapy (0.072 1), tumor location (0.057 5), age (0.042 3), pathological differentiation (0.034 0), sex (0.029 3), alpha-fetoprotein (0.028 9) and preoperative jaundice (0.008 5). A survival prediction table based on the variables with importance greater than 0.1 (microvascular invasion,perineural invasion,N stage,T staging) and ACT showed that all patients benefited from ACT (increase in the probability of RFS≥14 months from 2.21% to 7.68%), with a more significant increase in the probability of RFS≥14 months after ACT in early-stage patients. Conclusion: ACT after radical resection in patients with ICC significantly prolongs the OS and RFS of patients, and the benefit of ACT is greater in early patients.

[Risk factors of peritoneal metastasis in primary appendiceal tumor].

Objective: To investigate the risk factors of peritoneal metastasis in primary appendiceal tumor. Methods: The clinic data of 71 patients with primary appendiceal tumor admitted in the Sixth Affiliated Hospital of Sun Yat-sen University between Dec 2012 and Jan 2019 were enrolled retrospectively. Multivariate logistic regression analysis were carried out to evaluate the risk factors of appendiceal tumor with peritoneal metastasis. Results: Of the 71 patients, 33 were peritoneal metastasis (peritoneal metastasis group) and 38 were non-peritoneal metastasis (no peritoneal metastasis group). Twenty-one patients in the peritoneal metastasis group had increased preoperative cancer embryo antigen (CEA), while 3 cases in the non-peritoneal metastasis group, with statistically significant difference (P<0.001). Sixteen cases in peritoneal metastasis group had increased preoperative carbohydrate antigen 199, while only 2 cases in the non-peritoneal metastasis group, the difference was statistically significant (P<0.001). The pathological type of 30 cases in the peritoneal metastasis group was adenocarcinoma (including mucus adenocarcinoma and colon adenocarcinoma), while 12 cases of adenocarcinoma in the non-peritoneal metastasis group, with statistically significant difference (P<0.001). Twelve cases in the peritoneal metastasis group had lymph node metastasis, while 3 cases in the non-peritoneal metastasis group, the difference is statistically significant (P=0.003). Preoperative CEA elevation and pathological type is adenocarinoma were independent risk factors for peritoneal metastasis of appendiceal cancer (P<0.05). Conclusions: The propensity of peritoneal metastasis in primary appendiceal tumor is high and the outcome is poor. Patients with increased preoperative CEA, adenocarcinoma histopathology are more inclined to have peritoneal metastasis.

[Validation and modification of AJCC 8th edition staging system for hepatocellular carcinoma--analysis based on SEER database].

Objective: To assess the accuracy of the American Joint Committee on Cancer (AJCC) 8th edition staging system for hepatocellular carcinoma (HCC) and to make an appropriate modification. Methods: Data of patients diagnosed with HCC who underwent surgery were extracted from 2004 to 2015 within the SEER database. Overall survival (OS) and disease-specific survival (DSS) of patients were analyzed. Results: A total of 7 911 patients were included and there were 2 117 females and 5 794 males. The male-to-female ratio was 1.00: 0.36. There were 4 050 patients older than 60 years old. Tumor size ranged from 24 to 65 mm. Tumors with single lobes (80.8%) or single lesions (62.8%) were more common. There were 230 cases and 2 052 cases received radiotherapy and chemotherapy, accounting for 2.9% and 25.9%, respectively. The median follow-up was 42 months. Analysis of the 8th edition of AJCC staging system showed that the survival curves of ⅣA stage and ⅢA stage intersected in both OS and DSS, and the differences were not statistically significant between them (both P>0.05). Analysis of patients in subgroup of ⅣA stage showed that there was no statistically significant difference in the four groups of T1N1M0/T2N0M0, T2N1M0/T3N0M0, T3N1M0/T4N0-1M0 and T3N1M0/T1-4N0-1M1 (all P>0.05). Therefore, the modified 8th edition of the AJCC staging system was proposed after retaining the definition of T/N/M in the old edition: ⅠA and ⅠB stages were retained; ⅣA stage was split: T1N1M0 was included in Ⅱ stage, T2N1M0 in Ⅲ stage, and Ⅳ stage included T3N1M0, T4N0-1M0 and T1-4N0-1M1. Cox proportional risk regression analysis of the modified 8th edition of the AJCC staging showed that significant differences were observed among the four groups, with ⅠB/ⅠA (HR=1.462, 95%CI:1.294-1.651), Ⅱ/ⅠB (HR=1.091, 95%CI:1.003-1.186), Ⅲ/Ⅱ (HR=2.034, 95%CI: 1.793-2.307) and Ⅲ/Ⅳ (HR=1.374, 95%CI: 1.192-1.583) for OS, respectively. The similar findings were seen in DSS, with ⅠB/ⅠA (HR=2.007, 95%CI:1.671-2.411), Ⅱ/ⅠB (HR=1.140, 95%CI:1.023-1.271), Ⅲ/Ⅱ (HR=2.344, 95%CI: 2.018-2.724) and Ⅲ/Ⅳ (HR=1.391, 95%CI:1.180-1.639), respectively. Conclusion: The modified AJCC 8th edition staging system could predict the survival outcome of HCC more accurately.

[Choices of emergency treatment and surgical method for ruptured abdominal aortic aneurysms].

Objective: To investigate the emergency management process of ruptured abdominal aortic aneurysm (RAAA), and analyze the perioperative mortality factors of different surgical methods. Methods: The emergency data and hospitalization data of 91 patients with ruptured abdominal aortic aneurysm in Xiangya Hospital of Central South University from June 2010 to June 2019 were retrospectively analyzed.Twelve of the patients died preoperatively due to excessive blood loss, and the remaining 79 patients were hospitalized for open surgery (OSR) or endovascular repair (EVAR).The differences in age, time to hospital arrival, emergency preparation time, first creatinine value, emergency infusion volume, preoperative drop in blood pressure, preoperative use of vasoactive drugs and iliac artery involvement were compared between preoperative death group (n=12) and preoperative survival group (n=79), OSR group (n=50) and EVAR group (n=29), postoperative death group (n=23) and postoperative survival group (n=56). Results: Seventy-nine patients received open surgery or endovascular repair, and 23 died after operation. Age, time to hospital arrival, first creatinine value and emergency infusion volume were (77±11) years, (18±5)h, (469±150) µmol/L, (4 140±1 743) ml in the preoperative death group and (70±10) years, (12±8) h, (228±174) µmol/L, (1 358±1 211) ml in the preoperative survival group, respectively, and the differences were statistically significant (all P<0.05). There were no significant differences in preoperative data, intraoperative treatment and postoperative perioperative mortality between the open surgery group and the endovascular repair group (all P>0.05). The intraoperative blood loss, operation time and aortic occlusion rate in the endovascular repair group were 100 (50, 175) ml, (3.2±0.9) h, 13.8%, respectively, which were better than that in the open surgery group 1700 (600, 3425) ml, (5.2±1.1) h, 100%. The differences were statistically significant (all P<0.05). Age, emergency preparation time, first creatinine value, emergency infusion volume, blood pressure decline rate and vasoactive drug utilization rate in the death group were (77±8) years, (4.1±1.7) h, (456±172) µmol/L, (2 024±1 687) ml, 100%, 100%, respectively, and (68±10) years, (2.7±2.2) h, (135±26) µmol/L, (1 085±825) ml, 21.4%, 12.5% in the survival group, respectively. The differences were statistically significant (all P<0.05). Conclusions: Age, emergency preparation time, first creatinine value, emergency infusion volume, decreased blood pressure and use of vasoactive drugs are all associated with perioperative death in patients with ruptured abdominal aortic aneurysm. EVAR surgery is a better choice if conditions exist.

[Effect of early-life antibiotic exposure on allergic symptoms in children aged 6-11 months and 18-23 months based a birth cohort study].

Objective: To analyze the associations between prenatal and 1-year-old exposure to antibiotics and allergic symptoms in children aged 6-11 months and 18-23 months. Methods: In this study, a prospective birth cohort study was adopted. A total of 2 122 pregnant women were enrolled in Maternal and Child Health Care Center of Ma'anshan from June 2015 to June 2016, and they were followed up from the beginning of pregnancy to children's 24 months of age. Excluding 564 pairs of mothers and children who were lost to follow-up or with incomplete information on the use of antibiotics and children's allergic symptoms, a total of 1 558 pairs of mothers and children were included in the analysis of this study. The parents and children's general demographic information, early-life antibiotic exposure and other data were collected, the information about allergic symptoms in children aged 6-11 months and 18-23 months were investigated by reference to the "International Study of Asthma and Allergies in Childhood (ISAAC)". The univariate and multivariate binary unconditional logistic regression model was used to was used to estimate associations between the effects of early-life antibiotic exposure on allergic symptoms in 2-year-old children. Results: The antibiotic usage rate of pregnant women during pregnancy was 3.4% (53), and the antibiotic usage rates of children between 0 to 2 months, 3 to 5 months, and 6 to 11 months were separately 15.2%(237), 15.5%(242) and 17.3%(269). The total prevalence of allergic diseases in children aged 6 to 11 months was 24.1% (375 children), and the total prevalence of allergic diseases in children aged 18 to 23 months was 22.0% (342 children). After adjust parental (maternal) education level, family monthly income per capita, parental (maternal) allergy history, parental (maternal) age at pregnancy, mother's Body Mass Index (BMI) before pregnancy, exposure to second-hand smoke during pregnancy, delivery method, child gender, birth weight, preterm birth, the use of antibiotics when children were 3-5 months old (RR=1.61,95%CI:1.19-2.17) and 6-11 months old (RR=1.43,95%CI:1.06-1.93) were the risk factors for allergic symptoms at 6-11 months of age; and the use of antibiotics when children were 0-2 months old (RR=1.41, 95%CI: 1.03-1.95), 3-5 months old (RR=1.54, 95%CI: 1.12-2.11) and 6-11 months old (RR=1.58, 95%CI: 1.17-2.14) were the risk factors for allergic symptoms at 18-23 months of age. Conclusion: Children's exposure to antibiotics within 1 year of age was a risk factor for allergic symptoms in children aged 6-11 months and 18-23 months, children should avoid unnecessary antibiotic use in infancy.

[Analysis of related factors for gallstones related gallbladder intraepithelial neoplasia and establishment of prediction models].

Objective: To evaluate the related factors of gallstones related gallbladder intraepithelial neoplasia(GBIN) and establish the prediction models for gallstones related GBIN. Methods: The clinicopathological data of 750 patients who underwent cholecystectomy for gallstones at Department of Hepatobiliary Surgery of the First Affiliated Hospital of Xi'an Jiaotong University from January 2013 to December 2018 and the postoperative pathological examination showed chronic cholecystitis or GBIN were analyzed retrospectively,including 150 cases of gallstones with GBIN and 600 cases of gallstones with chronic cholecystitis.There were 264 males and 486 females with age of (51.3±14.5) years (range: 18 to 90 years).The related factors for gallstones related GBIN were screened by χ2 test and Logistic regression model,and the prediction models were established based on independent related factors and internal validation was conducted.The original data were randomly divided into a training cohort(526 cases) and a validation cohort(224 cases) at a ratio of 7∶3,and the nomogram and tree augmented naïve Bayes were conducted to establish the prediction model for gallstones related GBIN.The consistency index(C-index),calibration chart,area under the receiver operating characteristic curve(AUC) and confusion matrix were used to evaluate the prediction performance of the two models. Results: Univariate analysis showed that age,gallstones history(years),gallbladder size,whether the gallbladder mucosa smooth or not,whether the gallbladder wall thickened or not,gallstones diameter,and number of gallstones were related factors for the occurrence of gallstones related GBIN (χ²=19.957,8.599,9.724,9.301,8.341,15.288,9.169,all P<0.05).Multivariate analysis showed that age (OR=2.23,95%CI:1.50-3.31,P<0.01),gallbladder size (OR=2.11,95%CI:1.17-3.80,P=0.013),whether the gallbladder mucosa smooth or not (OR=1.80,95%CI=1.13-2.88,P=0.014),gallstones diameter(OR=2.98,95%CI:1.71-5.21,P<0.01),and number of gallstones (OR=2.14,95%CI=1.34-3.42,P<0.01) were independent related factors for the occurrence of gallstones related GBIN; the C-index of the nomogram in training cohort and validation cohort were 0.708 and 0.696,respectively.The AUC of the two models in training cohort were 70.60% and 70.73%,and in validation cohort were 68.14% and 67.47%,respectively.The accuracy of the two models in training cohort were 69.96% and 70.72%,and in validation cohort were 66.96% and 67.41%,respectively. Conclusion: Age,gallbladder size,whether the gallbladder mucosa smooth or not,gallstones diameter and number of gallstones are independent related factors for the occurrence of gallstones related GBIN,and the nomogram and tree augmented naïve Bayes prediction models based on the above factors can be used to predict the occurrence of GBIN.

[A prognostic model of intrahepatic cholangiocarcinoma after curative intent resection based on Bayesian network].

Objective: To examine a survival prognostic model applicable for patients with intrahepatic cholangiocarcinoma (ICC) based on Bayesian network. Methods: The clinical and pathological data of ICC patients who underwent curative intent resection in ten Chinese hepatobiliary surgery centers from January 2010 to December 2018 were collected.A total of 516 patients were included in the study.There were 266 males and 250 females.The median age(M(QR)) was 58(14) years.One hundred and sixteen cases (22.5%) with intrahepatic bile duct stones,and 143 cases (27.7%) with chronic viral hepatitis.The Kaplan-Meier method was used for survival analysis.The univariate and multivariate analysis were implemented respectively using the Log-rank test and Cox proportional hazard model.One-year survival prediction models based on tree augmented naive Bayesian (TAN) and naïve Bayesian algorithm were established by Bayesialab software according to different variables,a nomogram model was also developed based on the independent predictors.The receiver operating characteristic curve and the area under curve (AUC) were used to evaluate the prediction effect of the models. Results: The overall median survival time was 25.0 months,and the 1-,3-and 5-year cumulative survival rates was 76.6%,37.9%,and 21.0%,respectively.Univariate analysis showed that gender,preoperative jaundice,pathological differentiation,vascular invasion,microvascular invasion,liver capsule invasion,T staging,N staging,margin,intrahepatic bile duct stones,carcinoembryonic antigen,and CA19-9 affected the prognosis(χ2=5.858-54.974, all P<0.05).The Cox multivariate model showed that gender,pathological differentiation,liver capsule invasion,T stage,N stage,intrahepatic bile duct stones,and CA19-9 were the independent predictive factors(all P<0.05). The AUC of the TAN model based on all 19 clinicopathological factors was 74.5%,and the AUC of the TAN model based on the 12 prognostic factors derived from univariate analysis was 74.0%,the AUC of the naïve Bayesian model based on 7 independent prognostic risk factors was 79.5%,the AUC and C-index of the nomogram survival prediction model based on 7 independent prognostic risk factors were 78.8% and 0.73,respectively. Conclusion: The Bayesian network model may provide a relatively accurate prognostic prediction for ICC patients after curative intent resection and performed superior to the nomogram model.