Predicting lymph node metastasis in colorectal cancer: An analysis of influencing factors to develop a risk model.

BACKGROUND: Colorectal cancer (CRC) is a significant global health issue, and lymph node metastasis (LNM) is a crucial prognostic factor. Accurate prediction of LNM is essential for developing individualized treatment strategies for patients with CRC. However, the prediction of LNM is challenging and depends on various factors such as tumor histology, clinicopathological features, and molecular characteristics. The most reliable method to detect LNM is the histopathological examination of surgically resected specimens; however, this method is invasive, time-consuming, and subject to sampling errors and interobserver variability. AIM: To analyze influencing factors and develop and validate a risk prediction model for LNM in CRC based on a large patient queue. METHODS: This study retrospectively analyzed 300 patients who underwent CRC surgery at two Peking University Shenzhen hospitals between January and December 2021. A deep learning approach was used to extract features potentially associated with LNM from primary tumor histological images while a logistic regression model was employed to predict LNM in CRC using machine-learning-derived features and clinicopathological variables as predictors. RESULTS: The prediction model constructed for LNM in CRC was based on a logistic regression framework that incorporated machine learning-extracted features and clinicopathological variables. The model achieved high accuracy (0.86), sensitivity (0.81), specificity (0.87), positive predictive value (0.66), negative predictive value (0.94), area under the curve for the receiver operating characteristic (0.91), and a low Brier score (0.10). The model showed good agreement between the observed and predicted probabilities of LNM across a range of risk thresholds, indicating good calibration and clinical utility. CONCLUSION: The present study successfully developed and validated a potent and effective risk-prediction model for LNM in patients with CRC. This model utilizes machine-learning-derived features extracted from primary tumor histology and clinicopathological variables, demonstrating superior performance and clinical applicability compared to existing models. The study provides new insights into the potential of deep learning to extract valuable information from tumor histology, in turn, improving the prediction of LNM in CRC and facilitate risk stratification and decision-making in clinical practice.

Angiopoietin-2 induces angiogenesis via exosomes in human hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and is a highly vascularized solid tumor. Angiopoietin-2 (ANGPT2) has been described as an attractive target for antiangiogenic therapy. Exosomes are small extracellular vesicles secreted by most cell types and contribute to cell-to-cell communication by delivering functional cargo to recipient cells. The expression of ANGPT2 in tumor-derived exosomes remains unknown. METHODS: We detected the ANGPT2 expression in HCC-derived exosomes by immunoblotting, enzyme-linked immunosorbent assay and immunogold labeling, then observed exosomal ANGPT2 internalization and recycling by confocal laser scanning microscopy, co-immunoprecipitation and immunoblotting. We used two HCC cell lines (Hep3B and MHCC97H) to overexpress ANGPT2 by lentivirus infection or knockdown ANGPT2 by the CRISPR/Cas system, then isolated exosomes to coculture with human umbilical vein endothelial cells (HUVECs) and observed the angiogenesis by Matrigel microtubule formation assay, transwell migration assay, wound healing assay, cell counting kit-8 assay, immunoblotting and in vivo tumorigenesis assay. RESULTS: We found that HCC-derived exosomes carried ANGPT2 and delivered it into HUVECs by exosome endocytosis, this delivery led to a notable increase in angiogenesis by a Tie2-independent pathway. Concomitantly, we observed that HCC cell-secreted exosomal ANGPT2 was recycled by recipient HUVECs and might be reused. In addition, the CRISPR-Cas systems to knock down ANGPT2 significantly inhibited the angiogenesis induced by HCC cell-secreted exosomal ANGPT2, and obviously suppressed the epithelial-mesenchymal transition activation in HCC. CONCLUSIONS: Taken together, these results reveal a novel pathway of tumor angiogenesis induced by HCC cell-secreted exosomal ANGPT2 that is different from the classic ANGPT2/Tie2 pathway. This way may be a potential therapeutic target for antiangiogenic therapy. Video Abstract.

[Role of EuroSCORE and SinoSCORE in prediction of early postoperative quality of life in patients after coronary artery bypass surgery].

OBJECTIVE: To investigate the predicting value of European system for cardiac operative risk evaluation (EuroSCORE) and sino system for coronary operative risk evaluation (SinoSCORE) in early quality of life of patients after coronary artery bypass surgery (CABG). METHODS: A total of 218 consecutive patients who underwent CABG from March 2010 to January 2013 were evaluated with both systems before operation. Health related quality of life (QoL) was estimated by using 36-item short form health survey (SF-36) preoperatively and postoperatively in order to evaluate the predicting value of the two systems in early post-operative QoL. Calibration was evaluated by Hosmer-l,emeshow goodness-of-fit test.Discrimination was tested by determining the area under the receiver operating characteristic (ROC) curve. RESULTS: There was no significant difference between the accumulation of the EuroSCORE and SinoSCORE in the all patients (t=-0.904, P=0.368), When using Wilcoxon test on life quality in the preoperative and postoperative patients respectively,the data showed that the quality of life improved significantly in various dimensions of the postoperative patients (Z=-2.886, P<0.001).Except for bodily pain (BP) and mental health (MH), statistically significant correlation was found between the preoperative risk evaluation scores and the postoperative QoL scores (r:-0.203 to -0.493, P<0.05). Logistic regression analyses indicated that both the scores emerged as the independent predictor for a relatively worse QoL (OR>1, P<0.05). Furthermore, the EuroSCORE predicted the outcome with a higher OR. For SinoSCORE the Hosmer-Lemeshow test was significant (P=0.628) and the area under ROC curve was 0.754.For the EuroSCORE the Hosmer-Lemeshow test was significant (P=0.538) and the area under ROC curve was 0.854. CONCLUSION: Both EuroSCORE and SinoSCORE could be viewed as a predictor for several aspects of postoperative QoL, while EuroSCORE might have a greater predicting value.

Redo coronary artery bypass grafting: on-pump and off-pump coronary artery bypass grafting revascularization techniques.

OBJECTIVE: To analyze the short-term outcomes of redo coronary artery bypass grafting (CABG) using on-pump and off-pump CABG techniques. METHODS: From January 2003 to August 2013, non-randomized 80 patients were treated with redo CABG in the Department of Cardiac Surgery, Peking University Third Hospital. Among these patients, 40 underwent on-pump CABG technique (redo-ONCAB group) and 40 underwent off-pump CABG technique (redo-OPCAB group). Furthermore, transmyocardial laser revascularization was performed in high-risk patients who were not suitable to conventional grafting. Clinical data of the two groups were recorded and analyzed including operation time, coronary grafts, incomplete revascularization, postoperative ventilation, perioperative stroke, and low output syndrome, etc. RESULTS: There were no significantly differences in age, gender distribution, incidences of hypertension, stroke, and other clinical characteristics between redo-OPCAB group and redo-ONCAB group (all P>0.05), except for incidences of renal dysfunction and pulmonary disease (all P<0.05). The number of grafting vessels in the redo-ONCAB and redo-OPCAB groups was 2.1 ± 0.74 and 1.4 ±0.52 respectively. There was significant difference between the two groups (P=0.0243). Compared with the redo-ONCAB group, there was shorter operation time (P=0.0045), postoperative ventilation (P=0.0211) and intensive care unit stay (P=0.0400), as well as fewer use of platelet (P=0.0338) and blood transfusion (P=0.0034) in the redo-OPCAB group. The incidence of incomplete revascularization (P=0.0253) and the use of transmyocardial laser revascularization (P=0.0052) were higher in the redo-OPCAB group than those in the redo-ONCAB group (all P<0.05). However, no significant differences were showed for the incidence of the use of intra aortic balloon pump and continuous renal replacement therapy, perioperative stroke, low output syndrome, and in-hospital mortality between the two groups (all P>0.05). CONCLUSION: Redo CABG is the safety and efficacy surgical procedure, and redo-OPCAB technique with better outcomes is commended especially in high-risk patients.

Sternal reconstruction of deep sternal wound infections following median sternotomy by single-stage muscle flaps transposition.

OBJECTIVE: To assess clinical effectiveness of using bilateral pectoralis major or plus rectus abdominis muscle flaps in treating deep sternal wound infection (DSWI) following median sternotomy. METHODS: Between January 2009 and December 2013, 19 patients with DSWI after median sternotomy for cardiac surgery were admitted to our hospital, including 14 males (73.7%) and 5 females (26.3%), aged 55±13 (18-78) years. According to the Pairolero classification of infected median sternotomies, 3 (15.8%) patients were type II, and the other 16 (84.2%) were type III. Surgical procedure consisted of adequate debridement of infected sternum, costal cartilage, granulation, steel wires, suture residues and other foreign substances. Sternal reconstruction used the bilateral pectoralis major or plus rectus abdominis muscle flaps to obliterate dead space. The drainage tubes were placed and connected to a negative pressure generator for adequate drainage. RESULTS: There were no intraoperative deaths. In 15 patients (78.9%), bilateral pectoral muscle flaps were mobilized sufficiently to cover and stabilize the defect created by wound debridement. 4 patients (21.0%) needed bilateral pectoral muscle flaps plus rectus abdominis muscle flaps because their pectoralis major muscle flaps could not reach the lowest portion of the wound. 2 patients (10.5%) presented with subcutaneous infection, and 3 patients (15.8%) had hematoma. They recovered following local debridement and medication. 17 patients (89.5%) were examined at follow-up 12 months later, all healed and having stable sternum. No patients showed infection recurrence during the follow-up period over 12 months. CONCLUSION: DSWI following median sternotomy may be effectively managed with adequate debridement of infected tissues and reconstruction with bilateral pectoralis major muscle or plus rectus abdominis muscle flap transposition.

[Association between nuclear factor of activated T cells 1 gene mutation and simple congenital heart disease in children].

OBJECTIVE: To elucidate association between the mutation of nuclear factor of activated T cells 1 (NFATC1) gene in IPT-NFAT region and simple congenital heart disease (CHD) in children. METHOD: We used polymerase chain reaction (PCR) and the sequencing reaction to detect the mutations on the patients and their parents and (or) siblings. RESULTS: PCR amplification of the exon 7 region showed that 2 bands are obtained in 58% of patients with CHD and in 74% of their healthy parents and (or) siblings. Sequencing of the 2 bands revealed that both are amplicons of the exon 7 region, and that the additional band harbors an additional 44 nucleotides segment in the intronic region. The homozygous form of this allele was only present in patients with ventricular septal defect (2/24), atrial septal defect (3/18) and bicuspid aortic valve (1/4) in which G to A transition at nucleotide 17 of the third 44 bps was found. Neither the unrelated non-CHD individuals nor the ones with other CHD showed positive presence for the homozygous form of this allele. CONCLUSIONS: There is a differential amplification of a tandem repeat region in intron 7 of NFATC1 and homozygous form of this allele in patients with ventricular septal defect, atrial septal defect and bicuspid aortic valve. NFATC1 gene may be an a susceptibility marker for ventricular septal defect, atrial septal defect and bicuspid aortic valve.

[The role of European system for cardiac operative risk evaluation in the prediction of quality of life in patients after coronary artery bypass graft surgery].

OBJECTIVE: To assess the value of European system for cardiac operative risk evaluation (EuroSCORE) in predicting quality of life in patients post coronary artery bypass graft surgery (CABG). METHODS: A total of 387 patients underwent CABG in our institute from December of 2002 to December of 2007 were assessed by EuroSCORE before operation. Health-related quality of life (QoL) was estimated postoperatively with Seattle angina questionnaire (SAQ), Nottingham healthy profile (NHP) and Duke activity status index (DASI) in order to evaluate the value of EuroSCORE for predicting quality of life in patients post CABG. RESULTS: There were statistically significant but weak correlations between postoperative QoL score and preoperative EuroSCORE score (r: 0.010 - 0.276). Emotional and psychological experience subgroup analysis showed better predictive value of EuroSCORE score on postoperative QoL score in improved physical functioning subgroups (r > 0.2). Linear regression analysis showed that EuroSCORE score was significant but weakly (r(2) < 0.1) correlated with postoperative QoL score (P < 0.05). CONCLUSION: Preoperative EuroSCORE score is weakly correlated with postoperative QoL score in patients post CABG.

A novel mutation in GATA4 gene associated with dominant inherited familial atrial septal defect.

OBJECTIVE: Atrial septal defect (ASD) is a common congenital heart disease (CHD). Although most cases are sporadic, familial cases have been reported. The transcription factors NKX2.5 and GATA4 play important roles in the pathogenesis of ASD. Mutations in either gene have been identified in familial cases of ASD. Here, we examine a Chinese family with isolated ASD to find out whether there is any mutation in NKX2.5 or GATA4 accounting for the etiology. METHODS: We identified kindred spanning 3 generations in which 8 of 31 (38%) individuals had ASD. One hundred seventy unrelated individuals were included as controls. Peripheral blood samples were collected and genomic DNA was extracted from the leukocytes. NKX2.5 and GATA4 were amplified by polymerase chain reaction (PCR) with specific primers. The sequences of PCR products were compared between affected members and unaffected members, as well as controls. RESULTS: Direct sequencing of NKX2.5 from the genomic DNA of family members failed to identify mutations, whereas sequencing of GATA4 identified an A-to-G transition at nucleotide 928 in exon 5 that predicted a methionine to valine substitution at codon 310 (M310V) in the NLS region. All affected members and a patriarch of the family who was recognized as a carrier exhibited this mutation, whereas the other unaffected family members or control individuals did not. This mutation has not been reported previously in either familial or sporadic cases of CHD. CONCLUSIONS: We identified a novel M310V mutation in GATA4 gene that is located in the NLS region and leads to hereditary ASD in a Chinese family. In this family, we identified a carrier with incomplete penetrance and 8 patients with variable expressivity. However, the mechanism by which this mutation contributes to the development of a congenital heart defect remains to be ascertained.

[Quality of life five years after coronary artery bypass grafting].

OBJECTIVE: The quality of life (QOL) 5 years after coronary artery bypass grafting (CABG) was evaluated by NHP, SAQ and DASI questionnaires. METHODS: NHP, SAQ and DASI questionnaires were mailed to 287 patients who received CABG in our department between Jan 2001 and Jan 2002. The reliability and construct validity of the questionnaires and the influence factor of QOL were analyzed. RESULTS: Two hundred and seventy-three patients (95%) responded to the questionnaires. The reliability of three questionnaires about QOL was 0.81, 0.75 and 0.78, respectively. QOL at 5 years post CABG was significantly better in CCS I/II patients than CCS III/IV patients' according to SAQ. Exertional scale and disease perception scale according to SAQ, social isolation and physical abilities to NHP also significantly related to QOL 5 years post CABG. CONCLUSIONS: All 3 questionnaires had high reliability and statistical validity for evaluating QOL. CCS angina degree affect the quality of life in patients 5 years post CABG.

[A study on viral gastroenteritis attributed to noroviruses in hospitals].

OBJECTIVE: To better understand the clinical feature of viral gastroenteritis attributed to noroviruses and to summarize the experience on an outbreak of acute gastroenteritis through rapidly colleting and confirmation of related information regarding to noroviruses in hospitals. METHODS: Information on an outbreaks involving 18 patients with acute gastroenteritis in one hospital regarding its epidemiological and clinical features and to perform bacteria culture for stool specimens on every patient. On 7 patients, rotavirus antigen were RNA tested together with norovirus nucleic acid were examined by ELISA and PAGE and RT-PCR. RESULTS: (1) Most of the patients were elderly with several chronic diseases. (2) Watery diarrhea (12/18, 66.67%) and few with mucous (3/18, 16.67%) were seen. Most stool examination was normal (10/18, 55.56%) but few stool specimen could be found with some leucocytes (3/18, 16.67%) and little occult blood (4/18, 22.22%). (3) All bacteria culture in stools showed negative. There was no rotavirus RNA identified but 3 specimen showed norovirus nucleic acid positive as 42.86% (3/7). CONCLUSION: Norovirus was one of the important pathogens causing acute gastroenteritis outbreaks in hospitals attacking elderly with several chronic diseases in particular. Surveillance program targeting elderly inpatient with diarrhea should be enhanced, especially in autumn and winter.

[Chronic effects of transmyocardial laser revascularization combined with off-pump coronary artery by pass (OPCAB) compared with OPCAB alone in patients with ischemic heart disease: a prospective multicenter follow-up study].

OBJECTIVE: To approach the long term safety and efficacy of transmyocardial laser revascularization (TMLR, holmium: YAG) combined with off-pump coronary artery bypass (OPCAB) compared with OPCAB alone in patients with ischemic cardiac disease. METHODS: Between 1999 and 2005, 80 patients with diffusely diseased target vessels from two centers in Beijing were enrolled to the study and randomized to receive either TMLR/OPCAB (n = 40) or OPCAB (n = 40) operation. Baseline demographics and operative characteristics were similar between groups. Follow-up (mean 3.4 +/- 1.7 years) included CCS angina class and NYHA classification assessments, 6 minutes walking test (6MWT) and echocardiography. RESULTS: Perioperative mortality was 5% in both groups. No death occurred during follow up. At the end of follow-up, patients at both groups experienced significant improvement on angina score compared with baseline, and angina score was also significantly lower (1.21 +/- 0.42 vs. 1.57 +/- 0.87, P = 0.03) and 6MWT-distance significantly increased (518.0 +/- 65.5 m vs. 473.8 +/- 65.8m, P = 0.006) in OPCAB/TMLR group than that in the OPCAB group. Fewer patients developed recurrent severe angina and received re-CABG/PCI in OPCAB/TMLR group than that in the OPCAB (1 vs. 6 cases, P = 0.113). NYHA and LVEF were similar between the groups at the end of follow up. CONCLUSION: Our study showed that the addition of TMLR to OPCAB is superior in improving angina and exercise tolerance, but there is no further improvement in cardiac function compared to OPCAB alone.