Analysis of the Correlation between FH and PCSK9 and APOB Gene Mutations in Han and Mongolian Populations of the Hulunbuir.

BACKGROUND: The goal of the study was to provide an individual and precise genetic and molecular biological basis for the early prevention, diagnosis, and treatment of local FH by analyzing the risk factors for the development of FH in Han and Mongolian patients in the Hulunbuir, comparing the lipid levels of FH patients of the two ethnicities, and assessing differences in mutations to two genes between the two ethnic groups. METHODS: Twenty cases each of Han Chinese and Mongolian healthy controls and fifty patients who each met the inclusion criteria from November 2021 to December 2022 in five general hospitals in Hulunbuir were selected. Multifactor logistic analysis was used to analyze the risk factors associated with the development of FH. We used t-tests to analyze statistical differences in lipid levels between the groups, and Sanger sequencing to detect the dis-tribution of common mutation sites of PCSK9 and APOB in all study subjects. The mutation rates and differences between regions and ethnic groups were summarized and compared. RESULTS: 1) Gender, age, alcohol consumption, dietary status, and a family history of FH were risk factors associated with the development of FH. 2) TC, LDL-C, and APOB were significantly higher in Mongolian cases than Han cases (p < 0.05). sdLDL-C was not statistically different between the two ethnicities (p > 0.05). 3) We detected four (8%) heterozygous mutations at the PCSK9 gene E670G mutation site in the Han case group and a total of nine (18%) mutations at this site in the Mongolian cases, including one (2%) homozygous and eight (16%) heterozygous mutations. One case of a heterozygous mutation was detected in the Mongolian control group. We detected a total of ten (20%) mutations at the APOB gene rs1367117 mutation site in the Han case group, including eight (16%) heterozygous and two (4%) homozygous mutations, 11 cases (22%) of heterozygous mutations in the Mongolian case group, two cases of heterozygous mutations in the Han control group, and one case of a heterozygous mutation in the Mongolian control group. 4) The D374Y and S127R mutation sites of PCSK9 and the R3500Q mutation site of APOB were not detected in any of the study subjects. CONCLUSIONS: The mutation sites of the PCSK9 and APOB genes in FH patients in Hulunbuir are different from other regions, and the mutation rate is higher than in other regions. Therefore, we recommend that the mutation sites of the PCSK9 and APOB genes described herein be used as clinical detection indicators to assist the diagnosis of FH in this region.

Prognostic Significance of Preoperative and Postoperative Evaluation of Combined Tumor Markers for Patients With Colon Cancer.

BACKGROUND: The combined value of the tumor markers carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in patients with colon cancer (CC) is unclear. This study aimed to investigate the role of composite tumor markers in the prognosis of CC. METHODS: Patients who underwent curative resection of colon adenocarcinoma were enrolled. The tumor marker status before and after the operation was used to divide the patients into groups according to the number of tumor markers with abnormal expression, and recurrence-free survival (RFS) and overall survival (OS) of different groups were compared. The impact of changes in composite tumor markers in the perioperative period on outcomes was further explored. RESULTS: Ultimately, 531 patients were enrolled in the study. As the number of preoperative and postoperative elevated tumor markers increased, both RFS and OS rates became lower (both P<0.05). Further analysis revealed that the number of elevated tumor markers after resection can significantly affect the outcomes (both P<0.05). In patients with abnormal preoperative tumor markers, normalization of markers after surgery was a protective factor for prognosis (both P<0.05), and patients with postoperative elevated levels of both tumor markers had a 5.5-fold and 6-fold increase in the risk of recurrence and death. In addition, patients with elevated markers after surgery had a high risk of recurrence within 5 years after colectomy. CONCLUSIONS: Postoperative tumor markers had a better ability to differentiate postoperative outcomes in patients with CC than preoperative tumor markers. Patients whose tumor markers normalized after surgery had a better prognosis.

Unraveling variations and enhancing prediction of successful sphincter-preserving resection for low rectal cancer: A post hoc analysis of the multicenter LASRE randomized clinical trial.

BACKGROUND: Accurate prediction of successful sphincter-preserving resection (SSPR) for low rectal cancer enables peer institutions to scrutinize their own performance and potentially avoid unnecessary permanent colostomy. The aim of this study is to evaluate the variation in SSPR and present the first artificial intelligence (AI) models to predict SSPR in low rectal cancer patients. STUDY DESIGN: This was a retrospective post hoc analysis of a multicenter, noninferiority randomized clinical trial (LASRE, NCT XXXXXX) conducted in 22 tertiary hospitals across China. A total of 604 patients who underwent neoadjuvant chemoradiotherapy (CRT) followed by radical resection of low rectal cancer were included as the study cohort, which was then split into a training set (67%) and a testing set (33%). The primary end point of this post hoc analysis was SSPR, which was defined as meeting all the following criteria: (1) sphincter-preserving resection; (2) complete or nearly complete TME, (3) a clear CRM (distance between margin and tumor of 1 mm or more), and (4) a clear DRM (distance between margin and tumor of 1 mm or more). Seven AI algorithms, namely, support vector machine (SVM), logistic regression (LR), extreme gradient boosting (XGB), light gradient boosting (LGB), decision tree classifier (DTC), random forest (RF) classifier, and multilayer perceptron (MLP), were employed to construct predictive models for SSPR. Evaluation of accuracy in the independent testing set included measures of discrimination, calibration, and clinical applicability. RESULTS: The SSPR rate for the entire cohort was 71.9% (434/604 patients). Significant variation in the rate of SSPR, ranging from 37.7% to 94.4%, was observed among the hospitals. The optimal set of selected features included tumor distance from the anal verge before and after CRT, the occurrence of clinical T downstaging, post-CRT weight and clinical N stage measured by magnetic resonance imaging. The 7 different AI algorithms were developed and applied to the independent testing set. The LR, LGB, MLP and XGB models showed excellent discrimination with AUROC values of 0.825, 0.819, 0.819 and 0.805, respectively. The DTC, RF and SVM models had acceptable discrimination with AUROC values of 0.797, 0.766 and 0.744, respectively. LR and LGB showed the best discrimination, and all 7 AI models had superior overall net benefits within the range of 0.3-0.8 threshold probabilities. Finally, we developed an online calculator based on the LGB model to facilitate clinical use. CONCLUSIONS: The rate of SSPR exhibits substantial variation, and the application of AI models has demonstrated the ability to predict SSPR for low rectal cancers with commendable accuracy.

Safety and efficacy of indocyanine green fluorescence imaging-guided laparoscopic para-aortic lymphadenectomy for left-sided colorectal cancer:A preliminary case-matched study.

AIM: This study is aimed to explore the safety and feasibility of indocyanine green (ICG) fluorescence imaging guidance in laparoscopic para-aortic lymph node (PALN) dissection for left-sided colorectal cancer (CRC) patients with clinically suspected PALN metastasis. METHOD: A total of 151 patients who underwent primary tumor resection and laparoscopic PALN dissection for left-sided CRC were included, with 20 patients in the ICG group and 131 patients in the non-ICG group. The surgical outcomes, postoperative complications, and pathological results, such as the number of harvested and metastatic lymph nodes were compared between groups after propensity score matching. RESULTS: Following propensity score matching, the ICG group had 20 patients, and the non-ICG group had 53 patients, and the two groups were similar in baseline characteristics. No significant differences were observed in overall intraoperative and postoperative complications between groups, except for chylous leakage, where the ICG group had a longer time to a normal diet. The number of harvested pericolic/perirectal and intermediate lymph nodes were comparable between the two groups, while the ICG group had a significantly higher number of total harvested lymph nodes (39 [14-78] vs. 29 [11-70], P = 0.001), inferior mesenteric artery lymph nodes (IMALN, 6 [0-17] vs. 3 [0-11], P = 0.006), and PALNs (9 [3-29] vs. 5 [1-37], P = 0.001). CONCLUSION: ICG fluorescence imaging could increase the retrieval of IMALN, PALN, and total lymph nodes, and potentially improve the completeness of laparoscopic PALN dissection in patients with left-sided CRC.

Hypoxia induces mitochondrial protein lactylation to limit oxidative phosphorylation.

Oxidative phosphorylation (OXPHOS) consumes oxygen to produce ATP. However, the mechanism that balances OXPHOS activity and intracellular oxygen availability remains elusive. Here, we report that mitochondrial protein lactylation is induced by intracellular hypoxia to constrain OXPHOS. We show that mitochondrial alanyl-tRNA synthetase (AARS2) is a protein lysine lactyltransferase, whose proteasomal degradation is enhanced by proline 377 hydroxylation catalyzed by the oxygen-sensing hydroxylase PHD2. Hypoxia induces AARS2 accumulation to lactylate PDHA1 lysine 336 in the pyruvate dehydrogenase complex and carnitine palmitoyltransferase 2 (CPT2) lysine 457/8, inactivating both enzymes and inhibiting OXPHOS by limiting acetyl-CoA influx from pyruvate and fatty acid oxidation, respectively. PDHA1 and CPT2 lactylation can be reversed by SIRT3 to activate OXPHOS. In mouse muscle cells, lactylation is induced by lactate oxidation-induced intracellular hypoxia during exercise to constrain high-intensity endurance running exhaustion time, which can be increased or decreased by decreasing or increasing lactylation levels, respectively. Our results reveal that mitochondrial protein lactylation integrates intracellular hypoxia and lactate signals to regulate OXPHOS.

A clinical study on roxadustat for anemia in diabetic nephropathy: a 8-week study.

PURPOSE: The development of roxadustat is a standard treatment for renal anemia, and multiple clinical trials have proved its safety and efficacy. However, less information is available from trials of the population with diabetic nephropathy (DN). This study aimed to determine whether roxadustat is effective for treating DN. METHODS: This was a single-center, retrospective, institutional review board-approved cohort study. The patients with DN were chosen and given roxadustat or erythropoietin (EPO) for 8 weeks. The mean hemoglobin (Hb) level after 8 weeks of treatment served as the primary outcome. Alterations in the iron index and lipid levels were considered secondary objectives. Sub-group analysis was performed to observe the impact of inflammation and glycemic status on Hb. RESULTS: A total of 80 patients were enrolled, 40 in each group. After 8 weeks of treatment, the Hb levels in the roxadustat group were higher than those in the control group. The number of patients who achieved Hb response was higher in the roxadustat group than in the control group (77.5% versus 27.5%; P < 0.001). In addition to lowering total cholesterol and low-density lipoprotein cholesterol, roxadustat decreased ferritin and elevated total iron-binding capacity. Compared to the control group, roxadustat was more beneficial for patients with an inflammatory condition and poor glycemic control. CONCLUSIONS: Roxadustat treatment remarkably corrected anemia in patients with DN, and its effectiveness was unaffected by inflammation or glycemic control levels. In addition, roxadustat can also reduce a patient's blood lipid level and enhance the body's use of iron. CLINICAL TRIAL REGISTRATION: ChiCTR2200057232.

Effect of roxadustat on iron metabolism in patients with peritoneal dialysis: a real-world 24-week study.

BACKGROUND: Roxadustat is an oral hypoxia inducing factor-prolyl hydroxylase inhibitor (HIF-PHI) that regulates iron metabolism in patients with chronic kidney disease (CKD) primarily by reducing hepcidin levels and mobilizing internal iron stores. More data are needed to demonstrate the efficacy of roxadustat in regulating iron metabolism in patients with peritoneal dialysis (PD) compared with erythropoiesis stimulating agents (ESAs). METHODS: This prospective cohort study enrolled PD patients with a mean hemoglobin level of 60-100 g/L. All subjects were randomized into two groups at a ratio of 2:1 the roxadustat group (106 cases), and the ESA group (53 cases). The primary endpoint was the change in the iron biomarker levels and the proportion of patients with absolute iron deficiency and functional iron deficiency. RESULTS: Compared with ESAs, roxadustat significantly decreased hepcidin level (difference, - 20.09 ng/mL; 95% CI, - 30.26 to - 9.92), attenuated the increase in serum soluble transferrin receptor (sTFR) level (difference, - 7.87 nmol/L; 95% CI, - 12.11 to - 3.64), and reduced the proportion of patients with functional iron deficiency (roxadustat, 11.43%; ESA, 33.33%). There was no significant difference in safety of the two groups over the duration of the study. CONCLUSIONS: Compared with ESA group, roxadustat group showed significant differences in all iron biomarker levels except serum ferritin (sFt) and transferrin saturation (TSAT). These results suggest that roxadustat was superior to ESAs as a therapy for iron metabolism in PD patients. TRIAL REGISTRATION: This study completed Chinese Clinical Trial Registration on March 4, 2022 (registration number: ChiCTR2200057231).

Transverse Coloplasty Pouch versus Straight Coloanal Anastomosis Following Intersphincteric Resection for Low Rectal Cancer: the Functional Benefits May Emerge After Two Years.

PURPOSE: This study aimed to compare the oncological and functional outcomes following intersphincteric resection (ISR) with transverse coloplasty pouch (TCP) or straight coloanal anastomosis (SCAA) for low rectal cancer. METHODS: A single-center retrospective analysis was performed on patients with low rectal cancer who received ISR between January 2016 and June 2021. The primary endpoint was to compare the outcomes of bowel function within 1 year, 1 to 2 years, and 2 years after ileostomy closure in patients undergoing two different bowel reconstruction procedures (TCP or SCAA). The postoperative complications and oncological results were also compared between the two groups. RESULTS: A total of 235 patients were enrolled in this study (SCAA group: 166; TCP group: 69). There was no significant difference in complications, including grades A-C anastomotic leakage (9.6% vs 15.9%), 3-year local recurrence rates (6.1% vs 3.9%), disease-free survival (82.4%vs 83.8%), or overall survival (94.1% vs 94.7%) between the two groups. Two years after ileostomy closure, 52.7% of patients in the SCAA group were assessed as having major low anterior resection syndrome (LARS), which was significantly higher than the 25.9% of patients in the TCP group (P = 0.014), but no difference was found prior to 2 years. Similar differences were seen in Wexner scores 2 years after surgery (P = 0.032). Additionally, TCP was an independent protective factor for postoperative bowel function as measured by both the LARS (OR, 0.28; 95% CI, 0.10-0.82; p = 0.020) and Wexner scoring (OR, 0.28; 95% CI, 0.09-0.84; p = 0.023). CONCLUSION: This study suggests that TCP is a safe technique that may decrease bowel dysfunction after ISR for low rectal cancer compared with SCAA 2 years after ileostomy closure.

An analysis of risk factors for clinically relevant pancreatic fistulas after laparoscopic pancreaticoduodenectomy.

This study aimed to explore the risk factors of clinically relevant pancreatic fistulas (PF) after laparoscopic pancreaticoduodenectomy (LPD). The clinical data of 80 patients who underwent pancreaticoduodenectomy in our hospital were retrospectively analyzed. The potential risk factors for PF after LPD were determined using univariate and multivariate logistic regression analyses. Results from the univariate analyses showed that the pancreatic duct diameter (P < .001), pancreatic texture (P < .001), abdominal infection (P = .002), and reoperation (P < .001) were associated with clinically relevant PF. Results from the multivariate logistic regression analysis showed that the pancreatic duct diameter (P = .002) and pancreatic texture (P = .016) were significant risk factors for clinically relevant PF. Based on this study, the pancreatic duct diameter and pancreatic texture are independent risk factors for clinically relevant PF after LPD.

Study on the Correlation between Genital Tract Microenvironment and GBS Carrier Rate of Late-Stage Pregnant Women in Dongguan.

BACKGROUND: The carrier rate of group B Streptococcus (GBS) in the genital tract of women in the late stage of pregnancy and its correlation with the genital tract microenvironment were investigated in a group of pregnant women in Dongguan, China, to provide a basis for the clinical prevention and treatment of GBS. METHODS: A retrospective analysis was done of the results of routine testing for GBS, leucorrhea and bacterial vaginosis (BV) in 6,166 women in the late stage of pregnancy (35 - 37 weeks of gestation) who underwent a prenatal examination at Dongguan Southeast Central Hospital from January 2018 to December 2020. GBS positivity was detected by RT-PCR. Normal saline floating microscopy was used to detect routine indicators of leucorrhea, including white blood cells (WBCs), Lactobacillus (Lab), vulvovaginal Candida (VVC), and trichomoniasis (TV). BV was detected based on an enzymatic reaction. The correlation between GBS infection and age and the vaginal microenvironment was determined statistically. RESULTS: The rate of GBS positivity was 10.53% (649/6,166) and was statistically significant for women 20 years of age (p < 0.05). Logistic regression showed that abnormal VVC, TV, BV, WBCs, and Lactobacillus were associated with GBS infection. The results of a rank sum test of the WBC group showed that the infection risk in groups with < 15 WBCs/hpf increased as the WBC count increased, but there was no statistical difference between groups with > 15 WBCs/hpf. The rank sum test results for Lactobacillus showed a significant difference between the abnormal and normal and other groups, but no significant difference between the other groups. CONCLUSIONS: The overall carrier rate of GBS in the genital tract of late-stage pregnant women in Dongguan was 10.53%. GBS infection is related to the genital tract microenvironment. Our results provide a basis for the prevention and treatment of clinically confirmed GBS.

Risk factors for recurrent IgA nephropathy after renal transplantation: A meta-analysis.

Recurrent glomerulonephritis after renal transplantation is the third most common cause of allograft loss, the most frequent of which is associated with IgA nephropathy (IgAN). This study aims to provide a systematic review of the risk factors associated with recurrent IgAN after renal transplantation. We searched English and Chinese databases, including PubMed, Embase, Web of Science, CNKI, and others, and included all case-control studies involving risk factors for recurrent IgAN after renal transplantation from the databases' establishment to March 2022. Data were analyzed using the Stata 12.0. A total of 20 case-control studies were included in the meta-analysis, with 542 patients with recurrent IgAN and 1385 patients without recurrent IgAN. The results showed that donor age (standardized mean difference [SMD] -0.13 [95% CI -0.26, -0.001]; P = 0.048), patient age at transplantation (SMD -0.41 [95% CI -0.53, -0.29]; P < 0.001), time from diagnosis to end-stage renal disease (SMD -0.42 [95% CI -0.74, -0.10]; P = 0.010), previous transplantation (odds ratio [OR] 1.73 [95% CI 1.06, 2.81]; P = 0.027), living donor (OR 1.86 [95% CI 1.34, 2.58]; P < 0.001), related donor (OR 2.64, [95% CI 1.84, 3.79]; P < 0.001), tacrolimus use (OR 0.71 [95% CI 0.52, 0.98]; P = 0.035), basiliximab use (OR 0.39 [95% CI 0.27, 0.55]; P < 0.001), proteinuria (SMD 0.42 [95% CI 0.13, 0.71]; P = 0.005) and serum IgA level (SMD 0.48 [95% CI 0.27, 0.69]; P < 0.001) were associated with recurrent IgAN after renal transplantation. In general, tacrolimus and basiliximab use were protective factors against recurrent IgAN after renal transplantation, whereas donor age, patient age at transplantation, time from diagnosis to end-stage renal disease, previous transplantation, living donor, related donor, proteinuria, and serum IgA level were risk factors for recurrent IgAN after renal transplantation. Clinical decision making should warrant further consideration of these risk factors.

The global, regional, and national early-onset colorectal cancer burden and trends from 1990 to 2019: results from the Global Burden of Disease Study 2019.

PURPOSE: The incidence of early-onset colorectal cancer (EO-CRC), which occurs in people under age 50, has been increasing annually. The aim of this study was to provide an up-to-date estimate of the global EO-CRC burden. METHODS: We used Global Burden of Disease Study data and methodologies to describe changes in the EO-CRC burden from 1990 to 2019, including incidence, prevalence, mortality, and disability-adjusted life years (DALYs). The driving factors for cancer burden variation were further analyzed using decomposition analysis. Frontier analysis was used to visually demonstrate the potential for burden reduction in each country or region based on their development levels. RESULTS: The global EO-CRC incidence more than doubled, increasing from 95,737 (95% uncertainty interval (UI): 90,838-101.042) /100,000 in 1990 to 226,782 (95% UI: 207,495-248,604) /100,000 in 2019. Additionally, related deaths increased from 50,997 (95% UI: 47,692-54,410) /100,000 to 87,014 (95% UI: 80,259-94,339) /100,000, and DALYs increased from 256,1842 (95% UI: 239,4962-2,735,823) /100,000 to 4,297,573 (95% UI: 3,965,485-4,650,790) /100,000. Regarding age-standardized rates, incidence and prevalence increased significantly, while mortality and DALYs rate were basically unchanged. Decomposition analysis showed a significant increase in DALYs in the middle sociodemographic index (SDI) quintile region, in which aging and population growth played a major driving role. Frontier analysis showed that countries or regions with a higher SDI quintile tend to have greater improvement potential. CONCLUSION: The current EO-CRC burden was found to be the greatest in the high-middle SDI quintile region and East Asia, which may need to adjust screening guidelines accordingly and introduce more effective interventions.

A nomogram for predicting good response after neoadjuvant chemoradiotherapy for locally advanced rectal cancer: a retrospective, double-center, cohort study.

AIM: The purpose of this study was to explore the clinical factors associated with achieving good response after neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC) and to develop and validate a nomogram. METHODS: A total of 1724 consecutive LARC patients treated at Fujian Medical University Union Hospital from January 2010 to December 2021 were retrospectively evaluated as the training cohort; 267 consecutive LARC patients treated at Zhangzhou Affiliated Hospital of Fujian Medical University during the same period were evaluated as the external 2 cohorts. Based on the pathological results after radical surgery, treatment response was defined as follows: good response, stage ypT0∼2N0M0 and poor response, ypT3∼4N0M0 and/or N positive. Independent influencing factors were analyzed by logistic regression, a nomogram was developed and validated, and the model was evaluated using internal and external data cohorts for validation. RESULTS: In the training cohort, 46.6% of patients achieved good response after nCRT combined with radical surgery. The rate of the retained anus was higher in the good response group (93.5% vs. 90.7%, P < 0.001). Cox regression analysis showed that the risk of overall survival and disease-free survival was significantly lower among good response patients than poor response patients, HR = 0.204 (95%CI: 0.146-0.287). Multivariate logistic regression analysis showed an independent association with 9 clinical factors, including histopathology, and a nomogram with an excellent predictive response was developed accordingly. The C-index of the predictive accuracy of the nomogram was 0.764 (95%CI: 0.742-0.786), the internal validation of the 200 bootstrap replication mean C-index was 0.764, and the external validation cohort showed an accuracy C-index of 0.789 (95%CI: 0.734-0.844), with good accuracy of the model. CONCLUSION: We identified factors associated with achieving good response in LARC after treatment with nCRT and developed a nomogram to contribute to clinical decision-making.

Morphology of the anterior mesorectum: a new predictor for local recurrence in patients with rectal cancer.

BACKGROUND: Pre-operative assessment with high-resolution magnetic resonance imaging (MRI) is useful for assessing the risk of local recurrence (LR) and survival in rectal cancer. However, few studies have explored the clinical importance of the morphology of the anterior mesorectum, especially in patients with anterior cancer. Hence, the study aimed to investigate the impact of the morphology of the anterior mesorectum on LR in patients with primary rectal cancer. METHODS: A retrospective study was performed on 176 patients who underwent neoadjuvant treatment and curative-intent surgery. Patients were divided into two groups according to the morphology of the anterior mesorectum on sagittal MRI: (1) linear type: the anterior mesorectum was thin and linear; and (2) triangular type: the anterior mesorectum was thick and had a unique triangular shape. Clinicopathological and LR data were compared between patients with linear type anterior mesorectal morphology and patients with triangular type anterior mesorectal morphology. RESULTS: Morphometric analysis showed that 90 (51.1%) patients had linear type anterior mesorectal morphology, while 86 (48.9%) had triangular type anterior mesorectal morphology. Compared to triangular type anterior mesorectal morphology, linear type anterior mesorectal morphology was more common in females and was associated with a higher risk of circumferential resection margin involvement measured by MRI (35.6% [32/90] vs . 16.3% [14/86], P   =  0.004) and a higher 5-year LR rate (12.2% vs . 3.5%, P   =  0.030). In addition, the combination of linear type anterior mesorectal morphology and anterior tumors was confirmed as an independent risk factor for LR (odds ratio = 4.283, P  = 0.014). CONCLUSIONS: The classification established in this study was a simple way to describe morphological characteristics of the anterior mesorectum. The combination of linear type anterior mesorectal morphology and anterior tumors was an independent risk factor for LR and may act as a tool to assist with LR risk stratification and treatment selection.

Development and validation of artificial intelligence models for preoperative prediction of inferior mesenteric artery lymph nodes metastasis in left colon and rectal cancer.

BACKGROUND: Dissection of lymph nodes at the roots of the inferior mesenteric artery (IMAN) should be offered only to selected patients at a major risk of developing IMAN involvement. The aim of this study is to present the first artificial intelligence (AI) models to predict IMAN metastasis risk in the left colon and rectal cancer patients. METHODS: A total of 2891 patients with descending colon including splenic flexure, sigmoid colon and rectal cancer undergoing major primary surgery and IMAN dissection were included as a study cohort, which was then split into a training set (67%) and a testing set (33%). Feature selection was conducted using the least absolute shrinkage and selection operator (LASSO) regression model. Seven AI algorithms, namely Support Vector Machine (SVM), Logistic Regression (LR), Extreme Gradient Boosting (XGB), Light Gradient Boosting (LGB), Decision Tree Classifier (DTC), Random Forest (RF) classifier, and Multilayer Perceptron (MLP), as well as traditional multivariate LR model were employed to construct predictive models. The optimal hyperparameters were determined with 5 fold cross-validation. The predictive performance of models and the expert surgeon was assessed and compared in the testing set independently. RESULTS: The IMAN involvement incidence was 4.6%. The optimal set of features selected by LASSO included 10 characteristics: neoadjuvant treatment, age, synchronous liver metastasis, synchronous lung metastasis, signet ring adenocarcinoma, neural invasion, lymphovascular invasion, CA199, endoscopic obstruction, T stage evaluated by MRI. The most accurate model derived from MLP showed excellent prediction power with area under the receiver operating characteristic curve (AUROC) of 0.873 and produced 81.0% recognition sensitivity and 82.5% specificity in the testing set independently. In contrast, the judgment of IMAN metastasis by expert surgeon yield rather imprecise and unreliable results with a significantly lower AUROC of 0.509. Additionally, the proposed MLP had the highest net benefits and the largest reduction of unnecessary IMAN dissection without the cost of additional involved IMAN missed. CONCLUSION: MLP model was able to maintain its prediction accuracy in the testing set better than other models and expert surgeons. Our MLP model could be used to help identify IMA nodal metastasis and to select candidates for individual IMAN dissection.

Effect of Sacubitril/Valsartan on renal function in patients with chronic kidney disease and heart failure with preserved ejection fraction: A real-world 12-week study.

Patients with chronic kidney disease (CKD) are often complicated with heart failure with preserved ejection fraction (HFpEF). However, several drugs, including angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB), have not shown apparent benefits in terms of morbidity and mortality of HFpEF. PARAMOUNT and other studies have shown the potential benefits of Sacubitril/Valsartan on patients with HFpEF, but its effects on renal function and the effect of low-dose Sacubitril/Valsartan in actual clinical conditions have not been thoroughly evaluated. In our longitudinal and observational research, 353 patients were followed up for 12 weeks. We evaluated renal function [urinary protein, serum creatinine and estimated glomerular filtration rate (eGFR)] and cardiac function [NT-proBNP (brain natriuretic peptide), New York Heart Association (NYHA) classification, left ventricular ejection fraction (LVEF), left atrial width and left ventricular end-diastolic width] at baseline and during follow-up. Worsening renal function (WRF) was defined as an increased serum creatinine≥26.5umol/L or decreased eGFR≥20%. The decline of eGFR in the Sacubitril/Valsartan group was slower than that in the control group (p = 0.021). The outcome of proteinuria in the ACEI/ARB group was significantly better than that in the Sacubitril/Valsartan group (p = 0.001). In terms of echocardiogram, the average left atrial width in Sacubitril/Valsartan group decreased by 1.38 ± 3.02 mm, which was significantly lower than that in the ACEI/ARB group (p = 0.02). The increase of urine protein class in the ACEI/ARB group increased the risk of WRF with statistical significance (OR = 2.36, 95%CI 1.01-5.49, p = 0.047), but no statistical significance was found in all the patients or Sacubitril/Valsartan group. In conclusion, Sacubitril/Valsartan could more effectively slow down renal function decline and reverse myocardial remodeling in patients with CKD and HFpEF than ACEI/ARB, even at low doses, though its protective effect on urinary protein is not as good as that of ACEI/ARB.