The diagnostic value of tenascin-C in acute aortic syndrome.

OBJECTIVES: Misdiagnosis of acute aortic syndrome (AAS) significantly increases mortality. Tenascin-C (TN-C) is an extracellular matrix glycoprotein related to cardiovascular injury. The elevation of TN-C in AAS and whether it can discriminate sudden-onset of acute chest pain in Chinese remains unclear. METHODS: We measured the plasma concentration of TN-C by ELISA in a cohort of 376 patients with chest or back pain. Measures to discriminate AAS from acute coronary syndrome (ACS) were compared and calculated. RESULTS: From October 2016 to September 2021, 376 undiagnosed patients with chest or back pain were enrolled. 166 of them were finally diagnosed as AAS, 100 were ACS and 110 without cardiovascular diseases (NCV). TN-C was significantly elevated in AAS at 18.18 ng/mL (IQR: 13.10-27.68) compared with 7.51 ng/mL (IQR: 5.67-11.38) in ACS (P < 0.001) and 3.68 ng/mL (IQR: 2.50-5.29) in NCV (P < 0.001). There was no significant difference in TN-C level among the subtypes of AAS. Of the 166 AAS patients, the peaked level of TN-C was at acute stage (P = 0.012), then a slight of decrease was observed at subacute stage. The area under receiver operating characteristic curve for AAS patients versus NCV was 0.979 (95% CI: 0.964-0.994) for TN-C. At a cutoff level of 11.474 ng/mL, TN-C has a sensitivity of 76.0%, specificity of 85.5%, accuracy of 82.0%, positive predictive value (PPV) of 76.0%, negative predictive value (NPV) of 85.5%. Diagnostic performance of TN-C was superior to D-dimer and hs-cTnT. CONCLUSIONS: The concentration of serum TN-C in AAS patients was significantly higher than that in ACS patients and NCV. TN-C could be a new biomarker to distinguish AAS patients in the early stage after symptoms onset from other pain diseases.

Establishment and validation of symptomatic patients colorectal screening score for predicting colorectal neoplasia risk.

OBJECTIVES: Currently, most colorectal neoplasia (CRN) screening strategies target asymptomatic individuals. However, studies on patients with non-specific gastrointestinal symptoms (NSGS) are limited. We aimed to develop a CRN risk score specifically for patients with NSGS. METHODS: We prospectively enrolled patients who underwent initial colonoscopy between June 2020 and June 2021. A new risk scoring system was constructed and its applicability was evaluated. RESULTS: A total of 1522 consecutive patients were enrolled, among whom 1016 symptomatic patients were randomly divided into a training cohort and a validation cohort at a ratio of 7:3. The constructed Symptomatic Patients Colorectal Screening (SPCS) score showed higher diagnostic efficacy and sensitivity than several previous scoring systems. Using the SPCS score, the patients were divided into a low-risk group (-2 to 3 points) and a high-risk group (4-10 points) for CRN. Additionally, the detection rate of CRN in the training and validation cohorts of the high-risk group were 41.7% and 37.0%, respectively. The SPCS score detected 79.3% (188/237) of CRN and 87.5% (42/48) of advanced CRN in the high-risk group, which reduced the workload of colonoscopy to 45.9% (466/1016). CONCLUSION: An effective CRN risk scoring system was established and validated for symptomatic patients, which accurately classified individuals into low-risk and high-risk groups for CRN and might be used to optimize colonoscopic resource allocation.

Diagnosis of Early Bacterial Pneumonia and Sepsis After Cardiovascular Surgery: A Diagnostic Prediction Model Based on LASSO Logistic Regression.

Background: Early postoperative bacterial pneumonia and sepsis (ePOPS), which occurs within the first 48 hours after cardiovascular surgery, is a serious life-threatening complication. Diagnosis of ePOPS is extremely challenging, and the existing diagnostic tools are insufficient. The purpose of this study was to construct a novel diagnostic prediction model for ePOPS. Methods: Least Absolute Shrinkage and Selection Operator (LASSO) with logistic regression was used to construct a model to diagnose ePOPS based on patients' comorbidities, medical history, and laboratory findings. The area under the receiver operating characteristic curve (AUC) was used to evaluate the model discrimination. Results: A total of 1203 patients were recruited and randomly split into a training and validation set in a 7:3 ratio. By early morning on the 3rd postoperative day (POD3), 103 patients had experienced 133 episodes of bacterial pneumonia or sepsis (15 patients had both). LASSO logistic regression model showed that duration of mechanical ventilation (P=0.015), NYHA class ≥ III (P=0.001), diabetes (P<0.001), exudation on chest radiograph (P=0.011) and IL-6 on POD3 (P<0.001) were independent risk factors. Based on these factors, we created a nomogram named DICS-I with an AUC of 0.787 in the training set and 0.739 in the validation set. Conclusion: The DICS-I model may be used to predict the risk of ePOPS after cardiovascular surgery, and is also especially suitable for predicting the risk of IRAO. The DICS-I model could help clinicians to adjust antibiotics on the POD3.

Diagnosis Value of Procalcitonin Variation on Early Pneumonia after Adult Cardiac Surgery.

BACKGROUND: Postoperative pneumonia (PP) is a complication after cardiac surgery. This study aimed to investigate the ability of procalcitonin (PCT) variation to diagnose postoperative pneumonia. METHOD: In this prospective observational study, patients with PP and age- and sex-matched cases in our center from October 10, 2020, to January 31, 2021, were included. Patients diagnosed with PP in this study met both clinical and microbiological diagnostic criteria. Blood samples were collected in all patients from the first postoperative day (POD1) to POD5 to measure PCT, white blood cells (WBCs), and C-reactive protein (CRP). PCT variation was calculated by the equation: (PCTdelayed - PCTPOD1)/PCTPOD1. The receiver operating characteristic and area under the curve (AUC) analyses were used to evaluate the diagnostic performance of different biomarkers. RESULTS: Our study enrolled 272 patients, including 24 patients with PP and 248 age- and sex-matched cases. From POD1 to POD5, the absolute value of PCT showed diagnostic significance for pneumonia (P < .05), WBC showed no differences, and CRP had no diagnostic value until POD4. Furthermore, PCT variation showed the best diagnostic value among those biomarkers (AUC 0.84, 95% confidence interval [CI] 0.71, 0.91). Multivariable logistic regression showed that PCT variation on POD2 had significant value to predict PP (odds ratio 5.602, 95% CI 2.178, 14.409, P < .01). CONCLUSION: Compared with PCT level, WBC count, and CRP level, PCT variation had the best diagnostic value in predicting PP.

Bilirubin adsorption versus plasma exchange for hyperbilirubinemia in patients after cardiac surgery: a retrospective study.

OBJECTIVE: Hyperbilirubinemia after cardiac surgery increases in-hospital mortality and is associated with poor prognosis. Our present study aimed to compare the efficacy of bilirubin adsorption (BA) and plasma exchange (PEX) in patients with hyperbilirubinemia after cardiac surgery. METHODS: We retrospectively included patients who underwent BA treatment or PEX treatment due to severe hyperbilirubinemia after cardiac surgery at our center from 2015 to 2020. We collected results from urine and liver function tests before and after treatment and compared the in-hospital mortality and morbidity between the two treatment groups. RESULTS: A total of 56 patients were enrolled in this study: 14 patients received BA treatment, and 42 patients received PEX treatment. Compared to the PEX group, the BA group exhibited a statistically significant reduction in total bilirubin (p = 0.016) and direct bilirubin (p = 0.036) levels. The in-hospital mortality was 85.7% (48/56) in the whole group, and the BA group had a lower mortality than the PEX group (71.4% vs. 90.5%, p = 0.078). The BA group showed better circulatory support, including lower risks of IABP (21.4% vs. 52.4%, p = 0.044), ECMO (21.4% vs. 50.0%, p = 0.061), reintubation (64.3% vs. 40.5%, p = 0.122) and ventricular arrhythmias (64.3% vs. 45.2%, p = 0.217). The in-hospital mortality was still lower in the BA treatment group than in the PEX treatment group (71.4% vs. 100%, p = 0.049) in the matched cohort. CONCLUSIONS: Compared to PEX treatment, BA treatment had a higher bilirubin removal ability in patients with hyperbilirubinemia and could reduce the mortality and risks of poor clinical outcomes. BA treatment should be considered an effective treatment method for patients with higher total bilirubin or direct bilirubin levels.

Berberine versus placebo for the prevention of recurrence of colorectal adenoma: a multicentre, double-blinded, randomised controlled study.

BACKGROUND: Chemoprevention of colorectal adenoma and colorectal cancer remains an important public health goal. The present study aimed to investigate the clinical potential and safety of berberine for prevention of colorectal adenoma recurrence. METHODS: This double-blind, randomised, placebo-controlled trial was done in seven hospital centres across six provinces in China. Individuals aged 18-75 years who had at least one but no more than six histologically confirmed colorectal adenomas that had undergone complete polypectomy within the 6 months before recruitment were recruited and randomly assigned (1:1) to receive berberine (0·3 g twice daily) or placebo tablets via block randomisation (block size of six). Participants were to undergo a first follow-up colonoscopy 1 year after enrolment, and if no colorectal adenomas were detected, a second follow-up colonoscopy at 2 years was planned. The study continued until the last enrolled participant reached the 2-year follow-up point. All participants, investigators, endoscopists, and pathologists were blinded to treatment assignment. The primary efficacy endpoint was the recurrence of adenomas at any follow-up colonoscopy. Analysis was based on modified intention-to-treat, with the full analysis set including all randomised participants who received at least one dose of study medication and who had available efficacy data. The study is registered with ClinicalTrials.gov, number NCT02226185; the trial has ended and this report represents the final analysis. FINDINGS: Between Nov 14, 2014, and Dec 30, 2016, 553 participants were randomly assigned to the berberine group and 555 to the placebo group. The full analysis set consisted of 429 participants in the berberine group and 462 in the placebo group. 155 (36%) participants in the berberine group and 216 (47%) in the placebo group were found to have recurrent adenoma during follow-up (unadjusted relative risk ratio for recurrence 0·77, 95% CI 0·66-0·91; p=0·001). No colorectal cancers were detected during follow-up. The most common adverse event was constipation (six [1%] of 446 patients in the berberine group vs one [<0·5%] of 478 in the placebo group). No serious adverse events were reported. INTERPRETATION: Berberine 0·3 g twice daily was safe and effective in reducing the risk of recurrence of colorectal adenoma and could be an option for chemoprevention after polypectomy. FUNDING: National Natural Science Foundation of China.

Reevaluation of a rightward shift in colorectal cancer: A single-center retrospective study in Tianjin.

OBJECTIVES: Some Western reports have shown a proximal shift in colorectal cancer (CRC), but there are few studies in China. This study aimed to provide more information for the management and screening of CRC by investigating trends in the anatomic distribution of CRC among the Chinese population in recent years. METHODS: A retrospective study was conducted on patients with CRC admitted to the Digestive Endoscopy Center of Tianjin Medical University General Hospital between January 2000 and December 2017. Patients were divided into a left-sided colorectal cancer (LSCRC) group and a right-sided colon cancer (RSCC) group. The detection rates of LSCRC and RSCC based on patients' age and sex, and on the time periods were analyzed. RESULTS: A total of 2319 cases were diagnosed with CRC among 75 183 consecutive patients. The prevalence of CRC showed a significant reduction from 2000-2008 to 2009-2017 (3.8% vs 2.7%, P < .001). The proportion of RSCC presented a downtrend from 2000-2008 to 2009-2017 (40.6% vs 37.7%, P > .05). There were slightly more RSCCs in female patients than in male patients, with no significant difference (40.9% vs 36.5%, P > .05). The proportion of RSCC in patients aged ≥50 years was similar to that in younger patients. The alarming symptoms between LSCRC and RSCC showed a significant difference (P < .05). CONCLUSIONS: In the present study, the prevalence of CRC declined significantly with time. However, there did not appear to be a rightward shift in CRC among the patients in Tianjin over the past 18 years.

Clinicopathological features of advanced colorectal serrated lesions: A single-center study in China.

OBJECTIVE: A growing body of evidence indicates that patients with colorectal serrated lesions, especially advanced serrated lesions (ASLs), are at risk of subsequent malignancy. This study aimed to analyze the clinicopathological features of ASLs and the association between ASLs and synchronous advanced colorectal neoplasia (sACN) in a single center of China. METHODS: A retrospective cross-sectional study of consecutive symptomatic patients and healthy individuals who underwent colonoscopy between January 2010 and March 2016 was performed. Clinicopathological characteritics of the patients with ASLs were documented from the colonoscopy database. RESULTS: Colorectal serrated lesions were pathologically confirmed in 277 (N = 38 981, 0.7%) cases. Among them, 156 (56.3%) were found to have ASLs, with a total of 161 lesions including 71 sessile serrated adenoma/polyps (SSA/P) and 90 traditional serrated adenomas (TSAs). There were no differences in age and gender between the ASL and non-ASL patients. Among the 161 ASLs, 29 (18.0%) were ≥10 mm in diameter. Compared with non-ASLs, ASLs appeared more in the proximal colon (P = 0.007). Flat and subpedunculated lesions were more commonly found in the ASL group compared with the non-ASL group. Nearly all ASLs (160/161) had dysplasia. Moreover, 16 sACN lesions were found in 156 ASL patients, and large diameter (≥10 mm) might be a significant risk factor for sACN (odds ratio 4.35, 95% confidence interval 1.467-12.894, P < 0.05). CONCLUSIONS: ASLs are more likely to occur in the proximal colon, and mainly present as flat and sub-pedunculated types. Large ASLs are significantly associated with sACN.

Clinical features of upper gastrointestinal serrated lesions: An endoscopy database analysis of 98746 patients.

AIM: To analyse the clinical features of patients with the serrated lesions in the upper gastrointestinal tract (UPGI) tract. METHODS: Patients who underwent routine esophagogastroduodenoscopy (EGD) at the Digestive Endoscopy Centre of General Hospital, Tianjin Medical University between January 2011 and December 2015 were consecutively recruited. Patients with UPGI serrated lesions were consecutively identified. The patients' demographics and histopathology were recorded. The colorectal findings for patients who underwent colonoscopy simultaneously or within six months were also extracted from the colonoscopy database. In addition, we analysed differences in colorectal neoplasia detection between the study patients and randomly selected patients matched for age and gender who did not exhibit serrated lesions and who also underwent colonoscopy in the same period. RESULTS: A total of 21 patients out of 98746 patients (0.02%) who underwent EGD were confirmed to have serrated lesions with predominantly crenated, sawtooth-like configurations. The mean age of the 21 patients was (55.3 ± 17.2) years, and 11 patients were male (52.4%). In terms of the locations of the serrated lesions, 17 were found in the stomach (including 3 in the cardia, 9 in the corpus and 5 in the antrum), 3 were found in the duodenum, and 1 was found in the esophagus. Serrated lesions were found in different mucosal lesions, with 14 lesions were detected in polyps (8 hyperplastic polyps and 6 serrated adenomas with low grade dysplasia), 3 detected in Ménétrier gastropathy, 3 detected in an area of inflammation or ulcer, and 1 detected in the intramucosal carcinoma of the duodenum. In addition, colonoscopy data were available for 18 patients, and a significantly higher colorectal adenoma detection rate was observed in the UPGI serrated lesions group than in the randomly selected age- and gender-matched group without serrated lesions who also underwent colonoscopy in the same period (38.9% vs 11.1%, OR = 5.091, 95%CI: 1.534-16.890, P = 0.010). The detection rate of advanced adenoma was also higher in the UPGI serrated lesions group (22.2% vs 4.2%, OR = 6.571, 95%CI: 1.322-32.660, P = 0.028). CONCLUSION: Serrated lesions in the UPGI were detected in various mucosal lesions with different pathological morphologies. Moreover colonoscopy is recommended for the detection of concurrent colorectal adenoma for these patients.

Regulation of the serotonin transporter in the pathogenesis of irritable bowel syndrome.

Serotonin (5-HT) and the serotonin transporter (SERT) have earned a tremendous amount of attention regarding the pathogenesis of irritable bowel syndrome (IBS). Considering that enteric 5-HT is responsible for the secretion, motility and perception of the bowel, the involvement of altered enteric 5-HT metabolism in the pathogenesis of IBS has been elucidated. Higher 5-HT availability is commonly associated with depressed SERT mRNA in patients with IBS compared with healthy controls. The expression difference of SERT between IBS patients and healthy controls might suggest that SERT plays an essential role in IBS pathogenesis, and SERT was expected to be a novel therapeutic target for IBS. Progress in this area has begun to illuminate the complex regulatory mechanisms of SERT in the etiology of IBS. In this article, current insights regarding the regulation of SERT in IBS are provided, including aspects of SERT gene polymorphisms, microRNAs, immunity and inflammation, gut microbiota, growth factors, among others. Potential SERT-directed therapies for IBS are also described. The potential regulators of SERT are of clinical importance and are important for better understanding IBS pathophysiology and therapeutic strategies.

Detection Rate, Distribution, Clinical and Pathological Features of Colorectal Serrated Polyps.

BACKGROUND: Colorectal serrated polyp is considered as histologically heterogeneous lesions with malignant potential in western countries. However, few Asian studies have investigated the comprehensive clinical features of serrated polyps in symptomatic populations. The aim of the study was to evaluate the features of colorectal serrated polyps in a Chinese symptomatic population. METHODS: Data from all consecutive symptomatic patients were documented from a large colonoscopy database and were analyzed. Chi-square test or Fisher's exact test and logistic regression analysis were used for the data processing. RESULTS: A total of 9191 (31.7%) patients were detected with at least one colorectal polyp. The prevalence of serrated polyps was 0.53% (153/28,981). The proportions of hyperplastic polyp (HP), sessile serrated adenoma/polyp (SSA/P), and traditional serrated adenoma (TSA) of all serrated polyps were 41.2%, 7.2%, and 51.6%, respectively, which showed a lower proportion of HP and SSA/P and a higher proportion of TSA. Serrated polyps appeared more in males and elder patients while there was no significant difference in the subtype distribution in gender and age. The proportions of large and proximal serrated polyps were 13.7% (21/153) and 46.4% (71/153), respectively. In total, 98.9% (89/90) serrated adenomas were found with dysplasia. Moreover, 14 patients with serrated polyps were found with synchronous advanced colorectal neoplasia, and large serrated polyps (LSPs) (odds ratio: 3.446, 95% confidence interval: 1.010-11.750, P < 0.05), especially large HPs, might have an association with synchronous advanced neoplasia (AN). CONCLUSIONS: The overall detection rate of colorectal serrated polyps in Chinese symptomatic patient population was low, and distribution pattern of three subtypes is different from previous reports. Moreover, LSPs, especially large HPs, might be associated with an increased risk of synchronous AN.

Cloning, Expression, Characterization, and Mutagenesis of a Thermostable Exoinulinase From Kluyveromyces cicerisporus.

Inulinase is an enzyme that belongs to glycoside hydrolase family 32. It converts inulin into high-fructose syrups and fructoligosaccharides, both of which are widely used in pharmaceutical and food industries. In this study, the kcINU1 gene (GenBank accession number AF178979) encoding an exoinulinase was cloned from Kluyveromyces cicerisporus CBS4857 and expressed in Pichia pastoris X-33, yielding a maximum of 45.2 ± 0.6 U mL(-1) of inulinase activity of culture supernatant. The expressed inulinase was purified and characterized. The enzyme had an optimum temperature of 55 °C and an optimum pH of 4.5. It had a K m of 0.322 mM and a V max of 4317 µM min(-1) mg(-1) protein when inulin was used as a substrate. It retained nearly 90 % of the maximal activity after pre-incubation at 50 °C for 1 h or at pH ranging from 3.0 to 6.0 at 4 °C for 24 h, demonstrating that KcINU1 was stable at high temperature and low pH. Moreover, we constructed two KcINU1 mutants, Asp30Ala and Glu215Ala, by site-directed mutagenesis and confirmed via zymogram analysis that Asp-30 and Glu-215 of the enzyme were the catalytic active center. The present study has provided important information for understanding the catalytic mechanism of exoinulinase.

Potential role of TRIM3 as a novel tumour suppressor in colorectal cancer (CRC) development.

OBJECTIVE: Colorectal cancer (CRC) is the third leading cause of cancer-related mortality in the United States. Recent cancer genome-sequencing efforts and complementary functional studies have led to the identification of a collection of candidate 'driver' genes involved in CRC tumorigenesis. Tripartite motif (TRIM3) is recently identified as a tumour suppressor in glioblastoma but this tumour-suppressive function has not been investigated in CRC. MATERIAL AND METHODS: In this study, we investigated the potential role of TRIM3 as a tumour suppressor in CRC development by manipulating the expression of TRIM3 in two authentic CRC cell lines, HCT116 and DLD1, followed by various functional assays, including cell proliferation, colony formation, scratch wound healing, soft agar, and invasion assays. Xenograft experiment was performed to examine in vivo tumour-suppressive properties of TRIM3. RESULTS: Small-interfering RNA (siRNA) mediated knockdown of TRIM3 conferred growth advantage in CRC cells. In contrast, overexpression of TRIM3 affected cell survival, cell migration, anchorage independent growth and invasive potential in CRC cells. In addition, TRIM3 was found to be down-regulated in human colon cancer tissues compared with matched normal colon tissues. Overexpression of TRIM3 significantly inhibited tumour growth in vivo using xenograft mouse models. Mechanistic investigation revealed that TRIM3 can regulate p53 protein level through its stabilisation. CONCLUSIONS: TRIM3 functions as a tumour suppressor in CRC progression. This tumour-suppressive function is exerted partially through regulation of p53 protein. Therefore, this protein may represent a novel therapeutic target for prevention or intervention of CRC.

Fecal microbiota transplantation broadening its application beyond intestinal disorders.

Intestinal dysbiosis is now known to be a complication in a myriad of diseases. Fecal microbiota transplantation (FMT), as a microbiota-target therapy, is arguably very effective for curing Clostridium difficile infection and has good outcomes in other intestinal diseases. New insights have raised an interest in FMT for the management of extra-intestinal disorders associated with gut microbiota. This review shows that it is an exciting time in the burgeoning science of FMT application in previously unexpected areas, including metabolic diseases, neuropsychiatric disorders, autoimmune diseases, allergic disorders, and tumors. A randomized controlled trial was conducted on FMT in metabolic syndrome by infusing microbiota from lean donors or from self-collected feces, with the resultant findings showing that the lean donor feces group displayed increased insulin sensitivity, along with increased levels of butyrate-producing intestinal microbiota. Case reports of FMT have also shown favorable outcomes in Parkinson's disease, multiple sclerosis, myoclonus dystonia, chronic fatigue syndrome, and idiopathic thrombocytopenic purpura. FMT is a promising approach in the manipulation of the intestinal microbiota and has potential applications in a variety of extra-intestinal conditions associated with intestinal dysbiosis.

[The effects of Berberine on growth of Immorto-Min colonic epithelial cell line].

OBJECTIVE: To investigate the effects of Berberine on growth of Immorto-Min colonic epithelial cell line (IMCE) and explore its possible mechanisms. METHODS: IMCE cells were treated with Berberine in the absence or presence of epidermal growth factor (EGF) and TNFα. Ki-67 staining and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay were used to identify the cell proliferation and apoptosis respectively. Furthermore, Western blot analysis was performed to detect the epidermal growth factor receptor (EGFR), protein kinase B (Akt) and their phosphorylation. RESULTS: (1) Proliferating activity of IMCE cells was increased after adding EGF and the proportion of cell proliferation was (10.64 ± 1.41)%. The proportion was significantly lowed in EGF plus Berberine group [(1.81 ± 0.85)%] compared to the EGF group (P < 0.01), while the lowest was the Berberine group [(0.49 ± 0.42)%]. (2) The proportions of cell apoptosis were (8.47 ± 2.52)% and (9.39 ± 2.13)% in the Berberine group and TNFα group respectively which were significantly higher compared to the normal control [(0.27 ± 0.30)%], both P < 0.01. (3) The phosphorylation of EGFR was significantly increased after adding EGF and p-EGFR was decreased in EGF plus Berberine group at a concentration-dependent manner. (4) Moreover, the phosphorylation of Akt was enhanced after addition of TNFα, while the phosphorylation in the TNFα and Berberine group was inhibited compared to the TNFα group. CONCLUSIONS: Berberine may suppress the proliferation and promote the apoptosis of IMCE cells. The mechanisms may relate to the inhibition of the phosphorylation of EGFR and Akt.