Left Atrial Low Voltage Areas Predicts Recurrence of Atrial Fibrillation after Catheter Ablation: A Meta-Analysis.

BACKGROUND: Low voltage areas (LVAs) on left atrial (LA) voltage mapping correlate with atrial fibrosis. However, there is no uniform standard for the definition of LVAs, or mapping techniques and mapping rhythms, so that the predictive value of left atrial LVAs for recurrence of atrial fibrillation (AF) is uncertain. This study aimed to explore the relationship between the presence of pre-ablation left atrial LVAs and the risk of recurrent AF after catheter ablation. METHODS: The databases of PubMed, Embase, Web of science, Cochrane library, Scopus, Wanfang Datebase, China National Knowledge Infrastructure, China Biology Medicine and China Scientific Journal Datebase were searched from inception to 31 July 2023. Relevant studies regarding left atrial LVAs prior to ablation to predict postoperative recurrence of AF were identified and analyzed. The efficacy endpoints were defined as the recurrence of atrial arrhythmia lasting over 30 s. RESULTS: A total of 12 studies with 1070 patients were included. We found the presence of pre-ablation left atrial LVAs correlated with the risk of recurrent AF after ablation (hazard ratio (HR) = 2.87, 95% confidence interval (CI): 2.33-3.52). The presence of pre-ablation left atrial LVAs can predict the risk of recurrent AF after ablation both in the follow-up duration ≤12 months group and follow-up duration >12 months group (follow-up duration ≤12 months: HR = 2.93, 95% CI: 2.20-3.90; follow-up duration >12 months: HR = 2.80, 95% CI: 2.09-3.77). The presence of pre-ablation left atrial LVAs correlated with the risk of recurrent AF after ablation in paroxysmal AF (HR = 2.89, 95% CI: 1.97-4.24). CONCLUSIONS: The presence of pre-ablation left atrial LVAs correlate with the risk of recurrent AF after catheter ablation.

Effects of Total Intravenous Anesthesia on Circadian Rhythms in Patients Undergoing Cardiac Transcatheter Closure.

Objective To evaluate the effects of total intravenous anesthesia on the circadian rhythms in the patients undergoing cardiac transcatheter closure. Methods Thirty patients undergoing cardiac transcatheter closure under elective intravenous anesthesia were included in this study.Paired t-tests were performed to compare the mRNA levels of the genes encoding circadian locomotor output cycles kaput(CLOCK),brain and muscle ARNT-1 like protein-1(BMAL1),cryptochrome 1(CRY1),and period circadian clock 2(PER2),the Munich Chronotype Questionnaire(MCTQ)score,and the Pittsburgh Sleep Quality Index(PSQI)score before and after anesthesia.Multiple stepwise regression analysis was performed to screen the factors influencing sleep chronotype and PSQI total score one week after surgery. Results The postoperative mRNA level of CLOCK was higher [1.38±1.23 vs.1.90±1.47;MD(95%CI):0.52(0.20-0.84),t=3.327,P=0.002] and the postoperative mRNA levels of CRY1 [1.56±1.50 vs.1.13±0.98;MD(95%CI):-0.43(-0.81--0.05),t=-2.319,P=0.028] and PER2 [0.82±0.63 vs.0.50±0.31;MD(95%CI):-0.33(-0.53--0.12),t=-3.202,P=0.003] were lower than the preoperative levels.One week after surgery,the patients presented advanced sleep chronotype [3∶03±0∶59 vs.2∶42±0∶37;MD(95%CI):-21(-40--1),t=-2.172,P=0.038],shortened sleep latency [(67±64)min vs.(37±21)min;MD(95%CI):-30.33(-55.28--5.39),t=-2.487,P=0.019],lengthened sleep duration [(436±83)min vs.(499±83)min;MD(95%CI):62.80(26.93-98.67),t=3.581,P=0.001],increased sleep efficiency [(87.59±10.35)% vs.(92.98±4.27)%;MD(95%CI):5.39(1.21-9.58),t=2.636,P=0.013],decreased sleep quality score [1.13±0.78 vs.0.80±0.71;MD(95%CI):-0.33(-0.62--0.05),t=-2.408,P=0.023],and declined PSQI total score [6.60±3.17 vs.4.03±2.58;MD(95%CI):-2.57(-3.87--1.27),t=-4.039,P<0.001].Body mass index(BMI)(B=-227.460,SE=95.475,t=-2.382,P=0.025),anesthesia duration(B=-47.079,SE=18.506,t=-2.544,P=0.017),and mRNA level of PER2(B=2815.804,SE=1080.183,t=2.607,P=0.015)collectively influenced the sleep chronotype,and the amount of anesthesia medicine(B=0.067,SE=0.028,t=2.385,P=0.024)independently influenced the PSQI one week after surgery. Conclusions Total intravenous anesthesia can improve sleep habits by advancing sleep chronotype.BMI,anesthesia duration,and mRNA level of PER2 collectively influence sleep chronotype one week after surgery.The amount of anesthesia medicine independently influences the PSQI total score one week after surgery.

The efficiency and safety of modified tissue-selecting therapy stapler combined with complete anal canal epithelial preservation operation in circumferential mixed hemorrhoids: a randomized controlled trial.

PURPOSE: This study aimed to explore the efficiency and safety of modified tissue-selecting therapy stapler combined with complete anal canal epithelial preservation operation (M-TST-CACP) in the treatment of circumferential mixed hemorrhoids. METHODS: This was a single-center, statistical analyst-blinded, randomized controlled trial (RCT). A total of 306 patients were finally included for analysis. The efficiency (efficacy, recurrence, anal smoothness, quality of life, and wound healing time) and safety (anal incontinence, pain level, anal stenosis, urinary retention, perianal edema, and postoperative bleeding) were evaluated. The statistical difference in continuous data between M-TST-CACP group and procedure for prolapse and hemorrhoids (PPH) group was compared using t-test or Mann-Whitney U test. The statistical difference in counting data between the two groups were compared using Pearson χ2 test. Difference within each group in different time points was evaluated using repeated-measures analysis of variance. RESULTS: M-TST-CACP group showed a higher cure rate (6 months: 74.51% vs. 64.71%, P = 0.044), lower recurrence (6 months: 0% vs. 4.58%, P = 0.015; 12 months: 0.65% vs. 5.88%, P = 0.010), lower anal incontinence score (1 month: 1.29 ± 1.17 vs. 1.93 ± 1.33; 3 months: 1.07 ± 0.87 vs. 1.59 ± 1.01; 6 months: 0.58 ± 0.61 vs. 1.00 ± 0.90; all P < 0.001), and lower rate of anal stenosis (1 month: 0% vs. 7.84%; 3 months: 0% vs. 9.80%; both P < 0.001) than the PPH group. CONCLUSIONS: M-TST-CACP had better efficiency and safety than the PPH, which could be a reasonable adoption for the surgeons to treat circumferential mixed hemorrhoids.

Combined therapy with early initiation of infliximab following drainage of perianal fistulising Crohn's disease: a retrospective cohort study.

BACKGROUND: Recent studies have confirmed that combined surgery and anti-TNF therapy could improve outcomes in patients with perianal fistulising Crohn's disease (PFCD). However, the optimal timing for infliximab infusion after surgical intervention is uncertain. We aimed to determine the long-term efficacy of early initiation of infliximab following surgery among PFCD patients. METHODS: We performed a retrospective cohort study of PFCD patients who received combined infliximab and surgical treatment between 2010 and 2018 at a tertiary referral hospital. Patients were grouped according to the time interval between surgery and infliximab infusion, with < 6 weeks into early infliximab induction group and > 6 weeks into delayed infliximab induction group. The primary outcome was to compare surgical re-intervention between early and delayed infliximab induction groups. The secondary outcomes were fistula healing and predictors associated with these outcomes of early infliximab induction approach. RESULTS: One hundred and seventeen patients were included (73 in early infliximab induction, 44 in delayed infliximab induction). The median interval between surgery and infliximab initiation was 9.0 (IQR 5.5-17.0) days in early infliximab induction group and 188.0 (IQR 102.25-455.75) days in delayed infliximab induction group. After followed-up for a median of 36 months, 61.6% of patients in early infliximab induction group and 65.9% in delayed infliximab induction group attained fistula healing (p = 0.643). The cumulative re-intervention rate was 23%, 32%, 34% in early infliximab induction group and 16%, 25%, 25% in delayed infliximab induction group, at 1, 2, and 3 years respectively (p = 0.235). Presence of abscess at baseline (HR = 5.283; 95% CI, 1.61-17.335; p = 0.006) and infliximab maintenance therapy > 3 infusions (HR = 3.691; 95% CI, 1.233-11.051; p = 0.02) were associated with re-intervention in early infliximab induction group. Presence of abscess at baseline also negatively influenced fistula healing (HR = 3.429, 95% CI, 1.216-9.668; p = 0.02). CONCLUSION: Although no clear benefit was shown compared with delayed infliximab induction group, early initiation of infliximab after surgery could achieve promising results for PFCD patients. Before infliximab infusion, durable drainage is required for patients with concomitant abscess or prolonged infliximab maintenance therapy.

Hesperidin Improves Colonic Motility in Loeramide-Induced Constipation Rat Model via 5-Hydroxytryptamine 4R/cAMP Signaling Pathway.

Fructus has motivation effect on gastrointestinal tract. Hesperidin is extracts of Fructus, and we attempted to prove its effects on improving the gastrointestinal transmission function and determine the possible mechanisms by a loperamide-induced slow transit constipation (STC) model. Constipation phenotypes were measured in rats with Lop-induced constipation after treatment with hesperidin. The amounts and water content of stool were significantly higher in the hesperidin-treated group than the loperamide-induced model group, whereas food intake was maintained at constant levels. Moreover, intestinal transit rate was increased in the treatment group of hesperidin. Histological alteration was detected by H&E staining, we found that the colon smooth muscle cells and neuron cells of the rats were increased, and the infiltration of inflammatory cells was decreased in the hesperidin-treated group compared with the loperamide-induced model group. 5-Hydroxytryptamine (5-HT) receptor4 fluorescence intensity and intracellular-free calcium ions in colon tissue were increased, and relative protein of cAMP/PKA pathway and p-cAMP response component-binding protein (CREB) pathway were upregulated in the hesperidin-treated group compared with the loperamide-induced model group. Further, SMCs from colon tissue of rats were cultured and identified. We found hesperidin could significantly promote tegaserod-induced increase of 5-HTR4 fluorescence intensity, intracellular calcium ions, relative protein of cAMP/PKA pathway and p-CREB pathway, and cell proliferation and inhibit GR113808-induced decrease of 5-HTR4 fluorescence intensity, 5-HTR4 pathway-related proteins (ADCY3, cAMP, PKA, and p-CREB), intracellular calcium ions, and cell proliferation. The analysis of our data suggested that hesperidin could obviously improve the gastrointestinal transmission function in loperamide-induced STC rat model via increasing the 5-HTR4 and intracellular-free calcium ions to enhance the expression of relative protein of cAMP/PKA pathway and p-CREB pathway. Hesperidin could be used in the treatment of STC, and our data not only provide experimental basis for the treatment of STC in hesperidin but also provides a theoretical reference for clinical treatment.

Analysis of Risk Factors for Anorectal Stenosis of Perianal Fistulizing Crohn's Disease.

BACKGROUND To analyze the risk factors of anorectal stenosis associated with perianal fistulizing Crohn's disease (PFCD). MATERIAL AND METHODS We retrospectively analyzed 139 cases of PFCD from January 2010 to December 2017 at the Affiliated Hospital of Nanjing University of Chinese Medicine. They were divided into 2 groups according to whether anorectal stenosis occurred. The possible factors associated with anorectal stenosis of PFCD were selected based on the literature review and clinical observations. Univariate analysis was performed to screen the risk factors of anorectal stenosis, and multivariate logistic regression analysis was performed on these risk factors and factors that were clinically considered to be potentially influential, to screen out the independent risk factors of anorectal stenosis. RESULTS We found that 44 cases (31.7%) of PFCD were associated with anorectal stenosis. Univariate analysis showed that CDAI, lesion location, and age at diagnosis were risk factors for anorectal stenosis of PFCD. Logistic regression analysis showed that mild (fair to good) (OR=3.833, 95% CI: 1.123~13.080) to moderate (poor) (OR=7.345, 95% CI: 1.964~27.474) CDAI and age at diagnosis (OR=1.067, 95% CI: 1.013~1.124) were independent risk factors for anorectal stenosis of PFCD. CONCLUSIONS Higher CDAI and older age at diagnosis appear to confer higher risk of anorectal stenosis associated with PFCD.

Free triiodothyronine and global registry of acute coronary events risk score on predicting long-term major adverse cardiac events in STEMI patients undergoing primary PCI.

BACKGROUND: The aim of this study is to investigate the combined value of fT3 and GRACE risk score for cardiovascular prognosis in ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). METHODS: Three hundred and thirty eight patients with STEMI who received successful primary PCI were enrolled in our study. All patients underwent (33.5 ± 7.1) month's follow-up. Mace was defined as cardiac death and nonfatal myocardial infarction. RESULTS: Multivariate Cox analysis showed that both fT3 (HR = 0.462, 95%CI: 0.364-0.587, P < 0.001) and GRACE score (HR = 1.011, 95%CI: 1.004-1.018, P = 0.003) were independent predictors of Mace. Similarly, fT3 (HR = 0.495, 95%CI: 0.355-0.690, P < 0.001) and GRACE score (HR = 1.022, 95%CI: 1.011-1.034, P < 0.001) were the most important independent predictors of cardiac death. Kaplan-Meier analysis revealed that those patients with low fT3 and higher GRACE score had higher rates of Mace (Log-Rank χ2 = 25.087, P < 0.001). In ROC analysis, combining fT3 and GRACE risk score had a good area under the curve (AUC) value for Mace (AUC = 0.735, 95% CI: 0.680-0.790, P < 0.001), with net reclassification index of 11.1 and 5.3%, respectively. CONCLUSION: The low fT3 level, a common phenomenon, is a strong predictor of long-term poor prognosis in STEMI patients who underwent primary PCI. The combination of GRACE score and fT3 may be a more valuable predictor of Mace as compared to each measure alone.

Inhibitory effects of baicalin on orthotopic xenografts of colorectal cancer cells that are deficient in a mismatch repair gene in nude mice.

OBJECTIVE: The aim of this article is to study the inhibitory effects of baicalin on the growth and metastasis of orthotopic xenografts consisting of human HCT-116 colorectal cancer cells that are deficient in the mismatch repair gene hMLH1 in nude mice. METHODS: A fluorescent orthotopic transplantation model of HCT-116 cells was established. The treatment groups were administered baicalin 50 mg/kg (G2), 100 mg/kg (G3), and 200 mg/kg (G4), and the negative control group (G1) was administered 5 % NaHCO3. The volume and vascular density of the primary tumors, body weights, survival conditions, and death rates of the mice were analyzed. RESULTS: On the 14th, 21st, and 28th days, tumor volume in the treatment groups was significantly smaller than that in the control group, and the differences were statistically significant. At the end of the experiment, the survival rate of the experimental animals in the G3 was significantly higher than that in the G1 and G4 (P < 0.05). There were no significant differences in both the weights and surface vascular densities of the primary tumor and the metastatic tumor among all groups. CONCLUSION: Baicalin had a significant inhibitory effect on the growth of nude mouse orthotopic xenografts consisting of human HCT-116 colorectal tumor cells that are deficient in the mismatch repair gene hMLH1.

[A comparative study of induction of remission and cost-effectiveness of enteral nutrition versus infliximab in moderate-to-severe Crohn's disease].

OBJECTIVE: To compare the induction of remission and cost-effectiveness of enteral nutrition (EN) and infliximab (IFX) in moderate-to-severe active Crohn's disease(CD). METHODS: Moderate-to-severe active CD patients were divided into IFX group and EN group. Remission rate, time to remission and treatment cost were compared between the two groups. Clinical remission was defined as Crohn's disease activity index (CDAI) < 150. The quality of life was evaluated by inflammatory bowel disease questionnaire of quality of life (IBDQ). RESULTS: A total of 100 patients were analyzed, including 48 patients in IFX group and 52 patients in EN group. IFX group had higher remission rate [87.5% (42/48) vs 67.3% (35/52) , P = 0.017] and shorter time to remission [(11.00 ± 8.35) days vs (33.94 ± 14.60) days, P < 0.001] than EN group. Treatment costs before remission were similar in two groups (P = 0.351) . The increase of IBDQ scores before and after treatment in IFX group was much higher than that of EN group (42.74 ± 27.50 vs 7.57 ± 22.77, P < 0.001) . Similarly, patients in EN group had greater increase of body mass index (BMI) than that of IFX group [(1.32 ± 0.29)kg/m(2) vs (0.51 ± 0.07) kg/m(2), P < 0.001]. For patients with CDAI < 280, remission rate was not significantly different [85.7% (24/28) vs 81.8% (18/22) , P = 0.718] between the two groups, while treatment cost in EN group was less than that of IFX group [(16.1 ± 5.9)×10(3) RMB vs (22.9 ± 11.9)×10(3) RMB, P = 0.021]. CONCLUSIONS: For patients with severe CD (CDAI ≥ 280), IFX has higher remission rate, shorter time to remission and comparable treatment cost than EN. But for patients with CDAI < 280, EN group has comparable remission rate to IFX group with lower cost.

Research on the Heating Process of CFRP Circular Tubes Based on Electromagnetic Induction Heating Method.

Based on the electromagnetic induction heating method, heating and curing of Carbon Fiber Reinforced Polymer (CFRP) have the advantages of high energy utilization and no pollution. However, in the heating process, both the material weaving structure and mold material can affect the temperature field. Therefore, in this study, an electromagnetic heating finite element analysis model for CFRP circular tubes was established based on the equivalent electromagnetic thermal characteristics of CFRP. The study investigated the temperature rise mechanism of the material weaving structure under the magnetic field, and explored in-depth the influence of molds made of 45# steel and glass fiber-reinforced plastic (FRP) on the heating process of CFRP. The CFRP circular tubes with weaving structures of 89-degree winding angle, 45-degree winding angle, and plain weave were studied. The study found that when the metal mold was heated, the CFRP structure had almost no effect on the temperature distribution. However, when the glass fiber-reinforced plastic mold was heated, the temperature field changed with the CFRP structure, and the more fiber cross points, the more uniform the temperature field. The accuracy of the finite element model was verified through experiments. The aim of this research is to provide theoretical guidance for actual industrial production.

Research on Walking Gait Planning and Simulation of a Novel Hybrid Biped Robot.

A kinematics analysis of a new hybrid mechanical leg suitable for bipedal robots was carried out and the gait of the robot walking on flat ground was planned. Firstly, the kinematics of the hybrid mechanical leg were analyzed and the applicable relevant models were established. Secondly, based on the preliminary motion requirements, the inverted pendulum model was used to divide the robot walking into three stages for gait planning: mid-step, start and stop. In the three stages of robot walking, the forward and lateral robot centroid motion trajectories and the swinging leg joint trajectories were calculated. Finally, dynamic simulation software was used to simulate the virtual prototype of the robot, achieving its stable walking on flat ground in the virtual environment, and verifying the feasibility of the mechanism design and gait planning. This study provides a reference for the gait planning of hybrid mechanical legged bipedal robots and lays the foundation for further research on the robots involved in this thesis.

[Effects of Baicalin on an orthotopic transplantation mouse model of mismatch repair gene deficient colorectal cancer].

OBJECTIVE: To study the anticancer effects of Baicalin on an orthotopic transplantation mouse model of mismatch repair gene deficient colorectal cancer. METHODS: Sixty orthotopic transplantation mice model of human colon cancer cell line HCT-116 expressing eGFP were established, which were divided randomly into negative controlled group (5% NaHCO3) and 50, 100, 200 mg/kg Baicalin groups. The nude mice were treated with intragastric infusion twice a day. Nude mice growth state, average weigh, inhibition rate of transplanted tumor, tumor metastasis and survival state were observed. RESULTS: At 14, 21 and 28 days after treatment with different dose of Baicalin, tumor growth velocity was significantly slower in the treatment groups, and tumor volume was significantly smaller than the controlled group (there were (832 ± 637), (2012 ± 1566) and (2494 ± 1557) mm(3) respectively in 14, 21 and 28 days) (F = 4.433, P < 0.05). At the end point of study, survival state of 100 mg/kg group (13/15) was superior to controlled group (8/15) and 200 mg/kg group (8/15) (χ(2) = 4.665 and 3.980, P < 0.05).However, there were no significant differences in tumor metastasis and tumor surface vessel density. CONCLUSIONS: Baicalin has statistically significant effects in inhibiting tumor growth in an orthotopic transplantation mouse model of mismatch repair gene deficient colorectal cancer, and 100 mg/kg may be an ideal treatment dose.

Association between Platelet to Neutrophil Ratio (PNR) and Clinical Outcomes in STEMI Patients after Successful pPCI: A Secondary Analysis Based on a Cohort Study.

Purpose: This study was aimed at investigating whether the platelet-to-neutrophil ratio (PNR) is independently related to the prognosis of patients with ST-elevation myocardial infarction (STEMI) after successful primary percutaneous coronary intervention (pPCI). Methods: This was a secondary analysis of data retrieved from the DATADRYAD database, which was a prospective cohort study. A total of 464 STEMI patients who underwent successful pPCI were recruited between January 2010 and October 2014. The target-independent variable, PNR, was measured at the baseline. The dependent variable in the current study was the occurrence of major adverse cardiovascular events (MACEs) during the 30-month follow-up. Results: Two patients were excluded from the final analysis because their platelet counts were unavailable. The average age of the 462 participants was 63 ± 11.92 years, and approximately 76.6% were male. After adjusting for age, sex, anterior wall myocardial infarction (MI), history of MI, apelin-12, apelin-12 change rate, left ventricular end-diastolic diameter, peak cardiac troponin I, pathological Q wave, Killip classification grade, fasting blood glucose, albumin, GENSINI score, and estimated glomerular filtration rate, a nonlinear relationship was found between the PNR and MACEs in the included cohort. The threshold value of the PNR for MACEs was 23.1. Over this cutoff value, the incidence rate of MACEs increased by 43% per 10-unit change in PNR (95% CI: 1.16-1.75, p = 0.0006). Conclusion: There was a threshold relationship between PNR and MACEs in patients with STEMI who underwent successful pPCI. The incidence of MACEs was positively associated with the PNR when the PNR exceeded 23.1.

Efficacy and Safety of Sphincter-Preserving Surgery in the Treatment of Complex Anal Fistula: A Network Meta-Analysis.

BACKGROUND: There are many surgical methods of sphincter preservation in treating complex anal fistula, but the therapeutic effects of each operation are different. Therefore, this study aimed to compare the impact of other treatment methods through a network meta-analysis to evaluate the best sphincter preservation method for treating complex anal fistula. METHODS: We searched PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, VIP Journal Database, and the Wanfang Database to collate randomized controlled trials on sphincter-preserving surgery for complex anal fistula. RESULTS: A total of 29 articles were included in this meta-analysis. The cure rates showed no statistically significant differences between any two interventions (P > 0.05). The recurrence rate results showed that the rate of patients after Fistulectomy was higher than others (P < 0.05). The incidence rate of complications showed that the incidence rate after fistulectomy treatment was higher than that of others (P < 0.05). The surface under the cumulative ranking (SUCRA) was used to arrange their advantages and disadvantages, and a larger SUCRA value indicates that the intervention may be more effective. The results showed that TROPIS may have the highest cure rate (SUCRA = 78.6%), stem cell transplantation (SCT) may have the lowest recurrence rate (SUCRA = 85.5%), and imLIFT may have the least complications (SUCRA = 88.2%). CONCLUSION: According to the existing literature data, for patients with complex anal fistula, TROPIS may be the surgical method with the highest cure rate, SCT may be the treatment method with the lowest recurrence rate, and imLIFT may be the surgical method with the lowest incidence of postoperative complications. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, identifier: CRD42020221907.

Identification of KIF21B as a Biomarker for Colorectal Cancer and Associated with Poor Prognosis.

Objective: This study is aimed at exploring the function of KIF21B in colorectal cancer. Methods: The expression of KIF21B was analyzed by the UALCAN database, GEPIA site, and TIMER site. The survival rate was analyzed by Kaplan-Meier curves, and the prognosis was analyzed by ROC. Relevant signaling pathways and biological processes were analyzed by GO-KEGG enrichment analysis. The correlation between KIF21B and cancer immune infiltrates was analyzed by TIMER. The functional state of KIF21B in various types of cancers was conducted by single-cell RNA-sequencing. Furthermore, the expression of KIF21B was verified by real-time qPCR and Western blotting. The cell proliferation was measured by CCK8 assay. The cell apoptosis was analyzed by flow cytometry. Cell migration and invasion were determined by the transwell assay. Results: Combination analysis of bioinformatics methods revealed that KIF21B is high expression in CRC, associated with poor survival. KIF21B and associated genes were significantly enriched in covalent chromatin modification. The expression of KIF21B was positively correlated with infiltrating levels of CD4+ T cells and neutrophils, cell apoptosis, and metastasis. KIF21B was upregulated expression in CRC cell lines. KIF21B deficiency reduced cell proliferation, migration, and invasion. Conclusions: Our study suggested that KIF21B may be a biomarker in CRC.

Colorectal cancer stem cell-derived exosomal long intergenic noncoding RNA 01315 (LINC01315) promotes proliferation, migration, and stemness of colorectal cancer cells.

The effect of long intergenic noncoding RNA 01315 (LINC01315) on colorectal cancer has widely been proved. Nevertheless, how LINC01315 functions in the stemness of colorectal cancer and whether LINC01315 exists in colorectal cancer stem-like cell-derived exosomes remain dim, which are thus investigated in this research. CD133+/CD44+ colorectal cancer stem cells were sorted and verified through flow cytometry. Exosomes derived from CD133+/CD44+ colorectal cancer stem cells were collected. The viability, proliferation, stemness and migration of CD133+/CD44+, CD133-/CD44-, and colorectal cancer cells after transfection or the co-culture with exosomes were detected by MTT, colony formation, spheroid, and wound healing assays, respectively. Expressions of LINC01315, BCL-2, Bax, cleaved caspase-3, MMP-9, E-cadherin, and vimentin in cells or exosomes were analyzed using western blot or qRT-PCR. Genes interacted with LINC01315 in colorectal cancer were predicted by bioinformatics analysis. The results showed that LINC01315 was high-expressed in CD133+/CD44+ colorectal cancer stem cells and exosomes. Compared with colorectal cancer cells, the viability, proliferation, stemness, and migration of CD133+/CD44+ cancer cells were stronger, while these of CD133-/CD44- cancer cells were weaker. Besides, LINC01315 silencing decreased the viability, proliferation, stemness, and migration of CD133+/CD44+ cancer cells, while sh-LINC01315 inhibited the promotive effects of CD133+/CD44+ cancer cell-derived exosomes on the viability, proliferation, stemness, and migration of colorectal cancer cells. LINC01315 was also found to be correlated with DPEP1, KRT23, ASCL2, AXIN2, and DUSP4 in colorectal cancer. In conclusion, colorectal cancer stem cell-derived exosomal LINC01315 promotes the proliferation, migration, and stemness of colorectal cancer cells.

Neogambogic acid suppresses characteristics and growth of colorectal cancer stem cells by inhibition of DLK1 and Wnt/ß-catenin pathway.

PURPOSE: Targeting cancer stem cells (CSCs) may be an efficacious strategy against cancer. We were devoted to exploring the role of neogambogic acid in characteristics and growth of colorectal CSCs. METHODS: SW480 and HCT116 cells were treated with neogambogic acid at different concentrations and transfected with siDLK1 and pcDNA3.1-DLK1 plasmids. The effect of neogambogic acid on the viability of SW480 and HCT116 cells was assessed by MTT assay. Spheroid formation assay was adopted to enrich colorectal CSCs from SW480 and HCT116 cells. The effect of neogambogic acid on colony number, aldehyde dehydrogenase (ALDH) level, apoptosis and cell cycle of SW480 and HCT116 CSCs was detected by colony formation and flow cytometry assays. The expressions of CSC markers, proliferation marker (proliferation nuclear antigen (PCNA)), apoptosis markers (cleaved caspase-3, cleaved caspase-9), Wnt/ß-catenin pathway markers (P-GSK3ß, GSK3ß, ß-catenin and Wnt) and DLK1 were determined by qRT-PCR or Western blot. RESULTS: Neogambogic acid suppressed viability, the spheroid formation ability and the levels of CSC markers in colorectal cancer (CRC) cells, accompanied with inhibition of colony-formation and ALDH level, apoptosis induction and G0/G1 phase arrest. Furthermore, neogambogic acid inhibited expressions of PCNA, P-GSK3ß, P-GSK3ß/GSK3ß, ß-catenin and Wnt, but promoted those of cleaved caspase-3, cleaved caspase-9 and GSK3ß in colorectal CSCs. DLK1 silencing caused opposite results. DLK1 overexpression abrogated the effects of neogambogic acid on colorectal CSCs. CONCLUSION: Neogambogic acid could be an efficacious natural compound targeting colorectal CSCs via inhibition of DLK1 and Wnt/ß-catenin pathway. Thus, neogambogic acid may be an attractive agent against CRC.

LncRNA LINC01315 silencing modulates cancer stem cell properties and epithelial-to-mesenchymal transition in colorectal cancer via miR-484/DLK1 axis.

Long non-coding RNA long intergenic non-protein coding RNA 01315 (LncRNA LINC01315) has been found to be implicated in various cancers, but its role and functions in colorectal cancer (CRC) remain to be addressed. Data on LINC01315 expression in CRC were gathered using bioinformatics analysis, and cancer stem cells (CSCs) were sorted by aldehyde dehydrogenase (ALDH) assay and flow cytometry. Migration, invasion, and stemness of CSCs isolated from CRC cells after transfection were determined by scratch, Transwell, and sphere-formation assays, respectively. Tumor xenograft model was constructed. Target genes and potential-binding sites were predicted using online databases and further confirmed via dual-luciferase reporter assay. Relative factors expressions were determined via quantitative real-time polymerase-chain reaction and Western blot as needed. LINC01315 was high-expressed in CRC and ALDH+ cells. LINC01315 silencing suppressed the migration, invasion, and sphere formation of CRC cells and tumor growth, and downregulated expressions of CSC molecules (ALDH, cluster of difference 44 (CD44), Prominin, and sex determining region Y-box 2 (SOX2)), Zinc Finger E-Box Binding Homeobox 1 (ZEB1) and Vimentin but upregulated E-Cadherin expression. MiR-484 could competitively bind with LINC01315, and LINC01315 silencing promoted miR-484 expression. The level of Delta Like Non-Canonical Notch Ligand 1 (DLK1), the target gene of miR-484, was enhanced by overexpressed LINC01315 yet was suppressed by LINC01315 silencing. Also, DLK1 silencing reversed the effects of downregulated miR-484 on migration, invasion, sphere formation, and CSC molecules expressions in CRC cells. LINC01315 silencing modulated CSC properties and epithelial-to-mesenchymal transition via miR-484/DLK1 axis.

Modified tissue-selecting therapy stapler combined with complete anal canal epithelial preservation operation for the treatment of circumferential mixed haemorrhoids: a protocol for single-blind randomised controlled study.

INTRODUCTION: This protocol designed a randomised controlled trial (RCT) to evaluate the effectiveness, safety and prognostic outcomes of modified tissue selecting technique (M-TST) combined with complete anal canal epithelial preservation (CACP) among patients with circumferential mixed haemorrhoids. METHODS AND ANALYSIS: This study will be single-blinded, and recruit 348 patients who are admitted to the Changshu Hospital Affiliated to Nanjing University of Chinese Medicine and fulfil the inclusion criteria from January 2022 to December 2022. Patients will be randomly assigned to the treatment group and the control group in a 1:1 ratio. The statistician will be blinded for the allocation. The treatment group will receive M-TST combined with CACP (M-TST-CACP), while the control group will receive the procedure for prolapse and haemorrhoids. The two groups will receive the same preoperative and postoperative care. The primary outcome will be recurrence rate. The secondary outcomes will be operation time, intraoperative bleeding, incontinence, pain, postoperative complications (severe bleeding, perianal oedema, urinary retention, faecal urgency, skin tags and anal stenosis), prolapse, recovery time, quality of life, Haemorrhoid Severity Score, and Symptom Severity Score. ETHICS AND DISSEMINATION: This protocol has been approved by the Clinical Ethics Committee of the Changshu Hospital Affiliated to Nanjing University of Chinese Medicine (approval no. 202102001). TRIAL REGISTRATION NUMBER: ChiCTR2100042750.

Atractylenolide I inhibits antibiotic-induced dysbiosis of the intestinal microbiome.

BACKGROUND: Atractylenolide I (AT-I) is an active component that is isolated from Rhizoma Atractylodis macrocephalae and it exerts anti-apoptotic, anti-oxidant, and anti-coagulant properties, and has been widely applied in the treatment of cardiovascular and cerebrovascular diseases in China. This study aimed to investigate the effects and possible mechanism of AT-I on intestinal dysbacteriosis in a mouse model. METHODS: Mice dysbacteriosis models were established and treated with AT-I, and the intestinal microbiome of the mice were compared. Using antibiotics-induced bacterial elimination in an intestinal dysbacteriosis-associated xenograft model, the gut microbiota-mediated anti-tumor mechanism was investigated. RESULTS: The intestinal microbiome was changed in the dysbacteriosis mice compared to the control mice, and AT-I could affect the intestinal microbiome of the dysbacteriosis mice. Manipulation of gut bacteria in the intestines of the dysbacteriosis-associated xenograft model further confirmed that the inhibition of tumor progression by AT-I was mediated by the gut microbiota, and that the underlying mechanism involves down-regulation of TLR4/MyD88/NF-κB signaling. AT-I repressed the phosphorylation of p65-NF-κB as well as the downstream cytokines, IL-6 and IL-1ß, in dysbacteriosis mice. CONCLUSIONS: AT-I may inhibit dysbacteriosis by affecting the intestinal microbiome via the regulation of TLR4/MyD88/NF-κB signaling. The present study provides a basis for the application of AT-I as an alternative medication for treating gastrointestinal disorders.