Trans-Anastomotic Drainage Tube Placement After Hand-Sewn Anastomosis in Patients Undergoing Intersphincteric Resection for Low Rectal Cancer: An Alternative Drainage Method

Anastomotic leakage (AL) is a common complication after intersphincteric resection (ISR). It significantly reduces quality of life and causes great distress to patients. Although traditional drainage (e.g., anal and pelvic catheters) may reduce the impact of AL to some extent, their role in reducing the incidence of AL remains controversial. In this study, we developed a novel drainage technique involving the placement of drainage tubes through the gap between sutures during handsewn anastomosis, to reduce the occurrence of anastomotic leakage. We retrospectively analyzed 34 consecutive patients who underwent intersphincteric resection requiring handsewn anastomosis between February 1, 2017, and January 1, 2021. Patients were classified into the trans-anastomotic drainage tube group (TADT, n = 14) and the non-TADT group (n = 20) based on whether trans-anastomotic tube placement was performed. The incidence of postoperative complications, such as AL, was compared between the two groups, and anal function of patients at 1-year post-ISR was evaluated. Six cases of AL occurred in the non-TADT group, while none occurred in the TADT group; this difference was statistically significant (p=0.031). The TADT group also had a shorter hospital stay (p=0.007). There were no other significant intergroup differences in operation time, blood loss, pain score, anastomotic stenosis, intestinal obstruction, or incidence of wound infection. In the 30 patients (88.2%) evaluated for anal function, there were no significant intergroup differences in stool frequency, urgency, daytime/nocturnal soiling, Wexner incontinence score, or Kirwan grading. Taken together, trans-anastomotic tube placement is a novel drainage method that may reduce AL after ISR requiring handsewn anastomosis and without adversely affecting anal function

Pharmacokinetics, Tissue Distribution, Plasma Protein Binding Studies of 10-Dehydroxyl-12-Demethoxy-Conophylline, a Novel Anti-Tumor Candidate, in Rats

10-Dehydroxyl-12-demethoxy-conophylline is a natural anticancer candidate. The motivation of this study was to explore the pharmacokinetic profiles, tissue distribution, and plasma protein binding of 10-dehydroxyl-12-demethoxy-conophylline in Sprague Dawley rats. A rapid, sensitive, and specific ultra-performance liquid chromatography (UPLC) system with a fluorescence (FLR) detection method was developed for the determination of 10-dehydroxyl-12-demethoxy-conophylline in different rat biological samples. After intravenous (i.v.) dosing of 10-dehydroxyl-12-demethoxy-conophylline at different levels (4, 8, and 12 mg/kg), the half-life t1/2α of intravenous administration was about 7 min and the t1/2β was about 68 min. The AUC0→∞ increased in a dose-proportional manner from 68.478 μg/L·min for 4 mg/kg to 305.616 mg/L·min for 12 mg/kg. After intragastrical (i.g.) dosing of 20 mg/kg, plasma levels of 10-dehydroxyl-12-demethoxy-conophylline peaked at about 90 min. 10-dehydroxyl-12-demethoxy-conophyllinea absolute oral bioavailability was only 15.79%. The pharmacokinetics process of the drug was fit to a two-room model. Following a single i.v. dose (8 mg/kg), 10-dehydroxyl-12-demethoxy-conophylline was detected in all examined tissues with the highest in kidney, liver, and lung. Equilibrium dialysis was used to evaluate plasma protein binding of 10-dehydroxyl-12-demethoxy-conophylline at three concentrations (1.00, 2.50, and 5.00 µg/mL). Results indicated a very high protein binding degree (over 80%), reducing substantially the free fraction of the compound

Differential Proteomics Analysis of Colonic Tissues in Patients of Slow Transit Constipation

Objective. To investigate and screen the different expression of proteins in STC and normal group with a comparative proteomic approach. Methods. Two-dimensional electrophoresis was applied to separate the proteins in specimens from both 5 STC patients and 5 normal controls. The proteins with statistically significant differential expression between two groups were identified by computer aided image analysis and matrix assisted laser desorption ionization tandem time of flight mass spectrometry (MALDI-TOF-MS). Results. A total of 239 protein spots were identified in the average gel of the normal control and 215 in patients with STC. A total of 197 protein spots were matched and the mean matching rate was 82%. There were 14 protein spots which were expressed with statistically significant differences from others. Of those 14 protein spots, the expression of 12 spots increased markedly, while that of 2 spots decreased significantly. Conclusion. The proteomics expression in colonic specimens of STC patients is statistically significantly different from that of normal control, which may be associated with the pathogenesis of STC

A new method of Ionic Fragment Contribution-Gradient Boosting Regressor for predicting the infinite dilution activity coefficient of dichloromethane in ionic liquids

Ionic liquids (ILs) have shown huge potential advantages as solvents to absorb and recover dichloromethane (DCM) from waste gasses. The infinite dilution activity coefficient (gamma infinity) of DCM in ILs is an important parameter, which can be used to predict the vapor-liquid equilibrium of DCM-IL systems. In this work, a new model of calculating the gamma infinity of DCM in ILs is established based on ionic fragments contribution (IFC) and gradient boosting regressor (GBR) algorithm. IFC is used to obtain the surface charge density distribution area of ILs (S sigma-profile) that is the input of GBR. GBR is used to learn the mapping relationship between input feature and gamma infinity of DCM in ILs. The database of the gamma infinity of DCM in ILs composed of 29 cations and 22 anions includes 72 experimental data and 421 COSMO calculation data, which was employed to establish the IFC-GBR model and predict the gamma infinity of DCM in ILs. The coefficient of determination (R2) and mean absolute error (MAE) of the IFC-GBR model test set are 0.9703 and 0.0519, respectively. Also, this model has excellent generalization capability of predicting evidenced by high 10-fold cross-validation coefficients of determination in the range 0.9474-0.9481. These results indicate that the proposed model can accurately predict gamma infinity of DCM in ILs, then provide the important data for developing a new process of absorbing and desorbing DCM by IL-based technologies

A new method of Ionic Fragment Contribution-Gradient Boosting Regressor for predicting the infinite dilution activity coefficient of dichloromethane in ionic liquids

Ionic liquids (ILs) have shown huge potential advantages as solvents to absorb and recover dichloromethane (DCM) from waste gasses. The infinite dilution activity coefficient (gamma infinity) of DCM in ILs is an important parameter, which can be used to predict the vapor-liquid equilibrium of DCM-IL systems. In this work, a new model of calculating the gamma infinity of DCM in ILs is established based on ionic fragments contribution (IFC) and gradient boosting regressor (GBR) algorithm. IFC is used to obtain the surface charge density distribution area of ILs (S sigma-profile) that is the input of GBR. GBR is used to learn the mapping relationship between input feature and gamma infinity of DCM in ILs. The database of the gamma infinity of DCM in ILs composed of 29 cations and 22 anions includes 72 experimental data and 421 COSMO calculation data, which was employed to establish the IFC-GBR model and predict the gamma infinity of DCM in ILs. The coefficient of determination (R2) and mean absolute error (MAE) of the IFC-GBR model test set are 0.9703 and 0.0519, respectively. Also, this model has excellent generalization capability of predicting evidenced by high 10-fold cross-validation coefficients of determination in the range 0.9474-0.9481. These results indicate that the proposed model can accurately predict gamma infinity of DCM in ILs, then provide the important data for developing a new process of absorbing and desorbing DCM by IL-based technologies

m6A and m5C modification of GPX4 facilitates anticancer immunity via STING activation

Abstract Cancer immunotherapy is arguably the most rapidly advancing realm of cancer treatment. Glutathione peroxidase 4 (GPX4) has emerged as the vital enzyme to prevent lipid peroxidation and maintain cellular redox homeostasis. However, the mechanism of GPX4 in the regulation of cancer immunotherapy of colon adenocarcinoma (COAD) are incompletely understood. In pan-cancer analysis, we found that GPX4 showed remarkably upregulated expression and exhibited significant association with overall survival in multiple cancer types, especially COAD. Furthermore, upregulated GPX4 expression was positively correlated with increased immune cells infiltration and enhanced expression of immunomodulators. Mechanistically, RBM15B- and IGFBP2-mediated N6-methyladenosine (m6A) modification and NSUN5-mediated 5-methylcytosine (m5C) modification of GPX4 facilitated anticancer immunity via activation of cyclic GMP-AMP synthase (cGAS)-stimulator of interferon (STING) signaling by maintaining redox homeostasis in COAD. The risk model and nomogram model constructed based on the GPX4-derived genes further confirmed the prognostic and treatment-guiding value of GPX4. In all, our study demonstrated that m6A and m5C modification of GPX4 may be a promising target for cancer immunotherapy via activating the cGAS-STING signaling pathway in COAD