Individualized prediction of conditional survival for colorectal signet-ring cell carcinoma patients.

Background: Conditional survival (CS) considers the time already survived after surgery and may provide additional survival information. The authors sought to construct and validate novel conditional survival nomograms for the prediction of conditional overall survival (OS) and cancer-specific survival (CSS) of colorectal signet-ring cell carcinoma (SRCC) patients. Methods: Patients diagnosed with stage I-III SRCC between 2010 and 2019 were identified from the Surveillance, Epidemiology, and End Results database. The formula calculating CS was: CS(x|y) = S(x+y)/S(x), where S(x) represents the survival at x years. CS nomograms were then constructed to predict the 5-year conditional OS and CSS, followed by internal validation. Results: A total of 944 colorectal SRCC patients were finally identified in this study. The 5-year OS and CSS improved gradually with additional survival time. Univariate and multivariate Cox regression analysis conducted in training set revealed that age, race, T stage, LNR, and perineural invasion were independent risk factors for both OS and CSS. Two nomograms with considerable predictive ability were successfully constructed [area under the curve (AUC) for OS: 0.788; AUC for CSS: 0.847] and validated (AUC for OS: 0.773; AUC for CSS: 0.799) for the prediction of 5-year OS and CSS, based on the duration of 1-4 years post-surgery survival. Conclusions: The probability of achieving 5-year OS and 5-year CSS in colorectal SRCC patients improved gradually with additional time. Conditional nomograms considering survival time will be more reliable and informative for risk stratification and postoperative follow-up.

'Dumpling suture method' versus traditional suture method of protective loop ileostomy in laparoscopic anterior rectal resection with specimen extraction through stoma incision: a retrospective comparative cohort study.

BACKGROUND: A diverting loop ileostomy (DLI) is performed in laparoscopic anterior rectal resection (LAR) surgery at high risk of anastomotic fistula. Minimally invasive surgery promotes postoperative recovery and cosmetics. To reduce abdominal trauma, specimen extraction through stoma incision (EXSI) is usually performed to avoid auxiliary abdominal incision with enlarged stomal incision. The traditional suture method (TSM) reduces the incision size by suturing the ends of the enlarged incision, leading to peristomal incisions and a higher risk of stomal complications. The study aimed to introduce the dumpling suture method (DSM) of PLI and compare this new method with TSM. MATERIALS AND METHODS: The authors propose a novel stoma suture technique, which utilized a method of skin folding suture to reduce the enlarged incision size. A retrospective analysis was conducted on 71 consecutive patients with rectal cancer who underwent LAR-DLI with EXSI, and the intraoperative details and postoperative outcomes of the two groups were measured. RESULTS: The DSM group showed a lower stomal complication rate (10.3 vs. 35.7%, P=0.016) than that of the TSM group. The scores of DET (Discoloration, Erosion, Tissue overgrowth), stomal pain, quality of life were all significantly lower in DSM group than in TSM group. In multivariate analysis, DSM was an independent protective factor for stoma-related complications. Operative time, time to first flatus, defecation and eat, nonstomal related postoperative complications were similar in both groups. CONCLUSION: DSM utilizes a method of skin folding suture to reduce the enlarged incision size, which is safe and effective in reducing the incidence of peristomal skin infections and stomal complications. This procedure offers a novel suturing approach for loop ileostomy with enlarged incision, effectively reducing the postoperative trauma and incidence of stomal complications.

Effects of dapagliflozin on cardiac function and short-term prognosis of patients with both acute myocardial infarction and type 2 diabetes mellitus.

BACKGROUND: Dapagliflozin is a selective SGLT2 inhibitor, which has been widely used in the treatment of patients with type 2 diabetes mellitus (T2DM). By blocking the reabsorption of glucose in renal tubules, daglitazine can promote urinary glucose excretion, reduce blood glucose and blood pressure, and also shows a protective effect on the heart in clinical studies. Accordingly, this study was designed to explore the effects of dapagliflozin on cardiac function and short-term prognosis of patients with acute myocardial infarction (AMI) complicated with T2DM. METHODS: The clinical data of 100 patients with both AMI and T2DM treated at Shibei Hospital of Jingan District from January 2021 to January 2023 were analyzed retrospectively. Totally 47 patients treated with hypoglycemic agents other than SGLT-2i inhibitors on the basis of routine treatment were assigned to the control group, and 53 patients treated with dapagliflozin based on treatment of the control group were assigned to the study group. Relevant blood glucose-related indices and cardiac function-associated indices of the two groups before and after treatment were analyzed and compared: The adverse reactions of the two groups were statistically analyzed, including hypotension, hypoglycemia, diarrhea and abdominal pain, anorexia, and nausea and vomiting. The patients were followed-up for six months, on which the major cardiovascular adverse events (MACE) and incidence of readmission for heart failure in the two groups were analyzed and compared. RESULTS: Treatment, the FBG, 2h PG and HbA1c levels in both groups dropped significantly (P<0.05), with significantly lower levels in the study group (P<0.05). After treatment, both groups showed significantly dropped NT-pro BNP, LVEDD and LVESD levels (P<0.05) and a significantly increased LVEF level (P<0.05), with more significant drops/increase in the study group (P<0.05). No significant difference was found between the two groups in the total incidence of adverse reactions (P=0.586). During the follow-up period, there was no significant difference in the incidence of MACE between the two groups (P>0.05), and the study group showed a significantly lower incidence of readmission for heart failure than the control group (P<0.05). CONCLUSIONS: Dapagliflozin can substantially improve the blood glucose and cardiac function of patients with both AMI and T2DM. It can lower the rate of readmission for heart failure, and provide various cardiovascular benefits besides hypoglycemic effect.

The YAP-TEAD4 complex promotes tumor lymphangiogenesis by transcriptionally upregulating CCBE1 in colorectal cancer.

The secreted protein collagen and calcium-binding EGF domain 1 (CCBE1) is critical for embryonic lymphatic development through its role in the proteolytic activation of mature vascular endothelial growth factor C (VEGFC). We previously reported that CCBE1 is overexpressed in colorectal cancer (CRC) and that its transcription is negatively regulated by the TGFß-SMAD pathway, but the transcriptional activation mechanism of CCBE1 in CRC remains unknown. Recent studies have revealed the vital role of the hippo effectors YAP/TAZ in lymphatic development; however, the role of YAP/TAZ in tumor lymphangiogenesis has not been clarified. In this study, we found that high nuclear expression of transcription factor TEAD4 is associated with lymph node metastasis and high lymphatic vessel density in patients with CRC. YAP/TAZ-TEAD4 complexes transcriptionally upregulated the expression of CCBE1 by directly binding to the enhancer region of CCBE1 in both CRC cells and cancer-associated fibroblasts, which resulted in enhanced VEGFC proteolysis and induced tube formation and migration of human lymphatic endothelial cells in vitro and lymphangiogenesis in a CRC cell-derived xenograft model in vivo. In addition, the bromodomain and extraterminal domain (BET) inhibitor JQ1 significantly inhibited the transcription of CCBE1, suppressed VEGFC proteolysis, and inhibited tumor lymphangiogenesis in vitro and in vivo. Collectively, our study reveals a new positive transcriptional regulatory mechanism of CCBE1 via YAP/TAZ-TEAD4-BRD4 complexes in CRC, which exposes the protumor lymphangiogenic role of YAP/TAZ and the potential inhibitory effect of BET inhibitors on tumor lymphangiogenesis.

Construction of nanofibrous scaffolds with interconnected perfusable microchannel networks for engineering of vascularized bone tissue.

Vascularization and bone regeneration are two closely related processes during bone reconstruction. A three-dimensional (3D) scaffold with porous architecture provides a suitable microenvironment for vascular growth and bone formation. Here, we present a simple and general strategy to construct a nanofibrous poly(l-lactide)/poly(ε-caprolactone) (PLLA/PCL) scaffold with interconnected perfusable microchannel networks (IPMs) based on 3D printing technology by combining the phase separation and sacrificial template methods. The regular and customizable microchannel patterns within the scaffolds (spacings: 0.4 mm, 0.5 mm, and 0.6 mm; diameters: 0.8 mm, 1 mm, and 1.2 mm) were made to investigate the effect of microchannel structure on angiogenesis and osteogenesis. The results of subcutaneous embedding experiment showed that 0.5/0.8-IPMs (spacing/diameter = 0.5/0.8) and 0.5/1-IPMs (spacing/diameter = 0.5/1) scaffolds exhibited more vascular network formation as compared with other counterparts. After loading with vascular endothelial growth factor (VEGF), VEGF@IPMs-0.5/0.8 scaffold prompted better human umbilical vein endothelial cells (HUVECs) migration and neo-blood vessel formation, as determined by Transwell migration, scratch wound healing, and chorioallantoic membrane (CAM) assays. Furthermore, the microangiography and rat cranial bone defects experiments demonstrated that VEGF@IPMs-0.5/0.8 scaffold exhibited better performance in vascular network formation and new bone formation compared to VEGF@IPMs-0.5/1 scaffold. In summary, our results suggested that the microchannel structure within the scaffolds could be tailored by an adjustable caramel-based template strategy, and the combination of interconnected perfusion microchannel networks and angiogenic factors could significantly enhance vascularization and bone regeneration.

Manganese-doped gold core mesoporous silica particles as a nanoplatform for dual-modality imaging and chemo-chemodynamic combination osteosarcoma therapy.

In this study, an effective and facile strategy is reported to construct a multifunctional nanoplatform by in situ doping metal manganese on gold core mesoporous silica nanoparticles (Au@MMSN). After further modification of alendronate (Ald) on Au@MMSN, the obtained Au@MMSN-Ald efficiently integrates bone targeted chemo-chemodynamic combination therapy and dual-modality computed tomography/magnetic resonance (CT/MR) imaging into a single platform. In particular, Au@MMSN-Ald exhibits excellent tumor microenvironment responsive drug release efficiency. The doxorubicin hydrochloride (DOX) loaded Au@MMSN-Ald (DOX@Au@MMSN-Ald) is demonstrated with excellent targeted ability toward osteosarcoma. Accordingly, in a specific tumor microenvironment, DOX@Au@MMSN-Ald also displays outstanding combined efficiency for killing cancer cells in vitro and suppressing the osteosarcoma growth in vivo. Benefiting from the Au nanoparticles confined in the core and manganese ions released from the shell, CT and MR dual-modality imaging were performed to verify the effective accumulation of Au@MMSN-Ald at the tumor site. Overall, the constructed DOX@Au@MMSN-Ald nanoparticles integrated imaging guide, responsive drug release and combination therapy, which may provide some insight for further biomedical applications in efficient osteosarcoma therapy.

Construction of a nanofiber network within 3D printed scaffolds for vascularized bone regeneration.

Three-dimensional (3D) printed scaffolds provide a promising prospective for application in bone tissue engineering. 3D printed scaffolds with micro- and nano-fibrous structures that facilitate cell adhesion and migration, and combined vascularization and osteoinduction bioactivity will be ideal implants for bone defect repair. Here, we fabricated a 3D printed biodegradable poly (glycerol-co-sebacic acid-co-l-lactic acid-co-polyethylene glycol) (PGSLP)-based scaffold that was internally filled with gelatin nanofibers and allowed the local release of deferoxamine (DFO), which is essential for angiogenesis and osteogenesis in bone regeneration. The nanofibrous structured gelatin/PGSLP (NGP) scaffold was fabricated using a thermally induced phase separation (TIPS) technique, and the macroporous structured gelatin/PGSLP (MGP) scaffold was prepared by directly freeze-drying. The in vitro experiments demonstrated that both DFO-loaded NGP and DFO-loaded MGP scaffolds can promote the migration and tubular formation of human umbilical vein endothelial cells (HUVECs), and enhance the mineralized nodule formation and osteogenic-related gene expression during osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). In a rat critical-sized calvarial defect model, the results suggested that the scaffolds with DFO loading significantly promote the vascular formation and accelerate bone regeneration, while the enhancement of vascularization and osteogenesis in vivo in DFO-loaded NGP scaffold was better than that in DFO-loaded MGP scaffold. Therefore, the constructed PGLSP-based scaffolds with micro- and nano-fibrous structures would be promising candidates to match the structural and functional requirements for vascularized bone regeneration.

RuRh Bimetallene Nanoring as High-efficiency pH-Universal Catalyst for Hydrogen Evolution Reaction.

Electrocatalysis of the hydrogen evolution reaction (HER) is a vital and demanding, yet challenging, task to produce clean energy applications. Here, the RuRh2 bimetallene nanoring with rich structural defects is designed and successfully synthesized by a mixed-solvent strategy, displaying ascendant HER performance with high mass activity at -0.05 and -0.07 V, separately higher than that of the commercial Pt catalyst. Also, it maintains steady hydrogen bubble evolution even after 30 000 potential cycles in acid media. Furthermore, the RuRh2 bimetallene nanoring shows an outstanding activity in both alkaline and neutral media, outperforming that of Pt catalysts and other reported HER catalysts. A combination of atomic-scale structure observation and density functional theory calculations demonstrates that both the grain boundaries and symmetry breaking of RuRh2 bimetallene cannot only weaken the adsorption strength of atomic hydrogen, but also facilitate the transfer of electrons and the adsorption of reactants, further boosting the HER electrocatalytic performance in all pH values.

Comparison of two types of colectomy in treating slow transit constipation with or without melanosis coli.

AIM: To compare the follow-up outcomes of ileosigmoidal anastomosis (ISA) and caecorectal anastomosis (CRA) in patients with slow transit constipation (STC) with or without melanosis coli (MC). METHODS: We collected the clinical data of 48 STC patients with or without MC from May 2002 to May 2007. Twenty-six patients underwent CRA (14 with MC) and 22 cases received ISA (14 with MC). A 3-year postoperative follow-up was conducted. RESULTS: CRA improved the quality of life [evaluated by the gastrointestinal quality of life index (GIQLI)] in patients without MC, but was inferior to ISA in stool frequency and Wexner and GIQLI scores for MC patients. In the CRA group, patients with MC suffered worse outcomes than those without MC. CONCLUSION: CRA is more suitable for STC patients without MC; however, for STC patients with MC, ISA is a better choice.