Functionalized 3D Hydroxyapatite Scaffold by Fusion Peptides-Mediated Small Extracellular Vesicles of Stem Cells for Bone Tissue Regeneration.

3D printing technology offers extensive applications in tissue engineering and regenerative medicine (TERM) because it can create a three-dimensional porous structure with acceptable porosity and fine mechanical qualities that can mimic natural bone. Hydroxyapatite (HA) is commonly used as a bone repair material due to its excellent biocompatibility and osteoconductivity. Small extracellular vesicles (sEVs) derived from bone marrow mesenchymal stem cells (BMSCs) can regulate bone metabolism and stimulate the osteogenic differentiation of stem cells. This study has designed a functionalized bone regeneration scaffold (3D H-P-sEVs) by combining the biological activity of BMSCs-sEVs and the 3D-HA scaffold to improve bone regeneration. The scaffold utilizes the targeting of fusion peptides to increase the loading efficiency of sEVs. The composition, structure, mechanical properties, and in vitro degradation performance of the 3D H-P-sEVs scaffolds were examined. The composite scaffold demonstrated good biocompatibility, substantially increased the expression of osteogenic-related genes and proteins, and had a satisfactory bone integration effect in the critical skull defect model of rats. In conclusion, the combination of EVs and 3D-HA scaffold via fusion peptide provides an innovative composite scaffold for bone regeneration and repair, improving osteogenic performance.

Highly Tough and Biodegradable Poly(ethylene glycol)-Based Bioadhesives for Large-Scaled Liver Injury Hemostasis and Tissue Regeneration.

Conventional tissue adhesives face challenges for hemostasis and tissue regeneration in large-scaled hemorrhage and capillary hypobaric bleeding due to weak adhesion, and inability to degrade at specific sites. Herein, convenient and injectable poly(ethylene glycol) (PEG)-based adhesives are developed to address the issues for liver hemostasis. The PEG-bioadhesives are composed of tetra-armed PEG succinimide glutarate (PEG-SG), tetra-armed PEG amine (PEG-NH2 ), and tri-lysine. By mixing the components, the PEG-bioadhesives can be rapidly formulated for use of liver bleeding closure in hepatectomy. The PEG-bioadhesives also possess mechanical compliance to native tissues (elastic modulus ≈40 kPa) and tough tissue adhesion (≈28 kPa), which enables sufficient adhering to the injured tissues and promotes liver regeneration with the PEG-bioadhesive degradation. In both rats of liver injury and pigs of large-scaled hepatic hemorrhage, the PEG-bioadhesives show effective hemostasis with superior blood loss than conventional tissue adhesives. Due to biocompatibility and degradability, the PEG-bioadhesive is advantageous for liver regeneration, while commercial adhesives (e.g., N-octyl cyanoacrylate) display adhesion failure and limited liver reconstructions. These PEG-bioadhesive components are FDA-approved, and demonstrate excellent adhesion to various tissues not only for liver hemostasis, it is a promising candidate in biomedical translations and clinical applications.

The clinical effectiveness of staple line reinforcement with different matrix used in surgery.

Staplers are widely used in clinics; however, complications such as bleeding and leakage remain a challenge for surgeons. To tackle this issue, buttress materials are recommended to reinforce the staple line. This Review provides a systematic summary of the characteristics and applications of the buttress materials. First, the physical and chemical properties of synthetic polymer materials and extracellular matrix used for the buttress materials are introduced, as well as their pros and cons in clinical applications. Second, we review the clinical effects of reinforcement mesh in pneumonectomy, sleeve gastrectomy, pancreatectomy, and colorectal resection. Based on the analysis of numerous research data, we believe that buttress materials play a crucial role in increasing staple line strength and reducing the probability of complications, such as bleeding and leakage. However, considering the requirements of bioactivity, degradability, and biosafety, non-crosslinked small intestinal submucosa (SIS) matrix material is the preferred candidate. It has high research and application value, but further studies are required to confirm this. The aim of this Review is to provide comprehensive guidance on the selection of materials for staple line reinforcement.

Modification of the small intestinal submucosa membrane with oligopeptides screened from intrinsically disordered regions to promote angiogenesis and accelerate wound healing.

A slow vascularization rate is considered one of the major disadvantages of biomaterials used for accelerating wound healing. Several efforts, including cellular and acellular technologies, have been made to facilitate biomaterial-induced angiogenesis. However, no well-established techniques for promoting angiogenesis have been reported. In this study, a small intestinal submucosa (SIS) membrane modified by an angiogenesis-promoting oligopeptide (QSHGPS) screened from intrinsically disordered regions (IDRs) of MHC class II was used to promote angiogenesis and accelerate wound healing. Because the main component of SIS membranes is collagen, the collagen-binding peptide sequence TKKTLRT and the pro-angiogenic oligopeptide sequence QSHGPS were used to construct chimeric peptides to obtain specific oligopeptide-loaded SIS membranes. The resulting chimeric peptide-modified SIS membranes (SIS-L-CP) significantly promoted the expression of angiogenesis-related factors in umbilical vein endothelial cells. Furthermore, SIS-L-CP exhibited excellent angiogenic and wound-healing abilities in a mouse hindlimb ischaemia model and a rat dorsal skin defect model. The high biocompatibility and angiogenic capacity of the SIS-L-CP membrane make it promising in angiogenesis- and wound healing-related regenerative medicine.

Mechanically active small intestinal submucosa hydrogel for accelerating chronic wound healing.

The treatment of chronic wounds is still a challenge worldwide. Here, inspired by mechanically induced embryonic wound healing, we design a mechanically active small intestinal submucosa based hydrogel (SIS-PNIPAm). The mechanical activity, biocompatibility, and bioactivity (angiogenesis and immunoregulation) of the SIS-PNIPAm hydrogel enable the fast healing of diabetic rat full-thickness wounds.

Customer demand-driven low-carbon vehicles combined strategy and route optimisation integrated decision.

With the optimal operating cost and optimal carbon emission target of the chemical logistics companies, a low-carbon routing optimisation with a multi-energy type vehicle combined problem is proposed by considering the concept of the logistics companies' low-carbon behaviour. An integrated decision-making of multi-energy type vehicles combined strategy and route optimisation based on customer demand is presented, and an improved genetic algorithm is designed. A case study is then applied based on the data collected from the case research. The effectiveness of the improved genetic algorithm is tested. The two joint objectives of operating cost and carbon emission are examined through the cost analysis of environmental energy vehicles and traditional energy vehicles in different combination scenarios. The case analysis shows that a rational multi-energy type vehicle combination with route optimisation has a significant correlation with the operating cost and carbon emissions, while the environmental vehicle purchasing cost reduction and subsidy policy affect the operating cost.

miR-128 participates in the pathogenesis of chronic constipation by regulating the p38α/M-CSF inflammatory signaling pathway.

Chronic constipation (CC) is a gastrointestinal disorder that adversely affects the quality of life. MicroRNAs are involved in the pathogenesis of functional gastrointestinal disorders. This study aims to investigate the molecular mechanism of microRNA-128 in CC. Here, we successfully constructed a murine model of CC based on morphine and rhubarb. The expression of stem cell factor (SCF) and neuron-specific enolase (NSE) was low in the models. Using miRNA array and bioinformatic analysis, we predicted and confirmed the expression of miR-128 and its downstream target genes in CC model. Compared with the control group, CC group showed a significant downregulation of miR-128 and upregulation of p38α and macrophage colony-stimulating factors (M-CSFs). Moreover, we observed elevated inflammatory cytokine and decreased anti-inflammatory cytokine levels in colonic tissues. Furthermore, coculture assays indicated that regulating expression of miR-128 in colonic epithelial cells induced the secretion of IL-6 and TNF-α by macrophages. In conclusion, our study demonstrated that miR-128 regulated the p38α/M-CSF signaling pathway to promote chronic inflammatory responses and changes in the immune microenvironment of the colon, thereby offering potential insights into the pathogenesis of CC and therapeutic targets for its treatment.NEW & NOTEWORTHY In this study, we constructed a murine model and identified a novel signaling mechanism involved in the chronic constipation progression. Our findings on the role of miR-128/p38α/M-CSF axis provide new insights into the treatment of chronic constipation.

Dysregulation of CircRNA_0001946 Contributes to the Proliferation and Metastasis of Colorectal Cancer Cells by Targeting MicroRNA-135a-5p.

This study was aimed to evaluate the potential function of circ-0001946 in the progression of colorectal cancer (CRC) and the related regulatory mechanism. First, the expression levels of circRNA_0001946 and microRNA-135a-5p (miR-135a-5p) in normal and CRC tissues were measured by quantitative real-time polymerase chain reaction (RT-qPCR). In addition, cell proliferation was assessed by the Cell Counting Kit-8 (CCK-8) assay, cell migration and invasion were evaluated by Transwell assays, and the cell cycle patterns were determined by flow cytometry. The relationship between the expression levels of circ_0001946 and miR-135a-5p was determined by dual-luciferase reporter assays. Our data showed that the expression of circ_0001946 was upregulated in CRC tissues, which was negatively correlated with tumor size, histologic grade, lymphatic metastasis, and TMN stage, and patients with circ_0001946 overexpression were more likely to have a poor prognosis. In addition, in vitro experiments showed that silencing circ_0001946 inhibited the epithelial-mesenchymal transition (EMT) pathway and markedly suppressed CRC cell growth, migration, and invasion. Furthermore, we discovered that the transfection of miR-135a-5p mimics could reverse the antitumor effects of circRNA_0001946 downregulation. To summarize, this study revealed that circRNA_0001946 might act as a tumor promoter by activating the miR-135a-5p/EMT axis and may be a promising treatment target for CRC.

TRIM44 Promotes Colorectal Cancer Proliferation, Migration, and Invasion Through the Akt/mTOR Signaling Pathway.

PURPOSE: The tripartite motif protein 44 (TRIM44) participates in a variety of biological processes of malignant tumors. However, the expression and molecular mechanism of TRIM44 in colorectal cancer (CRC) remain unclear. PATIENTS AND METHODS: 123 CRC tissues were used for immunohistochemical assay and survival analysis. Small interfering RNA (siRNA) technology was used to silence the expression of TRIM44 in CRC cell lines. Then, we explored the effect of TRIM44 on the biological behavior of CRC cells. Finally, we studied the underlying mechanisms by Western blot. RESULTS: We found that TRIM44 is up-regulated in CRC tissues and cells. TRIM44 is a risk factor for poor prognosis in patients with CRC. In vitro, we effectively silenced the expression of TRIM44 in CRC cell lines. Silencing of TRIM44 inhibits the proliferation, migration and invasion of CRC cells. In terms of mechanistic studies, we found that high TRIM44 expression activates the Akt/mTOR signaling pathway. CONCLUSION: Our research showed that TRIM44 may serve as a biomarker for CRC patients.

Surgical outcomes of subtotal colectomy with antiperistaltic caecorectal anastomosis vs total colectomy with ileorectal anastomosis for intractable slow-transit constipation.

BACKGROUND: Few studies have compared the surgical outcomes of different surgical procedures currently used to treat refractory colonic slow-transit constipation (STC), despite the increase in the number of cases. This study aimed to analyse the long-term surgical outcomes of subtotal colectomy with antiperistaltic caecorectal anastomosis (SC-ACRA) vs total colectomy with ileorectal anastomosis (TC-IRA) for severe STC. METHODS: Between January 2005 and January 2015, we retrospectively collected clinical data of 55 patients who underwent TC-IRA (n = 35) or SC-ACRA (n = 20) for severe STC at our institution. The post-operative functional outcomes between the two groups were compared. RESULTS: There were no significant differences in age (P = 0.655), sex (P = 0.234), period of constipation (P = 0.105) and defecation frequency (P = 0.698) between the TC-IRA and SC-ACRA groups. During a median follow-up period of 72 months (range, 12-120 months), there were no significant differences between the TC-IRA and SC-ACRA groups regarding the median number of bowel movements per day [3 (1/6-7) vs 3 (1/6-5), P = 0.578], Cleveland Clinic Florida Constipation Score [2 (0-20) vs 2 (0-19), P = 0.454], Cleveland Clinic Incontinence Score [0 (0-5) vs 0 (0-2), P = 0.333] and Gastrointestinal Quality of Life Index [122 (81-132) vs 120 (80-132), P = 0.661]. Moreover, there was no significant difference in the incidence of post-operative complications between the two groups (37.1% vs 25.0%, P = 0.285). CONCLUSIONS: Our findings indicate that both TC-IRA and SC-ACRA are effective treatments for severe STC, with similar long-term outcomes.

Next-Generation Sequencing Analysis of mRNA Profile in Cisplatin-Resistant Gastric Cancer Cell Line SGC7901.

BACKGROUND Cisplatin-resistant gastric cancer (GC) occurs in patients with GC treated with cisplatin-based chemotherapy, which results in disease progression and early recurrence during the treatment. MATERIAL AND METHODS To understand the initiation and developmental mechanism underlying cisplatin-resistant GC, we developed cisplatin-resistant SGC7901 cells (SGC7901/DDP) from the parental cells (SGC7901/S) by continuous exposure to increasing concentrations of cisplatin and subjected these 2 cell lines to RNA sequencing analysis. The data were verified by quantitative polymerase chain reaction and their functional role was evaluated by cell counting kit 8 assay and cell apoptosis and cell cycle flow cytometric analysis. Bioinformatics analysis was performed to classify the differentially-expressed genes (DEGs) involved in the development of cisplatin resistance. RESULTS In comparison with SGC7901/S cells, SGC7901/DDP cells showed a total of 3165 DEGs (2014 upregulated and 1151 downregulated, fold change ≥2, and adjusted P value <0.001). qRT-PCR confirmed the reliability of the RNA sequencing results. Depletion of the top 5 upregulated mRNAs reversed the resistant index, increased apoptotic SGC7901/DDP cells, and arrested the cells at G2/M phase. Gene ontology analysis revealed that the DEGs mainly regulate metabolic process, immune system, locomotion, cell adhesion, cell growth, cell death, cytoskeleton organization, cell binding, signal transducing activity, and antioxidant activity. Kyoto Encyclopedia of Genes and Genomes analysis showed that the DEGs were mainly involved in the PI3K-Akt signaling pathway, Rap1 signaling pathway, proteoglycans in cancer, regulation of actin cytoskeleton, and pathways in cancer. CONCLUSIONS The present study is the first to interrogate mRNAs profiles in human GC cells with cisplatin resistance using RNA sequencing, which may assist in discovering potential therapeutic targets for cisplatin-resistant GC patients.

Spontaneous vaginal cuff dehiscence and evisceration of multiple organs: A case report.

RATIONALE: Vaginal cuff dehiscence and evisceration constitute a rare but potentially life-threatening event that usually occurs in postmenopausal patients who have undergone hysterectomy. This is a valuable case of spontaneous transvaginal evisceration without pelvic surgery history. PATIENT CONCERNS: A 74-year-old postmenopausal woman with an obstetric history of 7 full term vaginal deliveries, experienced sudden evisceration when she attempted to defecate. DIAGNOSES: Spontaneous vaginal cuff dehiscence and multiorgan evisceration. INTERVENTIONS: After physical examination and fluid resuscitation, the patient had underwent the Hartmann's procedure, total hysterosalpingo-oophorectomy, sacrocolpopexy, and posterior colporrhaphy. OUTCOMES: The patient recovered well and the constipation symptoms have significantly improved. One-year follow-ups examination revealed complete healing of the vaginal cuff, and there was no evidence of prolapse. LESSONS: We report a case of spontaneous vaginal cuff evisceration without pelvic surgery history but with constipation and redundant sigmoid colon. After resecting the necrotic sigmoid colon, the patient's constipation symptoms significantly improved. It is reasonable to speculate that the etiology was related to severe sigmoidocoele.

Rab3IP interacts with SSX2 and enhances the invasiveness of gastric cancer cells.

RAB3A interacting protein (Rab3IP) has been determined to be involved in cancer progression; however, its expression pattern and function in gastric cancer remain unknown. The aim of this study was to determine the association between Rab3IP and gastric cancer, in addition to its functional role in this disease. Overexpression of Rab3IP in gastric cancer was verified at both transcriptional and translational levels. Analysis of clinical data indicated its role as an independent risk factor for survival. Cellular studies showed that Rab3IP could induce an aggressive phenotype in gastric cancer cells and that its expression was correlated with markers of the epithelial-mesenchymal transition (EMT). In addition, we verified the co-expression of and interplay between Rab3IP and SSX2 during gastric cancer progression. Thus, these findings elucidated the central role of Rab3IP in inducing an invasive phenotype in gastric cancer cells, in addition to its involvement in EMT. Our results could be exploited for the clinical prognosis and treatment of this important disease.

Utility of colon leakage score in left-sided colorectal surgery.

BACKGROUND: The aim of the study was to evaluate the clinical utility of the colon leakage score (CLS) in predicting the risk of anastomotic leakage (AL) after left-sided colorectal surgery. MATERIALS AND METHODS: This investigation was designed as a retrospective study of 304 patients who underwent left-sided colorectal surgery. The patients were classified into two groups as those who developed AL and those who did not develop AL, and the CLSs of the two groups were compared. The predictive value and the cutoff value of the CLS were assessed by receiver operating characteristic and logistic regression analysis. RESULTS: A significant difference was noted in the mean CLSs of the groups with and without AL (P < 0.001). The values of the area under the receiver operating characteristic curve (0.965; confidence interval, 0.913-1.00) and the odds ratio (2.9; confidence interval, 1.59-4.83; P < 0.001) indicated that CLS was a good predictor of AL. A CLS of 11 was found to be the best cutoff value, with a sensitivity and specificity of 84.6% and 87.2%, respectively. CONCLUSIONS: Our findings indicate that CLS can effectively predict the risk of AL after left-sided colorectal surgery and that a CLS of 11 can be used as a cutoff value for the risk level.

[Value of self-expanding metallic stent for obstructing left-sided colon cancer or rectal cancer].

OBJECTIVE: To investigate the therapeutic value of self-expanding metallic stent (SEMS) for resectable obstructing left-sided colon cancer or rectal cancer. METHODS: Clinical data of 73 patients who had acute obstruction due to left-sided colon cancer or rectal cancer during May 2007 to January 2012 were retrospectively analyzed. The patients were divided into 2 groups: SEMS group (34 cases) underwent surgical resection after insertion of SEMS; emergency surgery group (39 cases) underwent emergency operation. The 2 group patients were compared for the incidence of primary anastomosis, stoma rate, laparoscopic surgery rate, mortality, postoperative morbidity, ICU admission rate, length of ICU stay, hospital stay, and hospitalization costs. RESULTS: The incidence of primary anastomosis in SEMS group was significantly higher than that in emergency surgery group (97.1% vs. 56.4%, χ(2) = 16.256, P < 0.001), and the protective stoma rate and permanent stoma rate in SEMS group were both lower than those in emergency surgery group (33.3% vs. 86.3%, 2.9% vs. 43.6%, χ(2) value were 14.972 and 16.156, both P < 0.001). Patients in SEMS group underwent significantly more laparoscopic surgery than in emergency surgery group (47.1% vs. 0, χ(2) = 23.505, P < 0.001). There were no significant difference in postoperative mortality (2.9% vs. 10.3%, P = 0.364). The postoperative morbidity in SEMS group was significantly lower than that in emergency surgery group (35.3% vs. 66.7%, P = 0.007). Incisional infection was the most common complication in both groups, and the incidence of which seemed to be more higher in emergency surgery group (17.6% vs. 38.5%, χ(2) = 3.840, P = 0.050). There was a lower ICU admission rate in SEMS group (24.2% vs. 53.9%, χ(2) = 6.972, P = 0.008), and the mean length of ICU stay and hospital stay were both shorter in SEMS group ((69.5 ± 7.4) hours vs. (114.3 ± 10.9) hours, t = -20.23, P < 0.001; (19.6 ± 4.8) days vs. (23.4 ± 6.2) days, t = -2.90, P = 0.005). The cost of hospitalization was less in SEMS group (45 383 ± 15 648 vs. 61 485 ± 20 380, t = -3.74, P < 0.001). CONCLUSIONS: SEMS can effectively relieve the large intestinal obstruction caused by left-sided colon cancer or rectal cancer, and change the traditional emergency surgery into a selective surgery with better outcomes. SEMS appears to be a valuable technique for resectable obstructing left-sided colorectal cancer.

Extensively infiltrating colon adenocarcinoma similar to Crohn's disease: a case report.

A 38-year-old Chinese man presenting with chronic diarrhea and secondary incomplete intestinal obstruction was hospitalized in April 2010. Electronic colonoscopy and barium enema examination initially showed longitudinal scar-like strictures and cobblestone appearance in the colon that was similar to those in Crohn's disease. After subtotal colectomy and partial intestinal resection, the pathological examination indicated colon adenocarcinoma that diffusely infiltrated along the colon longitudinal axis rather than the initial diagnosis of Crohn's disease. Pathological examination revealed colon adenocarcinoma with excessive desmoplastic reaction and infiltrating cancer cells along the colon longitudinal axis that may have accounted for the morphological similarities to Crohn's disease in this case. The findings in the present case suggest that colon carcinoma should be considered when Crohn's disease-like findings are encountered, not only in individuals with concurrent cancer in other sites, but also in patients with a long history of gastrointestinal symptoms such as chronic diarrhea or abdominal pain.