Hydrogel-based immunoregulation of macrophages for tissue repair and regeneration.

The rational design of hydrogel materials to modulate the immune microenvironment has emerged as a pivotal approach in expediting tissue repair and regeneration. Within the immune microenvironment, an array of immune cells exists, with macrophages gaining prominence in the field of tissue repair and regeneration due to their roles in cytokine regulation to promote regeneration, maintain tissue homeostasis, and facilitate repair. Macrophages can be categorized into two types: classically activated M1 (pro-inflammatory) and alternatively activated M2 (anti-inflammatory and pro-repair). By regulating the physical and chemical properties of hydrogels, the phenotypic transformation and cell behavior of macrophages can be effectively controlled, thereby promoting tissue regeneration and repair. A full understanding of the interaction between hydrogels and macrophages can provide new ideas and methods for future tissue engineering and clinical treatment. Therefore, this paper reviews the effects of hydrogel components, hardness, pore size, and surface morphology on cell behaviors such as macrophage proliferation, migration, and phenotypic polarization, and explores the application of hydrogels based on macrophage immune regulation in skin, bone, cartilage, and nerve tissue repair. Finally, the challenges and future prospects of macrophage-based immunomodulatory hydrogels are discussed.

Recent progress in bone-repair strategies in diabetic conditions.

Bone regeneration following trauma, tumor resection, infection, or congenital disease is challenging. Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia. It can result in complications affecting multiple systems including the musculoskeletal system. The increased number of diabetes-related fractures poses a great challenge to clinical specialties, particularly orthopedics and dentistry. Various pathological factors underlying DM may directly impair the process of bone regeneration, leading to delayed or even non-union of fractures. This review summarizes the mechanisms by which DM hampers bone regeneration, including immune abnormalities, inflammation, reactive oxygen species (ROS) accumulation, vascular system damage, insulin/insulin-like growth factor (IGF) deficiency, hyperglycemia, and the production of advanced glycation end products (AGEs). Based on published data, it also summarizes bone repair strategies in diabetic conditions, which include immune regulation, inhibition of inflammation, reduction of oxidative stress, promotion of angiogenesis, restoration of stem cell mobilization, and promotion of osteogenic differentiation, in addition to the challenges and future prospects of such approaches.

Promotion of uterine reconstruction by a tissue-engineered uterus with biomimetic structure and extracellular matrix microenvironment.

The recurrence rate for severe intrauterine adhesions is as high as 60%, and there is still lack of effective prevention and treatment. Inspired by the nature of uterus, we have developed a bilayer scaffold (ECM-SPS) with biomimetic heterogeneous features and extracellular matrix (ECM) microenvironment of the uterus. As proved by subtotal uterine reconstruction experiments, the mechanical and antiadhesion properties of the bilayer scaffold could meet the requirement for uterine repair. With the modification with tissue-specific cell-derived ECM, the ECM-SPS had the ECM microenvironment signatures of both the endometrium and myometrium and exhibited the property of inducing stem cell-directed differentiation. Furthermore, the ECM-SPS has recruited more endogenous stem cells to promote endometrial regeneration at the initial stage of repair, which was accompanied by more smooth muscle regeneration and a higher pregnancy rate. The reconstructed uterus could also sustain normal pregnancy and live birth. The ECM-SPS may thereby provide a potential treatment for women with severe intrauterine adhesions.

[Relationship Between Urban Spatial Pattern and Thermal Environment Response in Summer: A Case Study of Hefei City].

With the continuous expansion of cities, the land cover type of the region is transformed, a large number of natural landscapes are replaced by man-made landscapes, and the environmental temperature rises. The study of the response relationship between urban spatial pattern and thermal environment provides some guidance for improving the ecological environment and optimizing the urban spatial layout. Based on the Landsat 8 series remote sensing image data of Hefei City in 2020 and analysis platforms such as ENVI and ARCGIS, Pearson correlation and profile lines were used to reflect the correlation between the two. Then, the three spatial pattern components with the greatest correlation were selected to construct multiple regression functions to investigate the influence of urban spatial pattern on urban thermal environment and its mechanism of action. The results showed that:① the high temperature area of Hefei City increased significantly with the advance of time during 2013-2020. For different seasons, the urban heat island effect showed that summer>autumn>spring>winter. ② In the central urban area, the building occupancy, building height, imperviousness occupancy, and population density were significantly higher than those in the suburbs, whereas fractional vegetation coverage presented a higher suburban than urban area and mainly showed a point distribution in the urban area and an irregular distribution of water bodies. ③ The urban high-temperature zone was mainly distributed in various development zones in urban areas, whereas other places in urban areas were dominated by medium-high temperature and above-temperature zoning, and suburban areas were dominated by medium-low temperature. ④ The Pearson coefficients between the spatial pattern of each element and the thermal environment were positively correlated with the building occupancy (0.395), impervious surface occupancy (0.333), population density (0.481), and building height (0.188) and negatively correlated with fractional vegetation coverage (-0.577) and water occupancy (-0.384). The coefficients of the constructed multiple regression functions, including building occupancy, population density, and fractional vegetation coverage, were 8.372, 0.295, and -5.639 respectively, with a constant of 38.555. The results of this study can provide a reference basis for optimizing urban spatial layouts and improving urban living quality.

Polyphenolic-modified cellulose acetate membrane for bone regeneration through immunomodulation.

To enhance the bioactivity of cellulosic derivatives has become an important strategy to promote their value for clinical applications. Herein, protocatechualdehyde (PCA), a polyphenolic molecule, was used to modify a cellulose acetate (CA) membrane by combining with metal ions to confer an immunomodulatory activity. The PCA-modified CA membrane has shown a significant radical scavenging activity, thereby suppressed the inflammatory response and created a favorable immune microenvironment for osteogenesis and mineralization. Moreover, addition of metal ions could further stimulate the osteogenic differentiation of stem cells and accelerate bone regeneration both in vitro and in vivo. This study may provide a strategy to promote the immunomodulatory activity of cellulose-based biomaterials for bone regeneration.

Design of biopolymer-based hemostatic material: Starting from molecular structures and forms.

Uncontrolled bleeding remains as a leading cause of death in surgical, traumatic, and emergency situations. Management of the hemorrhage and development of hemostatic materials are paramount for patient survival. Owing to their inherent biocompatibility, biodegradability and bioactivity, biopolymers such as polysaccharides and polypeptides have been extensively researched and become a focus for the development of next-generation hemostatic materials. The construction of novel hemostatic materials requires in-depth understanding of the physiological hemostatic process, fundamental hemostatic mechanisms, and the effects of material chemistry/physics. Herein, we have recapitulated the common hemostatic strategies and development status of biopolymer-based hemostatic materials. Furthermore, the hemostatic mechanisms of various molecular structures (components and chemical modifications) are summarized from a microscopic perspective, and the design based on them are introduced. From a macroscopic perspective, the design of various forms of hemostatic materials, e.g., powder, sponge, hydrogel and gauze, is summarized and compared, which may provide an enlightenment for the optimization of hemostat design. It has also highlighted current challenges to the development of biopolymer-based hemostatic materials and proposed future directions in chemistry design, advanced form and clinical application.

Borderline Developmental Dysplasia of the Hip: A Risk Factor Predicting the Development and Poor Prognosis after Core Decompression for Idiopathic Osteonecrosis of the Femoral Head.

OBJECTIVE: It is unclear whether idiopathic osteonecrosis of the femoral head (ONFH) is associated with borderline developmental dysplasia of the hip (BDDH). This study aimed to compare the incidence of BDDH between patients with idiopathic ONFH and matched control subjects and determine the influence of BDDH on poor prognosis after core decompression (CD). METHODS: We retrospectively examined 78 consecutive patients (111 hips) with idiopathic ONFH undergoing CD and 1:2 matched with 156 control subjects (222 hips). The anteroposterior pelvic radiographs were used to measure the acetabular anatomical parameters and divide included subjects into BDDH or non-BDDH group. The incidence of BDDH and acetabular anatomical parameters were compared between patients with idiopathic ONFH and matched controls. Clinical outcomes, such as Harris Hip Score (HHS), progression of collapse, and conversion to total hip arthroplasty (THA), were compared between patients with BDDH and without BDDH in the idiopathic ONFH group, with a mean follow-up of 72.1 ± 36.6 months. RESULTS: Patients with idiopathic ONFH had a significantly higher incidence of BDDH than matched controls (29.7% vs 12.2%, p < 0.001). Less acetabular coverage was also found in patients with idiopathic ONFH than in matched controls as demonstrated by lower CEA (28.5° ± 4.7° vs 33.1° ± 5.7°, p < 0.001), AHI (82.4 ± 5.0 vs 86.3 ± 5.4, p < 0.001), ADR (299.6 ± 28.4 vs 318.8 ± 31.3, p < 0.001), and a higher sharp angle (40.0° ± 3.4° vs 37.4° ± 3.7°, p < 0.001). In patients with idiopathic ONFH, the BDDH group had a significantly lower mean HHS at the last follow-up (83.5 ± 17.4 vs 91.6 ± 9.7, p = 0.015) with a different score distribution (p = 0.004), and a lower 5-year survival rate with both clinical failure (66.7%, 95% CI 52.4%-84.9% vs 83.7%, 95% CI 75.2%-93.1%; p = 0.028) and conversion to THA (74.6%, 95% CI 60.7%-91.6% vs 92.1%, 95% CI 85.6%-99.0%; p = 0.008) as the endpoints than the non-BDDH group. CONCLUSION: The incidence of BDDH was significantly higher in patients with idiopathic ONFH than matched controls, and idiopathic ONFH patients who underwent CD with BDDH had lower mean HHS as well as 5-year survival rate than those without BDDH. Therefore, BDDH should be considered a risk factor predicting the development of idiopathic ONFH as well as poor prognosis after CD.

Application of antibody-conjugated small intestine submucosa to capture urine-derived stem cells for bladder repair in a rabbit model.

The need for bladder reconstruction and side effects of cystoplasty have spawned the demand for the development of alternative material substitutes. Biomaterials such as submucosa of small intestine (SIS) have been widely used as patches for bladder repair, but the outcomes are not fully satisfactory. To capture stem cells in situ has been considered as a promising strategy to speed up the process of re-cellularization and functionalization. In this study, we have developed an anti-CD29 antibody-conjugated SIS scaffold (AC-SIS) which is capable of specifically capturing urine-derived stem cells (USCs) in situ for tissue repair and regeneration. The scaffold has exhibited effective capture capacity and sound biocompatibility. In vivo experiment proved that the AC-SIS scaffold could promote rapid endothelium healing and smooth muscle regeneration. The endogenous stem cell capturing scaffolds has thereby provided a new revenue for developing effective and safer bladder patches.

Multi-crosslinking hydrogels with robust bio-adhesion and pro-coagulant activity for first-aid hemostasis and infected wound healing.

Bio-adhesive polysaccharide-based hydrogels have attracted much attention in first-aid hemostasis and wound healing for excellent biocompatibility, antibacterial property and pro-healing bioactivity. Yet, the inadequate mechanical properties and bio-adhesion limit their applications. Herein, based on dynamic covalent bonds, photo-triggered covalent bonds and hydrogen bonds, multifunctional bio-adhesive hydrogels comprising modified carboxymethyl chitosan, modified sodium alginate and tannic acid are developed. Multi-crosslinking strategy endows hydrogels with improved strength and flexibility simultaneously. Owing to cohesion enhancement strategy and self-healing ability, considerable bio-adhesion is presented by the hydrogel with a maximal adhesion strength of 162.6 kPa, 12.3-fold that of commercial fibrin glue. Based on bio-adhesion and pro-coagulant activity (e.g., the stimulative aggregation and adhesion of erythrocytes and platelets), the hydrogel reveals superior hemostatic performance in rabbit liver injury model with blood loss of 0.32 g, only 54.2% of that in fibrin glue. The healing efficiency of hydrogel for infected wounds is markedly better than commercial EGF Gel and Ag+ Gel due to the enhanced antibacterial and antioxidant properties. Through the multi-crosslinking strategy, the hydrogels show enhanced mechanical properties, fabulous bio-adhesion, superior hemostatic performance and promoting healing ability, thereby have an appealing application value for the first-aid hemostasis and infected wound healing.

Promotion of right ventricular outflow tract reconstruction using a novel cardiac patch incorporated with hypoxia-pretreated urine-derived stem cells.

Approximately 25% of patients with congenital heart disease require implantation of patches to repair. However, most of the currently available patches are made of inert materials with unmatched electrical conductivity and mechanical properties, which may lead to an increased risk for arrhythmia and heart failure. In this study, we have developed a novel Polyurethane/Small intestinal submucosa patch (PSP) with mechanical and electrical properties similar to those of the native myocardial tissue, and assessed its feasibility for the reconstruction of right ventricular outflow tract. A right ventricular outflow tract reconstruction model was constructed in 40 rabbits. Compared with commercially available bovine pericardium patch, the PSP patch has shown better histocompatibility and biodegradability, in addition with significantly improved cardiac function. To tackle the significant fibrosis and relatively poor vascularization during tissue remodeling, we have further developed a bioactive patch by incorporating the PSP composites with urine-derived stem cells (USCs) which were pretreated with hypoxia. The results showed that the hypoxia-pretreated bioactive patch could significantly inhibit fibrosis and promote vascularization and muscularization, resulting in better right heart function. Our findings suggested that the PSP patch combined with hypoxia-pretreated USCs may provide a better strategy for the treatment of congenital heart disease.

Hypotensive Anesthesia Combined with Tranexamic Acid Reduces Perioperative Blood Loss in Simultaneous Bilateral Total Hip Arthroplasty: A Retrospective Cohort Study.

OBJECTIVE: To assess the efficacy and safety of hypotensive anesthesia (HA) combined with tranexamic acid (TXA) for reducing perioperative blood loss in simultaneous bilateral total hip arthroplasty (SBTHA). METHODS: In this retrospective cohort study, a total of 183 eligible patients (15 females and 168 males, 44.01 ± 9.29 years old) who underwent SBTHA from January 2015 to September 2020 at our medical center were enrolled for analysis. Fifty-nine patients received standard general anesthesia (Std-GA group), the other 85 and 39 patients received HA with an intraoperative mean arterial pressure between 70 and 80 mmHg (70-80 HA group) and below 70 mmHg (<70 HA group), respectively. TXA was administrated to all patients. Perioperative blood loss (total, dominant, and hidden), transfusion rate and volume, hemoglobin and hematocrit reduction, duration of operation and anesthesia, length of hospitalization, range of hip motion as well as postoperative complications were collected from hospital's electronic records and compared between groups. RESULTS: All patients were followed for more than 3 months. Total blood loss in the two HA groups (1390.25 ± 595.67 ml and 1377.74 ± 423.46 ml, respectively) was significantly reduced compared with that in Std-GA group (1850.83 ± 800.73 ml, P < 0.001). Both dominant and hidden blood loss were dramatically decreased when HA was applied (both P < 0.001). Accordingly, the transfusion rate along with volume in 70-80 HA group (14.1%, 425.00 ± 128.81 ml) and <70 HA group (12.8%, 340.00 ± 134.16 ml) were reduced in comparison with those in Std-GA group (37.3%, 690.91 ± 370.21ml; P = 0.001 and P = 0.014, respectively). The maximal hemoglobin and hematocrit reduction in both HA groups were significantly less than those in Std-GA group (both P < 0.001). Of note, 70-80 and <70 HA groups exhibited comparable efficacy with no significant differences between them. Besides, significant difference in duration of surgery was found among groups (P = 0.044 and P < 0.001), while no differences in anesthesia time and postoperative range of hip motion were observed. Regarding complications, the incidence of both acute kidney injury and postoperative hypotension in <70 HA group was significantly higher than that in 70-80 HA and Std-GA groups (P = 0.014 and P < 0.001). Incidence of acute myocardial injury was similar among groups (P = 0.099) and no other severe complications or mortality were recorded. CONCLUSION: The combination of HA with a mean arterial pressure (MAP) of 70-80 mmHg and TXA could significantly reduce blood loss and transfusion during SBTHA, in addition to shortening operation time and length of hospitalization, and with no increase in complications.

Hypertriglyceridemia: A Neglected Risk Factor for Ischemic Stroke?

Hypertriglyceridemia is caused by defects in triglyceride metabolism and generally manifests as abnormally high plasma triglyceride levels. Although the role of hypertriglyceridemia may not draw as much attention as that of plasma cholesterol in stroke, plasma triglycerides, especially nonfasting triglycerides, are thought to be correlated with the risk of ischemic stroke. Hypertriglyceridemia may increase the risk of ischemic stroke by promoting atherosclerosis and thrombosis and increasing blood viscosity. Moreover, hypertriglyceridemia may have some protective effects in patients who have already suffered a stroke via unclear mechanisms. Therefore, further studies are needed to elucidate the role of hypertriglyceridemia in the development and prognosis of ischemic stroke.

Primary Ewing sarcoma/peripheral primitive neuroectodermal tumors in the cranial bone and mobile spine: what is the difference?

BACKGROUND: Primary Ewing sarcoma (ES)/peripheral primitive neuroectodermal tumors (pPNETs) are aggressive bone tumors that rarely occur in the axial skeleton, including the cranial bone and mobile spine. The purpose of this study was to investigate whether there were any differences in patient characteristics, treatment strategies, and outcomes between patients with ES/pPNETs of the cranial bone and those with ES/pPNETs of the mobile spine. METHODS: A retrospective study was performed on 33 patients with ES/pPNETs who had been surgically treated and pathologically confirmed at our institution between 2010 and 2020. Patient characteristics were compared using Fisher exact tests or independent t tests. Survival rates were estimated via Kaplan-Meier survival analysis and compared using log-rank tests. RESULTS: Thirteen patients had ES/pPNETs of the cranial bone (39.4%), while 20 patients had ES/pPNETs of the mobile spine (60.6%). Patients with ES/pPNETs of the cranial bone had a younger mean age (14.8 vs 22.6 years; p = 0.047) and longer mean disease duration (2.5 vs 1.9 months; p = 0.008) compared with those of patients with ES/pPNETs of the mobile spine. Kaplan-Meier analysis showed that gross total resection (GTR) and radiotherapy resulted in a longer median survival time. The overall survival rates and progression-free survival rates of patients with ES/pPNETs of the cranial bone versus those of the mobile spine were not significantly different (p = 0.386 and p = 0.368, respectively). CONCLUSIONS: Patients with ES/pPNETs of the cranial bone were younger compared to patients with ES/pPNETs of the mobile spine. There was no significant difference in the prognosis of patients with ES/pPNETs of the cranial bone versus those of the mobile spine. Taken together, our findings suggest that GTR and radiotherapy offer the best prognosis for improved long-term survival.

Evaluation of Four Lymph Node Classifications for the Prediction of Survival in Hilar Cholangiocarcinoma.

BACKGROUND: An important prognostic indicator of hilar cholangiocarcinoma (HCCA) in patients after surgery is metastasis of lymph nodes (LN). However, there are many types of LN staging systems to the issue of a better determination of the prognosis of patients through the lymphatic staging system which needs research. Based on the above, we tried to re-evaluate the staging system of HCCA LNs. We compared the American Joint Committee on Cancer (AJCC), number of metastatic LNs (MLN), ratio of LN (LNR), and log odds of MLNs (LODDS) in individuals undergoing curative resection to determine the best LN staging system. METHODS: In the current study, we retrospectively analyzed 229 patients undergoing curative resection. We evaluated the impact of the stage of AJCC pN, LNR, LODDS, and MLN on OS (overall survival) and RFS (recurrence-free survival). According to the curve of receiver operating characteristic (ROC), we compared the predictive capacity of different staging systems of LN for survival and recurrence. RESULTS: Multivariate analysis results revealed that LODDS > - 0.45 (95% CI = 1.115-2.709, P = 0.015; 95% CI = 1.187-2.780, P = 0.006) are independent risk factors affecting OS and RFS, respectively. Compared with LN status, AJCC pN stage, MLN, and LNR, the variable having the highest area under the ROC curve (AUC) was LODDS when predicting 1-year, 3-year, and 5-year OS and RFS. CONCLUSION: This study shows that metastasis of LNs is a key indicator for predicting patient death and recurrence. Among them, LODDS is the best LN staging system for the prognostic evaluation of HCCA patients after surgery. Clinicians can incorporate LODDS into HCCA patient lymphatic staging system for a more accurate prognosis of HCCA patients post-surgery.

Techniques for increasing the yield of stem cell-derived exosomes: what factors may be involved?

Exosomes are nano-scale extracellular vesicles secreted by cells and constitute an important part in the cell-cell communication. The main contents of the exosomes include proteins, microRNAs, and lipids. The mechanism and safety of stem cell-derived exosomes have rendered them a promising therapeutic strategy for regenerative medicine. Nevertheless, limited yield has restrained full explication of their functions and clinical applications To address this, various attempts have been made to explore the up- and down-stream manipulations in a bid to increase the production of exosomes. This review has recapitulated factors which may influence the yield of stem cell-derived exosomes, including selection and culture of stem cells, isolation and preservation of the exosomes, and development of artificial exosomes.

Minimally invasive transforaminal lumbar interbody fusion versus oblique lateral interbody fusion for lumbar degenerative disease: a meta-analysis.

BACKGROUND: Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) and oblique lateral interbody fusion (OLIF) are widely used in the treatment of lumbar degenerative diseases. In the present study, a meta-analysis was conducted to compare the clinical and radiographic efficacy of these two procedures. METHODS: A systematic literature review was performed, and the quality of retrieved studies was evaluated with the Newcastle-Ottawa Scale (NOS). Clinical outcomes, including operation time, intraoperative blood loss, improvement in Visual Analogue Scale (VAS), improvement in Oswestry Disability Index (ODI), Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) effectiveness rate and complications, in addition to radiographic outcomes, including restoration of disc height, disc angle, overall lumbar lordosis, fusion rate and subsidence, were extracted and input into a fixed or random effect model to compare the efficacy of MIS-TLIF and OLIF. RESULTS: Seven qualified studies were included. Clinically, OLIF resulted in less intraoperative blood loss and shorter operation time than MIS-TLIF. Improvement of VAS for leg pain was more obvious in the OLIF group (P < 0.0001), whereas improvement of VAS for back pain (P = 0.08) and ODI (P = 0.98) as well as JOABPEQ effectiveness rate (P = 0.18) were similar in the two groups. Radiographically, OLIF was more effective in restoring disc height (P = 0.01) and equivalent in improving the disc angle (P = 0.18) and lumbar lordosis (P = 0.48) compared with MIS-TLIF. The fusion rate (P = 0.11) was similar in both groups, while the subsidence was more severe in the MIS-TLIF group (P < 0.00001). CONCLUSIONS: The above evidence suggests that OLIF is associated with a shorter operation time (with supplementary fixation in the prone position) and less intraoperative blood loss than MIS-TLIF and can lead to better leg pain alleviation, disc height restoration and subsidence resistance. No differences regarding back pain relief, functional recovery, complications, disc angle restoration, lumbar lordosis restoration and fusion rate were found. However, due to the limited number of studies, our results should be confirmed with high-level studies to fully compare the therapeutic efficacy of MIS-TLIF and OLIF. TRIAL REGISTRATION: PROSPERO ID:  CRD42020201903 .

Decellularized scaffold and its elicited immune response towards the host: the underlying mechanism and means of immunomodulatory modification.

The immune response of the host towards a decellularized scaffold is complex. Not only can a number of immune cells influence this process, but also the characteristics, preparation and modification of the decellularized scaffold can significantly impact this reaction. Such factors can, together or alone, trigger immune cells to polarize towards either a pro-healing or pro-inflammatory direction. In this article, we have comprehensively reviewed factors which may influence the immune response of the host towards a decellularized scaffold, including the source of the biomaterial, biophysical properties or modifications of the scaffolds with bioactive peptides, drugs and cytokines. Furthermore, the underlying mechanism has also been recapitulated.

Procyanidins-crosslinked small intestine submucosa: A bladder patch promotes smooth muscle regeneration and bladder function restoration in a rabbit model.

Currently the standard surgical treatment for bladder defects is augmentation cystoplasty with autologous tissues, which has many side effects. Biomaterials such as small intestine submucosa (SIS) can provide an alternative scaffold for the repair as bladder patches. Previous studies have shown that SIS could enhance the capacity and compliance of the bladder, but its application is hindered by issues like limited smooth muscle regeneration and stone formation since the fast degradation and poor mechanical properties of the SIS. Procyanidins (PC), a natural bio-crosslinking agent, has shown anti-calcification, anti-inflammatory and anti-oxidation properties. More importantly, PC and SIS can crosslink through hydrogen bonds, which may endow the material with enhanced mechanical property and stabilized functionalities. In this study, various concentrations of PC-crosslinked SIS (PC-SIS) were prepared to repair the full-thickness bladder defects, with an aim to reduce complications and enhance bladder functions. In vitro assays showed that the crosslinking has conferred the biomaterial with superior mechanical property and anti-calcification property, ability to promote smooth muscle cell adhesion and upregulate functional genes expression. Using a rabbit model with bladder defects, we demonstrated that the PC-SIS scaffold can rapidly promote in situ tissue regrowth and regeneration, in particular smooth muscle remodeling and improvement of urinary functions. The PC-SIS scaffold has therefore provided a promising material for the reconstruction of a functional bladder.

MiR-21 antagomir improves insulin resistance and lipid metabolism disorder in streptozotocin-induced type 2 diabetes mellitus rats.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a major cause of death with an increasing incidence at an epidemic rate. The existing treatments for T2DM lack long-term effective blood glucose control. In this study, the effects of miR-21 antagomir on T2DM and the related mechanism were investigated using streptozotocin (STZ)-induced T2DM rats. METHODS: 30 T2DM rats were randomly divided into 3 groups (n=10): T2DM group, T2DM rats with miR-21 antagomir group, T2DM rats with NC antagomir group. The expression of miR-21 in rats was detected by qRT-PCR. blood glucose, triacylglycerol (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-Cho), insulin, adiponectin, ITT and GTT were detected. The expression of TIMP3 in si-TIMP3 rats and the expression of TIMP3 in T2DM rats with miR-21 antagomir and si-TIMP3 was detected by Western blotting. RESULTS: We found that miR-21 antagomir reduced blood glucose concentration in T2DM rats. MiR21 antagomir improved lipid metabolic disorder by decreasing the levels of triacylglycerol (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-Cho) and increasing the level of high-density lipoprotein cholesterol (HDL-Cho). Also, miR-21 antagomir reduced the value of homeostasis model assessment of insulin resistance (HOMA-IR), hemoglobin A1c (HbAc1), plasma insulin, and up-regulated the plasma adiponectin. These results, combined with insulin tolerance tests (ITT) and glucose tolerance tests (GTT) results, showed that miR-21 improved insulin resistance in STZ-induced T2DM rats. Then the target relationship between miR-21 and tissue inhibitor of metalloproteinases 3 (TIMP3) was proved by luciferase reporter assay. More impressively, miR-21 significantly increased the expression level of TIMP3 in STZ-induced T2DM rats. CONCLUSIONS: Our study taken together has shown that miR-21 antagomir improved insulin resistance and lipid metabolism disorder in STZ-induced T2DM rats by up-regulating the expression level of TIMP3. This study suggested that miR-21 antagomir could be used as an effective therapeutic strategy and the underlying mechanism was revealed.

A new technology for reducing anastomotic fistula in the neck after esophageal cancer surgery.

BACKGROUND: To explore the risk factors and prevention methods of cervical mechanical anastomotic fistula and stenosis after the radical resection of esophageal cancer. METHODS: From March 2018 to November 2018, 128 patients undergoing mechanical anastomosis of esophageal cancer were selected from the Department of Thoracic Surgery of The First Affiliated Hospital of Zhengzhou University. All the enrolled patients were operated on using the Mckeown method, and a retrospective study was conducted. Data for preoperative and postoperative test indices, intraoperative embedding materials, postoperative complications, and preoperative and postoperative treatment were collected, and the relationship between various factors and the incidence of cervical anastomotic fistula and stenosis was analysed. Univariate analysis was conducted using t tests or Fisher's exact probability method, and multivariate analysis was conducted using logistic regression models. RESULTS: All 128 patients successfully underwent surgery without dying. The enrolled patients were evaluated using the Stooler classification, with 28 patients having grade 0, 41 patients having grade 1, 34 patients having grade 2, 21 patients having grade 3, and 4 patients having grade 4 stenosis. Patients with stenosis of grade 3 or above had obvious choking sensation, which could only be relieved by balloon dilation. Symptoms in all patients with stenosis were relieved by balloon dilation. There were no significant differences between the two groups regarding embedding materials, preoperative choking history, history of alcohol consumption, history of hypertension, history of coronary heart disease, history of diabetes, postoperative calcium concentration, average albumin concentration, average platelet concentration, body mass index, anastomotic fistula, preoperative chemotherapy, postoperative chemotherapy, or postoperative cough (P>0.05). There were significant differences in postoperative reflux (χ2=11.338, P<0.05) and scar constitution (χ2=12.497, P<0.05). The effects of embedding materials in patients with anastomotic fistula were significantly different (χ2=4.372, P<0.05). CONCLUSIONS: Postoperative reflux and scar constitution may be risk factors for postoperative anastomotic stenosis after resection of esophageal cancer. There was almost no difference in the effects on esophageal anastomotic stenosis between embedding materials and the omentum majus, but Neoveil® may have certain advantages in preventing cervical anastomotic fistula, and thus may have certain clinical application value.