OBJECTIVE:There is a lack of evidence to support a consensus on whether surgery or radiotherapy is optimal for elderly or very elderly patients with early-stage non-small cell lung cancer (NSCLC). We aimed to assess the impact of surgery or radiotherapy on survival in elderly (≥70 years) and very elderly (≥80 years) patients with early-stage NSCLC. METHODS:Patients aged ≥70 years diagnosed with early-stage NSCLC between January 1, 1975, and December 31, 2018, were identified in the Surveillance, Epidemiology, and End Results (SEER) database. Overall survival (OS) and cancer-specific survival (CSS) were assessed based on surgery, radiotherapy, and no-treatment groups. RESULTS:Data for 15,224 NSCLC patients aged ≥70 years were collected, which consisted of 6949 (45.6%) patients who underwent surgery alone, 5014 (32.9%) who underwent radiotherapy alone, and 3261 (21.5%) who received no treatment. Surgery significantly improved patient survival compared with no treatment (MST: 74 months vs. 7 months, HR: 0.201, 95% CI: 0.186-0.217, P < 0.001), as did radiotherapy (MST: 28 months vs. 7 months, HR: 0.440; 95% CI: 0.413-0.469, P < 0.001). Surgery also resulted in improved survival compared with radiotherapy (74 months vs. 28 months, HR: 0.455; 95% CI: 0.430-0.482, P < 0.001). A similar conclusion was made from the analysis of CSS. A subgroup analysis further confirmed the survival benefits. CONCLUSIONS:The results of this large-scale retrospective study indicate that both surgery and radiotherapy significantly enhance survival outcomes in patients aged ≥70 or ≥80 years with early-stage NSCLC. The survival benefits of surgery were particularly notable.

To evaluate the safety and clinical outcome of two-session catheter-directed sclerotherapy (CDS) with 99

Prophylactic embolization is usually performed using gelatin sponge particles, which are absorbed within several weeks, for managing angiographically negative gastrointestinal bleeding. This study aimed to evaluate the safety and effectiveness of transcatheter arterial embolization (TAE) with quick-soluble gelatin sponge particles (QS-GSP) that dissolve in less than 4 h for treating angiographically negative gastrointestinal bleeding. We included ten patients (M:F = 7:3; mean age, 64.3 years) who underwent prophylactic TAE with QS-GSP for angiographically negative acute gastrointestinal bleeding between 2021 and 2023. The technical success rate of TAE, clinical outcomes focusing on rebleeding, and procedure-related complications were evaluated. The embolized arteries were the gastroduodenal (n = 3), jejunal (n = 4), and ileal (n = 3) arteries. QS-GSP (150–350 µm or 350–560 µm) were used alone (n = 8) or in combination with a coil (n = 1). A 100% technical success rate was accomplished. In 1 patient (10%), rebleeding occurred 2 days after prophylactic TAE of the gastroduodenal artery, and this was managed by repeat TAE. There were no procedure-related complications. The use of QS-GSP for prophylactic TAE appears to be safe and effective for controlling bleeding among patients with angiographically negative gastrointestinal bleeding. There were no cases of related ischemic complications of the embolized bowels likely attributable to recanalization of the affected arteries following biodegradation of QS-GSP.

BACKGROUND Vaginal myomectomy is the most common form of radical treatment for prolapsed submucosal leiomyoma and is typically performed under general anesthesia. However, an alternative treatment approach is needed for patients who cannot tolerate general anesthesia. We describe a case with such a patient who was successfully treated via a minimally invasive method under local anesthesia.CASE SUMMARY A 46-year-old female suffered from abnormal uterine bleeding, severe anemia,and a reduced quality of life attributed to a massive prolapsed submucosal leiomyoma. She could not tolerate general anesthesia due to a congenital thoracic malformation and cardiopulmonary insufficiency. A new individualized combined treatment, consisting uterine artery embolization（UAE）, percutaneous microwave ablation（PMWA） of the pedicle and the endometrium, and transvaginal removal of the leiomyoma by twisting, was performed. The lesion was completely removed successfully under local anesthesia without any major complications. The postoperative follow-up showed complete symptom relief and a significant improvement in the quality of life.CONCLUSION UAE combined with PMWA can be performed under local anesthesia and is a promising alternative treatment for patients who cannot tolerate general anesthesia.

Objective: To investigate the effects of combined treatment of Scutellaria baicalensis (SB) and polygonatum (HH) for lung cancer and explore the underlying mechanism. Purpose: The study was designed to investigate the anti-tumor effect of HH and reveal its mechanisms. Methods: Based on the Traditional Chinese Medicine (TCM) theory and network pharmacological analysis. The inhibitory effect of HH on the proliferation of A549 and LLC lung cancer cells was predicted by CCK8 assay in a subcutaneous tumor model in vivo. Tumor tissues were collected for proteomics, qPCR and immunohistochemistry assays. A549 and LLC cell proliferation was detected by CCK8 assay after treatment with HH combined with ferroptosis inhibitors and ferroptosis inducer Erastin for 48 h respectively. The expression of Transferrin Receptor (TFRC) was detected by qPCR and Western Blot. Changes in free iron content and lipid peroxide in cytoplasm and mitochondria were observed by laser confocal microscopy. Changes in Mitochondrial Membrane Potential (MMP, Δψm) and ROS content were detected by flow cytometry. Results: Search of Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database demonstrated that HH played a role in lung cancer treatment. CCK8 assay showed that lung cancer cell proliferation was inhibited by HH in a dose-dependent manner. The animal experiment results showed that the tumor volume in HH-treated group was significantly smaller than that in Control group in the LLC allograft model (P<0.01). The expression level of TFRC in HH-treated group was higher than that in Control group, which was verified by proteomics, qPCR assay and immunohistochemistry. Two ferroptosis specific inhibitors could block HH-induced ferroptosis (P<0.05). Compared with Control group, free iron and lipid peroxide contents were significantly increased in cytoplasm and mitochondria while MMP was decreased and the level of ROS was augmented in HH group (P<0.01). Conclusion: HH increased the content of free iron and lipid peroxide in cytoplasm and mitochondria by upregulating the expression of TFRC in lung cancer cells, which further led to the accumulation of lipid peroxide, caused mitochondrial dysfunction, and finally induced ferroptosis in lung cancer cells.

Background:In recent years, Chinese clinicians are frequently encountered by patients with multiple lung nodules and these intensity ground-glass nodules (GGNs) are usually small in size and some of them have no spicule sign. In addition, early lung cancer is diagnosed in large numbers of non-heavy smokers and individuals with no caner history. Obviously, the Mayo model is not applicable to these patients. The aim of the present study is to develop a new and more applicable model that can predict malignancy or benignancy of pulmonary GGNs based on the inflammation-cancer transformation theory. Materials and methods:Included in this study were patients who underwent surgical resection or lung puncture biopsy of GGNs in Shanghai 10th People's Hospital between January 1, 2018 and May 31, 2021 with the inclusion criterion of the maximum diameter of GGN < 1.0 cm. All the included patients had their pulmonary GGNs diagnosed by postoperative pathology. The patient data were analyzed to establish a prediction model and the predictive value of the model was verified. Results:Altogether 100 GGN patients who met the inclusion criteria were included for analysis. Based on the results of logistic stepwise regression analysis, a mathematical predication equation was established to calculate the malignancy probability as follows: Malignancy probability rate (p) = ex/(1 + ex); p > 0.5 was considered as malignant and p ≤ 0.5 as benign, where x = 0.9650 + [0.1791 × T helper (Th) cell] + [0.2921 × mixed GGN (mGGN)] + (0.4909 × vascular convergence sign) + (0.1058 × chronic inflammation). According to this prediction model, the positive prediction rate was 73.3% and the negative prediction rate was 100% versus the positive prediction rate of 0% for the Mayo model. Conclusion:By focusing on four major factors (chronic inflammation history, human Th cell, imaging vascular convergence sign and mGGNs), the present prediction model greatly improves the accuracy of malignancy or benignancy prediction of sub-centimeter pulmonary GGNs. This is a breakthrough innovation in this field.

Purpose GAS41 is a YEATS domain protein that binds to acetylated histone H3 to promote the chromatin deposition of H2A.Z in non-small cell lung cancer. The role of GAS41 in pancreatic cancer is still unknown. Here, we aimed to reveal this role. Methods GAS41 expression in pancreatic cancer tissues and cell lines was examined using qRT-PCR, Western blotting and immunohistochemistry. MTT, colony formation, spheroid formation and in vivo tumorigenesis assays were performed to assess the proliferation, tumorigenesis, stemness and gemcitabine (GEM) resistance of pancreatic cancer cells. Mechanistically, co-immunoprecipitation (co-IP) and chromatin immunoprecipitation (ChIP) assays were used to evaluate the roles of GAS41, H2A.Z.2 and Notch1 in pancreatic cancer. Results We found that GAS41 is overexpressed in human pancreatic cancer tissues and cell lines, and that its expression increases following the acquisition of GEM resistance. We also found that GAS41 up-regulates Notch, as well as pancreatic cancer cell stemness and GEM resistance in vitro and in vivo. We show that GAS41 binds to H2A.Z.2 and activates Notch and its downstream mediators, thereby regulating stemness and drug resistance. Depletion of GAS41 or H2A.Z.2 was found to down-regulate Notch and to sensitize pancreatic cancer cells to GEM. Conclusion Our data indicate that GAS41 mediates proliferation and GEM resistance in pancreatic cancer cells via H2A.Z.2 and Notch1.

Objective ：To explore the potential impact of interleukin-6 (IL-6) in promoting the development and progression of lung ground-glass nodules (GGN) based on multiple clinical features using multi-dimensional analysis (MDA). Methods: Sample collected from data taken from patients with lung GGN who received treatment in Shanghai Tenth People's Hospital, between September 2018 and September 2020. Sample data were grouped according to GGN diameter as well as IL-6 levels and screened according to the solitary GGN (d<0.8cm) after more than one year of follow-up observation. Differences in associated complications, peripheral superoxide dismutase (SOD), IgE and T cell subsets, tumor markers, and CT malignant signs were compared between the two sample groups. Results ：A total of 145 patients was included in the study. From the results, the diameter of GGN was ≥5mm in 95 patients and <5mm in 50 patients. There were significant differences in peripheral IL-6 levels between the two groups (p<0.05). Whereas the IL-6 level was elevated in 53 patients, the levels were normal in 92 patients. There was a corresponding significant increase in complications such as anxiety, sleep disturbances, feeling of fatigue, and history of coronary stent implantation in the group of GGN patients with elevated levels of IL-6, when compared to the group with the normal IL-6 levels (p<0.05). Peripheral SOD and IgE levels were observed to be significantly higher in the group with elevated IL-6 levels than seen in the group with normal IL-6 levels (p<0.05). In addition, there was also a significant difference in T helper (Th) and T suppressor (Ts) cell levels between the two groups (p<0.05). Levels of tumor markers such as NSE and CY21-1 were also found to be elevated in the group with elevated IL-6 levels than in the group with normal IL-6 levels (p<0.05). Finally, the group with elevated Il-6 levels was observed to have a higher proportion of patients with vascular convergence sign (VCS) and mixed ground-glass opacity (mGGO) as compared to the sample with normal IL-6 levels (p<0.05). Conclusion: Chronic inflammation is an important factor in the malignant transformation of GGN. IL-6 plays a significant role in promoting the formation of early lung cancer through multiple pathways, including mediating imbalance of the human mitochondrial antioxidant system and reactive elevation of IgE, inhibiting the anti-tumor immune function of T cells, and promoting tumor tissue angiogenesis. The probability of malignant transformation is even higher in lung GGN accompanied with IL-6 elevation.

OBJECTIVES:This retrospective cohort study investigated the efficacy of routine intravenous chemotherapy (the control group), transcatheter arterial infusion (TAI) chemotherapy, and TAI combined with radioactive particles as therapeutic methods for advanced body/tail pancreatic cancer by assessing the short-term and overall survival rates.METHODS:We screened our prospective database for patients with advanced body/tail pancreatic cancer, which tumor deemed unresectable, and no other confirmed malignant tumors, patients were assigned into 3 groups according to their treatment: routine intravenous chemotherapy, TAI, and TAI combined with radioactive particles.RESULTS:The median survival time was 6 months in the control group, 10 months in the TAI group, and 13 months in the TAI combined group. The Kaplan-Meier estimates of the overall survival among the 3 groups, indicating that there is significant difference among 3 groups (P < 0.000). The clinical remission rates were 17.5% in the control group, 41.5% in the TAI group, and 48.0% in the TAI combined group. Covariates analyzed showed that different treatment methods and times affected the results significantly (P < 0.002).CONCLUSIONS:In the treatment of advanced body/tail pancreatic cancer, TAI and TAI combined with radioactive particles significantly improved the clinical outcomes in patients compared with routine intravenous chemotherapy.

BackgroundThere are few reports of renal artery embolization (RAE) via transradial access (TRA) for renal hemorrhage, and none have compared outcomes of RAE via TRA and transfemoral access (TFA). The objective was to compare technical and clinical outcomes in patients undergoing RAE via TRA or TFA for iatrogenic renal hemorrhage.Materials and methodsThis study included 45 RAE procedures (16 TRA and 29 TFA) for iatrogenic renal hemorrhage in 43 patients performed at a tertiary referral center between October 2018 and December 2020. Information regarding underlying diseases, coagulation status, angiographic and embolization procedure details, technical and clinical successes, and complications were retrospectively evaluated.ResultsThere were no differences in demographics, underlying diseases, updated Charlson comorbidity scores, angiographic findings, and volume of contrast material between the TRA and TFA groups. By contrast, prothrombin time and international normalized ratio were significantly lower in the TRA than in the TFA group. Embolic materials differed significantly in the two groups. Procedure duration, fluoroscopy time, digital subtraction angiography number, and dose area product were slightly lower in the TRA than in the TFA group, but the differences were not statistically significant. Technical and clinical success rates in the TRA and TFA groups were 100% and 96.6%, and 100% and 96.6%, respectively. No patient in either group experienced procedure-related complications during a 4 week follow-up period.ConclusionRAE via TRA in the management of iatrogenic renal hemorrhage was safe and feasible, with similar procedure duration and radiation exposure to RAE via TFA. TRA may be an acceptable alternative to TFA in these patients.

This brief report presents 8 patients with silicone-covered metallic stent placement for ureteral strictures refractory to double-J stent placement, following kidney transplantation. Stent removal was successfully performed in 7 patients via antegrade (n = 4) or retrograde (n = 3) access 6 weeks to 6 months after stenting for elective removal (6-month interval, n = 3), urothelial hyperplasia (n = 2), or stent migration (n = 2), and their mean primary ureteral patency after stent removal was 15.4 months (range, 2-27 months). Hematuria (n = 2) and pain (n = 3) occurred, but resolved within 1 week. One stent was removed during reconstructive surgery. During follow-up of mean 22.6 months after stent removal, ureteral strictures recurred in 2 patients.

Diabetic foot ulcer (DFU) is one of diabetic complications, which is frequently present and tormented in diabetes mellitus. Most multipotent mesenchymal stromal cells (MSCs) are capable of immune evasion, providing an allogeneic, ready-to-use, cell product option for therapeutic applications. The beneficial effect of MSCs for the treatment of a variety of traumatic injuries, such as open wounds, has been extensively explored. In this study, a rat DFU model was used to simulate the pathophysiology of clinical patients and to investigate the localization of human umbilical cord mesenchymal stem cells (hUC-MSCs) after intravenous transplantation and its role in DFU healing, so as to evaluate the potential of hUC-MSCs in the treatment of DFU. The diabetic rat model was established by streptozotocin injection, which was used to create full-thickness foot dorsal skin wounds to mimic DFU by a 6-mm skin biopsy punch and a Westcott scissor. The hUC-MSCs were transplanted through femoral vein, and the ulcer cicatrization situation and the fate of hUC-MSCs were evaluated. Our data suggest that intravenously transplantated hUC-MSCs have the ability to migrate and locate to the wound tissue and are helpful to wound healing in DFU rats, partly by regulating inflammation, trans-differentiation and providing growth factors that promote angiogenesis, cell proliferation and collagen deposition. Herein, we demonstrate that hUC-MSC transplantation is able to accelerate DFU healing in rats and transplantation of exogenous stem cells may be a potential strategy for clinical application in DFUs.

Abstract Background Patients with advanced body/tail pancreatic cancer have poor quality of life and low overall survival rate. In recent years, interventional diagnosis and treatment of advanced pancreatic cancer have become increasingly widespread. This retrospective cohort study investigated the efficacy of routine intravenous chemotherapy (the control group), transcatheter arterial infusion (TAI) chemotherapy, and TAI combined with radioactive particles as therapeutic methods for advanced body/tail cancer pancreatic by assessing the short-term and overall survival rates. Methods We screened our prospective database for patients with advanced body/tail pancreatic cancer, which tumor deemed unresectable and no other confirmed malignant tumors, patients were assigned into three groups according to their treatment. Analyses with regard to the clinical responses, the 6, 12, and 18-month survival rates and overall survival rates were performed. Results The median survival time was 6 months in the control group, 10 months in the TAI group and 13 months in the TAI combined group. The Kaplan–Meier estimates of the OS among the three groups, indicating that there is significant difference among three groups (P༜0.000). The clinical remission rates were 17.5% in the control group, 41.5% in the TAI group, and 48.0% in the TAI combined group. Covariates analyzed showed that different treatment methods and times affected the results significantly (P༜0.002). Conclusions In the treatment of advanced body/tail pancreatic cancer, TAI and TAI combined with radioactive particles significantly improved the clinical outcomes in patients compared with routine intravenous chemotherapy.

More and more evidence advises that circular RNAs (circRNAs) function critically in regulating different disease microenvironments. Our previous study found that autotransplantation of adipose-derived mesenchymal stem cells (ADSCs) promotes diabetes wound healing. Exosomes derived in ADSCs play an important regulatory role. This study aimed to characterize if mmu_circ_0000250 played a role in ADSC-exosome-mediated full-thickness skin wound repair in diabetic rats. Endothelial progenitor cells (EPCs) were selected to study the therapeutic mechanism of exosomes in high-glucose (HG)-induced cell damage and dysfunction. Analysis and luciferase reporter assay were utilized to explore the interaction among mmu_circ_0000250, miRNA (miR)-128-3p, and sirtuin (SIRT)1. The diabetic rats were used to confirm the therapeutic effect of mmu_circ_0000250 against exosome-mediated wound healing. Exosomes containing a high concentration of mmu_circ_0000250 had a greater therapeutic effect on restoration of the function of EPCs by promotion autophagy activation under HG conditions. Expression of mmu_circ_0000250 promoted SIRT1 expression by miR-128-3p adsorption, which was confirmed via luciferase reporter assay and bioinformatics analysis. In vivo, exosomes containing a high concentration of mmu_circ_0000250 had a more therapeutic effect on wound healing when compared with wild-type exosomes from ADSCs. Immunohistochemistry and immunofluorescence detection showed that mmu_circ_0000250 increased angiopoiesis with exosome treatment in wound skin and suppressed apoptosis by autophagy activation. In conclusion, we verified that mmu_circ_0000250 enhanced the therapeutic effect of ADSC-exosomes to promote wound healing in diabetes by absorption of miR-128-3p and upregulation of SIRT1. Therefore, these findings advocate targeting the mmu_circ_0000250/miR-128-3p/SIRT1 axis as a candidate therapeutic option for diabetic ulcers.

BACKGROUND:Circular RNAs are implicated in a variety of cancers. This investigation found that hsa_circ_0000291 expression was upregulated in gastric cancer (GC) cell lines, yet its role in GC has not yet been reported.OBJECTIVE:To explore the effects of hsa_circ_0000291 on GC cell proliferation and invasion.MATERIALS AND METHODS:In the current research, we used the gastric cancer cell lines MGC803 and MKN-28 to study hsa_circ_0000291 function. The relationship between hsa_circ_0000291, miR-183 and ITGB1 was analyzed by firefly luciferase analysis and Western blots, and qRT-PCR approaches were used for protein and gene expression analysis, respectively. Tumor growth and metastasis were determined in nude mice xenografts using MKN-28 cells, with or without hsa_circ_000r0291 downregulation.RESULTS:Our data showed that hsa_circ_0000291 was upregulated in GC cell lines, whereas hsa_circ_0000291 silencing suppressed cell metastasis and proliferation in in vivo and in vitro studies. Our results showed that the downregulation of hsa_circ_0000291 suppressed integrin beta 1 (ITGB1) expression via miR-183 "sponging," which was validated by rescue experiments using the luciferase reporter assay. Our observations suggested that hsa_circ_0000291 silencing suppressed the aggressive, metastatic GC phenotype.CONCLUSION:Taken together, hsa_circ_0000291 knockdown inhibited GC cell metastasis and growth by regulating the miR-183/ITGB1 axis. Importantly, this approach could provide a therapy target and potential biomarker for the diagnosis and treatment of GC.

Endothelial malfunctions in patients with diabetes are known to result in vascular diseases, and endothelial progenitor cells (EPCs) are indispensable for the functional preservation of the vascular endothelium. MicroRNA-31 (miR-31) has been found to be able to modulate the differentiation of stem cells. However, it is still unclear how miR-31 functions in diabetic EPCs. The aim of this study was to investigate how miR-31 regulates diabetic EPC function. In the current study, miR-31 expression was compared between normal and diabetic EPCs. Satb2 was recognized as a functionally related target of miR-31 in EPCs according to computational prediction. We also explored the role of miR-31 in terms of its anti-apoptotic effects. A remarkable elevation in miR-31 expression was found in diabetic EPCs, and this elevated expression resulted in suppressed cell proliferation under high glucose. It was also found that miR-31 targets Satb2, leading to the anti-apoptotic effect and maintenance of the functions of EPCs. Furthermore, knockdown of Satb2 exhibited an inhibitory effect on proliferation and migration of EPCs in both healthy and diabetic subjects, which showed the same trend as miR-31 overexpression. Conversely, overexpression of Satb2 showed the opposite effect. Moreover, overexpression of Satb2 attenuated the miR-31-induced migration and colony-forming ability reduction and apoptosis induction of EPCs in both healthy and diabetic subjects. In diabetic EPCs, elevated glucose level was found to up-regulate miR-31 expression, which in turn enhanced the malfunction and death of EPCs. In conclusion, our results indicate that up-regulation of miR-31 may underlie endothelial dysfunction in diabetes by targeting Satb2.

OBJECTIVE:To investigate the incidence, management, and outcome of a liver abscess after transarterial embolization/chemoembolization (TAE/TACE) therapy for hepatocellular carcinoma (HCC). MATERIALS AND METHODS:From May 2007 to May 2014, all patients complicated with liver abscess following TAE/TACE for HCC were identified and analyzed at four medical centers. RESULTS:During the study period, a total of 6984 TAE/TACE procedures were performed among 3129 patients, and a total of 23 patients developed liver abscess with the incidence of 0.33% (23/6984) per procedure. There were 21 males and 2 females, and mean age of 52.1 ± 12.1 years. The mean interval from last TAE/TACE procedure to the diagnosis of liver abscess was 12.9 ± 6.6 days. All the patients received intravenous antibiotics, with ten patients had a percutaneous drain, one each for percutaneous aspiration and surgery. Complications related to the liver abscess were hepatorrhexis and pleural effusion (n = 1), pleural effusion (n = 1), and obstructive jaundice (n = 1), all of which were resolved after conservative treatments. The serum alpha-fetoprotein (AFP) levels were significantly reduced at 6 months after treatment (P < 0.01) in 15 patients whose AFP > 400 ng/mL preprocedure. Complete or partial tumor response at 6 months after TAE/TACE was achieved in three and twenty patients, respectively; and 6 months survival was 100%. CONCLUSIONS:The incidence of a liver abscess after TAE/TACE is low; antibiotics therapy along was successful in about half patients, and percutaneous abscess aspiration/drainage were necessary in large size abscess and severely symptomatic patients; the outcomes are benign without worsening of the progression of underlying HCC.

Diabetic ischemic ulcer is an intractable diabetic complication. Angiogenesis is a critical factor for wound healing in patients with diabetic foot wounds. Sustained gene delivery could be notably necessary in modulating gene expression in chronic ulcer healing and might be a promising approach for diabetic foot ulcers. In the present study, Sprague–Dawley rats were used to establish diabetic foot ulcer models by streptozotocin and skin biopsy punch. The plasmids expressing VEGF-A and PDGF-B were prepared and then incorporated with polylactic-co-glycolic acid (PLGA) nanospheres to upregulate genes expression. The aim of this study was to explore whether the engineered VEGF-A and PDGF-B based plasmid-loaded nanospheres could be upregulated in streptozotocin-induced diabetic rats and improve the wound healing. The cultured fibroblasts could be effectively transfected by means of nanosphere/plasmid in vitro. In vivo, the expression of VEGF-A and PDGF-B was significantly upregulated at full-thickness foot dorsal skin wounds and the area of ulceration was progressively and significantly reduced following treatment with nanosphere/plasmid. These results indicated that combined gene transfer of VEGF-A and PDGF-B could improve reparative processes in the wounded skin of diabetic rats and nanosphere may be a potential non-viral vector for gene therapy of the diabetic foot ulcer.

The aim of the present study was to investigate the relative regulation of human circular RNA‑0054633 (hsa_circ_0054633), microRNA‑218 (miR‑218), roundabout 1 (ROBO1) and heme oxygenase‑1 (HO‑1) in human umbilical vein endothelial cells (HUVECs) in high glucose conditions. Initially, the expression of hsa_circ_0054633 in HUVECs was detected in high glucose conditions by reverse transcription‑quantitative polymerase chain reaction. Next, a small interfering RNA against hsa_circ_0054633 was constructed to investigate the function of jsa_circ_0054633 in HUVECs by transwell migration, cell counting kit‑8, flow cytometry and tube formation assays. In addition, the effect of hsa_circ_0054633 on the expression levels of ROBO1, HO‑1 and vascular endothelial growth factor were examined. The regulation effects of hsa_circ_0054633 on high glucose‑induced HUVEC proliferation, migration, and angiopoiesis were also analyzed. Bioinformatics analysis and dual‑luciferase assay were then used to confirm the direct or specific regulation of hsa_circ_0054633, miR‑218, ROBO1 and HO‑1. It was observed that high glucose levels increased the expression of hsa_circ_0054633, while downregulation of hsa_circRNA‑0054633 increased the high glucose‑induced endothelial cell dysfunction, including proliferation, migration and angiopoiesis suppression. Bioinformatics analysis revealed that the expression of circRNA‑0054633 was able to inhibit miR‑218 expression, which was clarified by the dual‑luciferase assay. It was also demonstrated that downregulating the expression of miR‑218 inhibited the high glucose‑induced endothelial cell dysfunction by promoting the expression of ROBO1 and HO‑1. These results suggest that the expression of hsa_circRNA‑0054633 has a protective effect against high glucose‑induced endothelial cell dysfunction by targeting ROBO1 and HO‑1.

BackgroundThe goal of this study was to characterize the properties of human CD34+ cells in culture and investigate the feasibility and efficacy of CD34+ transplantation in a mouse model of limb ischemia and in patients with no‐option critical limb ischemia.MethodsHuman CD34+ cells isolated from peripheral blood and grown in culture for up to four passages stained positively for the surface markers CD34 and CD133 and showed high viability after cryopreservation and recovery. Seven days after surgery to induce limb ischemia, ischemic muscles of nude mice were injected with CD34+ cells. Two weeks later, mice were scored for extent of ischemic injury, and muscle tissue was collected for immunohistochemical analysis of vascular endothelial cells and RT‐PCR analysis of cytokine expression.ResultsInjury scores of CD34+‐treated, but not control, mice were significantly different before and after transplantation. Vascular density and expression of VEGF and bFGF mRNAs were also significantly increased in the treated mice. Patients with severe lower extremity arterial ischemia were injected with their own CD34+ cells in the affected calf, foot, or toe. Significant improvements were observed in peak pain‐free walking time, ankle‐brachial index, and transcutaneous partial oxygen pressure. These findings demonstrate that growth of human CD34+ cells in vitro and cryopreservations are feasible.ConclusionSuch cells may provide a renewable source of stem cells for transplantation, which appears to be a feasible, safe, and effective treatment for patients with critical limb ischemia.