BACKGROUND Rapid wound healing remains a pressing clinical challenge,necessitating studies to hasten this process.A promising approach involves the utilization of human umbilical cord mesenchymal stem cells(hUC-MSCs)d...BACKGROUND Rapid wound healing remains a pressing clinical challenge,necessitating studies to hasten this process.A promising approach involves the utilization of human umbilical cord mesenchymal stem cells(hUC-MSCs)derived exosomes.The hypothesis of this study was that these exosomes,when loaded onto a gelatin sponge,a common hemostatic material,would enhance hemostasis and accelerate wound healing.AIM To investigate the hemostatic and wound healing efficacy of gelatin sponges loaded with hUC-MSCs-derived exosomes.METHODS Ultracentrifugation was used to extract exosomes from hUC-MSCs.Nanoparticle tracking analysis(NTA),transmission electron microscopy(TEM),and western blot techniques were used to validate the exosomes.In vitro experiments were performed using L929 cells to evaluate the cytotoxicity of the exosomes and their impact on cell growth and survival.New Zealand rabbits were used for skin irritation experiments to assess whether they caused adverse skin reactions.Hemolysis test was conducted using a 2%rabbit red blood cell suspension to detect whether they caused hemolysis.Moreover,in vivo experiments were carried out by implanting a gelatin sponge loaded with exosomes subcutaneously in Sprague-Dawley(SD)rats to perform biocompatibility tests.In addition,coagulation index test was conducted to evaluate their impact on blood coagulation.Meanwhile,SD rat liver defect hemostasis model and full-thickness skin defect model were used to study whether the gelatin sponge loaded with exosomes effectively stopped bleeding and promoted wound healing.RESULTS The NTA,TEM,and western blot experimental results confirmed that exosomes were successfully isolated from hUC-MSCs.The gelatin sponge loaded with exosomes did not exhibit significant cell toxicity,skin irritation,or hemolysis,and they demonstrated good compatibility in SD rats.Additionally,the effectiveness of the gelatin sponge loaded with exosomes in hemostasis and wound healing was validated.The results of the coagulation index experiment indicated that the gelatin sponge loaded with exosomes had significantly better coagulation effect compared to the regular gelatin sponge,and they showed excellent hemostatic performance in a liver defect hemostasis model.Finally,the full-thickness skin defect healing experiment results showed significant improvement in the healing process of wounds treated with the gelatin sponge loaded with exosomes compared to other groups.CONCLUSION Collectively,the gelatin sponge loaded with hUC-MSCs-derived exosomes is safe and efficacious for promoting hemostasis and accelerating wound healing,warranting further clinical application.展开更多
Hepatic arterioportal fistulas(APFs)are common in hepatocellular carcinoma(HCC).Moreover,correlated with poor prognosis,APFs often complicate antitumor treatments,including transarterial chemoembolization(TACE).AIM To...Hepatic arterioportal fistulas(APFs)are common in hepatocellular carcinoma(HCC).Moreover,correlated with poor prognosis,APFs often complicate antitumor treatments,including transarterial chemoembolization(TACE).AIM To compare the efficacy of ethanol-soaked gelatin sponges(ESG)and microspheres in the management of APFs and their impact on the prognosis of HCC.METHODS Data from patients diagnosed with HCC or hepatic APFs between June 2016 and December 2019 were retrospectively analyzed.Furthermore,APFs were embolized with ESG(group E)or microspheres(group M)during TACE.The primary outcomes were disease control rate(DCR)and objective response rate(ORR).The secondary outcomes included immediate and first follow-up APF improvement,overall survival(OS),and progression-free survival(PFS).RESULTS Altogether,91 participants were enrolled in the study,comprising 46 in group E and 45 in group M.The DCR was 93.5%and 91.1%in groups E and M,respectively(P=0.714).The ORRs were 91.3%and 66.7%in groups E and M,respectively(P=0.004).The APFs improved immediately after the procedure in 43(93.5%)patients in group E and 40(88.9%)patients in group M(P=0.485).After 2 mo,APF improvement was achieved in 37(80.4%)and 33(73.3%)participants in groups E and M,respectively(P=0.421).The OS was 26.2±1.4 and 20.6±1.1 mo in groups E and M,respectively(P=0.004),whereas the PFS was 16.6±1.0 and 13.8±0.7 mo in groups E and M,respectively(P=0.012).CONCLUSION Compared with microspheres,ESG embolization demonstrated a higher ORR and longer OS and PFS in patients of HCC with hepatic APFs.展开更多
Purpose: A series of clinical studies have established the safety and efficacy of transcatheter arterial chemoembolization(TACE) with gelatin sponge microparticles(GSMs) in treating hepatocellular carcinoma(HCC). HCC ...Purpose: A series of clinical studies have established the safety and efficacy of transcatheter arterial chemoembolization(TACE) with gelatin sponge microparticles(GSMs) in treating hepatocellular carcinoma(HCC). HCC can lead to obvious necrosis inside tumors, especially larger ones, although it is unclear whether such necrotic tumor tissue can induce favorable immune reactions against the tumor. Myeloid-derived suppressor cells(MDSCs)have immunosuppressive functions and are currently considered a very important cell type affecting tumor immunity. This study observed changes in MDSC frequency in peripheral blood before and after GSM–TACE to evaluate the effect on the immune function of HCC patients.Methods: Eight patients diagnosed with HCC underwent GSM–TACE treatment in the Hepatobiliary Interventional Department of Beijing Tsinghua Chang Gung Hospital, Beijing, China;we followed up with the patients over a period of 30 days post-surgery. We used flow cytometry(FCM) to quantify the frequency of MDSCs in peripheral blood before TACE, 10 days after surgery and 30 days after surgery.Results: MDSC frequency after GSM–TACE had a significant downward trend. Pre-TACE, it was 30.73% ? 11.93%,decreasing to 18.60% ? 11.37% at 10 days after operation. This decrease was not statistically significant(P > 0.05). MDSC frequency was even lower 30 days after TACE(7.63% ? 7.32%) than at 10 days after TACE(P < 0.05), and there was a significant difference compared with pre-TACE(P < 0.001). We evaluated tumor response at 30 days after GSM–TACE according to the Modified Response Evaluation Criteria in Solid Tumors(mRECIST), and all eight patients showed partial response(PR).Conclusion: Our results confirmed that GSM–TACE was beneficial for improving anti-tumor immunity in the treatment of HCC.展开更多
Gelatin (Gel) and chitosan (CTS) have several biomedical applications because of their biodegradability and biocompatibility. Crosslinking of Gel and Gel/CTS systems was evaluated using N-acetyl-D-glucosamine (GlcNAc)...Gelatin (Gel) and chitosan (CTS) have several biomedical applications because of their biodegradability and biocompatibility. Crosslinking of Gel and Gel/CTS systems was evaluated using N-acetyl-D-glucosamine (GlcNAc) formed into sponges by lyophilization. The prepared sponges were used to study the adsorption and desorption of fluorescein isothiocyanate (FITC) labeled bovine serum albumin (BSA) as a model instead of a growth factor. The effect of FITC-BSA concentration and temperature on the adsorption behavior of Gel/CTS sponges was investigated. The Langmuir adsorption isotherm model was used on the basis of the assumption that monolayer adsorption occurs on the surface;the results fit with the experiment data. The adsorption constants were 5.77 and 9.68 mL/mg for Gel and Gel/CTS sponges, respectively. The adsorption thermodynamic constants were found;adsorption onto sponges was an exothermic reaction. In particular, Gibbs free energy (ΔG) exhibited negative values in the range of 283 - 343 K for both Gel and Gel/CTS sponges, demonstrating the spontaneous nature of adsorption reaction. In addition, desorption behavior was evaluated for different concentrations and pH values of the FITC-BSA solution. The high adsorbed amounts of FITC-BSA on sponge resulted in high desorbed amounts in sponge, up to 55% from 3.5 mg/mL adsorbed concentration (around 1.5 mg from 3 mg adsorb amount). Desorption decreased following the buffer solution pH decrease, from 7.4 to 4 and 2 in Gel and Gel/CTS sponges, respectively. Based on the results of this preliminary study, these composite sponges could have significant application in biomedical materials.展开更多
BACKGROUND Compared with traditional open surgery,laparoscopic surgery is preferred due to the advantages of less trauma,less pain,and faster recovery.Nevertheless,many patients still suffer from postoperative pain re...BACKGROUND Compared with traditional open surgery,laparoscopic surgery is preferred due to the advantages of less trauma,less pain,and faster recovery.Nevertheless,many patients still suffer from postoperative pain resulting from the surgical incision and associated tissue injury.Many researchers have reported methods to improve postoperative pain control,but there is not a simple and effective method that can be clinically adopted in a widespread manner.We designed this study to prove the hypothesis that application of ropivacaine in the port site and operative site in patients is an effective and convenient method which can decrease postoperative pain and accelerate recovery.AIM To evaluate the effects of ropivacaine on pain control after laparoscopic hepatectomy and its contribution to patient recovery.METHODS From May 2017 to November 2018,146 patients undergoing laparoscopic hepatectomy were randomized to receive infiltration of either 7.5 mg/mL ropivacaine around the trocar insertions,incision,and cutting surface of the liver(with a gelatin sponge soaked with ropivacaine)at the end of surgery(ropivacaine group),or normal saline(5 mL)at the same sites at the end of surgery(control group).The degree of pain,nausea,vomiting,heart rate(HR),and blood pressure were collected.The length of postoperative hospitalization,complications,and the levels of stress hormones were also compared between the two groups.RESULTS Compared with the control group,the ropivacaine group showed reduced postoperative pain at rest within 12 h(P<0.05),and pain on movement was reduced within 48 h.The levels of epinephrine,norepinephrine,and cortisol at 24 and 48 h,HR,blood pressure,and cumulative sufentanil consumption in the ropivacaine group were significantly lower than those in the control group(P<0.05).In the ropivacaine group,hospitalization after operation was shorter,but the difference was not statistically significant.There were no significant differences in postoperative nausea,vomiting,or other complications,including hydrothorax,ascites,peritonitis,flatulence,and venous thrombus(P>0.05),although fewer patients in the ropivacaine group experienced these situations.CONCLUSION Infiltration with ropivacaine in the abdominal wound and covering the cutting surface of the liver with a gelatin sponge soaked with ropivacaine significantly reduce postoperative pain and the consumption of sufentanil.展开更多
基金the National Key R&D Program of China,No.2018YFA0108304the National Natural Science Foundation of China,No.81771721 and 81971505the Innovation Project of Guangxi Graduate Education,No.YCBZ2022004 and YCBZ2022045。
文摘BACKGROUND Rapid wound healing remains a pressing clinical challenge,necessitating studies to hasten this process.A promising approach involves the utilization of human umbilical cord mesenchymal stem cells(hUC-MSCs)derived exosomes.The hypothesis of this study was that these exosomes,when loaded onto a gelatin sponge,a common hemostatic material,would enhance hemostasis and accelerate wound healing.AIM To investigate the hemostatic and wound healing efficacy of gelatin sponges loaded with hUC-MSCs-derived exosomes.METHODS Ultracentrifugation was used to extract exosomes from hUC-MSCs.Nanoparticle tracking analysis(NTA),transmission electron microscopy(TEM),and western blot techniques were used to validate the exosomes.In vitro experiments were performed using L929 cells to evaluate the cytotoxicity of the exosomes and their impact on cell growth and survival.New Zealand rabbits were used for skin irritation experiments to assess whether they caused adverse skin reactions.Hemolysis test was conducted using a 2%rabbit red blood cell suspension to detect whether they caused hemolysis.Moreover,in vivo experiments were carried out by implanting a gelatin sponge loaded with exosomes subcutaneously in Sprague-Dawley(SD)rats to perform biocompatibility tests.In addition,coagulation index test was conducted to evaluate their impact on blood coagulation.Meanwhile,SD rat liver defect hemostasis model and full-thickness skin defect model were used to study whether the gelatin sponge loaded with exosomes effectively stopped bleeding and promoted wound healing.RESULTS The NTA,TEM,and western blot experimental results confirmed that exosomes were successfully isolated from hUC-MSCs.The gelatin sponge loaded with exosomes did not exhibit significant cell toxicity,skin irritation,or hemolysis,and they demonstrated good compatibility in SD rats.Additionally,the effectiveness of the gelatin sponge loaded with exosomes in hemostasis and wound healing was validated.The results of the coagulation index experiment indicated that the gelatin sponge loaded with exosomes had significantly better coagulation effect compared to the regular gelatin sponge,and they showed excellent hemostatic performance in a liver defect hemostasis model.Finally,the full-thickness skin defect healing experiment results showed significant improvement in the healing process of wounds treated with the gelatin sponge loaded with exosomes compared to other groups.CONCLUSION Collectively,the gelatin sponge loaded with hUC-MSCs-derived exosomes is safe and efficacious for promoting hemostasis and accelerating wound healing,warranting further clinical application.
文摘Hepatic arterioportal fistulas(APFs)are common in hepatocellular carcinoma(HCC).Moreover,correlated with poor prognosis,APFs often complicate antitumor treatments,including transarterial chemoembolization(TACE).AIM To compare the efficacy of ethanol-soaked gelatin sponges(ESG)and microspheres in the management of APFs and their impact on the prognosis of HCC.METHODS Data from patients diagnosed with HCC or hepatic APFs between June 2016 and December 2019 were retrospectively analyzed.Furthermore,APFs were embolized with ESG(group E)or microspheres(group M)during TACE.The primary outcomes were disease control rate(DCR)and objective response rate(ORR).The secondary outcomes included immediate and first follow-up APF improvement,overall survival(OS),and progression-free survival(PFS).RESULTS Altogether,91 participants were enrolled in the study,comprising 46 in group E and 45 in group M.The DCR was 93.5%and 91.1%in groups E and M,respectively(P=0.714).The ORRs were 91.3%and 66.7%in groups E and M,respectively(P=0.004).The APFs improved immediately after the procedure in 43(93.5%)patients in group E and 40(88.9%)patients in group M(P=0.485).After 2 mo,APF improvement was achieved in 37(80.4%)and 33(73.3%)participants in groups E and M,respectively(P=0.421).The OS was 26.2±1.4 and 20.6±1.1 mo in groups E and M,respectively(P=0.004),whereas the PFS was 16.6±1.0 and 13.8±0.7 mo in groups E and M,respectively(P=0.012).CONCLUSION Compared with microspheres,ESG embolization demonstrated a higher ORR and longer OS and PFS in patients of HCC with hepatic APFs.
基金Supported by a grant from National Natural Science Foundation of China(grant number 81571783)National Major Project for Infectious Diseases of China(2017ZX100203205005)
文摘Purpose: A series of clinical studies have established the safety and efficacy of transcatheter arterial chemoembolization(TACE) with gelatin sponge microparticles(GSMs) in treating hepatocellular carcinoma(HCC). HCC can lead to obvious necrosis inside tumors, especially larger ones, although it is unclear whether such necrotic tumor tissue can induce favorable immune reactions against the tumor. Myeloid-derived suppressor cells(MDSCs)have immunosuppressive functions and are currently considered a very important cell type affecting tumor immunity. This study observed changes in MDSC frequency in peripheral blood before and after GSM–TACE to evaluate the effect on the immune function of HCC patients.Methods: Eight patients diagnosed with HCC underwent GSM–TACE treatment in the Hepatobiliary Interventional Department of Beijing Tsinghua Chang Gung Hospital, Beijing, China;we followed up with the patients over a period of 30 days post-surgery. We used flow cytometry(FCM) to quantify the frequency of MDSCs in peripheral blood before TACE, 10 days after surgery and 30 days after surgery.Results: MDSC frequency after GSM–TACE had a significant downward trend. Pre-TACE, it was 30.73% ? 11.93%,decreasing to 18.60% ? 11.37% at 10 days after operation. This decrease was not statistically significant(P > 0.05). MDSC frequency was even lower 30 days after TACE(7.63% ? 7.32%) than at 10 days after TACE(P < 0.05), and there was a significant difference compared with pre-TACE(P < 0.001). We evaluated tumor response at 30 days after GSM–TACE according to the Modified Response Evaluation Criteria in Solid Tumors(mRECIST), and all eight patients showed partial response(PR).Conclusion: Our results confirmed that GSM–TACE was beneficial for improving anti-tumor immunity in the treatment of HCC.
文摘Gelatin (Gel) and chitosan (CTS) have several biomedical applications because of their biodegradability and biocompatibility. Crosslinking of Gel and Gel/CTS systems was evaluated using N-acetyl-D-glucosamine (GlcNAc) formed into sponges by lyophilization. The prepared sponges were used to study the adsorption and desorption of fluorescein isothiocyanate (FITC) labeled bovine serum albumin (BSA) as a model instead of a growth factor. The effect of FITC-BSA concentration and temperature on the adsorption behavior of Gel/CTS sponges was investigated. The Langmuir adsorption isotherm model was used on the basis of the assumption that monolayer adsorption occurs on the surface;the results fit with the experiment data. The adsorption constants were 5.77 and 9.68 mL/mg for Gel and Gel/CTS sponges, respectively. The adsorption thermodynamic constants were found;adsorption onto sponges was an exothermic reaction. In particular, Gibbs free energy (ΔG) exhibited negative values in the range of 283 - 343 K for both Gel and Gel/CTS sponges, demonstrating the spontaneous nature of adsorption reaction. In addition, desorption behavior was evaluated for different concentrations and pH values of the FITC-BSA solution. The high adsorbed amounts of FITC-BSA on sponge resulted in high desorbed amounts in sponge, up to 55% from 3.5 mg/mL adsorbed concentration (around 1.5 mg from 3 mg adsorb amount). Desorption decreased following the buffer solution pH decrease, from 7.4 to 4 and 2 in Gel and Gel/CTS sponges, respectively. Based on the results of this preliminary study, these composite sponges could have significant application in biomedical materials.
基金Supported by the National Natural Science Foundation of China,No.81571367Technological Project of Shandong Province,No.2017GSF218021
文摘BACKGROUND Compared with traditional open surgery,laparoscopic surgery is preferred due to the advantages of less trauma,less pain,and faster recovery.Nevertheless,many patients still suffer from postoperative pain resulting from the surgical incision and associated tissue injury.Many researchers have reported methods to improve postoperative pain control,but there is not a simple and effective method that can be clinically adopted in a widespread manner.We designed this study to prove the hypothesis that application of ropivacaine in the port site and operative site in patients is an effective and convenient method which can decrease postoperative pain and accelerate recovery.AIM To evaluate the effects of ropivacaine on pain control after laparoscopic hepatectomy and its contribution to patient recovery.METHODS From May 2017 to November 2018,146 patients undergoing laparoscopic hepatectomy were randomized to receive infiltration of either 7.5 mg/mL ropivacaine around the trocar insertions,incision,and cutting surface of the liver(with a gelatin sponge soaked with ropivacaine)at the end of surgery(ropivacaine group),or normal saline(5 mL)at the same sites at the end of surgery(control group).The degree of pain,nausea,vomiting,heart rate(HR),and blood pressure were collected.The length of postoperative hospitalization,complications,and the levels of stress hormones were also compared between the two groups.RESULTS Compared with the control group,the ropivacaine group showed reduced postoperative pain at rest within 12 h(P<0.05),and pain on movement was reduced within 48 h.The levels of epinephrine,norepinephrine,and cortisol at 24 and 48 h,HR,blood pressure,and cumulative sufentanil consumption in the ropivacaine group were significantly lower than those in the control group(P<0.05).In the ropivacaine group,hospitalization after operation was shorter,but the difference was not statistically significant.There were no significant differences in postoperative nausea,vomiting,or other complications,including hydrothorax,ascites,peritonitis,flatulence,and venous thrombus(P>0.05),although fewer patients in the ropivacaine group experienced these situations.CONCLUSION Infiltration with ropivacaine in the abdominal wound and covering the cutting surface of the liver with a gelatin sponge soaked with ropivacaine significantly reduce postoperative pain and the consumption of sufentanil.
