Objective:To investigate the role of keloid fibroblast-derived exosomes (KF-Exos) in inducing the phenotypic transformation of normal fibroblasts (NFs) into myofibroblasts and to assess their significance in keloid formation.Methods:Normal skin tissues and keloid tissues were collected from female patients aged 20-49 years who underwent surgery at the Department of Plastic Surgery, the Second Hospital of Harbin Medical University from October 2022 to March 2023. Normal fibroblasts and keloid fibroblasts (KFs) were extracted, and the supernatant of KFs was collected to isolate their exosomes. The exosomes were characterized using nanoparticle size analysis (NTA) and transmission electron microscopy (TEM). The samples were divided into the control, KEFS, and KF-Exos groups, then cell proliferation and migration abilities of groups were assessed by scratch assay and Edu assay. The samples were divided into the control, KEFS, KF-Exos, and KFs groups, real-time fluorescence quantitative PCR was used to measure the gene expression levels of Col1a1, Col1a2, Col3a1, α-SMA, TGF-β1, TGF-β2, and TGF-β3. The samples were divided into the control, and KF-Exos groups, Western blot analysis was conducted to evaluate the protein expression levels of Col-1, α-SMA, TGF-β1, Smad2/3, and Smad4. Statistical analysis and plotting were conducted using GraphPad Prism 9.0 software and Image J. Comparisons among multiple groups were analyzed using one-way ANOVA, then comparison of subgroups with the control group was performed using the Dunnett- t test. Independent samples t-test was used to compare the control group with the KF-Exos group in Western blot. P<0.05 was considered statistically significant. Results:The extracted KF-Exos was identified by TEM as a bilayer lipid membrane vesicles. NTA revealed that the average diameter of KF-Exos was 105.4 nm. Scratch and Edu assays demonstrated statistically significant differences in proliferation and migration abilities among the control, KEFS, and KF-Exos groups (all P<0.05). Compared to the control group, the KF-Exos group exhibited statistically significant differences in both proliferation and migration abilities (both P<0.05), while the KEFS group did not show statistically significant differences in these abilities (both P>0.05). Quantitative PCR results showed that, among the control, KEFS, KF-Exos, and KFs groups, there were significant differences in the mRNA expression levels of Col1a1, Col1a2, Col3a1, α-SMA, TGF-β1, TGF-β2, and TGF-β3 (all P<0.05). Compared with the control group, the Col3a1 mRNA level in the KEFS group was significantly different ( P<0.05), whereas the differences in Col1a1, Col1a2, and α-SMA levels were not statistically significant (all P>0.05). The expression levels of Col1a1, Col1a2, Col3a1, α-SMA, TGF-β1, TGF-β2, and TGF-β3 mRNA of the KFs group, and the expression levels of Col1a1, Col1a2, Col3a1, α-SMA, TGF-β1, and TGF-β3 mRNA of the KFs-Exos group had significant differences compared with the control group (all P<0.05), while the difference of TGF-β2 between the KF-Exos group and the control group was not statistically significant ( P>0.05). Western blotting results showed that the protein expression levels of TGF-β1, Smad2/3 and Smad4 were significantly up-regulated in the KF-Exos group compared to the control group (all P<0.05). Conclusion:KF-Exos successfully induced the differentiation of NFs into myofibroblasts and enhanced the expression of extracellular matrix-related factors. This phenomenon may be mediated by the upregulation of the TGF-β1-Smad2/3 and Smad4 signaling pathways.

Objective:To investigate the role of keloid fibroblast-derived exosomes (KF-Exos) in inducing the phenotypic transformation of normal fibroblasts (NFs) into myofibroblasts and to assess their significance in keloid formation.Methods:Normal skin tissues and keloid tissues were collected from female patients aged 20-49 years who underwent surgery at the Department of Plastic Surgery, the Second Hospital of Harbin Medical University from October 2022 to March 2023. Normal fibroblasts and keloid fibroblasts (KFs) were extracted, and the supernatant of KFs was collected to isolate their exosomes. The exosomes were characterized using nanoparticle size analysis (NTA) and transmission electron microscopy (TEM). The samples were divided into the control, KEFS, and KF-Exos groups, then cell proliferation and migration abilities of groups were assessed by scratch assay and Edu assay. The samples were divided into the control, KEFS, KF-Exos, and KFs groups, real-time fluorescence quantitative PCR was used to measure the gene expression levels of Col1a1, Col1a2, Col3a1, α-SMA, TGF-β1, TGF-β2, and TGF-β3. The samples were divided into the control, and KF-Exos groups, Western blot analysis was conducted to evaluate the protein expression levels of Col-1, α-SMA, TGF-β1, Smad2/3, and Smad4. Statistical analysis and plotting were conducted using GraphPad Prism 9.0 software and Image J. Comparisons among multiple groups were analyzed using one-way ANOVA, then comparison of subgroups with the control group was performed using the Dunnett- t test. Independent samples t-test was used to compare the control group with the KF-Exos group in Western blot. P<0.05 was considered statistically significant. Results:The extracted KF-Exos was identified by TEM as a bilayer lipid membrane vesicles. NTA revealed that the average diameter of KF-Exos was 105.4 nm. Scratch and Edu assays demonstrated statistically significant differences in proliferation and migration abilities among the control, KEFS, and KF-Exos groups (all P<0.05). Compared to the control group, the KF-Exos group exhibited statistically significant differences in both proliferation and migration abilities (both P<0.05), while the KEFS group did not show statistically significant differences in these abilities (both P>0.05). Quantitative PCR results showed that, among the control, KEFS, KF-Exos, and KFs groups, there were significant differences in the mRNA expression levels of Col1a1, Col1a2, Col3a1, α-SMA, TGF-β1, TGF-β2, and TGF-β3 (all P<0.05). Compared with the control group, the Col3a1 mRNA level in the KEFS group was significantly different ( P<0.05), whereas the differences in Col1a1, Col1a2, and α-SMA levels were not statistically significant (all P>0.05). The expression levels of Col1a1, Col1a2, Col3a1, α-SMA, TGF-β1, TGF-β2, and TGF-β3 mRNA of the KFs group, and the expression levels of Col1a1, Col1a2, Col3a1, α-SMA, TGF-β1, and TGF-β3 mRNA of the KFs-Exos group had significant differences compared with the control group (all P<0.05), while the difference of TGF-β2 between the KF-Exos group and the control group was not statistically significant ( P>0.05). Western blotting results showed that the protein expression levels of TGF-β1, Smad2/3 and Smad4 were significantly up-regulated in the KF-Exos group compared to the control group (all P<0.05). Conclusion:KF-Exos successfully induced the differentiation of NFs into myofibroblasts and enhanced the expression of extracellular matrix-related factors. This phenomenon may be mediated by the upregulation of the TGF-β1-Smad2/3 and Smad4 signaling pathways.

Objective: Whether peripheral blood 5-hydroxytrptamine (5-HT) levels serve as biomarker for depression diagnosis/response evaluation has not been well determined. This work was explored to address this inconclusive issue. Methods: Animals were randomized into normal control group (NC, n = 10) and chronic unpredictable mild stress model group (CUMS-model, n = 20), respectively. Animals in CUMS-model group were subjected to chronic stress, then they were randomly subdivided into CUMS subgroup and CUMS + fluoxetine subgroup (CUMS + FLX). After FLX treatment, blood and tissues were collected. 5-HT and relevant protein expression were measured. Results: In mice model, there was a significant increase in serum and a significant reduction in plasma 5-HT levels in CUMS-model group versus NC group, while platelet 5-HT levels change little. After FLX treatment, serum and platelet 5-HT levels were significantly decreased in CUMS + FLX subgroup, while plasma 5-HT levels had not much change versus CUMS subgroup. Chronic stress enhanced colon and platelet serotonin transporter (SERT) expression and FLX treatment mitigated SERT expression. In rats’ model, there was a significant increase in serum 5-HT levels while plasma and platelet 5-HT levels showed little change in CUMS group versus NC group. After FLX treatment, serum, plasma and platelet 5-HT levels were significantly decreased in CUMS + FLX subgroup versus CUMS subgroup. The profile of relevant proteins expression changed by FLX were like those in mice. Conclusion Serum 5-HT levels might serve as a potential biomarker for depression diagnosis, meanwhile serum and platelet 5-HT levels might respond to antidepressant treatment.

Objective By population survey,to explore the epidemiological characteristics of gastric precancerous lesions in Lishui District of Nanjing and provide objective basis for the prevention and treatment of early gastric cancer.Methods From July 2021 to December 2022,21 977 patients who received endoscopy and/or 13C-UBT in Lishui District People's Hospital and 6 medical community units in Nanjing City were retrospectively analyzed for demography characteristics,detection rate of gastric precancerous lesions,and H.Pylori infection rate.Results(1)590 cases of gastric precancerous lesions were detected(detection rate 2.68%);(2)The total detection rate of precancerous lesions and three pathological types in males were all higher than those in females(all P<0.001);(3)The minimum age for the total detection rate of precancerous lesions in males and the mini-mum age for each pathological type were lower than in females(P<0.001,0.009,0.005,0.002);(4)The popu-lation total H.pylori infection rate was 23.10%,the H.pylori infection rate in patients with precancerous lesions was higher than that in non-precancerous lesions(P<0.001),both H.pylori infection rate of male and female in precancerous lesions were all higher than those of non-precancerous lesions of the same sex(all P<0.001),in addition,the H.pylori infection rate of male whether in precancerous or non-precancerous lesions was higher than that of female(all P<0.001);(5)The precancerous lesions detection rate in male,female,and the overall age range of 20～29 to 70～79 years is positively correlated with age growth(P<0.001),and rapidly decreases after the age of 79,the of H.pylori infection rate was also positively correlated with age growth(P<0.001),and the trend of age change(P<0.001)was parallel to the precancerous lesions detection rate.Conclusions The detec-tion rate of gastric precancerous lesions in this region is above the average level in China;the total H.pylori infec-tion rate is at a relatively low level in China;the H.pylori infection rate is parallel to the age trend of the detection rate of gastric precancerous lesions,and increases with age.

Objective: Whether peripheral blood 5-hydroxytrptamine (5-HT) levels serve as biomarker for depression diagnosis/response evaluation has not been well determined. This work was explored to address this inconclusive issue. Methods: Animals were randomized into normal control group (NC, n = 10) and chronic unpredictable mild stress model group (CUMS-model, n = 20), respectively. Animals in CUMS-model group were subjected to chronic stress, then they were randomly subdivided into CUMS subgroup and CUMS + fluoxetine subgroup (CUMS + FLX). After FLX treatment, blood and tissues were collected. 5-HT and relevant protein expression were measured. Results: In mice model, there was a significant increase in serum and a significant reduction in plasma 5-HT levels in CUMS-model group versus NC group, while platelet 5-HT levels change little. After FLX treatment, serum and platelet 5-HT levels were significantly decreased in CUMS + FLX subgroup, while plasma 5-HT levels had not much change versus CUMS subgroup. Chronic stress enhanced colon and platelet serotonin transporter (SERT) expression and FLX treatment mitigated SERT expression. In rats’ model, there was a significant increase in serum 5-HT levels while plasma and platelet 5-HT levels showed little change in CUMS group versus NC group. After FLX treatment, serum, plasma and platelet 5-HT levels were significantly decreased in CUMS + FLX subgroup versus CUMS subgroup. The profile of relevant proteins expression changed by FLX were like those in mice. Conclusion Serum 5-HT levels might serve as a potential biomarker for depression diagnosis, meanwhile serum and platelet 5-HT levels might respond to antidepressant treatment.

Objective:To investigate the anatomic classification and reconstruction of right intrahepatic bile duct in the donor liver of split liver transplantation (SLT).Methods:The retrospective and descriptive study was constructed. The clinical data of 85 patients who underwent SLT in the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to January 2022 were collected. There were 65 males and 20 females, aged 45(range, 1-82)years. Observation indicators: (1) surgical conditions; (2) anatomy of right intrahepatic bile duct; (3) bile duct reconstruction; (4) postoperative biliary complications; (5) follow-up. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range) or M( Q1, Q3).Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Results:(1) Surgical conditions. Of the 85 donor livers, 11 donor livers were split between the left and right hemilivers, and 74 donor livers were split between the classic right trilobe and left lateral lobe. The cold ischemia time of 85 donor livers was 291(273, 354)minutes, and the operation time, anhepatic phase time and volume of intraoperative blood transfusion of 85 recipients were (497±97)minutes, 51(40, 80)minutes and 8(7, 12)U. (2) Anatomy of right intrahepatic bile duct. Of the 85 donor livers, there were 47 donor livers with classic bile duct anatomical model (type 1), of the ratio as 55.3%(47/85), and 38 donor livers with anatomical variants, of the ratio as 44.7%(38/85). Of the 38 donor livers with anatomical variants, 7 donor livers were type 2, 16 donor livers were type 3a, 2 donor livers were type 3b, 2 donor livers were type 3c, 1 donor liver was type 4, 3 donor livers were type 5a, 4 donor livers were type 5b, 3 donor livers were type 6. For bile duct splitting patterns of the 85 donor livers, 84 donor livers were split with the main trunk of common hepatic duct preserving in the right hemiliver or right trilobe, and 1 donor liver were treated with complete left and right hemiliver splitting to preserve the main trunk of the common hepatic duct in the left hemiliver and the right hemiliver in the right hepatic duct (type 1 bile duct anatomical model). There were 84 donor livers with only one bile duct opening, and 1 donor liver with two bile duct openings (type 3c bile duct anatomical model). (3) Bile duct reconstruction. Of the 85 recipients, there were 69 recipients with common bile duct end-to-end anastomosis to common bile duct of donor liver (38 donor livers with type 1 bile duct anatomical model, 5 donor livers with type 2 bile duct anatomical model, 14 donor livers with type 3a bile duct anatomical model, 2 donor livers with type 3b bile duct anatomical model, 1 donor liver with type 4 bile duct anatomical model, 3 donor livers with type 5a bile duct anatomical model, 4 donor livers with type 5b bile duct anatomical model, 2 donor livers with type 6 bile duct anatomical model), 11 recipients with jejunum anastomosis to common bile duct of donor liver (7 donor livers with type 1 bile duct anatomical model, 2 donor livers with type 2 bile duct anatomical model, 1 donor liver with type 3c bile duct anatomical model, 1 donor liver with type 6 bile duct anatomical model), 3 recipients with jejunum anastomosis to common hepatic duct of donor liver (1 donor liver with type 1 bile duct anatomical model, 2 donor livers with type 3a bile duct anatomical model), 1 recipient with jejunum anastomosis to right hepatic duct of donor liver (type 1 bile duct anatomical model), 1 recipient with common hepatic duct end-to-end anastomosis to right posterior branch of donor liver combined with jejunum of the recipient Roux-en-y anastomosis to common hepatic duct of donor liver (type 3c bile duct anatomical model). (4) Postoperative biliary complications. Of the 85 recipients, 6 cases had postoperative biliary complications, with an incidence of 7.1% (6/85). Of the 6 recipients with postoperative biliary complications, there were 5 recipients with donor liver with type 1 bile duct anatomical model, including 3 cases undergoing postoperative biliary stricture with biliary leakage and 2 cases undergoing postoperative biliary anastomotic stricture, 1 recipient with donor liver with type 3b bile duct anatomical model and undergoing postoperative biliary anastomotic stricture and bile leakage in the liver section. Cases with biliary complications were 5 in the 47 recipients with donor liver with classic bile duct anatomical model and 1 in the 38 recipients with donor liver with anato-mical variants, showing no significant difference between them ( P>0.05). (5) Follow-up. There were 83 recipients receiving followed up for 52(12,96)months. During the follow-up period, 2 recipients died due to non-biliary complication factors (1 donor liver with type 1 bile duct anatomical model and 1 donor liver with 3a bile duct anatomical model). Conclusion:The anatomical classification of right intrahepatic bile duct of donor liver in SLT is mainly classical bile duct anatomical model, and the bile duct reconstruction scheme is mainly common bile duct of donor liver end-to-end anasto-mosis to common bile duct of recipient.

Natural compounds demonstrate unique therapeutic advantages for cancer treatment, primarily through direct tumor suppression or interference with the tumor microenvironment (TME). Glycyrrhizic acid (GL), a bioactive ingredient derived from the medicinal herb Glycyrrhiza uralensis Fisch., and its sapogenin glycyrrhetinic acid (GA), have been recognized for their ability to inhibit angiogenesis and remodel the TME. Consequently, the combination of GL with other therapeutic agents offers superior therapeutic benefits. Given GL's amphiphilic structure, self-assembly capability, and liver cancer targeting capacity, various GL-based nanoscale drug delivery systems have been developed. These GL-based nanosystems exhibit angiogenesis suppression and TME regulation properties, synergistically enhancing anti-cancer effects. This review summarizes recent advances in GL-based nanosystems, including polymer-drug micelles, drug-drug assembly nanoparticles (NPs), liposomes, and nanogels, for cancer treatment and tumor postoperative care, providing new insights into the anti-cancer potential of natural compounds. Additionally, the review discusses existing challenges and future perspectives for translating GL-based nanosystems from bench to bedside.
Animals ; Humans ; Antineoplastic Agents/therapeutic use* ; Glycyrrhizic Acid/therapeutic use* ; Liposomes/chemistry* ; Micelles ; Nanoparticles/chemistry* ; Neoplasms/pathology* ; Tumor Microenvironment/drug effects* ; Nanoparticle Drug Delivery System/therapeutic use*

Objective: Whether peripheral blood 5-hydroxytrptamine (5-HT) levels serve as biomarker for depression diagnosis/response evaluation has not been well determined. This work was explored to address this inconclusive issue. Methods: Animals were randomized into normal control group (NC, n = 10) and chronic unpredictable mild stress model group (CUMS-model, n = 20), respectively. Animals in CUMS-model group were subjected to chronic stress, then they were randomly subdivided into CUMS subgroup and CUMS + fluoxetine subgroup (CUMS + FLX). After FLX treatment, blood and tissues were collected. 5-HT and relevant protein expression were measured. Results: In mice model, there was a significant increase in serum and a significant reduction in plasma 5-HT levels in CUMS-model group versus NC group, while platelet 5-HT levels change little. After FLX treatment, serum and platelet 5-HT levels were significantly decreased in CUMS + FLX subgroup, while plasma 5-HT levels had not much change versus CUMS subgroup. Chronic stress enhanced colon and platelet serotonin transporter (SERT) expression and FLX treatment mitigated SERT expression. In rats’ model, there was a significant increase in serum 5-HT levels while plasma and platelet 5-HT levels showed little change in CUMS group versus NC group. After FLX treatment, serum, plasma and platelet 5-HT levels were significantly decreased in CUMS + FLX subgroup versus CUMS subgroup. The profile of relevant proteins expression changed by FLX were like those in mice. Conclusion Serum 5-HT levels might serve as a potential biomarker for depression diagnosis, meanwhile serum and platelet 5-HT levels might respond to antidepressant treatment.

Objective: Whether peripheral blood 5-hydroxytrptamine (5-HT) levels serve as biomarker for depression diagnosis/response evaluation has not been well determined. This work was explored to address this inconclusive issue. Methods: Animals were randomized into normal control group (NC, n = 10) and chronic unpredictable mild stress model group (CUMS-model, n = 20), respectively. Animals in CUMS-model group were subjected to chronic stress, then they were randomly subdivided into CUMS subgroup and CUMS + fluoxetine subgroup (CUMS + FLX). After FLX treatment, blood and tissues were collected. 5-HT and relevant protein expression were measured. Results: In mice model, there was a significant increase in serum and a significant reduction in plasma 5-HT levels in CUMS-model group versus NC group, while platelet 5-HT levels change little. After FLX treatment, serum and platelet 5-HT levels were significantly decreased in CUMS + FLX subgroup, while plasma 5-HT levels had not much change versus CUMS subgroup. Chronic stress enhanced colon and platelet serotonin transporter (SERT) expression and FLX treatment mitigated SERT expression. In rats’ model, there was a significant increase in serum 5-HT levels while plasma and platelet 5-HT levels showed little change in CUMS group versus NC group. After FLX treatment, serum, plasma and platelet 5-HT levels were significantly decreased in CUMS + FLX subgroup versus CUMS subgroup. The profile of relevant proteins expression changed by FLX were like those in mice. Conclusion Serum 5-HT levels might serve as a potential biomarker for depression diagnosis, meanwhile serum and platelet 5-HT levels might respond to antidepressant treatment.