Ischemic stroke (IS) is a prevalent neurological disorder often resulting in significant disability or mortality. Resveratrol, extracted from Polygonum cuspidatum Sieb. et Zucc. (commonly known as Japanese knotweed), has been recognized for its potent neuroprotective properties. However, the neuroprotective efficacy of its derivative, (E)-4-(3,5-dimethoxystyryl) quinoline (RV02), against ischemic stroke remains inadequately explored. This study aimed to evaluate the protective effects of RV02 on neuronal ischemia-reperfusion injury both in vitro and in vivo. The research utilized an animal model of middle cerebral artery occlusion/reperfusion and SH-SY5Y cells subjected to oxygen-glucose deprivation and reperfusion to simulate ischemic conditions. The findings demonstrate that RV02 attenuates neuronal mitochondrial damage and scavenges reactive oxygen species (ROS) through mitophagy activation. Furthermore, Parkin knockdown was found to abolish RV02's ability to activate mitophagy and neuroprotection in vitro. These results suggest that RV02 shows promise as a neuroprotective agent, with the activation of Parkin-mediated mitophagy potentially serving as the primary mechanism underlying its neuroprotective effects.
Animals ; Ubiquitin-Protein Ligases/genetics* ; Mitophagy/drug effects* ; Resveratrol/analogs & derivatives* ; Neuroprotective Agents/pharmacology* ; Humans ; Neurons/metabolism* ; Reactive Oxygen Species/metabolism* ; Ischemic Stroke/genetics* ; Male ; Quinolines/pharmacology* ; Mice ; Fallopia japonica/chemistry* ; Mitochondria/metabolism* ; Reperfusion Injury/metabolism* ; Rats ; Mice, Inbred C57BL ; Disease Models, Animal

BACKGROUND:Intra-articular injection played an important role in the treatment of osteoarthritis and has more options with the development of novel drug delivery systems.The cartilage targeting function is aimed at the adhesion or retention of drugs in the cartilage layer to form a drug bank to achieve slow release and precise drug delivery. OBJECTIVE:To review various cartilage targeting biomaterials and their characteristics in the treatment of osteoarthritis by articular injection. METHODS:Using the term"osteoarthritis,drug carrier,drug delivery,cartilage targeting,penetrate"as key words,relevant articles were searched in CNKI,WanFang and PubMed databases.According to inclusion and exclusion criteria,67 articles were finally selected for further review. RESULTS AND CONCLUSION:The research on cartilage-targeting biomaterials is mainly divided into two directions.One is the combination of electrostatic interaction,such as the combination of positively charged biomaterials and negatively charged polysaccharides in cartilage.This kind of scheme is operable and easy to modify,but limited by the shortcomings of electrostatic interaction itself,it performs badly in advanced osteoarthritis.Another one is the specific binding of various components in cartilage which is strong and reliable,and related biomaterials have excellent performance in advanced osteoarthritis,which is an important direction for future cartilage-targeted therapy.

Objective:To explore the protective effect of AGK2, a selective inhibitor of sirtuin 2 (SIRT2), on the mitochondria of L02 hepatocytes induced by thioacetamide (TAA) and its related mechanism.Methods:Human-derived hepatocyte line L02 cells were cultured in vitro. Different concentrations of SIRT2 inhibitor AGK2 were used as intervention drugs. Cell counting kit-8 (CCK8) was used to detect the effects of different concentrations of AGK2 on the activity of L02 cells, and the appropriate concentration was selected as the AGK2 intervention group. The normal group was not given any drug intervention. The model group was given 90 mmol/L TAA for modeling. Low, medium and high dose AGK2 groups were added with 1, 2 and 4 μmol/L AGK2, respectively 2 h before modeling. CCK8 was used to detect cell activity in each group. Morphological changes of cells were observed under inverted light microscope. The relative protein expression levels of isocitrate dehydrogenase (IDH1), malate dehydrogenase (MDH1), SIRT2 and fission protein 1 homologue (FIS1) were detected by Western blot. The expression of SIRT2 in cells of each group was observed by confocal laser scanning microscope. The mitochondrial membrane potential of cells in each group was observed under a fluorescence microscope. Results:When AGK2 concentration was 1, 2 and 4 μmol/L, the survival rate of cells were 98.05%, 95.76% and 91.65%, respectively, with no statistical significance compared with normal group (all P>0.05). When AGK2 concentration was 8, 16, 32, 64, 128 μmol/L, the cell survival rate was significantly decreased compared with normal group (all P<0.05). Compared with the model group, the L02 cells in low, medium and high AGK2 groups had better activity and adherence, and the floating cells were significantly reduced. The higher the concentration of AGK2, the better the cell activity and adherence, and the less floating cells. Compared with the model group, the red fluorescence of L02 cells in AGK2 group was enhanced, while the green fluorescence was weakened. The higher the AGK2 concentration was, the stronger the red fluorescence was, and the weaker the green fluorescence was. Compared with the model group, the fluorescence of SIRT2 in L02 cells of low, medium and high AGK2 groups was weakened, and the higher the concentration of AGK2, the weaker the fluorescence of SIRT2. The protein expressions of IDH1 and MDH1 in L02 cells of low, medium and high AGK2 groups were significantly higher than those of model group (all P<0.05), and were positively correlated with the concentration of AGK2 ( r=0.818, P<0.05; r=0.960, P<0.05); the protein expressions of SIRT2 and FIS1 were significantly lower than those of the model group (all P<0.05), and were negatively correlated with the concentration of AGK2 ( r=-0.992, P<0.05; r=-0.998, P<0.05). Conclusions:AGK2 can reduce the mitochondrial membrane potential stimulated by TAA in L02 cells, increase the protein expression of IDH1 and MDH1, and inhibit the protein expression of SIRT2 and FIS1 in L02 cells in a dose-dependent manner.

OBJECTIVE: To investigate the chemical constituents from the leaves of Jatropha curcas and evaluate their inhibition on lipopolysaccharide (LPS)-activated BV-2 microglia cells. METHODS: The n-BuOH extract of the leaves of J. curcas was isolated by macroporous adsorption resin, silica gel, ODS, column chromatography and semi-preparative HPLC. The structures of the compounds were identified by MS, NMR, ECD, and other spectroscopic methods. In addition, anti-neuroinflammatory effects of isolated compounds were evaluated by measuring the production of nitric oxide (NO) in over-activated BV-2 cells. RESULTS: Seventeen compounds, including (7R,8S)-crataegifin A-4-O-β-D-glucopyranoside ( 1), (8R,8'R)-arctigenin ( 2), arctigenin-4'-O-β-D-glucopyranoside ( 3), (-)-syringaresinol ( 4), syringaresinol-4'-O-β-D-glucopyranoside ( 5), (-)-pinoresinol ( 6), pinoresinol-4'-O-β-D-glucopyranoside ( 7), buddlenol D ( 8), (2R,3R)-dihydroquercetin ( 9), (2S,3S)-epicatechin ( 10), (2R,3S)-catechin ( 11), isovitexin ( 12), naringenin-7-O-β-D-glucopyranoside ( 13), chamaejasmin ( 14), neochamaejasmin B ( 15), isoneochamaejasmin A ( 16), and tomentin-5-O-β-D-glucopyranoside ( 17) were isolated and identified. Compounds 2, 4 and 8 significantly inhibited the release of NO in BV-2 microglia activated by LPS, with IC₅₀ values of 18.34, 29.33 and 26.30 μmol/L, respectively. CONCLUSION Compound 1 is a novel compound, and compounds 2, 3, 8, 14- 17 are isolated from Jatropha genus for the first time. In addition, the lignans significantly inhibited NO release and the inhibitory activity was decreased after glycosylation.

Objective:To investigate the application value of intrathoracic double-flap tech-nique (Kamikawa anastomosis) in combined thoracoscopic and laparoscopic radical resection for esophagogastric junction cancer.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 10 patients with esophagogastric junction cancer who were admitted to the First Affiliated Hospital of Xiamen University between July 2022 and April 2023 were collec-ted. There were 7 males and 3 females, aged 62(range, 53-71)years. All the 10 patients underwent combined thoracoscopic and laparoscopic radical resection for esophagogastric junction cancer. Reconstruction was performed with an intrathoracic Kamikawa anastomosis. Observation indicators: (1) intraoperative and postoperative situations; (2) postoperative pathological examination; (3) follow-up and survival. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Results:(1) Intraoperative and postoperative situations. All the 10 patients underwent surgery successfully. The operation time and volume of intraoperative blood loss were (347±41)minutes and (91±41)mL. The time to postoperative fluid diet intake, time to removal of postoperative abdominal drainage tube, time to removal of postoperative chest drainage tube, duration of postoperative hospital stay were (4.3±1.1)days, (5.0±1.6)days, (10.5±3.9)days, (13.3±3.8)days. Six patients had postoperative complications, including 1 case of Clavien-Dindo grade ⅢB, 3 cases of Clavien Dindo grade Ⅱ, 2 cases of Clavien Dindo grade Ⅰ. An upper gastrointestinal contrast at postoperative day 7 showed no anastomotic leak or anastomotic stricture in the 10 patients. (2) Postoperative pathological examination. Results of postoperative pathological examination in the 10 patients showed negative surgical margin. The number of lymph node dissected was 22±6. There were 3 patients with 5 positive lymph nodes. The tumor diameter and distance from center of tumor to squamocolumnar mucosal junction were (3.3±0.5)cm and (1.9±1.4)cm. One patient had tumor differentiation degree as high and moderate differentiation, 5 cases as moderate differentiation, 3 cases as moderate and low differentiation, 1 case as low differentiation. There were 5 patients with squamous cell carcinoma of the esophagogastric junction and 5 patients with adenocarcinoma of the esophagogastric junction. (3) Follow-up and survival. All the 10 patients were followed up for 7(range, 3?12)months, achieving disease-free survival. The visick quality of life grade Ⅰ, Ⅱ, Ⅲ, Ⅳ were observed in 7, 3, 0, 0 patients. Postoperative gastroscopy was completed in 7 patients, in which mild anastomotic strictures were noted in 2 patients, but no treatment was required. There was no reflux esophagitis.Conclusion:Intrathoracic Kamikawa anastomosis in combined thoracoscopic and laparoscopic radical resection for esophagogastric junction cancer is safe and feasible, with satisfactory short-term efficacy.

Objective:To improve the understanding of indolent mantle cell lymphoma (MCL).Methods:The data of a patient with indolent leukemic MCL in the Second Affiliated Hospital of Nanjing Medical University in May 2013 were collected. The cell morphology was analyzed by using cell smear, the flow cytometry was used to make immunophenotype analysis, the karyotype analysis was performed by usig cytogenetic technique, and polymerase chain reaction (PCR) was used to make the immunoglobulin gene analysis. At the same time, lymph node pathology and immunohistochemistry were also analyzed. The related articles published were reviewed to sum up the characteristics and the treatment of indolent MCL.Results:The male patient aged 60 years was obviously asymptomatic accompanied with slow disease progression, leukemic manifestation and without lymphadenopathy. He received pathological biopsy because of located lymphadenopathy in 2008. Small cell morphology, Kappa light chain immunophenotype, t(11;14) translocation showed after the cytogenetic examination, clonal immune globulin gene rearrangement and low Ki-67 positive index were identified. In situ MCL was diagnosed by retrospective pathology.Conclusions:Indolent MCL is extremely rare. It is typically asymptomatic with none or minimal nodal involvement, indolent disease course, leukemic phase with mild lymphocytosis, Kappa light chain expression, simple karyotype, classical or small cell morphology of tumor cells and the positive index of Ki-67 <10%. In situ MCL can be seen in pathology examination. IgVH gene mutation positive and SOX11 negative expression are notable in indolent MCL. International prognostic index of MCL is probably not appropriate in the prognostic analysis of leukemic indolent MCL. It is emphasized that initial observation and having therapies only after the disease progression can be suited for indolent MCL.

Objective:To investigate the application value of transanal endoscopic partial intersphincteric resection for ultra-low rectal cancer.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 9 ultra-low rectal cancer patients undergoing transanal endoscopic partial intersphincteric resection at the First Affiliated Hospital of Xiamen University from December 2017 to August 2020 were collected. There were 8 males and 1 female, aged from 39 to 62 years, with a median age of 58 years. Observation indicators: (1) surgical and postoperative situations; (2) postoperative pathological examination; (3) follow-up. Follow-up was conducted using outpatient examination and telephone interview to detect postoperative tumor local recurrence and distant metastasis, survival of patients, ileostomy closure, anus function at 3 months after ileostomy closure, male urinary and sexual function and female sexual function at 6 months after rectal surgery. The follow-up was up to February 2021. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Results:(1)Surgical and postoperative situations: all 9 patients underwent surgery successfully, without conversion to open surgery. Seven of the 9 patients underwent transanal endoscopic partial intersphincteric resection and the rest of 2 patients with tumor close to the dentate line underwent transanal endoscopic modified partial intersphincteric resection. The operation time and volume of intraoperative blood loss of 9 patients were (267±48)minutes and 50 mL(range, 30?60 mL), respectively. Five of the 9 patients underwent transanal specimen extraction, and 4 patients underwent specimen extraction by an abdominal incision. All 9 patients underwent transanal hand-sewn coloanal anastomosis and protective ileostomy, and two pelvic drainage tubes were indwelled. Transanal drainage tube was placed after anastomosis in 3 of 9 patients. Three cases had intraoperative adverse events and there were no intraoperative adverse event reported in the remaining 6 cases. The time to postoperative initial stoma exhausting and time to postoperative first semi-liquid food intake of 9 patients were 3 days(range, 2?4 days) and 5 days(range, 4?7 days), respectively. One case had Clavien-Dindo grade Ⅰ complication and 2 cases had Clavien-Dindo grade Ⅱ complication during postoperative 30 days and the rest of 6 cases had no postoperative complication. No anastomotic stricture, hemorrhage or urinary retention occurred in 9 patients. The duration of postoperative hospital stay and cost of hospitalization of 9 patients were 11 days(range, 9?23 days) and (6.8±1.3)×10 4 yuan, respectively. (2) Postoperative pathological examination: the diameter of tumor, the distance of distal resection margin, the number of lymph node dissected and the number of positive lymph node of 9 patients were (3.2±1.4)cm, 0.6 cm(range, 0.5?1.5 cm), 17±7 and 0(range, 0?7), respectively. The tumor histopathological type was adenocarcinoma with negative tumor nodule and nerve infiltration in all 9 patients. Only 1 case of 9 patients was found vascular tumor thrombus. The surgical specimens of all 9 patients showed negative for distal and circumferential margins and complete mesorectum. Results of postoperative pathological TNM staging showed that of 6 cases with preoperative T1-T2 staging tumors, 3 cases were classified as pT2N0M0 stage, and 3 cases were classified as pT2N1M0 stage, pT2N2M0 stage or pT3N1M0 stage, respectively. Three cases with preoperative T3 staging tumors were classified as ypT0N0M0 stage, ypT2N0M0 stage or ypT3N0M0 stage, respectively. (3) Follow-up: all 9 patients were followed up for 6 to 13 months, with a median follow-up time of 9 months. No local recurrence, distant metastasis or tumor-related death was found during follow-up. Of the 9 patients, only 1 case did not receive stoma closure and undergo anus function assessment, and the rest of 8 cases underwent stoma closure. Results of postoperative anus function assessment showed 5 cases of accessibility, 2 cases of mild impairment and 1 case of severe impairment. Results of urogenital function assessment showed 6 cases of the 8 male patients of mild impairment, 1 case of moderate impairment and 1 case of severe impairment in micturition function, respectively, and 3 cases of accessibility, 2 cases of mild impairment and 3 cases of moderate impairment in sexual function, respectively. The female patient underwent accessibility of sexual function and the six-item version of the female sexual function index was 25. Conclusion:Transanal endoscopic partial intersphincteric resection can be used for the treatment of ultra-low rectal cancer.

Objective:To investigate the reparative efficacy and mechanism of pressure-adjustable macroporous antibacterial hydrogel in the treatment of infected wounds.Methods:Staphylococcus aureus was used to establish wound infection models in healthy C57BL/6 mice. The models were divided into 3 groups subjected to 3 different treatments: a negative control group with no hydrogel treatment (group A), a control group treated by common medical hydrogel (group B) and an experiment group treated by pressure-adjustable macroporous antibacterial hydrogel (group C). On days 1, 3, 6, 9 and 12, the effects of 3 treatments were compared on the wound area and the number of bacterial colonies under scab, on the apoptosis of fibroblasts based on the changes of type Ⅰ procollagen, and on the inhibition of inflammation during wound repair by detecting the expression of interleukin-6 (IL-6) and tumor necrosis factor (TNF-α).Results:On days 1 and 3, there was no significant difference between the 3 groups in the wound area ( P>0.05), but on days 6, 9 and 12, there were significant differences between the 3 groups in the wound area ( P<0.05). On day 6, the wound areas in group B (1.23 cm 2 ± 0.16 cm 2) and in group C (1.14 cm 2 ± 0.12 cm 2) were significantly smaller than that in group A (1.56 cm 2 ± 0.16 cm 2) ( P<0.05), but there was no significant difference between groups B and C ( P>0.05). On days 9 and 12, the wound areas in group B (0.97 cm 2 ± 0.13 cm 2 and 0.76 cm 2 ± 0.10 cm 2) and in group C (0.66 cm 2 ± 0.06 cm 2 and 0.48 cm 2 ± 0.07 cm 2) were significantly smaller than those in group A (1.49 cm 2 ± 0.11 cm 2 and 1.39 cm 2 ± 0.13 cm 2), and those in group C were significantly smaller than those in group B (all P<0.05). On day 1, there was no significant difference between the 3 groups in the number of bacterial colonies under scab ( P>0.05). On days 3, 6, 9 and 12, the numbers of bacterial colonies under scab in groups B and C were significantly smaller than that in group A ( P<0.05), and that in group C was significantly smaller than that in group B ( P< 0.05). The nucleic acid electrophoresis showed that the grayscale bands in group C were significantly darker than those in groups A and B. The early apoptosis rate of the fibroblasts in group C[low-right positive fluorescence (LR%): 9.72%] was significantly lower than that in group A (43.99%) and that in group B (38.43%), and that in group B was significantly lower than that in group A ( P<0.05). On day 12, the ratio of the gray values of IL-6 and β-actin (0.64 ± 0.10) and the ratio of the gray values of TNF-α and β-actin (0.34 ± 0.05) in the fibroblasts in group C were significantly higher than those in group A (1.22 ± 0.21 and 0.60 ± 0.14) and in group B (0.88 ± 0.02 and 0.41 ± 0.06) ( P<0.01). Conclusion:The pressure-adjustable macroporous antibacterial hydrogel is an effective treatment of infected wounds and its mechanism may be related to the reduced apoptosis of fibroblasts.

Objective: To investigate the serum levels and clinical significances of microRNA-205 (miR-205) and microRNA-221 (miR-221) in patients with colon cancer. Methods: A total of 172 patients with colon cancer (colon cancer group), 130 patients with benign diseases of colon (benign lesion group) and 70 healthy persons (control group) admitted to Central Hospital of Western Hainan from January 2016 to December 2018 were selected. The serum levels of miR-205 and miR-221 in each group were detected, and their relationships with clinicopathological characteristics of patients with colon cancer were analyzed. The diagnostic values of the serum levels of miR-205 and miR-221 in colon cancer were analyzed by receiver operating characteristic (ROC) curve. Pearson correlation analysis was used to analyze the correlation between the serum levels of miR-205 and miR-221. Results: The serum levels of miR-205 in colon cancer group, benign lesion group and control group were 2.84±0.96, 1.16±0.27 and 1.05±0.23, with a statistically significant diffe-rence (F=10.113, P<0.001). The serum levels of miR-221 in the three groups were 1.95±0.74, 0.37±0.08 and 0.32±0.05, with a statistically significant difference (F=12.416, P<0.001). Further pairwise comparisons found that the serum levels of miR-205 and miR-221 in colon cancer group were significantly higher than those in benign lesion group and control group (all P<0.001). The serum levels of miR-205 and miR-221 in patients with colon cancer were related with TNM stage (t=5.412, P<0.001; t=6.103, P<0.001), degree of tumor differentiation (t=4.573, P=0.028; t=4.805, P=0.013) and with or without lymph node metastasis (t=5.837, P<0.001; t=7.410, P<0.001). ROC curve analysis showed that the optimal cut-off values of the serum levels of miR-205 and miR-221 for the diagnosis of colon cancer were 2.17 and 1.30, respectively. The area under the curve of the two combined diagnostic method for colon cancer was the largest (0.924, 95%CI: 0.865-0.983), with the sensitivity and specificity of 91.3% and 87.4%. The correlation analysis showed that the serum levels of miR-205 and miR-221 were positively correlated in patients with colon cancer (r=0.837, P<0.001). Conclusion The serum levels of miR-205 and miR-221 are significantly increased in patients with colon cancer, and the two combined detection has a high value for the diagnosis of colon cancer.