OBJECTIVE To explore the effect of superoxide dismutase （SOD） administration on the malignant behavior of PLC/PRF/5 liver cancer cells， and analyze the correlation between SOD and alpha-fetoprotein （AFP） expression， to provide new ideas for targeting AFP with SOD as a drug for hepatocellular carcinoma. METHODS Normal human liver cells L-02， AFP- negative human liver cancer cells HLE， and AFP-positive human liver cancer cells PLC/PRF/5 were used as experimental cells. Western blot assay and SOD activity detection kit were used to detect the expression of AFP， SOD and activity of SOD in cells before and after changing AFP expression； the effects of different concentrations of SOD [0 （control）， 0.188， 0.375， 0.75， 1.5， 3 U/mL] administration on the migration and proliferation of PLC/PRF/5 cells were detected using cell scratch assay and CCK-8 assay. The effects of SOD overexpression on the expression of malignant biological behavior-related proteins AFP and sarcoma virus protein （Src） in PLC/PRF/5 cells were detected using Western blot. RESULTS Compared with L-02 group and HLE group， the expression levels of SOD1 and SOD2， and SOD activity in PLC/PRF/5 cells were significantly reduced （P＜0.05）. After down-regulating AFP expression in PLC/PRF/ 5 cells， compared with PLC/PRF/5 group， the expression levels of SOD1 and SOD2， as well as SOD activity， were significantly increased in the PLC/PRF/5-shAFP group （low-expression） （P＜0.05）. After 48 hours of SOD treatment， compared with control group， the scratch healing rates of PLC/PRF/5 cells in the 0.375， 0.75， 1.5 and 3 U/mL SOD groups were significantly reduced （P＜0.05）； after 72 hours of SOD treatment， compared with control group， the scratch healing rates of PLC/PRF/5 cells in the 0.375， 0.75， and 1.5 U/mL SOD groups were significantly reduced （P＜0.05 or P＜0.01）. Compared with control group， proliferation rates of PLC/PRF/5 cells were significantly reduced in the 0.375， 0.75， 1.5 and 3 U/mL SOD groups （P＜0.05 or P＜0.01）. Compared with the PLC/PRF/5 group before up-regulating SOD1 and SOD2 expression， the expression levels of AFP and Src in the PLC/PRF/5-oeSOD1 and PLC/PRF/5-oeSOD2 groups （over-expression） after up-regulating SOD1 and SOD2 expression were significantly reduced （P＜0.05）. CONCLUSIONS A certain concentration of SOD can inhibit malignant behavior such as migration and proliferation of PLC/PRF/5 cells， and the expression level and activity of SOD are negatively correlated with AFP.

Insufficient alveolar bone thickness increases the risk of periodontal dehiscence and fenestration, especially in orthodontic tooth movement. Abaloparatide (ABL), a synthetic analog of human PTHrP (1-34) and a clinical medication for treating osteoporosis, has recently demonstrated its potential in enhancing craniofacial bone formation. Herein, we show that intraoral submucosal injection of ABL, when combined with mechanical force, promotes in situ alveolar bone thickening. The newly formed bone is primarily located outside the original compact bone, implying its origin from the periosteum. RNA sequencing of the alveolar bone tissue revealed that the focal adhesion (FA) pathway potentially mediates this bioprocess. Local injection of ABL alone enhances cell proliferation, collagen synthesis, and phosphorylation of focal adhesion kinase (FAK) in the alveolar periosteum; when ABL is combined with mechanical force, the FAK expression is upregulated, in line with the accomplishment of the ossification. In vitro, ABL enhances proliferation, migration, and FAK phosphorylation in periosteal stem cells. Furthermore, the pro-osteogenic effects of ABL on alveolar bone are entirely blocked when FAK activity is inhibited by a specific inhibitor. In summary, abaloparatide combined with mechanical force promotes alveolar bone formation via FAK-mediated periosteal osteogenesis. Thus, we have introduced a promising therapeutic approach for drug-induced in situ alveolar bone augmentation, which may prevent or repair the detrimental periodontal dehiscence, holding significant potential in dentistry.
Osteogenesis/drug effects* ; Periosteum/cytology* ; Parathyroid Hormone-Related Protein/administration & dosage* ; Animals ; Focal Adhesion Protein-Tyrosine Kinases/metabolism* ; Alveolar Process/drug effects* ; Cell Proliferation/drug effects* ; Phosphorylation ; Rats ; Male ; Humans ; Focal Adhesion Kinase 1/metabolism* ; Cell Movement/drug effects*

Objective:To investigate the clinical efficacy of open anterior myofascial repair surgery on abdominal wall incision hernia.Methods:The retrospective cohort study was conducted. The clinical data of 188 patients who underwent open anterior myofascial repair surgery on abdo-minal wall incision hernia at three medical centers, including Xiangya Hospital of Central South University et al, from December 2016 to December 2024 were collected. There were 85 males and 103 females, aged (62±12)years. Of the 188 patients, 55 cases had large incisional hernia and 133 cases had non-large incisional hernia. Observation indicators: (1) intraoperative conditions; (2) postopera-tive conditions; (3) follow-up. Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test or Fisher exact test. Comparison of ordinal data between groups was conducted using the nonparametic test. Results:(1) Intra-operative conditions. The operation time of the 55 patients with large incisional hernia was (145±40)minutes, and the volume of intraoperative blood loss was 40.0(22.5,55.0)mL, cases with fascial defect located in the central anterior abdominal wall, the superolateral quadrant, the inferolateral quadrant were 26, 7, 22, the fascial defect area was 140(99,169)cm2, cases used with self-fixating mesh and flat mesh were 29, 26. The above indicators of the 133 patients with non-large incisional hernia were (124±34)minutes, 35.0(30.0,45.0)mL, 47, 26, 60, 25(12,40)cm2, 67, 66, respectively. There were significant differences in operation time and fascial defect area between patients with large incisional hernia and non-large incisional hernia ( t=-3.651, Z=-10.339, P<0.05), and there was no significant difference in the volume of intraoperative blood loss, defect quadrant distribution, and mesh type ( Z=-0.501, χ2=2.692, 0.086, P>0.05). (2) Postoperative conditions. Of the 55 patients with large incisional hernia, 7 cases developed postoperative seroma, including 5 cases combined with concomitant surgical-site infection, and 4 additional cases developed with surgical-site infection. Of the 133 patients with non-large incisional hernia, 15 cases developed postoperative seroma, including 3 cases combined with concomitant surgical-site infection. There was a significant difference in surgical-site infection between patients with large incisional hernia and non-large incisional hernia ( χ2=10.707, P<0.05), and there was no significant difference in postoperative seroma ( χ2=0.079, P>0.05). The duration of postoperative hospital stay was 7(6, 9)days for the 55 patients with large incisional hernia and 5(4, 6)days for the 133 patients with non-large incisional hernia, showing a significant difference between them ( Z=-6.292, P<0.05). (3) Follow-up. All 188 patients were followed up for 43(range, 29-67)months. During the follow-up, 9 patients experienced hernia recurrence, including 7 patients with large incisional hernia and 2 patients with non-large incisional hernia. For the 7 patients of large incisional hernia with hernia recurrence, 4 cases underwent reoperation and 3 cases received conservative treatment. All 2 patients of non-large incisional hernia with hernia recurrence received conservative treatment. There was no significant difference in hernia recurrence between patients with large incisional hernia and non-large incisional hernia ( χ2=8.432, P<0.05). Results of chronic pain score at postoperative 3 month showed that among 55 patients with large incisional hernia, 40 cases had mild pain, 7 cases had moderate pain, and 8 cases had severe pain. Among 133 patients with non-large incisional hernia, the above indicators were 102, 28, and 3, respectively. There was no significant difference in chronic pain score at postoperative 3 month between patients with large incisional hernia and non-large incisional hernia ( Z=-0.968, P>0.05). Conclusions:Open anterior myofascial repair surgery can be used for the treatment of abdominal wall incision hernia. Compared with non-large incisional hernia, patients with large incisional hernia have longer operation time, are more prone to surgical-site infection, have longer postoperative hospital stay, and are more likely to experience hernia recurrence.

AIM:To investigate whether melatonin can ameliorate acute myocardial infarction(AMI)by in-hibiting ferroptosis.METHODS:H9C2 cells were cultured in AnaeroPack system with low sugar and serum-free medium for 10 h to construct a cell model of AMI.Then cells were treated with melatonin and ferroptosis inducer erastin.The cell activity,reactive oxygen species(ROS),lipid peroxidation,mitochondrial membrane potential(MMP),and ferroptosis related protein expression were detected.A rat model of AMI induced by isoprenaline(ISO)injection was established to evaluate the effects of melatonin,in which the myocardial infarction size,cardiac injury,pathological changes,oxidative stress,iron ion and ferroptosis related protein expression were examined.RESULTS:Melatonin decreased the oxidative stress,lipid peroxidation and expression of ferroptosis protein in cardiomyocytes induced by hypoxia,but these effects could be impeded by the ferroptosis inducer erastin.Furthermore,in vivo experiments,we also found that melatonin im-proved the myocardial infarction size,cardiac injury,pathological changes,oxidative stress,and alleviated iron ion accu-mulation and ferroptosis.CONCLUSION:The cardioprotective effects of melatonin in AMI are associated with the inhi-bition of ferroptosis.

Objective To construct an animal model of post-stroke depression(PSD)based on the theory of"depression,stasis,phlegm",with the aim of developing and validating an objective assessment system.Methods Rats were divided randomly into five groups:control,depression,stroke,PSD,and Baishile decoction groups.A PSD syndrome-based animal model was established in rats using a combination of middle cerebral artery occlusion(MCAO)and chronic unpredictable mild stress(CUMS)."Depression,stasis,phlegm"were then evaluated in the model rats using the Morris water maze,open field,forced swimming,and sucrose preference tests,and by detection of neurotransmitter levels,brain tissue pathology,tongue and forepaw color RGB values,and blood rheology.Results PSD rats exhibited significantly shorter target quadrant dwelling times,platform crossings,and climbing and rearing frequencies,a significantly lower sucrose preference,and a significantly higher immobility time in the forced swim test compared with control rats.Hematoxylin and eosin and Nissl staining revealed brain tissue damage in PSD rats.Serum and cerebrospinal fluid levels of 5-hydroxytryptamine(5-HT)were significantly decreased,glutamate levels were significantly increased,and tongue and forepaw RGB values were all decreased.Blood rheology showed a hypercoagulable state and blood lipid metabolism-related indicators were significantly abnormal.Rats in the Baishile decoction group showed significant improvements compared with the PSD group,including increased target quadrant dwelling times,number of platform crossings,and climbing and rearing frequencies,increased sucrose preference,decreased immobility time in the forced swim test,improved brain tissue pathology,increased serum and cerebrospinal fluid levels of 5-HT,decreased glutamate levels,increased tongue and claw RGB values,and varying degrees of improvement in blood rheology and blood lipid metabolism-related indicators.Conclusions The combination of MCAO and CUMS successfully established a syndrome-based animal model of PSD exhibiting the characteristics of"depression,stasis,phlegm",with corresponding objective assessment criteria.

Objective To investigate the effects of electroacupuncture(EA)at"Baihui(GV 20),""Pishu(BL 20),"and"Zusanli(ST 36)"on the learning and memory functions of rats with Alzheimer's disease(AD)induced by Aβ1-42.Additionally,the mechanism of EA in treating AD was explored from the perspective of the inflammatory cascade mediated by the NF-κ B/NLRP3/Caspase-1 signaling pathway.Methods A rat model of Alzheimer's disease was established by bilateral injection of Aβ1-42 solution into the C1 region of the hippocampus.According to the random number table method,32 male SPF-grade rats were divided into four groups(n=8 per group):a sham-operated group,a model group,an electroacupuncture(EA)group,and a Western medicine group(donepezil hydrochloride).The EA group received electroacupuncture at the"Baihui","Pishu",and"Zusanli"acu-points;the Western medicine group received donepezil hydrochloride via gavage.After the treatment period,Morris water maze experiments were conducted to evaluate learning and memory abilities.Hematoxylin and eosin(HE)staining was used to examine morphological changes in hippocampal tissues.Enzyme-linked immunosorbent assay(ELISA)was employed to measure serum levels of TNF-α and IL-1β.Western blotting and immunofluorescence staining were utilized to assess the co-expression levels of NF-κB p65,NLRP3,and Caspase-1 proteins in the hippocampal region.Results Compared with the sham-operated group,rats in the post-modeling group exhibited significantly prolonged escape latency(P<0.05),reduced crossings of the original platform location,and decreased time spent in the target quadrant(P<0.05).Additionally,nuclear morphology was altered,neurons surrounding the hippocampus displayed necrosis,vacuolar degeneration,and chromatin marginalization.Serum levels of TNF-α and IL-1β were elevated(P<0.05),and protein expression levels as well as fluorescent positivity for NF-κB p65,NLRP3,and caspase-1 in the hippocampus were increased(P<0.05).Compared with the model group,rats in both the EA and Western medicine groups showed a trend toward shorter escape latency(P<0.05),increased crossings of the original platform location and time spent in the target quadrant(P<0.05).Cell structures were largely intact,with only a few nuclei showing slight irregularities and some chromatin accumulation at the edges.Serum levels of TNF-α and IL-1β were reduced(P<0.05),and protein expression levels and fluorescence positivity for NF-κB p65,NLRP3,and caspase-1 in the hippocampus were also decreased(P<0.05).Conclusion EA enhances the learning and memory capabilities of AD rats,potentially by downregulating the NF-κ B/NLRP3/Caspase-1+signaling+pathway and decreasing the release of neuroinflammatory factors,thereby alleviating cognitive dysfunction in AD rats.

Objective To investigate the effects of electroacupuncture(EA)at"Baihui(GV 20),""Pishu(BL 20),"and"Zusanli(ST 36)"on the learning and memory functions of rats with Alzheimer's disease(AD)induced by Aβ1-42.Additionally,the mechanism of EA in treating AD was explored from the perspective of the inflammatory cascade mediated by the NF-κ B/NLRP3/Caspase-1 signaling pathway.Methods A rat model of Alzheimer's disease was established by bilateral injection of Aβ1-42 solution into the C1 region of the hippocampus.According to the random number table method,32 male SPF-grade rats were divided into four groups(n=8 per group):a sham-operated group,a model group,an electroacupuncture(EA)group,and a Western medicine group(donepezil hydrochloride).The EA group received electroacupuncture at the"Baihui","Pishu",and"Zusanli"acu-points;the Western medicine group received donepezil hydrochloride via gavage.After the treatment period,Morris water maze experiments were conducted to evaluate learning and memory abilities.Hematoxylin and eosin(HE)staining was used to examine morphological changes in hippocampal tissues.Enzyme-linked immunosorbent assay(ELISA)was employed to measure serum levels of TNF-α and IL-1β.Western blotting and immunofluorescence staining were utilized to assess the co-expression levels of NF-κB p65,NLRP3,and Caspase-1 proteins in the hippocampal region.Results Compared with the sham-operated group,rats in the post-modeling group exhibited significantly prolonged escape latency(P<0.05),reduced crossings of the original platform location,and decreased time spent in the target quadrant(P<0.05).Additionally,nuclear morphology was altered,neurons surrounding the hippocampus displayed necrosis,vacuolar degeneration,and chromatin marginalization.Serum levels of TNF-α and IL-1β were elevated(P<0.05),and protein expression levels as well as fluorescent positivity for NF-κB p65,NLRP3,and caspase-1 in the hippocampus were increased(P<0.05).Compared with the model group,rats in both the EA and Western medicine groups showed a trend toward shorter escape latency(P<0.05),increased crossings of the original platform location and time spent in the target quadrant(P<0.05).Cell structures were largely intact,with only a few nuclei showing slight irregularities and some chromatin accumulation at the edges.Serum levels of TNF-α and IL-1β were reduced(P<0.05),and protein expression levels and fluorescence positivity for NF-κB p65,NLRP3,and caspase-1 in the hippocampus were also decreased(P<0.05).Conclusion EA enhances the learning and memory capabilities of AD rats,potentially by downregulating the NF-κ B/NLRP3/Caspase-1+signaling+pathway and decreasing the release of neuroinflammatory factors,thereby alleviating cognitive dysfunction in AD rats.

Objective:To investigate the clinical efficacy of open anterior myofascial repair surgery on abdominal wall incision hernia.Methods:The retrospective cohort study was conducted. The clinical data of 188 patients who underwent open anterior myofascial repair surgery on abdo-minal wall incision hernia at three medical centers, including Xiangya Hospital of Central South University et al, from December 2016 to December 2024 were collected. There were 85 males and 103 females, aged (62±12)years. Of the 188 patients, 55 cases had large incisional hernia and 133 cases had non-large incisional hernia. Observation indicators: (1) intraoperative conditions; (2) postopera-tive conditions; (3) follow-up. Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test or Fisher exact test. Comparison of ordinal data between groups was conducted using the nonparametic test. Results:(1) Intra-operative conditions. The operation time of the 55 patients with large incisional hernia was (145±40)minutes, and the volume of intraoperative blood loss was 40.0(22.5,55.0)mL, cases with fascial defect located in the central anterior abdominal wall, the superolateral quadrant, the inferolateral quadrant were 26, 7, 22, the fascial defect area was 140(99,169)cm2, cases used with self-fixating mesh and flat mesh were 29, 26. The above indicators of the 133 patients with non-large incisional hernia were (124±34)minutes, 35.0(30.0,45.0)mL, 47, 26, 60, 25(12,40)cm2, 67, 66, respectively. There were significant differences in operation time and fascial defect area between patients with large incisional hernia and non-large incisional hernia ( t=-3.651, Z=-10.339, P<0.05), and there was no significant difference in the volume of intraoperative blood loss, defect quadrant distribution, and mesh type ( Z=-0.501, χ2=2.692, 0.086, P>0.05). (2) Postoperative conditions. Of the 55 patients with large incisional hernia, 7 cases developed postoperative seroma, including 5 cases combined with concomitant surgical-site infection, and 4 additional cases developed with surgical-site infection. Of the 133 patients with non-large incisional hernia, 15 cases developed postoperative seroma, including 3 cases combined with concomitant surgical-site infection. There was a significant difference in surgical-site infection between patients with large incisional hernia and non-large incisional hernia ( χ2=10.707, P<0.05), and there was no significant difference in postoperative seroma ( χ2=0.079, P>0.05). The duration of postoperative hospital stay was 7(6, 9)days for the 55 patients with large incisional hernia and 5(4, 6)days for the 133 patients with non-large incisional hernia, showing a significant difference between them ( Z=-6.292, P<0.05). (3) Follow-up. All 188 patients were followed up for 43(range, 29-67)months. During the follow-up, 9 patients experienced hernia recurrence, including 7 patients with large incisional hernia and 2 patients with non-large incisional hernia. For the 7 patients of large incisional hernia with hernia recurrence, 4 cases underwent reoperation and 3 cases received conservative treatment. All 2 patients of non-large incisional hernia with hernia recurrence received conservative treatment. There was no significant difference in hernia recurrence between patients with large incisional hernia and non-large incisional hernia ( χ2=8.432, P<0.05). Results of chronic pain score at postoperative 3 month showed that among 55 patients with large incisional hernia, 40 cases had mild pain, 7 cases had moderate pain, and 8 cases had severe pain. Among 133 patients with non-large incisional hernia, the above indicators were 102, 28, and 3, respectively. There was no significant difference in chronic pain score at postoperative 3 month between patients with large incisional hernia and non-large incisional hernia ( Z=-0.968, P>0.05). Conclusions:Open anterior myofascial repair surgery can be used for the treatment of abdominal wall incision hernia. Compared with non-large incisional hernia, patients with large incisional hernia have longer operation time, are more prone to surgical-site infection, have longer postoperative hospital stay, and are more likely to experience hernia recurrence.

AIM:To investigate whether melatonin can ameliorate acute myocardial infarction(AMI)by in-hibiting ferroptosis.METHODS:H9C2 cells were cultured in AnaeroPack system with low sugar and serum-free medium for 10 h to construct a cell model of AMI.Then cells were treated with melatonin and ferroptosis inducer erastin.The cell activity,reactive oxygen species(ROS),lipid peroxidation,mitochondrial membrane potential(MMP),and ferroptosis related protein expression were detected.A rat model of AMI induced by isoprenaline(ISO)injection was established to evaluate the effects of melatonin,in which the myocardial infarction size,cardiac injury,pathological changes,oxidative stress,iron ion and ferroptosis related protein expression were examined.RESULTS:Melatonin decreased the oxidative stress,lipid peroxidation and expression of ferroptosis protein in cardiomyocytes induced by hypoxia,but these effects could be impeded by the ferroptosis inducer erastin.Furthermore,in vivo experiments,we also found that melatonin im-proved the myocardial infarction size,cardiac injury,pathological changes,oxidative stress,and alleviated iron ion accu-mulation and ferroptosis.CONCLUSION:The cardioprotective effects of melatonin in AMI are associated with the inhi-bition of ferroptosis.