Polycystic ovary syndrome (PCOS) is the predominant cause of subfertility in reproductive-aged women; however, its pathophysiology remains unknown. Neurotensin (NTS) is a member of the gut-brain peptide family and is involved in ovulation; its relationship with PCOS is unclear. Here, we found that NTS expression in ovarian granulosa cells and follicular fluids was markedly decreased in patients with PCOS. In the in vitro culture of cumulus-oocyte complexes, the neurotensin receptor 1 (NTSR1) antagonist SR48692 blocked cumulus expansion and oocyte meiotic maturation by inhibiting metabolic cooperation and damaging the mitochondrial structure in oocytes and surrounding cumulus cells. Furthermore, the ERK1/2-early growth response 1 pathway was found to be a key downstream mediator of NTS/NTSR1 in the ovulatory process. Animal studies showed that in vivo injection of SR48692 in mice reduced ovulation efficiency and contributed to irregular estrus cycles and polycystic ovary morphology. By contrast, NTS partially ameliorated the ovarian abnormalities in mice with dehydroepiandrosterone-induced PCOS. Our findings highlighted the critical role of NTS reduction and consequent abnormal NTSR1 signaling in the ovulatory dysfunction of PCOS, suggesting a potential strategy for PCOS treatment.
Polycystic Ovary Syndrome/physiopathology* ; Female ; Animals ; Neurotensin/metabolism* ; Receptors, Neurotensin/antagonists & inhibitors* ; Mice ; Ovulation/drug effects* ; Humans ; Granulosa Cells/metabolism* ; Adult ; Oocytes/metabolism* ; MAP Kinase Signaling System ; Signal Transduction ; Follicular Fluid/metabolism* ; Disease Models, Animal ; Gonadotropin-Releasing Hormone/analogs & derivatives*

BACKGROUND:Previous studies have demonstrated that acupuncture at the governor meridian has precise efficacy in the treatment of ischemic stroke and can improve cerebral ischemia-reperfusion injury by attenuating pyroptosis,but the upstream regulatory mechanisms are not yet fully clarified.OBJECTIVE:To observe the neuroprotective effect of electroacupuncture in model rats of cerebral ischemia-reperfusion injury.METHODS:Twenty-seven Sprague-Dawley rats were randomly divided into sham surgery,model,and electroacupuncture groups,with nine rats in each group.Modified suture method was used to establish cerebral ischemia-reperfusion model rats in the model and electroacupuncture groups.The electroacupuncture group was subjected to electroacupuncture at"Baihui,""Fengfu,"and"Dazhui"acupoints,20 minutes each,once a day,for 7 consecutive days.After treatment,neurological deficit scoring and pole test were performed to assess behavioral changes.Tri-phenyl tetrazolium chloride staining was used to assess cerebral infarction size in rats.Hematoxylin-eosin staining was performed to observe morphological changes in cerebral cortex tissue on the infarcted side of rats.Immunofluorescence analysis was used to determine Iba-1 and reactive oxygen species levels in cerebral cortex tissue on the infarcted side of rats,ELISA method was used for measuring interleukin-1β,interleukin-6 and tumor necrosis factor α levels in cerebral cortex tissue on the infarcted side of rats.Real-time fluorescence quantitative PCR and western blot were used to detect mRNA and protein expression levels of thioredoxin interaction protein,nod-like receptor associated protein 3(NLRP3),Caspase-1 and interleukin-1β in cerebral cortex tissue on the infarcted side of rats respectively,and the interaction between thioredoxin interaction protein and NLRP3 was analyzed by immunoprecipitation.RESULTS AND CONCLUSION:(1)Compared with the sham surgery group,rats in the model group showed an increase in neurological deficit score,pole test score,cerebral infarction volume(P<0.05),the immunofluorescence expression of Iba-1 and reactive oxygen species(P<0.05),the levels of interleukin-1β,interleukin-6 and tumor necrosis factor α(P<0.05),and the mRNA and protein expression of thioredoxin interaction protein,NLRP3,Caspase-1 and interleukin-1β in cerebral cortex tissue(P<0.05).Hematoxylin-eosin staining in the model group showed neuronal degeneration and necrosis,with fragmented and dissolved nuclei and cellular vacuoles.(2)Compared with the model group,rats in the electroacupuncture group showed a reduction in neurological deficit score,pole climbing test score,cerebral infarction volume(P<0.05),the immunofluorescence expression of Iba-1 and reactive oxygen species(P<0.05),the levels of interleukin-1β,interleukin-6 and tumor necrosis factor α(P<0.05),and the mRNA and protein expression of thioredoxin interaction protein,NLRP3,Caspase-1 and interleukin-1β in cerebral cortex tissue(P<0.05).Hematoxylin-eosin staining showed that the pathological damage of neurons in cerebral cortex tissue on the infarcted side of rats in the electroacupuncture group was significantly attenuated,with significantly reduced cell necrosis and vacuolation.(3)Immunoprecipitation assay showed an interaction between thioredoxin interaction proteins and NLRP3 in the cerebral cortical tissues on the infarcted side of rats in the model group.To conclude,electroacupuncture has a significant therapeutic effect against cerebral ischemia-reperfusion injury,possibly by inhibiting the reactive oxygen species/thioredoxin interaction protein/NLRP3 cell pyroptosis signaling pathway and activation of microglia to reduce the release of inflammatory factors.

BACKGROUND:Previous studies have demonstrated that acupuncture at the governor meridian has precise efficacy in the treatment of ischemic stroke and can improve cerebral ischemia-reperfusion injury by attenuating pyroptosis,but the upstream regulatory mechanisms are not yet fully clarified.OBJECTIVE:To observe the neuroprotective effect of electroacupuncture in model rats of cerebral ischemia-reperfusion injury.METHODS:Twenty-seven Sprague-Dawley rats were randomly divided into sham surgery,model,and electroacupuncture groups,with nine rats in each group.Modified suture method was used to establish cerebral ischemia-reperfusion model rats in the model and electroacupuncture groups.The electroacupuncture group was subjected to electroacupuncture at"Baihui,""Fengfu,"and"Dazhui"acupoints,20 minutes each,once a day,for 7 consecutive days.After treatment,neurological deficit scoring and pole test were performed to assess behavioral changes.Tri-phenyl tetrazolium chloride staining was used to assess cerebral infarction size in rats.Hematoxylin-eosin staining was performed to observe morphological changes in cerebral cortex tissue on the infarcted side of rats.Immunofluorescence analysis was used to determine Iba-1 and reactive oxygen species levels in cerebral cortex tissue on the infarcted side of rats,ELISA method was used for measuring interleukin-1β,interleukin-6 and tumor necrosis factor α levels in cerebral cortex tissue on the infarcted side of rats.Real-time fluorescence quantitative PCR and western blot were used to detect mRNA and protein expression levels of thioredoxin interaction protein,nod-like receptor associated protein 3(NLRP3),Caspase-1 and interleukin-1β in cerebral cortex tissue on the infarcted side of rats respectively,and the interaction between thioredoxin interaction protein and NLRP3 was analyzed by immunoprecipitation.RESULTS AND CONCLUSION:(1)Compared with the sham surgery group,rats in the model group showed an increase in neurological deficit score,pole test score,cerebral infarction volume(P<0.05),the immunofluorescence expression of Iba-1 and reactive oxygen species(P<0.05),the levels of interleukin-1β,interleukin-6 and tumor necrosis factor α(P<0.05),and the mRNA and protein expression of thioredoxin interaction protein,NLRP3,Caspase-1 and interleukin-1β in cerebral cortex tissue(P<0.05).Hematoxylin-eosin staining in the model group showed neuronal degeneration and necrosis,with fragmented and dissolved nuclei and cellular vacuoles.(2)Compared with the model group,rats in the electroacupuncture group showed a reduction in neurological deficit score,pole climbing test score,cerebral infarction volume(P<0.05),the immunofluorescence expression of Iba-1 and reactive oxygen species(P<0.05),the levels of interleukin-1β,interleukin-6 and tumor necrosis factor α(P<0.05),and the mRNA and protein expression of thioredoxin interaction protein,NLRP3,Caspase-1 and interleukin-1β in cerebral cortex tissue(P<0.05).Hematoxylin-eosin staining showed that the pathological damage of neurons in cerebral cortex tissue on the infarcted side of rats in the electroacupuncture group was significantly attenuated,with significantly reduced cell necrosis and vacuolation.(3)Immunoprecipitation assay showed an interaction between thioredoxin interaction proteins and NLRP3 in the cerebral cortical tissues on the infarcted side of rats in the model group.To conclude,electroacupuncture has a significant therapeutic effect against cerebral ischemia-reperfusion injury,possibly by inhibiting the reactive oxygen species/thioredoxin interaction protein/NLRP3 cell pyroptosis signaling pathway and activation of microglia to reduce the release of inflammatory factors.

Objective:To explore the evaluation of 256 slice spiral computed tomography angiography(CTA)of coronary,serum lipoprotein associated phospholipase A2(Lp-PLA2)and angiopoietin like protein 3(ANGPTL3)on the severity of coronary artery stenosis of patients with coronary heart disease.Methods:A total of 102 patients with coronary heart disease who were diagnosed and treated at Hebei Chest Hospital from July 2022 to March 2023 were selected as the study subjects.According to the Gensini score about the severity of coronary artery stenosis,they were divided into mild stenosis group(0 score≤Gensini score≤20 scores),moderate stenosis group(20 scores60 scores),with 34 cases in each group.The minimum lumen diameter(MLD),percentage of area of stenosis(%AS),percentage of diameter of stenosis(%DS),minimum lumen area(MLA),Lp-PLA2 and ANGPTL3 among three groups were compared.The diagnostic efficiency of the severity of coronary artery stenosis was predicted according to receiver operating characteristic(ROC)curve.Results:The MLA and MLD values in severe stenosis group were significantly lower than those in moderate and mild stenosis groups,while%AS and%DS were significantly higher than those in moderate and mild stenosis groups(t=6.905,4.083,5.871,6.976,3.387,2.198,2.668,3.505,P<0.05),respectively.The Lp-PLA2 and ANGPTL3 values in severe stenosis group were significantly higher than those in moderate and mild stenosis groups(t=4.164,8.220,2.575,3.050,P<0.05),respectively.ROC curve analysis showed that the area under curve(AUC)values of MLA,MLD,%AS,%DS,CCTA comprehensive parameter,LpPLA2 and ANGPTL3 were respectively were 0.838,0.690,0.742,0.801,0.904,0.808 and 0.807 in predicting the severity of coronary artery stenosis.The sensitivities of them were respectively 91.20%,91.20%,64.70%,94.10%,97.10%,70.60%and 88.20%.The specificities of them were respectively 76.50%,57.40%,75.00%,50.00%,70.60%,97.10%and 70.60%.The AUC value of CCTA comprehensive parameter was respectively higher than that of LpPLA2 and ANGPTL3,but the difference was not statistically significant(P>0.05).Conclusion:256 slice spiral CCTA,serum Lp-PLA2 and ANGPTL3 have a certain efficiency in assessing the severity of coronary artery stenosis of coronary heart disease,and 256 slice spiral CCTA has higher predictive efficiency.

ObjectiveTo comprehensively elucidate the potential mechanisms of Xiao Xumingtang （XXMT） combined with electroacupuncture （EA） collaboratively in alleviating cerebral ischemia/reperfusion （I/R） injury. MethodThe rat model of cerebral I/R injury was established using the modified suture-occluded method. Seven days after modeling， rats in the XXMT+EA groups were administered XXMT at low （15 g·kg^-1）， medium （30 g·kg^-1）， and high （60 g·kg^-1） doses， alongside daily 20-min EA treatment （stimulating acupoints GV14 and GV20）. Cerebral infarction and neuronal damage were evaluated using the Zea Longa test score， TTC staining， and TUNEL staining. Real-time fluorescence quantitative PCR and Western blot were used to detect the expression of NOD-like receptor hot protein domain related protein 3 （NLRP3）， Gasdermin D （GSDMD）， cysteinyl aspartate specific proteinase-1 （Caspase-1）， interleukin-1β （IL-1β）， and interleukin-18 （IL-18） in the ischemic area of the cerebral cortex. ResultCompared with the sham group， the I/R group showed a significant increase in neurological deficit scores and infarct volume （P<0.01）， along with a higher apoptosis rate of cortical neurons and elevated mRNA and protein expression levels of NLRP3， GSDMD， Caspase-1， IL-1β， and IL-18 （P<0.05）. In contrast， the medium- and high-dose XXMT combined with EA treatment significantly reduced neurological deficit scores and infarct volume （P<0.01）， and decreased the apoptosis rate of cortical neurons as well as the mRNA and protein expression levels of NLRP3， GSDMD， Caspase-1， IL-1β， and IL-18 （P<0.05）. The improvement showed a dose-dependent relationship with XXMT. ConclusionThe combined use of XXMT and EA can exert neuroprotective effects by modulating the NLRP3/GSDMD/Caspase-1 signaling pathway， thereby reducing neurological deficits， minimizing brain infarct size， and improving cortical neuronal damage.

Objective:To explore the effects of neutrophilic granule protein (NGP) on the expression of lipocalin 2 (LCN2) in inflammatory macrophages and its mechanism.Methods:NGP-high-expressed RAW264.7 cells (NGP/RAW cells) and negative control RAW264.7 cells (NC/RAW cells) were cultured in vitro. Primary peritoneal macrophages of NGP-high-expressed mice and wild-type C57BL/6 mice were extracted, then cultured in vitro. The cell inflammatory model was established by stimulating with 10 mg/L lipopolysaccharide (LPS, LPS group), and the phosphate buffer solution (PBS) control group was set up. Enzyme-linked immunosorbent assay (ELISA) was used to detect the level of LCN2 in different types of cells. The protein expression of phosphorylated signal transduction and activator of transcription 1 (p-STAT1) was detected with Western blotting. Other NGP/RAW cells and NC/RAW cells were treated with 10 mg/L LPS, 5 mg/L STAT1 pathway inhibitor (fludarabine)+10 mg/L LPS, respectively. The PBS control group was set up. ELISA was used to detect the level of LCN2. Results:In different types of cells, the levels of LCN2 were increased significantly after LPS stimulation in the LPS group as compared with those in the PBS control group, and peaked at 24 hours (μmol/L: 25.61±1.02 vs. 0.46±0.02 in NC/RAW cells, 74.51±2.14 vs. 0.25±0.04 in NGP/RAW cells, 10.13±0.22 vs. 0.01±0.01 in primary macrophages of wild-type C57BL/6 mice, 28.35±0.61 vs. 0.08±0.01 in primary macrophages of NGP-high-expressed mice, all P < 0.05), indicating that the expression of LCN2 in macrophages altered during inflammation reaction. The level of LCN2 in NGP/RAW cells was found significantly increased at different time points after LPS stimulation comparing with that in NC/RAW cells (μmol/L: 8.32±0.22 vs. 3.12±0.11 at 6 hours, 23.12±0.86 vs. 8.12±0.32 at 12 hours, 74.51±2.14 vs. 25.61±1.02 at 24 hours, all P < 0.05), along with the expression of p-STAT1 was significantly up-regulated. The level of LCN2 in the primary macrophages of NGP-high-expressed mice was also significantly increased at 24 hours after LPS stimulation comparing with that in the primary macrophages of wild-type C57BL/6 mice (μmol/L: 28.35±0.61 vs. 10.13±0.22, P < 0.05). However, after pretreated with STAT1 pathway inhibitors, the production of LCN2 in NGP/RAW cells was decreased significantly comparing with that in the LPS group (μmol/L: 6.81±0.19 vs. 22.54±0.58, P < 0.05). But the inhibitors had no significant effect on LCN2 production in NC/RAW cells showing no significant difference as compared with LPS group (μmol/L: 8.04±0.20 vs. 7.86±0.15, P > 0.05), indicating that NGP could up-regulate the expression of LCN2 in macrophages stimulated by LPS by promoting STAT1 activation. Conclusion:NGP could positively regulate LCN2 expression in inflammatory macrophages by activating STAT1 pathway.

Objective:To evaluate the feasibility of the screw and plate for clival fixation using a transoral expanded approaches.Methods:The transoral expanded approaches were performed on craniocervical segment specimens obtained from 7 subjects, including transoral approach (TO), transoral with soft (TOP) or hard (TOHP) palate split, mandibulotomy (MO) and mandibuloglossotomy (MLO). The distribution and thickness of soft tissue, the configuration of the vertebral arteries, the distance between the midline and the vertebral arteries, the exposed area of the clivus and cervical spine, and the range of screw angle (the angle between the line from the lower incisor or the central base of the mandible to the exposed area of the clivus and the tangent line of the clivus) were evaluated.Results:The thickness of the soft tissue on the posterior pharyngeal wall above the clival pharyngeal nodules was 3.5±0.6 mm. That on the anterior C 1-C 5 vertebrae was 5.0±0.5 mm. The distances from the bilateral vertebral arteries to the midline was 19.5±1.2 mm at C 1, 2, 14.6±2.7 mm at C 2, 3, 14.0±2.7 mm at C 3, 4, and 13.9±2.7 mm at C 4, 5. For the TO approach, the longitudinal diameter of the exposed clivus was 8.3±3.0 mm. The distance from the lower incisor to the superior margin of the exposed clivus, the lower margin of the exposed clivus, the anterior arch of C 1, the vertebral body of C 2 and C 3 were 104.7±4.3 mm, 99.2±6.8 mm, 81.4±4.3 mm, 75.1±4.0 mm and 68.7±6.5 mm, respectively. Six specimens were exposed to the C 3, while one was exposed to the C 2. For the TOP approach, the longitudinal diameter of the exposed clivus was 18.5±4.8 mm. The distance from the lower incisor to the superior margin of the exposed clivus and the pharyngeal nodules were 107.9±6.7 mm and 104.8±6.7 mm, respectively. For the TOHP approach, the longitudinal diameter of the exposed clivus was 26.3±1.8 mm (the clival length) with distance from the lower incisor to the superior margin of the clivus 112.4±12.6 mm. For the MO/MLO approach, the entire clivus was exposed. The distance from the central base of the mandible to the superior and inferior margin of the exposed clivus and the pharyngeal nodules were 141.8±15.7 mm, 131.0±9.9 mm and 120.5±8.2 mm, respectively. The inferior margin of the exposed cervical vertebra was C 5, 6. The rate of the clival screw placement through anterior occipitocervical fixation using TO, TOP, TOHP, MO and MLO was 0%, 71% (5/7), 86% (6/7), and 100%, respectively. The screw angle was 99.0°±1.8°, 92.6°±7.7°, 92.6°±7.7°, 75.1°±7.7°, and 75.1°±7.7°, respectively. Conclusion:Occipitocervical fixation with clival screw and plate could be conducted in most cases via TOP and TOHP approaches. However, in some cases with small split-mouth or mouth opening limited, smaller clival screw angle caused by basilar impression or basilar invagination, requiring fixation and reconstruction of the lower cervical spine, and the MO/MLO approaches could be still required to achieve the fixation.

BACKGROUND:The majority of rheumatoid arthritis treatment is chronic anti-arthritis drugs, biological agents and plant drugs. Among them, plant drugs have been widely concerned due to low cost and few adverse effects. OBJECTIVE:To observe the expression of tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) in the
synovium of col agen-induced arthritis rats, and explore the effect of Aconitum leucostomum Worosch. on the expression.
METHODS:Forty-five rats were randomly divided into normal control group (8 rats) and model group (37 rats). The col agen-induced arthritis model was established with the injection of type II bovine col agen into the end of the tail and paws. After the success of modeling, the 24 successful model rats were randomly selected and divided into model group (8 rats), Tripterygium wolfprdi polyglycoside group (8 rats) and Aconitum leucostomum Worosch. group (8 rats). The arthritis index of the rats in the three intervention groups and one control group were evaluated weekly. After treated by intragastric administration for 4 weeks (Tripterygium wolfprdi polyglycoside group and Aconitum leucostomum Worosch. group were taken by the corresponding drug solution, model group and normal control group were taken by the same volume of physiological saline), the expressions of TNF-αand IL-1βin the synovium were tested by immunohistochemistry.
RESULTS AND CONCLUSION:Compared with the model group, the arthritis index of mice in Tripterygium wolfprdi polyglycoside group and Aconitum leucostomum Worosch. group was decreased significantly after treatment (P<0.05). The expression levels of TNF-αand IL-1βin the synovium of model group were significantly higher than those of the normal control group (P<0.05). After treatment with Aconitum leucostomum Worosch. and Tripterygium wolfprdi polyglycoside, the expression levels of TNF-αand IL-1βin the synovium was decreased compared with the model group (P<0.05). Experimental findings indicated that, the mechanism that Aconitum leucostomum Worosch. treats rheumatoid arthritis is related to the inhibition of TNF-αand IL-1β.

Obesity is a prevalent metabolic disorder, which seriously affects human health and has become the world's public health problem. Kinase S6K1, an important downstream effector of mammalian target of rapamycin (mTOR), influences specific pathological responses, including obesity, type 2 diabetes and cancer. Presently, S6K1 has become an attractive therapeutic target in the treatment of these disorders. Here, the functions of kinase S6K1, its molecular regulation mechanisms, related pathogenesis of disease and relevant small molecular inhibitors are reviewed. Finally, the prospect of research toward S6K1 is expected as well.
Animals ; Diabetes Mellitus, Type 2 ; Humans ; Neoplasms ; Obesity ; Ribosomal Protein S6 Kinases, 70-kDa ; metabolism ; Signal Transduction ; TOR Serine-Threonine Kinases ; metabolism

Objective: to study the effect of stress management training for mental health of teachers in primary school. Method: 35 teachers and 39 teachers were used as the intervention group and the control group respectively. The teachers of intervention group got stress management training for 6 times in 12 weeks. The intervention included the knowledge of stress, cognitive restructure, coping strategies etc, and SCL-90 Scale was used for effect evaluation. Result: although the scores of SCL-90 all raised, the control group raised higher than the intervention group, and there were significant differences in factors of somatization, interpersonal sensitivity and anxiety. Conclusion: stress management training can alleviate the teacher's stress.