1.Mechanism of acupuncture on cerebral ischemia-reperfusion injury via p53/SLC7A11/GPX4 signaling pathway in rat models.
Qi WANG ; Ziwen HOU ; Yaoyao LIU ; Dan WEI ; Qingjie KONG ; Xia CHEN
Chinese Acupuncture & Moxibustion 2025;45(8):1099-1110
OBJECTIVE:
To explore the neuroprotective effect and underlying mechanism of Xingnao Kaiqiao acupuncture (acupuncture for regaining consciousness and opening orifices) in the rat models of cerebral ischemia-reperfusion injury (CIRI) based on the p53 protein (p53)/solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) signaling pathway.
METHODS:
Of 102 male Wistar rats, 20 rats were randomly collected as a sham-operation group. Using a modified external carotid artery filament insertion method, CIRI models were prepared by occluding the middle cerebral artery in the rest rats. After modeling and excluding 1 non-successfully modeled rat and 1 dead one, the other modeled rats were randomized into a model group, an agonist group, an acupuncture group, and an acupuncture + agonist group, 20 rats in each one. Xingnao Kaiqiao acupuncture therapy was delivered in the rats of the acupuncture group and the acupuncture + agonist group. The acupoints included "Shuigou" (GV26), bilateral "Neiguan" (PC6), and "Sanyinjiao" (SP6) on the affected side. Electroacupuncture was attached to "Neiguan" (PC6) and "Sanyinjiao" (SP6) on the affected side, with dense-disperse wave, a frequency of 2 Hz/15 Hz and intensity of 1 mA. The intervention was delivered twice daily, 20 min each time and for 7 consecutive days. In the agonist group and acupuncture+agonist group, p53 agonist, COTI-2 was intraperitoneally injected (15 mg/kg), once daily for 7 consecutive days. Neurological deficit was evaluated using Zausinger's six-point scale. Cerebral infarction volume was quantified by triphenyl tetrazolium chloride (TTC) staining. Histopathological changes were observed using hematoxylin-eosin (HE) staining. Iron deposition was assessed by Prussian blue staining. Mitochondrial ultrastructure in the ischemic cortex was examined under transmission electron microscopy (TEM). Serum iron (Fe2+) was measured with chromometry. Malondialdehyde (MDA) and glutathione (GSH) levels in the ischemic hippocampus were determined using thiobarbituric acid and microplate assays, respectively. The mean fluorescence intensity of reactive oxygen species (ROS) in the ischemic cortex was analyzed by flow cytometry. The mRNA and protein expression of GPX4, SLC7A11, and p53 in the ischemic hippocampus were evaluated using quantitative real-time PCR (qRT-PCR) and Western blotting, respectively.
RESULTS:
Compared with the sham-operated group, the model group exhibited the decrease in neurological deficit score (P<0.01), and the increase in cerebral infarction volume percentage (P<0.01). The changes of brain tissue were presented in extensive cellular necrosis, pyknotic and deeply-stained nuclei, and vacuolar degeneration. The iron deposition was elevated in cortex and hippocampus (P<0.01), mitochondrial membrane density increased, the cristae was broken or reduced, and the outer membrane ruptured. The levels of Fe2+ and MDA, as well as the mean flourscence intensity of ROS were elevated (P<0.01) and the level of GSH was reduced (P<0.01). The mRNA and protein expression of GPX4 and SLC7A11 was reduced (P<0.01), while that of p53 rose (P<0.01). When compared with the model group, in the agonist group, the neurological deficit score was reduced (P<0.05), the percentage of infarction volume was higher (P<0.01), the histopathological damage was further exacerbated, and the percentage of iron deposition increased in the cortex and hippocampus (P<0.01). The mitochondrial quantity decreased, the membrane density increased, the mitochondrial cristae were broken or reduced, and the outer membrane was ruptured. The levels of Fe2+ and MDA, as well as the mean flourscence intensity of ROS were higher (P<0.01, P<0.05) and the level of GSH was reduced (P<0.05). The mRNA and protein expression of GPX4 and SLC7A11 decreased (P<0.01, P<0.05), while that of p53 was elevated (P<0.01). Besides, in comparison with the model group, the neurological deficit score was higher in the acupuncture group and the acupuncture + agonist group (P<0.01, P<0.05), the percentage of cerebral infarction volume was lower in the acupuncture group (P<0.01), the pathological damage of brain tissue was alleviated in the acupuncture group and the acupuncture + agonist group, and the percentage of iron depositiondecreased in the cortex and hippocampus (P<0.01). The mitochondrial structure was relatively clear, the mitochondrial cristae were fractured or reduced mildly in the acupuncture group and the acupuncture + agonist group. The levels of Fe2+ and MDA, as well as the mean flourscence intensity of ROS were lower (P<0.01) and the level of GSH was higher (P<0.01) in the acupuncture group. The mean fluorescence intensity of ROS were dropped (P<0.01) in the acupuncture + agonist group. The mRNA expression of GPX4 and SLC7A11 was elevated (P<0.01) and that of p53 was reduced (P<0.01, P<0.05) in either the acupuncture group or the acupuncture + agonist group; the protein expression of GPX4 and SLC7A11 rose (P<0.05, P<0.01) and that of p53 was dropped (P<0.01) in the acupuncture group; and the protein expression of p53 was also lower in the acupuncture + agonist group (P<0.05). When compared with the agonist group, in the acupuncture + agonist group, neurological deficit score increased (P<0.01), the percentage of cerebral infarction volume decreased (P<0.01), the pathological brain tissue damage was reduced, the percentage of iron deposition in cortex and hippocampus decreased (P<0.01), the mitochondrial structure was relatively clear and the cristae broken or reduced slightly; the levels of Fe2+ and MDA, as well as the mean fluorescence intensity of ROS were dropped (P<0.01), while the level of GSH increased (P<0.05); the mRNA and protein expression of GPX4 and SLC7411 was elevated (P<0.01, P<0.05), and that of p53 reduced (P<0.01). In comparison with the acupuncture + agonist group, in the acupuncture group, the neurological deficit score increased (P<0.05), the percentage of cerebral infarction volume decreased (P<0.05), the pathological brain tissue damage was alleviated, the percentage of iron deposition in cortex and hippocampus decreased (P<0.01), the mitochondrial structure was normal in tendency; the levels of Fe2+ and MDA, as well as the mean fluorescence intensity of ROS were reduced (P<0.05), while the level of GSH rose (P<0.01); the mRNA and protein expression of GPX4 and SLC7411 was elevated (P<0.01, P<0.05), and that of p53 reduced (P<0.01, P<0.05).
CONCLUSION
Xingnao Kaiqiao acupuncture can alleviate neurological damage in CIRI rats, which is obtained probably by inhibiting ferroptosis through p53/SLC7A11/GPX4 pathway.
Animals
;
Reperfusion Injury/metabolism*
;
Male
;
Acupuncture Therapy
;
Rats
;
Tumor Suppressor Protein p53/genetics*
;
Brain Ischemia/metabolism*
;
Rats, Wistar
;
Signal Transduction
;
Humans
;
Phospholipid Hydroperoxide Glutathione Peroxidase/genetics*
;
Disease Models, Animal
;
Acupuncture Points
;
Amino Acid Transport System y+/genetics*
2.Impact of excessive pregnancy weight gain on pregnancy outcomes and neonatal conditions in pre-pregnancy overweight and obese women
Xia CHEN ; Yunlan YUAN ; Yan ZHANG ; Ziwen MA ; Jianmin ZHANG
Shanghai Journal of Preventive Medicine 2024;36(3):255-261
ObjectiveTo explore the influence of excessive weight gain during pregnancy in pre-pregnancy overweight and obese women on pregnancy outcomes and neonatal conditions, and to provide scientific evidence for formulating weight management strategies before and during pregnancy and prevent adverse pregnancy outcomes. MethodsClinical data of 2 172 parturients collected from a community in Huangpu District from 2017 to 2021 were retrospectively analyzed, and they were divided into pre-pregnancy overweight and obesity group (n=530), normal pre-pregnancy weight group(n=937), and underweight pre-pregnancy group(n=705) according to maternal precursor body mass index (BMI). Based on their weight gain during pregnancy,the parturient were divided into moderate gestational weight gain (MGWG) group and excessive gestational weight gain (EGWG) group. Meanwhile, the pregnancy and neonatal outcomes such as postpartum hemorrhage, puerperal infection, placental abruption, premature rupture of membranes, mode of delivery, premature birth, stillbirth, fetal distress, admission to the intensive care unit (ICU), macrosomia, and Apgar score, were recorded. Then the differences in pregnancy and neonatal outcomes between groups were compared. The effects of pre-pregnancy BMI and gestational weight gain on pregnancy outcomes and neonatal conditions was retrospectively analyzed. ResultsThe pre-pregnancy overweight and obese group had higher proportions of placental abruption, premature rupture of membranes, cesarean section, premature birth, fetal distress, and macrosomia compared to the normal pre-pregnancy weight group and the underweight pre-pregnancy group, with Apgar scores lower than the normal pre-pregnancy weight group and the underweight pre-pregnancy group (all P<0.05). The EGWG group had higher proportions of postpartum hemorrhage, placental abruption, premature rupture of membranes, cesarean section, premature birth, fetal distress, admission to the ICU, and macrosomia than the MGWG group (all P<0.05). In the pre-pregnancy overweight and obese group, the EGWG group had higher proportions of placental abruption, premature rupture of membranes, premature birth, fetal distress, admission to the ICU, and macrosomia than the MGWG group, with lower Apgar scores than the MGWG group (all P<0.05). In the normal pre-pregnancy weight group, the EGWG group had higher proportions of placental abruption, premature rupture of membranes, premature birth, fetal distress, admission to the ICU, and macrosomia than the MGWG group (all P<0.05). In the pre-pregnancy overweight and obese group, the EGWG group had higher proportions of premature rupture of membranes, cesarean section, premature birth, fetal distress, and macrosomia than the EGWG group in the normal pre-pregnancy weight group(all P<0.05). Logistic regression analysis showed that EGWG in pre-pregnancy overweight and obese women was a risk factor for placental abruption (OR=2.971, 95%CI: 1.098‒8.042), premature rupture of membranes (OR=4.662, 95%CI: 2.798‒7.770), cesarean delivery (OR=1.375,95%CI: 1.260‒2.541), premature birth (OR=4.249, 95%CI: 2.384‒7.573), fetal distress (OR=3.238, 95%CI: 1.589‒6.598), admission to the ICU (OR=3.010, 95%CI: 1.265‒7.164), and macrosomia (OR=5.437, 95%CI: 3.392‒8.716) (all P<0.05). ConclusionExcessive gestational weight gain in pre-pregnancy overweight and obese women is a risk factors for placental abruption, premature rupture of membranes, cesarean section, premature birth, fetal distress, admission to the ICU, and macrosomia.
3.Survival of patients with brain metastases from small cell lung cancer under different intracranial radiotherapy modalities
Fangfang CHANG ; Xiaodong XIA ; Mengni LI ; Ziwen GUO ; Jia LIU ; Hao JIANG ; Zhen CUI
Chinese Journal of Radiological Medicine and Protection 2024;44(11):924-930
Objective:To explore the prognostic impact of different intracranial radiotherapy modalities in patients with a limited number (≤10) of brain metastases from small cell lung cancer (SCLC-BM).Methods:The data of 143 cases with SCLC-BM that received intracranial radiotherapy at the First Affiliated Hospital of Bengbu Medical University in 2019-2022 were analyzed. The patients were grouped by radiotherapy modalities: whole brain radiotherapy (WBRT, 58 cases), WBRT combined with simultaneous integrated boost (WBRT+ SIB, 53 cases), and WBRT combined with sequential integrated boost (WBRT+ SEB, 32 cases). The overall survival (OS) and intracranial progression-free survival (IPFS) were calculated using the Kaplan-Meier method, and the Cox proportional hazard model was used for prognostic analysis.Results:In the whole group, the median OS and IPFS were 11.9 and 9.9 months, and the 1-, 2-, and 3-year survival rates were 49.7%, 15.3%, and 2.9%, respectively. The difference in OS among patients in the WBRT+ SIB, WBRT+ SEB, and WBRT groups was not significant (median OS: 13.0 months vs. 12.5 months vs. 11.2 months, P>0.05). The WBRT+ SIB and WBRT+ SEB groups were preferred over the WBRT group in terms of IPFS (median IPFS: 11.7 months vs. 10.4 months vs. 8.1 months, χ2=21.69, P<0.001). For patients with few brain metastases (≤3) analyzed separately, the WBRT+ SIB and WBRT+ SEB groups were preferred over the WBRT group in terms of OS and IPFS (median OS: 14.4 months vs. 13.7 months vs. 11.5 months, χ2=8.72, P=0.013; median IPFS: 12.6 months vs. 10.4 months vs. 8.9 months, χ2=12.37, P=0.002). Evaluation of the central nervous system as well as hematological acute radiological reactions reaching grade 2 and above showed no significant differences among the three groups ( P>0.05). Multivariate analysis showed that subsequent chemotherapy, targeted therapy, and immunotherapy were common independent influencing factors for patients′ OS and IPFS. Body mass index (BMI) level was an independent influencing factor for patients′ OS, and the number of brain metastases, lymph node metastasis, and radiotherapy modality were independent influencing factors for patients′ IPFS. Conclusions:BMI level and subsequent treatment (chemotherapy, targeted therapy, and immunotherapy) are independent influencing factors for patients' prognosis. WBRT+ SIB and WBRT+ SEB modalities are associated with increased IPFS.
4.Establishment of Thromboelastography reference interval for healthy adults in Hainan
Dejuan CHEN ; Jufeng WU ; Xingquan CAI ; Chunliu XU ; Ziwen XIA
Chinese Journal of Blood Transfusion 2022;35(4):441-443
【Objective】 To establish the reference interval of Thromboelastography(TEG)of healthy adult in Hainan, compare with the interval provided by the manufacturers, and analyze the influencing factors. 【Methods】 A total of 308 healthy adult volunteers were included according to the inclusion and exclusion criteria. The TEG was analyzed based on adequate quality control, and the reference interval of each parameter was calculated with 95% CI. 【Results】 The reference interval of these volunteers were R 4.27~9.20 min, K 1.60~3.83 min, Angle 44.22°~67.78°, MA 47.82~64.17 mm, CI -5.63~1.12 and G 4.58~9.03. 14.94% (46/308) of these volunteers had at least one index exceeded the reference interval provided by manufacturers. A total of 74 healthy volunteers were diagnosed with coagulation disorder, with the specificity at 79.22%. Significant differences of R, K, Angle, MA, CI, G were observed between males and females (P<0.05). Hypercoagulability was not associated with the age. 【Conclusion】 This study established a reference interval of TEG of healthy adults in Hainan, which provided reference for related clinical and basic science study.
5.Electromechanical delay is a key to neuromuscular transmission
Ziwen PEI ; Xia XU ; Jian CHEN
Chinese Journal of Tissue Engineering Research 2017;21(24):3931-3936
BACKGROUND:With the development of sports medicine and rehabilitation medicine, electromechanical delay has been looked as an important index for evaluating the neuromuscular function at abroad. But the relevant research is little reported in China. OBJECTIVE:To review the literatures related to electromechanical delay published in recent years, and to explore the mechanisms, influential factors and the application status of the electromechanical delay, thereby providing reference for clinical practice and research. METHODS:A computer-based search of CNKI, WanFang and PubMed databases was performed for articles addressing electromechanical delay published from February 1979 to February 2017. The keywords were electromechanical delay, electro-mechanical response time in English and Chinese, respectively.Repeated and old studies were excluded, and finally 44 eligible literatures were included, including 3 Chinese and 41 English articles. RESULTS AND CONCLUSION: The mechanisms of electromechanical delay have been clarified. The type of muscle fiber and the level of muscle fatigue can influence electromechanical delay, but the underlying mechanisms still remain unclear. Whether age and gender make effect on electromechanical delay is controversial. Electromechanical delay is not only used for evaluating the athletes' ability to reaction, but also wildly used to investigate the mechanism of various sports injuries and evaluate the effectiveness of rehabilitation.

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