Cerebral ischemia-reperfusion injury(CIRI)is an important component of ischemic stroke,specifically referring to the phenomenon where reperfusion exacerbates tissue damage after the restoration of blood flow.The underlying mechanisms involve factors such as free radical damage,calcium overload,and in-flammatory damage.Currently,there are no particularly effective treatments for this injury clinically.Phos-phatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling is a classical cellular pathway that regulates downstream substrates through Akt phosphorylation to regulate cell growth,differentiation,and apoptosis.Studies have shown that PI3K/Akt is involved in regulating multiple forms of programmed cell death inclu-ding apoptosis within the organism,and this pathway plays a role in antioxidant stress and anti-inflammatory responses during the process of combating CIRI.This review summarizes recent advances of PI3K/Akt path-way in CIRI regulation,this paper provides new ideas and reference for basic and clinical research.

Objective:To investigate the expression level of methyltransferase-like 3 (METTL3) in nasopharyngeal carcinoma cells CNE2 and CNE-2R, and to evaluate the effect of METTL3 on cell invasion, metastasis and radiosensitivity.Methods:Real-time reverse transcription PCR and Western blot were used to detect the expression levels of METTL3 in normal nasopharyngeal epithelial cells NP69 and nasopharyngeal carcinoma cells CNE2 and nasopharyngeal carcinoma radioresistant cells CNE-2R cells. METTL3 in CNE2 and CNE-2R cells was silenced by lentivirus-mediated RNA interference technology. The metastasis and invasion abilities of the cells were detected by the scratch assay and Transwell assay. Clonogenic assay and CCK-8 assay were employed to detect the proliferation capacity and viability of cells irradiated with different X-ray doses (0, 2, 4, 6 and 8 Gy). Apoptosis was detected by flow cytometry. Methylated RNA immunoprecipitation (Me-RIP) assay was used to detect the difference in m6A modification level of c-Jun in CNE2 and CNE-2R cells after METTL3 silencing. The transcriptional stability of c-Jun in cells after silencing METTL3 was detected by actinomycin D assay. A nude mouse xenograft model was constructed to detect the effect of METTL3 on the radiosensitivity of nasopharyngeal carcinoma in vivo. Results:Compared with NP69 cells, the expression levels of METTL3 mRNA and protein were significantly increased in CNE2 cells, and the expression level was even higher in CNE-2R cells (all P<0.01). Lentivirus-mediated RNA interference technology was used to construct a stable METTL3-silencing CNE2 and CNE-2R cell lines (both P<0.01). Scratch assay and Transwell assay showed that the metastasis and invasion abilities of CNE2 and CNE-2R cells were decreased significantly after METTL3 silencing (all P<0.05). Clonogenic assay showed that silencing METTL3 significantly reduced the number of colonies and survival fraction of CNE2 and CNE-2R cells after irradiation with different doses of X-rays (all P<0.05). CCK-8 assay showed that the proliferation ability of CNE2 and CNE-2R cells was significantly reduced by silencing METTL3 (all P<0.05). After different doses of irradiation, silencing METTL3 significantly reduced the survival fraction of CNE2 and CNE-2R cells (all P<0.05). The apoptotic rate after METTL3 silencing was higher than that in the control group at the irradiation dose of 0 and 8 Gy (all P<0.05). The Me-RIP assay showed that the m6A modification level of c-Jun in CNE2 and CNE-2R cells was significantly reduced after METTL3 silencing (both P<0.01), and the actinomycin D assay showed that transcriptional stability of c-Jun was reduced. Nude mouse xenograft experiment showed that silencing METTL3 inhibited xenograft proliferation and improved its radiosensitivity. Conclusion:METTL3 is highly expressed in nasopharyngeal carcinoma cells, and METTL3 mediates m6A modification of c-Jun to improve the transcriptional stability of c-Jun and promote the expression of c-Jun, thereby promoting the invasion and metastasis of nasopharyngeal carcinoma cells and reducing their radiosensitivity.

Objective:To investigate the expression level of methyltransferase-like 3 (METTL3) in nasopharyngeal carcinoma cells CNE2 and CNE-2R, and to evaluate the effect of METTL3 on cell invasion, metastasis and radiosensitivity.Methods:Real-time reverse transcription PCR and Western blot were used to detect the expression levels of METTL3 in normal nasopharyngeal epithelial cells NP69 and nasopharyngeal carcinoma cells CNE2 and nasopharyngeal carcinoma radioresistant cells CNE-2R cells. METTL3 in CNE2 and CNE-2R cells was silenced by lentivirus-mediated RNA interference technology. The metastasis and invasion abilities of the cells were detected by the scratch assay and Transwell assay. Clonogenic assay and CCK-8 assay were employed to detect the proliferation capacity and viability of cells irradiated with different X-ray doses (0, 2, 4, 6 and 8 Gy). Apoptosis was detected by flow cytometry. Methylated RNA immunoprecipitation (Me-RIP) assay was used to detect the difference in m6A modification level of c-Jun in CNE2 and CNE-2R cells after METTL3 silencing. The transcriptional stability of c-Jun in cells after silencing METTL3 was detected by actinomycin D assay. A nude mouse xenograft model was constructed to detect the effect of METTL3 on the radiosensitivity of nasopharyngeal carcinoma in vivo. Results:Compared with NP69 cells, the expression levels of METTL3 mRNA and protein were significantly increased in CNE2 cells, and the expression level was even higher in CNE-2R cells (all P<0.01). Lentivirus-mediated RNA interference technology was used to construct a stable METTL3-silencing CNE2 and CNE-2R cell lines (both P<0.01). Scratch assay and Transwell assay showed that the metastasis and invasion abilities of CNE2 and CNE-2R cells were decreased significantly after METTL3 silencing (all P<0.05). Clonogenic assay showed that silencing METTL3 significantly reduced the number of colonies and survival fraction of CNE2 and CNE-2R cells after irradiation with different doses of X-rays (all P<0.05). CCK-8 assay showed that the proliferation ability of CNE2 and CNE-2R cells was significantly reduced by silencing METTL3 (all P<0.05). After different doses of irradiation, silencing METTL3 significantly reduced the survival fraction of CNE2 and CNE-2R cells (all P<0.05). The apoptotic rate after METTL3 silencing was higher than that in the control group at the irradiation dose of 0 and 8 Gy (all P<0.05). The Me-RIP assay showed that the m6A modification level of c-Jun in CNE2 and CNE-2R cells was significantly reduced after METTL3 silencing (both P<0.01), and the actinomycin D assay showed that transcriptional stability of c-Jun was reduced. Nude mouse xenograft experiment showed that silencing METTL3 inhibited xenograft proliferation and improved its radiosensitivity. Conclusion:METTL3 is highly expressed in nasopharyngeal carcinoma cells, and METTL3 mediates m6A modification of c-Jun to improve the transcriptional stability of c-Jun and promote the expression of c-Jun, thereby promoting the invasion and metastasis of nasopharyngeal carcinoma cells and reducing their radiosensitivity.

Objective To evaluate the effects of total intravenous anesthesia on the circadian rhythms in the patients undergoing cardiac transcatheter closure.Methods Thirty patients undergoing cardiac transcathe-ter closure under elective intravenous anesthesia were included in this study.Paired t-tests were performed to com-pare the mRNA levels of the genes encoding circadian locomotor output cycles kaput(CLOCK),brain and mus-cle ARNT-1 like protein-1(BMAL1),cryptochrome1(CRY1),and period circadian clock 2(PER2),the Munich Chronotype Questionnaire(MCTQ)score,and the Pittsburgh Sleep Quality Index(PSQI)score be-fore and after anesthesia.Multiple stepwise regression analysis was performed to screen the factors influencing sleep chronotype and PSQI total score one week after surgery.Results The postoperative mRNA level of CLOCK was higher[1.38±1.23 vs.1.90±1.47;MD(95％CI):0.52(0.20-0.84),t=3.327,P=0.002]and the postoperative mRNA levels of CRY1[1.56±1.50 vs.1.13±0.98;MD(95％CI):-0.43(-0.81--0.05),t=-2.319,P=0.028]and PER2[0.82±0.63 vs.0.50±0.31;MD(95％CI):-0.33(-0.53--0.12),t=-3.202,P=0.003]were lower than the preoperative levels.One week after surgery,the pa-tients presented advanced sleep chronotype[3:03±0:59 vs.2:42±0:37;MD(95％CI):-21(-40--1),t=-2.172,P=0.038],shortened sleep latency[(67±64)min vs.(37±21)min;MD(95％CI):-30.33(-55.28--5.39),t=-2.487,P=0.019],lengthened sleep duration[(436±83)min vs.(499±83)min;MD(95％CI):62.80(26.93-98.67),t=3.581,P=0.001],increased sleep efficiency[(87.59±10.35)％vs.(92.98±4.27)％;MD(95％CI):5.39(1.21-9.58),t=2.636,P=0.013],decreased sleep quality score[1.13±0.78 vs.0.80±0.71;MD(95％CI):-0.33(-0.62--0.05),t=-2.408,P=0.023],and declined PSQI total score[6.60±3.17 vs.4.03±2.58;MD(95％CI):-2.57(-3.87--1.27),t=-4.039,P＜0.001].Body mass index(BMI)(B=-227.460,SE=95.475,t=-2.382,P=0.025),anesthesia duration(B=-47.079,SE=18.506,t=-2.544,P=0.017),and mRNA level of PER2(B=2815.804,SE=1080.183,t=2.607,P=0.015)collectively influenced the sleep chronotype,and the amount of anesthesia medicine(B=0.067,SE=0.028,t=2.385,P=0.024)independently influenced the PSQI one week after surgery.Conclusions Total intravenous anesthe-sia can improve sleep habits by advancing sleep chronotype.BMI,anesthesia duration,and mRNA level of PER2 collectively influence sleep chronotype one week after surgery.The amount of anesthesia medicine independently influences the PSQI total score one week after surgery.

Objective To explore the effect of Shuanglu Tongnao Formula on neuronal ferroptosis in ischemic stroke rats and its regulatory mechanism on the silent information regulator 2 homolog 1(SIRT1)/nuclear factor erythroid 2-related fac-tor 2(Nrf2)/glutathione peroxidase 4(GPx4)signaling pathways.Methods Twenty rats were selected as sham operation group by the random number table method,and the remaining seventy rats were made ischemic stroke rat models by the middle cerebral artery occlusion method.The rats that had been successfully modeled were randomly divided into the model control group,Shuanglu Tongnao formula group,Shuanglu Tongnao formula+SIRT1 inhibitor group(Shuanglu Tongnao formula+EX527 group),with 20 rats in each group.After 14 days,the rats were scored for neurological injury;TTC staining was applied to detect the area of cerebral infarction in rats;HE staining was applied to detect pathological changes in rat brain tissue;Nissl staining was applied to detect the number of neurons in rat brain tissue;the kit was applied to detect the levels of ferri ion(Fe2+),superoxide dismutase(SOD),glutathione(GSH),and malonaldehyde(MDA)in rat brain tissue;immunohistochemistry was applied to de-tect the positive expression of acyl-CoA synthetase long-chain family member 4(ACSL4),transferrin receptor(TFR),and ferritin heavy polypeptide 1(FTH1)proteins in rat brain tissue;Western blotting method was applied to detect the expression of SIRT1,Nrf2,GPx4,and cystine/glutamate antiporter solute carrier family 7 member 11(SLC7A11)proteins in rat brain tissue.Results Compared with the sham operation group,the neurological deficit score,cerebral infarction area,the contents of Fe2+and MDA,and the protein expressions of ACSL4 and TFR in model control group were increased(P<0.05);the number of neurons,the con-tents of SOD and GSH,the protein expression of FTH1,SIRT1,Nrf2,GPx4,and SLC7A11 were all reduced(P<0.05).Compared with the model control group,the neurological deficit score,cerebral infarction area,the contents of Fe2+and MDA,and the protein expression of ACSL4 and TFR in the Shuanglu Tongnao formula group were reduced(P<0.05),and the number of neurons,the contents of SOD and GSH,the protein expressions of FTH1,SIRT1,Nrf2,GPx4,and SLC7A11 are all increased(P<0.05).The results of the SIRT1 inhibitor supplementation experiment showed that the SIRT1 inhibitor reversed the inhibitory effect of Shuan-glu Tongnao formula on neuronal ferroptosis,while also inhibited the expression of Nrf2 and GPx4(P<0.05).Conclusion The Shuanglu Tongnao formula may inhibit neuronal ferroptosis in ischemic stroke rats by activating the SIRT1/Nrf2/GPx4 signa-ling pathway.

BACKGROUND:In clinical application,the therapeutic effect of transcranial magnetic stimulation depends on the ability to accurately target the areas of the brain that need to be stimulated.In recent years,with the development of neuronavigation systems,mobile augmented reality technology,and the new methods of processing magnetic resonance imaging(MRI)data,the accuracy of stimulus target localization and the optimization of target selection are expected to improve further. OBJECTIVE:To review the principle of MRI-based image navigation and its application in transcranial magnetic stimulation and summarize the roles of different modal MRI data analyses in guiding the selection of target areas for transcranial magnetic stimulation. METHODS:An online computer search for relevant literature was performed in PubMed,CNKI database and WanFang database,with the keywords"transcranial magnetic stimulation,coil positioning,neuronavigation,augmented reality,magnetic resonance,theory."Finally,63 documents were included for review. RESULTS AND CONCLUSION:Among the traditional methods of positioning transcranial magnetic stimulation coils,the"5 cm rule"and the international electroencephalogram 10-20 positioning method are the most commonly used.These methods have the advantages of simplicity and economy,but they rely too much on the operator's experience and there were technical differences between operators.The neuronavigation system,which is based on stereotactic technology,is the guiding method for positioning transcranial magnetic stimulation coils with the highest visual degree and accuracy.It achieves visual positioning through MRI data acquisition,3D brain reconstruction,head model registration and stereogeometric positioning.It has high application value in clinical treatment and scientific research,but it cannot be promoted in medical institutions due to its high cost.For various medical institutions,mobile augmented reality is a cost-effective and efficient alternative to the neuronavigation system,which achieves visual positioning of brain tissue under the scalp through MRI data acquisition,2D/3D image construction,virtual image and real brain image superposition.It has the advantages of directly visualization and low cost,and is expected to be popularized and applied in primary medical units.Although the superiority of clinical efficacy of visual coil positioning over the electroencephalogram 10-20 localization strategy has not yet been fully demonstrated,with the progress of brain MRI data analysis,visual positioning is expected to further optimize the target selection strategy of transcranial magnetic stimulation therapy and to improve the response rate and individuation degree of transcranial magnetic stimulation treatment.This is a promising and challenging research direction in the future.

The paraventricular thalamic nucleus (PVT) is a key nucleus involved in wakefulness. PVT plays an important role in normal sleep-wake regulation, but its role may vary during anesthesia depending on the stage of anesthesia. This article will review the role of PVT in sleep and anesthesia based on its wakefulness function neural pathways.

Objective:To compare the efficacy and adverse events of induction chemotherapy combined with radiotherapy alone (IC+ RT) and induction chemotherapy combined with concurrent chemoradiotherapy (IC+ CCRT) for nasopharyngeal carcinoma in the era of intensity-modulated radiation therapy in this Meta-analysis.Methods:Retrospective or randomized controlled clinical studies published between 2010 and 2020 were searched from the Cochrane Library, PubMed, and Web of Science databases. The selected studies included nasopharyngeal carcinoma patients treated with IC+ CCRT or IC+ RT. STATA 12 software was used to combine the hazard ratio (HR), risk ratio (RR) and 95% confidence interval (CI), and random or fixed effect models were used for statistical analysis.Results:A total of 2483 patients from eight retrospective studies were included. The overall survival in the IC+ CCRT group was similar to that in the IC+ RT group ( HR=0.78, 95% CI: 0.58-1.04, P=0.091). However, the distant metastasis-free survival ( HR=0.56, 95% CI: 0.42-0.74, P<0.001) and progression-free survival ( HR=0.65, 95% CI: 0.54-0.77, P<0.001) were improved in the IC+ CCRT group compared with those in the IC+ RT group. In terms of adverse reactions, the acute adverse reactions in the IC+ CCRT group were increased significantly compared with those in the IC+ RT group. Conclusions:In the treatment of nasopharyngeal carcinoma, the overall survival of two treatment modes is similar, but the distant metastasis-free survival and progression-free survival in the IC+ CCRT group are better than those in the IC+ RT group, whereas the incidence of adverse reactions is also increased. IC+ CCRT may be a recommended treatment for nasopharyngeal carcinoma patients, but more research is needed.

Objective:To explore the application value of preoperative multimodal image fusion 3D reconstruction technology in brain tumor surgery.Methods:The preoperative cranial CT and MR imaging data of 46 patients with brain tumors admitted to our hospital from October 2019 to September 2020 were collected. The image registration and fusion of above imaging data were performed by AW workstation software (GE company), and 3D reconstruction was performed to construct 3D digital anatomic image of brain tumor and its surrounding anatomic structure. Based on this, the surgical approach and surgical plan were designed, and its application value was evaluated by consistency grading.Results:The reconstructed 3D digital anatomical image could clearly show the size, location, shape of the tumors and the anatomical relationships between the tumors and surrounding structures, which was consistent with the original image before and during the surgery. Among the 46 patients, 43 were completely resected and 3 were partially resected. There were no approach-related complications after surgery. The application value of preoperative 3D image fusion was evaluated as 36 with outstanding value, 8 with value, and 2 without value.Conclusion:Preoperative multimodal image fusion 3D reconstruction technology can provide a large amount of visual information during brain tumor surgery, guide the choice of surgical approach and precise resection of tumors.

Objective:To investigate the effect of oblique lateral lumbar intervertebral fusion (OLIF) on inflammatory factors in patients with degenerative spinal canal stenosis (DLSS).Methods:Retrospective analysis of clinical data of 64 DLSS patients in the department of orthopedics, Jizhong Energy Fengfeng Group Hospital from June 2016 to June 2018 was performed. There were 35 males and 34 females, aged (60.70±6.27) years, and the age range was 20 to 80 years. According to the different surgical methods, they were divided into posterior decompression and internal fixation fusion (PLIF) group ( n=32) and OLIF group ( n=32). The coperation time, intraoperative bleeding volume, postoperative bed rest time, hospitalization time , the back and leg pain visual analogue score (VAS) , Japanese Orthopaedic Association(JOA) score of lumbar vertebrae and serum inflammatory factors [tumor necrosis factor-alpha(TNF-α), interleukin-1alpha(IL-1α), C-reactive protein(CRP)] were observed at preoperative, 3 months and last follow-up. Follow-up using outpatient examination and telephone interview was performed and survial up to March 2019. Measurement data were expressed as mean±standard deviation ( Mean± SD), comparison between groups was performed using independent sample t test or analysis of variance of repeated measurement data. Internal comparisons were performed using paired t tests. Count data were expressed as percentage (%), and χ2 test was used. Results:There was no significant difference in operation time between OLIF group and PLIF group ( P>0.05). In OLIF group, the amount of blood loss (119.72±30.41) mL, bedridden time (2.16±0.35) d and postoperative hospital stay (5.18±2.06) d were significantly lower than that of PLIF group[(318.26±94.62) mL, (3.17±0.54) d, (7.35±1.24) d], the differences between the two groups were statistically significant( P<0.05). All patients were followed for 8 months. The 3 months after operation and last follow-up, the VAS scores of back pain in OLIF group [(1.93±0.54) scores, (1.74±0.63) scores]were significantly lower than that in PLIF group [(4.05±0.62) scores, (3.87±0.74) scores]. The VAS scores of leg pain in OLIF group [(1.56±0.71) scores, (1.37±0.52) scores] were significantly lower than that of PLIF group [(3.74±0.79) scores, (2.53±0.59) scores]. The JOA scores of lumbar vertebrae in PLIF group [(22.57 ±1.83) scores, (24.38±1.65) scores] were significantly higher than that of PLIF group [(20.35±1.78) scores, (22.14±1.35) scores], the differences between the two groups were statistically significant( P<0.05). At 3 months after operation, the levels of serum TNF-α(16.95±3.92) ng/L, IL-1α(9.17±3.78) ng/L and CRP (1.97±0.24) mg/L in OLIF group were significantly lower than those in PLIF group [(20.46 ±4.27) ng/L, (11.51±4.25) ng/L, (2.36±0.32) mg/L]. Last follow-up, the level of serum TNF-α(13.47±3.54) ng/L, IL-1α(6.52±2.09) ng/L and CRP (1.42±0.16) mg/L in the OLIF group were significantly lower than those in the PLIF group [(18.08±3.84) ng/L, (8.73±5.43) ng/L, (2.04±0.25) mg/L], the differences between the two groups were statistically significant ( P<0.05). Conclusion:Compared with PLIF, OLIF can reduce the amount of intraoperative bleeding, shorten the recovery time, reduce the expression of inflammatory factors and improve the prognosis of patients with DLSS.