Objective To observe the distribution and possible mechanism of P2X7R in periaq-ueductal gray matter (PAG)in a rat model with chronic neuropathic pain in vivo.Methods The in-trathecal catheterization and sciatic nerve injury (SNI)were performed.All animals were randomly assigned into 3 groups with 26 rats in each,which was group Sham,control group (group C)and brilliant blue G (BBG)group (group BBG),respectively.Normal saline or BBG 10 μl were intrathe-cally injected after SNI and repeated for seven days.Paw-withdrawal mechanical thresholds (PWT) were measured on day 0,day 7,day 14,and day 21 after SNI.The rats were sacrificed and PAG tis-sues were collected on day 14 and day 21,separately.The distributions of P2X7R were observed by immunofluorescence.The protein contents of P2X7R and GFAP were assessed by Western blot assays.Results The P2X7R was expressed in PAG in rats.The PWTs of the control group showed a significant decrease during the 21-day period compared with the sham group.The P2X7R signals were predominantly expressed in astrocytes in PAG after SNI.Both P2X7R and GFAP expression remark-ably increased.Administration of BBG increased the PWTs,and inhibited the P2X7R and GFAP ex-pressions compared with those atthe same point of time of the control group.Conclusion These results indicated that P2X7R in PAG might participate in nociception modulation in the midbrain in chronic neuropathic pain.

Objective: To explore sarcoplasmic reticulum ryanodine receptor2 (RyR 2) expression and calcium releasing function in chronic heart failure (CHF) rabbits and to study the impact of long term valsartan treatment in relevant animals. Methods: HF model was established by volume overloading with pressure overloading in experimental rabbits. 27 rabbits were divided into 3 groups: Sham group, HF group and HF+valsartan group. n=9 in each group and the animals were treated for 7 weeks. Left ventricular structure, hemodynamic parameters, expression and functional changes of myocardiocyte sarcoplasmic reticulum RyR 2 were observed and compared among different groups. Results: Compared with Sham group, HF group had increased left ventricular mess index (LVMI), left ventricular end diastolic pressure (LVEDP) and decreased left ventricular shortening fraction, LVEF, all P<0.05. Compared with HF group, HF+valsartan group showed decreased LVMI, LVEDP and increased left ventricular shortening fraction, LVEF, all P<0.05. Sarcoplasmic reticulum RyR 2 expression and calcium releasing function were lower in HF group than Sham group, P<0.05; while they were both higher in HF+valsartan group than HF group, P<0.05. Conclusion: Long term application of valsartan could improve the cardiac function which might be related to increased myocardial sarcoplasmic reticulum RyR 2 expression and calcium releasing function in experimental CHF rabbits.

Objective The finite element method was used to analyze the effect of height of bone graft on adjacent segment stress after anterior cervical decompression and fusion.Methods One healthy adult male was included in this study.A detailed,geometrically accurate three-dimensional cervical spine model had been successfully developed from computed tomography (CT) scanning of a healthy adult male.A pure moment of 1.0 N· m was applied in different directions on the upper endplate of C3 to simulate flexion,extension,left-right lateral bending,and left-right axial rotation.We did biomechanical experiment with goat cervical specimens in terms of the moment-rotation responses.The finite element (FE) model was compared and validated with the experimental data.The relevant data in the literature was also applied for comparison and validation.To construct the post-surgery model,we turned the property of disk annulus and disk nucleus into that of the cancellous bone at C4-5.The internal fixation systems were also implanted.We changed the height of bone graft in C4-5 to be 90％,150％,175％ and 200％ of the height between C4-5 pre-surgery.The finite element models were built to simulate the post-surgery scenarios with different bone graft height,respectively.A stress analysis was conducted on the bone graft and adjacent disks.Results Under different height of bone graft,the maximum yon Mises stress on C3-4 showed when the height of bone graft was 200％.The values were 0.99 MPa,0.85 MPa,0.91 MPa and 0.89 MPa in different loading condition.The values at 150％ of the height between C4-5 pre-surgery were only 81％,73％,80％ and 87％ of the values at 200％.For C5-6,the maximum yon Mises stress were 0.77 MPa,0.83 MPa,0.91 MPa and 0.81 MPa,observed at the height of bone graft was 175％ except extension.The values at 150％ of the height between C4-5 pre-surgery were only 76％,93％,86％ and 78％ of the biggest values.With regard to C4-5,the biggest yon Mises stress was 1.25 MPa,1.77 MPa,1.75 MPa and 1.81 MPa.It was observed when the height of bone graft was 200％ of the height between C4-5 pre-surgery.The values were smallest under height of 150％ of the height between C4-5 pre-surgery.The smallest values were 63％,63％,75％ and 52％ of the biggest values.The higher the bone graft was,the bigger the maximum von Mises stress on bone graft.In a word,it seems that the smallest stress was observed when the bone graft height was 150％.Concltusion The height of bone graft makes an important difference on the stress of adjacent segment after anterior cervical decompression and fusion.150％ of the height between C4-5 presurgery was proper bone graft height.In this case,the stress on the adjacent segments intervertebral disc is smaller.The probability of adjacent segments degeneration is smaller.

Objective To investigate the effect of electroacupuncture preconditioning on microglia polarization in rats after cerebral ischemia reperfusion(IR)injury and explore the role of tyrosine kinase 2(J AK2)/signal transducer and activator of transcription 3(STAT3)pathway in the process.Methods Forty-five clean-grade healthy male Sprague-Dawley rats were randomly and equally divided into sham operation group,IR group and electroacupuncture preconditioning group.Rat model of IR injury was induced with thread occlusion of the internal carotid artery.Before modeling,electroacupuncture preconditioning was applied to Baihui acupoint for 5 consec-utive days in the preconditioning group,and exposure of the cervical blood vessels were inflicted in the sham-operation group.At 24 h after reperfusion,the severity of neurological deficit was observed by modified neurological deficit score(mNSS),and the cerebral infarct volume was observed by TTC staining.Western blotting was used to detect the protein levels of classical acti-vated type(M1)marker inducible nitric oxide synthase(iNOS),alternative activated type(M2)marker arginase 1(Arg-1),JAK2 and p-JAK2,and STAT3 and p-STAT3,and q-PCR was applied to detect the mRNA expression of iNOS and Arg-1.The expression of TNF-α and IL-10 was measured by ELISA.Results Compared with the sham operation group,the mNSS,infarct vol-ume,protein levels of p-JAK2/JAK2,p-STAT3/STAT3,protein and mRNA levels of iNOS and Arg-1,and expression of TNF-α and IL-10 were significantly increased in the IR and electroacu-puncture preconditioning groups(P＜0.01).The preconditioning group had obviously lower mNSS,smaller infarct volume,decreased protein levels of p-JAK2/JAK2,p-STAT3/STAT3,re-duced protein and mRNA levels of iNOS,and declined TNF-α expression,but elevated expression of Arg-1 at protein(2.0±0.2 vs 1.5±0.1)and mRNA(4.2±0.8 vs 3.1±0.3)levels and increased IL-10 expression(49.1±7.1 pg/mg vs 27.9±5.9 pg/mg)when compared with the IR group(P＜0.01).Conclusion Electroacupuncture preconditioning can promote the polarization of microglia to M2 and inhibit the polarization of microglia to M1 after cerebral IR injury,which may be relat-ed to the inhibition of JAK2/STAT3 pathway.

Objective To calculate the pre-stretching of the microscopic components of the aortic wall under physiological homeostasis by considering a three-dimensional(3D)residual stress field.Methods The aortic wall was simplified into a double-layer ideal circular tube,and the 3D residual stress field of the vascular wall was calculated based on a 3D expansion angle experiment.Then,the in vivo stress distribution characteristics under mean blood pressure and the pre-stretching of each microscopic constituent of the vascular wall under a physiologically steady state were obtained.The inverse problem was constructed according to the internal pressure-radius relationship measured in vivo.Physiological homeostasis of the aorta was considered the reference state,and inversion identification of the material parameters of the aorta in vivo was realized while integrating the three residual stress fields.Results When residual stress was not considered,the mean stress of the middle membrane was greater than that of the outer membrane.When residual stress was considered,the outer membrane bore more stress than the middle membrane,and the outer membrane protected the middle membrane.The pre-stretching of the middle film with residual stress was lower than that without residual stress,whereas the pre-stretching of the outer film was higher than that without residual stress.Moreover,the pre-stretching of the outer membrane collagen fibers was greater than that of the middle membrane collagen fibers.The in vivo calculations of the material parameters of the aorta were performed using physiological homeostasis as the reference configuration,and the proportion of each component was consistent with the experimental results.However,the proportion of elastin in the outer membrane was significantly overestimated when the non-stress configuration was used as the initial configuration,which was inconsistent with the experimental results.Conclusions Residual stress significantly influences the pre-stretching and physiologically steady mechanical states of the microscopic components of the aortic wall.Therefore,it is necessary to fully consider the influence of residual stress to establish the physiologically steady state of the aortic wall accurately.Furthermore,it is also necessary to fully consider the 3D characteristics and layer specificity of residual stress in the in vivo identification of material parameters.

Objective:To evaluate the effect of selective cerebral mild hypothermia on small ubiquitin-like modifier 2/3 (SUMO2/3) modification of dynamin-related protein 1 (Drp1) in a rat model of cerebral ischemia-reperfusion (I/R).Methods:Sixty clean-grade healthy male Sprague-Dawley rats, aged 6-8 weeks, weighing 240-260 g, were divided into 4 groups ( n=15 each) using a random number table method: sham operation group (S group), cerebral I/R group (I/R group), selective cerebral mild hypothermia group (HT group) and normal temperature group (NT group). The operation was performed under the monitoring of cerebral temperature and rectal temperature.Only the cervical blood vessels were exposed in S group, while focal cerebral I/R was induced by 2 h middle cerebral artery occlusion (MCAO) followed by 24 h reperfusion in anesthetized animals in the other three groups.In HT group and NT group, 4 and 37 ℃ normal saline was perfused through the left internal carotid artery at a rate of 80 ml·kg -1·h -1 for 15 min, respectively. Modified neurological severity score (mNSS) was assessed at 24 h of reperfusion. Then the rats were sacrificed under deep anesthesia, brains were removed, brain tissues were obtained for determination of the percentage of cerebral infarct size (by TTC staining), and the ischemic penumbra tissues in the cerebral cortex were removed for examination of the ultra-structural changes of mitochondria (with a transmission electron microscope) and for determination of the SUMO2/3 modification of Drp1 (by CO-IP), expression of total Drp1 (T-Drp1) and total cytochrome c (T-Cytc) (by Western blot), and expression of mitochondrial outer membrane Drp1 (M-Drp1) and cytoplasmic Cytc (C-Cytc) (by Western blot) after isolation of mitochondria and cytoplasm. Results:Compared with S group, the mNSS and percentage of cerebral infarct size were significantly increased, the expression of M-Drp1, T-Drp1, C-Cytc and T-Cytc was up-regulated, and SUMO2/3 modification of Drp1 in ischemic penumbra area was increased ( P<0.05), the fragmentation of mitochondria was aggravated, and cristae rupture and vacuolation were obvious in the other three groups. Compared with I/R group, the mNSS and percentage of cerebral infarct size were significantly decreased, the expression of M-Drp1, T-Drp1, C-Cytc and T-Cytc was down-regulated, SUMO2/3 modification of Drp1 was increased ( P<0.05), the fragmentation of mitochondria was significantly attenuated, and cristae rupture and vacuolation were weakened in HT group. There were no significant differences in these detection parameters between NT group and I/R group ( P>0.05). Conclusions:The mechanism by which selective cerebral mild hypothermia alleviates the cerebral I/R injury is related to increased SUMO2/3 modification of Drp1, decreased binding of Drp1 to mitochondrial outer membrane, and reduced mitochondrial excessive fission in rats.

Ischemic stroke is a common cerebrovascular disease， characterized by hypoxia and nutritional deficiency in local brain tissue due to insufficient blood supply. Angiogenesis， the formation of new vascular networks on the basis of existing blood vessels， is of great significance for increasing blood flow in the ischemic area of brain tissue， restoring blood and oxygen supply， and improving disease prognosis. This complex process is regulated by various factors， including cytokines， growth factors， and signaling pathways. Among these， the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway is considered a key regulatory pathway. It not only plays an important role in anti-apoptosis and promoting cell survival， but also regulates cell growth， differentiation， migration， and survival， while deeply participating in the regulation of angiogenesis. Chinese medicine offers unique advantages with its multi-component， multi-target， and multi-pathway approach in the treatment of stroke， showing significant potential in treating ischemic stroke. In recent years， it has been found that Chinese medicine can promote angiogenesis after ischemic stroke through the PI3K/Akt signaling pathway. This paper focuses on the PI3K/Akt signaling pathway as the research entry point， and explores in-depth the mechanisms by which Chinese medicine monomers， active components， extracts， derivatives， drug pairs， and Chinese medicine compounds promote angiogenesis after ischemic stroke. The research discusses the regulation of microRNAs （miRNA）， endothelial progenitor cells （EPCs）， apoptosis， upstream pro-angiogenic factors， and downstream target molecules. The paper also elaborates on related research progress， aiming to reveal how Chinese medicine can exert its potential utility in ischemic stroke treatment through this key signaling pathway， providing a theoretical basis for clinical treatment.

Ischemic stroke is a common cerebrovascular disease， characterized by hypoxia and nutritional deficiency in local brain tissue due to insufficient blood supply. Angiogenesis， the formation of new vascular networks on the basis of existing blood vessels， is of great significance for increasing blood flow in the ischemic area of brain tissue， restoring blood and oxygen supply， and improving disease prognosis. This complex process is regulated by various factors， including cytokines， growth factors， and signaling pathways. Among these， the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway is considered a key regulatory pathway. It not only plays an important role in anti-apoptosis and promoting cell survival， but also regulates cell growth， differentiation， migration， and survival， while deeply participating in the regulation of angiogenesis. Chinese medicine offers unique advantages with its multi-component， multi-target， and multi-pathway approach in the treatment of stroke， showing significant potential in treating ischemic stroke. In recent years， it has been found that Chinese medicine can promote angiogenesis after ischemic stroke through the PI3K/Akt signaling pathway. This paper focuses on the PI3K/Akt signaling pathway as the research entry point， and explores in-depth the mechanisms by which Chinese medicine monomers， active components， extracts， derivatives， drug pairs， and Chinese medicine compounds promote angiogenesis after ischemic stroke. The research discusses the regulation of microRNAs （miRNA）， endothelial progenitor cells （EPCs）， apoptosis， upstream pro-angiogenic factors， and downstream target molecules. The paper also elaborates on related research progress， aiming to reveal how Chinese medicine can exert its potential utility in ischemic stroke treatment through this key signaling pathway， providing a theoretical basis for clinical treatment.

OBJECTIVETo summarize our experience with video-assisted thoracoscopic (VATS) removal of esophageal leiomyoma located with endoscopy during operation.

METHODSBetween January 2006 and December 2010, 55 patients with esophageal leiomyoma underwent VATS enucleation. The surgical procedure was similar to that of open thoracotomy with intraoperative endoscopic location of the tumor and examination of the mucosal integrity especially for tumors less than 1 cm in diameter.

RESULTSOf the 55 patients undergoing VATS tumor removal, 54 patients completed the procedures smoothly, and 1 patient experienced ventricular fibrillation during the operation to require an open thoracotomy. Endoscopy was used in 38 patients during the operation. VATS enucleation differed significantly from open thoracotomy in the volume of bleeding, postoperative fasting days and postoperative hospital stay (P<0.05). The symptoms were completely relieved after the operation without postoperative complications. The patients were followed up for 8 to 59 months (mean 23.0 months) and no recurrence was found.

CONCLUSIONVATS removal of esophageal leiomyomas is minimally invasive, safe and effective and can serve as the primary option for surgical removal of esophageal leiomyomas.

Adolescent ; Adult ; Aged ; Esophageal Neoplasms ; surgery ; Female ; Gastroscopy ; methods ; Humans ; Leiomyoma ; surgery ; Male ; Middle Aged ; Thoracic Surgery, Video-Assisted ; methods ; Thoracoscopy ; Thoracotomy ; Treatment Outcome ; Young Adult

Objective To assess the rate achieving the target vancomycin trough level (VTL) and its influencing factors in critically ill patients.Methods The retrospective observational study recruited adult patients treated with intravenous vancomycin in the intensive care unit (ICU) at Zhongda Hospital from January 2015 to December 2017.Serum VTL was tested at steady state.Patients' demographics,the sites of infection,microbial culture results,the severity of illness,laboratory data and vancomycin regimen were obtained at the baseline.The rate achieving target VTL (15-20 mg/L) was analyzed based on renal function.Linear regression was performed to determine the influencing factors of VTL.Results A total of 85 patients were enrolled,among whom only 23.5％ (20/85) achieved the target VTL.In patients with normal renal function,the achieving rate was only 11.4％ (4/35),and 80.0％ (28/35) was lower than the target trough level multiple linear regression analysis showed that procalcitonin (PCT),estimated glomerular filtration rate (eGFR) and acute physiology and chronic health disease classification system Ⅱ (APACHE Ⅱ) score were independent factors associated with VTL.Conclusion Achieving target VTL in critically ill patients is not satisfactory.Further study to optimize the administration is needed to facilitate prompt attainment of target VTL.