Objective To develop a new method to expose the stellate ganglion to increase the success rate of establishing a dog model of atrial fibrillation indinced by sympathetic stimulation .Methods A total of 28 adult dogs were randomly divided into traditional group and improvement group , 14 dogs in each group .The stellate ganglions were separated by the two different methods , respectively , to establish a sympathetic stimulation induced atrial fibrillation model in all the dogs .Changes of vital signs , survival rate of the dogs and the voltage required to stimulate the stellate ganglion were recorded intraoperatively .Changes of cardiac electrophysiology were recorded before and after electric stimulation . The levels of released neurotransmitters were detected by immunohistochemistry . Results The survival rate of the improvement group was 100%(14/14), significantly higher than the 64.3%(9/14) of the traditional group (P<0.05). The operation time of the improvement group was 122.71 ±3.62 min, significantly shorter than the 269.44 ±8.79 min of the traditional group (P<0.05).The threshold voltage of the improvement group was significantly lower than that of the traditional group ( P<0.05) .Conclusions Our modified surgical procedure can effectively reduce the mortality of dogs , significantly shorten the operation time , and reduce the intraoperative blood loss , keeping a more intact stellate ganglion , and maintains a more stable voltage of electric stimulation , Therefore, it is a new method more suitable for establishment of a sympathetic stimulation induced atrial fibrillation model in dogs .

Objective To investigate the changes in myocardial proteomics in the late phase of limb ischemic preconditioning (LIP) in rats.Methods Twelve pathogen-free adult male Sprague-Dawley rats,aged 8-9 weeks,weighing 260-280 g,were randomly assigned into LIP group (n=6) and control group (group C,n=6) using a random number table.Limb ischemia was preceded by 3 cycles of 5-min ischemia which was induced by ligation of the root of the right hindlimb with a rubber band followed by 5-min reperfusion in group LIP.At 24 h after LIP,the tissues were obtained from the left ventricle,and the isobaric tags for relative and absolute quantification technique and liquid chromatography-mass spectrometry were applied to detect the differences in protein expression profiles between the two groups (the difference in expression between the two groups＞ 1.2 times and P＜0.05).The identified differentially expressed proteins were analyzed using the bioinformatics,and some were further verified by Western blot.Results A total of 55 proteins were identified to be differentially expressed,and among the 55 proteins,the expression of 35 proteins was up-regulated,and the expression of 20 proteins was down-regulated.Bioinformatics analysis showed that most of the 55 proteins were organelles,cell membrane or macromolecular compounds,were involved in the process such as metabolism,biological regulation,stress response and signal transduction,and showed functions such as the binding affinity to molecules,catalytic activity,anti-oxidant activity,and modulation of the activity of enzyme.The results verified by Western blot were consistent with those shown by using the isobaric tags for relative and absolute quantification analysis.Conclusion The late phase of LIP can induce changes in the expression of the 55 proteins involving regulation of energy metabolism,anti-oxidant action,regulation of gene expression,and protein folding and degradation in the myocardium,which may be the mechanism of myocardial protection in rats.

Objective To explore the effect of dronedaronel on hyperpolarization-activated cyclic-nucleotide-gated(HCN) channel expression by detecting the change of HCN channel mRNA and protein level before and after giving dronedarone in neonatal rat ventricular myocytes.Methods Neonatal rat ventricular myocytes were separated and digested by type Ⅱ collagenase,and then single ventricular myocytes were collected through differential sticking wall separation method.According to the concentrations (0.1,0.5,1.0,5.0,10.0,20.0 μmol/L of dronedaronel for treating myocytes for 48 h) and time(10 μmol/L of dronedaronel for treating myocytes for 1,6,12,24,48 h)the gradient grouping was conducted.The levels of HCN2 and HCN4 channel mRNA and protein level were determined by real-time PCR and Western blot.Results The HCN2 mRNA and HCN4 mRNA expression levels in concentration gradient group and time gradient group were lower than those in the control group(P＜0.05);compared with the control group,the protein level in the 10 umol/L dronedaronel treatment for 12 h group was significantly down-regulated(P＜ 0.01).Conclusion Dronedaronel could inhibit the expression of HCN2/HCN4 channel mRNA and protein,moreover its action shows the concentration dependency and reaches the maximum at 12 h after medication.

The concept that peri-operative treatment could improve long-term survival of esophageal cancer patients has been universally accepted, including radiation alone, chemotherapy alone, and chemoradiation. The most controversial therapy is perioperative chemotherapy. Here we review the published literatures for reference. The result shows that perioperative chemotherapy is effective for esophageal cancer patients, especially for the so-called chemo-sensitive patients, and the preferred delivering time is before surgery. According to the current data, it is still unclear whether the efficacy of neoadjuvant chemotherapy is inferior to that of neoadjuvant chemoradiation.
Chemoradiotherapy ; Esophageal Neoplasms ; drug therapy ; surgery ; Humans ; Neoadjuvant Therapy ; Survival Rate

Objective: To evaluate the role of extracellular signal-regulated kinase (ERK) signaling pathway in intrathecal dexmedetomidine-induced reduction of spinal cord ischemia-reperfusion (I/R) injury in rats. Methods: Eighty clean-grade male Sprague-Dawley rats, aged 9-10 weeks, weighing 300-350 g, were divided into 4 groups (n=20 each) using a random number table method: sham operation group (group S), spinal cord I/R group (group I/R), dexmedetomidine group (group D), and dexmedetomidine plus ERK signaling pathway blocker PD98059 group (group P). Spinal cord ischemia was produced by cross-clamping of the abdominal aorta distal to the left renal artery for 25 min followed by reperfusion to establish the model of spinal cord I/R injury.Dexmedetomidine 1 μg/kg was intrathecally injected at 20 min before establishing the model in D and P groups, PD98059 2 mg/kg was given via the tail vein at the same time in group P, and the equal volume of normal saline was given instead in S and I/R groups.Five rats were selected at 6, 8, 10 and 12 h of reperfusion, and the modified Basso, Beattie, Bresnahan (BBB) scale was used to assess the hindlimb locomotor function.Five rats were sacrificed after assessing the locomotor function at 6 h of reperfusion, and the L_3-5 segments of the spinal cord were taken for determination of cell apoptosis (by TUNEL) and expression of phosphorylated ERK (p-ERK) (by Western blot). The apoptosis index was calculated. Results: Compared with group S, the BBB scores were significantly decreased at each time point of reperfusion, the apoptosis index was increased, and the expression of p-ERK was up-regulated in the other three groups (P<0.05). Compared with I/R group, the BBB scores were significantly increased at each time point of reperfusion, the apoptosis index was increased, and the expression of p-ERK was up-regulated in group D, and no significant change was found in the apoptosis index or p-ERK expression in group P (P>0.05). Compared with group D, the BBB scores were significantly decreased at each time point of reperfusion, the apoptosis index was increased, and the expression of p-ERK was down-regulated in group P (P<0.05). Conclusion The mechanism by which intrathecal dexmedetomidine reduces spinal cord I/R injury is related to activating ERK signaling pathway in rats.

Background: and Purpose Collateral circulation is considered an important factor affecting the risk of stroke, but the factors that affect collateral circulation remain unclear. This study was performed to identify the factors associated with collateral circulation, especially blood lipids. Methods: The study involved patients who had undergone digital subtraction angiography and were confirmed as having severe unilateral stenosis or occlusion of the internal carotid artery (ICA). We classified the collateral circulation status of each patient as good (Grade 3 or 4) or poor (Grade 0, 1, or 2) according to the grading system of the American Society of Interventional and Therapeutic Neuroradiology/American Society of Interventional Radiology. We collected data on patients’ characteristics and identified the factors that affect collateral circulation. Results: This study included 212 patients. The multivariate logistic regression analysis showed that the high-density lipoprotein cholesterol (HDL-C) concentration and a complete anterior half of the circle of Willis were independent protective factors for good collateral circulation, whereas elevated lipoprotein(a) [Lp(a)] and serum creatinine concentrations were independent risk factors for good collateral circulation. The area under the receiver operating characteristics curve (AUC) was 0.68 (95% confidence interval [CI], 0.61–0.76) for HDL-C and 0.69 (95% CI, 0.62–0.76) for Lp(a). A binary logistic regression model analysis of the joint factor of HDL-C and Lp(a) yielded an AUC of 0.77 (95% CI, 0.71–0.84). Conclusions In patients with severe unilateral ICA stenosis or occlusion, the combination of HDL-C and Lp(a) is a useful predictor of collateral circulation.

Objective:To clarify peripheral Th17 level in SSc patients and its correlation with disease.Methods:Chinese databases CNKI, CBM, Wanfang and VIP, and English databases PubMed, EMBASE, Web of Science, Cochrane Library and Science Direct were searched to collect a case-control study on the content of Th17 cells in peripheral blood of patients with SSc. The papers published when the database was first developed in 25 February 2021. Meta-analysis was conducted using Stata 12.0 software, and I2 and Egger tests were used to evaluate the heterogeneity and publication bias between studies. Results:A total of 26 case-controls were included in the study, including 1 160 patients with SSc and 778 healthy controls. Overall, the percentage of Th17 cells in SSc patients was higher than in healthy controls [SMD(95% CI)=1.85 (1.33, 2.38), P<0.001], which was most significant in IL-17 +Th17 concentration [SMD(95% CI)=1.88 (1.28, 2.48), P<0.001]. As for disease activity, the proportion of Th17 cells in active SSc patients was much higher than those of patients in remission [SMD(95% CI)=1.92 (1.12, 2.71), P<0.001]. SSc patients had a reduced Th17 level after receiving DMARDs treatment [SMD(95% CI)=-0.74 (-1.05, -0.42), P=0.029]. Conclusion:The number of Th17 cells increase significantly in the peripheral blood of patients with SSc, and is related to disease activity. DMARDs can be used to treat this disease by downregulating Th17 levels.

Neoadjuvant therapy has become the first choice for locally advanced esophageal carcinoma. Patients with post-neoadjuvant positive lymph node staging (ypN+) have poor prognosis, and there is no effective adjuvant therapy. Programmed death protein-1 (PD-1) antibody can obtain better clinical efficacy in the treatment of advanced esophageal cancer. The authors designed a multicenter, prospective, randomized controlled clinical trial of Toripalimab (PD-1 antibody) adjuvant therapy on esophageal squamous cell carcinoma patients with ypN+ after the treatment of neoadjuvant chemotherapy combined with surgical resection, in order to provide clinical practices for the adjuvant treatment of ypN+ patients.

OBJECTIVE： To study the mechanism of analgesic effect of 8-O-acetyl-safalinoside （8-OaS） on chronic inflammatory pain model rats. METHODS ：Totally 30 male SD rats were divided into sham operation group （normal saline ）， model group （normal saline ），8-OaS low-dose ，medium-dose and high-dose groups （3，10，30 μg/kg），with 6 rats in each group. Except for sham operation group ，other groups were given planter injection of Freund ’s complete adjuvant to induce chronic inflammatory pain model. After successful modeling ，the rats in each group were given corresponding drugs intrathecally ，once a day，for 7 consecutive days. Then Von-Frey filaments were used to detect the planter pain threshold of the rats in each group ；the area under the planter pain threshold curve of each group and the half effective dose （ED50）of 8-OaS were calculated. Another 36 male SD rats were divided into sham operation group （normal saline ），model group （normal saline ）and 8-OaS group （dose of ED50），and the modeling method and administration route were the same as above. Immunofluorescence histochemical staining was used to observe the positive expression of ionized calcium binding adapter molecule 1（Iba-1）and signal molecule phosphorylated p38 mitogen-activated protein kinase （p-p38 MAPK）；Western blotting assay was used to determine the expression of Iba- 1，p-p38 MAPK，IL-1β，IL-6 and TNF-α in spinal dorsal horn of rats. RESULTS：Compared with sham operation group ，plantar pain threshold and area under the curve in model group were reduced significantly （P＜0.01）. Compared with model group ，plantar pain threshold increased significantly after 5，6，7 days of administration in 8-OaS low-dose group （P＜0.05），plantar pain threshold and area under the curve in 8-OaS medium-dose and high-dose groups were increased significantly （P＜0.05 or P＜0.01）. Most of above indexes in each dose group of 8-OaS were signifficantly different ，and ED 50 of 8-OaS was 18.87 μ g/kg. Results of immunohistochemistry staining and Western blotting showed that p-p 38 MAPK was mainly expressed in Iba- 1 positive cells. Compared with sham operation group ，the fluorescence density of Iba- 1 and p-p 38 MAPK in spinal dorsal horn ，the expression of Iba-1，p-p38 MAPK，IL-6，IL-1β and TNF-α were significantly increased in model group（P＜0.05 or P＜0.01）. Compared with model group ，the fluorescence density of Iba- 1 and p-p 38 MAPK in spinal dorsal horn ，the expression of Iba- 1，p-p38 MAPK， IL-6，IL-1β and TNF-α were decreased significantly in 8-OaS group （P＜0.05）. CONCLUSIONS ：Intrathecal administration of 8-OaS can effectively alleviate chronic inflammatory pain in rats. The mechanism may be related to the inhibition of the phosphorylation of p 38 MAPK and the expression of IL- 6，IL-1β and TNF-α.

Objective:To evaluate the efficacy and safety of oral anisodine hydrobromide tablets in the treatment of nonarteritic anterior ischemic optic neuropathy (NAION).Methods:A multicenter nonrandomized controlled trial was conducted.A total of 282 acute NAION patients (282 eyes) were recruited from 16 hospitals in China from July 2020 to May 2021.Patients were divided into two groups according to treatment methods, which were control group (124 cases, 124 eyes) receiving regular treatment including citicoline sodium plus Ginkgo biloba leaf liquid extract or Ginkgo biloba leaf extract tablets plus mecobalamin, and experimental group (158 cases, 158 eyes) receiving treatment in control group plus oral anisodine hydrobromide tablets 1 mg, twice daily for 2 to 3 months.Best corrected visual acuity (BCVA), visual field index (VFI), peripapillary retinal nerve fiber layer (pRNFL) and radial peripapillary capillary vessel density (RPC) were assessed at 1, 2, 3, and 6 months after enrollment using the standard decimal visual acuity chart, 750i Humphery visual field analyzer, Cirrus HD-OCT 4000/Cirrus HD-OCT 5000, RTVue-XR optical coherence tomography respectively.The primary outcomes were BCVA and VFI, and the secondary outcomes were pRNFL, RPC, and the side effects during the follow-up.The study adhered to the Declaration of Helsinki.All patients were fully informed about the treatment and purpose of this study and voluntarily signed the informed consent form.The study protocol was approved by Chinese PLA General Hospital (No.S2020-021-01). Results:In all, 242 patients (242 eyes) completed the follow-up of BCVA, and 98 patients (98 eyes) completed the VFI follow-up.In terms of visual function, BCVA and VFI improved significantly over time in the two groups, and BCVA and VFI were better in experimental group than in control group at various follow-up time points (all at P<0.05). In terms of structure, pRNFL gradually decreased in both groups with the extension of treatment, and pRNFL was significanthy thinner in experimental group than in control group at various follow-up time points (all at P<0.05). There was no significant difference in RPC between the two groups at the last follow-up ( P>0.05). There were two cases with side effects and one case was discontinued due to side effects 25 days after enrollment. Conclusions:Oral anisodine hydrobromide can improve visual acuity and visual field in NAION and accelerate the regression of optic disc edema, with good safety.