Objective The purpose of this research is to study the preventive and therapeutic effects of suramin on lipopolysaccharide (LPS)-induced mouse model of acute lung injury and its molecular mechanism.Methods A total of 24 healthy male C57BL/6 mice were randomly divided into two groups: Control group and suramin group.LPS (5 mg/kg, iv) induced acute lung injury model was used in this study.The severity of lung injury was evaluated using haematoxylin-eosin (HE) staining after the injection of LPS for 0, 24 and 72 hours.The expression of TNF-α and IL-6 mRNA levels were also detected by RT-PCR.In vitro, THP-1 cells were stimulated by LPS (100 ng/mL) with saline or suramin pre-treatment.The expressions of p-ERK1/2, p-JNK and p-P38 were analyzed by Western blot at 10 min, 20 min and 30 min after LPS insult.A 2-tailed Student's t test was used to compare difference between two independent groups.Results Compared with the saline group, the lung tissues injury were significantly decreased in the suramin group of 72 hours after the injection of LPS (saline 3.90 ±0.35;suramin 2.50 ±0.12) (t =7.668, P ＜ 0.01).The expressions of TNF-α (saline 8.35 ± 1.63;suramin 4.62 ± 0.70) (t =4.187, P＜0.01) andIL-6 (saline10.53 ± 2.10;suramin5.53±1.10) (t=4.224, P＜0.01) mRNA were also obviously reduced in suramin group after the injection of LPS for 24 hours.The expression levels of pERK1/2, p-JNK and p-P38 were obviously down-regulated by suramin at 10 min, 20 min and 30 min after LPS stimulation.Conclusion Suramin protected LPS-induced acute lung injury through down-regulating the expression of pro-inflammatory factors, which was closely relative to the inhibition of the MAPK pathway.

Objective To observe the application value of PET glucose metabolic imaging and MR structural imaging in diagnosis of Alzheimer disease (AD) and mild cognitive impairment (MCI).Methods Totally 18 patients with AD (AD group),6 patients with MCI (MCI group) and 10 healthy volunteers (HC group) were enrolled.There were 11 cases of moderate or severe AD and 7 cases of mild AD in AD group.PET and structural MR imaging of the brain were performed.The radioactivity distribution in the brain and the hippocampal atrophy were observed through visually evaluation and quantitative analysis.Results The glucose metabolism reduced in certain regions of the brain in all AD patients (18/18,100％).Among them,11 patients with moderate or severe AD accompanied hippocampal atrophy,while 3 of 7 patients with mild AD showed hippocampal atrophy.No hippocampal atrophy was found in 5 patients with MCI (5/6,83.33 ％),but 2 of them showed decreased radioactivity in the brain.The symmetric mild diminution of radioactivity distribution without hippocampal atrophy was found in all subjects in HC group (10/10,100％).Two cases in HC group showed mild encephalanalosis.Conclusion Both of PET glucose metabolic imaging and MR structural imaging can be used to diagnose AD or MCI with different focus.Combination of these two techniques is helpful to improving diagnostic accuracy.

Objective:To evaluate the relationship between early postoperative recovery and frailty after digestive endoscopy-assisted minimally invasive surgery under intravenous anesthesia in the elderly.Methods:This study retrospectively selected hospitalized patients, aged ≥65 yr, scheduled for elective gastrointestinal endoscopic treatment.Early postoperative recovery time was defined as the period from the end of propofol administration to the achievement of a modified Aldrete score of 9.All the patients were divided into 2 groups according to whether the early recovery time after operation was less than 75%: normal early postoperative recovery time group and delayed early postoperative recovery time group.Frailty was assessed using the frailty phenotype (FP score 0-5), and the patient was diagnosed as frail (FP ≥3) or non-frail (FP 0-2). The age, sex, height, weight, smoking history, American Society of Anesthesiologists (ASA) Physical Status classification, type of operation, and baseline mean arterial pressure and heart rate were recorded.Logistic regression analysis was used to identify the risk factors for delayed early postoperative recovery time after minimally invasive digestive endoscopy under intravenous anesthesia in elderly patients.Results:A total of 214 patients were enrolled and divided into normal early postoperative recovery time group ( n=169) and delayed early postoperative recovery time group ( n=45). There were significant differences in frailty, age, drinking history of more than 10 yr, preoperative ASA Physical Status classification and propofol administration time between delayed early postoperative recovery time group and normal early postoperative recovery time group ( P<0.05). The results of logistic regression analysis indicated that frailty, age, ASA Physical Status classification Ⅲ, and propofol administration time were independent risk factors for the occurrence of delayed early postoperative recovery ( P<0.05). Conclusions:Frailty, age, ASA Physical Status classification Ⅲ and propofol administration time are independent risk factors for delayed early postoperative recovery time following digestive endoscopy-assisted minimally invasive surgery under intravenous anesthesia in elderly patients.

Objective:To design a modified S1PR3 specific agonist, GPS-725.017, and investigate its protective effect on acute lung injury by promoting macrophage clearance of bacteria.Methods:A short peptide derived from the intracellular region of S1PR3 receptor was named GPS725.017, which was modified with norleucine (Nle) and myristicacid (myr) at its N terminus. Mice were divided into the sham operation group, solvent group and GPS-725.017 treatment group. The acute lung injury model was induced by endotracheal injection of E. coli (5×10 6 CFU), and the experimental group was treated with GPS-725.017 (10 mg/kg). The 48-h survival rate of mice was recorded. After 5 h of modeling, the bacterial load and inflammatory cytokines in peripheral blood and lung were detected, and Vps34 protein content in alveolar macrophages was determined by Western blot. After 12-h of modeling, lung tissues were collected for H&E staining and pathological scores. Results:Compared with the solvent group, the survival rate of mice in the GPS-725.017 treatment group was significantly improved ( P<0.01), the bacterial CFU in blood and alveolar lavage fluid was significantly lower than that in the solvent group ( P<0.001), and the levels of TNF-α and IL-1β in blood and alveolar lavage fluid were significantly lower than those in the solvent group ( P<0.001). Western blot showed that the expression level of Vps34 protein in alveolar macrophages was significantly higher than that in the solvent group ( P<0.01). Histopathology result showed that the pathological damage of lung in the treatment group was significantly less than that in the solvent group ( P<0.001). Conclusions:The modified synthetic S1PR3 specific agonist GPS-725.017 could specifically activate the S1PR3 receptor on the membrane of alveolar macrophages and up-regulate the expression level of intracellular Vps34 protein, which can promote the removal of bacteria in alveolar macrophages, significantly reduce the degree of lung injury and improve the survival rate in ALI mice.

Objective:To explore the advantages of the novel individualized 3D printing artificial vertebral body in spine reconstruction and to evaluate its clinical effect.Methods:From January 2017 to December 2018, the 15 patients who underwent total vertebrectomy and spine reconstruction with individualized 3D printing artificial vertebral body were analyzed retrospectively. There were 8 males and 7 females, with the mean age 39.5 years (range: 20-57), including 12 primary tumors and 3 metastatic tumors. According to tumor location and surrounding soft tissue invasion range, simple posterior or combined anterior and posterior approach were used for total vertebral resection, and the defection was reconstructed by 3D printing artificial vertebral body. The operation time, intraoperative bleeding volume, postoperative stability of artificial vertebral body and bone ingrowth of adjacent vertebral body, preoperative and postoperative neurological changes, preoperative and postoperative VAS score, local control and survival of patients were analyzed.Results:The mean operation time was 412.0 min (range: 135-740 min), and the mean blood loss was 4 140.0ml (range: 100-14 000 ml). The mean follow-up time was 23.2 months (range: 12-35 months), and no one loss to follow-up. One case had pleural rupture, one case had cerebrospinal fluid leakage and one case had L5 nerve root palsy. All patients recovered after active symptomatic treatment. Compare with the preoperative VAS score (4.7±1.1), the differences of VAS score at 7 d postoperative and last follow-up (1.6±0.6 and 1.0±0.5) were significantly reduced ( P<0.001). Three patients with Frankel grade C gradually recovered to grade D, and no change were found in grade D and Grade E patients, there was no significant improved at last follow-up. Preliminary bone growth was found between the artificial vertebral body and the adjacent vertebral body 3 months after operation. The bone growth was more obvious at 12 months post-operation, and the artificial vertebral body fused with the adjacent vertebral bodies to form bone integration. At 24 months post-operation, the integration of the artificial vertebral body was more accurate. During the follow-up period, there was no loosening or displacement of the artificial vertebral body and no failure of internal fixation. A case of hemangioendothelioma and a case of epithelioid angiosarcoma died at 33 months and 35 months postoperatively. One patient with chondrosarcoma had local recurrence at16 months post-operation. After treated with arotinib, the tumor did not progress. The other 12 patients had no tumor recurrence or distant metastasis. Conclusion:After spinal tumor resection, individualized 3D printing artificial vertebral body can be used to accurate restoration of spinal continuity, and provide nice interface matching and bone growth between artificial vertebral body and the adjacent vertebral endplates. Moreover, the immediate and long-term stability of the artificial vertebral body can meet the needs of spinal reconstruction.

Objective RY-15, a specific agonist of Sphingosine 1-phosphate Receptor 3, was synthesized for investigating the function and mechanism of S1PR3 in bacterial clearance. Methods Measure the ability of RY-15 with FITC to enter the THP-1 cell after coculture for 5 min, 10 min, 20 min, 30 min through confocal microscopy. The function of GY-5 and RY-15 in bacterial clearance was observed by gentamicin protection test. The phosphorylation level of ERK and p-ERK in THP-1 cell was detected by Western Blot after GY-5 and RY-15 stimulation for different times. Results According to confocal microscopy, RY-15 started to enter the THP-1 cell after stimulating for 10 min and the effect of entering cell was very obvious after stimulating for 30 min. Compared to GY-5 group, live bacteria in the macrophage were largely decreased in the RY-15 group( P<0.05). Conmpared to GY-5 group, the p-ERK level raised largely at different poins. Conclusions RY-15, a specific agonist of Sphingosine 1-phosphate Receptor 3, can promote bacterial clearance through entering cell and the phosphorylation level of ERK is a possible mechanism.

Objective To screen the risk factors for blood coagulation abnormality in patients undergoing off-pump coronary artery bypass grafting (OPCABG).Methods A total of 140 patients undergoing elective OPCABG were included in this study,and combined intravenous-inhalational anesthesia was performed during operation.The patients were divided into normal group and abnormal group according to whether or not blood coagulation abnormality developed during operation and within 48 h after operation.The data such as gender,age,body mass index,American Society of Anesthesiologists physical status,the number of operation per year for surgeons,comorbidities (hypertension and diabetes mellitus),preoperative hematocrit (Hct),left ventricular ejection fraction,arterial oxygen pressure,liver function,operation time and requirement for intraoperative continuous cardiac output monitoring,positive end expiratory pressure,tranexamic acid,ulinastatin and hydroxyethyl starch,postoperative acidosis and hypothermia were recorded.Results Blood coagulation abnormality was found in 43 patients,and the incidence was 31％.The results of logistic regression analysis showed that the number of operation per year for surgeons＜ 50,preoperative abnormal liver function,preoperative Hct＜35％,surgery time≥240 min,no use of continuous cardiac output monitoring during operation and postoperative hypothermia were risk factors for blood coagulation abnormality in patients undergoing OPCABG.Conclusion The number of operation per year for surgeons＜50,preoperative abnormal liver function,preoperative Hct ＜ 35％,operation time ≥ 240 min,no use of continuous cardiac output monitoring during operation and postoperative hypothermia are risk factors for blood coagulation abnormality in patients undergoing OPCABG.

OBJECTIVES: Peroxisome proliferator-activated receptor gamma coactivator 1α (PGC1α) controls mitochondrial biogenesis, but its role in cardiovascular diseases is unclear. The purpose of this study is to explore the effect of PGC1α on myocardial ischemia-reperfusion injury and the underlying mechanisms. METHODS: The transverse coronary artery of SD rat was ligated for 30 minutes followed by 2 hours of reperfusion. Triphenyltetrazolium chloride (TTC) staining was performed to measure the area of myocardial infarction. Immunohistochemistry and Western blotting were used to detect the PGC1α expression in myocardium. The rat cardiomyocyte H9C2 was subjected to hypoxia/reoxygenation (H/R) with the knockdown of PGC1α or hypoxia- inducible factor 1α (HIF-1α), or with treatment of metformin. Western blotting was used to detect the expression of PGC1α, HIF-1α, p21, BAX, and caspase-3. CCK-8 was performed to detect cell viability, and flow cytometry was used to detect apoptosis and mitochondrial superoxide (mitoSOX) release. RT-qPCR was used to detect the mRNA expression of PGC1α and HIF-1α. Besides, chromatin immunoprecipitation (ChIP)-qPCR and luciferase reporter gene assay were applied to detect the transcriptional regulation effect of HIF-1α on PGC1α. RESULTS: After I/R, the PGC1α expression was increased in infarcted myocardium. H/R induced H9C2 cell apoptosis ( CONCLUSIONS After I/R, HIF-1α up-regulates the expression of PGC1α, leading to an increase in ROS production and aggravation of injury. Metformin can inhibit the accumulation of HIF-1α during hypoxia and effectively protect myocardium from ischemia/reperfusion injury.
Animals ; Apoptosis ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Myocardial Reperfusion Injury/genetics* ; Myocytes, Cardiac/metabolism* ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism* ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury

【Objective】 To analyze the correlation of whole body tumor burden of ¹⁸F-prostate specific membrane antigen positron emission computed tomography （¹⁸F-PSMA PET/CT） with prostate specific antigen （PSA） and Gleason score so as to evaluate the value of ¹⁸F-PSMA PET/CT whole body tumor burden for predicting serum PSA progression in prostate cancer. 【Methods】 We retrospectively recruited 213 patients with prostate cancer who underwent ¹⁸F-PSMA PET/CT scanning from March 2019 to April 2021. The serum PSA and Gleason score were collected. Whole body tumor burden was measured by a semi-automatic method. The correlation of tumor burden with serum PSA and Gleason score was analyzed. After radical prostatectomy， the patients were divided into groups according to negative or positive ¹⁸F-PSMA PET/CT. PSA differences between groups were compared， and the receiver operating characteristic curve （ROC） of the subjects was drawn so as to obtain the threshold value of PSA to predict the positive rate of ¹⁸F-PSMA PET/CT. The patients were followed up for PSA after radical surgery， divided into groups according to the progress of PSA， and the differences in tumor burden between groups were compared. 【Results】 In Gleason score ≤7， =8， and ≥9 groups， whole body tumor burden was correlated with PSA in each group （P=0.001）， and tumor burden significantly differed between the groups （P<0.001）. In initial diagnosis and treatment group， biochemical recurrence group， and medication group， the correlation between tumor burden and PSA was statistically significant （P=0.001）. The Gleason score of primary prostate lesion was significantly correlated with systemic tumor burden （P<0.001）. The area under ROC curve of PSA predicting the positive rate of ¹⁸F-PSMA PET/CT after radical prostatectomy was 0.821； when PSA>0.577 ng/mL， the sensitivity and the specificity were 66.7% and 96.8%， respectively. The mean whole body tumor burden in ¹⁸F-PSMA PET/CT positive patients with PSA progression was higher than that in patients without PSA progression. 【Conclusion】 The whole body tumor burden of ¹⁸F-PSMA PET/CT is significantly correlated with PSA， which is helpful in predicting the serum PSA progression in prostate cancer. PSA can predict the positive rate of ¹⁸F-PSMA PET/CT to a certain extent. At the same time， PSA can also predict positive results of ¹⁸F-PSMA PET/CT to a certain extent， and guide clinical rational selection of this examination.

【Objective】 To investigate the value of prostate-specific antigen （PSA） level， Gleason score， and PSMA PET/CT maximum standardized uptake value （SUVmax） in predicting prostate cancer （PCa） metastasis and the treatment option of oligometastatic PCa. 【Methods】 We retrospectively recruited 170 patients with PCa confirmed by pathology， 97 of whom were untreated， and divided them into nonmetastatic group， oligometastatic group （metastasis≤5）， and polymetastatic group. In addition， 28 patients with oligometastatic PCa underwent radical prostatectomy and 45 patients underwent androgen-deprivation therapy. We compared the differences in SUVmax， PSA， and Gleason scores between the three sub-groups of untreated patients， and also analyzed the correlation between SUVmax of local cancer lesions， Gleason score and PSA level. We further compared the differences in SUVmax and PSA levels between radical prostatectomy and androgen-deprivation therapy of oligometastatic PCa patients. According to Gleason score， patients with oligometastatic PCa were divided into two groups （low-intermediate risk group with Gleason score ≤7 and high-risk group with Gleason score ≥8）， and the levels of SUVmax and PSA between the groups were compared. 【Results】 With the increasing number of metastases， SUVmax， PSA levels and Gleason scores all showed an upward trend， and there were significant differences among the three groups （P=0.029， P=0.001， P=0.046）. The post-hoc test found significant difference in Gleason score between the oligometastatic group and the other two groups （P=0.043， P=0.002） as well as correlation of SUVmax level of the primary tumor with Gleason score and PSA （P=0.002， r=0.315； P<0.001， r=0.430）. There was significant difference in PSA level between the two groups after radical prostatectomy and androgen-deprivation therapy （P=0.017）. The difference in PSA between the two treatments persisted in the low-intermediate risk groups （P=0.021）. 【Conclusion】 PSA level， Gleason score and SUVmax have some value in predicting PCa metastasis. Radical prostatectomy is an effective treatment strategy for patients with oligometastatic PCa， especially those with low-intermediate Gleason score.