ObjectiveTo explore the risk factors and alterations in functional connectivity of brain networks in end-stage renal disease （ESRD） patients complicated by frailty. MethodsA total of 84 patients with ESRD were enrolled and divided into the frailty group （31 cases） and non-frailty group （53 cases） according to the Chinese version of the Tilburg Frailty Indicator （TFI）. Cranial magnetic resonance imaging （MRI） data， neuropsychological test results and clinical data were collected for all subjects. Logistic regression analysis was used to explore risk factors for frailty in ESRD patients， and image preprocessing and independent component analysis were performed to compare differences in brain network functional connectivity between the two groups. ResultsLogistic regression analysis showed that high blood urea nitrogen level， depression， malnutrition， and sleep disturbance were risk factors for frailty in patients with ESRD （P<0.05）， while a higher level of education served as a protective factor （P<0.05）. Compared with the non-frailty group， the frailty group exhibited significantly weakened functional connectivity between the sensorimotor network and the visual network （P<0.05）. ConclusionHigh levels of blood urea nitrogen， depression， malnutrition， and sleep disorders can increase the risk of frailty in patients with end-stage renal disease （ESRD）， while a higher educational level may reduce this risk. Patients with ESRD complicated by frailty exhibit a significant decrease in functional connectivity between the sensorimotor network （SMN） and visual network （VN）， which provides novel imaging evidence for exploring the central neural mechanisms underlying the development of frailty in ESRD patients.

Objective     To identify the preoperative risk factors for prolonged mechanical ventilation (PMV) after pulmonary thromboendarterectomy (PTE). Methods    The clinical data of patients who underwent PTE from December 2016 to August 2021 in our hospital were retrospectively analyzed. The patients were divided into two groups according to the postoperative mechanical ventilation time, including a postoperative mechanical ventilation time≤48 h group (≤48 h group) and a postoperative mechanical ventilation time>48 h (PMV) group (>48 h group). Univariable and logistic regression analysis were used to identify the preoperative risk factors for postoperative PMV. Results    Totally, 90 patients were enrolled in this study. There were 40 patients in the ≤48 h group, including 30 males and 10 females, with a mean age of 45.48±12.72 years, and there were 50 patients in the >48 h group, including 29 males and 21 females, with a mean age of 55.50±10.42 years. The results showed that in the ≤48 h group, the median postoperative ICU stay was 3.0 days, and the median postoperative hospital stay was 15.0 days; in the >48 h group, the median postoperative ICU stay was 7.0 days, and the median postoperative hospital stay was 20.0 days. The postoperative PMV was significantly correlated with tricuspid annular plane systolic excursion (TAPSE) [OR=0.839, 95%CI (0.716, 0.983), P=0.030], age [OR=1.082, 95%CI (1.034, 1.132), P=0.001] and pulmonary vascular resistance (PVR) [OR=1.001, 95%CI (1.000, 1.003), P=0.028]. Conclusion    Age and PVR are the preoperative risk factors for PMV after PTE, and TAPSE is the preoperative protective factor for PMV after PTE.

Objective:To analyze the correlation between the severity of acute pancreatitis (AP) and the levels of zonulin, zonula occludens protein-1 (ZO-1), tumor necrosis factor -α (TNF -α) in the peripheral blood of patients with acute pancreatitis (AP), and the value of predicting moderate and severe AP.Methods:The clinical data of 115 AP patients admitted to the Second Affiliated Hospital of Anhui Medical University from June 2020 to January 2022 were retrospectively analyzed. They were divided into mild group (69 cases) and moderate severe group (46 cases). The blood levels of zonulin, ZO-1, and TNF-α were measured for all patients on the 1st, 3rd, and 7th day after admission, and the results of the two group tests were compared. The correlation between zonulin, ZO-1, TNF -α and Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) scores on the 1st day was and the value of various indicators for predicting moderate to severe AP were analyzed.Results:The C-reactive protein (CRP) levels of AP patients in the moderate to severe group were higher than those in the mild group, and the difference was statistically significant (all P<0.05). The levels of zonulin, ZO-1, and TNF -α in AP patients in the moderate to severe group showed an upward trend on the 1st, 3rd, and 7th days after admission. The levels of zonulin, ZO-1, and TNF -α in AP patients in the moderate to severe group were higher than those in the mild group at the same time point, and the differences were statistically significant (all P<0.05). The APACHE Ⅱ score of AP patients on the first day of admission was positively correlated with the levels of zonulin, ZO-1, and TNF -α ( r=0.736, 0.552, 0.621, all P<0.05). Zonulin had the highest area under the curve (AUC) for predicting moderate to severe AP, at 0.892, with an optimal threshold of 2.075 pg/ml. Zonulin had the highest sensitivity, at 0.804, and ZO-1 had the highest specificity, at 0.926. Using zonulin ≥2.075 pg/ml, ZO-1≥399.4 ng/ml, and TNF -α≥40.88 pg/ml as thresholds; the sensitivity and specificity obtained from parallel experiments were 0.976 and 0.710, respectively; The sensitivity and specificity obtained from the series of experiments were 0.326 and 0.999, respectively. Conclusions:There is a correlation between the serum levels of zonulin, ZO-1, and TNF -α in AP patients and the severity of AP. Zonulin, ZO-1, and TNF -α have certain clinical value in predicting moderate to severe AP.

Objective:To explore the effect of radiofrequency heating on the morphology of articular cartilage in the knee and the expression of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the synovium using a rabbit model of knee osteoarthritis (OA).Methods:Fifty-four male rabbits had OA induced in their right hind limbs using the modified Hulth method. They were then randomly divided into a model group, a cervus and cucumis polypeptide (CCP) group and a radiofrequency thermotherapy (RT) group, each of 18. The CCP group was injected with deer melon peptide intramuscularly every day, while the RT group was given daily radiofrequency hyperthermia treatment at 36.5-38.5 ℃. The model group was not provided with any special treatment. On the 6th, 12th and 18th day of the treatment, 6 rabbits in each group were sacrificed to resect the right femur′s medial condyle cartilage. The morphological characteristics of the cartilage were evaluated using modified Mankins scoring, while the contents of lL-1B and TNF-a in the synovial membrane were detected using enzyme-linked immuno-sorbent assays.Results:The average Mankins scores and the levels of IL-1β and TNF-α decreased significantly at each time point, and significant differences were observed among the three groups. In the RT group the average Mankins score as well as the IL-1β and TNF-α levels decreased significantly with time throughout the experiment.Conclusions:Radiofrequency hyperthermia is superior to the injection of deer melon polypeptide in knee osteoarthritis, at least in rabbits. The therapeutic mechanism may be related to the control of IL-1β and TNF- α levels in the synovial membrane.

Objective    To evaluate the feasibility, safety, and short-term effect of minimally invasive ascending aorta surgery through a right anterior thoracotomy via the second intercostal incision. Methods    The clinical data of 13 patients who underwent minimally invasive ascending aorta surgery (including minimally invasive Bentall operation in 7 patients, minimally invasive Wheat operation in 2 patients, and minimally invasive ascending aorta replacement in 4 patients) through a right anterior thoracotomy via the second intercostal incision in our center from October, 2019 to September, 2020 were retrospectively analyzed. There were 12 males and 1 female at age of 19-69 (52.4±13.7) years. Results    The aortic cross-clamping time was 84.3±18.3 min. Three patients received blood transfusion, with the rate of 23.1%. The drainage volume in the first 24 hours after operation was 214.5±146.3 mL, with no redo for bleeding. The duration of mechanical ventilation was 19.0±11.3 hours and the length of intensive care unit stay was 1.8±1.3 days. The drainage tube was removed 2.5±1.0 days after operation. All the 13 patients recovered and discharged 6.4±2.0 days after operation, with no dead patients found. All patients survived with New York Heart Association (NYHA) functional classⅠandⅡduring a median follow-up of 8 months. Conclusion    Minimally invasive ascending aorta surgery through a right anterior thoracotomy via the second intercostal incision may be a safe and effective method with less injury and quick recovery.

OBJECTIVE: To investigate the effects of blocking the activation of ERK pathway on the expression of matrix metalloproteinase-9 (MMP-9) and the formation of cerebral edema in SD rats after brain injury. METHODS: Ninety SD rats were randomly divided into 3 equal groups, including a sham-operated group, modified Feeney's traumatic brain injury model group, and ERK inhibition group where the ERK inhibitor SCH772984 (500 μg/kg) was injected via the femoral vein 15 min before brain trauma. At 2 h and 2 days after brain trauma, the permeability of blood-brain barrier was assessed by Evans blue method, the water content of the brain tissue was determined, and the phosphorylation level of ERK and the expression level of MMP-9 mRNA and protein were measured by RT-PCR and Western blotting. RESULTS: Compared with the sham-operated group, the rats with brain trauma exhibited significantly increased level of ERK phosphorylation at 2 h and significantly increased expression of MMP-9 mRNA and protein 2 days after the injury ( < 0.01). Treatment with the ERK inhibitor significantly decreased the phosphorylation level of ERK after the injury ( < 0.01), suppressed over-expression of MMP-9 mRNA and protein 2 days after the injury ( < 0.01). The permeability of blood-brain barrier increased significantly 2 h after brain trauma ( < 0.05) and increased further at 2 days ( < 0.01); the water content of the brain did not change significantly at 2 h ( > 0.05) but increased significantly 2 d after the injury ( < 0.01). Treatment with the ERK inhibitor significantly lowered the permeability of blood-brain barrier and brain water content after brain trauma ( < 0.01). CONCLUSIONS Blocking the activation of ERK pathway significantly reduced the over-expression of MMP-9 and alleviates the damage of blood-brain barrier and traumatic brain edema, suggesting that ERK signaling pathway plays an important role in traumatic brain edema by regulating the expression of MMP-9.
Animals ; Brain Edema ; drug therapy ; etiology ; Brain Injuries, Traumatic ; complications ; drug therapy ; Gene Expression Regulation, Enzymologic ; drug effects ; Indazoles ; pharmacology ; therapeutic use ; MAP Kinase Signaling System ; drug effects ; Matrix Metalloproteinase 9 ; genetics ; Piperazines ; pharmacology ; therapeutic use ; Protein Kinase Inhibitors ; pharmacology ; therapeutic use ; Random Allocation ; Rats ; Rats, Sprague-Dawley

Objective:To evaluate the efficacy of hemoperfusion (HP) combined with continuous veno-venous hemofiltration (CVVH) on the treatment of acute paraquat (PQ) poisoning.Methods:Prospective randomized controlled trials and retrospective studies on the efficacy of HP combined CVVH in patients with oral PQ poisoning (poisoning time ≤ 24 hours) were found by searching from PubMed, Embase, Cochrane Library, Web of Science, SinoMed, CNKI and Wanfang databases before November 1st, 2019. The experimental group was treated with HP+CVVH, and the control group was treated with HP. Data included the general information of the literature, mortality, survival time, the incidence of respiratory failure and circulatory failure. The bias risk and the data were analyzed using the RevMan 5.3 software.Results:A total of 1 041 literatures were retrieved, and 7 literatures were finally enrolled, including 1 199 patients, with 735 patients in the control group and 464 patients in experimental group. Meta-analysis showed that compared with HP alone, HP+CVVH could significantly reduce the short-term mortality [4-day mortality: hazard ratio ( HR) = 0.52, 95% confidence interval (95% CI) was 0.38-0.71, P < 0.000 1], but no significant improvement in long-term mortality was found (28-day or 30-day mortality: HR = 0.68, 95% CI was 0.39-1.21, P = 0.19; 90-day mortality: HR = 1.13, 95% CI was 0.61-2.10, P = 0.07; total mortality: HR = 0.96, 95% CI was 0.72-1.29, P = 0.78). The survival time of patients treated with HP+CVVH was significantly longer than that of HP patients [mean difference ( MD) = 2.02, 95% CI was 0.81-3.22, P = 0.001], but the heterogeneity between studies was large. According to the type of literature, a subgroup analysis showed that the survival time of patients treated with HP+CVVH in prospective randomized controlled trials and retrospective studies were significantly longer than that of HP patients (prospective studies: MD = 1.53, 95% CI was 0.94-2.12, P < 0.000 01; retrospective studies: MD = 2.40, 95% CI was 0.08-4.73, P = 0.04). Compared with HP group, HP+CVVH could significantly reduce the incidence of circulatory failure [relative risk ( RR) = 0.40, 95% CI was 0.30-0.52, P < 0.000 01], but the incidence of respiratory failure significantly increased ( RR = 2.75, 95% CI was 2.18-3.48, P < 0.000 01). Conclusion:HP combined with CVVH can reduce the short-term mortality and the incidence of circulatory failure, prolong the survival time, and save time for further rescue, but it can't improve the long-term prognosis of patients.

OBJECTIVE: To investigate the effects of blocking the activation of ERK pathway on the expression of matrix metalloproteinase-9 (MMP-9) and the formation of cerebral edema in SD rats after brain injury. METHODS: Ninety SD rats were randomly divided into 3 equal groups, including a sham-operated group, modified Feeney's traumatic brain injury model group, and ERK inhibition group where the ERK inhibitor SCH772984 (500 μg/kg) was injected via the femoral vein 15 min before brain trauma. At 2 h and 2 days after brain trauma, the permeability of blood-brain barrier was assessed by Evans blue method, the water content of the brain tissue was determined, and the phosphorylation level of ERK and the expression level of MMP-9 mRNA and protein were measured by RT-PCR and Western blotting. RESULTS: Compared with the sham-operated group, the rats with brain trauma exhibited significantly increased level of ERK phosphorylation at 2 h and significantly increased expression of MMP-9 mRNA and protein 2 days after the injury ( < 0.01). Treatment with the ERK inhibitor significantly decreased the phosphorylation level of ERK after the injury ( < 0.01), suppressed over-expression of MMP-9 mRNA and protein 2 days after the injury ( < 0.01). The permeability of blood-brain barrier increased significantly 2 h after brain trauma ( < 0.05) and increased further at 2 days ( < 0.01); the water content of the brain did not change significantly at 2 h ( > 0.05) but increased significantly 2 d after the injury ( < 0.01). Treatment with the ERK inhibitor significantly lowered the permeability of blood-brain barrier and brain water content after brain trauma ( < 0.01). CONCLUSIONS Blocking the activation of ERK pathway significantly reduced the over-expression of MMP-9 and alleviates the damage of blood-brain barrier and traumatic brain edema, suggesting that ERK signaling pathway plays an important role in traumatic brain edema by regulating the expression of MMP-9.
Animals ; Blood-Brain Barrier ; Brain Edema ; Brain Injuries, Traumatic ; MAP Kinase Signaling System ; Matrix Metalloproteinase 9 ; Rats ; Rats, Sprague-Dawley

Objective: To analyze the epidemiological characteristics of acute paraquat(PQ)poisoning in children in southwest Shandong, and the risk factors for pulmonary interstitial fibrosis. Methods: This retrospective study was performed on the clinical data of children with acute PQ poisoning admitted from January 2013 to December 2017 in 12 hospitals in southwest Shandong.All participants were divided into pulmonary interstitial fibrosis group and no pulmonary interstitial fibrosis group on the basis of the chest CT 14 days after poisoning.The epidemiological characteristics and risk factors of pulmonary interstitial fibrosis were analyzed. Results: During the study period, a total of 307 children with acute PQ poisoning were admitted to 12 hospitals, of which 61 (19.87%) were suffering from acute PQ poisoning.Forty-nine cases with complete clinical data were analyzed, including 26 male and 23 female patients poisoned by oral.The age distribution ranged from 8 months to 14 years.Poisoning mainly occured from July to September of each year.The mortality of acute PQ poisoning was 8.2%(4/49), and the incidence of pulmonary interstitial fibrosis in survival patients was 44.4%(20/45). Statistical differences (P<0.05) were found between the pulmonary interstitial fibrosis and no pulmonary interstitial fibrosis, with regard to the times of blood purification, the time from poison exposure to blood purification, the application rate of glucocorticoids, the concentration of PQ in urine, the pediatric critical illness score, the time from poison exposure to gastric lavage, the white blood count at admission, serum creatinine, arterial blood lactate, PaO₂, PaCO₂, and PaO₂/FiO₂; however, there was no significant difference in the proportion of blood purification treatment, the mode of blood purification treatment, alanine aminotransferase, aspartate aminotransferase, urea nitrogen, creatine kinase and troponin.Stepwise logistic regression analysis showed that the time from exposure to poison to gastric lavage(OR=0.683, 95%CI 0.210-2.222)and to blood purification(OR=0.0133, 95%CI 0.004-0.042), the times of blood purification(OR=2.862, 95%CI 1.450-5.648), concentration of PQ in urine(OR=1.435, 95%CI 1.085-1.898), and the use of glucocorticoids(OR=0.190, 95%CI 0.048-0.757) were the risk factors for pulmonary interstitial fibrosis(P<0.05). Conclusion Early gastric lavage and blood purification, increasing the frequence of adminitrating purification appropriately, using low-dose glucocorticoids can reduce the incidence of pulmonary interstitial fibrosis of children with acute PQ poisoning.

Cyclosporine A( CsA) , as an immune inhibitor, is commonly used after organ transplantation.It has been found that the long-term use of CsA produced serious testicular toxicity and affected the fertility of organ transplantation patients.In order to investigate male reproductive damage induced by CsA, this article reviews its impact on reproductive organ development, its damage mechanism on the male reproductive system and drug research for alleviating its reproductive toxicity.It helps to make medical workers pay more attention to reproductive toxicity produced by CsA and make their efforts to develop some special drugs to lessen CsA reproductive toxicity.