Objective To understand the trends and characteristics of clinical trials on cancer pain medications in recent years,and to provide a reference basis for the development and clinical research of cancer pain medications.Methods Relevant information on clinical trials of cancer pain medications from 1987 to 2022 was retrieved from the ClinicalTrials.gov database,and a descriptive analysis was conducted from the perspectives of trial types,registration dates,reporting regions,cancer pain type,and cancer pain medications.Results A total of 376 clinical trials were selected,Among them,the number of investigator-initiated trials(IIT)was greater than that of industry-sponsored trials(IST).North America had the highest total number of projects,IIT and IST projects.The total number of trials and IST projects increased first and then decreased,while the number of IIT trials steadily increased.There was relatively higher amount nof research focused on chronic cancer pain,breakthrough cancer pain,and severe cancer pain.The highest proportion of subjects studied were opioids,with fentanyl being particularly prominent among them.Conclusion Clinical trials of cancer pain medications have played an important role in advancing cancer pain medication,but there is a need to further strengthen IST research on novel cancer pain medications and conduct more IIT studies to better optimize cancer pain treatment outcomes.

Objective To observe the clinical efficacy of Redo-Bentall surgery in the reoperation of aortic root lesions.Methods A retrospective analysis was performed on 46 patients who underwent Redo-Bentall surgery for aortic root lesions in our department from June 2010 to April 2022.They were 35 males and 11 females,at a mean age of 43.37±12.79 years,in 4.96±6.76 years since the last operation.General clinical data in perioperative period and during follow-up were collected and analyzed.Kaplan-Meier survival analysis was used to compare the survival rates of each etiological group.Results There were 9 cases of central end otitis,12 cases of Behset's disease,and 25 cases of other causes.After operation,4 cases(8.70％)experienced cardiac arrest,4 cases(8.70％)renal failure,2 cases(4.35％)gastrointestinal bleeding,2 cases(4.35％)new third-degree atrioventricular block and 2 cases(4.35％)permanent pacemaker placement.In perioperative period,3 cases(6.52％)died in hospital.During a mean follow-up of 5.03±3.27 years after discharge,5 cases(11.63％)were lost to follow-up,1 case died(2.33％),1 case had lacunar infarction(2.33％),and no severe bleeding or embolism complications was observed in the rest patients.The long-term survival rate was significantly lower in the endocarditis group(62.3％)and the Behcet's disease group(70％)than the other etiological groups(80％,P＜0.05).Conclusion The application of Redo-Bentall in the reoperation of aortic root lesions is safe and effective,but the survival rate is quite lower in the patients with infective endocarditis and Behcet's disease.

Objective:To investigate the short-term and medium-term changes of the left ventricular ejection fraction (LVEF) and the predictive value of relevant electrocardiogram (ECG) indexes in children with dilated cardiomyopathy (DCM) complicated with complete left bundle branch block (CLBBB).Methods:Children clinically diagnosed with DCM in the Department of Heart Center, Women and Children′s Hospital, Qingdao University and Beijing Anzhen Hospital, Capital Medical University between November 2011 and August 2020 were retrospectively recruited.According to the combination of CLBBB, they were divided into CLBBB group and non-CLBBB group.Echocardiogram and ECG were regularly performed.Short-term and medium-term changes of LVEF based on the 1-5-year follow-up data were compared between groups.COX proportional hazards model and Kaplan-Meier multiplicative limit method were used to analyze the predictive value of ECG indexes of LVEF changes in children with DCM combined with CLBBB.Results:Ninety-four children with DCM were enrolled, including 35 cases in CLBBB group and 59 cases in non-CLBBB group.There was no difference in baseline LVEF between groups.However, significant differences were found in QRS duration, corre-cted QT interval(QTc), R peak time in lead V 5 (T V5R) and QRS notching or slurring between groups ( P<0.05). LVEF of all children showed an upward trend within one year after onset, while the Z value of eft ventricular end diastolic diameter(LVEDd) showed a downward trend, and the two indexes tended to be stable within 1 - 5 years.The Z value of LVEDd in CLBBB group was significantly higher than that of non-CLBBB group, while LVEF was significantly lower (all P<0.05). The mean LVEF of CLBBB group slightly fluctuated around 50%, that of LVEF in non-CLBBB group was 60%.The multivariate COX regression analysis showed that QRS duration ( HR=0.979; 95% CI: 0.960-0.999, P<0.05) and QTc ( HR=0.988; 95% CI: 0.979-0.998, P<0.05) were independent predictors of LVEF recovery in children with DCM.Kaplan-Meier method showed a significant difference of LVEF normalization between DCM children with different QRS durations ( P<0.05), which was also detected in those with QTc interval ( P<0.05). Conclusions:LVEF of children with DCM combined with CLBBB increases in the short term after standard treatment, and then being stable.CLBBB can affect the recovery of left ventricular systolic function in children with DCM.Moreover, QRS duration and QTc interval are independent predictors of LVEF recovery in DCM children.

Background: Bovine papillomatosis is a type of proliferative tumor disease of skin and mucosae caused by bovine papillomavirus (BPV). As a transboundary and emerging disease in cattle, it poses a potential threat to the dairy industry. Objectives: The aim of this study is to detect and clarify the genetic diversity of BPV circulating in dairy cows in Xinjiang, China. Methods: 122 papilloma skin lesions from 8 intensive dairy farms located in different regions of Xinjiang, China were detected by polymerase chain reaction. The genetic evolution relationships of various types of BPVs were analyzed by examining this phylogenetic tree. Results: Ten genotypes of BPV (BPV1, BPV2, BPV3, BPV6, BPV7, BPV8, BPV10, BPV11, BPV13, and BPV14) were detected and identified in dairy cows. These were the first reported detections of BPV13 and BPV14 in Xinjiang, Mixed infections were detected, and there were geographical differences in the distribution of the BPV genotypes. Notably, the BPV infection rate among young cattle (< 1-year-old) developed from the same supply of frozen sperm was higher than that of the other young cows naturally raised under the same environmental conditions. Conclusions Genotyping based on the L1 gene of BPV showed that BPVs circulating in Xinjiang China displayed substantial genetic diversity. This study provided valuable data at the molecular epidemiology level, which is conducive to developing deep insights into the genetic diversity and pathogenic characteristics of BPVs in dairy cows.

Objective    To investigate the multidisciplinary management of patients with acute type A aortic dissection in late pregnancy. Methods    The clinical data of 3 patients admitted to the Second Affiliated Hospital of Army Medical University from 2018 to 2019 were analyzed. Their age ranged from 27 to 32 years, while gestational age was 34-37 weeks. Sudden chest pain was the main clinical symptom before operation. All 3 patients underwent Bentall surgery after cesarean section under general anesthesia, of whom 2 patients received total arch replacement (TAR) combined with frozen elephant trunk (FET) implantation and 1 received coronary artery bypass grafting (CABG) additionally. Results    No patient died during the perioperative period, and all the newborns were delivered successfully and survived healthily. The ICU stay was 3-5 d. The postoperative hospital stay was 15-18 d. The follow-up was 250-751 d. There was no recurrence or death. One patient who developed spontaneous pneumothorax and hydropneumothorax was cured in our center. Conclusion    The multidisciplinary diagnosis and treatment strategy plays a crucial role in saving the life of pregnant patients with acute type A aortic dissection.

Background: Bovine papillomatosis is a type of proliferative tumor disease of skin and mucosae caused by bovine papillomavirus (BPV). As a transboundary and emerging disease in cattle, it poses a potential threat to the dairy industry. Objectives: The aim of this study is to detect and clarify the genetic diversity of BPV circulating in dairy cows in Xinjiang, China. Methods: 122 papilloma skin lesions from 8 intensive dairy farms located in different regions of Xinjiang, China were detected by polymerase chain reaction. The genetic evolution relationships of various types of BPVs were analyzed by examining this phylogenetic tree. Results: Ten genotypes of BPV (BPV1, BPV2, BPV3, BPV6, BPV7, BPV8, BPV10, BPV11, BPV13, and BPV14) were detected and identified in dairy cows. These were the first reported detections of BPV13 and BPV14 in Xinjiang, Mixed infections were detected, and there were geographical differences in the distribution of the BPV genotypes. Notably, the BPV infection rate among young cattle (< 1-year-old) developed from the same supply of frozen sperm was higher than that of the other young cows naturally raised under the same environmental conditions. Conclusions Genotyping based on the L1 gene of BPV showed that BPVs circulating in Xinjiang China displayed substantial genetic diversity. This study provided valuable data at the molecular epidemiology level, which is conducive to developing deep insights into the genetic diversity and pathogenic characteristics of BPVs in dairy cows.

Objective: To summarize the clinical and electrophysiological characteristics of children with Wolff-Parkinson-White syndrome or ventricular pre-excitation. Methods: One hundred and seventy-nine consecutive children with Wolff-Parkinson-White syndrome or ventricular pre-excitation who were hospitalized at Beijing Anzhen Hospital Affiliated to Capital Medical University and planned to accept radiofrequency ablations were selected.Electrocardiogram and echocardiography were completed and detailed clinical data were collected before ablations.Anterograde refractory period of accessory pathways (ERPAPA) and retrograde ventriculoatrial conduction were measured during electrophysiology studies.The clinical and electrophysiological characteristics of these children were analyzed. Results: The ratio of left-sided to right-sided accessory pathways was 1.001.93(61 cases vs.118 cases). Six out of 61 patients with left-sided accessory pathways were verified by electrophysiology study.There was no statistical difference of P-R interval and QRS duration between patients with right-sided and left-sided accessory pathways(all P>0.05). Twelve patients were combined with congenital heart diseases.Fourteen patients with right-sided accessory pathways were of ventricular pre-excitation induced dilated cardiomyopathy.ERPAPA was measured successfully in 110 patients, ERPAPA less than 250 ms accounted for 32.7%(36/110 cases). Six children with two pathways were recognized.Antidromic atrioventricular reentrant tachycardia was induced in 3 children.One child had slow conduction pathway localized in right-sided septum. Conclusions Right-sided overt accessory pathways are more common in children with Wolff-Parkinson-White syndrome or ventricular pre-excitation.Organic heart diseases are not uncommon.Besides congenital heart disease, a small proportion of patients with right overt accessory pathways may develop ventricular pre-excitatory induced dilated cardiomyopathy resulting from ventricular wall dyskinesia.Most of the decremental retrograde ventriculoatrial conduction is the characteristic of ventricular muscles rather than the accessory pathways in nature.Two pathways are not uncommon in children with Wolff-Parkinson-White syndrome or ventricular pre-excitation.Before finishing radiofrequency ablation, the anterograde and retrograde function of the accessory pathway should be evaluated in detail again because it is easy to neglect the existence of another accessory pathway.

Brucella is an intracellular pathogen that invades a host and settles in its immune cells; however, the mechanism of its intracellular survival is unclear. Modification of small ubiquitin-related modifier (SUMO) occurs in many cellular activities. E2 conjugating enzyme 9 (Ubc9) is the only reported ubiquitin-conjugating enzyme that links the SUMO molecule with a target protein. Brucella's intracellular survival mechanism has not been studied with respect to SUMO-related proteins and Ubc9. Therefore, to investigate the relationship between Brucella melitensis 16M and SUMO, we constructed plasmids and cells lines suitable for overexpression and knockdown of SUMO1 and Ubc9 genes. Brucella 16M activated SUMO1/Ubc9 expression in a time-dependent manner, and Brucella 16M intracellular survival was inhibited by SUMO1/Ubc9 overexpression and promoted by SUMO1/Ubc9 depletion. In macrophages, Brucella 16M-dependent apoptosis and immune factors were induced by SUMO1/Ubc9 overexpression and restricted by SUMO1/Ubc9 depletion. We noted no effect on the expressions of SUMO1 and Ubc9 in B. melitensis 16M lipopolysaccharide-prestimulated mouse RAW264.7 macrophages. Additionally, intracellular survival of the 16M△VirB2 mutant was lower than that of Brucella 16M (p < 0.05). VirB2 can affect expression levels of Ubc9, thereby increasing intracellular survival of Brucella in macrophages at the late stage of infection. Collectively, our results demonstrate that B. melitensis 16M may use the VirB IV secretion system of Brucella to interact with SUMO-related proteins during infection of host cells, which interferes with SUMO function and promotes pathogen survival in host cells.
Animals ; Apoptosis ; Brucella melitensis ; Brucella ; Immunologic Factors ; Macrophages ; Mice ; Plasmids

PURPOSE: Previous studies have confirmed that microRNAs play important roles in the pathogenesis of acute aortic dissection (AAD). Here, we aimed to explore the role of miR-145 and its regulatory mechanism in the pathogenesis of AAD. MATERIALS AND METHODS: AAD tissue samples were harvested from patients with aortic dissection and normal donors. Rat aortic vascular smooth muscle cells (VSMCs) were transfected with miR-145 mimic/inhibitor or negative control mimic/inhibitor. Gene and protein expression was measured in human aortic dissection tissue specimens and VSMCs by qRT-PCR and Western blot. Luciferase reporter assay was applied to verify whether connective tissue growth factor (CTGF) was a direct target of miR-145 in VSMCs. Methyl thiazolyl tetrazolium assay was used to detect VSMC viability. RESULTS: miR-145 expression was downregulated in aortic dissection tissues and was associated with the survival of patients with AAD. Overexpression of miR-145 promoted VSMC proliferation and inhibited cell apoptosis. Moreover, CTGF, which was increased in aortic dissection tissues, was decreased by miR-145 mimic and increased by miR-145 inhibitor. Furthermore, CTGF was confirmed as a target of miR-145 and could reverse the promotion effect of miR-145 on the progression of AAD. CONCLUSION: miR-145 suppressed the progression of AAD by targeting CTGF, suggesting that a miR-145/CTGF axis may provide a potential therapeutic target for AAD.
Animals ; Apoptosis ; Blotting, Western ; Connective Tissue Growth Factor ; Humans ; Luciferases ; MicroRNAs ; Muscle, Smooth, Vascular ; Rats ; Tissue Donors

Objective To identify the importance of ISO9001 in project management and explore the procedure of establishing it,to provide reference for further practice.Methods According to prior studies,the formation procedure of this quality management system was described in detail.Results Quality management system could improve project management in multiple aspects,such as explicit regulation,orderly implementation,effective supervision,timely feedback and effective reform.Conclusions As the unique national project management institution on medical science and health,it is crucial to establish a institutionalized,standardized and international scientific research management system,especially on medical science and health field.