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Objective:To investigate whether ultra-high dose rate (FLASH) irradiation can reduce radiation-induced intestinal injuries of mice compared to conventional dose rate (CONV) irradiation.Methods:Both FLASH and CONV irradiation were delivered with electron beam, with dose rates of 750 Gy/s and 0.5G y/s, respectively. A total of 105 mice were randomly divided into groups using a simple randomization method. Twenty-one mice were selected for weight observation, 7 mice in each group. After 9 Gy FLASH and CONV irradiation on the abdomen, the weight changes of mice were measured every other day, and compared among three groups. Twenty-four mice were selected for pathological examination including 5 mice in the control group. Three-and-a-half-day days after 12 Gy FLASH ( n=10) and CONV irradiation ( n=9) on the abdomen, the intestines of the mice were taken. Pathological sections were stained with hematoxylin-eosin (HE) to compare the number and percentage of regenerated crypts of the small intestine between two groups. After 12 Gy FLASH ( n=10) and CONV irradiation ( n=10) on the abdomen, the survival of 20 mice was observed. After FLASH using 4.5 Gy×2 times ( n=10) and CONV irradiation at 9 Gy×1 time ( n=10) on the abdomen, the weight changes were observed. After FLASH using 6 Gy×2 times ( n=10) and CONV irradiation at 12 Gy×1 time ( n=10) on the abdomen, the survival of mice was observed. The time interval between two irradiation was 1 min. EBT3 film was employed to monitor the actual exposure dose of the mice. The variables conforming to normal distribution were expressed by Mean±SD. Inter group comparison was performed by independent t-test. The survival of mice among different groups was compared by log-rank test. Results:After 9 Gy of abdominal irradiation, the mean weight of mice in the FLASH group was significantly higher than that in the CONV group. The weight of mice in the FLASH and CONV groups was (19.8±0.8) g and (18.0±1.8)g ( P=0.036) at 7 days after irradiation, (22.0±1.0)g and (21.2±0.5)g ( P=0.075) at 15 days after irradiation, and (24.2±1.4)g and (22.0±1.2)g ( P=0.012) at 25 days after irradiation, respectively. After 12 Gy irradiation, the mean survival of mice in FLASH and CONV groups was 4 days and 4.7 days ( P=0.029). After 12 Gy total abdominal irradiation, the mean number of intestinal regenerative crypts in the FLASH and CONV groups was 2.9/mm and 1.2/mm ( P=0.041), and the percentage of intestinal regenerative crypts was 34.1% and 14.1%, respectively. The survival of mice irradiated by FLASH using 6 Gy×2 times was longer compared with that of mice after CONV irradiation at 12 Gy×1 time. The weight of mice after 4.5 Gy×2 times irradiation was higher than that of mice after CONV irradiation at 9 Gy×1 time. Conclusion:Weight, survival and the number of intestinal regenerative crypts in the FLASH group are higher than those in the CONV group after irradiation, indicating that radiation-induced intestinal injury caused by FLASH irradiation is slighter than that of CONV irradiation.
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Radiotherapy is one of the important treatment modalities for malignant tumors. Conventional fractionation is the most commonly-used radiotherapy mode, but it has disadvantages such as long treatment time and low efficiency, etc. With the advancement of radiotherapy equipment and technology, moderately hypofractionated radiotherapy has become the standard treatment for tumors such as breast cancer and prostate cancer, etc. However, the efficacy and safety of moderately hypofractionated radiotherapy have not been fully confirmed in a wider range of tumors. In this article, the application, efficacy, and safety of moderately hypofractionated radiotherapy in malignant tumors were reviewed.
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ObjectiveThe purpose of this study was to investigate the effects of transcutaneous electrical acupoint stimulation (TEAS) on cognitive function of vascular dementia (VD) rats and its mechanism. MethodsVD rat model was established by modified two-vessel occlusion (2-VO). After modeling, TEAS and electroacupuncture (EA) were used to stimulate Baihui and Zusanli points of rats respectively for 14 d. After treatment, novel object recognition test, Morris water maze test, and Y maze test were used to evaluate the spatial memory and learning ability of rats. Hematoxylin and eosin staining was used to observe the morphology of hippocampal neurons. Transmission electron microscopy was used to observe the ultrastructure of hippocampal mitochondria. Enzyme-linked immunosorbent assay kits were used to detected the levels of SOD, CAT, GSH-Px, MDA and ROS in serum of rats. Western blot was used to detect the expression of PGC-1α, TFAM, HO-1, NQO1 proteins in the hippocampus, Keap1 protein in the cytoplasm and Nrf2, NRF1 proteins in the nucleus. ResultsAfter treatment for 14 d, compared to the model group, the escape latency of VD rats decreased, while the discrimination index, the times of rats crossing the original platform area, the residence time in the original platform quadrant, and the percentage of alternation increased. TEAS can improve the structure of hippocampal neurons and mitochondria of VD rats, showing that neurons were arranged more regularly and distributed more evenly, nuclear membrane and nucleoli were clearer, and mitochondrial swelling were reduced, mitochondrial matrix density were increased, and mitochondrial cristae were more obvious. The levels of SOD, GSH-Px and CAT in serum increased significantly, while the concentration of MDA and ROS decreased. TEAS also up-regulated the expression levels of PGC-1α TFAM, NQO1 and HO-1 proteins in the hippocampus and Nrf2, NRF1 proteins in the nucleus, but down-regulated the Keap1 protein in the cytoplasm. ConclusionTEAS can improve cognition, hippocampal neurons and mitochondrial structure of VD rats, and the effect is better than EA. The mechanism may be the activation of PGC-1α mediated mitochondrial biogenesis and antioxidant stress, which also provides a potential therapeutic technology and experimental basis for the treatment of VD.
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Objective To explore the impact of macrophage-to-myofibroblast transition(MMT)on pulmonary fibro-sis induced by acute lung injury by LPS.Methods Totally 21 male mice were randomly classified into 7 groups:control group,model group(LPS-PF)at different time points and intervention group of clodronate-liposomes(CL-LIP)treatement at different time points(n=3).Pulmonary fibrosis was identified by HE and Masson staining microscopy.The immuno-fluorescence technology was used for the evaluation of numbers of macrophage-to-myofi-broblast transition cells(MMT cell which co-expressed CD68 and α-SMA).Bone marrow-derived macrophages(BMDMs)were randomly classified into two group:control(Ctrl)group and TGF-β1-treated group induced by transforming growthfactor-β1.α-SMA,FN and Col1 were detected by RT-qPCR.The expression of α-SMA,Smad3 and p-Smad3 protein was evaluated by Western blot.Results At day 7,the Ashcroft score of lung tissue in LPS-PF mouse model was significantly increased when compared with the Ctrl group(P＜0.01);While the score signifi-cantly declined when the model was pretreated with CL-LIP(P＜0.05).As detected by immuno-fluorescence stai-ning,in CL-LIP group the number of CD68-positive cells co-labeled with α-SMA was obviously less then that of LPS-PF group of the corresponding time point(P＜0.01).When the BMDMs were stimulated by TGF-β1 at 24 h,48 h and 96 h respectively,a higher expression of α-SMA,FN,Col1,were found in TGF-β1-treated group than that in Ctrl group at the corresponding time point(P＜0.01).The expression of Smad3,p-Smad3 significantly higher in LPS-PF group(at both day 7 and day 10)and TGF-β1-treated group(at both 48 h and 96 h)as compared to cor-responding control group(P＜0.01).Conclusions MMT promotes pulmonary fibrosis induced by ALI via LPS.Smad3 is proved to be involved in the MMT process.
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Recent studies have shown that ozone therapy, a widely used immunotherapy in various diseases, can play a therapeutic role in the novel coronavirus infection by enhancing lung function, reducing inflammatory reactions, and bolstering immune system performance. This article reviews the pathophysiological basis of novel coronavirus infection and the mechanisms involved in ozone therapy for its treatment, also summarizes the clinical evidence and safety assessment of ozone therapy in combating novel coronavirus infections.
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OBJECTIVES@#To summarize the clinical characteristics and nutrition therapy for children with lysinuric protein intolerance (LPI).@*METHODS@#The clinical manifestations, laboratory test results and enteral nutrition treatment in a girl with LPI diagnosed in Xiangya Hospital, Central South University were retrospective analyzed. Additionally, the data of the children with LPI reported in China and overseas were reviewed.@*RESULTS@#A case of 4-year-old girl was presented, who exhibited significant gastrointestinal symptoms, such as chronic abdominal distension, prolonged diarrhea, recurrent pneumonia, and limited growth. She had a poor response to anti-infection treatment. After receiving enteral nutrition therapy, she did not experience any gastrointestinal discomfort, and there were improvements in the levels of hemoglobin, albumin, and blood ammonia. Unfortunately, due to serious illness, she declined further treatment and later passed away. A total of 92 cases of pediatric patients with LPI have been reported to date, including one case reported in this study. Most children with LPI experienced disease onset after weaning or introduction of complementary foods, presenting with severe digestive system symptoms, malnutrition, and growth retardation. It is noteworthy that only 50% (46/92) of these cases received nutritional therapy, which effectively improved their nutritional status. Among the 92 children, 8 (9%) died, and long-term follow-up data were lacking in other reports.@*CONCLUSIONS@#LPI often involves the digestive system and may result in growth restriction with a poor prognosis. Nutritional therapy plays a crucial role in the comprehensive treatment of LPI.
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Child, Preschool , Female , Humans , Amino Acid Metabolism, Inborn Errors/therapy , Enteral Nutrition/methods , Malnutrition , Retrospective Studiesالملخص
Diabetic retinopathy(DR)is the most prevalent and severe ocular complication in people with diabetes, and it is one of the leading causes of blindness in adults. In recent years, drug therapy represented by anti-vascular endothelial growth factor(VEGF)agents has become the first-line therapy in DR treatment, but it cannot reverse retinal non-perfusion areas, microaneurysms and abnormal teleangiectatic capillaries, those who cannot be treated on time are at risk of disease progression. Laser photocoagulation has been widely applied for more than 40 years, it can effectively reduce the rate of blindness by eliminating the non-perfusion areas of capillaries, and panretinal photocoagulation(PRP)has been the primary treatment for DR. With the continuing innovations in laser technology, on the basis of maintaining the curative effect, the aim of minimizing retinal damage and adverse side effects has been realized. A combination of laser photocoagulation and anti-VEGF agents can achieve complementary advantages and better efficacy. Deepening the clinical research on laser therapy and laser therapy combined with anti-VEGF agents in the treatment of DR may help to establish the personalized treatment corresponds with our national conditions. This article briefly reviews the latest application progress of laser therapy in DR treatment in the era of anti-VEGF agents.
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Diabetic macular edema(DME)and age-related macular degeneration(ARMD)are the leading causes of visual impairment and blindness worldwide, and their common pathological features are increased vascular permeability and abnormal neovascularization, in which cytokines such as vascular endothelial growth factor(VEGF)and angiopoietin-2(Ang-2)play an important role. Intravitreal injection of anti-VEGF agents significantly changed the clinical management of DME and ARMD, but limitations such as the non-responsive cases, the treatment burden and risks caused by frequent injections need to be overcome. Faricimab, a novel bispecific monoclonal antibody that simultaneously targets VEGF-A and Ang-2, can effectively reduce vascular permeability, decrease the number of neovascularization and alleviate retinal edema. Registered clinical studies have shown that Faricimab is effective in improving vision and reducing retinal edema, which is non-inferior to Aflibercept and Ranibizumab, maintains a long dosing interval, and has a high safety profile. This article reviews the latest advances in the treatment of DME and ARMD with Faricimab.
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Objective: To explore the long-term effect of combined surgery for the treatment of congenital tibial pseudarthrosis in children. Methods: The clinical data of 44 children with congenital tibial pseudarthrosis who underwent combined surgery (tibial pseudarthrosis tissue resection, intramedullary rod fixation, Ilizarov external fixator fixation, wrapped autologous iliac bone graft) from August 2007 to October 2011 at the Department of Pediatric Orthopedics, Hunan Children's Hospital were collected retrospectively. There were 33 males and 11 females. The age at the time of surgery was (3.7±2.2)years (range:0.6 to 12.4 years), including 25 cases under 3 years old and 19 cases above 3 years old.Among them, 37 cases were complicated with neurofibromatosis type 1.The operation status, postoperative complications and follow-up results were recorded. Results: The follow-up time after surgery was (10.9±0.7)years (range:10 to 11 years).Thirty-nine out of 44 patients (88.6%) achieved initial healing of tibial pseudarthrosis, with an average healing time of (4.3±1.1)months (range:3 to 10months).In the last follow-up, 36 cases (81.8%) had unequal tibial length, 20 cases (45.4%) had refractures, 18 cases (40.9%) had ankle valgus, 9 cases (20.4%) had proximal tibial valgus, and 11 cases (25.0%) had high arched feet.Nine cases (20.4%) developed distal tibial epiphyseal plate bridging.17 cases (38.6%) had abnormal tibial mechanical axis.Seven cases (15.9%) developed needle infection, and one case (2.3%) developed tibial osteomyelitis. 21 patients (47.7%) had excessive growth of the affected femur.Five patients (11.3%) had ankle stiffness, and 34 patients (77.2%) had intramedullary rod displacement that was not in the center of the tibial medullary cavity.Among them, 8 cases (18.1%) protruded the tibial bone cortex and underwent intramedullary rod removal.18 children have reached skeletal maturity, while 26 children have not been followed up until skeletal maturity. Conclusion: Combined surgery for the treatment of congenital pseudarthrosis of the tibia in children has a high initial healing rate, but complications such as unequal tibia length, refracture, and ankle valgus occur during long-term follow-up, requiring multiple surgical treatments.
الموضوعات
Male , Female , Humans , Child , Child, Preschool , Pseudarthrosis/congenital , Follow-Up Studies , Retrospective Studies , Tibia/surgery , Neurofibromatosis 1 , Tibial Fractures/surgeryالملخص
Lysinuric protein intolerance (LPI) is an autosomal recessive disorder caused by defective plasma membrane transport of cationic amino acids (lysine, arginine, and ornithine). LPI is characterized by recurrent vomiting and diarrhea, coma following intake of protein-rich foods, and aversion to high-protein foods, further leading to malnutrition and even death. Some children with LPI also develop alveolar proteinosis. Nutrition support is an important part of treatment. Here we report a case of a 4-year-old girl with LPI, alveolar proteinosis, systemic lupus erythematosus, and cellular immune dysfunction, where nutrition support successfully improved her nutritional status. The relevant literatures are reviewed to provide guidance on the nutritional diagnosis and treatment of LPI.
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ObjectiveXenotransplantation is an effective way to address the shortage of human organ donors, but it faces serious immune rejection reactions, including hyperacute rejection caused by blood type differences. Establishing a stable, convenient, and reliable method for pig blood type identification can quickly screen suitable donor pigs for xenograft research.MethodsBanna miniature inbred pigs, Diannan small eared pigs, and Bama Xiang pigs were selected as the research objects. DNA was extracted from the blood, oral buccal mucosa, and fetal fibroblasts of the three strains of pigs using DNA extraction kits. The target fragment of the ABO homologous gene EAA intron 7 in pigs was amplified using PCR method. Blood agglutination reaction was used to detect hemolysis in pig anterior vena cava whole blood after adding anti A and B antibodies. Immunohistochemical method was used to detect the expression level of A antigen in pig heart, liver, spleen, lung, and kidney tissues. Immunofluorescence method was used to detect the expression level of A antigen in pig oral mucosa. By comparing the results of different methods for determining pig blood types, the stability and reliability of the PCR method were verified, and a convenient PCR based pigblood type identification method was established.Results Firstly, the blood PCR results of 69 inbred strains of Banna miniature pigs, 7 Diannan small eared pigs, and 34 Bama Xiang pigs showed 20 AO blood types, 66 AA blood types, and 24 O blood types. The PCR results of fetal fibroblasts from 47 Diannan small eared pigs showed that all 47 fetuses were O blood type. Among them, the oral mucosal PCR results of 8 gene edited cloned pigs were consistent with those of donor fetal fibroblasts, all of which were O blood type. The oral mucosal PCR results of 8 wild-type pigs (2 inbred lines of Banna miniature pigs, 4 Diannan small eared pigs, and 2 Bama Xiang pigs) were consistent with the blood PCR identification results. Then, 11 inbred lines of Banna miniature pigs, 4 Diannan small eared pigs, and 2 Bama Xiang pigs were randomly selected for blood agglutination reaction validation, and the results were consistent with the PCR identification results of both blood samples and oral mucosa samples. Moreover, immuno-histochemical analysis was performed on the heart, liver, lung, kidney, and spleen tissues of one Banna miniature pig inbred line and two Bama Xiang pigs, and the results were consistent with blood PCR identification and blood agglutination reaction results. Finally, oral mucosal samples were collected from 2 inbred strains of Banna miniature pigs and 1 Bama Xiang pig for immunofluorescence detection, and the results were consistent with the blood PCR identification results.ConclusionBy collecting fetal cells and oral mucosal samples from live pigs for PCR detection, the blood type of pigs can be accurately and efficiently identified, providing a convenient method for blood type screening of xenograft donor pigs.
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@#Proliferative vitreoretinopathy(PVR)is a serious complication that occurs in the natural history of rhegmatogenous retinal detachment(RRD)or after retinal detachment surgery, often resulting in vision loss. Currently, there has no effective treatment. The pathological characteristics of PVR are the excessive inflammatory response and abnormal proliferation of various cells under the action of cytokines, which eventually form a layer of proliferative membrane around the retinal surface, and further lead to traction retinal detachment(TRD). In-depth studies on the pathogenesis of PVR will help to find promising molecular targets for its treatment. Recent studies have found that vascular endothelial growth factor(VEGF)and the epithelial-mesenchymal transition(EMT)of retinal pigment epithelium(RPE)cells play an important role in the pathogenesis of PVR. This article summarizes the roles of VEGF and RPE cell EMT in the pathogenesis of PVR and the interaction mechanism between them, with the aim to provide new ideas for the treatment and clinical research of PVR.
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Objective:To evaluate and summarize the teaching effect of" New Technology of Radiotherapy and Oncology" in the form of questionnaire, understand the degree of demand for the course of all kinds of medical students and improve the teaching contents and methods.Methods:The course of" New Technology of Radiotherapy and Oncology" was a specialized elective course in Peking Union Medical College. After two rounds of teaching practices, we evaluated the students participating in the course or non-course participants by anonymous questionnaire. The questionnaire items include the course content, setting, teachers and improvement suggestions.Results:A total of 73 questionnaires were sent out, and the recovery rate was 100%. Among them, 52(71%) were from students who chose the courses. 83% of the students" strongly agree" that the teaching content of this course is the latest development, the latest achievement or the problem to be solved, 94% were" satisfied" or" very satisfied" with their learning effect, and 92% and 83% were satisfied with the teachers and teaching plan, respectively. After taking the course, students rated" broadening of mind" (96%) as the biggest gain, followed by" facilitating interdisciplinary collaboration" (79%). 86% of the non-course participants felt the need to supplement the existing curriculum with new techniques in oncology radiotherapy, hoping that the curriculum would" broaden the mind" (76%), improve clinical application (81%) and facilitate interdisciplinary collaboration (71%).Conclusion:The questionnaire results show that the teaching practice of this course covers the different needs of all kinds of students, which is worthy of implementation and further improvement.
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Objective:To assess the clinical characteristics of patients with chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) or other comorbidities.Methods:In this cross sectional study, a total of 2 090 patients with confirmed COPD which came from Renmin Hospital of Wuhan University from August 2017 to October 2021 were included to investigate the prevalence of comorbidities (hypertension, diabetes, cardiovascular disease, cerebrovascular disease, metabolic diseases and osteoporosis) and clinical characteristics. All subjects underwent overnight polysomnography, clinical symptom questionnaire and sleep questionnaire. The data of baseline, blood biochemistry, arterial blood gas, lung function, sleep questionnaire, sleep monitoring and other indicators were compared between group with COPD only and with COPD and OSA.Results:55.84% of COPD patients (1 167/2 090) with OSA were included in the study. By analyzing the prevalence of comorbidities (hypertension, diabetes, cardiovascular disease, cerebrovascular disease, metabolic diseases and osteoporosis), this study found that only the prevalence of hypertension was significantly higher in the group with COPD and OSA ( P<0.01) when compared with the COPD only group (35.2%). As the severity of OSA increased in COPD patients, the incidence of hypertension increased. The prevalence of hypertension was 35.2%, 37.5%, 44.9%, 53.2% in non-OSA, mild, moderate, and severe OSA patients, respectively. By binary logistic regression analysis, the BMI ( OR=1.067, 95% CI: 1.043-1.091, P<0.01) , neck circumference ( OR=1.019, 95% CI: 1.002-1.036, P<0.05), smoking history ( OR=1.345, 95% CI: 1.028-1.760, P<0.05), hypertension ( OR=1.249, 95% CI: 1.024-1.522, P<0.05) were regarded as independent risk factors for patients with COPD and OSA. Conclusions:COPD patients have a high rate of OSA. In clinical practice, greater emphasis on primary/secondary prevention should be paid to COPD patients with OSA and hypertension. The management and intervention of OSA and hypertension may improve the prognosis of CODP patients.
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BACKGROUND@#Acupuncture has been widely used to relieve migraine-related symptoms. However, the findings of previous systematic reviews (SRs) and meta-analyses (MAs) are still not completely consistent. Their quality is also unknown, so a comprehensive study is needed.@*OBJECTIVE@#To evaluate the reporting and methodological quality of these MAs concerning acupuncture for migraine, and summarize evidence about the efficacy and safety of acupuncture for migraine.@*SEARCH STRATEGY@#PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese Biomedical Databases, Wanfang Data, and VIP databases were searched from inception to September 2020, with a comprehensive search strategy.@*INCLUSION CRITERIA@#The pairwise MAs of randomized controlled trials (RCTs) concerning migraine treated by acupuncture or acupuncture-based therapies, with a control group that received sham acupuncture, medication, no treatment, or acupuncture at different acupoints were included.@*DATA EXTRACTION AND ANALYSIS@#Two independent investigators screened studies, extracted relevant data, and assessed reporting and methodological quality using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2009 and A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2), then all results were cross-checked. Spearman correlation test was used to evaluate the correlation between reporting and methodological quality scores.@*RESULTS@#A total of 20 MAs were included in this study. The included MAs indicated that acupuncture was efficacious and safe in preventing and treating migraine when compared with control intervention. There was a high correlation between reporting and methodological quality scores (rs = 0.87, P < 0.001). The quality of the included SRs needs to be improved mainly with regard to protocol and prospective registration, using a comprehensive search strategy, summarizing the strength of evidence body for key outcomes, a full list of excluded studies with reasons for exclusion, reporting of RCTs' funding sources, and assessing the potential impact of risk of bias in RCTs on MA results.@*CONCLUSION@#Acupuncture is an effective and safe intervention for preventing and treating migraine, and could be considered as a good option for patients with migraine. However, the reporting and methodological quality of MAs included in this overview is suboptimal. In the future, AMSTAR 2 and PRISMA tools should be followed when making and reporting an SR with MA.
الموضوعات
Humans , Acupuncture Points , Acupuncture Therapy/methods , China , Meta-Analysis as Topic , Migraine Disorders/therapy , Research Reportالملخص
Objective:To investigate the effects of laparoscopic surgery versus open surgery on acute appendicitis in children. Methods:We retrospectively analyzed the data of 50 children with acute appendicitis who underwent surgery in Zhoushan Women and Children Hospital from December 2016 to December 2019. They were randomly divided into observation ( n = 27) and control ( n = 23) groups. The observation group underwent three-port laparoscopy. The control group underwent open surgery. Operation-related indicators, postoperative recovery, parental satisfaction, and complications were compared between the two groups. Results:Operative time was significantly longer in the observation group than in the control group [(56.57 ± 5.35) minutes vs. (40.23 ± 6.31) minutes, t = 9.78, P < 0.001). Intraoperative blood loss was significantly less in the observation group than in the control group [(10.11 ± 2.36) mL vs. (18.36 ± 3.21) mL, t = 10.45, P < 0.001]. Duration of pain was significantly shorter in the observation group than in the control group [(1.23 ± 0.23) days vs. (2.98 ± 0.87) days, t = 10.06, P < 0.001). Time to postoperative exhaust was significantly shorter in the observation group than in the control group [(21.39 ± 4.35) minutes vs. (39.88 ±5.39) minutes, t = 13.35, P < 0.001]. Time to defection was significantly shorter in the observation group than in the control group [(50.12 ± 3.35) minutes vs. (61.23 ± 4.21) minutes, t = 10.33, P < 0.001]. Time to first diet was significantly shorter in the observation group than in the control group [(13.25 ± 2.56) hours vs. (19.96 ± 2.67) hours, t = 9.07, P < 0.001]. Length of hospital stay in the observation group was significantly shorter in the observation group than in the control group [(4.13 ± 1.12) days vs. (7.98 ± 1.96) days, t = 8.53, P < 0.001). Parental satisfaction was significantly higher in the observation group than in the control group [96.30% vs. 47.83%, χ2 = 13.360, P < 0.001]. The incidence of complications was significantly lower in the observation group than in the control group [7.41% vs. 52.17%, χ2 = 10.58, P < 0.001]. Conclusion:Laparoscopic surgery is superior and safer to open surgery in the treatment of acute appendicitis in children.
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OBJECTIVE@#To investigate the role of acetylated modification induced by coactivator p300 in lipopolysaccharide (LPS)- induced inflammatory mediator synthesis and its molecular mechanism.@*METHODS@#Agilent SurePrint G3 Mouse Gene Expression V2 microarray chip and Western blotting were used to screen the molecules whose expression levels in mouse macrophages (RAW246.7) were correlated with the stimulation intensity of LPS. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (chip-qPCR) were used to verify the binding of the molecules to the promoters of IL-6 and TNF-α genes. The effects of transfection of RAW246.7 cells with overexpression or interfering plasmids on IL-6 and TNF-α synthesis were evaluated with ELISA, and the binding level of the target molecules and acetylation level of H3K27 in the promoter region of IL-6 and TNF-α genes were analyzed by chromatin immunoprecipitation sequencing technique (chip-seq).@*RESULTS@#Gene microarray chip data and Western blotting both confirmed a strong correlation of p300 expression with the stimulation intensity of LPS. Immunocoprecipitation confirmed the binding between p300 and c-myb. The results of EMSA demonstrated that c-myb (P < 0.05), but not p300, could directly bind to the promoter region of IL-6 and TNF-α genes; p300 could bind to the promoters only in the presence of c-myb (P < 0.05). The expressions of p65, p300 and c-myb did not show interactions. Both p300 overexpression and LPS stimulation could increase the level of promoter-binding p300 and H3K27 acetylation level, thus promoting p65 binding and inflammatory gene transcription; such effects were obviously suppressed by interference of c-myb expression (P < 0.05). Interference of p65 resulted in inhibition of p65 binding to the promoters and gene transcription (P < 0.05) without affecting p300 binding or H3K27 acetylation level.@*CONCLUSION@#LPS can stimulate the synthesis of p300, whose binding to the promoter region of inflammatory genes via c-myb facilitates the cohesion of p65 by inducing H3K27 acetylation, thus promoting the expression of the inflammatory genes.
الموضوعات
Animals , Mice , Acetylation , Inflammation Mediators , Interleukin-6/metabolism , Lipopolysaccharides/pharmacology , Tumor Necrosis Factor-alpha/metabolismالملخص
ObjectiveTo explore the anti-testicular inflammation mechanism of Wuzi Yanzongwan through network pharmacological analysis and experimental verification. MethodThe active ingredients of Wuzi Yanzongwan were searched in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， and their targets were predicted via SwissTargetPredicition. GeneCards and Online Mendelian Inheritance in Man （OMIM） were used to obtain the known targets for the treatment of testicular inflammation. STRING 11.0 was employed to construct the protein-protein interaction （PPI） network， and Cytoscape 3.7.1 to construct the “herbal medicine-active ingredient-target” network of Wuzi Yanzongwan and “active ingredient-disease target” network. Metascape was used for gene ontology （GO） annotation and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment of signaling pathways. ResultA total of 72 active ingredients and 624 potential targets of Wuzi Yanzongwan were screened out， and 196 key targets were identified for the treatment of testicular inflammation by Wuzi Yanzongwan. The results of GO annotation showed that the anti-testicular inflammation targets of Wuzi Yanzongwan were involved in the biological processes such as the response to molecule of bacterial origin， the positive regulation of response to external stimulus， and the response to extracellular stimulus. KEGG pathway enrichment revealed that the major pathways associated with the treatment （P<0.01） included the pathways in cancer， epidermal growth factor receptor （EGFR） tyrosine kinase inhibitor resistance， transcriptional misregulation in cancer， calcium signaling pathway， apelin signaling pathway， and NOD-like receptor signaling pathway. Wuzi Yanzongwan may exert the anti-testicular inflammation effect by inhibiting the activation of the NLR family pyrin domain-containing 3 （NLRP3） inflammasome pathway to alleviate the inflammatory response， which verifies the prediction results based on network pharmacology to a certain extent. ConclusionThe inhibitory effect of Wuzi Yanzongwan on testicular inflammation is multi-target， multi-pathway， and multi-mechanism. The findings of this study provide evidence support for the clinical application of Wuzi Yanzongwan.
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Diabetic macular edema(DME)has become the leading cause of vision loss in patients with diabetes. Currently, intravitreal injection of anti-vascular endothelial growth factor(VEGF)therapy is the first-line treatment for DME. However, the economic burden and related complications brought by frequent injections should not be ignored. Therefore, the drugs with longer-lasting effects and longer injection intervals must be explored. Brolucizumab is a single-chain antibody fragment(scFv)with a high affinity for VEGF. Compared with other available anti-VEGFs, it has the characteristics of smaller molecular weight, higher tissue permeability and durable therapeutic effect. Clinical studies and real-world evidences showed that Brolucizumab is non-inferior to aflibercept in improving visual acuity in patients with DME. And Brolucizumab is more effective in regressing intra-retinal fluid and reducing central foveal thickness(CSFT)with longer injection interval. At the same time, Brolucizumab has a low incidence of adverse events and favourable safety after intraocular injection. This article reviews the latest progress of Brolucizumab in the treatment of DME.
الملخص
Objective To systematically identify, describe, and evaluate research evidence related to exercise intervention in patients with depression through the evidence mapping method. Methods Related studies on exercise intervention for patients with depression were searched in CNKI, Wanfang Data, CBM, VIP, Web of Science, EMBASE, Cochrane library, and PubMed from inception to July, 2021. The quality of the studies was assessed using the risk of bias (RoB) tool recommended by the Cochrane Handbook Version 5.1.0 and A Measurement Tool to Assess Systematic Review-2 (AMSTAR-2). Based on World Health Organization Family International Classifications (WHO-FICs) framework, an evidence mapping framework was established, using EPPI software and Microsoft Excel 2019 tools for data extraction and coding, and using bubble charts to comprehensively present the research population, intervention categories, original research sample size, and the number of studies included in the systematic review/meta-analysis, conclusion classification and other information. Results A total of 101 randomized controlled trials and 52 systematic reviews/meta-analyses were included. The randomized controlled trials involved three types of intervention strategies with 15 different interventions, mainly including unspecified exercise intervention (28, 27.72%) and yoga intervention (19, 18.81%). The main research outcomes included b1. Global mental functions (92, 91.09%) and d9. Community, social and civic life (19, 18.81%). Among the three types of intervention strategies, rehabilitation accounted for the highest proportion, with 47 studies in total, accounting for 46.53%. The main research population was patients with other specified depression (19, 40.42%), such as patients with major depression and elderly depression. Forty-six research conclusions (97.87%) were classified as "beneficial" or "probably beneficial". In 52 systematic reviews/meta-analyses, nine interventions were involved, mainly including unspecified exercise intervention (17, 32.69%) and yoga intervention (12, 23.08%). The main study outcomes included b1. Global mental functions (41, 78.85%) and adverse reactions (12, 23.08%). Among the three types of intervention strategies, the treatment type accounted for the highest proportion, with a total of 34 studies, accounting for 65.38%. The study population was mainly patients with other specific depression (27, 79.41%), such as adult depression and pregnant women with depression, 28 (82.35%) of the research conclusions were classified as "beneficial" or " probably beneficial". At the same time, the intervention environment/background was mainly outpatient and inpatient environment. Conclusion Exercise intervention may be beneficial for patients with depression. However, the effectiveness of walking, cycling, Qigong, resistance training, and sports game interventions, the optimal intervention duration or intensity, and the adverse effects of the intervention, still need to be further explored by high-quality study in the future.