BACKGROUND:Studies have found that inhibition of tumor necrosis factor receptor-associated factor 6 improves myocardial function and promotes myocardial autophagy in sepsis,but the specific mechanism is not clear.OBJECTIVE:To explore the effect of inhibiting tumor necrosis factor receptor-associated factor 6-regulated mTORC1/ULK1 autophagy signaling pathway on myocardial injury in sepsis mice.METHODS:Thirty male Kunming mice were randomly divided into sham operation group,cecal ligation and puncture group(model group),model+tumor necrosis factor receptor-associated factor 6 specific inhibitor C25-140(model+C)group,model+C25-140+autophagy inhibitor 3-methyladenine(model+C+3-MA)group,and model+C25-140+mTORC1-specific agonist MHY1485(model+C+M)group.The cecum of mice in the sham operation group was not ligated or punctured.The mice in the other groups underwent cecum ligation and puncture to establish the mouse sepsis model.C25-140,3-methyladenine,and MHY1485 were intraperitoneally injected 0.5 hours after surgery according to the grouping.Myocardial tissue was obtained 24 hours after surgery.Hematoxylin-eosin staining was used to evaluate myocardial inflammatory lesions.Transmission electron microscopy was used to observe the changes in the autophagic bodies and mitochondrial microstructures of myocardial cells.TUNEL assay was used to detect myocardial cell apoptosis.PCR was used to detect the relative expression of tumor necrosis factor receptor-associated factor 6 mRNA.Western blot assay was used to detect the expression of related proteins.RESULTS AND CONCLUSION:(1)Compared with sham operation group,myocardial inflammatory cell infiltration and fibrous edema were observed in the model group.The mitochondria of the cells were obviously swollen,and autophagosomes were occasionally seen;cardiomyocyte apoptosis increased significantly;the expression of tumor necrosis factor receptor-associated factor 6,phosphorylated nuclear factor κB P65/P65,p-mTOR/mTOR,p-ULK1/ULK1,P62 and Bax protein increased,and the expression of Bcl2 protein decreased(P＜0.05).(2)Compared with the model group,myocardial inflammation and fibrous edema were alleviated in the model+C group.Myocardial mitochondrial swelling was reduced and autophagosomes increased;cardiomyocyte apoptosis decreased;the expression of phosphorylated nuclear factor κB P65/nuclear factor-κB P65,p-mTOR/mTOR,p-ULK1/ULK1,P62,and Bax protein decreased,while the Beclin-1 and Bcl2 protein increased(P＜0.05).(3)Compared with the model+C group,myocardial autophagosomes decreased and myocardial mitochondrial swelling was more obvious in the model+C+3-MA group.Myocardial inflammation was aggravated;myocardial cell apoptosis increased;the expression of phosphorylated nuclear factor κB P65/nuclear factor κB P65,P62,and Bax protein increased,and the Beclin-1 and Bcl2 protein decreased(P＜0.05).(4)Compared with the model+C group,the expression of p-mTOR/mTOR and p-ULK1/ULK1 in the model+C+M group increased,and the Beclin-1 and microtubule-associated protein 1 light chain 3 Ⅱ/Ⅰ protein expression decreased(P＜0.05).It is concluded that inhibition of tumor necrosis factor receptor-associated factor 6 regulates mTORC1/ULK1 autophagy signal to promote myocardial autophagy and participate in the protection of myocardial injury in sepsis.

BACKGROUND:Studies have found that inhibition of tumor necrosis factor receptor-associated factor 6 improves myocardial function and promotes myocardial autophagy in sepsis,but the specific mechanism is not clear.OBJECTIVE:To explore the effect of inhibiting tumor necrosis factor receptor-associated factor 6-regulated mTORC1/ULK1 autophagy signaling pathway on myocardial injury in sepsis mice.METHODS:Thirty male Kunming mice were randomly divided into sham operation group,cecal ligation and puncture group(model group),model+tumor necrosis factor receptor-associated factor 6 specific inhibitor C25-140(model+C)group,model+C25-140+autophagy inhibitor 3-methyladenine(model+C+3-MA)group,and model+C25-140+mTORC1-specific agonist MHY1485(model+C+M)group.The cecum of mice in the sham operation group was not ligated or punctured.The mice in the other groups underwent cecum ligation and puncture to establish the mouse sepsis model.C25-140,3-methyladenine,and MHY1485 were intraperitoneally injected 0.5 hours after surgery according to the grouping.Myocardial tissue was obtained 24 hours after surgery.Hematoxylin-eosin staining was used to evaluate myocardial inflammatory lesions.Transmission electron microscopy was used to observe the changes in the autophagic bodies and mitochondrial microstructures of myocardial cells.TUNEL assay was used to detect myocardial cell apoptosis.PCR was used to detect the relative expression of tumor necrosis factor receptor-associated factor 6 mRNA.Western blot assay was used to detect the expression of related proteins.RESULTS AND CONCLUSION:(1)Compared with sham operation group,myocardial inflammatory cell infiltration and fibrous edema were observed in the model group.The mitochondria of the cells were obviously swollen,and autophagosomes were occasionally seen;cardiomyocyte apoptosis increased significantly;the expression of tumor necrosis factor receptor-associated factor 6,phosphorylated nuclear factor κB P65/P65,p-mTOR/mTOR,p-ULK1/ULK1,P62 and Bax protein increased,and the expression of Bcl2 protein decreased(P＜0.05).(2)Compared with the model group,myocardial inflammation and fibrous edema were alleviated in the model+C group.Myocardial mitochondrial swelling was reduced and autophagosomes increased;cardiomyocyte apoptosis decreased;the expression of phosphorylated nuclear factor κB P65/nuclear factor-κB P65,p-mTOR/mTOR,p-ULK1/ULK1,P62,and Bax protein decreased,while the Beclin-1 and Bcl2 protein increased(P＜0.05).(3)Compared with the model+C group,myocardial autophagosomes decreased and myocardial mitochondrial swelling was more obvious in the model+C+3-MA group.Myocardial inflammation was aggravated;myocardial cell apoptosis increased;the expression of phosphorylated nuclear factor κB P65/nuclear factor κB P65,P62,and Bax protein increased,and the Beclin-1 and Bcl2 protein decreased(P＜0.05).(4)Compared with the model+C group,the expression of p-mTOR/mTOR and p-ULK1/ULK1 in the model+C+M group increased,and the Beclin-1 and microtubule-associated protein 1 light chain 3 Ⅱ/Ⅰ protein expression decreased(P＜0.05).It is concluded that inhibition of tumor necrosis factor receptor-associated factor 6 regulates mTORC1/ULK1 autophagy signal to promote myocardial autophagy and participate in the protection of myocardial injury in sepsis.

Objective:To investigate the safety and efficacy of pseudomonas aeruginosa Injection (PAI) in the treatment of coeliac leakage after cervical lymph node dissection for robotic thyroid cancer.Methods:Retrospective analysis of 1262 patients who underwent robotic thyroid surgery at the 960th Hospital of the People’s Liberation Army from Jan. 2021 to Aug. 2023 was made. Postoperative celiac leakage happened in 28 patients. The control and injection groups were divided according to whether pseudomonas aeruginosa injection was used or not. In the control group, there were 4 males and 11 females out of 15 patients, with an average age of (46.20±9.02) years old, and the treatment methods of low-fat diet, negative pressure suction, and pressure bandage were used. In the injection group, there were 7 males and 6 females among 13 patients, with an average age of (41.00±8.87) years. They were treated with low-fat diet, negative pressure suction, pressure bandage, and PAI .The number of lymph node dissection, total drainage volume, peak drainage volume, days of hospitalization and the rate of decline in drainage volume within 24 h after the use of PAI in the injection group, post-injection temperature, number of injections, and post-injection extubation time were statistically analyzed in both groups. Independent samples t test, Mann-Whitney U test, χ2 test or Fisher’s exact test were used for comparison between groups. Results:There was no statistically significant difference in age, gender, extent of thyroidectomy, highest daily drainage volume, and total drainage volume between the two groups ( P>0.05). The difference in the number of lymph node dissection (49.15±23.05 vs. 30.80±11.76, P=0.012) and hospitalization time (11.77±4.64 vs. 16.40±6.42, P=0.041) between the injection group and the control group was statistically significant. After the use of pseudomonas aeruginosa injection, the draining fluid decreased from the previous day (69.56± 20.82) % in the injection group; Twelve patients were successfully extubated after one injection of pseudomonas aeruginosa injection, and one patient was successfully extubated after two injections; the mean time to extubation after injection was (3.85±1.28) days; 76.9% patients (10/13) had fever symptoms within 48 h with body temperature (38.05±0.89) ℃ after injection, body temperature returned to normal after symptomatic treatment,and no other adverse reactions occurred except fever. Conclusion:Pseudomonas aeruginosa injection is safe and effective in the treatment of celiac leakage after cervical lymph node dissection for robotic thyroid cancer, effectively reducing cervical drainage and shortening hospitalization days.

Objective: To investigate the indication, feasibility, and safety of da Vinci robotic surgical system in pharyngolaryngeal tumor resection. Methods: Thirty patients were diagnosed with pharyngolaryngeal tumors and treated with a transoral robotic surgery (TORS) in Beijing Anzhen Hospital from June 1, 2016 through November 30, 2017. Inclusion criteria included lesions of the oropharynx (n=13), parapharyngeal space (n=7), larynx (n=6) and hypopharynx (n=4). Twenty cases were males and ten cases were females. The median age was 56 years old (ranging from 30 to 81 years). Results: The robotic surgeries were performed successfully on 30 patients. One patient (3.3%) underwent TORS combined with a neck incision. The mean operative time was 40.7 min. The mean blood loss was 15.8 ml. The mean recovery time for oral intake was 5.3 days. The mean hospital stay was 9 days. None of the patients underwent tracheotomy or mandible split. Postoperative pathological examination showed that 18 cases (60.0%) were malignant and 1 case (5.6%) had positive surgical margin. Sixteen cases received neck dissection. No serious complications occurred during or after the operation. There was no local recurrence, metastasis or death except for regional recurrences in 2 cases (11.1%) with a follow-up of 1 to 18 months(median 13 months). Conclusion Transoral robotic surgery is a feasible, safe and effective surgical procedure with clear operation field, rapid surgical access, minimally invasive surgery, lesser hemorrhage, good cosmetic effect and fast recovery.

Sixteen experts were invited and two-round Delphi expert consultation of admission and discharge criteria for stroke patients in home-based rehabilitation were conducted from April to October 2015.Results showed that the enthusiasm and authority degree of experts in two rounds consultation were favorable.The modified admission criteria included 8 inclusive conditions and 6 exclusive conditions.Among 8 inclusive conditions,home-based rehabilitation intervention time and NIHSS score were the necessary conditions for admission,in addition to 6 exclusion conditions.With the necessary conditions,if patients had disturbances of one or more following conditions:motor function,tactile and proprioceptive function,communication function,cognitive function,quality of life and other symptoms,they were eligible to be admitted in home-based rehabilitation in community.The discharged criteria contained two aspects:1.the conditions in admitted criteria reaching the plateau;2.the occurrence of unexpected situations,including disease worsening,deep vein thrombosis and stroke recurrence.The admission and discharged criteria developed in this study has high credibility and can be recommended for practical application in other communities in home-based rehabilitation of stroke patients,which also can be used for implementation of level-classified rehabilitation for stroke patients.

Objective To investigate the characteristics,trauma mechanism and treatment of the hyperplantarflexion ankle fracture variant.Methods Between January 2013 and June 2015,125 consecutive patients with ankle fracture received operative treatment.In 18 of them,the ankle joint had been subjected to excessive violence of plantarflexion.They were 6 males and 12 females,aged from 15 to 67 years (average,47.6 years).Their pre-operative ankle radiographs showed sagittal ankle instability and posterior ankle dislocation or subluxation.The injury was complicated with medial malleolus fracture and fibular fracture.Posterolateral approach or posterolateral and posteromedial approach was adopted to treat the patients.Lag screws and anti-glide plates were applied.Results All the 18 patients were followed up for 10 to 25 months (average,16.8 months).All their fractures healed after 11 to 16 weeks (average,13 weeks).Superficial skin necrosis occurred in one patient undergoing dual-plate fixation of the dual malleoli but responded to change of dressing 3 weeks later.No screw loosening,fixation breakage or failure,nonunion or malunion happened.Their final follow-ups showed an average American Orthopedic Foot Ankle Society score of 94.8 ponits (from 76 to 100 points),yielding 13 excellent and 5 good cases (an excellent to good rate of 100％).Conclusions The hyperplantarflextion ankle fracture variant is caused by excessive violence of planter flexion to the ankle joint,with the force on the sagittal plane going from anteriorly to posteriorly,resulting in posterior talar displacement.Its treatment should vary from that for other ankle fractures because it has its own characteristics.Appropriate treatment may lead to satisfactory outcomes.

β-Thalassemia is a global health issue, caused by mutations in the HBB gene. Among these mutations, HBB -28 (A>G) mutations is one of the three most common mutations in China and Southeast Asia patients with β-thalassemia. Correcting this mutation in human embryos may prevent the disease being passed onto future generations and cure anemia. Here we report the first study using base editor (BE) system to correct disease mutant in human embryos. Firstly, we produced a 293T cell line with an exogenous HBB -28 (A>G) mutant fragment for gRNAs and targeting efficiency evaluation. Then we collected primary skin fibroblast cells from a β-thalassemia patient with HBB -28 (A>G) homozygous mutation. Data showed that base editor could precisely correct HBB -28 (A>G) mutation in the patient's primary cells. To model homozygous mutation disease embryos, we constructed nuclear transfer embryos by fusing the lymphocyte or skin fibroblast cells with enucleated in vitro matured (IVM) oocytes. Notably, the gene correction efficiency was over 23.0% in these embryos by base editor. Although these embryos were still mosaic, the percentage of repaired blastomeres was over 20.0%. In addition, we found that base editor variants, with narrowed deamination window, could promote G-to-A conversion at HBB -28 site precisely in human embryos. Collectively, this study demonstrated the feasibility of curing genetic disease in human somatic cells and embryos by base editor system.
APOBEC-1 Deaminase ; genetics ; metabolism ; Base Sequence ; Blastomeres ; cytology ; metabolism ; CRISPR-Cas Systems ; Embryo, Mammalian ; metabolism ; pathology ; Female ; Fibroblasts ; metabolism ; pathology ; Gene Editing ; methods ; Gene Expression ; HEK293 Cells ; Heterozygote ; Homozygote ; Humans ; Point Mutation ; Primary Cell Culture ; Promoter Regions, Genetic ; Sequence Analysis, DNA ; beta-Globins ; genetics ; metabolism ; beta-Thalassemia ; genetics ; metabolism ; pathology ; therapy

Objective To discuss the efficacy of the modified subinguinal approach for the treatment of acetabular anterior column and wall fractures.Methods A clinical retrospective study was performed of the 5 patients who had been treated at our department from January 2011 to April 2015 for acetabular anterior column and wall fractures and conformed to follow-ups.They were 3 males and 2 females,aged from 19 to 45 years (mean,35.6 years).The duration from injury to surgery averaged 7.6 days (range,from 4 to 10 days).The subinguinal ligament approach was adopted in the 5 cases,through which the inguinal ligament was preserved intact after sharp dissection of its insertion at the anterior superior iliac spine and medial-upper advancement,the advantage of expanded exposure of the first window by the Farid sub-ilioinguinal approach was retained,and additional lesions due to iliac osteotomy were avoided.The operation time,intraoperative bleeding,postoperative reduction and time for fracture union were documented.Merle d' Aubigne and Postel scoring system was used to assess the hip joint function of the affected limb at the final follow-ups.Results The operation time ranged from 110 to 150 minutes (mean,125 minutes);the intraoperative bleeding ranged from 415 to 550 mL (mean,450.2 mL).By the Matta's criteria,the postoperative reduction was rated as excellent in 4 cases and good in one.The 5 patients were followed up for an average of 32.4 months (range,from 6 to 43 months).Their fractures united clinically after an average of 4.6 months (range,from 3 to 6 months).The hip joint function was rated as excellent in 2 and good in 3 by the Merle d' Aubigne and Postel scoring system at the final follow-ups.Follow-ups observed no serious complications like inguinal hernia,internal fixation failure,myositis ossificans,or avascular necrosis of the femoral head.Conclusions As the modified subinguinal approach can provide a broad surgical exposure,lead to minimal injury to the inguinal ligament,avoid lesions caused by iliac osteotomy,and decrease operation time and bleeding,it may be a better approach for acetabular anterior column and wall fractures.

Abdominal compartment syndrome (ACS) has been increasingly recognized as a cause for significant morbidity and mortality in many diseases.Great advances have been made in many researches that are dedicated to the treatment of ACS.However,in the field of orthopedics,it has still not aroused enough attention from the orthopaedic surgeons,as the occurrence and development of ACS are occult following pelvic fracture trauma.This review introduces the relevant data and researches about ACS resulting from pelvic fractures.

Objective To investigate the risk factors of electrocoagulation syndrome after endoscopic submucosal dissection (ESD) in patients with colorectal lesions.Methods Clinical data of 145 patients with colorectal mucosal lesions undergoing ESD in People's Hospital of Wuhan University between September 2010 and September 2015 were retrospectively studied.Results Among 45 patients,post endoscopic submucosal dissection electrocoagulation syndrome (PEECS) was developed in 32 cases (22％).The median age in PEECS group was higher (t =-5.783,P =0.000),the median lesion size was larger(t =-5.590,P =0.000),the median length of hospital stay was longer (t =-6.841,P =0.000) than those in non-PEECS group.Univariate regression analysis showed PEECS was associated with the age,lesion size,lesion location,length of hospital stay,malignant tumor,polyps type,resection modality.Multivariable logistic regression analysis showed that the independent risk factors for the development of electrocoagulation syndrome were age ＞65 year (OR =1.123,95％ CI:1.013-1.244,P =0.027),lesion size ＞ 3.5 cm (OR =1.173,95％ CI:1.015-1.357,P =0.031),malignant tumor (OR =3.498,95 ％ CI:1.460-8.379,P =0.005),hospital stay ＞ 10 d (OR =2.480,95％ CI:1.346-4.569,P =0.004),non-rectal lesions (OR =12.612,95％ CI:3.446-46.157,P =0.000).Conclusion Attention should be paid for colorectal lesion patients with high risk of PEECS,when endoscopic submucosal dissection is performed.