Effect of Linggui Zhugantang on Mitochondrial Fusion-fission and Sirt3/ AMPK Signaling Pathway in Chronic Heart Failure Rats After Myocardial Infarction / 中国实验方剂学杂志

ObjectiveTo investigate the effects of Linggui Zhugantang on mitochondrial fission and fusion and silencing information regulator 3（Sirt3）/adenosine monophosphate dependent protein kinase （AMPK） signaling pathway in chronic heart failure （CHF） rats after myocardial infarction （MI）. MethodSD rats randomly divide into sham operation group （normal saline ，thread only without ligature）， model group （normal saline， ligation of the left anterior descending coronary artery proximal to the heart）， Linggui Zhugantang group （4.8 g·kg-1） and Captopril group （0.002 57 g·kg-1）， with 10 rats in each group. Administere drug continuously for 28 days. Echocardiography detected cardiac function parameters. Hematoxylin eosin （HE） staining observed the pathological changes of the heart. Immunofluorescence detected the levels of reactive oxygen species （ROS）. JC-1 detect mitochondrial membrane potential. Colorimetry measure adenosine triphosphate （ATP）， superoxide dismutase （SOD）， malondialdehyde （MDA）， mitochondrial respiratory chain complex activity （Ⅰ-Ⅳ）. TdT-mediated dUTP nick end labeling （TUNEL） staining detected the apoptosis rate of myocardial tissue. Western blot detected protein expression levels of Sirt3， phosphorylated AMPK （p-AMPK）， phosphorylated dynamic-related protein 1（p-Drp1）， mitochondrial fission protein 1（Fis1）， mitochondrial fission factor （MFF）， optic atrophy protein 1（OPA1）. ResultCompared to the sham group， the left ventricular end diastolic diameter （LVIDd） and left ventricular end systolic diameter （LVIDs） were significantly increased in model group （P<0.01）， while the left ventricular short axis shortening rate （LVFS） and left ventricular ejection fraction （LVEF） were significantly decreased （P<0.01）. There were inflammatory cell infiltration and obvious pathological injury in myocardial tissue. ROS， MDA levels and myocardial cell apoptosis rate were significantly increased （P<0.01）， SOD level， ATP content， and membrane potential were significantly decreased （P<0.01）. The activity of mitochondrial respiratory chain complexes （Ⅰ-Ⅳ） was significantly decreased （P<0.01）. Levels of p-Drp1， Fis1， MFF proteins were significantly up-regulated （P<0.01）， while Sirt3， p-AMPK， OPA1 proteins level were significantly down-regulated （P<0.01）. Compared with model group， LVIDd and LVIDs were significantly decreased （P<0.01）， LVEF and LVFS were significantly increased （P<0.01）. Inflammatory cell infiltration and pathological damage of myocardial tissue were significantly relieved. ROS， MDA levels and myocardial cell apoptosis rate were significantly decreased in Linggui Zhugantang group and Captopril group （P<0.01）， SOD level， ATP content， and membrane potential significantly increased （P<0.01）. The activity of mitochondrial respiratory chain complexes （Ⅰ-Ⅳ） increased significantly （P<0.01），and p-Drp1， Fis1， MFF protein levels were significantly down-regulated （P<0.01）， Sirt3， p-AMPK， OPA1 protein were significantly up-regulated （P<0.01）. ConclusionLinggui Zhugantang can alleviate oxidative stress and apoptosis damage of myocardial cells， maintain mitochondrial function stability， and its effect may be related to mitochondrial mitosis fusion and Sirt3/AMPK signaling pathway.

Experiential Avoidance and Hyperreflexivity as Variables Associated with Depression: A Process-Based Approach

La depresión es un problema importante de salud pública que afecta a una proporción significativa de adultos jóvenes, como los estudiantes universitarios. Para su estudio se ha propuesto un enfoque basado en procesos, que busca identificar variables psicológicas transdiagnósticas que puedan ser objeto de cambio en las intervenciones psicoterapéuticas. El propósito de este trabajo fue analizar la interrelación entre un conjunto de variables de proceso (fusión cognitiva, rumia y evitación experiencial), así como examinar la relación entre cada una de estas variables y la depresión en 368 estudiantes universitarios de entre 18 y 29 años (M = 21.35, DE = 2.36, 77.7 % mujeres). Se halló que la fusión cognitiva y la rumia conformaban una variable global denominada hiperreflexividad, mientras que la evitación experiencial constituía un constructo diferente. Al analizar un modelo de ecuaciones estructurales, se encontró que solo la hiperreflexividad predecía significativamente la depresión. Se discuten estos resultados y sus posibles implicaciones para la práctica clínica. Se recomienda seguir estudiando la hiperreflexividad como una variable supraordinada de relevancia para la psicopatologia.

Depression is a major public health problem that affects a significant proportion of young adults, such as college students. A process-based approach has been proposed for its study, which seeks to identify transdiagnostic psychological variables that can be the target of change in psychotherapeutic interventions. The purpose of this paper was to analyze the interrelation between a set of process variables (cognitive fusion, rumination, and experiential avoidance), as well as to examine the relationship between each of these variables and depression in 368 college students aged 18-29 years (M = 21.35, SD = 2.36, 77.7% female). Cognitive fusion and rumination were found to comprise an overarching variable termed hyperreflexivity, while experiential avoidance constituted a different construct. By analyzing a structural equation model, it was found that only hyperreflexivity predicted depression significantly. These findings and their possible implications for clinical practice are discussed. Further study of hyperreflexivity as a superordinate variable of relevance to psychopathology is recommended.

STRN-ALK rearranged malignant peritoneal mesothelioma—Presenting with bilateral extensive pelvic masses in a young woman: Mimicking low-grade serous ovarian carcinoma

Malignant peritoneal mesothelioma (MPM) is an exceptionally rare tumor type. Although some somatic/germline genetic alterations including BAP1 loss have been identified in some cases, the molecular properties of MPMs are remained poorly understood. In recent years, anaplastic lymphoma kinase (ALK) gene rearrangement was revealed in a subset of (3.4%) MPMs. Low-grade serous carcinomas (LGSCs) are a rare subtype of ovarian carcinoma and have some morphologic and immunophenotypic overlapping features with MPMs and this may cause misdiagnosis in daily practice. Here, we report a case of 18-year-old women with STRN-ALK-rearranged MPM and no previous exposure to asbestos. This case was presented with bilateral pelvic masses and histologically was displaying pure papillary morphology with mild-to-moderate nuclear atypia, psammoma bodies, and diffuse PAX8 expression as LGSCs. With the detection of ALK alteration in some of the MPMs, a targeted treatment option has emerged for these unusual tumor types.

A rare case of sirenomelia

Sirenomelia also called mermaid syndrome is a congenital, rare, lethal, multisystemic human malformation of unknown etiology. The characteristic feature of sirenomelia is the fusion of the lower limbs, resulting in the appearance of a mermaid’s tail, and thus the name “mermaid syndrome.” This condition is also characterized by various severe urogenital abnormalities and the presence of a singular umbilical cord blood vessel, and it is more common in infants of diabetic mothers and in monozygotic twins. The incidence is around 1 in 60,000–70,000 pregnancies. The majority of affected fetuses are stillborn, whereas the rest of the live-born die in the early neonatal period due to complications of the gastrointestinal and urogenital systems. We are reporting a case of sirenomelia in a neonate born to an unregistered multipara mother. The baby had perinatal asphyxia, sirenomelia, dextrocardia, low set ears, lymphatic malformation, bilateral renal agenesis, absent external genitalia and anus, single umbilical artery, and congenital corneal clouding. There was no antenatal ultrasonography done and the baby died at 6 h of life.

Pre and Postoperative Complication of Anterior Cervical Decompression and Interbody Fusion by Stand Alone Anchored Spacer in Cervical Degenerative Disc Disease

Background: The anterior cervical decimpression and fusion (ACDF) surgery was first described by Smith and Robinson and Cloward RB in the 1950s. This procedure has since become the standard for treating degenerative cervical disc disease. Material & Methods: This Prospective Quasi-Experimental Study was conducted at the department of National Institute of Traumatology and Orthopaedic Rehabilitation (NITOR) and Dhaka Medical College Hospital, Bangladesh. The study was conducted during the period of 06 May 2019 to 05 May 2020 and 24 Patients were included by non-randomized purposive sampling according to the availability of the patient and strictly considering the inclusion and exclusion criteria. The analysis was done by SPSS 20.0 for windows software. Results: The age range of patients was 32 to 68 years, with a mean age of 51.67 (±11.15) and male-female ratio was 11:1. Occupation of the subjects demonstrates that service holder comprised the main bulk 8 (33.3%). Other occupants were farmer 6 (25.0%), businessman 4 (16.7%), driver 2 (8.3%), house wife 2 (8.3%) & manual labour 2 (8.3%). 4 (16.7%) patients had per-operative hemorrhage. There were no dural injuries or recurrent laryngeal nerve palsy. It was observed that 4 (16.7%) patients developed dysphagia, 2 (8.3%) patient had infection and 6 (25%) patients had neck pain. There was no temporay hoarseness or respiratory problems. Conclusion: The study shows that the anterior cervical decompression and interbody fusion by stand-alone anchored spacer are relatively easy, safe and an effective procedure for patients with cervical degenerative disc disease with good neurological and radiological outcome. It provides immediate stability to the affected area, reduces the risk of graft extrusion, avoids the need for extended post-operative external immobilization, and significantly shortens the rehabilitation period.

Sagittal Alignment Concepts and Spinopelvic Parameters / Conceitos de alinhamento sagital e parâmetros espinopélvicos

Abstract Spinal surgery continues to expand its horizons to care for disabled patients presenting pain and deformities. Over the past decade, our knowledge of spinal alignment, from the skull to the pelvis, has increased considerably. Such knowledge must expand to reach general orthopedists and improve the care required for so many people. Global spinal alignment is a critical concept in understanding the impact of pathological conditions (degenerative diseases, traumas, deformities) and their treatment, including spinal instrumentation and arthrodesis. Therefore, the treatment of any spinal disease must include the knowledge of the complexity of the spinopelvic alignment. At first, all parameters seem like pure mathematics, hardly applicable to the everyday life of the inattentive reader. However, it gradually becomes clear that, like everything else in orthopedics, biomechanics is an essential part of the knowledge of the musculoskeletal system, revealing the logic behind the physiology of movements. The knowledge of the sagittal alignment concepts and spinopelvic parameteres provide a better comprehension of the axial and appendicular skeletons, increasing the understanding of the physiological and adaptive spinal processes in the face of the degenerative process that increases throughout life.

Resumo A cirurgia da coluna continua a expandir seus horizontes para cuidar dos pacientes incapacitados com dor e deformidades. Desde a última década, nosso conhecimento sobre o alinhamento espinal, do crânio à pelve, aumentou consideravelmente. Portanto, faz-se necessária a expansão de tal conhecimento para o ortopedista geral, para que possamos proporcionar melhores cuidados para essa população. O alinhamento espinal global é um conceito crítico no entendimento do impacto ocasionado pela condição patológica (doença degenerativa, trauma, deformidade) e mesmo do seu tratamento, como na instrumentação e artrodese da coluna. O tratamento de qualquer doença na coluna deve incluir o entendimento da complexidade do alinhamento espinopélvico. A princípio, todos os parâmetros parecem puramente matemáticos e pouco aplicáveis à realidade do leitor mais desatento. Mas, aos poucos, fica claro que, como tudo em ortopedia, a biomecânica faz parte essencial do conhecimento do sistema musculoesquelético, tornando mais claras as lógicas da fisiologia do movimento. O conhecimento dos conceitos de alinhamento sagital e dos parâmetros espinopélvicos proporcionam uma melhor compreensão dos esqueletos axial e apendicular, além de um melhor entendimento dos processos fisiológicos e adaptativos da coluna frente ao processo degenerativo crescente que ocorre ao longo da vida.

Assessment of YME1L and mitofusin2 as a possible diagnostic and/or therapeutic target in hepatocellular carcinoma

Mitochondrial dynamics are a contraversal issue in hepatocellular carcinoma. The present study tries to illustrate the role of mitochondrial dynamics proteins (mitofusin-2 (Mfn2) and YME1L) in hepatocarcinogenesis. Five groups were used: the control group and three HCC groups (after 8, 16, and 24 weeks from DENA induction). The last group was treated with Sorafenib (SP) (10 mg/kg), via oral gavage for 4 weeks after cancer induction. This study revealed that Mfn-2 was downregulated and YME1l was overexpressed in different HCC groups. This dysregulation of mitochondrial dynamics proteins was associated with high hepatic levels of cyclin D1, MMP-9, and MDA and overexpression of ki67 as well as decreasing the hepatic expression of tissue inhibitor of matrix metalloproteinase-3 (Timp-3) and Bax. To confirm the possible role of Mfn2 and YME1L in HCC, we assessed the effect of sorafenib on these parameters and its related HCC characteristics. Sorafenib corrected the level of Mfn2 and YME1L and decreased tumor cell proliferation as well. We also elucidated that mitochondrial dynamics proteins (Mfn2 and YME1L) could be a good therapeutic target for HCC.

Establishment of leukemia cell model with inducible AML1-ETO expression and its effect on fatty acid metabolism in leukemia cells / 中华血液学杂志

Objective: To investigate the effect of the AML1-ETO (AE) fusion gene on the biological function of U937 leukemia cells by establishing a leukemia cell model that induces AE fusion gene expression. Methods: The doxycycline (Dox) -dependent expression of the AE fusion gene in the U937 cell line (U937-AE) were established using a lentivirus vector system. The Cell Counting Kit 8 methods, including the PI and sidanilide induction, were used to detect cell proliferation, cell cycle-induced differentiation assays, respectively. The effect of the AE fusion gene on the biological function of U937-AE cells was preliminarily explored using transcriptome sequencing and metabonomic sequencing. Results: ①The Dox-dependent Tet-on regulatory system was successfully constructed to regulate the stable AE fusion gene expression in U937-AE cells. ②Cell proliferation slowed down and the cell proliferation rate with AE expression (3.47±0.07) was lower than AE non-expression (3.86 ± 0.05) after inducing the AE fusion gene expression for 24 h (P<0.05). The proportion of cells in the G(0)/G(1) phase in the cell cycle increased, with AE expression [ (63.45±3.10) %) ] was higher than AE non-expression [ (41.36± 9.56) %] (P<0.05). The proportion of cells expressing CD13 and CD14 decreased with the expression of AE. The AE negative group is significantly higher than the AE positive group (P<0.05). ③The enrichment analysis of the transcriptome sequencing gene set revealed significantly enriched quiescence, nuclear factor kappa-light-chain-enhancer of activated B cells, interferon-α/γ, and other inflammatory response and immune regulation signals after AE expression. ④Disorder of fatty acid metabolism of U937-AE cells occurred under the influence of AE. The concentration of the medium and short-chain fatty acid acylcarnitine metabolites decreased in cells with AE expressing, propionyl L-carnitine, wherein those with AE expression (0.46±0.13) were lower than those with AE non-expression (1.00±0.27) (P<0.05). The metabolite concentration of some long-chain fatty acid acylcarnitine increased in cells with AE expressing tetradecanoyl carnitine, wherein those with AE expression (1.26±0.01) were higher than those with AE non-expression (1.00±0.05) (P<0.05) . Conclusion: This study successfully established a leukemia cell model that can induce AE expression. The AE expression blocked the cell cycle and inhibited cell differentiation. The gene sets related to the inflammatory reactions was significantly enriched in U937-AE cells that express AE, and fatty acid metabolism was disordered.

The clinical characteristics and treatment of "sandwich" atlantoaxial dislocation / 中华骨科杂志

Objective:To evaluate the specialty of the clinical features, treatment procedure, clinical outcome, and prognosis in the patients with "sandwich" atlantoaxial dislocation (AAD).Methods:From 2008 to 2018, 160 cases with "sandwich" AAD were retrospectively selected from the case series of AAD in Peking University Third Hospital. The case series had 80 males and 80 females. The mean age at the initial visit was 35.5±14.6 years (range, 5-77). The clinical courses, treatment methodology and prognosis were reviewed. And the surgical approach, posterior fixation segment and the recovery of neurological function were mainly summarized. The atlantodental interval (ADI), the distance by which the odontoid exceeded the Chamberlain line and the cervical-medullary angle were analyzed.Results:The most common symptoms included weakness or numbness of the limbs (67.5%, 108/160), unstable gait (30%, 48/160) and vertigo (20%, 32/160). Among all, 130 cases (81.3%, 130/160) had myelopathy, with the Japanese Orthopaedic Association (JOA) scores from 4 to 16 (mean JOA scores 13.5±2.5). Cranial neuropathy was involved in 20 cases (12.5%). Radiological findings showed brainstem and/or cervical-medullar in 130 cases (81.3%), syringomyelia in 37 cases (23.1%) and Chiari malformation in 30 cases (18.8%). Computed tomography angiography (CTA) was performed in 90 cases, which showed vertebral artery anomalies in 55 cases (61.0%) and excessive medialized internal carotid artery in 5 cases (5.6%). All cases had no spinal cord or vertebral artery injury. The surgery included posterior occipito-cervical fusion (reducible dislocation, 145 cases), and transoral release followed by posterior fusion (irreducible dislocation, 15 cases). Fifty-seven cases were treated using alternative fixation technique. The average follow-up time was 50.5±22.4 months (range, 24 to 120 months). All of 152 cases (95.0%) achieved solid atlantoaxial fusion; there was no obvious osseous fusion formation on postoperative images in 6 cases (3.8%), but no atlantoaxial instability was found on dynamic radiographs; screw loosening happened in 2 patients (1.2%). Nine patients (5.6%) suffered complications, including 4 cases with recurrent dislocation, 2 screw loosening, 2 cases with bulbar paralysis and 1 wound infection. The mean postoperative JOA was 15.1±1.8 (range, 5-17), and the mean neurological improvement rate was 42.9%±33.3% in the patients with myelopathy.Conclusion:"Sandwich" AAD, a subgroup of AAD, has unique clinical features: earlier onset age and more severe myelopathy. The incidence of bone and vascular malformation is higher. So alternative surgical plan and hybrid fixation should be prepared for this subgroup of AAD.

An analysis on the optimal match between thoracolumbar kyphosis and lower lumbar lordosis in adult spinal deformity after long-fusion surgery / 中华骨科杂志

Objective:To explore the optimal match degree between thoracolumbar kyphosis (TLK) and lower lumbar lordosis (LLL) in adult spinal deformity (ASD) after correction surgery.Methods:Data of 119 ASD patients (male: 28, female: 91), belonging to the Affiliated Hospital of Jining Medical University (19 cases), the Affiliated Hospital of Shandong University of Traditional Chinese Medicine (11 cases), and the First Medical Center of Chinese PLA General Hospital (89 cases) were reviewed and documented from March 2019 to March 2020. All patients (age, 64.48±8.88 years; range, 45-79 years) underwent the surgical procedure of thoracolumbar fusion with instrumentations were followed up over 24 months (51.68±15.60 months; range, 24-87 months) after surgery. Postoperative proximal interface failure, Oswestry disability index (ODI) score and Scoliosis Research Society-22 (SRS-22) score were recorded for all patients. The immediate match of TLK to LLL postoperatively was calculated as follows: TLM=TLK/LLL. The data of those individuals with excellent improvements in the ODI (>50%) at the final follow-up were recorded and analyzed. Then the mean value and the 95% CI of TLM in those individuals were calculated. All participants were subdivided into three groups according to the 95% CI value of TLM. After the receiver operating characteristic curve (ROC) analyzing, the area under the ROC curve (AUC) was the best cutoff value of TLM. The association of proximal junctional failure (PJF) developing with the abnormal TLM postoperatively was analyzed with logistic regression, and the odds ratio (OR) was calculated. Results:62 patients had significant improvements in ODI (>50%) at the final follow-up, and the mean TLM in those individuals was 0.41 [95% CI (0.2, 0.5)]. All patients were divided into three groups: TLM<0.2 (35 cases), 0.2≤TLM≤0.5 (48 cases) and TLM>0.5 (36 cases). The preoperative TLK (13.87°±16.61°) and T 1 pelvic angle (19.69°±10.55°) in the those patients with TLM<0.2 were the smallest, and those were the largest in those with TLM>0.5 (30.59°±16.68°, 28.30°±14.46°). The individuals with TLM<0.2 still had the smallest TLK (2.89°±1.78°), however, those with TLM>0.5 had the largest TLK (17.13°±12.13°) and the smallest LLL (-26.16°±11.02°) accordingly. Additionally, the ODI and SRS-22 for those with 0.2≤TLM≤0.5 at the final follow-up were the best ( P<0.05). ROC curve analysis results showed that the best cutoff value of TLM was 0.4 (sensitivity=78.9%, specificity=76.2%; AUC=0.802, 95% CI (0.708, 0.896) , P<0.001). During the follow-up after orthopedic surgery, there were 19 patients with postoperative proximal junction failure, including 16 patients in the mismatched group (6 patients in the TLM<0.2 group, 10 patients in the TLM>0.5 group) and 3 patients in the matched group (0.2≤TLM≤0.5 group), with the incidence of 23% (16/71) and 6% (3/48), respectively. The difference was statistically significant (χ 2=5.66, P=0.017). Thoracolumbar mismatch was significantly associated with proximal borderline failure after orthosis [ OR=4.35, 95% CI (1.196, 15.924)]. Conclusion:The abnormal correction in thoracolumbar kyphosis and lower lumbar lordosis may result in mismatch between thoracolumbar segments, which would undermine the quality of life, and increase the incidence of proximal junctional failure developing in those ASD patients underwent long-fusion surgeries. The match between TLK and LLL should be 0.2 to 0.5.

A retrospective research of combined anterior and posterior approach in total hip arthroplasty for fused/ankylosed hips / 中华骨科杂志

Objective:To investigate the safety and efficacy of a combined anterior and posterior approach in total hip arthroplasty (THA) for fused/ankylosed hip.Methods:37 patients who underwent THA for fused/ankylosed hip from January 2015 to December 2020 were retrospectively analyzed, including 28 males and 9 females, with an average age of 47.9±12.0 years (range, 26-72 years). Etiologies included 23 cases of ankylosing spondylitis, 9 cases of infectious arthritis of the hip in youth, and 5 cases of traumatic arthritis after acetabulum or femoral neck fracture. All patients underwent THA with combined anterior and posterior approach. These factors include operation time, blood loss, amount of transfused blood, blood transfusion rate, preoperative and postoperative Harris score, postoperative range of motion of the hip, and perioperative complications, etc. were evaluated. Postoperative radiography of the hip was performed to evaluate acetabular abduction angle, anterior inclination angle, the prosthesis fixation, osteolysis and heterotopic ossification around the hip.Results:A total of 37 patients were enrolled. The mean operative time was 147.6±16.8 min (range, 129-190 min); the mean estimated blood loss (EBL) was 850.0±10.8 ml (range, 600-1,200 ml); the blood transfusion rate was 59% (22/37), and the mean blood transfusion was 420±45.0 ml (range, 0-800 ml). All patients were followed up for 4.2±0.9 years (range, 1.2-7.2 years). The average abductor angle of the acetabular was 43.7°±5.4° (range, 31°-55°), and the average inclination angle was 20.9°±6.7° (range, 10°-35°); the preoperative Harris score was 47.1±9.9 (range, 40-55) and the mean Harris score at the last follow-up was 83.4±12.4 (range, 75-90). The preoperative range of motion of the hip in all directions was 0°. Postoperative hip range of motion was good, with a mean hip flexion of 95.5°±12.2° (range, 80°-110°), mean extension of 10.5°±3.4° (range, -10°-25°), and mean abduction of 38.0°±8.2° (range, 10°-50°). Postoperative complications were minor, including 2 case with poor wound healing, 2 cases with paresthesia or tingling sensation in the anterior or anterolateral thigh, which returned to normal within 3 months after surgery, and no deep infection or dislocation occurred. The acetabular cup was in poor position in 2 cases and the femoral stem was varus in 1 case, but the prosthesis was stable and no treatment was needed. All the acetabular cups and femur stems were confirmed with bone ingrowth on the last follow-up radiographs, and one patient had heterotopic ossification (Brooker grade 1). No osteolysis or wear of the acetabular liner was observed.Conclusion:Combined anterior and posterior approach (Gibson posterolateral approach + modified Hardinge approach) in THA for fusion/ankylosed hip can fully expose the operative field and sufficiently release the soft tissue, and the function of hip recovered well postopratively.

Automatic segmentation of organs at risk in head and neck carcinoma from radiation therapy using multi-scale fusion and attention based mechanisms / 中华放射肿瘤学杂志

Objective:To develop a multi-scale fusion and attention mechanism based image automatic segmentation method of organs at risk (OAR) from head and neck carcinoma radiotherapy.Methods:We proposed a new OAR segmentation method for medical images of heads and necks based on the U-Net convolution neural network. Spatial and channel squeeze excitation (csSE) attention block were combined with the U-Net, aiming to enhance the feature expression ability. We also proposed a multi-scale block in the U-Net encoding stage to supplement characteristic information. Dice similarity coefficient (DSC) and 95% Hausdorff distance (HD) were used as evaluation criteria for deep learning performance.Results:The segmentation of 22 OAR in the head and neck was performed according to the medical image computing computer assisted intervention (MICCAI) StructSeg2019 dataset. The proposed method improved the average segmentation accuracy by 3%-6% compared with existing methods. The average DSC in the segmentation of 22 OAR in the head and neck was 78.90% and the average 95%HD was 6.23 mm.Conclusion:Automatic segmentation of OAR from the head and neck CT using multi-scale fusion and attention mechanism achieves high segmentation accuracy, which is promising for enhancing the accuracy and efficiency of radiotherapy in clinical practice.

Image fusion-based recurrence patterns and dosimetry after concurrent chemoradiotherapy for thoracic esophageal squamous cell carcinoma / 中华放射医学与防护杂志

Objective:To analyze the local recurrence patterns after concurrent chemoradiotherapy (CCRT) for thoracic esophageal squamous cell carcinoma (ESCC) through image fusion, and to explore the risk factors of local recurrence and its relationships with dosimetric indices.Methods:A retrospective analysis was conducted for 209 thoracic ESCC patients who received radical CCRT in Fourth Hospital of Hebei Medical University during 2016-2019. For the patients diagnosed as the local recurrence of esophageal lesions, their CT images were fused with the original planning CT images using image registration software to identify the recurrence sites. Through 1∶1 propensity score matching (PSM) of the clinal data of patients with local recurrence (the recurrence group, nbefore = 81, nafter = 62) and those without local recurrence (the recurrence-free group, nbefore = 128, nafter=62), the dose and volume parameters of the treatment plans for the two groups were compared. Univariate and multivariate analyses were conducted using the Kaplan-Meier method and the Cox regression model to analyze the factors affecting the overall survival (OS), progression-free survival (PFS), and recurrence-free survival (RFS). Results:All patients had 1-, 3-, and 5-year OS rates of 80.9%, 42.6%, and 33.0%, respectively, 1-, 3-, and 5-year PFS rates of 67.9%, 34.0%, and 27.9%, respectively, and 1-, 3-, and 5-year RFS rates of 71.3%, 39.2%, and 30.5%, respectively. T stage, N stage, and radiation dose were independent prognostic factors for the OS, PFS, and RFS ( HR = 1.42-1.87, P < 0.05) of the patients, respectively. Among 68 patients with local recurrence, 62 cases (91.2%) suffered recurrence within the gross tumor volume (GTV). The dose and volume parameters of patients with local recurrence, such as GTV- D95%, clinical target volume (CTV)- D95%, GTV- D50%, CTV- D50%, and planning target volume (PTV)- D50%, GTV- V60, CTV- V60, and PTV- V60, were significantly lower than those of patients free from the local recurrence ( t=1.90-2.15, P < 0.05). Conclusions:Local recurrence of patients with thoracic ESCC after radical CCRT occurs mainly within the GTV. Increasing radiation doses may contribute to their survival benefits. The D50% for each target volume in the radiotherapy plan may be related to local recurrence, and it is necessary to conduct further research.

Posterior reduction for treatment of acute severe traumatic lumbar spondylolisthesis / 中华创伤骨科杂志

Objective:To evaluate the clinical effects of posterior reduction in the treatment of acute severe traumatic lumbar spondylolisthesis.Methods:A retrospective study was conducted to analyze the clinical data of 12 patients with acute severe traumatic lumbar spondylolisthesis who had been treated by posterior reduction at Department of Spinal Surgery, Zhengzhou Orthopaedic Hospital from June 2010 to December 2018. There were 7 males and 5 females with an age of (25.7±1.8) years. The spondylolisthesis was at L4 in 4 cases and at L5 in 8 cases, and grade Ⅲ in 7 cases, grade Ⅳ in 4 cases and grade Ⅴ in 1 case according to the Meyerding classification. By the American Spinal Injury Association (ASIA) grading, the preoperative neurological function was at level B in 6 cases, at level C in 4 cases, and at level D in 2 cases. All the 12 patients underwent posterior reduction and internal fixation with pedicle screws, as well as intervertebral bone graft fusion. Operation time and intraoperative blood loss were recorded. Clinical efficacy was evaluated by visual analogue scale (VAS) and Oswestry disability index (ODI) before and after surgery, and neurological function was evaluated by ASIA grading. X-ray, CT plain scan and reconstruction were used to observe internal fixation and bone grafting.Results:All patients were followed up for (18.5±2.1) months. The operation time was (165.7±42.3) min and the blood loss (497.7±75.3) mL. The VAS pain scores [(2.7±0.3) points and (1.8±0.2) points] and ODIs (18.2%±2.3% and 14.5%±2.6%) at 2 weeks after operation and at the last follow-up were significantly lower than the preoperational values [(8.5±0.6) points and 72.3%±12.3%] ( P<0.05), but there was no statistically significant difference between 2 weeks after operation and the last follow-up ( P>0.05). At the last follow-up, X-rays and CT scans showed good fixation and adequate bone grafting; the spondylolisthesis was grade 0 in 10 cases and grade I in 2 cases; the ASIA level of neurological function was C in 2 cases, D in 3 cases, and E in 7 cases. Healing of surgical incision was delayed in 2 patients but responded to symptomatic treatment. Follow-ups observed no such complications as loosening or pulling out of internal fixation. Conclusion:In the treatment of acute severe traumatic lumbar spondylolisthesis, posterior reduction can effectively restore the spondylolisthesis sequence and restore spinal stability, leading to satisfactory curative outcomes.

Risk factors for adjacent vertebral compression fracture after fusion surgery of lumbar canal stenosis in the elderly / 中华创伤杂志

Objective:To evaluate the risk factors for adjacent vertebral compression fracture (AVCF) after fusion surgery of lumbar canal stenosis in the elderly.Methods:A retrospective cohort study was designed for 297 patients with lumbar canal stenosis who underwent fusion surgery in Hubei Provincial Hospital of Integrated Chinese and Western Medicine from January 2017 to December 2020. There were 42 males and 255 females, aged 68-85 years [(76.3±7.2)years]. The patients were divided into AVCF group ( n=67) and non-AVCF group ( n=230) according to with or without the occurrence of AVCF. The indicators recorded were the gender, age, body mass index, education level, number of combined basic diseases, course of the disease, preoperative bone mineral density, intraoperative bleeding volume, number of level fused during operation, postoperative blood transfusion volume, postoperative observation in the ICU, types of postoperative external fixation and time of external fixation. Univariate analysis was conducted to analyze the correlation between above risk factors and AVCF after fusion surgery of lumbar canal stenosis in the elderly. Multivariate Logistic regression analysis was used to determine the independent risk factors for the occurrence of AVCF in these patients. Results:In the univariate analysis, age, education level, preoperative bone mineral density, intraoperative bleeding volume, postoperative blood transfusion volume and postoperative observation in the ICU were correlated with AVCF after fusion surgery of lumbar canal stenosis in the elderly ( P<0.05 or 0.01), while there was no correlation of AVCF with gender, body mass index, number of combined basic diseases, course of the disease, number of level fused during operation, types of postoperative external fixation and time of external fixation (all P>0.05). Multivariate Logistic regression analysis showed that gender ( OR=4.02, 95% CI 1.35, 12.00, P<0.05), preoperative bone mineral density≤-2.5 SD ( OR=2.01, 95% CI 1.47, 2.75, P<0.01), intraoperative bleeding volume≥475 ml ( OR=1.01, 95% CI 1.00, 1.01, P<0.01) and postoperative blood transfusion volume≥434 ml ( OR=0.99, 95% CI 0.98, 1.00, P<0.01) were significantly associated with AVCF after fusion surgery of lumbar canal stenosis in the elderly. Conclusion:The female, bone mineral density≤-2.5 SD, intraoperative bleeding volume≥476 ml and postoperative blood transfusion volume≥434 ml are independent risk factors for AVCF after fusion surgery of lumbar canal stenosis in the elderly.

Clinical efficacy analysis of DELTA endoscopic lumbar interbody fusion for the treatment of lumbar spondylolisthesis / 中国医师杂志

Objective:To explore the clinical efficacy of DELTA endoscopic lumbar interbody fusion for the treatment of mild to moderate, single segment lumbar spondylolisthesis.Methods:A retrospective analysis was conducted on the clinical data of 48 surgical cases of grade Ⅰ to Ⅱ lumbar spondylolisthesis admitted to the First Affiliated Hospital of Hunan University of Traditional Chinese Medicine from February 2020 to March 2022. Among them, 24 cases treated with DELTA endoscopic lumbar interbody fusion surgery were classified as the DELTA group, and 24 cases treated with traditional minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) surgery were classified as the MIS-TLIF group. Two groups of patients were compared in terms of perioperative indicators (surgical time, postoperative drainage volume, incision length, hospital stay), clinical efficacy [Visual Analogue Scale (VAS) score for low back and leg pain, lumbar Japanese Orthopaedic Association Scores (JOA), improved MacNab standard excellence rate], and lumbar fusion rate (Bridwell intervertebral fusion grade).Results:The DELTA group had longer surgical time than the MIS-TLIF group, and the postoperative drainage volume, incision length, and hospital stay were all lower than the MIS-TLIF group, with statistically significant differences (all P<0.05). The VAS score of lower back and leg pain and lumbar JOA score of the two groups of patients at 1 week, 3 months, and the last follow-up were significantly improved compared to those before surgery (all P<0.01), and the DELTA group had better VAS score of lower back and leg pain and lumbar JOA score at all time points after surgery than the MIS-TLIF group, with statistically significant differences (all P<0.05). The improved MacNab standard was used to evaluate the efficacy of the two groups of patients at the last follow-up after surgery, and there was no statistically significant difference in the excellent and good rates ( P>0.05); There was no statistically significant difference ( P>0.05) in the fusion rate between the two groups. Conclusions:DELTA endoscopic lumbar interbody fusion has a significant therapeutic effect on lumbar spondylolisthesis, with the advantages of small surgical incision and fast recovery; After crossing the DELTA endoscopic learning curve and optimizing surgical procedures, this technology can become an alternative to MIS-TLIF technology.

Construction, identification and expression of recombinant Schistosoma japonicum vaccine mediated by Enterococcus faecalis / 中华地方病学杂志

Objective:To construct a recombinant vaccine of Schistosoma japonicum (Sj) mediated by Enterococcus faecalis (Efs, rEfs-Sj26GST vaccine), and to study the expression of Sj26GST-GST fusion protein in the recombinant vaccine. Methods:The recombinant plasmid pGEX-Sj26GST was transformed into the susceptible strain Efs ATCC47077 by electroporation to construct rEfs-Sj26GST vaccine, and the plasmid was extracted for PCR identification. After induction of expression with isopropyl-beta-D-thiogalactopyranoside (IPTG), the products were analyzed and identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot.Results:After PCR identification, a 676 bp fragment was amplified, which was consistent with the length of Sj26GST amplification fragment. SDS-PAGE analysis showed that the relative molecular mass was 52 × 10 3, which was consistent with the band of Sj26GST-GST fusion protein. Western blot results showed that the Sj26GST-GST fusion protein expressed by rEfs-Sj26GST vaccine could be specifically recognized by the serum of Sj infected patients. Conclusion:The rEfs-Sj26GST vaccine is successfully constructed, and the Sj26GST-GST fusion protein expressed by recombinant vaccine can be specifically recognized by the serum of Sj infected patients.

PKM2-mediated neuronal hyperglycolysis enhances the risk of Parkinson's disease in diabetic rats / 药物分析学报

Epidemiological and animal studies indicate that pre-existing diabetes increases the risk of Parkinson's disease(PD).However,the mechanisms underlying this association remain unclear.In the present study,we found that high glucose(HG)levels in the cerebrospinal fluid(CSF)of diabetic rats might enhance the effect of a subthreshold dose of the neurotoxin 6-hydroxydopamine(6-OHDA)on the development of motor disorders,and the damage to the nigrostriatal dopaminergic neuronal pathway.In vitro,HG promoted the 6-OHDA-induced apoptosis in PC12 cells differentiated to neurons with nerve growth factor(NGF)(NGF-PC12).Metabolomics showed that HG promoted hyperglycolysis in neurons and impaired tricarboxylic acid cycle(TCA cycle)activity,which was closely related to abnormal mito-chondrial fusion,thus resulting in mitochondrial loss.Interestingly,HG-induced upregulation of pyruvate kinase M2(PKM2)combined with 6-OHDA exposure not only mediated glycolysis but also promoted abnormal mitochondrial fusion by upregulating the expression of MFN2 in NGF-PC12 cells.In addition,we found that PKM2 knockdown rescued the abnormal mitochondrial fusion and cell apoptosis induced by HG+6-OHDA.Furthermore,we found that shikonin(SK),an inhibitor of PKM2,restored the mito-chondrial number,promoted TCA cycle activity,reversed hyperglycolysis,enhanced the tolerance of cultured neurons to 6-OHDA,and reduced the risk of PD in diabetic rats.Overall,our results indicate that diabetes promotes hyperglycolysis and abnormal mitochondrial fusion in neurons through the upre-gulation of PKM2,leading to an increase in the vulnerability of dopaminergic neurons to 6-OHDA.Thus,the inhibition of PKM2 and restoration of mitochondrial metabolic homeostasis/pathways may prevent the occurrence and development of diabetic PD.

Eukaryotic expression and biological activity identification of fusion protein ABD-Fc-IL-2 / 中国生物制品学杂志

@#Objective To express the fusion protein ABD-Fc-IL-2 in eukaryotic cells and detect its biological activity. Methods The target gene SP-ABD-Fc-IL-2 was amplified by direct and overlapping PCR,and then ligated to vector pcDNA3. 1(+).The obtained recombinant plasmid pcDNA3. 1/SP-ABD-Fc-IL-2 was transiently transfected into CHO-S cells to express the fusion protein ABD-Fc-IL-2,which was purified by Protein A beads affinity chromatography. The specificity of the purified fusion protein was detected by Western blot,the biological activity was detected by CTLL-2/MTT cell proliferation colourimetry,and the interaction between ABD fragment and human serum albumin(HSA)was detected by pull down/Western blot. Results The recombinant plasmid pcDNA3. 1/SP-ABD-Fc-IL-2 was constructed correctly as identified by restriction analysis and sequencing. The purified fusion protein ABD-Fc-IL-2 showed a purity of 90% and bound specifically to mouse anti-IL-2 monoclonal antibody with the biological activity of 3. 29 × 108IU/mL. The ABD of fusion protein and HSA bound to each other. Conclusion The eukaryotic fusion protein ABD-Fc-IL-2 had high biological activity,which promoted the proliferation of CTLL-2 cells and maintained the binding ability of ABD fragment to HSA.

Optimization of glycosylation type of recombinant human growth hormone-Fc fusion protein expressed in CHO cells / 中国生物制品学杂志

@#Objective To optimize the expression of recombinant human growth hormone-Fc(rhGH-Fc)fusion protein in CHO cells in order to obtain better glycosylation ratio and lower content of highmannose.Methods CHO cells expressing rhGH-Fc were cultured in a 7 L bioreactor.The glycosylation modifications of rhGH-Fc were adjusted by improving the composition of feeding media(using three commercial media:Gly-1:EX-CELL Glycosylation Adjust,Gly-2:SHEFF-CHO PLUS PG ACF and Gly-3:EfficientFeed C + AGT Supplement & GlycanTune C + Total Feed),and the glycosylation type and proportion of the target proteins were analyzed by mass spectrometry.Results The G0F(main glycosylation types:G0,G1 and G2;F:fucose)of Gly-1,Gly-2 and Gly-3 were 32.89%,58.66% and 33.28%,the G1F were 31.39%,18.03%and 34.90%,and the G2F were 31.39%,18.03% and 34.90%,respectively.Gly-1 and Gly-3 made the target protein contain less G0F while more G2F;Gly-3 feeding scheme-showed less high mannose modification than the other two schemes.Conclusion Gly-1 medium changed the glycosylation modification from G0F to G1F and G2F,while Gly-2 medium changed that from G2F and G1F to G0F.However,Gly-3 medium changed the glycosylation modification from G0F to G1F and G2F,and the contentof high mannose was less than 5%,which may have a better effect on modifying glycosylation type and proportion of the target protein.