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.

Blood Loss Control in Patients with Idiopathic Scoliosis Undergoing Spinal Fusion: Prospective Evaluation of a Cohort / Controle de sangramento em pacientes com escoliose idiopática submetidos a artrodese da coluna: Avaliação prospectiva de uma coorte de pacientes

Abstract Objective This study aimed to identify risk factors for increased perioperative bleeding in scoliosis surgery. Methods This is a prospective cohort study including 30 patients with idiopathic scoliosis undergoing posterior instrumentation using the pedicle screw system at a university hospital. Results Intraoperative blood losses totaled 798.6 ± 340 mL (24.8% of blood volume). Nine subjects presented massive blood loss. On average, hemoglobin dropped by 3.7g/dL, and each patient received 1.4 blood bags. Postoperative blood loss was 693.4±331.1 mL, and the total number of days using a drain was 2.7±0.7. Intraoperatively, the following variables showed significant correlations (p<0.05) with increased bleeding: age, time from diagnosis to treatment, preoperative Cobb angle, amount of curve correction, number of instrumented and fixated levels, total number of screws, and the number of transfused bags. Postoperatively, the following variables had significant correlations (p < 0.05): age, preoperative Cobb angle, length of hospital stay, number of blood bags transfused, and number of levels fixated with screws. Conclusion The variables most contributing to blood loss were age, preoperative Cobb angle, number of blood bags transfused, and number of levels fixated with a screw. Therefore, patients may benefit from surgical treatment while younger and

Resumo Objetivo O objetivo deste estudo é identificar os fatores de risco para o aumento de sangramento perioperatório em cirurgias para tratamento de escoliose. Métodos Estudo de coorte prospectivo incluindo 30 pacientes com escoliose idiopática submetidos à instrumentação posterior com o uso do sistema de parafusos pediculares em um hospital universitário. Resultados As perdas sanguíneas intraoperatórias totalizaram 798,6 ml ±340 ml (24,8% do volume sanguíneo). Houve perda maciça de sangue em 9 pacientes. Em média, a hemoglobina caiu 3,7 g/dl e foram transfundidas 1,4 bolsas de sangue por paciente. A perda sanguínea pós-operatória foi de 693,4 ml ± 331,1ml, e o total de dias utilizando dreno foi 2,7 ± 0,7. No intraoperatório, as seguintes variáveis apresentaram correlações significativas (p < 0,05) com o aumento do sangramento: idade, intervalo entre diagnóstico e tratamento, Cobb pré-operatório, quantidade de correção da curva, número de níveis instrumentados e fixados, número total de parafusos e o número de bolsas transfundidas. No pós-operatório, as seguintes variáveis apresentaram relação (p<0,05): idade, Cobb pré-operatório, tempo de internação, quantidade de bolsas de sangue transfundidas e o número de níveis fixados com parafuso. Conclusão As variáveis que mais contribuíram para a perda sanguínea foram idade, Cobb pré-operatório, quantidade de bolsas de sangue transfundidas e número de níveis fixados com parafuso. Portanto, os pacientes podem se beneficiar do tratamento cirúrgico

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.

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.

Mechanism of disordered subcellular localization of TFE3 fusion protein in TFE3 translocation renal cell carcinoma / 现代泌尿外科杂志

【Objective】 To investigate the effects of the loss of exon 1 of TFE3 on nuclear localization of chimeric TFE3 protein in TFE3 translocation renal cell carcinoma (TFE3 tRCC). 【Methods】 The localization of TFE3 protein in TFE3 tRCC and clear cell renal cell carcinoma (ccRCC) were detected with immunochemistry. The exon retention of TFE3 gene in TFE3 tRCC was analyzed in databases and literatures. The plasmids containing TFE3 full-length and different-length of TFE3 exons which were constructed to pCDH-MCS-EGFP-Puro were transfected into HEK293T using Lipo FiterTM. The localization of EGFP protein in HEK293T cells were detected with confocal microscopy. The localization of TFE3 protein and truncated TFE3 protein were detected with Western blotting. The mRNA expression of the downstream genes of TFE3 protein were detected with q-PCR. 【Results】 Strong nuclear signal of TFE3 protein was observed in TFE3 tRCC, whereas TFE3 protein in ccRCC was mainly localized in cytoplasm. The results of fluorescence imaging and Western blotting showed that TFE3 full-length protein was expressed both in nucleus and cytoplasm, and the expression of truncated TFE3 protein was mainly localized in nucleus. The q-PCR analysis demonstrated that the deletion of exon 1 in TFE3 gene led to a higher transcriptional level of targeted genes of TFE3 protein. 【Conclusion】 The loss of exon 1 in TFE3 played a critical role in preventing TFE3 protein from entering the nucleus. In TFE3 tRCC, the loss of exon 1 in TFE3 gene leads to the nuclear localization of TFE3 fusion protein and activation of its downstream target genes. This mechanism promises to uncover the occurrence and development of TFE3 tRCC.

Penetration ability and biological activity of fusion protein PTD4-Cu, Zn-SOD in human astrocytes in vitro by immunofluorescence test / 西安交通大学学报(医学版)

【Objective】 To observe the penetration and biological activity of PTD4-Cu, Zn-SOD into human astrocytes and whether it can mitigate hypoxia damages. 【Methods】 ①Immunohistochemistry and fluorescence test: We labeled the Cu, Zn-SOD by a monoclonal antibody, combined it with the fluorescent secondary antibody labeled with fluorescein isothiocyanate (FITC) to observe the effect of transduced PTD4-Cu, Zn-SOD on the viability of human astrocytes. ② The experimental group: After hypoxic damage model, the cells were divided into three groups: blank control, group Cu, Zn-SOD, and group PTD4-Cu, Zn-SOD. Group blank was added with DMEM medium (excluding serum) as control; DMEM medium was added to the other two for one hour (excluding serum) with its fusion proteins (Cu, Zn-SOD and PTD4 -Cu, Zn-SOD) with the final concentration of 2 μmoL/L. After the intervention, we used SOD and MDA test kits to observe PTD4-Cu, Zn-SOD and Cu, Zn-SOD in astrocytes after fusion protein intervention. 【Results】 The PTD4-Cu, Zn-SOD fusion protein could have aggregation distribution in the nucleus by FITC fluorescently labeled. After the intervention, it could increase the SOD activity in astrocytes in group PTD4-Cu, Zn-SOD and group Cu, Zn-SOD compared with control group, but the SOD activity was more obvious in the fusion proteins PTD4-Cu, Zn-SOD group. And the dose of MDA was reduced in group PTD4-Cu, Zn-SOD compared with group Cu, Zn-SOD and control group. 【Conclusion】 PTD4-Cu, Zn-SOD fusion protein can transcellular membrane of human astrocytes. The fusion protein PTD4-Cu, Zn-SOD can increase the SOD activity and reduce the content of MDA by human astrocytes from hypoxia injury.

FBDD and drugs originated from FBDD / 药学学报

The binding of small molecule drugs to targets is mostly through non-covalent bonds, and hydrogen bond, electrostatic, hydrophobic and van der Waals interactions function to maintain the binding force. The more these binding factors lead to strong bindings and high activities. However, it is often accompanied by the increase of molecular size, resulting in pharmacokinetic problems such as membrane penetration and absorption, as well as metabolism, which ultimately affects the drug success. Fragment-based drug discovery (FBDD) is to screen high-quality fragment library to find hits. Combine with structural biology, FBDD generates lead compounds by means of fragment growth, linking and fusion, and finally drug candidates by the optimization operation. During the value chain FBDD is closely related to structure-based drug discovery (SBDD). In this paper, the principle of FBDD is briefly described by several launched drugs.

Research progress of multimodal medical image fusion methods / 中国辐射卫生

In the current clinical diagnosis, medical images have become an important basis for diagnosis, and different modes of medical images provide different tissue information and functional information. Single-mode images can only provide single diagnostic information, by which difficult and complicated diseases cannot be diagnosed, and comprehensive and accurate diagnostic results can be obtained only with the help of multiple diagnostic information. The multimodal fusion technology fuses multiple modes of medical images into single-mode images, and thus the single-mode images contain complementary information between multiple modes of images, so that sufficient information for clinical diagnosis can be obtained in a single image. In this paper, the multimodal medical image fusion methods are sorted into two types, namely the traditional fusion method and the fusion method based on deep learning.