N6-Methyladenosine Methyltransferase METTL3 Alleviates Diabetes-Induced Testicular Damage through Modulating TUG1/Clusterin Axis

Background@#The present study investigated the regulatory effects of N6-methyladenosine (m6A) methyltransferase like-3 (METTL3) in diabetes-induced testicular damage. @*Methods@#In vivo diabetic mice and high glucose (HG) treated GC-1 spg cells were established. The mRNA and protein expressions were determined by real-time quantitative polymerase chain reaction, Western blot, immunofluorescence and immunohistochemistry staining. Levels of testosterone, blood glucose, cell viability, and apoptosis were detected by enzyme-linked immunosorbent assay, MTT, and flow cytometry, respectively. Molecular interactions were verified by RNA immunoprecipitation and RNA pull-down assay. Histopathological staining was performed to evaluate testicular injury. @*Results@#METTL3 and long non-coding RNA taurine up-regulated 1 (lncRNA TUG1) were downregulated in testicular tissues of diabetic mice and HG-treated GC-1 spg cells. METTL3 overexpression could reduce the blood glucose level, oxidative stress and testicular damage but enhance testosterone secretion in diabetic mouse model and HG-stimulated GC-1 spg cells. Mechanically, METTL3-mediated m6A methylation enhanced the stability of TUG1, then stabilizing the clusterin mRNA via recruiting serine and arginine rich splicing factor 1. Moreover, inhibition of TUG1/clusterin signaling markedly reversed the protective impacts of METTL3 overexpression on HG-stimulated GC-1 spg cells. @*Conclusion@#This study demonstrated that METTL3 ameliorated diabetes-induced testicular damage by upregulating the TUG1/clusterin signaling. These data further elucidate the potential regulatory mechanisms of m6A modification on diabetes-induced testicular injury.

Synovial Osteochondromatosis: Clinical Characteristics Unique to the Shoulder

Background@#Synovial osteochondromatosis (SOC) of the shoulder is a rare condition with unclear characteristics. This study evaluated the clinical features and postoperative functional outcomes of SOC of the shoulder that are distinct from SOC of other joints. @*Methods@#The characteristics of 28 shoulders with SOC that underwent arthroscopy were retrospectively assessed. Ten shoulders (35.7%) had rotator cuff tears (RCTs) and underwent concomitant arthroscopic rotator cuff repair. The mean follow-up period was 83.6 months (range, 24–154 months). Demographic characteristics and loose bodies localized under arthroscopy were compared between cases with and without concomitant RCTs. Radiography, ultrasonography, or magnetic resonance imaging were performed preoperatively and postoperatively. Visual analog scale (VAS) scores for pain and satisfaction were evaluated for all cases, and functional scores were assessed in shoulders with concomitant RCTs. @*Results@#The average age was 36.2 ± 15.6 years among patients without RCTs and 58.3 ± 7.2 years among patients with RCTs.Seven shoulders (7%) had osteoarthritis. Arthroscopy revealed loose bodies in multiple spaces, including the glenohumeral joint, subacromial (SA) space, and biceps tendon sheath. Overall, loose bodies were found in multiple spaces in 12 shoulders (42.9%). Loose bodies were found in the SA space only in 4 shoulders (22.2%) without RCTs and in 7 shoulders (70.0%) with RCTs. VAS for pain decreased significantly from 3.9 ± 2.3 to 1.1 ± 1.3 (p < 0.001). The functional scores increased significantly after arthroscopic management for patients with concurrent RCTs (all p < 0.05). Recurrence of SOC occurred in 3 of the 22 shoulders (13.6%) who underwent postoperative imaging, but no patient had a recurrent RCT. @*Conclusions@#Pain relief and patient satisfaction were achieved via arthroscopic management. Unlike in other joints, loose bodies can occur simultaneously in several spaces in the shoulder, including the glenohumeral joint, SA space, and biceps tendon sheath. Early diagnosis of SOC of the SA space can help prevent osteoarthritis and RCT progression.

Design of an anatomic plate of ulna coronoid process by 3D printing and computer software / 中华创伤骨科杂志

Objective:To design an anatomical plate of ulna coronoid process using 3D printing and computer model design software based on a collection of CT scanning data of the ulna coronoid process.Methods:The CT scans of the elbow joint with no obvious anatomic variation, no fracture, or no history of elbow operation were collected which had been taken at Trauma Center, The First Affiliated Hospital of Kunming Medical University from September 2017 to January 2022. There were 52 males and 50 females. RadiAnt DICOM Viewer and Mimics Medical 21.0 were used to visualize the CT data of the elbow joint of 102 volunteers. The software was used to measure the angle between the tip of the ulna coronoid process and the tuberosity of the ulna, the width at 1/2 height of the ulna coronoid process, the distance between the tip of the ulna coronoid process and the horizontal plane of the ulna tuberosity, and the safety angle for screw placement. After the values were measured, Siemens Ungraphics NX12.0 software was used to design the anatomical plate and the screw guide device of the ulna coronoid process. After the plate model was designed, a 1:1 actual plate model of the ulna coronoid process was produced by 3D printing. The actual plate model was placed onto an adult model of the ulna coronoid process and an adult cadaveric specimen of the ulna coronoid process to verify its matching degree. An in vitro operation was simulated using the plate model to verify its operability. Results:There were no significant differences between the left and right sides in the angle between the tip of the ulna coronoid process and the tuberosity of the ulna, the width at 1/2 height of the ulna coronoid process, the distance between the tip of the ulna coronoid process and the horizontal plane of the ulna tuberosity, or the safety angle for screw placement in either males or females ( P>0.05). There were no significant differences between males and females in the angle between the tip of the ulna coronoid process and the tuberosity of the ulna or in the safety angle for screw placement ( P>0.05). There were statistically significant differences between males and females in the width of 1/2 height of the ulna coronoid process and the distance between the tip of the ulna coronoid process and the horizontal plane of the ulna tuberosity ( P<0.05). However, the experiments on computer simulative adaptation and plate model simulative adaptation found that the anatomical plates of the ulna coronoid process designed on various parameters of males and females were exchangeable, leading to similarly good marching degrees and safe angles for screw placement. Conclusions:The anatomical plate of the ulna coronoid process designed in this study demonstrates a good fit and a safe angle for screw placement, basically achieving the goal expected to provide a basis for fabrication of a titanium alloy plate. In design of an anatomical plate of ulna coronoid process, it is not necessary to differentiate males from females or to differentiate the left side from the right one, because only a general plate can be used for both males and females and for both the left and the right sides.

Effect of Sanhuang Tangshenkang on Wnt/β-catenin Signaling Pathway in Bone Tissue of Diabetic Rats / 中国实验方剂学杂志

ObjectiveTo observe the effect of Sanhuang Tangshenkang on the Wnt/β-catenin signaling pathway in the bone tissue of diabetic rats. MethodA high-sugar and high-fat diet was administered for 4 weeks， along with intraperitoneal injection of freshly prepared 2% streptozotocin （pH 4.5） at 30 mg·kg-1 body weight to induce a diabetes model in rats. The rats with diabetes were randomly divided into model group， low- and high-dose Sanhuang Tangshenkang groups （12.8， 38.4 g·kg-1）， and Gushukang group （1.8 g·kg-1） according to the blood glucose level. Rats of the same age were fed on a regular diet and assigned to the control group. After 12 weeks of respective treatments with drugs or physiological saline， the fasting blood glucose （FBG） levels of the rats were measured using an automated biochemical analyzer. Enzyme-linked immunosorbent assay （ELISA） was used to detect fasting serum insulin （FINS）， bone-specific alkaline phosphatase （BALP）， and tartrate-resistant acid phosphatase （TRAP） levels. Micro-computed tomography （Micro-CT） was used to scan the femurs of rats to observe bone tissue microstructure and measure bone mineral density （BMD）. Hematoxylin-eosin （HE） staining and safranin O/fast green staining were performed to observe pathological changes in the femoral bone tissue. Immunohistochemistry （IHC） and Western blot were used to detect the expression of Wnt3a， low-density lipoprotein receptor-related protein 5 （LRP-5）， and β-catenin proteins. ResultCompared with the control group， the model group showed a significant increase in FBG， FINS， and TRAP levels （P<0.01）， a significant decrease in BALP level （P<0.01）， a significant decrease in BMD （P<0.01）， and disorganized， elongated， and sparse bone trabecular structures with fractures and increased lipid droplets. Additionally， the expression of Wnt3a， LRP-5， and β-catenin proteins decreased （P<0.05， P<0.01）. Compared with the model group， the low- and high-dose Sanhuang Tangshenkang groups showed a reduction in FBG and an increase in BALP （P<0.05）. The low-dose Sanhuang Tangshenkang group also exhibited a decrease in FINS （P<0.05）. All treatment groups showed a significant decrease in TRAP （P<0.01）， varying degrees of improvement in BMD （P<0.05， P<0.01））， increased and denser bone trabeculae with more regular arrangements and reduced lipid droplets， and improved bone microstructure morphology. The average optical density values of Wnt3a， LRP-5， and β-catenin proteins were significantly increased in all drug-treated groups （P<0.05， P<0.01）， and the expression of Wnt3a， LRP-5， and β-catenin proteins was elevated （P<0.05， P<0.01）. ConclusionSanhuang Tangshenkang may regulate the imbalance of the Wnt/β-catenin signaling pathway by increasing the expression of Wnt3a， LRP-5， and β-catenin proteins in bone tissue， which may promote bone formation， reduce bone resorption， and lower blood glucose levels， thereby achieving the effect of preventing and treating diabetic osteoporosis.

Clinical effect of balloon pressurized kyphoplasty for fresh single-segment vertebral compression fractures / 国际外科学杂志

Objective:To study the clinical effect of balloon compression closure kyphoplasty in the treatment of fresh single-segment vertebral compression fracture.Methods:A retrospective study was used to analyze the clinical data of 80 patients with osteoporotic vertebral compression fracture (OVCF) admitted to Gansu Provincial Hospital of Traditional Chinese Medicine from June 2019 to June 2021. They were divided into two groups according to the surgical methods: the simple percutaneous kyphoplasty (PKP) group and the percutaneous kyphoplasty compression group, with 40 patients in each group. The PKP group was routinely treated with PKP, and the PKP compression group was treated with balloon compression occlusion technology on the basis of the PKP group. The amount of bone cement injected, the leakage of bone cement, the height of the anterior edge of the injured vertebra, the Cobb angle of kyphosis, the visual analogue score (VAS) and the Oswestry dysfunction index (ODI) were compared between the two groups. The measurement data conforming to the normal distribution were expressed as ( ± s), and the comparison between the two groups was conducted by t-test; The counting data were expressed by n(%) and the comparison between the two groups adopts Chi-square or Fisher exact probability. Results:The amount of bone cement injected and the leakage rate of bone cement in the PKP compression group were significantly higher than those in the simple PKP group ( P<0.05). The height of the anterior edge of the injured vertebra in the two groups was significantly higher than that before the operation on the first day and three months after the operation ( P<0.05). The Cobb angle, VAS score and ODI index of the injured vertebra in the two groups were significantly lower than that before the operation on the first day and three months after the operation ( P<0.05). The height of the anterior edge of the injured vertebra in the PKP compression group was significantly higher than that in the PKP group ( P<0.05). The Cobb angle of kyphosis in the PKP compression group was significantly lower than that in the simple PKP group at 1 day and 3 months after operation ( P<0.05). There was no significant difference in VAS score between PKP compression group and PKP group on 1 day after operation ( P>0.05), and compared with PKP group on 3 months after operation ( P<0.05). There was no significant difference in the ODI index between the PKP compression group and the two groups 1 day and 3 months after PKP ( P>0.05). Conclusion:Balloon compression closure technology can significantly reduce the leakage of bone cement in PKP and increase the amount of bone cement injected, which is beneficial to reduce the pain of vertebral body and improve the function of OVCF patients, and can improve the clinical treatment effect, which is worth promoting.

The role of regulated cell death in renal ischemia-reperfusion injury / 生理学报

Renal ischemia-reperfusion injury (IRI) is histologically characterized by tubular cell death. Diverse pathways of regulated cell death (RCD) have been reported to contribute to renal IRI in recent studies. In this review, we discuss the signaling pathways, regulators and crosstalk of RCD, including necroptosis, ferroptosis and pyroptosis, and their role in renal IRI in order to pave the way for new therapeutic opportunities.

Ambient air pollution in the development and exacerbation of autoimmune diseases: a systematic review of literature / 中华风湿病学杂志

Objective:To systematically evaluate the role of air pollutants in the development and exacerbation of autoimmune rheumatic diseases.Methods:We followed PRISMA guidelines and searched EMBASE, Scopus, PubMed, and Cochrane Library databases using keywords and MeSH terms from inception to July 2019. Observational studies reporting the relationship between autoimmune rheumatic diseases and exposure to certain air pollutants were included. Screening of literature according to established inclusion and exclusion criteria. No meta-analysis but the qualitative analysis was conducted due to the high methodological heterogeneity.Results:A total of 24 studies were included. Rheumatoid arthritis (RA) ( n=6), anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) ( n=1), ankylosing spondylitis (AS) ( n=1), systemic lupus erythematosus (SLE) ( n=3), childhood-onset systemic lupus erythematosus (cSLE) ( n=3), juvenile idiopathic arthritis (JIA) ( n=2), Kawasaki disease (KD) ( n=4), systemic autoimmune rheumatic diseases (SARD) ( n=4). The results of the study suggested that short-term elevation in particulate matter (PM)2.5 concentration was possibly associated with an increased risk of SLE and cSLE flare-ups, disease activity of AS, JIA and SARDs exacerbation. Studies demonstrated an increased risk of RA with cumulative exposure to carbon monoxide (CO), nitrogen dioxide (NO 2), ozone (O 3), and sulfur dioxide (SO 2). Only one study demonstrated an increased risk of KD admission with elevated O 3 levels. No association was found between AAV and ambient air pollution. Conclusion:Air pollution is likely to be involved in the development and exacerbation of certain autoimmune diseases. At the same time, the mechanism of autoimmune diseases of ambient air pollutants should be actively studied, so as to promote the early prevention of cardiovascular diseases.

Centromere protein U enhances the progression of bladder cancer by promoting mitochondrial ribosomal protein s28 expression

Bladder cancer is one of the most common types of cancer. Most gene mutations related to bladder cancer are dominantly acquired gene mutations and are not inherited. Previous comparative transcriptome analysis of urinary bladder cancer and control samples has revealed a set of genes that may play a role in tumor progression. Here we set out to investigate further the expression of two candidate genes, centromere protein U (CENPU) and mitochondrial ribosomal protein s28 (MRPS28) to better understand their role in bladder cancer pathogenesis. Our results confirmed that CENPU is up-regulated in human bladder cancer tissues at mRNA and protein levels. Gain-of-function and loss-of-function studies in T24 human urinary bladder cancer cell line revealed a hierarchical relationship between CENPU and MRPS28 in the regulation of cell viability, migration and invasion activity. CENPU expression was also up-regulated in in vivo nude mice xenograft model of bladder cancer and mice overexpressing CENPU had significantly higher tumor volume. In summary, our findings identify CENPU and MRPS28 in the molecular pathogenesis of bladder cancer and suggest that CENPU enhances the progression of bladder cancer by promoting MRPS28 expression.

The value of hs-CRP and albumin ratio in predicting the prognosis of patients with in-hospital cardiac arrest / 中华急诊医学杂志

Objective:To investigate the predicting value of high sensitivity C-reactive protein (hs-CRP) and albumin (Alb) ratio on prognosis of patients with in-hospital cardiac arrest (IHCA).Methods:A total of 107 patients with IHCA and spontaneous circulation recovery (ROSC) after cardiopulmonary resuscitation (CPR) in the Affiliated Hospital of Xuzhou Medical University during January 1, 2017 and September 30, 2020 were selected as the subjects and divided into the survival group and death group according to the survival condition on day 14 after IHCA. The correlation between ratio of high sensitivity C-reactive protein/albumin (hs-CRP/Alb) and the prognosis of patients was analyzed.Results:No statistical significant differences were found between the survival and death groups in sex, age, medical history, ECG monitoring, recovery ventilation mode, percentage of first monitoring of heart rate and pre-resuscitation Alb (all P > 0.05). However, there were significant differences in the percentage of non-cardiogenic CA and adrenaline dose > 5 mg, time of CPR, concentrations of blood lactic acid, Alb, hs-CRP, and ratio of hs-CRP/Alb (all P < 0.05). Logistic regression analysis showed that percentage of adrenaline dose > 5 mg, concentration of blood lactic acid, time of CPR, and ratio of hs-CRP/Alb were independent risk factors for predicting death. ROC curve analysis showed that hs-CRP/Alb ratio, and concentration of hs-CRP and Alb had predictive value on the death of patients with IHCA; the areas under the curves of hs-CRP/Alb ratio, hs-CRP and Alb concentration were 0.876, 0.864 and 0.745, respectively. The predictive efficiency of hs-CRP/Alb ratio was better than that of hs-CRP concentration or Alb concentration. Conclusions:hs-CRP/Alb ratio has predictive value for the prognosis of patients with IHCA and the predictive value is superior to that of hs-CRP and Alb concentration.

Centromere protein U enhances the progression of bladder cancer by promoting mitochondrial ribosomal protein s28 expression

Bladder cancer is one of the most common types of cancer. Most gene mutations related to bladder cancer are dominantly acquired gene mutations and are not inherited. Previous comparative transcriptome analysis of urinary bladder cancer and control samples has revealed a set of genes that may play a role in tumor progression. Here we set out to investigate further the expression of two candidate genes, centromere protein U (CENPU) and mitochondrial ribosomal protein s28 (MRPS28) to better understand their role in bladder cancer pathogenesis. Our results confirmed that CENPU is up-regulated in human bladder cancer tissues at mRNA and protein levels. Gain-of-function and loss-of-function studies in T24 human urinary bladder cancer cell line revealed a hierarchical relationship between CENPU and MRPS28 in the regulation of cell viability, migration and invasion activity. CENPU expression was also up-regulated in in vivo nude mice xenograft model of bladder cancer and mice overexpressing CENPU had significantly higher tumor volume. In summary, our findings identify CENPU and MRPS28 in the molecular pathogenesis of bladder cancer and suggest that CENPU enhances the progression of bladder cancer by promoting MRPS28 expression.

Modified Dihuang Decoction improves ovarian reserve in mice by regulating Bcl-2-related mitochondrial apoptosis pathway / 中国中药杂志

The present study investigated the effect of Modified Dihuang Decoction in improving ovarian reserve in mice through the Bcl-2-related mitochondrial apoptosis pathway. Forty-eight adult female BALB/c mice were randomly divided into the following six groups with eight mice in each group: a blank group, a model group, a femoston group(three cycles of treatment with 0.13 mg·kg~(-1) estradiol tablets for 2 days and 1.43 mg·kg~(-1) estradiol and dydrogesterone tablets for 3 days), and high(64.74 g·kg~(-1))-, medium(43.16 g·kg~(-1))-, and low-dose(21.58 g·kg~(-1)) Modified Dihuang Decoction groups. Mice in other groups except the blank group received a single intraperitoneal injection of 12 mg·kg~(-1) cyclophosphamide and 1.2 mg·kg~(-1) busulfan to induce a model of diminished ovarian reserve(DOR), while those in the blank group received an equal volume of normal saline. Mice were treated with corresponding drugs for 15 d from the 36 th day, once per day, and the mice in the blank group and the model group were treated with an equal volume of normal saline. The general condition and oestrous cycle were observed. The serum hormone levels were detected with the enzyme-linked immunosorbent assay(ELISA). The morphological changes of ovaries were observed by HE staining. Western blot was used to detect the protein expression of cysteinyl aspartate specific proteinase-9(caspase-9), cleaved caspase-3, Bcl-2 associated X protein(Bax), Bcl-2, superoxide dismutase-2(SOD-2), and glutathione peroxidase-1(GPx-1). The mRNA expression of Bax and Bcl-2 was detected by real-time fluorescence-based quantitative polymerase chain reaction(real-time PCR). The results showed that compared with the blank group, the model group showed body weight loss, disordered oestrous cycle, elevated serum levels of follicle-stimulating hormone(FSH) and luteinizing hormone(LH), reduced serum levels of estradiol(E_2), anti-mullerian hormone(AMH), and inhibin B(INHB), the declining number of ovarian follicles and granulosa layers, increased number of atretic follicles, up-regulated protein expression of caspase-9, cleaved caspase-3, and Bax and Bax mRNA expression in ovaries, and down-regulated protein expression of Bcl-2, SOD-2 and GPx-1, and Bcl-2 mRNA expression. Compared with the model group, the Modified Dihuang Decoction groups displayed restored body weight and oestrous cycle, decreased serum levels of FSH and LH, elevated serum levels of E_2, AMH, and INHB, increased number of ovarian follicles, thickened granulosa layers, and declining number of atretic follicles. Additionally, the protein expression of caspase-9, cleaved caspase-3, and Bax, and Bax mRNA expression was down-regulated, and the protein expression of Bcl-2, SOD-2, and GPx-1, and Bcl-2 mRNA expression was up-regulated. The results suggest that Modified Dihuang Decoction can regulate endocrine hormone, promote follicle growth and improve ovarian reserve by enhancing ovarian anti-oxidant capacity, inhibiting the Bcl-2-related mitochondrial apoptosis pathway, and further inhibiting cell apoptosis.

Advances in Treatment of Transfusion-dependent Lower-risk Myelodysplastic Syndromes / 肿瘤防治研究

At present, the patients with transfusion-dependent lower-risk myelodysplastic syndromes (MDS) have limited treatment options when erythropoiesis-stimulating agent is ineffective or relapsed. With more understanding of the pathological and molecular genetics characteristics of MDS, the development of precise medical treatment of MDS has been promoted. Small-molecule inhibitors, such as transforming growth factor β inhibiter, telomerase inhibiter and hypoxia-inducible factor prolyl hydroxylase inhibitor, provide novel therapeutic strategies for patients. This article reviews the treatment of transfusion-dependent lower-risk MDS patients and discusses the latest clinical research and development of novel targeted agents.

Application of New Single-cell Analysis Technology——Cytometry by Time-of-flight in Treatment of Leukemia / 肿瘤防治研究

Cytometry by time-of-flight (CyTOF) is an innovative single-cell analysis technique combining with mass spectrometry principles and flow cytometry. In recent years, CyTOF has been widely used in the study of leukemia treatment for its advantages of multi-parameter, high-throughput, compensation without calculation and diversified data analysis. It can accurately determine intracellular element contents and analyze the changes of unique phenotype and complex signaling pathways of leukemia cells at the single-cell level, to study the mechanism of action of anti-leukemia drugs, discover the potential therapeutic targets of leukemia, assess the therapeutic response and deeply understand the mechanism of leukemia relapse and drug resistance. This article reviews the research progress of CyTOF principle, characteristics, advantages and its application in leukemia treatment.

Genetic analysis and clinical phenotype of a family with lymphedema-distichiasis syndrome / 浙江大学学报·医学版

OBJECTIVE@#To identify the genetic causes of a family with lymphedema-distichiasis syndrome (LDS).@*METHODS@#The whole exome sequencing was performed in a aborted fetus as the proband, and a candidate gene was identified. Peripheral blood of 8 family members were collected. Genotypic-phenotypic analysis were carried out through PCR amplification and Sanger sequencing.@*RESULTS@#The proband, and the mother, grandmother, uncle, granduncle of the proband all had distichiasis or varix of lower limb carried a @*CONCLUSIONS@#The

The association between the two more common genetic causes of spermatogenic failure: a 7-year retrospective study / 亚洲男科学杂志(英文版)

Chromosomal abnormalities and Y chromosome microdeletions are considered to be the two more common genetic causes of spermatogenic failure. However, the relationship between chromosomal aberrations and Y chromosome microdeletions is still unclear. This study was to investigate the incidence and characteristics of chromosomal aberrations and Y chromosome microdeletions in infertile men, and to explore whether there was a correlation between the two genetic defects of spermatogenic failure. A 7-year retrospective study was conducted on 5465 infertile men with nonobstructive azoospermia or oligozoospermia. Karyotype analysis of peripheral blood lymphocytes was performed by standard G-banding techniques. Y chromosome microdeletions were screened by multiplex PCR amplification with six specific sequence-tagged site (STS) markers. Among the 5465 infertile men analyzed, 371 (6.8%) had Y chromosome microdeletions and the prevalence of microdeletions in azoospermia was 10.5% (259/2474) and in severe oligozoospermia was 6.3% (107/1705). A total of 4003 (73.2%) infertile men underwent karyotyping; 370 (9.2%) had chromosomal abnormalities and 222 (5.5%) had chromosomal polymorphisms. Karyotype analysis was performed on 272 (73.3%) patients with Y chromosome microdeletions and 77 (28.3%) had chromosomal aberrations, all of which involved sex chromosomes but not autosomes. There was a significant difference in the frequency of chromosomal abnormalities between men with and without Y chromosome microdeletions (P< 0.05).

Mechanism of Nardostachyos Radix et Rhizoma and Corydalis Rhizoma on Atrial Fibrillation Based on Network Pharmacology / 中国实验方剂学杂志

Objective:To investigate the mechanism of Nardostachyos Radix et Rhizoma and Corydalis Rhizoma in treatment of atrial fibrillation by predicting targets and signaling pathways based on network pharmacology.Method:The traditional Chinese medicine system platform (TCMSP) database was used to screen out active components of Nardostachyos Radix et Rhizoma and Corydalis Rhizoma,predict targets,and construct the active component-predicted target network.Through the Online Mendelian Inheritance in Man (OMIM),Therapeutic Target Database (TTD),and Genecards databases,potential target information of atrial fibrillation was retrieved.STRING 11.0 database was used to obtain the protein-protein interaction data of relevant targets,and the results were visualized by Cytoscape 3.7.1 software to construct protein-protein interaction network relating to atrial fibrillation.The predicted targets of Nardostachyos Radix et Rhizoma and Corydalis Rhizoma were mapped to the potential targets of atrial fibrillation.The intersection targets were the potential targets for the treatment of atrial fibrillation with Nardostachyos Radix et Rhizoma and Corydalis Rhizoma.Then,Visualization and Integrated Discovery (DAVID),a database for annotation,was used to analyze biological functions and pathways of the potential targets of Nardostachyos Radix et Rhizoma and Corydalis Rhizoma in the treatment of atrial fibrillation.Finally,Cytoscape3.7.1 software was utilized to construct active component-potential target-signal pathway network of Nardostachyos Radix et Rhizoma and Corydalis Rhizoma in treatment of atrial fibrillation.Result:Totally 51 active components of Nardostachyos Radix et Rhizoma and Corydalis Rhizoma were screened out,and 18 potential targets for the treatment of atrial fibrillation with Nardostachyos Radix et Rhizoma and Corydalis Rhizoma were predicted.The effect was mainly correlated with the regulation of interleukin-6 (IL-6),sodium channel protein type 5 subunit alpha (SCN5A),tumor necrosis factor (TNF),nitric-oxide synthase,endothelial (NOS3),potassium voltage-gated channel subfamily hmember 2 (KCNH2),collagen alpha-1(I) chain (COL1A1),retinoic acid receptor RXR-alpha (RXRA),tissue factor (F3),alpha-1B adrenergic receptor (ADRA1B) and other target proteins,cyclic guanosine monophosphate (cGMP)/cGMP-dependent protein kinase G (PKG) signaling pathway,phosphatidylinositol-3-kinases (PI3K)/protein kinase B (Akt) signaling pathway,transcriptional disorders in cancer,calcium signaling pathways,and adrenergic signals in cardiomyocytes.Conclusion:Nardostachyos Radix et Rhizoma and Corydalis Rhizoma treat atrial fibrillation based on multiple components,multiple targets and multiple channels,and provide a scientific basis for subsequent experimental studies for further explainning its mechanism of action.

Aerobic exercise reduces the expression of pyroptosis-related proteins and inflammatory factors in hippocampus of mice with insulin resistance / 生理学报

The aim of the present study was to observe the expression of pyroptosis- and inflammation-related proteins in the hippocampus of mice with insulin resistance (IR) after aerobic exercise, and to explore the possible mechanism of exercise to improve IR. C57BL/6J male mice of 6 weeks old were randomly fed with normal diet (n = 12) and high-fat diet (HFD) (n = 26) for 12 weeks respectively. Glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed to determine whether IR occurred in HFD mice. Then the mice were randomly divided into control group (n = 12), IR group (n = 10) and IR + aerobic exercise group (AE, n = 10). Mice in AE group performed a 12-week progressive speed treadmill training after being adapted to the treadmill for one week. After the intervention, the expression of pyroptosis- and inflammation-related proteins in hippocampus was detected by Western blot. The results showed that compared with control group, NFκB, Nod-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing CARD (ASC), pyroptosis-related proteins like pro-Caspase-1, gasdermin D (GSDMD), GSDMD-N, and inflammatory factors IL-1β, IL-18 were significantly increased. The inflammasome-related protein NIMA-related kinase 7 (NEK7) and pyroptosis-related protein Caspase-1 showed an increasing trend, but there was no significant difference. Compared with the IR group, progressive speed treadmill training significantly reduced the expression of NFκB, NLRP3, NEK7, ASC, pro-Caspase-1, GSDMD, GSDMD-N, IL-1β, and IL-18 in the hippocampus of mice with IR. These results suggested 12-week progressive speed treadmill training can significantly reduce the expression of pyroptosis-related proteins and inflammatory factors in the hippocampus of mice with IR, and inhibit pyroptosis.

Expression of N-myc downstream regulated gene 2 in hippocampus of epileptic mice and its effect on glutamate and glucose uptake in astrocytes of mice / 中华行为医学与脑科学杂志

Objective:To investigate the expression of N-myc downstream regulated gene 2(NDRG2) in hippocampus of epileptic mice and its effect on glutamate and glucose uptake in astrocytes of mice.Methods:The epileptic mouse model was induced by lithium chloride and pilocarpine nitrate. The mice were sacrificed at 1 d, 7 d, 15 d and 6 weeks after model establishment and the brain tissues of hippocampus were taken. Western blot was used to detect the expression of NDRG2 protein in hippocampus.The primary astrocytes of wild-type, NDRG2 + /+ and NDRG2 -/- mice were cultured and the NDRG2 phenotype of astrocytes was identified after primary culture. Glutamate content in the supernatant of astrocyte culture was determined by glutamate assay kit and ultraviolet spectrophotometer. Flow cytometry was used to detect the positive rate of 2-NBDG fluorescently labeled astrocytes. Results:(1) Compared with the control group (0.25±0.07), the expression of NDRG2 in the hippocampus of mice increased significantly in the acute phase of epilepsy (1 d(0.45±0.06, t=-3.84, P<0.05), 7 d(0.54±0.09, t=-4.30, P<0.05), 15 d(1.04±0.06, t=-15.08, P<0.01)), and remained significantly high in the chronic phase of epilepsy( 6 weeks (1.30±0.16, t=-10.40, P<0.01)). (2) The content of residual glutamate in the supernatant fluid of primary cell culture medium was detected.It was found that the uptake of glutamate by astrocytes in the NDRG2 -/- group was significantly lower than that in the NDRG2 + /+ group ((689.03±101.78) μmol/L, (113.67±37.35) μmol/L; t=9.19, P<0.01). (3) Western blot results showed that the expression of EAAT1 protein in NDRG2 -/- primary astrocyte was significantly lower than that of NDRG2 + /+ primary astrocyte(0.34±0.03, 1.16±0.21), and the difference was statistically significant ( t=-6.59, P<0.01). (4) Flow cytometry results showed that the positive rate of astrocyte in NDRG2 -/- group cells was significantly lower than that in NDRG2 + /+ group cells ((17.60±5.72)%, (72.22±8.35)%), and the difference was statistically significant ( t=-13.22, P<0.01). Conclusion:NDGR2 is closely related to the occurrence and development of epileptic diseases. The expression of NDRG2 is beneficial to exert its physiological function of EAAT1 and promotes the uptake of glutamate and glucose by astrocyte. It may be a potential cell protective factor to promote nerve protection and repairment.

Effects of conbercept on haze formation after photorefractive keratectomy in rabbit eyes / 中华实验眼科杂志

Objective To investigate the effect of conbercept on rabbit's haze after photorefractive keratectomy (PRK).Methods Sixty-four pedigree New Zealand white rabbits were randomly divided into PRK group,normal saline solution group,conbercept 0.5 mg group,conbercept 1.0 mg group,with 16 rabbits in each group.PRK was performed on right eyes,PRK group only received PRK,the other three surgery groups were given postoperative subconjunctival injection of 0.05 ml normal saline solution,0.5 mg (0.0:5 ml) conbercept and 1.0 mg(0.10 ml) conbercept,respectively.In addition,another 8 rabbits were randomly chosen as normal control group.The healing of postoperative corneal epithelial was observed by slit lamp biomicroscope,and the degrees of haze were graded based on Fantes.Eight rabbits in the surgery groups and 4 rabbits in the normal control group were killed in the first week and the fourth week.The corneal tissue was stained by hematoxylin-eosin,and the expressions of transforming growth factor-β1 (TGF-β1),α-smooth muscle actin (α-SMA) and matrix metalloproteinase-2 (MMP-2)were detected by immunochemistry.The use and feeding of experimental animals followed the Relevant Regulations of the Animal Management Committee of Binzhou Medical University.This study protocol was approved by Ethic Committee of the Affiliated Hospital of Binzhou Medical University (No.201701-08).Results Corneal epithelium of all operative rabbits healed completely at 3-5 days and no significant difference in healing time between the groups after operation (F=0.37,P =0.77).The degree of haze in each surgery group reached the highest value at about 4 weeks after operation,and haze in the conbercept 1.0 mg group was the most serious,followed by PRK group and normal saline solution group,haze in conbercept 0.5 mg group was significantly alleviated (Fgroup =20.114,P =0.000;Ftime =8.084,P =0.006).Hematoxylin-eosin staining showed that corneal epithelial cells and fibroblasts in superficial stroma proliferated in one week after PRK,which lead to the disorder of cells and collagen fibers,and the extent of hyperplasia was the same as that of haze.Immunohistochemistry showed that at one week after operation,the expressions of factors in PRK group and normal saline solution group were apparently lower than that of conbercept 1.0 mg group,but were apparently higher than that of conbercept 0.5 mg group,and the expressions of the factors were the weakest in normal control group,with significant differences between them (all at P ＜ 0.05).Conclusions Subconjunctival injection of appropriate conbercept can inhibit the formation of haze and the proliferation of corneal epithelium and superficial stroma,but overdose of conbercept leads to opposite effects.

Study on ASI Ⅱ triggered CD4+T cells activation through regulating CD45 molecular / 国际中医中药杂志

[Absract] Objective This paper was designed to reveal the new mechanism on ASI Ⅱ triggered CD4+T cells activation via regulating CD45 molecular and provide a basis for the theoretical foundation of antitumor immunotherapy of Astragalus.Methods The CD4+T cells were randomly divided into negative group,stimulated control group,ASI Ⅱ group,CD45 inhibitor group,and the combination of ASI Ⅱ and CD45 inhibitor group.Besides negative group,the cells from other groups were activated by anti-CD3/CD28 antibody.ASI Ⅱ group was treated with 10 nmol/L ASI Ⅱ,CD45 inhibitor group was treated with 0.8 μmol/L CD45 inhibitor,and the combination group were treated with 10 nmol/L ASI Ⅱ and 0.8 iμmol/L CD45 inhibitor.After 36h culture,the proliferation of CD4+T cells was detected by Ki-67 intracellular staining assay.Cytokine production of Th1 and Th2 were examined ELISA method.The proportion of surface marker (CD44 and CD25)and Th1 intracellular cytokines (IFN-γ) were detected by flow cytometry.Results Compared with stimulated group,Astragaloside Ⅱ group in CD4+Ki67+T positive proportion (5.37％ ± 0.92％ vs.1.19％ ± 0.23％),in CD4+CD25+ positive proportion (50.23％ ± 4.65 ％ vs.15.89％ ± 1.13％),in CD4+CD44+ positive proportion (33.16％ ± 6.08％ vs.15.36％ 4 1.45％),in CD4+IFN-γ+ positive proportion (1.42％ ± 0.44 ％ vs.0.38％ ± 0.06％) were significntly increased.And the secretion of IFN-γ,IL-4 and IL-2 in ASI Ⅱ group were higher than stimulated group.The anti-mouse CD45 Ab treatment markedly blocked the proliferation and Th1 cytokines production which induced by ASI Ⅱ.Furthermore,the anti-mouse CD45 Ab treatment significantly decreased the expression of surface marker (CD44 and CD25).Conclusions Activating CD45 protein tyrosine phosphatase may be involved in ASI Ⅱ triggered CD4+T cells activation.This study will provide a basis for antitumor immunotherapy of Astragalus.