Establishment and characterization of bone marrow mesenchymal stem cell lines stably synthesizing high-level dopamine / 生物工程学报

A triple-transgenic (tyrosine hydroxylase/dopamine decarboxylase/GTP cyclohydrolase 1, TH/DDC/GCH1) bone marrow mesenchymal stem cell line (BMSCs) capable of stably synthesizing dopamine (DA) transmitters were established to provide experimental evidence for the clinical treatment of Parkinson's disease (PD) by using this cell line. The DA-BMSCs cell line that could stably synthesize and secrete DA transmitters was established by using the triple transgenic recombinant lentivirus. The triple transgenes (TH/DDC/GCH1) expression in DA-BMSCs was detected using reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, and immunofluorescence. Moreover, the secretion of DA was tested by enzyme-linked immunosorbent assay (ELISA) and high-performance liquid chromatography (HPLC). Chromosome G-banding analysis was used to detect the genetic stability of DA-BMSCs. Subsequently, the DA-BMSCs were stereotactically transplanted into the right medial forebrain bundle (MFB) of Parkinson's rat models to detect their survival and differentiation in the intracerebral microenvironment of PD rats. Apomorphine (APO)-induced rotation test was used to detect the improvement of motor dysfunction in PD rat models with cell transplantation. The TH, DDC and GCH1 were expressed stably and efficiently in the DA-BMSCs cell line, but not expressed in the normal rat BMSCs. The concentration of DA in the cell culture supernatant of the triple transgenic group (DA-BMSCs) and the LV-TH group was extremely significantly higher than that of the standard BMSCs control group (P < 0.000 1). After passage, DA-BMSCs stably produced DA. Karyotype G-banding analysis showed that the vast majority of DA-BMSCs maintained normal diploid karyotypes (94.5%). Moreover, after 4 weeks of transplantation into the brain of PD rats, DA-BMSCs significantly improved the movement disorder of PD rat models, survived in a large amount in the brain microenvironment, differentiated into TH-positive and GFAP-positive cells, and upregulated the DA level in the injured area of the brain. The triple-transgenic DA-BMSCs cell line that stably produced DA, survived in large numbers, and differentiated in the rat brain was successfully established, laying a foundation for the treatment of PD using engineered culture and transplantation of DA-BMSCs.

Visual analysis of literature on intestinal flora and bone metabolism by Citespace / 西安交通大学学报(医学版)

【Objective】 To analyze the literature on the relationship between gut microbiota and bone metabolism, identify the current research hotspots and difficulties, and provide research ideas and directions for the clinical prevention and treatment of bone metabolism related diseases. 【Methods】 Based on the Citespace literature visualization analysis software, the co-occurrence and cluster analysis of keywords and other information of the included 394 literatures were performed, and the visual map was drawn. 【Results】 Among the included literatures, the keywords such as inflammatory bowel disease, T cells, dendritic cells, short-chain fatty acids, and chronic kidney disease appeared with high frequency. The cluster of intestinal alkaline phosphatase, metabolic osteoarthritis, dendritic cells, and signaling pathway was the current research hotspot. Recent years have witnessed a rapid increase in published articles in this field, with the United States as the leading origin. 【Conclusion】 The mechanism by which gut microbiota interferes with the immune system and regulates bone metabolism to maintain bone homeostasis is still the core of current research.

Study on the influence of Barbecure combined with Epley on residual dizziness of horizontal canal benign paroxysmal positional vertigo by SRM-vertigo diagnosis system / 临床耳鼻咽喉头颈外科杂志

Objective:To investigate the influence of Barbecure combined with Epley on residual dizziness of horizontal canal benign paroxysmal positional vertigo（HC-BPPV） by SRM-vertigo diagnosis system. Methods:A total of 406 patients diagnosed with HC-BPPV from Nov 2021 to Nov 2022 were enrolled by rapid axial roll test and Dix-Hallpike in the department of Otorhinolaryngology Head and Neck Surgery, the First Affiliated Hospital of Xi'an Jiaotong University. The patients were divided into two groups by hospital card numbers, in which the numbers that were odd were considered as group A, and the numbers that were even were considered as group B. The group A underwent two circles of Barbecure repositioning procedure by SRM-vertigo diagnosis system, while the group B underwent two circles Barbecure combined with Epley repositioning procedure by SRM-vertigo diagnosis system. The treatment was stopped on the next day when two groups of patients were cured, and those who were not cured will continue treatment with the same method. Results:The cure rate of group A was 83.41%, and the cure rate of group B was 80.51%, the difference between the two groups was not-statistically significant difference（P>0.05）. The rate of residual dizziness of group A was 23.30%, the rate of residual dizziness of group B was 11.46%, the difference between the two groups was statistically significant（P<0.05）. Conclusion:The Barbecure combined with Epley otoliths repositioning maneuver by SRM-vertigo diagnosis system can significantly reduce the rate of residual dizziness after the treatment of HC-BPPV, and improve the quality of life of patients.

Research progress of the effect of "gut-immune" axis on bone homeostasis / 细胞与分子免疫学杂志

Bone homeostasis is based on the dynamic balance of bone formation and bone resorption. An imbalance in bone homeostasis is a major contributor to many skeletal diseases, including osteoporosis. Changes in the composition and diversity of the gut microbiota (GM) are supposed to have a significant impact on bone homeostasis and are closely correlated with changes in bone mass and bone microarchitecture. The "gut-immune" axis, which is formed by the interaction between the host intestinal immune system and GM, is essential for maintaining bone homeostasis, as well as regulating the body's immunological response and maintaining immune homeostasis throughout the intestine and body. The article reviews recent advances in the study of GM, the immune system, and their synergistic impact on bone homeostasis.

The influence of additional roll test on the repositioning procedure by SRM-vertigo diagnosis system for horizontal canal benign paroxysmal positional vertigo / 临床耳鼻咽喉头颈外科杂志

Objective:To evaluate the influence of an additional roll test on the repositioning procedure by SRM-vertigo diagnosis system for horizontal canal benign paroxysmal positional vertigo（HC-BPPV）. Methods:A total of 713 patients diagnosed with HC-BPPV in Department of Otolaryngology Head and Neck Surgery，the First Affiliated Hospital of Xi'an Jiaotong University from Jan 2020 to Feb 2022 were enrolled. The patients were divided into two groups by hospital card numbers, in which the number is odd were considered as group A, and the number is even were considered as group B. The group A underwent two circles of Barbecue repositioning procedure by SRM-vertigo diagnosis system, while the group B first performed an additional roll test and then underwent two circles of Barbecue repositioning procedure by SRM-vertigo diagnosis system, to observe the cure rate and compare influence of HC-BPPV by an additional roll test. The quality of life and sleep of patients before and one-month after the treatment were assessed by the dizziness handicap inventory（DHI） and the pittsburgh sleep quality（PSQI）. Results:The cure rate of group A was 63.21%, and the cure rate of group B was 87.68%，the difference between the two groups was statistically significant（P<0.05）; The DHI score of patients after the repositioning was significantly lower than that before the repositioning（P<0.05）. The PSQI score after the repositioning was significantly lower than that before the repositioning（P<0.05）. The DHI and the PSQI scores after the repositioning were significantly lower than that before the repositioning, with a statistically significant difference （P< 0.05）. The total score of DHI in group B after treatment was lower than that in group A, with a statistically significant difference（P<0.05）. The total score of PSQI in group B after treatment was lower than that in group A, with non-statistically significant difference （P< 0.05）. Conclusion:An additional roll test before the repositioning procedure by SRM-vertigo diagnosis system can significantly improve the cure rate of HC-BPPV, relieve anxiety, and improve the quality of life.

Identification of key molecules in miRNA-mRNA regulatory network associated with high-grade serous ovarian cancer recurrence using bioinformatic analysis / 南方医科大学学报

OBJECTIVE@#To investigate the correlation of the potential functional microRNA (miRNA)-mRNA regulatory network with recurrence of high-grade serous ovarian carcinoma (HGSOC) and its biological significance.@*METHODS@#This study was performed based on the data of 354 patients with HGSOC from the Cancer Genome Atlas database. In these patients, HGSOC was divided into different subtypes based on the pathways identified by GO analysis, and the correlations of the subtypes with HGSOC recurrence and differentially expressed miRNAs and mRNAs were assessed. Two relapse-related datasets were identified using the Gene Set Enrichment (GSE) database, from which the differentially expressed miRNAs were identified by intersection with the TCGA data. The target genes of these miRNAs were predicted using miRWalk 2.0 database, and these common differentially expressed miRNAs and mRNAs were used to construct the key miRNA-mRNA network associated with HGSOC recurrence. The expression of miR-506-3p and SNAI2 in two ovarian cancer cell lines was detected using RT-qPCR and Western blotting, and their targeted binding was verified using a double luciferase assay. The effect of miR-506-3p expression modulation on ovarian cancer cell migration was detected using scratch assay and Transwell assay.@*RESULTS@#We screened 303 GO terms of HGSOC-related pathways and identified two HGSOC subtypes (C1 and C2). The subtype C1 was associated with a significantly higher recurrence rate than C2. The differentially expressed genes between C1 and C2 subtypes were mainly enriched in epithelial-mesenchymal transition (EMT). Five miRNAs were identified as potential regulators of EMT, and a total of 41 target genes were found to be involved in the differential expressions of EMT pathway between C1 and C2 subtypes. The key miRNA-mRNA network associated with HGSOC recurrence was constructed based on these 5 miRNAs and 41 mRNAs. MiR-506-3p was confirmed to bind to SNAI2, and up-regulation of miR-506-3p significantly inhibited SNAI2 expression and reduced migration and invasion of SKOV3 and CAOV3 cells (P < 0.05), while miR-506-3p knockdown produced the opposite effects (P < 0.05).@*CONCLUSION@#MiR-506-3p and SNAI2 are the key molecules associated with HGSOC recurrence. MiR-506-3p may affect EMT of ovarian cancer cells by regulating cell migration and invasion via SNAI2, and its expression level has predictive value for HGSOC recurrence.

Study on the pharmacodynamic material basis of Xiangju Preparations in the treatment of rhinitis and sinusitis based on network pharmacology / 药学学报

In order to clarify the pharmacodynamic substances and mechanism of Xiangju Preparations (Xiangju Tablets, Xiangju Drops) in the treatment of rhinitis and sinusitis, the multi-level network integration analysis of "ingredients-targets-pathways" was conducted. 137 chemical constituents were identified in Xiangju Preparations by high pressure liquid chromatography-quadrupole-time of flight mass spectrometry (HPLC-QTOF/MS) for the first time. Network pharmacology analysis was performed on 59 potential active components. The results of network pharmacology analysis demonstrated that the medicinal ingredients in Xiangju Preparations included caffeic acid, senkyunolide F, rosmarinic acid, ligustilide, prim-O-glucosylcimifugin, linarin, magnolin, luteolin, senkyunolide I and gallic acid. These ingredients act on the crucial targets of tumor necrosis factor (TNF), interleukin 1B (IL1B), protein kinase B (AKT1), vascular endothelial growth factor A (VEGFA), signal transducer and activator of transcription 3 (STAT3) and participate in the regulation of advanced glycosylation end products-receptor of AGEs (AGE-RAGE), TNF, nuclear factor kappa B (NF-κB), and cyclic guanosine monophosphate-protein kinase G (cGMP-PKG) signaling pathways to effectively treat rhinitis and sinusitis. The excellent binding performance between above 10 active components and 5 key target proteins was further confirmed by molecular docking, indicating that these 10 ingredients are pharmacodynamic substances of Xiangju preparations. In conclusion, this study preliminarily clarified the effective components and mechanism of Xiangju preparations in the treatment of rhinitis and sinusitis, and provided a theoretical basis for the clinical application of Xiangju preparations.

miR-146b suppresses LPS-induced M1 macrophage polarization via inhibiting the FGL2-activated NF-κB/MAPK signaling pathway in inflammatory bowel disease

Abstract Objectives: M1 macrophage polarization and phenotype in Inflammatory Bowel Disease (IBD) are common biological responses. Method: Herein, IBD mice models were constructed and macrophages were derived. Results: It was discovered that microRNA-146b (miR-146b) was downregulated in IBD mice and Lipopolysaccharide (LPS)-induced macrophages. Moreover, the inhibitory role of overexpressed miR-146b in reducing the inflammation level and blocking M1 macrophage polarization was confirmed. Further investigation indicated that Fibrinogen Like 2 (FGL2) acted as the target gene of miR-146b, and FGL2 mediated activation of NLRP3, NF-κB-p65, and p38-MAPK. More importantly, it was validated that miR-146b could ameliorate inflammatory pheno-type and prevent M1 macrophage polarization via inhibiting FGL2 in vitro, and miR-146b overexpression alleviated the intestinal injury of IBD mice in vivo. Conclusions: Overall, it is potential to use miR-146b for the amelioration of IBD. HIGHLIGHTS miR-146b was downregulated in Inflammatory Bowel Disease (IBD) mice and LPS-induced macrophages. Fibrinogen Like 2 (FGL2) was identified as the target gene of miR-146b. miR-146b ameliorated the inflammation and blocked M1 macrophage polarization via inhibiting FGL2. miR-146b ameliorated the symptoms and pathological injury of IBD via inhibiting FGL2.

Research progress on effects of per- and polyfluoroalkyl substances on female reproductive health / 环境与职业医学

Per- and polyfluoroalkyl substances (PFASs) represent a group of organic chemicals with structures consisting of fluorinated carbon backbone in different lengths, and they are bioaccumulative and endocrine-disrupting. Humans can be exposed to PFASs through a variety of routes such as inhalation, ingestion, and dermal contact. Population studies have found that PFASs can be detected in urine, blood, and follicular fluid from females. Toxicological studies have demonstrated that PFASs can cause adverse reproductive health outcomes, including decreased fertilization and implantation rate, disturbance of reproductive hormone levels, abnormal egg cell development, and abnormal fetal absorption and fetal development. Limited epidemiological studies have also revealed that exposure to environmental levels of PFASs is related to female reproductive health, but the conclusions remain inconsistent. This study aimed to review the PFAS exposure levels and epidemiological research results from different biological samples in the female population, as well as the female reproductive toxicity and mechanisms of PFASs, and further elaborate the effects of environmental PFAS exposure on female reproduction health.

Architecture of the herpesvirus genome-packaging complex and implications for DNA translocation

Genome packaging is a fundamental process in a viral life cycle and a prime target of antiviral drugs. Herpesviruses use an ATP-driven packaging motor/terminase complex to translocate and cleave concatemeric dsDNA into procapsids but its molecular architecture and mechanism are unknown. We report atomic structures of a herpesvirus hexameric terminase complex in both the apo and ADP•BeF3-bound states. Each subunit of the hexameric ring comprises three components-the ATPase/terminase pUL15 and two regulator/fixer proteins, pUL28 and pUL33-unlike bacteriophage terminases. Distal to the nuclease domains, six ATPase domains form a central channel with conserved basic-patches conducive to DNA binding and trans-acting arginine fingers are essential to ATP hydrolysis and sequential DNA translocation. Rearrangement of the nuclease domains mediated by regulatory domains converts DNA translocation mode to cleavage mode. Our structures favor a sequential revolution model for DNA translocation and suggest mechanisms for concerted domain rearrangements leading to DNA cleavage.

Architecture of the herpesvirus genome-packaging complex and implications for DNA translocation

Genome packaging is a fundamental process in a viral life cycle and a prime target of antiviral drugs. Herpesviruses use an ATP-driven packaging motor/terminase complex to translocate and cleave concatemeric dsDNA into procapsids but its molecular architecture and mechanism are unknown. We report atomic structures of a herpesvirus hexameric terminase complex in both the apo and ADP•BeF3-bound states. Each subunit of the hexameric ring comprises three components-the ATPase/terminase pUL15 and two regulator/fixer proteins, pUL28 and pUL33-unlike bacteriophage terminases. Distal to the nuclease domains, six ATPase domains form a central channel with conserved basic-patches conducive to DNA binding and trans-acting arginine fingers are essential to ATP hydrolysis and sequential DNA translocation. Rearrangement of the nuclease domains mediated by regulatory domains converts DNA translocation mode to cleavage mode. Our structures favor a sequential revolution model for DNA translocation and suggest mechanisms for concerted domain rearrangements leading to DNA cleavage.

Inhibition of hydroxysafflor yellow A on apoptosis of endothelial cells EA.hy926 after hypoxia-reoxygenation / 中草药

Objective: To observe the effect of hydroxysafflower yellow A (HSYA) on the apoptosis of human umbilical vein endothelial cells EA.hy926 induced by hypoxia-reoxygenation. Methods: MTT colorimetry method was used to detect the effects of different hypoxia time (8, 12 h) and different reoxygenation time (4, 8, 12 h) on the cell viability. And after the cell had been in the status of hypoxia for 12 h and reoxygenation for 8 h, this method was adapted once again to evaluate the effects of different concentrations of HSYA (0.1, 1, 10, and 100 μmol/L) on cell viability in different time stages. After the cell had been in the status of hypoxia for 12 h, reoxygenation for 8 h, Western blotting was used to test its effects on the expressions of the following proteins in different time stages, which contained Bcl-2, Bax, cleaved Caspase-3, and activated cleaved Caspase-9. This method was also used to detect whether it had an improvement effect on the above proteins after the pr-treat the cells with HSYA. Real-time PCR was used to evaluate the mRNA expressions of Bax, Bcl-2 after the cell had been in the status of hypoxia for 12 h, reoxygenation for 8 h, and this method was also used to test the effect of HSYA on the expressions of Bax, Bcl-2 after the same time stages. Hoechest staining and flow cytometry were used to detect the apoptosis situation of the cell after it was in the status of hypoxia for 12 h and reoxygenation for 8 h. And this method was also adapted to detect the effect of HSYA on apoptosis of the cell after the same time stage. Results: Compared with the control group, the EA.hy926 cell viability decreased significantly after hypoxia for 8, 12 h, reoxygenation for 4, 8, and 12 h (P < 0.01). The cell viability decreased the most significantly after hypoxia for 12 h and reoxygenation for 8 h (P < 0.01), and during this period, the expression of Bax, cleaved Caspase-9, cleaved Caspase-3 protein increased significantly, and Bcl-2 protein was decreased significantly. Compared with the H/R group, HSYA (10 μmol/L) significantly increased the cell viability (P < 0.01) after hypoxia-reoxygenation, and significantly up-regulated the protein expression of Bcl-2, and down-regulated the protein expressions of Bax, cleaved Caspase-9, and cleaved Caspase-3. Conclusion: Hydroxysafflor yellow A can effectively inhibit the apoptosis of EA.hy926 induced by hypoxia and reoxygenation. The mechanism may be related to the down-regulation of Bax, cleaved Caspase-9, cleaved Caspase-3 protein as well as the up-regulation of Bcl-2 protein.

The imaging features, clinical diagnosis value of fulminant hepatic fasciola gigantica disease / 实用放射学杂志

Objective To investigate the clinical manifestations and imaging modality for the diagnosis of hepatic fasciola gigantica disease.Methods Thirty eight patients with abdominal pain were admitted in our hospital and underwent investigations with different imaging modalities.Thirty-eight cases underwent abdominal CT scan,among which 5 cases underwent follow-up with abdominal ultrasonography,10 patients with routine MRI scan and CT scan examination,and 2 cases with liver biopsy.Results Thirty-eight cases with CT scan showed the hepatomegaly,with decreased attenuation of the hepatic parenchyma,unclear boundaries.Thirteen cases showed decreased densities (suggesting hydroperitonium),including 10 cases with enhanced CT showed mild inhomogenous enhancement.Five cases with color doppler ultrasound showed inhomogenous hepatic echogenicity,and multiple liver parenchyma echogenecity showedirregular,cluttered cystic dark areas and spleenomegaly,among which two cases had evident hydroperitonium.Ten cases with MRI scan showed liver enlargement,abnormal diffuse signal of hepatic parenchymal lesions and splenomegaly.Two cases who underwent needle biopsy showed parasitic granulomas and necrosis,surrounded by a large number of monocytes andeosinophilic infiltration.Clinical manifestations:All cases were presented with fever,abdominal pain,liver tenderness,etc.Twenty-five cases presented with nausea,vomiting,loss of appetite,15 cases presented with ascites,5 cases presented with pericardial effusion,5 cases with lung parenchymal changes on CT,others showed generalised systemic edema and malena,very few patients had utricaria,itching and other symptoms.Conclusion CT and MRI scanning in patients suspected with human fasciola hepatica showed multiple small hepatic subcapsular abscess,of which some were clustered or tunnel-like.Combined with parasites,imaging manifestations are helpful for the early diagnosis.

The binding of a monoclonal antibody to the apical region of SCARB2 blocks EV71 infection

Entero virus 71 (EV71) causes hand, foot, and mouth disease (HFMD) and occasionally leads to severe neurological complications and even death. Scavenger receptor class B member 2 (SCARB2) is a functional receptor for EV71, that mediates viral attachment, internalization, and uncoating. However, the exact binding site of EV71 on SCARB2 is unknown. In this study, we generated a monoclonal antibody (mAb) that binds to human but not mouse SCARB2. It is named JL2, and it can effectively inhibit EV71 infection of target cells. Using a set of chimeras of human and mouse SCARB2, we identified that the region containing residues 77-113 of human SCARB2 contributes significantly to JL2 binding. The structure of the SCARB2-JL2 complex revealed that JL2 binds to the apical region of SCARB2 involving α-helices 2, 5, and 14. Our results provide new insights into the potential binding sites for EV71 on SCARB2 and the molecular mechanism of EV71 entry.

Pedicle screw fixation with kyphoplasty decreases the fracture risk of the treated and adjacent non-treated vertebral bodies: a finite element analysis / 华中科技大学学报（医学）（英德文版）

Adjacent vertebral fractures are common in patients with osteoporotic vertebral compression fractures (OVCFs) after kyphoplasty. This finite element study was to examine whether short segment pedicle screw fixation (PSF) with kyphoplasty may decrease the fracture risk of the treated and adjacent non-treated vertebrae after kyphoplasty for OVCFs. By simulating cement augmentation with or without short segment pedicle screw fixation (PSF), two tridimensional, anatomically detailed finite element models of the T10-L2 functional spinal junction were developed. The insertion of pedicle screws into the intact vertebra apparently decreased the stress distribution of the treated vertebra in vertical compression and other load situations. The stress distribution in the bone structures of the intact vertebra adjacent to the intact-screwed vertebra was much less than that in the one adjacent to the treated vertebra. The insertion of pedicle screws into the intact vertebra greatly decreased the maximum displacement of the cortical bones and cancellous bones of the vertebrae. Our results indicated that short segment PSF with kyphoplasty may decrease the fracture risk of the treated and adjacent non-treated vertebrae in the management of OVCFs.

A detailed criterion of BI-RADS assessment category based on US-BI-RADS: a preliminary study / 中华超声影像学杂志

Objective To set up an objective criterion for BI-RADS assessment.Methods The breast sonograms of 1 938 female cases were retrospectively studied which had been confirmed by pathology from January to September 2011 and 2012 January.1 660 cases during 2011 were model cases,and the importance of each single feature in distinguishing between benign and malignant was obtained with Chi square and OR value.A detailed criterion of BI-RADS assessment category was set up based on US-BI-RADS.Results Eighteen of 24 lexicons were statistically significant distinguished between benign and malignant breast masses(P ＜ 0.05).The lexicons were divided into major suspicious signs,middle ones and minor ones assigned 3 points,2 points and 1 point,and a scoring model was established as follows:Score =3 * (X1 + X2 + … + X6) + 2 * (X7 + X8 + … + X12) + (X9 + X10 + … + X18).Based on BI-RADS,the positive predictive value of model cases was 1.5％,6.9％,22.1％,62.5％,96.1％ followed by category 3,4A,4B,4C and 5,and it was 1.4％,3.4％,21.1％,69.4％,92.7％ in test cases.Conclusions The scoring model could be useful for BI-RADS final assessment more objectively,and could make it more convenient to predict the risk of breast cancer.