Correlation between macrophage chemotaxis and disease severity in patients with knee osteoarthritis / 中国骨伤

OBJECTIVE@#To investigate the enhancement of macrophage chemotaxis in patients with knee osteoarthritis (KOA) and its correlation with the disease severity.@*METHODS@#Eighty patients with KOA admitted from July 2019 to June 2022 were enrolled as the observation group and divided into 29 cases of moderate group, 30 cases of severe group and 21 cases of extremely severe group. At the same time, 30 healthy subjects were included as the control group. The gene expressions of NF-κB, CXC chemokine receptor 7 (CXCR7) and CXC chemokine ligand 12 (CXCL12) in macrophages of each group were analyzed. Visual analogue scale(VAS) was used to evaluate the degree of joint pain. Joint function was evaluated by knee Joint Society Scoring system(KSS). Finally, data analysis was carried out.@*RESULTS@#The expression levels of NF-κB, CXCR7 and CXCL12 in moderate group, severe group and extreme recombination group were higher than those in control group. The VAS, the expression of NF-κB, CXCR7 and CXCL12 in the severe group and the extreme recombination group were higher than those in the moderate group, whereas KSS was lower than that in the moderate group. The VAS, expression levels of NF-κB, CXCR7 and CXCL12 in the extremely severe group were higher than those in the severe group, and KSS was lower than that in the severe group (all P<0.01). The expression levels of NF-κB, CXCR7 and CXCL12 in macrophages were positively correlated with VAS score, but negatively correlated with KSS(all P<0.01). The expression levels of NF-κB, CXCR7 and CXCL12 in macrophages were positively correlated with the severity of disease. After excluding the influence of traditional factors (gender, age and disease duration), multiple linear regression analysis further showed that the expression levels of NF-κB, CXCR7 and CXCL12 were still positively correlated with the severity of disease(all P<0.01).@*CONCLUSION@#The chemotaxis of macrophages in patients with KOA increased with the aggravation of the disease, and was related to the degree of pain and function impairment.

Experience in the handover of manned space medical rescue support / 中华急诊医学杂志

To analyze how the handover were effected by the conditions of manned spaceflight medical support mission through the practice of medical equipment and drugs in Shenzhou-12 and Shenzhou-13 manned spaceflight medical rescue support missions, this article discussed the preparation, organization and implementation in the handover of medical equipment and drugs in the changing of medical rescue teams, summarized the notices in the work of handover, and provided experience for the smooth handover of different manned spaceflight medical rescue teams in the future.

Experience of medical rescue support and nursing in space station mission / 中华急诊医学杂志

Objective:To explore the characteristics and nursing measures of medical rescue support in space station.Methods:According to the characteristics of medical rescue support task of manned space mission, practical nursing schemes and corresponding nursing measures were formulated from the aspects of personnel selection, personnel training, material preparation, process formulation, training exercise and epidemic prevention.Results:The "Shenzhou-12" mission includes the whole launch phase, operation phase and return phase. There are many tasks that cover a long time. The contents of medical rescue support include personnel's physical and mental quality, technical ability, environmental equipment, the possible injuries of astronauts, and the normalization of COVID-19's task guarantee. In view of this content, a practical nursing scheme was formulated to enable nurses to quickly master and skillfully cooperate with the treatment, win more time for the treatment and improve the overall rescue level.Conclusions:Various process plans have been integrated and optimized for medical rescue support of space mission. The equipment carried is advanced, and can be used in various complex environments and complex working conditions. The rescue support personnel have also done their best, kept improving and solidified the state. We should constantly sum up experience, explore and study new problems, and make new achievements in medical rescue support for space missions.

Research on the emergency surgery risks of medical support and coping strategies for taikonauts of Shenzhou-12 astronauts / 中华急诊医学杂志

Objective:This study aims to analyze the characteristics and basic principles of emergency surgery risks and anesthesia care of medical support at the landing site for China’s taikonauts of the Shenzhou-12, and to summarize China’s experience in medical support at the landing site for manned spaceflight, and ensure supports in special environments such as an emergency return of manned spaceflight.Methods:This study was carried out through literature research on relevant reports on the emergency surgery risks and aids of domestic and foreign astronauts at the landing sites, and summaries of the experience in medical support for taikonauts of spacecrafts from Shenzhou-5 to Shenzhou-11 at the landing sites. At the same time, according to the characteristics of Shenzhou-12 such as the long on-orbit time, the adjustment in the landing area, the optimization of the mission mode, and new search and rescue power, a series of organization, pre-arranged planning, equipment allocation, and effective anesthesia treatment plan were proposed and inspected in practice.Results:Based on the original anesthesia care plan of medical support, the first-aid carrier was adjusted and modified, the first-aid procedure was optimized, a new generation of supraglottic airway opening tool, video laryngoscope, portable ultrasound, and other devices were added, and the anesthesia care plan at the landing site for manned spaceflight was formulated to provide strong support for the medical care of taikonauts that had stayed in the outer space for a long time.Conclusions:Upon the targeted improvement and process optimization, the anesthesia care plan of medical support for taikonauts of Shenzhen-12 in the landing area fully meets the anesthesia requirement of medical support in special environments such as the emergency return of the taikonauts that have stayed in the outer space for a long time under the new orbital altitude.

Metagenomic data-analysis reveals enrichment of lipopolysaccharide synthesis in the gut microbiota of atrial fibrillation patients / 中华心血管病杂志

Objective: To investigate the functional changes of key gut microbiota (GM) that produce lipopolysaccharide (LPS) in atrial fibrillation (AF) patients and to explore their potential role in the pathogenesis of AF. Methods: This was a prospective cross-sectional study. Patients with AF admitted to Beijing Chaoyang Hospital of Capital Medical University were enrolled from March 2016 to December 2018. Subjects with matched genetic backgrounds undergoing physical examination during the same period were selected as controls. Clinical baseline data and fecal samples were collected. Bacterial DNA was extracted and metagenomic sequencing was performed by using Illumina Novaseq. Based on metagenomic data, the relative abundances of KEGG Orthology (KO), enzymatic genes and species that harbored enzymatic genes were acquired. The key features were selected via the least absolute shrinkage and selection operator (LASSO) analysis. The role of GM-derived LPS biosynthetic feature in the development of AF was assessed by receiver operating characteristic (ROC) curve, partial least squares structural equation modeling (PLS-SEM) and logistic regression analysis. Results: Fifty nonvalvular AF patients (mean age: 66.0 (57.0, 71.3), 32 males(64%)) were enrolled as AF group. Fifty individuals (mean age 55.0 (50.5, 57.5), 41 males(82%)) were recruited as controls. Compared with the controls, AF patients showed a marked difference in the GM genes underlying LPS-biosynthesis, including 20 potential LPS-synthesis KO, 7 LPS-biosynthesis enzymatic genes and 89 species that were assigned as taxa harbored nine LPS-enzymatic genes. LASSO regression analysis showed that 5 KO, 3 enzymatic genes and 9 species could be selected to construct the KO, enzyme and species scoring system. Genes enriched in AF group included 2 KO (K02851 and K00972), 3 enzymatic genes (LpxH, LpxC and LpxK) and 7 species (Intestinibacter bartlettii、Ruminococcus sp. JC304、Coprococcus catus、uncultured Eubacterium sp.、Eubacterium sp. CAG:251、Anaerostipes hadrus、Dorea longicatena). ROC curve analysis revealed the predictive capacity of differential GM-derived LPS signatures to distinguish AF patients in terms of above KO, enzymatic and species scores: area under curve (AUC)=0.957, 95%CI: 0.918-0.995, AUC=0.940, 95%CI 0.889-0.991, AUC=0.972, 95%CI 0.948-0.997. PLS-SEM showed that changes in lipopolysaccharide-producing bacteria could be involved in the pathogenesis of AF. The key KO mediated 35.17% of the total effect of key bacteria on AF. After incorporating the clinical factors of AF, the KO score was positively associated with the significantly increased risk of AF (OR<0.001, 95%CI:<0.001-0.021, P<0.001). Conclusion: Microbes involved in LPS synthesis are enriched in the gut of AF patients, accompanied with up-regulated LPS synthesis function by encoding the LPS-enzymatic biosynthesis gene.

Evaluation of microvascular flow imaging combined with high-frequency ultrasonography in children with haemophilic arthropathy A / 中华实用儿科临床杂志

Objective:To explore the application of microvascular flow imaging (MVFI) combined with high-frequency ultrasonography in children with haemophilic arthropathy A (HAA).Methods:Retrospective study.A total of 82 children diagnosed with HAA in the First Affiliated Hospital of Zhengzhou University from October 2018 to October 2020 were recruited.The elbow, knee and ankle joints of each child were examined by high-frequency ultrasonography.The numbers of thickened synovial joints were recorded.Blood flow signals of the thickening of synovial joints was checked by the MVFI and power Doppler ultrasound (PDUS), respectively.Color flow signals were graded by the semi-quantitative scoring systems.The chi- square test and independent multi-group ordinal multi-category rank-sum test were used to compare the differences of MVFI and PDUS in the display of thickened synovial blood flow. Results:A total of 254 joints were involved in 82 children with HAA, including synovial hypertrophy in 188 joints, hydrops articuli in 146 joints, fibrotic septa in 66 joints, cartilage damage in 63 joints, haemosider indeposition in 45 joints, bone erosion in 25 joints, osteophytes in 15 joints and bone remodeling in 8 joints.Grade Ⅱ synovial thickened joints were the most common.The proportion of blood flow signals detected by PDUS in thickened synovial membranes was significantly higher than that detected MVFI (52.66% vs.70.21%, χ2=12.225, P<0.05). Numbers of grade 0 and Ⅰ joints with thickened synovial membranes detected by MVFI were less than those of PDUS, while the opposite result was obtained in detecting grade Ⅱ and Ⅲ joints ( H=21.158, P<0.05). Compared with PDUS, MVFI more sensitively visualized the blood flow of the thickened synovial membrane. Conclusions:MVFI can more prominently detect the thickened synovial blood flow in children with HAA.A combined application of MVFI and high-frequency ultrasonography contributes to the evaluation of children with HAA.

Application of event-related potential in Alzheimer's disease and mild cognitive impairment / 中华行为医学与脑科学杂志

Alzheimer's disease (AD) is one of the major diseases that harmful to healthy elderly, and mild cognitive impairment (MCI) is the early clinical stage of AD. There is a lag in the clinical diagnosis of both diseases. An objective and reliable auxiliary diagnostic method is urgently needed to provide early diagnosis and differential indicators for AD and MCI, to predict the probability of individuals suffering from AD and MCI transforming into AD, and to reduce the overall incidence of AD and reduce the huge medical and economic burden for the country and society. Event-related potential is widely used in AD and MCI, and the resolution at the millisecond level can truly reflect the time course of cognitive processing and the degree of impairment of cognitive function in patients. In this study, we investigated the differences in the amplitude and latency of ERP components in healthy elderly, MCI and AD patients, and the correlation between ERP components and cognitive impairment. Early N170 and P200 showed high sensitivity and specificity in differentiating MCI from healthy elderly or MCI from AD. The late perception-related ERPs also showed high sensitivity and specificity in differentiating healthy elderly from MCI/AD. The differences in ERPs between MCI and AD may be related to the etiology, the degree of disease progression and the site of brain damage. The specific brain mechanism still need to be further explored and will be the focus of future research. With the progress of the research, the relationship between the specific ERP manifestations and the mechanism of brain injury as well as the impairment of cognitive function will be more clear. It is believed that the application of ERP in clinical will bring more benefits to AD and its early clinical MCI.

Isolation of Fusarium and identification of its toxins from tuberous root of Pseudostellaria heterophylla / 中国中药杂志

Fusarium is the major pathogen of root rot of Pseudostellaria heterophylla. This study aims to explain the possible distribution of Fusarium species and the contamination of its toxin-chemotypes in tuberous root of P. heterophylla. A total of 89 strains of fungi were isolated from the tuberous root of P. heterophylla. Among them, 29 strains were identified as Fusarium by ITS2 sequence, accounting for 32.5%. They were identified as five species of F. avenaceum, F. tricinctum, F. fujikuroi, F. oxysporum, and F. graminearum based on β-Tubulin and EF-1α genes. LC-MS/MS detected 18, 1, and 5 strains able to produce ZEN, DON, and T2, which accounted for 62.1%, 3.4%, and 17.2%, respectively. Strain JK3-3 can produce ZEN, DON, and T2, while strains BH1-4-1, BH6-5, and BH16-2 can produce ZEN and T2. PCR detected six key synthase genes of Tri1, Tri7, Tri8, Tri13, PKS14, and PKS13 in strain JK3-3, which synthesized three toxins of ZEN, DON, and T2. Four key synthase genes of Tri8, Tri13, PKS14, and PKS13 were detected in strains BH1-4-1, BH6-5, and BH16-2, which were responsible for the synthesis of ZEN and T2. The results showed that the key genes of toxin biosynthesis were highly correlated with the toxins produced by Fusarium, and the biosynthesis of toxin was strictly controlled by the genetic information of the strain. This study provides a data basis for the targeted prevention and control of exo-genous mycotoxins in P. heterophylla and a possibility for the development of PCR for rapid detection of toxin contamination.

A study on the correlation between semantic distance and cognitive function in schizophrenia / 中华行为医学与脑科学杂志

Objective:To investigate the relationship between lexical semantic processing abnormalities and cognitive function and clinical symptoms in schizophrenia based on the activation diffusion model and semantic distance.Methods:All subjects matched with demographic data were randomly divided into experiment group( n=27) and control group( n=30). The semantic distance of words of different semantic categories and lexical categories were assigned at a level of 1-7.The semantic distance between the two groups was analyzed by repeated measures of variance, and the correlation analysis was conducted on the scores of the MATRICS Consensus Cognitive Battery (MCCB) and positive and negative syndrome scale (PANSS) in the experimental group. Results:The main effects of the groups in semantic distance were statistically significant( F(1, 55)=7.460, P=0.008, ηp2=0.981). The semantic distance in the experimental group (3.672±0.105)was lower than that in the control group (4.068±0.100). The main effect of the semantic category was statistically significant( F(1, 55)= 833.37, P<0.01, ηp2=0.938), and the semantic distance in the relative condition (1.965±0.074) was lower than that in the unrelative condition(5.775±0.117). Under the relative condition, concrete semantic deviation was negatively correlated with the total score of MCCB( r=-0.405, P=0.036)and speech learning ( r=-0.569, P=0.002). Abstract semantic deviation was negatively correlated with speech learning( r=-0.429, P=0.026). Under the unrelative condition, concrete semantic deviation was negatively correlated with MCCB total score ( r=-0.597, P=0.001), speech learning( r=-0.399, P=0.039)and other dimensions.Abstract semantic deviation was negatively correlated with MCCB total score( r=-0.593, P=0.001) and speech learning( r=-0.285, P=0.050). Under the relative condition, the abstract semantic deviation was positively correlated with the general symptom scale score( r=0.448, P=0.019). Under the unrelative condition, abstract vocabulary semantic deviation was positively correlated with PANSS total score( r=0.120, P=0.010), negative scale score( r=0.047, P=0.030) and general symptom scale score ( r=0.306, P=0.010). Conclusion:The semantic distance of lexical processing is abnormal in schizophrenia. The semantic deviation is related to the cognitive function index and symptom index.

miR-133b inhibits myocardial ischemia-reperfusion-induced cardiomyocyte apoptosis and accumulation of reactive oxygen species in rats by targeting YES1 / 南方医科大学学报

OBJECTIVE@#To investigate the effect of miR-133b on cardiomyocyte apoptosis induced by myocardial ischemia-reperfusion (I/R) and explore the mechanism.@*METHODS@#Thirty-six adult SD rats were randomized into sham-operated group, I/R group, AdmiR-NC group and AdmiR-133b group, and rat models of myocardial I/R were established in the latter 3 groups with myocardial injections of saline or recombinant adenoviruses in the left ventricle. The expression of MiR-133b was detected using RT-qPCR, and cardiac function of the rats was determined using FDP 1 HRV and BRS analysis system. Serum CK-MB and cTnI levels were determined by ELISA, myocardial injury was evaluated with HE staining, cardiomocyte apoptosis was detected by flow cytometry, and ROS content was determined using a DCFH-DA probe. In the in vitro experiment, H9C2 myocardial cells with hypoxia/reoxygenation (H/R) treatment were transfected with Mir-NC or MiR-133b mimic, and the cellular expression of MiR-133b, cell apoptosis, and ROS content were determined. Dual luciferase reporter assay was performed to verify the targeting relationship between miR-133b and YES1. The effects of pc-YES1 or miR-133b mimic transfection on YES1 expression, apoptosis, and ROS content in H9C2 cells were evaluated.@*RESULTS@#Compared with those in I/R group, miR-133b expression was obviously up-regulated, LVEDP, cTnI and CK-MB levels were significantly decreased, and LVSP, +dp/dt, -dp/dt, HR and CF levels were increased in admiR-133b group (@*CONCLUSIONS@#miR-133b can inhibit I/R-induced myocardial cell apoptosis and ROS accumulation by targeting YES1 to reduce myocardial I/R injury in rats.

Clinical significance of sinus heart rate turbulence in aged patients with stable angina pectoris / 心血管康复医学杂志

Objective:To explore clinical significance of sinus heart rate turbulence (HRT) phenomenon in aged pa‐tients with stable angina pectoris (SAP) .Methods :A total of 120 aged SAP patients ,who received 24h DCG in our hospital from Jan 2013 to Oct 2015 ,were selected as SAP group .Meanwhile ,another 144 aged patients ,who re‐ceived 24h DCG examination simultaneously and coronary angiography results were normal ,were regarded as nor‐mal control group .According to coronary lesion severity ,SAP group was further divided into single vessel coronary disease group (single vessel group ,n=35) ,double‐vessel coronary disease group (double‐vessel group ,n=48) and multi‐vessel coronary disease group (multi‐vessel group ,n=37) .The 24h DCG ,HRT indexes ,including turbulence onset (TO) and turbulence slope (TS) ,were measured and compared among all groups .Results:Compared with normal control group ,there was significant rise in TO [(0.77 ± 0.37)% vs .(1.26 ± 0.92)% ] and significant reduc‐tion in TS [(5.45 ± 4.02) ms/RR interval vs .(1.53 ± 0.70) ms/RR interval] ,P<0.01 both ;significant rise in ab‐normal rates of TO (19.44% vs .42.50% ) ,TS (15.97% vs .31.67% ) and TO + TS (11.11% vs .30.83% ) in SAP group ,P<0.01 all .Compared with single vessel group ,there was significant rise in TO [(0.66 ± 0.22)% vs .(1.28 ± 1.11)% vs .(1.46 ± 1.20)% ] and significant reduction in TS [ (2.04 ± 0.82) ms/RR interval vs .(1.66 ± 0.38) ms/RR interval vs .(1.29 ± 0.58) ms/RR interval] in double‐vessel group and multi‐vessel group ,and TO of multi‐vessel group was significantly higher than that of double‐vessel group ,TS of multi‐vessel group was significantly low‐er than that of double‐vessel group , P<0.01 all .Conclusion:Sinus heart rate turbulence can be used as risk predic‐tor for aged patients with stable angina pectoris ,which can provide basis for clinical effective treatment and progno‐sis assessment .

High-throughput sequencing for analysis of structural change of intestinal microbiota in patients with colorectal adenoma / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the taxonomic richness and diversity of gut microbiota in patients with colorectal adenoma and elucidate the role of gut microorganisms in precancerous lesions in the colon and rectum.</p><p><b>METHOD</b>Adenomatous tissues from 31 patients with colorectal adenoma and normal intestinal mucosal tissues from 20 healthy control subjects were collected through colonoscopy. The total bacterial genomic DNA was extracted, and the V-Vhypervariable region in bacterial 16S rRNA gene was amplified using polymerase chain reaction and sequenced on an Illumina MiSeq platform.</p><p><b>RESULTS</b>Patients with colorectal adenomas had a higher alpha diversity and richness indices compared to the healthy controls (P<0.01). The mucosal microbiota in colorectal adenoma tissue showed a distinctive structural difference from that in normal intestinal mucosal tissues. At the phylum level, a large decrease in Firmicutes with concomitant relative expansion of Proteobacteria was observed in patients with colorectal adenomas, resulting in a significant decrease in the Firmicutes/Bacteroidetes ratio (P<0.01). At the genus level, Lactococcus and Pseudomonas were enriched whereas Enterococcus, Bacillus, and Solibacillus were reduced obviously in the preneoplastic tissues (P<0.01). We also found a similar gut microbiome composition between low-grade and high-grade intraepithelial neoplasia; the ratio of Escherichia-Shigella tended to increase in high-grade intraepithelial neoplasia, but this change was not statistically significant (P%0.28).</p><p><b>CONCLUSION</b>Significant changes in the structure of the intestinal flora occur in patients with colorectal adenomas, indicating that the association of dysbiosis of the gut microbiota with the occurrence of a pro-oncogenic microenvironment.</p>

Research Progress of Trx/TXNIP in Stroke / 现代生物医学进展

Cerebral apoplexy is one of the main causes of death in the middle-aged and elderly population,which has higher mortality and disability rate.The incidence of the disease is increasing year by year and it is a serious threat to human life and health.Therefore,it is of great significance to find an effective target for the diagnosis and treatment of stroke.Thioredoxin (Trx) is the major thiol reducing agent in the cells,it is involved in many signal transduction pathways in the cells by regulating the redox state of the cell.It has disulphide reductase activity,which can reduce the oxidative stress injury in the rats after the stroke.Thioredoxin interacting protein (TXNIP) is an endogenous inhibitor of Trx,it can destroy the redox balance and promote the oxidative stress by binding/inhibiting the activity of Trx,while the inhibition or knockdown of TXNIP has obvious neuroprotective effects.Recent studies suggest that Trx/TXNIP may be involved in the pathophysiology of cerebral apoplexy by a variety of pathways.This article analyses the research status of Trx/TXNIP and studies the localization of Trx system in the central nervous system and the progress of Trx system in ischemic cerebral apoplexy.It reviews the mechanism of Trx/TXNIP in cerebral apoplexy and prospectes the signaling pathways involved in the pathophysiological process of Trx/TXNIP to provide new ideas for the treatment of cerebral apoplexy.

Effects of Embolization and Clipping Therapy on Cognitive Function in Patients with Intracranial Aneurysms / 现代生物医学进展

Objective:To evaluate the effects of endovascular embolization and microsurgical clipping on cognitive function in patients with intracranial aneurysm.Methods:A total of 80 patients with intracranial aneurysms,who were treated in Chongqing Hospital of Traditional Chinese Medicine from March 2014 to September 2015,were selected and randomly divided into control group(n=40) and experimental group (n=40).The control group was treated with microsurgical clipping,and the experimental group,with endovascular embolization.The postoperative cognitive function was assessed by the mini mental state examination scale (MMSE),and length of stay,in-hospital mortality rate,mortality rate in 1 year and the incidence of postoperative adverse reactions were compared between the two groups.Results:The total score (26.78± 0.85) of MMSE in the experimental group was higher than that (22.25± 0.63) of the control group (P＜0.05).The cognitive dysfunction rate (37.50％) of the experimental group was lower than that (55.00％) of the control group (P＜0.05).The length of stay [(6.7± 3.9) days] of the experimental group was lower than that [(9.6± 4.5) days] of the control group(P＜0.05).There were no significant differences in in-hospital mortality rate and mortality rate in 1 year,and the incidence of adverse reactions between the two groups (P＞0.05).Conclusion:Endovascular interventional therapy can improve the cognitive function of the patients with intracranial aneurysms and shorten the length of hospital stay.

Effect of deoxycholic acid intervention on growth of ileum organoids derived from C57BL/6 mice / 南方医科大学学报

<p><b>OBJECTIVE</b>To establish a culture system for mouse intestinal organoids and investigate the effect of deoxycholic acid (DCA) on organoids growth.</p><p><b>METHODS</b>The terminal ileum was collected from 8-month-old C57BL<6 mice. The tissue blocks were treated with EDTA and the crypts were collected and embedded in Matrigel Matrix. Orgnoids growth and buddings were observed in the control group, anhydrous alcohol group, short-term (2 days) 100 µmol<L DCA treatment group, and long-term (10 days) 10 µmol<L DCA treatment group; the orgnoids were further cultured for 10 days after removal of DCA from the medium and observed for orgnoids growth and buddings.</p><p><b>RESULTS</b>Short-term treatment with high-concentration DCA resulted in significantly reduced enterosphere formation, enteroids formation, progression from enterospheres to enteroids and number of crypt buds per enteroid (P<0.05), which remained unchanged even after removal of DCA for a short time (P<0.05); long after DCA removal, the enteroids formation rate and number of the crypt buds still remained lower than those in normal organoids (P<0.05). Short-term treatment with low-concentration DCA only resulted in reduced enteroids formation rate and number of crypt buds (P<0.05), and prolonged treatment caused reduced enterospheres formation rate, enteroids formation rate and number of crypt buds (P<0.05). After DCA removal, enteroids formation rate and the number of crypt buds still remained lower than those in the normal group (P<0.05).</p><p><b>CONCLUSION</b>We successfully established an organoids culture system. The presence of DCA in the culture system affects the growth of the organoids, which can partly recover following a prolonged period after the removal of DCA.</p>

Effects of uranium dust on collagen synthesis in lung fibroblasts / 中国职业医学

OBJECTIVE: To observe the effects and mechanism of uranium dust on collagen synthesis in fibroblastic cells.METHODS: i) RAW264. 7 macrophages were divided into solvent-control group and dust-affected group,and then treated with 0 and 120 mg / L( final concentration) uranium dust suspension for 0,2,4,8,16,24 and 32 hours. The supernatants of cells from these two groups were collected,and transforming growth factor beta 1( TGF-β1) levels were measured by enzyme-linked immunosorbent assay( ELISA). The best time phase was defined,and the supernatant of RAW264. 7 macrophages culture were separated as the conditioned medium( CM) for subsequent experiments. ii) Normal mouse lung fibroblasts L929 cells were divided into control group and uranium dust group,and treated with the CM of solvent-control group and dust-affected group respectively. After cultivated for 0,6,12,18,24,30 and 36 hours,the expression of α-smooth muscle actin( α-SMA) in L929 cells was detected by immunocytochemistry. The levels of extrac ellular collagen type Ⅰ( Col Ⅰ),collagen type Ⅲ( Col Ⅲ) and hydroxyproline( HYP) were detected by ELISA.RESULTS: i) The level of TGF-β1 in RAW264. 7 macrophages supernatant of the dust-affected group was higher than that of the solvent-control group after treatment with uranium dust for 4 hours,and showed an increasing trend with increasing time during 4-24 hours( P < 0. 05). The peak value was in 24 hours. The best time phase was 24 hours and used for CM of the two groups in subsequent experiments. ii) Compared with the control group at the same time points, the α-SMA expressions of L929 cells in uranium dust group increased after treatment with CM for 18-36 hours( P < 0. 05),the levels of Col Ⅰ,Col Ⅲ and HYP in uranium dust group increased after treatment with CM for 12-36 hours( P < 0. 05); both the expression of α-SMA and levels of Col Ⅲ and HYP increased with increasing time,showing a time-effect relationship( P <0. 05). CONCLUSION: Uranium dust can induce macrophages to secret TGF-β1 and affect fibroblast,increase α-SMAexpression,and increase the Col Ⅰ,Col Ⅲ and HYP synthesis. These might be the important mechanisms of lung fibrosis.

Current approaches to the configurational assignment of marine natural products / 国际药学研究杂志

Marine natural products are a significant and important source for new small molecule drug leads. In most cases, marine natural products have unique structure skeletons and stereo complexity. Their absolute configurations and biologically activities are closely related, which highlights the importance of absolute configurational assignment. The stereo-configurational evaluation of marine natural products is one of the most difficulties in determining natural structure, and also very important contents of natural products research. In this review we summarized a variety of cases with different structural types that often dictate some valuable approach to configurational assignment. Hopefully, the selected case studies could provide some inspiration to a readership with broad interests: natural products chemists and synthetic organic chemists.

Pyrrolidine Dithiocarbamate Inhibits Nuclear Factor kappaB and Toll-Like Receptor 4 Expression in Rats with Acute Necrotizing Pancreatitis

BACKGROUND/AIMS: To investigate the expression of Toll-like receptor 4 (TLR4) in the pancreases of rats with acute necrotizing pancreatitis (ANP) and any changes upon treatment with pyrrolidine dithiocarbamate (PDTC), an inhibitor of nuclear factor kappaB (NF-kappaB), as well as to determine the relationship between TLR4 and NF-kappaB in ANP pathogenesis. METHODS: A total of 72 SD rats were randomly divided into three groups, namely, the control (sham-operation), ANP, and ANP with PDTC pretreatment groups. The PDTC-pretreated group was intraperitoneally injected with PDTC at a dose of 100 mg/kg 1 hour before the induction of ANP. The expressions of TLR4 and NF-kappaB in pancreatic tissue were evaluated by immunohistochemistry and Western blot analysis. The mRNA levels of cytokines tumor necrosis factor alpha, interleukin (IL)-1beta, and IL-6 were measured by reverse transcription polymerase chain reaction. RESULTS: The expressions of TLR4, NF-kappaB, and cytokine (NF-kappaB target) genes in the pancreatic tissue increased more significantly in the ANP groups than in the sham-operation group at 3, 6, and 12 hours. Pretreatment with PDTC alleviated the inflammatory activation in the pancreas with ANP, causing a significant decrease in the expressions of TLR4, NF-kappaB, and cytokine genes in the pancreatic tissue. CONCLUSIONS: The expressions of TLR4 and NF-kappaB were increased in the pancreases of rats with ANP. PDTC not only inhibits NF-kappaB but also suppresses the expression of TLR4 and downregulates the expression of the related cytokine genes.

Pyrrolidine Dithiocarbamate Inhibits Nuclear Factor kappaB and Toll-Like Receptor 4 Expression in Rats with Acute Necrotizing Pancreatitis

BACKGROUND/AIMS: To investigate the expression of Toll-like receptor 4 (TLR4) in the pancreases of rats with acute necrotizing pancreatitis (ANP) and any changes upon treatment with pyrrolidine dithiocarbamate (PDTC), an inhibitor of nuclear factor kappaB (NF-kappaB), as well as to determine the relationship between TLR4 and NF-kappaB in ANP pathogenesis. METHODS: A total of 72 SD rats were randomly divided into three groups, namely, the control (sham-operation), ANP, and ANP with PDTC pretreatment groups. The PDTC-pretreated group was intraperitoneally injected with PDTC at a dose of 100 mg/kg 1 hour before the induction of ANP. The expressions of TLR4 and NF-kappaB in pancreatic tissue were evaluated by immunohistochemistry and Western blot analysis. The mRNA levels of cytokines tumor necrosis factor alpha, interleukin (IL)-1beta, and IL-6 were measured by reverse transcription polymerase chain reaction. RESULTS: The expressions of TLR4, NF-kappaB, and cytokine (NF-kappaB target) genes in the pancreatic tissue increased more significantly in the ANP groups than in the sham-operation group at 3, 6, and 12 hours. Pretreatment with PDTC alleviated the inflammatory activation in the pancreas with ANP, causing a significant decrease in the expressions of TLR4, NF-kappaB, and cytokine genes in the pancreatic tissue. CONCLUSIONS: The expressions of TLR4 and NF-kappaB were increased in the pancreases of rats with ANP. PDTC not only inhibits NF-kappaB but also suppresses the expression of TLR4 and downregulates the expression of the related cytokine genes.

Progress in the biomarker discovery for drug-induced liver injury / 药学学报

The leading cause of drug withdrawal from market and clinical trials failure is drug-induced liver injury (DILI). Varying clinical, histological and laboratory features of DILI, as well as undefined underlying mechanisms, hinder patients to be diagnosed in the early-stage of the disease and receive effective treatments. Conventional indicators, like serum transaminases and bilirubin, have inevitable limitations referring to sensitive prediction and specific detection of DILI. In order to reduce the occurrence of DILI, researchers have attempted to discover potential biomarkers with higher specificity and sensitivity from blood and urine in recent years. This article aims to review recent advances in biomarkers of DILI.