Use of Thread-hanging Microwave Antenna to Assist in Precise Puncture of Lung Nodule and Influencing Factors / 肿瘤防治研究

Objective To explore a precise method with a microwave antenna for puncture of pulmonary nodules and analyze phenomena that affect the puncture results. Methods Clinical data of 107 cases with solitary malignant pulmonary nodules were collected, and the mean length of pulmonary nodules was 13.6±0.6 mm in CT axial position. A thread-hanging method was used to assist the puncture of pulmonary nodules. The procedure was successful when the needle was not withdrawn and inserted into the central region of the nodule. The success rate and complications of the pulmonary procedure were recorded. The incidence of the following phenomena were also documented: needle coercing, needle slipping, needle tip pushing, pulmonary nodule prolapsing, radial nodule deformation, nodular masking, and radial movement distance of needle tip. Results In all of 107 cases evaluated, the antenna puncture was successful in 101 cases (94.4%) but failed in 6 cases (5.6%). Pneumothorax and pulmonary hemorrhage occurred in 23 (21.5%) and 19 cases (17.8%), respectively. The following phenomena occurred: needle coercing in 9 cases (8.4%), needle slipping in 6 cases (5.6%), needle tip pushing in 19 cases (17.8%), pulmonary nodule prolapsing in 15 cases (14%), radial nodule deformation in 14 cases (13.1%), and nodular masking in 5 cases (4.7%). The mean radial adjusting distance of needle tip was 0.7±0.4 cm. Conclusion The thread-hanging method can assist in the accurate puncture of microwave antenna for pulmonary nodules. We should focus and deal with phenomena that may occur and affect the result of puncture.

Characteristics of phytoplankton community and its influencing factors in the Yanhe River Basin, Northwest China.

Yanhe River is one of the important tributaries of the Yellow River, with a vital role in the maintenance of biodiversity and ecological conservation in the middle reaches of the Yellow River. In this study, we conducted a systematic aquatic ecological survey of the Yanhe River Basin in spring (April-May) and autumn (September-October) of 2021, with phytoplankton as indicator organism. A total of 33 sampling sections were selected in the mainstem, five first-class tributaries, and impounded water bodies (reservoir and check dam water bodies) of the Yanhe River Basin. The results showed that a total of 253 phytoplankton species, belonging to 7 phyla and 91 genera, were detected in the two surveys. Diatoms and green algae prevailed in spring (168 species), while diatoms and cyanobacteria dominated in autumn (179 species). The mean phytoplankton density and biomass were 316.07×104 cells·L-1 and 6.41 mg·L-1 in spring, and 69.56×104 cells·L-1 and 1.59 mg·L-1 in autumn, respectively. At the temporal scale, phytoplankton abundance in spring was higher than that in autumn. At the spatial scale, the phytoplankton abundance in the middle and lower reaches of the mainstream was higher than that in the upper reaches. Phytoplankton biomass in the impounded water bodies formed by dam interception was maintained at a high level, which was significantly higher than that in the mainstem and tributary water bodies in autumn. The phytoplankton diversity, as indicated by Shannon diversity index, Margalef richness index, and Pielou evenness index, in spring was greater than that in autumn. Phytoplankton diversity was greater in the trunk and tributary waters than that in impounded waters. The results of redundancy analysis showed that the key factors driving the phytoplankton community structure in spring were flow velocity, dissolved oxygen, nitrite nitrogen, and water depth. In contrast, the key driving factors in autumn were nitrate nitrogen, water depth, and dissolved oxygen.

Comprehensive insights into the structures and dynamics of plant telomeric G-quadruplexes.

Telomeres, which are located at the ends of eukaryotic chromosomes, are crucial for genomic maintenance. Most telomeric DNA is composed of tandemly repeated guanine (G)-rich sequences, which form G-quadruplexes (G4s). The structures and dynamics of telomeric G4s are essential for telomere functioning and helpful for G4-based biosensing. However, they are far from being understood, especially for plants. In this contribution, the folding, environment-induced G4 dynamics, and protein-catalyzed unfolding of plant telomeric G4s were comprehensively studied. It was found that diverse plant telomeric sequences from land plants to green algae could fold into G4 structures. In addition, 5'-proximal ssDNA but not 3'-proximal ssDNA drove conversion of anti-parallel G4 structures to parallel structures, and both 5' and 3' ssDNA decreased the stability of G4s in dilute solution. Furthermore, molecular crowding promoted the formation of parallel structures for three-layer but not for two-layer G4s, and increased the stability of all selected G4s. Finally, AtRecQ2 helicase resolved the stable parallel structure of typical plant telomeric G4 in crowded solution, but ssDNA binding protein AtRPA did not. Furthermore, AtRecQ2 unwound the structure more efficiently in the presence of AtRPA. The results may expand our understanding on the structures and dynamics of plant telomeric G4s.

Synthesis, evaluation and proteomic analysis of PROTAC based on parthenolide / 药学学报

As a natural product with a long history of medicinal use, parthenolide has aroused great interest of chemists and biologists. Existing studies have shown that it has anti-inflammatory, antitumor and other pharmacological activities, and also revealed its action on NF-κB signaling pathway, DNMT1 enzyme and Wnt/β-catenin signaling pathway. But its biological targets remain to be elucidated systematically. Proteolysis Targeting Chimeras (PROTAC) provides a new strategy for target discovery of natural products, which can be used to explore the panorama of protein changes in cells through proteomic investigation, so as to analyze their potential targets. Based on this idea, current study designed and synthesized 20 parthenolide-derived degraders. After measured their antitumor activity in vitro, selected compounds were carried out the proteomic experiment. Finally, 139 down-regulated differentially expressed proteins were identified and the discovery of parthenolide interacting protein was preliminarily explored.

Effect of electroacupuncture on liver Akt/FoxO1 signaling pathway in rats with diabetic fatty / 中国针灸

OBJECTIVE@#To observe the effect of electroacupuncture (EA) on liver protein kinase B (Akt)/forkhead box transcription factor 1 (FoxO1) signaling pathway in Zucker diabetic fatty (ZDF) rats, and to explore the possible mechanism of EA on improving liver insulin resistance of type 2 diabetes mellitus.@*METHODS@#Twelve male 2-month-old ZDF rats were fed with high-fat diet for 4 weeks to establish diabetes model. After modeling, the rats were randomly divided into a model group and an EA group, with 6 rats in each group. In addition, six male Zucker lean (ZL) rats were used as the blank group. The rats in the EA group were treated with EA at bilateral "Zusanli" (ST 36), "Sanyinjiao" (SP 6), "Weiwanxiashu" (EX-B 3), and "Pishu" (BL 20). The ipsilateral "Zusanli" (ST 36) and "Weiwanxiashu" (EX-B 3) were connected to EA device, continuous wave, frequency of 15 Hz, 20 min each time, once a day, six times a week, for a total of 4 weeks. The fasting blood glucose (FBG) in each group was compared before modeling, before intervention and after intervention; the serum levels of insulin (INS) and C-peptide were measured by radioimmunoassay method, and the insulin resistance index (HOMA-IR) was calculated; HE staining method was used to observe the liver tissue morphology; Western blot method was used to detect the protein expression of Akt, FoxO1 and phosphoenolpyruvate carboxykinase (PEPCK) in the liver.@*RESULTS@#Before intervention, compared with the blank group, FBG was increased in the model group and the EA group (P<0.01); after intervention, compared with the model group, FBG in the EA group was decreased (P<0.01). Compared with the blank group, the serum levels of INS and C-peptide, HOMA-IR, and the protein expression of hepatic FoxO1 and PEPCK were increased (P<0.01), while the protein expression of hepatic Akt was decreased (P<0.01) in the model group. Compared with the model group, the serum levels of INS and C-peptide, HOMA-IR, and the protein expression of hepatic FoxO1 and PEPCK were decreased (P<0.01), while the protein expression of hepatic Akt was increased (P<0.01) in the EA group. In the model group, the hepatocytes were structurally disordered and randomly arranged, with a large number of lipid vacuoles in the cytoplasm. In the EA group, the morphology of hepatocytes tended to be normal and lipid vacuoles were decreased.@*CONCLUSION@#EA could reduce FBG and HOMA-IR in ZDF rats, improve liver insulin resistance, which may be related to regulating Akt/FoxO1 signaling pathway.

Study on the relationship between intestinal flora analysis and CD4 +T lymphocyte subsets in patients with systemic lupus erythematosus / 中华风湿病学杂志

Objective:To explore the characteristics of intestinal microbiota in patients with systemic lupus erythematosus (SLE), and further explore the relationship between microbiota and CD4 +T lymphocyte subsets and disease activity. Methods:Fecal samples were collected from 96 patients with SLE, and 96 sex- and age-matched healthy controls (HCs). The gut microbiota were investigated via 16s rRNA sequencing. Flow cytometry was used to detect peripheral CD4 +T lymphocyte subsets of Th1, Th2, Th17 and Treg cells. Indicators of disease activity such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), complement C3 and C4, Systemic lupus erythematosus disease activity index(SLEDAI) for each patient were recorded. Differential abundance analysis was carried out using the edgeR algorithm. The Wilcoxon rank-sum test was used to compare alpha diversity indices, bacterial abundances, and the F/B ratio between groups. R (version 4.0.1) was used for comparative statistics, and Pearson′s correlation analysis was used to assess the correlations between the relative abundances of bacterial genera and serum levels of ESR, CRP, C3 and C4 in the samples. Results:The alpha estimators of richness (ACE and Chao 1) were significantly reduced in SLE feces samples compared with those of HCs ( P<0.01). Bacterial diversity estimators, including the Shannon ( P<0.01) and Simpson′s ( P<0.01) indices, were also significantly lower in SLE. Significant differences in gut microbiota composition between SLE and HCs were found using the edgeR algorithm. Compared with HC, 24 species of bacteria were significantly different in SLE patients at the genus level ( P<0.05). Moreover, there was a significant positive correlation between CRP and Coprococcus ( r=0.30, P=0.014), C4 and Corynebacterium ( r=0.31, P=0.013) and Faecalibacterium( r=0.25, P=0.048), Hemoglobin and Morganella( r=0.41, P=0.001), as well as SLIDA and Corynebacterium( r=0.25, P=0.047). In terms of lymphocyte subsets, there was significant positive correlation between B cells, Treg cells and Eubacterium eligens group, as well as CD8 +T, CD4 +T, NK cells and Corynebacterium. In additional, Th1 was positively correlated with Shigella Escherichia coli ( r=0.52, P=0.008), and Th2 was positively correlated with Dielma ( r=0.51, P<0.001). Conclusion:The abundance and diversity of intestinal flora in SLE patients were significantly reduced, and the differentially expressed bacteria were closely related to the CD4 +T lymphocyte subsets and disease activity indicators of patients.

Effects of electroacupuncture on the glucose-lipid metabolism and the expression of ZAG and GLUT4 in the femoral quadriceps and adipose tissue in the rats with type 2 diabetes mellitus / 中国针灸

OBJECTIVES@#To observe the effects on the glucose-lipid metabolism and the expression of zinc-α2-glycoprotein (ZAG) and glucose transporter 4 (GLUT4) in the femoral quadriceps and adipose tissue after electroacupuncture (EA) at "Pishu" (BL 20), "Weiwanxiashu" (EX-B 3), "Zusanli" (ST 36) and "Sanyinjiao" (SP 6) in the rats with diabetes mellitus type 2 (T2DM), so as to explore the effect mechanism of EA in treatment of T2DM.@*METHODS@#Twelve ZDF male rats were fed with high-sugar and high-fat fodder, Purina #5008 for 4 weeks to induce T2DM model. After successfully modeled, the rats were randomly divided into a model group and an EA group, with 6 rats in each one. Additionally, 6 ZL male rats of the same months age were collected as the blank group. The rats in the EA group were treated with EA at bilateral "Pishu" (BL 20), "Weiwanxiashu" (EX-B 3), "Zusanli" (ST 36) and "Sanyinjiao" (SP 6), with continuous wave, 15 Hz in frequency, and 2 mA in intensity. The electric stimulation lasted 20 min each time. EA was delivered once daily, 6 times a week for 4 weeks. Separately, the levels of fasting blood glucose (FBG) was measured before modeling, before and after intervention, and the body mass of each rat was weighted before and after intervention. After intervention, the levels of the total cholesterol (TC), triacylglycerol (TG) and free fatty acid (FFA) in serum were detected using enzyme colorimetric method; and the levels of the serum insulin (INS) and ZAG were detected by ELISA. Besides, the insulin sensitivity index (HOMA-ISI) was calculated. With Western blot technique adopted, the protein expressions of ZAG and GLUT4 in the femoral quadriceps and adipose tissue were determined.@*RESULTS@#After intervention, compared with the blank group, the levels of FBG and body mass, and the levels of serum TC, TG, FFA and INS increased (P<0.01), while HOMA-ISI decreased (P<0.01); the level of ZAG in the serum and the protein expressions of ZAG and GLUT4 in the femoral quadriceps and adipose tissue dropped (P<0.01) in the model group. In the EA group, compared with the model group, the levels of FBG and body mass, and the levels of serum TC, TG, FFA and INS were reduced (P<0.01), and HOMA-ISI increased (P<0.01); the level of ZAG in the serum and the protein expressions of ZAG and GLUT4 in the femoral quadriceps and adipose tissue increased (P<0.01, P<0.05).@*CONCLUSIONS@#Electroacupuncture can effectively regulate glucose-lipid metabolism, improve insulin resistance and sensitivity in the rats with T2DM, which is associated with the modulation of ZAG and GLUT4 expression in the skeletal muscle and adipose tissue.

Mechanistic insights into poly(C)-binding protein hnRNP K resolving i-motif DNA secondary structures.

I-motifs are four-strand noncanonical secondary structures formed by cytosine (C)-rich sequences in living cells. The structural dynamics of i-motifs play essential roles in many cellular processes, such as telomerase inhibition, DNA replication, and transcriptional regulation. In cells, the structural dynamics of the i-motif can be modulated by the interaction of poly(C)-binding proteins (PCBPs), and the interaction is closely related to human health, through modulating the transcription of oncogenes and telomere stability. Therefore, the mechanisms of how PCBPs interact with i-motif structures are fundamentally important. However, the underlying mechanisms remain elusive. I-motif structures in the promoter of the c-MYC oncogene can be unfolded by heterogeneous nuclear ribonucleoprotein K (hnRNP K), a PCBP, to activate its transcription. Here, we selected this system as an example to comprehensively study the unfolding mechanisms. We found that the promoter sequence containing 5 C-runs preferred folding into type-1245 to type-1234 i-motif structures based on their folding stability, which was further confirmed by single-molecule FRET. In addition, we first revealed that the c-MYC i-motif structure was discretely resolved by hnRNP K through two intermediate states, which were assigned to the opposite hairpin and neighboring hairpin, as further confirmed by site mutations. Furthermore, we found all three KH (hnRNP K homology) domains of hnRNP K could unfold the c-MYC i-motif structure, and KH2 and KH3 were more active than KH1. In conclusion, this study may deepen our understanding of the interactions between i-motifs and PCBPs and may be helpful for drug development.

Insights into the structural dynamics and helicase-catalyzed unfolding of plant RNA G-quadruplexes.

RNA G-quadruplexes (rG4s) are noncanonical RNA secondary structures formed by guanine (G)-rich sequences. These complexes play important regulatory roles in both animals and plants through their structural dynamics and are closely related to human diseases and plant growth, development, and adaption. Thus, studying the structural dynamics of rG4s is fundamentally important; however, their folding pathways and their unfolding by specialized helicases are not well understood. In addition, no plant rG4-specialized helicases have been identified. Here, using single-molecule FRET, we experimentally elucidated for the first time the folding pathway and intermediates, including a G-hairpin and G-triplex. In addition, using proteomics screening and microscale thermophoresis, we identified and validated five rG4-specialized helicases in Arabidopsis thaliana. Furthermore, DExH1, the ortholog of the famous human rG4 helicase RHAU/DHX36, stood out for its robust rG4 unwinding ability. Taken together, these results shed light on the structural dynamics of plant rG4s.

Current status and influencing factors of health behaviors in stroke patients / 中华行为医学与脑科学杂志

Objective:To investigate the current status and influencing factors of stroke patients.Methods:Using stratified sampling method, 458 stroke patients was investigated for the health behavior from October to December, 2015. Based on PROCEDE-PROCEED model, logistic regression analysis was conducted with the health behavior level of the subjects as the dependent variable, and the characteristic factors in the chi-square test as the independent variables to analyze the factors which influence the health behavior level of stroke patients from predisposing factors, enabling factors and reinforcing factors.Results:The health behavior score of stroke patients was (14.5±3.9), which was at medium level. The score of each dimension was nutrition (0.80±0.25), disease management (0.60±0.26), interpersonal relationship (0.57±0.33), and medication compliance (0.49±0.41). The multiple logistic regression analysis showed that the predisposition factors including age ( OR=2.03, 95% CI=1.08-3.80) and history of hypertension( OR=2.35, 95%=1.16-4.76), the enabling factors including the allocation of social resources ( OR=1.73, 95% CI=0.89-3.36), and the reinforcing factors including family support ( OR=2.03, 95% CI=0.99-4.17) were important factors which affect the health behavior of stroke patients. Conclusion:The health behavior level of stroke patients need to be improved. The relevant community resource allocation system continuously, and focus on the impact of family environment and particularly the elderly and patients with a history of hypertension should be attentioned when improving the health behavior of patients.

Utilizing benchmarked dataset and gene regulatory network to investigate hub genes in postmenopausal osteoporosis.

OBJECTIVE: The objective of this paper was to investigate hub genes of postmenopausal osteoporosis (PO) utilizing benchmarked dataset and gene regulatory network (GRN). MATERIALS AND METHODS: To achieve this goal, the first step was to benchmark the dataset downloaded from the ArrayExpress database by adding local noise and global noise. Second, differentially expressed genes (DEGs) between PO and normal controls were identified using the Linear Models for Microarray Data package based on benchmarked dataset. Third, five kinds of GRN inference methods, which comprised Zscore, GeneNet, context likelihood of relatedness (CLR) algorithm, Partial Correlation coefficient with Information Theory (PCIT), and GEne Network Inference with Ensemble of trees (Genie3), were described and evaluated by receiver operating characteristic (ROC) and precision and recall (PR) curves. Finally, GRN constructed according to the method with best performance was implemented to conduct topological centrality (closeness) for the purpose of investigate hub genes of PO. RESULTS: A total of 236 DEGs were obtained based on benchmarked dataset of 20,554 genes. By assessing Zscore, GeneNet, CLR, PCIT, and Genie3 on the basis of ROC and PR curves, Genie3 had a clear advantage than others and was applied to construct the GRN which was composed of 236 nodes and 27,730 edges. Closeness centrality analysis of GRN was carried out, and we identified 14 hub genes (such as TTN, ACTA1, and MYBPC1) for PO. CONCLUSION: In conclusion, we have identified 14 hub genes (such as TN, ACTA1, and MYBPC1) based on benchmarked dataset and GRN. These genes might be potential biomarkers and give insights for diagnose and treatment of PO.

Anti-depressant Mechanism of Qing' ewan in CUMS Rats Based on Estrogen Receptor Pathway / 中国实验方剂学杂志

Objective::To study the anti-depressive effect of Qing' ewan in treating chronic unpredictable mild stress (CUMS) in rats, and the regulatory effect on estrogen receptor and estrogen receptor-related signaling pathways, in order to explore its anti-depressive mechanism. Method::The CUMS model was established. The experiment was divided into normal control group, model group, escitalopram oxalate group (positive control) and Qing' ewan groups (1.71, 5.13, 15.39 g·kg-1). After 4 weeks of modeling, rats were treated with corresponding drugs for 2 weeks. Behavioral evaluation [sucrose preference test (SPT), forced swimming test (FST), open field test (OFT)] was conducted to assess if the CUMS model was successful. Western blot was used to analyze the protein expression levels of estrogen receptor α (ERα), estrogen receptor β (ERβ), brain-derived neurotrophic factor (BDNF) and tyrosine kinase receptor B (TrkB). Result::Compared with the normal group, the sucrose consumption rate and the score of OFT in the model group decreased(P<0.05, P<0.01), the immobility time of FST prolonged significantly(P<0.01), and the protein expression levels of ERα, ERβ, BDNF and TrkB decreased(P<0.05, P<0.01). Compared with the model group, the behavioral performance of the treated group was improved, the sucrose consumption rate and the score of OFT increased(P<0.05, P<0.01), and the immobility time decreased(P<0.05). The protein expressions of ERα, ERβ, BDNF and TrkB in the treated group were significantly up-regulated(P<0.05, P<0.01), especially the middle-dose Qing' ewan group (5.13 g·kg-1). Conclusion::Qing' ewan can improve depression-like behavior in CUMS rats. Its mechanism may be related to the neuroprotective effect by up-regulating the expressions of ERα and ERβ and activating estrogen receptor-mediated ERβ/BDNF/TrkB pathways.

Therapeutic treatment of a novel selective JAK3/JAK1/TBK1 inhibitor, CS12192, in rat and mouse models of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a representative autoimmune disease characterized by chronic inflammation and joint destruction. Although biological inhibitors such as TNF-α and IL-6 antibodies have achieved success in clinical therapy, small molecule inhibitors against the Janus kinases (JAKs) involved in the signaling pathways of various cytokine receptors have gained more attraction as safe and efficacious options. In this study, we identified CS12192 as a novel selective JAK3/JAK1/TBK1 inhibitor and investigated its pharmacological effects on the experimental arthritis models in rat and mouse. We found that CS12192 showed a more selective inhibitory activity on JAK3, and to a less extent on JAK1 and TBK1, that were verified by decreased activation of p-STATs and p-IRF3 as well as down-regulation of IFN gene expression in the cultured cells with relevant stimuli. Furthermore, oral treatment with CS12192 dose-dependently ameliorated the disease severity, hind paw swelling, body weight loss, and bone destruction in rat models of adjuvant-induced arthritis (AIA) and collagen-induced arthritis (CIA). In a mouse CIA model, CS12192 also attenuated the disease severity, which was correlated with the suppressed CD4+ T cell activation and Th17 function, as well as the reduced cytokine levels in sera and pro-inflammatory cytokine and chemokine gene expression in joint tissue. Corroboratively, RANKL-induced osteoclast formation was inhibited by CS12192. Thus, these results suggest that CS12192 as a novel selective JAK inhibitor has therapeutic potential for the treatment of RA and may provide a new strategy for the control of autoimmune diseases.

Antitumor and immunomodulatory effects of a novel multitarget inhibitor, CS2164, in mouse hepatocellular carcinoma models.

As a novel orally active multitarget small molecule inhibitor, CS2164 has shown broad antitumor activities against several human tumor xenograft models in immune-compromised mice. However, the ability of CS2164 to modulate antitumor immunity in an immune-competent mouse tumor model remains undefined, although antiangiogenic treatment has been reported to affect immune cell infiltration and remodel the tumor immune microenvironment. In the present study, the subcutaneous and ascites hepatocellular carcinoma (HCC) models in syngeneic Balb/c mice established by inoculation of an H22 hepatoma cell line were utilized to investigate the antitumor and immunomodulatory effects of CS2164. Although the antitumor effects of CS2164 were validated in both subcutaneous and ascites HCC models in syngeneic mice, CS2164 treatment consistently modulated immune cell populations, both in the periphery and in tumor microenvironments, with upregulation of CD4 and CD8 T cells in the spleen, but downregulation of immunosuppressive populations including regulatory T cells, myeloid-derived suppressor cells, and tumor-associated macrophages in the spleen and tumor tissues. Furthermore, CS2164 increased the relative gene expression and protein production of several proinflammatory cytokines in tumor-related ascites. These results indicate that CS2164 exerts an antitumor effect associated with its immunomodulatory activities in mouse HCC models, and may also provide evidence for the immunotherapy potentiation of CS2164 in future cancer treatment.

Effect of materials and superstructure designs on the passive fit of implant-supported fixed prostheses / 华西口腔医学杂志

OBJECTIVE@#This study aimed to compare the passive fits of implant-supported cement-retained computer aided design/computer aided manufacturing (CAD/CAM) bridges fabricated with different implant superstructure designs from zirconia and titanium.@*METHODS@#A total of 32 cubic clods with the same dimensions and with elastic modulus similar to that of mandibles were used. Each clod received two one-stage implants to simulate a partially edentulous jaw that was missing teeth between the lower left second premolar and second molar. Four linear strain gauges were bonded on the region surrounding each implant on the mesial, buccal, distal, and lingual aspects. A total of 32 identical frameworks were fabricated through CAD/CAM after scanning. The frameworks were allocated into four different groups (n=8) in accordance with material types and superstructure designs. Group A included zirconia ceramic implant-supported fixed prostheses with regular marginal designs. Group B comprised zirconia ceramic implant-supported fixed prostheses with full circumferential zirconia-collar marginal designs. Group C consisted of titanium ceramic implant-supported fixed prostheses with regular marginal designs. Group D included titanium ceramic implant-supported fixed prostheses with full circumferential titanium-collar marginal designs. Strain development before and after ceramic veneering was recorded during cement setting. Data were statistically analyzed by using SPSS software.@*RESULTS@#Before ceramic veneering, material types affected the strains of prostheses, and zirconia frameworks showed lower strain than other frameworks (P0.05). Nevertheless, the full circumferential collar marginal design reduced discrepancies among groups (P<0.01).@*CONCLUSIONS@#The passive fits of zirconia prostheses were better than those of titanium-based porcelain-fused-to-metal restorations. The full circumferential collar marginal design can help reduce fit inaccuracy, as well as the adverse effects of ceramic veneering.

Simultaneous determination of nine bioactive components in Bazhen Yimu Pills by HPLC-ESI-MS/MS / 中草药

Objective To develop and validate a high performance liquid chromatography coupled with electrospray tandem mass spectrometry (HPLC-ESI-MS/MS) method for simultaneously qualitative and quantitative determination of nine major bioactive components (stachydrine hydrochloride, leonurine hydrochloride, paeoniflorin, ferulic acid, liquiritin, lobetyolin, verbascoside, atracylenolide I, and polyporenic acid C) in Bazhen Yimu Pills (BYP). Methods The chromatographic separation was performed on an Waters Atlantis T3 column (150 mm × 4.6 mm, 3.0 μm) with a gradient elution of methanol and 0.1% formic acid in water at a flow rate of 0.5 mL/min, and the injection volume was 10 μL. The nine major bioactive components were detected using an electrospray ionization source in negative ionization mode (ESI-) and quantified by multiple reaction monitor (MRM) scanning at the same time. Results The linear ranges of stachydrine hydrochloride, leonurine hydrochloride, paeoniflorin, ferulic acid, liquiritin, lobetyolin, verbascoside, atracylenolide I, and polyporenic acid C were 0.04-40.00 μg/mL (r = 0.999 2), 0.04-40.00 μg/mL (r = 0.999 3), 1.0-100.0 μg/mL (r = 0.999 1), 0.2-20.0 μg/mL (r = 0.999 6), 0.2-20.0 μg/mL (r = 0.997 5), 0.05-5.00 μg/mL (r = 0.999 4), 0.1-10.0 μg/mL (r = 0.999 4), 0.1-10.0 μg/mL (r = 0.999 2), 0.1-10.0 μg/mL (r = 0.999 2), and the average recoveries were 99.7% (RSD = 0.52%), 98.1% (RSD = 0.64%), 98.5% (RSD = 1.08%), 101.5% (RSD = 1.12%), 99.5% (RSD = 0.39%), 98.4% (RSD = 0.74%), 99.1% (RSD = 0.91%), 101.2% (RSD = 0.54%), and 100.1% (RSD = 0.47%), respectively. The content of nine batches of the nine major bioactive components were 0.423-0.752, 0.505-0.722, 0.613-1.300, 0.102-0.184, 0.195-0.255, 0.021-0.035, 0.034-0.072, 0.039-0.063, and 0.051-0.095 mg/g, respectively. Conclusion The developed method is simple, specific, and sensitive, and it can be applied for the determination of nine major bioactive components and the quality control of BYP collected from different production batches.

The expression and clinical importance of Reg IV in different molecular subtypes of breast cancer / 医学研究生学报

Objective RegIV, which is the latest member of the regenerative gene family, has been found to be closely related to the development of various tumors, but rarely reported in invasive breast cancer. This article is intended to explore the expression levels of regenerative factor 4(regeneration islet-derived family, member 4, RegIV), and the correlation with clinicopathological features and prognosis in 4 molecular subtypes of breast cancer(LA, LB,HER-2+, TNBC). Methods Pathological data of 284 breast cancer patients from March 2011 to October 2017 in the department of pathology, Lianyungang first people’s hospital were collected. To analyze the expression of RegIV in different molecular subtypes (LA, LB, HER-2+, TNBC) and its relationship with clinicopathological features, we analyzed the expression level of RegIVmRNA in breast cancer and its prognosis of patients. Results The positive rates of Reg IV in Luminal A group, Luminal B group, HER-2 positive group and triple negative breast cancer were 52.11%（37/71）, 50.00%（42/84）, 65.22%（45/69）and 20.00%（12/60）,which was statistically significant when comparing them in pairs(P<0.01). The expression of RegIV was associated with tumor diameter, lymph node metastasis, TNM stage(P<0.01). The recurrence risk of breast cancer patients with high RegIV expression was lower than those with low RegIV expression (HR=0.59,95%CI:0.50-0.69). Further analysis found that the recurrence risk of LA breast cancer patients with high RegIV expression (HR=0.63,95%CI:0.48-0.82), and so it was with LB(HR=0.56,95%CI:0.40-0.76) and TNBC(HR=0.51,95%CI:0.36-0.71). Conclusion RegIV can provide reference for molecular subtypes diagnosis and it may be one of the indicators to evaluate the prognosis of breast cancer patients.

Analysis on drug resistance characteristics and risk factors for extensively drug resistant tuberculosis patients / 中华疾病控制杂志

@# Objective To analyze the drug resistance profile and risk factors for extensively drug resistant tuberculosis (XDR-TB) patients. Methods XDR-TB cases were identified by sixteen anti-TB drug susceptibility kits among inpatients with a diagnosis of laboratory-confirmed mycobacterium tuberculosis. Single-factor and Logistic analysis were used to analyze the risk factors for drug resistant of the first and second-line anti-TB drugs in XDR-TB patients. Results Resistant rate of rifampin, isoniazid and rifampicin were 100%, Resistant rate of streptomycin, rifampicin and dean, b sulfur isoniazid, levofloxacin and capreomycin were from 90% to 100%, resistant rate of kanamycin and amino salicylic acid were from 70% to 80%, resistant rate of amikacin from 60% to 70%, resistant rate of sulfur isoniazid was from 50% to 60%, resistant rate of ethambutol and moxifloxacin were from 40% to 50%, resistant rate of clarithromycin was from 10% to 20%, resistant rate of clofazimine 5.2%. 92.1% of XDR-TB patients were resistant to more than 10 anti-TB drugs, and the least of the patients were resistant to 6 anti-TB drugs.Logistic regression analysis showed the risk factors for XDR-TB first-and second-line anti-tb drugs included age ［20-40 year (OR=6.318, 95% CI:1.204-33.15, P=0.029;40-60 year (OR=4.772, 95% CI:0.973-23.392, P=0.054); 60 year (OR=41.366, 95% CI:2.909-588.265, P=0.006)］and anti-TB treatment history was retreatment(OR=28.013, 95% CI:3.357-233.766, P=0.002). Conclusions XDR-TB patients have serious drug resistance, but there were some drug treatable drug resistance types, and the risk factors mainly come from age and anti-TB treatment history.

Mid-term follow-up and clinical efficacy of total knee arthroplasty for osteoarthritis patients with Parkinson's disease / 中国骨伤

<p><b>OBJECTIVE</b>To investigate clinical efficacy and experience of total knee arthroplasty in treating knee osteoarthritis patients with Parkinson's disease.</p><p><b>METHODS</b>From January 2011 to January 2014, 19 knee osteoarthritis patients with Parkinson's disease treated with total knee arthroplasty were collected. Among them, including 9 males and 10 females aged from 61 to 83 years old with an average of 71.3 years old. Radiology results were checked before and after operation. VAS score and KSS score were applied to evaluate clinical effects. Patients were classified according to HoehnYahr grade, 3 cases in grade 1, 4 cases in grade 1.5, 2 cases in grade 2, 4 cases in grade 2.5, 2 cases in grade 3 and 1 case in grade 4.</p><p><b>RESULTS</b>Nineteen patients were followed up from 3 to 7 years with an average of 4.3 years. The pain of patients was significantly reduced or disappeared. All incisions were healed at stage I. At the latest follow-up, 3 patients had knee pain, and mild pain in 1 patient, moderate in 1 patient without severe pain. VAS score was reduced from preoperative 8.4±1.3 to the latest follow-up 3.1±1.2, the difference was statistically significant (0.05). KSS score improved from 43.6±7.3 before operation to 91.8±10.6 after operation. The condition of Parkinson's were controlled by medicine. No loosening and subsidence of prosthesis by X-ray examination.</p><p><b>CONCLUSIONS</b>Total knee arthroplasty is a safe and effective method for the treatment of Parkinson's disease and has satisfactory mid-term clinical effect.</p>

Chiglitazar Preferentially Regulates Gene Expression via Configuration-Restricted Binding and Phosphorylation Inhibition of PPARγ.

Type 2 diabetes mellitus is often treated with insulin-sensitizing drugs called thiazolidinediones (TZD), which improve insulin resistance and glycemic control. Despite their effectiveness in treating diabetes, these drugs provide little protection from eminent cardiovascular disease associated with diabetes. Here we demonstrate how chiglitazar, a configuration-restricted non-TZD peroxisome proliferator-activated receptor (PPAR) pan agonist with moderate transcription activity, preferentially regulates ANGPTL4 and PDK4, which are involved in glucose and lipid metabolism. CDK5-mediated phosphorylation at serine 273 (S273) is a unique regulatory mechanism reserved for PPARγ, and this event is linked to insulin resistance in type 2 diabetes mellitus. Our data demonstrates that chiglitazar modulates gene expression differently from two TZDs, rosiglitazone and pioglitazone, via its configuration-restricted binding and phosphorylation inhibition of PPARγ. Chiglitazar induced significantly greater expression of ANGPTL4 and PDK4 than rosiglitazone and pioglitazone in different cell models. These increased expressions were dependent on the phosphorylation status of PPARγ at S273. Furthermore, ChIP and AlphaScreen assays showed that phosphorylation at S273 inhibited promoter binding and cofactor recruitment by PPARγ. Based on these results, activities from pan agonist chiglitazar can be an effective part of a long-term therapeutic strategy for treating type 2 diabetes in a more balanced action among its targeted organs.