Design, synthesis, and antifungal mechanism of carbaline fluorescent probes / 药学学报

Three carboline fluorescent probes F1-F3 were designed and synthesized, based on lead compound JYJ-19, an antifungal compound discovered previously by our group. The antifungal activity in vitro results showed that compound F1 had moderate antifungal activity (MIC80 = 32 μg·mL-1). The stokes shift of F1 is 70 nm. The fluorescent probe F1 has good optical properties and can be used for fluorescence imaging research. Subcellular localization experiments results showed that F1 was enriched in the mitochondria of fungal cells. The detection of intracellular reactive oxygen species levels shows that JYJ-19 enhances intracellular reactive oxygen species levels. The above results indicated that carboline compounds could exert antifungal effects by acting on fungal mitochondria.

Hospitalization costs of pediatric community-acquired pneumonia in Shanghai / 中华儿科杂志

Objective: To investigate the epidemiology and hospitalization costs of pediatric community-acquired pneumonia (CAP) in Shanghai. Methods: A retrospective case summary was conducted on 63 614 hospitalized children with CAP in 59 public hospitals in Shanghai from January 2018 to December 2020. These children's medical records, including their basic information, diagnosis, procedures, and costs, were extracted. According to the medical institutions they were admitted, the patients were divided into the children's hospital group, the tertiary general hospital group and the secondary hospital group; according to the age, they were divided into <1 year old group, 1-<3 years old group, 3-<6 years old group, 6-<12 years old group and 12-18 years old group; according to the CAP severity, they were divided into severe pneumonia group and non-severe pneumonia group; according to whether an operation was conducted, the patients were divided into the operation group and the non-operation group. The epidemiological characteristics and hospitalization costs were compared among the groups. The χ2 test or Wilcoxon rank sum test was used for the comparisons between two groups as appropriate, and the Kruskal-Wallis H test was conducted for comparisons among multiple groups. Results: A total of 63 614 hospitalized children with CAP were enrolled, including 34 243 males and 29 371 females. Their visiting age was 4 (2, 6) years. The length of stay was 6 (5, 8) days. There were 17 974 cases(28.3%) in the secondary hospital group, 35 331 cases (55.5%) in the tertiary general hospital group and 10 309 cases (16.2%) in the children's hospital group. Compared with the hospitalizations cases in 2018 (27 943), the cases in 2019 (29 009) increased by 3.8% (1 066/27 943), while sharply declined by 76.2% (21 281/27 943) in 2020 (6 662). There were significant differences in the proportion of patients from other provinces and severe pneumonia cases, and the hospitalization costs among the children's hospital, secondary hospital and tertiary general hospital (7 146 cases(69.3%) vs. 2 202 cases (12.3%) vs. 9 598 cases (27.2%), 6 929 cases (67.2%) vs. 2 270 cases (12.6%) vs. 9 397 cases (26.6%), 8 304 (6 261, 11 219) vs. 1 882 (1 304, 2 796) vs. 3 195 (2 364, 4 352) CNY, χ2=10 462.50, 9 702.26, 28 037.23, all P<0.001). The annual total hospitalization costs of pediatric CAP from 2018 to 2020 were 110 million CNY, 130 million CNY and 40 million CNY, respectively. And the cost for each hospitalization increased year by year, which was 2 940 (1 939, 4 438), 3 215 (2 126, 5 011) and 3 673 (2 274, 6 975) CNY, respectively. There were also significant differences in the hospitalization expenses in the different age groups of <1 year old, 1-<3 years old, 3-<6 years old, 6-<12 years old and 12-18 years old (5 941 (2 787, 9 247) vs. 2 793 (1 803, 4 336) vs. 3 013 (2 070, 4 329) vs. 3 473 (2 400, 5 097) vs. 4 290 (2 837, 7 314) CNY, χ2=3 462.39, P<0.001). The hospitalization cost of severe pneumonia was significantly higher than that of non-severe cases (5 076 (3 250, 8 364) vs. 2 685 (1 780, 3 843) CNY, Z=109.77, P<0.001). The cost of patients who received operation was significantly higher than that of whom did not (10 040 (4 583, 14 308) vs. 3 083 (2 025, 4 747) CNY, Z=44.46, P<0.001). Conclusions: The number of children hospitalized with CAP in Shanghai decreased significantly in 2020 was significantly lower than that in 2018 and 2019.The proportion of patients from other provinces and with severe pneumonia are mainly admitted in children's hospitals. Hospitalization costs are higher in children's hospitals, and also for children younger than 1 year old, severe cases and patients undergoing operations.

Clinical characteristics and risk factors for bronchoscopic airway mucus hypersecretion in childhood pneumonia infected by different pathogens / 中华儿科杂志

Objective: To investigate the risk factors for airway mucus hypersecretion in childhood pneumonia infected by different pathogens. Method: A retrospective cohort included 968 children who were hospitalized for Mycoplasma pneumoniae pneumonia (MPP), respiratory syncytial virus (RSV) pneumonia, adenovirus pneumonia and underwent bronchoscopy in Respiratory Department of Children's Hospital of Chongqing Medical University from January 2019 to December 2021 was conducted. The children were divided into two groups distinguished by airway mucus secretion according to the airway mucus hypersecretion score which were scored according to the mucus secretion under the bronchoscope. The demographic characteristics, clinical characteristics, laboratory tests and disease severity of the two groups were compared. And the risk factors for the development of airway mucus hypersecretion in two groups were analyzed. Chi square test, Mann-Whithey U test and Fisher exact test were used to analyze the differences between the two groups, and multivariate Logistic regression was used to analyze the influencing factors. Result: There were 559 males and 409 females in the 968 children, with an age of 4.0 (1.4, 6.0) years. Among the 642 children with MPP, 185 cases were in the hypersecretion group and 457 cases were in the non-hypersecretion group. There were 41 cases in the hypersecretion group and 160 cases in the non-hypersecretion group of 201 children with RSV pneumonia. In the 125 children with adenovirus pneumonia, there were 39 cases in the hypersecretion group and 86 cases in the non-hypersecretion group. In these children, the age of children in the hypersecretion group was older than that in the non-hypersecretion group (6.0 (4.0, 7.0) vs. 5.0 (3.0, 7.0) years old, 1.5 (0.5, 3.6) vs. 0.8 (0.4, 1.6) years old, 2.0 (1.2, 4.5) vs. 1.3 (0.8, 2.0) years old, U=35 295.00, 2 492.00, 1 101.00, all P<0.05). Through multivariate Logistic regression analysis it found that increased risk of airway mucus hypersecretion was present in childhood MPP with increase in peripheral blood white blood cell count (OR=3.30, 95%CI 1.51-7.93, P=0.004) or increase in neutrophil ratio (OR=2.24, 95%CI 1.16-4.33, P=0.016) or decrease in lymphocyte count (OR=3.22, 95%CI 1.66-6.31, P<0.001) or decrease in serum albumin (OR=2.00, 95%CI 1.01-3.98, P=0.047). The risk of airway mucus hypersecretion was increased in children with RSV pneumonia combined with elevated peripheral blood eosinophils (OR=3.04, 95%CI 1.02-8.93, P=0.043). Meanwhile, airway mucus hypersecretion was associated with severe pneumonia (OR=2.46, 95%CI 1.03-6.15, P=0.047) in children with RSV pneumonia. Older age was associated with increased risk of airway mucus hypersecretion in children with adenovirus pneumonia (OR=1.02, 95%CI 1.00-1.04, P=0.026). In these children with occurrence of pulmonary rales, wheezes or sputum sounds (OR=3.65, 95%CI 1.22-12.64, P=0.028) had an increased risk of airway mucus hypersecretion. Neutrophils in bronchoalveolar lavage fluid (BALF) demonstrated higher ratio in hypersecretion group from children with MPP (0.65 (0.43, 0.81) vs. 0.59 (0.34, 0.76), U=24 507.00, P<0.01), while the proportion of macrophages in BALF was lower (0.10 (0.05, 0.20) vs. 0.12 (0.06, 0.24), U=33 043.00, P<0.05). Nucleated cell count and neutrophil ratio in BALF were higher in hypersecretion group of children with RSV pneumonia (1 210 (442, 2 100)×106 vs. 490 (210, 1 510)×106/L, 0.43 (0.26, 0.62) vs. 0.30 (0.13, 0.52), U=2 043.00, 2 064.00, all P<0.05). Conclusions: The increase in peripheral blood white blood cell count, neutrophil ratio and decrease in lymphocyte count, serum albumin in children with MPP is related to the development of airway mucus hypersecretion. In children with RSV pneumonia, the abnormal increase of eosinophils in peripheral blood has relationship with hypersecretion. The appearance of lung rale, wheezing, and sputum rale are associated with airway mucus hypersecretion in children with adenovirus pneumonia. In addition, local neutrophil infiltration in the respiratory tract is closely related to the occurrence of airway mucus hypersecretion caused by Mycoplasma pneumoniae and RSV infection.

Comparative analysis of therapeutic plasma exchange with different types of blood cell separators / 医疗卫生装备

Objective To analyze and compare the therapeutic effects of COM.TEC and COBE Spectra blood cell separators in therapeutic plasma exchange.Methods Totally 20 patients admitted to some hospital from March to July 2022 were selected as the study subjects prospectively,and then divided into A and B groups randomly.Therapeutic plasma exchange was carried out with COM.TEC blood cell separator in group A(10 cases,42 treatments)and COBE Spectra blood cell separator in group B(10 cases,36 treatments).The two groups were compared in terms of anticoagulant dosage,plasma exchange time and adverse events.SPSS 25.0 software was used for statistical analysis.Results The anticoagulant dosage for per liter of circulating blood volume in group A was(76.83±7.80)mL,which was significantly lower than that((83.89±1.16)mL)in group B(t=5.040,P＜0.05).When the fluid balance was set to 100％,the plasma exchange time for per liter of plasma in group A was(38.39±5.74)min,which was statistically shorter than that((42.30±5.35)min)in group B(t=3.528,P＜0.05).There were 11 adverse events in group A including 2 allergic reactions and 9 instrument alarms,and 8 adverse events in group B including 4 allergic reactions and 4 instrument alarms.Conclusion Both COM.TEC and COBE Spectra blood cell separators can meet the requirements for clinical treatment in spite of differences in performances,and the blood cell separator has to be selected properly for therapeutic plasma exchange based on patient conditions.[Chinese Medical Equipment Journal,2023,44(10):55-58]

Molecular Mechanism of Jingfang Mixture Against H1N1 Influenza Based on Network Pharmacology and Experimental Verification / 中国实验方剂学杂志

ObjectiveTo predict the potential targets and mechanism of Jingfang mixture in the treatment of H1N1 influenza and provide references for clinical application of Jingfang mixture. MethodThe active components and targets of Jingfang mixture against H1N1 influenza were screened out by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP），SwissTargetPrediction， and TargetNet. The targets of H1N1 influenza were obtained from GeneCards，Online Mendelian Inheritance in Man （OMIM）， and DisGeNET and standardized by UniProt KB. The intersection targets were obtained by Venny 2.1.0. The "drug-component-target" network was constructed with Cytoscape 3.2.1 and analyzed for the topological attributes. The intersection targets were uploaded to STRING 11.5 to obtain the protein-protein interaction （PPI） network. Gene Ontology （GO） enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） analysis were carried out by Metascape. Finally，the top active components ranked by degree were docked to the core targets by Autodock vina and visually analyzed by PyMOL. Balb/c female rats were used for experimental verification. Hematoxylin-eosin（HE） staining was used to observe the pathological changes in lung tissues. Enzyme-linked immunosorbent assay（ELISA）was used to detect the levels of tumor necrosis factor-α（TNF-α），interleukin-10（IL-10）， and interleukin-17（IL-17）. Real-time fluorescence-based quantitative polymerase chain reaction（Real-time PCR） and Western blot were used to detect the mRNA and protein expression levels in lung tissues. ResultThere were 144 active components in Jingfang mixture. A total of 421 target genes of Jingfang mixture and 2 956 targets of H1N1 influenza were identified，including 199 common targets. Topological analysis showed that the core components of Jingfang mixture against H1N1 influenza included quercetin，luteolin， and kaempferol，and the core targets included prostaglandin-endoperoxide synthase 2（PTGS2），estrogen receptor alpha（ESR1），inducible nitric oxide synthase 2（iNOS2），peroxisome proliferator-activated receptorγ（PPARγ），and cyclooxygenase-1（PTGS1）. GO enrichment yielded 697 items in biological process （BP） （P<0.01）， 59 items in molecular function （MF）（P<0.01）， and 21 items in cellular component （CC） （P<0.01）. A total of 132 signaling pathways （P<0.01） were obtained by KEGG enrichment analysis， including phosphatidylinositol 3-kinases（PI3K）/protein kinase B（Akt） signaling pathway and mitogen-activated protein kinase（MAPK） signaling pathway，most of which were related to the regulation of immune inflammation. Molecular docking showed that the binding energy of the active components of Jingfang mixture to the core targets was less than -5.0 kcal·mol-1，indicating good binding activity. HE staining showed that the lung tissues were significantly improved after drug intervention，and Real-time PCR and Western blot showed that Jingfang mixture could reduce the mRNA and protein expression of PI3K and Akt in lung tissues. ConclusionJingfang mixture can play an anti-viral effect against the influenza A virus through multiple components，multiple targets， and multiple pathways. The active components quercetin，luteolin， and kaempferol may control the inflammation and regulate immunity on the PI3K/Akt，MAPK， and other signaling pathways by acting on targets such as PTGS2，ESR1，iNOS2，PPARγ， and PTGS1.

Effect of Yupingfeng San on Expressions of GATA3，Foxp3 in Allergic Rhinitis Mice / 中国实验方剂学杂志

Objective:To study the effect of Yupingfeng San （YPFS） on the expressions of GATA binding protein 3 （GATA3） and forkhead transcription factor3 （Foxp3） in ovalbumin （OVA）-induced lung tissue of allergic rhinitis （AR） mice， and explore the mechanism of YPFS on AR. Method:The allergic rhinitismice model was established by intraperitoneally injecting with OVA and Al （OH）3， and challenged with OVA intranasally. The mice were divided into four groups： normal，model，chloretadine（3 mg·kg-1） and YPFS（6.5 g·kg-1） group， the corresponding drugs were orally administrated for three weeks. At the end of administration，the infiltration of inflammatory cells， such as mast cells， eosinophils and neutrophils in nasal mucosa， were observed by htoxylin eosin （HE） staining. The serum concentrations of OVA-specific IgE and cytokines ［interleukin-4（IL-4）， IL-5 and γ-interferon （INF-γ）］ were determined by enzyme-linked immune sorbent assay （ELISA）. The expressions of GATA3 and Foxp3 proteins in nasal mucosa tissue were detected by Western blot. Result:The AR mice had such symptoms as scratching， sneezing and running nose. Nasal mucosa section by HE staining showed significant desquamation of AR mouse nasal mucosa cilia， obvious tissue stromal edema， telangiectasia， and a large number of eosinophilic cells， lymphocytes， plasma cells infiltration. YPFS obviously improved nasal symptoms of allergic rhinitis mice. Nasal mucosa epithelial structure was complete and arranged evenly， with no obvious tissue clearance edema and vasodilation， and inflammatory cell infiltration was significantly reduced. Compared with normal group， the levels of OVA specific IgE， IL-4 and IL-5 in peripheral blood of AR model group were significantly higher（P<0.01）， and the INF-γ level was significantly lower （P<0.01）. Compared with AR model group， the administration of chloretadine and YPFS can significantly reduce the level of OVA specific IgE and IL-4， IL-5， and increase the level of INF-γ in AR mice peripheral blood （P<0.05， P<0.01）. Western blot results showed that compared with normal group， GATA3 protein expression was significantly increased， while Foxp3 protein expression was significantly decreased in AR model group （P<0.05， P<0.01）. Compared with AR model group， YPFS inhibited GATA3， and promoted Foxp3 protein expression （P<0.01）. Conclusion:YPFS has an effect in alleviating OVA-induced allergic rhinitis．YPFS may modulate the immune response by regulating the balance of Th2/Treg cells.

Flavonoids from stem and leaf of Scutellaria baicalonsis Georgi inhibit PHF abnormality and regulatory mechanism of protein phosphatase in rats' brain induced by okadaic acid / 中国病理生理杂志

AIM:To investigate the effect of flavonoids from stem and leaf of Scutellaria baicalonsis Georgi(SSF)on paired helical filament(PHF)abnormality and the regulatory mechanism of protein phosphatase(PP)in rats' brain induced by okadaic acid(OA).METHODS:Male Sprague-Dawley(SD)rats were microinjected with OA(200 ng/kg)by the lateral ventricle to establish a memory impairment model.Morris water maze was used to screen the memory impairment model.The successful model rats were continuous intragastric infusion(ig)SSF for 36 days.The relative pro-tein expression of PHF,PP1,PP2A-Cα,PP2A-Cβ,PP2CA and PP2CB in the rat cerebral cortex and hippocampus were detected by Western blot.GinKgo biloba leaf flavonoids(GLF)were used as positive control drug.RESULTS:Compared with the sham-operated rats ,the relative protein expression of PHF in the cerebral cortex and hippocampus and PP 1 in cor-tex of model rats were significantly increased(P<0.01),and the protein expression of PP2A-Cα,PP2A-Cβin the cere-bral cortex and hippocampus and PP2CB in the hippocampus were decreased(P<0.05),while the relative protein expres-sion of PP2CA and PP2CB in the cortex were significantly increased(P<0.01).SSF reversed the abnormality in the pro-tein expression of PHF,PP2A-Cαand PP2A-Cβin rat cortex and hippocampus and PP1 in rat cortex induced by OA(P<0.01),which had no significant effect on the relative protein expression of PP 2CA and PP2CB.GLF also showed similar results to SSF.CONCLUSION:SSF significantly reduces the abnormal formation of PHF in rats ' brain induced by OA ,which may be related to the regulation of PP 1,PP2A-Cαand PP2A-Cβexpression,but not with PP2CA and PP2CB ex-pression.

Determination of Trace ZnⅡ, CdⅡ and PbⅡ Metal Ions Using In-situ Bismuth-modified Boron Doped Diamond Electrode / 分析化学

Bismuth modified boron doped diamond (BDD) film electrode was employed for simultaneous determination of trace ZnⅡ,CdⅡand PbⅡby anodic stripping voltammetry.BiⅢwas simultaneously in-situ deposited on bismuth modified boron doped diamond electrode with ZnⅡ,CdⅡ and PbⅡ by pre-concentration.In the presence of BiⅢ,the sensitivity for determination of ZnⅡ,CdⅡ and PbⅡ was remarkably enhanced.Influence factors such as bismuth concentration,boron doped concentrations of BDD electrode,pH,preconcentration potential were investigated and optimized.Under the optimal conditions,the stripping peak currents increased linearly with the increasing concentration of ZnⅡ,CdⅡ and PbⅡ in the range of 10-300 μg/L.The limit of detection was 0.56 μg/L for ZnⅡ,0.32 μg/L for CdⅡand 0.75 μg/L for PbⅡ (S/N=3),respectively.The interference experiments showed that common ions had little influence on the determination except CuⅡ.In addition,the developed electrode displayed a good repeatability.The method was successfully applied to determination of ZnⅡ,CdⅡ and PbⅡ in real water samples with the standard addition recoveries of 92.0%-114.0%.

Research progress of Notch signaling pathway in tumor / 基础医学与临床

Notch gene encodes a class of highly conserved cell surface receptors that determine the fate of cells in embryonic development and mature tissue, which is an important pathway of communication between adjacent cells, and then regulates of cell development, proliferation and apoptosis. The occurrence and progression of multiple tumors are associated with abnormal Notch signaling pathways. For different tumors, it is important significance for anti-tumor therapy to effectively regulate the Notch participants and target molecules.

Correlations between Mitofusin 2 Expression in Fibroblasts and Pelvic Organ Prolapse: AnStudy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Both Mitofusin 2 (Mfn2) and pelvic organ prolapse (POP) are related to aging. The aim of the present study was to investigate the variations of Mfn2 expression in the uterosacral ligaments of patients with and/or without POP and their correlations with the expression of procollagen.</p><p><b>METHODS</b>Fibroblasts were cultured using tissue specimens that were harvested from the uterosacral ligaments of POP and non-POP (NPOP) patients (n = 10 for each group) from September 2016 to December 2016. The Cell Counting Kit-8 (CCK-8) assay was used to compare the differences in cell proliferation between the two groups. Relative quantitative reverse transcription-polymerase chain reaction and Western blotting assays were employed to assess the differences in the mRNA and protein expression levels of Mfn2 and procollagen 1A1/1A2/3A1 between the two groups. The changes in procollagen expression were assessed following the downregulation of Mfn2 in the POP group using RNAi. The data were assessed with independent sample t- test or general linear model univariate analysis using the SPSS 13.0 software.</p><p><b>RESULTS</b>The results from CCK-8 assay indicated that cell viability in the POP group was significantly lower compared with that of the NPOP group (td5, 7, 9, 11= -5.925, -6.851, -9.129, and -9.661, respectively, all P < 0.001, from D5 to D11). The mRNA and protein expression levels of Mfn2 in the cultured fibroblasts of the POP group were significantly higher compared with those of the NPOP group (mRNA: t = 2.425, P = 0.032; protein: t = 2.392, P = 0.037, respectively), whereas only the expression levels of procollagen 1A1/1A2/3A1 were significantly higher in the NPOP group (mRNA: t = -2.165, P1A1 = 0.041; t = -2.741, P1A2 = 0.026; t = -2.147, P3A1 = 0.045, respectively; protein: t = -2.418, P1A1 = 0.029; t = -2.405, P1A2 = 0.033; t = -2.470, P3A1 = 0.012, respectively). The expression levels of procollagen in the POP group increased following the downregulation of Mfn2.</p><p><b>CONCLUSIONS</b>The proliferation rate and cell viability of the fibroblasts in the POP group were significantly lower compared with those in the NPOP group. In the POP fibroblasts, Mfn2 expression was increased, while procollagen expression was decreased.</p>

Clinical features of mild encephalitis/encephalopathy with a reversible splenial lesion in children / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the clinical features of mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) in children.</p><p><b>METHODS</b>The clinical data of 8 children with MERS were retrospectively analyzed.</p><p><b>RESULTS</b>The mean age of onset was 5 years and 2 months (range 10 months to 12 years). The major clinical features included a history of prodromal infection, and among these children, 5 had pyrexia and 4 had vomiting. Of all the children, 6 were manifested as convulsion and 3 each were manifested as disturbance of consciousness and paroxysmal paropsia. Cranial diffusion-weighted magnetic resonance imaging (MRI) showed high signals in the splenium of the corpus callosum. Among these children, one child had symmetric and multiple long T1 and long T2 signals in the bilateral centrum semiovale and part of the temporal white matter. MRI reexamination performed after 5-30 days showed the disappearance of abnormal signals in all the children. The children were followed up for 3 months to 2 years, and no child experienced abnormal neurodevelopment.</p><p><b>CONCLUSIONS</b>The development of MERS in children is closely associated with infection. MERS is characterized by high signals in the splenium of the corpus callosum on cranial diffusion-weighted MRI. Most children have good prognosis.</p>

Dynamic Alterations in Microarchitecture, Mineralization and Mechanical Property of Subchondral Bone in Rat Medial Meniscal Tear Model of Osteoarthritis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The properties of subchondral bone influence the integrity of articular cartilage in the pathogenesis of osteoarthritis (OA). However, the characteristics of subchondral bone alterations remain unresolved. The present study aimed to observe the dynamic alterations in the microarchitecture, mineralization, and mechanical properties of subchondral bone during the progression of OA.</p><p><b>METHODS</b>A medial meniscal tear (MMT) operation was performed in 128 adult Sprague Dawley rats to induce OA. At 2, 4, 8, and 12 weeks following the MMT operation, cartilage degeneration was evaluated using toluidine blue O staining, whereas changes in the microarchitecture indices and tissue mineral density (TMD), mineral-to-collagen ratio, and intrinsic mechanical properties of subchondral bone plates (BPs) and trabecular bones (Tbs) were measured using micro-computed tomography scanning, confocal Raman microspectroscopy and nanoindentation testing, respectively.</p><p><b>RESULTS</b>Cartilage degeneration occurred and worsened progressively from 2 to 12 weeks after OA induction. Microarchitecture analysis revealed that the subchondral bone shifted from bone resorption early (reduced trabecular BV/TV, trabecular number, connectivity density and trabecular thickness [Tb.Th], and increased trabecular spacing (Tb.Sp) at 2 and 4 weeks) to bone accretion late (increased BV/TV, Tb.Th and thickness of subchondral bone plate, and reduced Tb.Sp at 8 and 12 weeks). The TMD of both the BP and Tb displayed no significant changes at 2 and 4 weeks but decreased at 8 and 12 weeks. The mineral-to-collagen ratio showed a significant decrease from 4 weeks for the Tb and from 8 weeks for the BP after OA induction. Both the elastic modulus and hardness of the Tb showed a significant decrease from 4 weeks after OA induction. The BP showed a significant decrease in its elastic modulus from 8 weeks and its hardness from 4 weeks.</p><p><b>CONCLUSION</b>The microarchitecture, mineralization and mechanical properties of subchondral bone changed in a time-dependent manner as OA progressed.</p>

Progress in promoting mechanism of tunneling nanotubes formation / 第二军医大学学报

Tunneling nanotubes (TNT) is a newly discovered connection mode between animal cells, and its formation is of great importance in physiological and pathological processes of animals and humans. The forming conditions and the promoting mechanism of TNT are not fully understood yet. It has been known that the state of cells (such as inflammatory conditions and stress reaction), molecular level (Fas ligand, cell adhesion molecules and the ligand interactions, M-Sec/TNFaip2/B94 and lipid molecules), and pathogenic infection are important for the formation of TNT. In this paper we reviewed the promoting mechanisms for TNT formation.

Plasma levels of omentin-1 and visfatin in senile patients with coronary heart disease and heart failure

OBJECTIVE@#To investigate the alteration of plasma levels of omentin-1 and visfatin in elderly patients with coronary heart disease (CHD) and heart failure.@*METHODS@#Plasma omentin-1 and visfatin levels were measured in 90 subjects (29 stable angina pectoris (SAP) cases, 30 unstable angina pectoris (UAP) cases and 31 age- and sex-matched healthy controls (age ≥ 60 years) by enzyme-linked immunosorbent assay methods. According to the New York Heart Association classification, 59 CHDs were divided into three groups: functional I class, 11 cases; functional II/III class, 36 cases; and functional IV class, 12 cases.@*RESULTS@#The plasma level of omentin-1 in CHD patients was significantly lower than that of the control group. Omentin-1in SAP group and UAP group were significantly lower compared to the control group (there was no statistical significance between UAP group and SAP group; P >0.05). The plasma level of visfatin in CHD patients was significantly higher than that of the control group. Similarly, visfatin in SAP group and UAP group were all significantly higher compared to the control group, while there was no statistical significance between UAP group, and SAP group. The plasma omentin-1 level was negatively correlated with SBP (r=-0.264, P<0.05), positively correlated with HDL-c level (r=0.271, P<0.05); the plasma visfatin level was positively correlated with TC (r=0.292,P<0.05), negatively correlated with HDL-c level (r=-0.266,P<0.05). There was a negative correlation between plasma omentin-1 and visfatin levels (r=-0.280, P<0.05). Moreover, multiple linear stepwise regression analysis showed that omentin-1 and visfatin levels might be affected by HDL-c level. Logistic regression analysis showed that visfatin could be an independent risk factor of CHD.@*CONCLUSIONS@#Decreased levels of omentin-1 and increased levels of visfatin may be involved in the occurrence and development of CHD. Omentin-1 and visfatin, independently, may be protective and pro-inflammatory cytokines. Additionally, both omentin-1 and visfatin may be related to lipid metabolism. Visfatin may be an independent risk factor of CHD.

Modified method for whole bone marrow adherent culture of human bone marrow mesenchymal stem cells / 中国实验血液学杂志

This study was aimed to investigate a more convenient and efficient method to cultivate the human bone marrow mesenchymal stem cells by means of natural erythrocyte sedimentation principle, based on the whole bone marrow adherent method. The bone marrow was cultured with a six-well plate instead of the flasks.Firstly, the bone marrow specimen was cultivated with the MSC complete medium for 48 h, then the upper RBC-free supernatant layer was drawn and placed into the new wells to isolate MSC. Inverted microscope was used to observe the cell morphology and to record the adherent time of first cell passage, first passaging time. The traditional whole bone marrow adherent method was used as the control. The cell cycle and cell surface markers were detected by flow cytometry,and the differentiative capacity of MSC into osteocyte and adipocyte was identified by alkaline phosphatase kit and oil red O, respectively. Besides, the proliferative curve of P1,P3,P5 of BMSC was depicted by counting method. The results showed that MSC cultured by the modified method highly expressed CD90, CD105, CD13, CD44 and lowly expressed CD14, CD45, CD34. Concerning the cell cycle feature, it was found that most of the cells were in G0/G1 phase (88.76%) , followed by G2/M phase (3.04%) and S phase (8.2%), which was in accordance with stem cell cycle characteristics. The proliferative curve showed a typical "S" type, and both the oil red O and alkaline phosphatase staining of MSC were positive. Compared with the traditional method, the modified method had the advantage of high adherence rate (P = 0.0001) and shorter passaging time for the first passage (P = 0.001), with the statistically significant difference. It is concluded that there is a large number of adherent, active and suspended MSC in the RBC-free supernatant layer after the culture of bone marrow for 48 h. Isolating MSC by the modified method is more convenient and efficient than the traditional whole bone marrow adherent method.

Value of contrast-enhanced ultrasound (CEUS) in the differential diagnosis between benign and malignant renal neoplasms / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the value of contrast enhanced ultrasound (CEUS) imaging in the differential diagnosis between benign and malignant renal neoplasms.</p><p><b>METHODS</b>Two hundred and forty-five cases of renal space-occupying lesions confirmed by biopsy or surgical pathology were included in this study. The CEUS features of the renal space-occupying lesions, i.e., the enhancement degree, homogeneity of enhancement, washing-in and washing-out time and enhancement pattern, were retrospectively analyzed.</p><p><b>RESULTS</b>There were 210 cases of malignant renal tumors and 35 cases of benign lesions. The CEUS modes of the malignant renal tumors included "quick in and quick out" 82 cases, "quick in and slow out" 64 cases, "slow in and quick out" 18 cases and "slow in and slow out" 46 cases; good enhancement 150 cases (71.4%) and inhomogeneous enhancement 180 cases (85.7%).Both the contrast agent filling defect area and solid component enhancement of solid-cystic tumors were important features of malignant renal tumors. In the 35 cases of benign lesions,the CEUS modes included "quick in and quick out" 4 cases, "quick in and slow out" 8 cases, "slow in and quick out" 10 cases and "slow in and slow out" 13 cases. Most of the benign tumors showed low enhancement 51.4% (18/35) and inhomogeneous enhancement 54.3% (19/35). There were significant differences between the malignant and benign renal neoplasms in CEUS mode, degree of enhancement and homogeneity of enhancement (P < 0.05), and in time of increasing, peak time, peak intensity and peak intensity ratio (P < 0.05). The accuracy rates of contrast-enhanced ultrasound for diagnosis of benign and malignant tumors were 77.1% and 83.8%, respectively, while the two-dimensional ultrasound diagnosis of benign and malignant tumors were 68.6% and 76.7%, respectively, with a significant difference (P < 0.05).</p><p><b>CONCLUSIONS</b>CEUS may provide more information to improve the diagnostic accuracy for renal neoplasms, and may play important role in differential diagnosis between benign and malignant renal lesions.</p>

Efficacy evaluation for the treatment of unstable lumbar disc herniation by traditional and modified lamina osteotomy replantation / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The traditional lamina osteotomy replantation method is prone to nerve root injury and low back pain recurrence. Our team has proposed a modified approach that improves the osteotomy site and its fixation procedure. The aim of this study was to evaluate the clinical efficacy of traditional and modified lamina replantation methods in treating unstable lumbar disc herniation.</p><p><b>METHODS</b>From March 2008 to August 2011, 124 patients with unstable lumbar disc herniation were enrolled and randomly divided into the following two groups according to random digital table: group A (traditional group) consisting of 61 patients who underwent traditional laminectomy replantation, and group B (modified group) consisting of 63 patients who underwent modified lamina replantation. Both surgeries were performed by the same surgeons. The two groups had no significant difference in gender, age, symptoms, time of onset and the prominent segment. Visual analogue scale (VAS), Oswertry disability index (ODI), and Japanese Orthopaedic Association (JOA) scores, operative time, blood loss, complication rate, radiographic healing rates, and low back pain recurrence rates were compared between the two groups.</p><p><b>RESULTS</b>There were 121 patients followed up for more than one year, and the follow-up rate was 97.6%. Nerve injury occurred in two patients (3.3%) in the modified group and 12 patients (20.0%) in the traditional group. Dural injury occurred in one patient (1.6%) in the modified group and seven patients (11.7%) in the traditional group. Pseudarthrosis occurred in two patients in the modified group and in 18 patients in the traditional group with 1-year fusion rates of 96.7% and 70.0%, respectively. Recurrence of lower back pain after one year was noted in three patients (4.9%) in the modified group, and in 15 (25.0%) in the traditional group. Leg pain recurrence was noted in one patient (1.6%) in the modified group and in three cases (5.0%) in the traditional group. The one-year healing rates of nerve injury, dural injury, replantation lamina and low back pain recurrence rates after one year were significantly different (P < 0.05) between the two groups. At two weeks, three months, six months and one year postoperatively, both groups had significant improvement in VAS, ODI, and JOA scores from their preoperative values (P < 0.05). No significant difference was detected between the short term postoperative scores between groups A and B (P > 0.05). However, a significant difference was found one year later (P < 0.05).</p><p><b>CONCLUSIONS</b>Compared to the traditional approach, the modified technique for lamina replantation showed lower rates of dural and nerve damage, a higher lamina healing rate, a lower back pain recurrence rate, and better clinical scores. It is a safe and effective operation for lumbar spine surgery.</p>

Research progress of mesenchymal stem cell-derived microvesicle / 中国实验血液学杂志

Mesenchymal stem cell-derived microvesicle (MSC-MV) is a membrane secretory system which includes microparticle and exosome, and MSC-MV is released by MSC in resting or activated state. MSC-MV selectively package the biological active substances such as lipids, proteins, mRNA and miRNA but not loads them randomly. It has definitive effect of reducing tissue injury, promoting morphological and functional recovery of the injured tissue, and this effect is probably mediated by miRNA. What is more, the MSC-MV may also possess the biological function of immunological regulation, modulation of cell growth and differentiation. The generation, constitution, and function of MSC-MV are reviewed in this article.

Effect of Dingguier umbilical paste on rats with functional dyspepsia and mice with splenic asthenia / 中国中药杂志

<p><b>OBJECTIVE</b>To observe the effect of Dingguier umbilical paste on rats with functional dyspepsia and mice with splenic asthenia, and investigate the related mechanism.</p><p><b>METHOD</b>Functional dyspepsia models of rats were made by irregular food intake plus diluted hydrochloric acid. Successional treatments were offered for 14 days. The rats weights, contents of serum NO, AChE and MC were measured. The rats with splenic asthenia were made by rhubarb feed, and observed the affection of gastric emptying.</p><p><b>RESULT</b>Compared with those in the model control group, the weight of rats in all dosages Dingguier umbilical paste groups increased obviously (P < 0.05), pepsin activity of rats in the dosage (1.34 g x kg(-1)) Dingguier umbilical paste groups was significantly higher and the contents of NO and quantities of MC in the dosage (2.67 g x kg(-1)) Dingguier umbilical paste groups decreased clearly (P < 0.05), and the contents of serum AChE in all dosages Dingguier umbilical paste groups rose apparently. The weight of mice with splenic asthenia increased obviously, accelerated gastric emptying, and improved the symptom.</p><p><b>CONCLUSION</b>Dingguier umbilical paste has significant improvement of indigestion. The related mechanism may be to reduce the content of serum NO and the quantity of MC and enhance the content of serum AChE.</p>

Analysis of the immunohistochemical subtypes and prognosis of primary diffuse large B cell lymphoma of the central nervous system / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To analyze the subtypes of primary diffuse large B cell lymphoma of the central nervous system (CNS DLBCL) and to explore the relationship between the subtype classification and prognosis.</p><p><b>METHODS</b>Immunohistochemical staining was used to determine the expression of CD20, CD3, CD10, Bcl-6, Mum-1, CD5, Bcl-2, Ki-67, FOXP-1, GCET-1, BLIMP-1 and LMO-2 antigens on paraffin-embedded sections of 47 cases. Hans, Choi and Tally subtypes were classified, and univariate and multivariate analyses were used to elucidate the relationship between the subtypes and prognosis.</p><p><b>RESULTS</b>In the 47 cases, the expression of Bcl-2 in the tumor cells was 46.8%, CD10 4.3%, Bcl-6 70.2%, Mum-1 53.2%, GCET-1 36.2%, BLIMP-1 4.3%, FOXP-1 63.8% and LMO-2 19.2%. The positive rate of Ki-67 was 30% to 95%, with a median of 80%, of which 12 cases (25.5%) was > or = 90%. The Hans subtype classification showed 16 cases (34.0%) were of GCB type and 31 cases (66.0%) of non-GCB type. The Choi subtype classification showed 16 cases (34.0%) were of GCB type and 31 cases (66.0%) of ABC type. The Tally subtype classification showed 6 cases (12.8%) were of GCB type and 41 cases (87.2%) of non-GCB type.</p><p><b>CONCLUSIONS</b>The results of this study show that there is no significant correlation between the three subtypes and prognosis. The prognosis is correated with post-operative radiotherapy, chemotherapy and MTX therapy.</p>