Objective:To observe the the effects of sustained-release coatings of HU-308 on the biological characteristics of rat oste-oblasts(ROBs)on Ti surface.Methods:The heparin/chitosan sustained release coatings containing HU-308 at different concentra-tions were prepared by layer-by-layer assembly technology on the alkali-and heat-treated Ti surface.The alkali-and heat-treated Ti samples were randomly divided into six groups,the samples in C group were used as control,in P group were treated by heparin/chi-tosan coatings and in T1,T2,T3 and T4 groups were treated by heparin/chitosan sustained-release coating containing HU-308 at dif-ferent concentrations.The adhesion,proliferation and ALP activity of ROBs cultured on the coatings were assessed at different times. Results:The adhesion,proliferation and ALP activity of ROBs of T4 group (the impregnating concentration of HU-308 was 0.025 mg/L)were the highest.Conclusion:The sustained-release coating with low concentration of HU-308 may improve the adhesion , proliferation and ALP activity of ROBs.

To better understand the drugs, frequency and other factors involved in the drug-induced renal failure, 227 cases of renal failure reported in the Chinese medical and pharmaceutical journals were statistically analyzed. Our results showed that the drugs that tend to cause renal failure are antibiotics, involving 80 cases, followed by antituberculosis agents(38 eases)and dehydration agents. Gentamycin (47 cases) and rifrimactane(36 cases) were among the drugs with highest incidence. There were 58 cases of death due to drug-related renal failure.

Objective To investigate the molecular mechanisms of synergistic effects of BFA and CDDP on human lung cancer GLC-82 cells, and to test the levels of PERK-ATF4 pathway. Methods GLC-82 cells were incubated with 50 ng/mL of BFA or/and 2 μg/mL of CDDP for 24 or 48 hours. The levels of PERK, p-PERK and ATF4 in GLC-82 were analyzed by real-time PCRand/or Western Blot. Results The levels of PERK were lowest in CDDP group, but higher in BFA group (P < 0.05), the highest in group of BFA+CDDP (P < 0.05 or P < 0.01). The p-PERK level decreased in group of BFA+CDDP (P < 0.05 or P < 0.01). There was no significant change of ATF4 expression in CDDP group, but ATF4 expression increased slightly in BFA group, and increased further in group of BFA+CDDP (P < 0.05 or P < 0.01)which was also higher than that in BFA group or CDDP group (P < 0.05 or P < 0.01). Conclusions The upregulated levels of PERK and ATF4 by the combination of BFA and CDDP may be one of the mechanisms of synergistic anti-cancer effect of BFA and CDDP on GLC-82 cells.

3-Hydroxy-3-methylglutaryl coenzyme-A reductase (HMGR), the first enzyme of mavalonic acid pathway, is one of the key devices involved in ginsenoside biosynthesis based on synthetic biology approach. The open reading frame of a novel HMGR gene from Panax ginseng (PgHMGR2) was cloned and analyzed in this study. PgHMGR2-encoding protein showed 71.6% sequence similarity to a P. ginseng HMGR in GenBank. The full-length cDNA sequence of PgHMGR2 containing 1 770 bp, which encodes 589 amino acids, was cloned by RT-PCR strategy from P. ginseng. The bioinformatic analysis showed that PgHMGR2-encoding protein contained two transmembrane regions and the HMG_CoA_reductase domain, without signal peptide. The protein sequence of PgHMGR2 had the highest sequence similarity (99%) with Panax quinquefolius HMGR (GenBank accession No. ACV65036). The expression level of PgHMGR2 was the highest in flower based on a real-time PCR analysis, followed by leaf and root, and the lowest was in stem. The result will provide a foundation for exploring the molecular function of PgHMGR2 involved in ginsenoside biosynthesis based on synthetic biology approach in P. ginseng plants.

To observe the relationship between positive rate of β1-adrenergic and AT1 receptors autoantibodies with serum concentration of cystatin C in 371 patients with diabetic nephropathy patients,107 patients with type 2 diabetes,and 47 subjects as healthy control.In patients with diabetic nephropathy,the positive rates of the β1 and AT1 receptors autoantibodies were significantly higher than those in patients with type 2 diabetes and normal controls.The titers of β1 and AT1 receptors autoantibodies in diabetic nephropathy patients with abnormal cystatin C were significantly higher than those with normal cystatin C concentration.These findings suggested that β1 and AT1 receptors autoantibodie may play important roles in the pathogenesis of diabetic nephropathy.

OBJECTIVETo evaluate the value of the clinical use of CT perfusion imaging (CTPI) and CT subtraction angiography (CTSA) for diagnosing acute ischemic cerebrovascular disease (AICVD).

METHODSTwenty-four patients with AICVD onset within 24 hours were examined with regular CT, CTPI, and CTSA. Some cases received CTPI, magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), digital subtraction angiography (DSA) or single photon emission computer tomography (SPECT) during follow-up examinations.

RESULTSOf the 24 cases, 11 had negative results from regular CT scans 3 - 6 hours after onset of stroke in 6 cases, 6 - 12 hours in 3 cases, and 12 - 24 hours in 2 cases. Ten of these cases were then confirmed by CTPI as having ischemic lesions, 2 with middle cerebral artery occlusion (MCAO), and 1 case with transient ischemic attack (TIA) with CTPI negative. Of the 24 cases, 13 had positive results from regular CT, 9 were diagnosed with ischemic lesions larger by using CTPI than regular CT, 1 case had MCAO and 1 had internal carotid artery occlusion (ICAO). There were 4 cases with ischemic lesions observed with regular CT having nearly the same range as that of lacunar infarctions using CTPI. Another 4 cases had more than 2 lesion areas. The peak time (PT), mean transit time (MTT) and relative flow (RF) of 24 cases were markedly different. The sides of ischemic lesions compared to each other and the core of the lesion compared to peripheral zones were also altered significantly (P < 0.01).

CONCLUSIONSCombined CTPI with CTSA can detect acute ischemic lesions at early and hyper-early stages and could distinguish between TIA, lacunar infarction and a larger area of infarction. Using semiquantitative blood perfusion analysis status, CTPI with CTSA could define position, area and range of the ischemic lesion and penumbra. These scans can also analyze the brain blood perfusion status. It is important to early diagnose the occlusion of the entire division of the internal carotid artery or middle cerebral artery and it is meaningful to assess prognosis and assignment of therapy.

Adult ; Aged ; Angiography, Digital Subtraction ; Brain Ischemia ; diagnostic imaging ; Cerebral Angiography ; Cerebrovascular Circulation ; Female ; Humans ; Male ; Middle Aged ; Tomography, X-Ray Computed

Objective To investigate the synergistic effects of tannic acid(TA) and cis-dichlorodiamine platinum(CDDP) on hepatocellular carcinoma HepG2 cells and its activation situation of endoplasmic reticulum stress(ERS) pathway.Methods Human hepatocellular carcinoma HepG2 cells were divided into the control group,TA group,CDDP group and TA+CDDP group,and were cultured in vitro for 24 h.The growth inhibitory effect of medication on HepG2 cells was detected by MTT assay.The pharmacodynamics synergistic effect between the two drugs was analyzed by the drug interaction index,drug dose reduction index and equivalent graphical method.The nucleus changes were observed by DAPI staining.Real time fluorescent quantitative PCR(q-RT-PCR) and Western blot were used to detect the levels of ERS markers glucose regulated protein (GRP)78 and GRP94.Results TA and CDDP had dose-dependent growth inhibition effect on HepG2 cells,their median effective concentrations(IC50) were 360.00 μmol/L and 1.80 μg/mL respectively.The combination treatment of 180.00 μmol/L TA and 0.90 μg/mL CDDP on HepG2 cells could enhance the inhibitory effect on cell growth.Ta and CDDP had synergistic effect for inhibiting hepatocellular carcinoma cells growth.Compared with the TA group and CDDP group,cell shrinkage and rounding were accelerated in the combined group,apoptotic cells were increased,nuclear had pyknosis,irregular edge and dense staining,nuclear fragmentations were increased and the expressions of GRP78 and GRP94 were up-regulated.Conclusion TA can enhance the effect of CDDP on anti-hepatic carcinoma HepG2 cells,and the synergy mechanism may be related to the activation of ERS pathway.

Objective To establish a clinical cytokine test method based on flow multiple microarray technology,and discuss its clinical significance by observing the change of cytokines level in the early stage of influenza.Methods 54 cases of influenza A virus positive and 20 cases of influenza A virus negative influenza like patients were selected as influenza group.Among them,influenza A virus positive patients were divided into mild group and severe group,influenza A virus negative influenza like patients were as neg-ative group.In addition,35 healthy people were selected as the control group,and the cytokine of all the whole blood samples was detected and statistically analyzed.Results Interleukin-6(IL-6),interleukin-21(IL-21),interleukin-12p70(IL-12p70),interleukin-1 β(IL-1 β)and interleukin-10(IL-10),chemokine-10(IP-10),interleukin-2(IL-2),monocyte chemoattractant protein-1(MCP-1)lev-els were significantly higher in the patients with early onset of influenza,and the difference was statistically significant(P<0.05). The difference of interferon-γ(IFN-γ)between the influenza group and the control group was not statistically significant(P> 0. 05).The levels of IL-6 and IP-10 in the severe group were higher than that of the mild group and the negative group,and the differ-ence was statistically significant(P<0.05).Conclusion IL-6,IL-21,IL-12p70,IL-1 beta,IL-10,IP-10,IL-2 and MCP-1 levels can be used as clinical biological evaluation indicators of patients with fever,of which IL-6 and IP-10 can be used as important indicators for disease progression assessment.

Objective:To investigate the effect and molecular mechanism of tumor necrosis factor-α-inducible protein 8-like 2(TIPE2)on lipopolysaccharide(LPS)or interleukin-4(IL-4)-induced phenotypic switch of adipose tissue macrophages(ATM).Methods:The expression levels of TIPE2, inducible nitric oxide synthase(iNOS), monocyte chemoattractant protein 1(MCP-1), CD206, and arginase 1(Arg-1)in the visceral adipose tissue of obese mice, TIPE2-knockout(KO)mice, and control mice were detected by immunohistochemistry, Western blotting, and real-time PCR(RT-qPCR). Peritoneal macrophages isolated from KO and wild-type mice and RAW 264.7 mouse macrophage cell line were cultured, and then stimulated with LPS(100 ng/mL)or IL-4(20 ng/mL)for 6 hours. The expression levels of TIPE2, iNOS, MCP-1, CD206, and Arg-1 were detected by Western blotting and RT-qPCR.Results:Obese mice showed down-regulated TIPE2 expression, up-regulated pro-inflammatory markers iNOS and MCP-1 expressions, and down-regulated anti-inflammatory markers CD206 and Arg-1 expressions. LPS decreased the expression of TIPE2 in RAW 264.7 cells and peritoneal macrophages from mice, increased the expression of the classically activated macrophages(M1 phenotype)markers iNOS and MCP-1, and decreased the expression of the substituting activated macrophages(M2 phenotype)markers CD206 and Arg-1. IL-4 increased the expression of TIPE2 in RAW 264.7 cells and peritoneal macrophages, decreased the expression of iNOS and MCP-1, and increased the expression of CD206 and Arg-1. During the M1 polarization of macrophages, LPS increased toll-like receptor(TLR4)expression as well as nuclear transcription factor κBα suppressor protein(IκBα) and NF-κB phosphorylations in macrophages. Knockout of TIPE2 further increased the expression of the TLR4/IκBα/NF-κB signaling pathway and M1 macrophage markers, and further reduced the expression of the M2 macrophage markers.Conclusion:TIPE2 regulates ATM phenotypic transformation through inhibition of the TLR4/IκBα/NF-κB signaling pathway, which ameliorates adipose tissue inflammation in obese states.

Objective:To disclose the genome characteristics and mutations of 2019 novel coronavirus (2019-nCoV) strains from the imported cases of Coronavirus Disease 2019 (COVID-19) in Gansu province, thereby to provide scientific reference for the prevention and control of COVID-19 in Gansu province. Methods:The respiratory tract specimens of imported COVID-19 cases from seven countries in Gansu province in 2020 were collected. The virus genome was sequenced by the second-generation sequencing technology, the whole genome sequences were compared and analyzed, and the MEGA software was used to construct a phylogenetic tree based on the neighbor-joining method.Results:A total of 46 2019-nCoV genome sequences with a length of 29 605~29 903 bp were obtained. Compared with the Wuhan reference strain (GenBank ID: NC_045512.2), it was found that the median (minimum to maximum) number of the nucleotide mutations of the 2019-nCoV genome sequence of the imported cases was 10 (7-24). A total of 134 nucleotide mutation sites were found in all 2019-nCoV genome sequences from 7 entry countries in Gansu province, distributed in 11 open reading frames (ORFs). The top three nucleotide mutations in different proteins: ORF1ab (78), S(20), N(12). Among the 134 nucleotide mutations, 82 caused amino acid mutations, and all of them were missense mutations. No insertions or deletions were seen. Types of deletion mutations, the top three amino acid mutations in different proteins: ORF1ab (46), S(11), N(10); the key sites of the receptor binding domain (RBD) of the S protein have not been mutated.Conclusions:No imported cases in Gansu province have been found to carry the reported mutations that can clearly lead to changes in the spread and pathogenicity of 2019-nCoV.