Objective The dynamic changes of hematopoietic function of bone marrow in patients with renal anemiabefore and after treatment and the curative effect of drug treatment were discussed through the detection of the related parameters of the red blood cell.Methods Reticulated red cells using Mindray-6900 automatic blood cell analyzer,54 cases of renal anemia patients were divided into three groups,respectively for renal function of compensatory group,renal function insufficiency decompensation group and renal failure group,and 45 cases of normal healthy group for comparison analysis were used to detect the reticulocyte percentage (RET),immature red blood cell index (IRF),red blood cell (RBC) count,hemoglobin (HB),serum creatinine (CR) and blood urea nitrogen (BUN) were detected before and after treatment of red blood cell hematocrit (HCT) and RET,and through the correction formula to calculatethe net knits red blood cell production index (RPI).The results were compared and analyzed.Results RET in renal failure compensatory group and renal failure group was significantly higher than that of the control group (P＜0.05);IRF％ in renal insufficiency compensatory group was significantly lower than that of control group (P＜0.05).and renal failure compensatory group and renal failure group were significantly higher than those of the control group (P＜0.05);RBC,Hb levels with the levels of bun and Cr increased significantly reduced,in kidney function not full decompensated group was significantly lower than that of control group (P＜0.05).and with the severity of the kidney was decreased gradually.Renal insufficiency compensatory group before and after treatment with HCT(％),Ret(％),HFR(％),MFR(％),RPI the difference was statistically significant (t=2.103,2.062,2.079,2.354,2.368;all P＜0.05),LFR (％) showed no significant difference (t=1.812,P＞ 0.05);renal insufficiency decompensation group before and after treatment with HCT(％),Ret(％),HFR(％),MFR(％),LFR(％),HFR showed significant differences (t =2.228,2.172,2.894,2.185,2.023,2.455;all P＜ 0.05);renal failure group HCT (％),Ret (％),HFR(％),MFR(％) HFR was statistically significant differences before and after the treatment (t=2.148,2.351,2.642,2.086,2.686;all P＜0.05),LFR(％) showed no significant difference (t=1.921,P＞0.05).The ROC area of IRF％ waslarger than other hematological indexes,and its diagnostic sensitivity and specificity were 88.4 ％ and 80.2 ％,respectively,when the critical value was 22.3 ％.Conclusion Reticulocyte erythrocyte parameters can effectively assist physicians in renal anemia patients for diagnosis and treatment,especially the IRF％ and RPI is net woven red cells more sensitive,and the index can more accurately reflect the growth of hematopoietic function of bone marrow and erythroid,worthy of clinical application.

Objective Analyze the relationship between high sensitivity C‐reactive protein (hs‐CRP) ,homocysteine (Hcy) ,D‐di‐mer (D‐D) levels and atherosclerosis (AS) .Methods A total of 92 patients with AS were analyzed retrospectively ,including acute coronary syndrome (ACS) group with 61 cases ,stable angina pectoris (SAP) group with 31 cases .According to the result of coro‐nary artery plaque CT detection was further divided into plaque group ,non plaque group ,stable plaque subgroup ,and unstable plaque subgroup .Meanwhile 42 healthy subjects were selected as control group .The levels of the three indicators were compared . Results The serum hs‐CRP ,Hcy and plasma D‐D concentration in the ACS group and SAP group were significant higher than those of the control group (P< 0 .05) ,and those of the ACS group were significant higher than those of the SAP group(P< 0 .05) . The serum hs‐CRP ,Hcy and plasma D‐D concentration in the plaque group were significant higher than those of the non plaque group ,those in the unstable plaque subgroup were significant higher than those of the stable plaque subgroup(P< 0 .05) .The serum hs‐CRP ,Hcy and plasma D‐D concentration of the ACS patients were all correlated positively .Conclusion Serum hs‐CRP ,Hcy and plasma D‐D levels are closely related to the development of AS ,the combined detection of three indexes is value for the prevention , treatment and prognosis of AS .

The transcellular process of coumarin 6 (C6) loaded poly(ethyl ethylene phosphate)-co-poly (epsilon-caprolactone) (PEG-PCL) micelles on Madin-Darby Canine Kidney (MDCK) epithelial cells was investigated. C6 loaded PEG-PCL micelles were prepared using the thin-film hydration method. The size of the micelles was characterized by dynamic light scattering analysis using a Malvern Zetasizer Nano ZS. The critical micelle concentration (CMC) was determined by pyrene fluorescence probe method. And the transcellular process of the micelles on MDCK epithelial cells was investigated by using transmission electron microscope, laser confocal scanning microscope and Förster resonance energy transfer technology. It turned out that the size of PEG-PCL micelles was about 30 nm and CMC was 1.01 microg x mL(-1). PEG-PCL micelles were endocytosed in intact form and they could deliver hydrophobic drugs across the basolateral membrane of the epithelial cells. However, PEG-PCL is hardly being transported in micelle formation itself. The transportation of C6 by PEG-PCL micelles was through the transcellular pathway, yet not the paracellular pathway.

iRGD-modified sterically stabilized liposomes loaded doxorubicin (iRGD-SSL-DOX) were prepared and their cellular toxicity and anti-tumor efficacy were evaluated, comparing to doxorubixin loaded sterically stabilized liposomes (SSL-DOX) and RGD modified doxorubixin loaded sterically stabilized liposomes (RGD-SSL-DOX). The iRGD peptide, with both tumor targeting and cell penetrating functions, was conjugated to DSPE-PEG-NHS and DSPE-PEG-iRGD was obtained. DSPE-PEG-RGD was gained in the same way. iRGD-SSL-DOX, RGD-SSL-DOX and SSL-DOX were prepared by ammonium sulfate gradient method. The size and zeta potential of the liposomes were characterized by dynamic laser light scattering. The cellular toxicity study was done on B16 melanoma cell line and the anti-tumor efficacy study was carried on B16 cell line bearing C57BL/6 mice. The results showed that the particle sizes of liposomes were all around 90-100 nm. DOX entrapment efficiency was above 95%. The formulations were with good preparation reproducibility. iRGD-SSL-DOX showed no significant difference in B16 cellular toxicity with SSL-DOX and RGD-SSL-DOX, but the anti-tumor efficacy on B16 melanoma bearing C57BL/6 mice was significantly better than that of SSL-DOX, similar as that of RGD-SSL-DOX. Therefore, iRGD modified liposomes loaded DOX would be a promising drug delivery system for tumor therapy.

The aimed of this study was to prepare stabilized thiomers to overcome the poor stability character of traditional thiomers. Poly(acrylic acid)-cysteine (PAA-Cys) was synthesized by conjugating cysteine with poly(acrylic acid) and poly(acrylic acid)-cysteine-6-mercaptonicotinic acid (PAA-Cys-6MNA, stabilized thiomers) was synthesized by grafting a protecting group 6-mercaptonicotinic acid (6MNA) with PAA-Cys. The free thiol of PAA-Cys was determined by Ellmann's reagent method and the ratio of 6MNA coupled was determined by glutathione reduction method. The study of permeation enhancement and stabilized function was conducted by using Franz diffusion cell method, with fluorescein isothiocyanate dextran (FD4) used as model drug. The influence of polymers on tight junctions of Caco-2 cell monolayer was detected with laser scanning confocal fluorescence microscope. The results indicated that both PAA-Cys and PAA-Cys-6MNA could promote the permeation of FD4 across excised rat intestine, and the permeation function of PAA-Cys-6MNA was not influence by the pH of the storage environment and the oxidation of air after the protecting group 6MNA was grafted. The distribution of tight junction protein of Caco-2 cell monolayer F-actin was influenced after incubation with PAA-Cys and PAA-Cys-6MNA. In conclusion, stabilized thiomers (PAA-Cys-6MNA) maintained the permeation function compared with the traditional thiomers (PAA-Cys) and its stability was improved. The mechanism of the permeation enhancement function of the polymers might be related to their influence on tight junction relating proteins of cells.

AIM: To observe the effects of Egr-1 gene knockout on the expression of inflammatory-related factors in pancreatic tissue in a mouse acute pancreatitis model.METHODS: The experimental pancreatitis was induced by high-dose of cearulein in wildtype mice and Egr-1 knockout mice.The pancreatitis indexes,such as serum amylase,pancreata edema,and myeloperoxidase(MPO) levels in pancreata and lungs were recorded.The mRNA levels of tissue factor(TF),plasminogen activator inhibitor(PAI-1),monocyte chemoattractant protein(MCP-1),Gro-1,IL-6 and ICAM-1 were measured by quantitative PCR.RESULTS: Contrary to wildtype mice,typical pancreatitis was not induced by high-dose cearulein in the Egr-1 knockout mice,not only markedly reduced edema in pancreata and lungs,but decreased MPO levels in lungs as well were found.Furthermore,the mRNA of TF,PAI,MCAP,ICAM-1 and IL-6 in pancreata were significantly decreased in Egr-1 knockout mice.CONCLUSION: The severity of pancreatitis and lung damage is ameliorated in Egr-1 knockout mice stimulated by high-dosage of cearulein,which was probably mediated by decreasing expression of inflammatory-related factors in pancreata,such as TF,PAI,MCP-1,ICAM-1 and IL-6.

OBJECTIVETo investigate the expression of programmed death-1 (PD-1) and programmed death ligand-1(PD-L1) in peripheral T-lymphocytes from patients with chronic periodontitis and its significance and to clarify its role in the development of chronic periodontitis.

METHODSA total of 73 subjects were included in the study and divided into three groups, chronic periodontitis(30 cases), chronic gingivitis(25 cases) and 18 healthy controls. The peripheral blood was collected and PD-1/PD-L1 expression in the surface of CD(+)4 T lymphocytes and CD(+)8 T lymphocytes was examined by flow cytometry. Blood samples from 16 chronic periodontitis patients were collected at week 0 and 6 after initial therapy for 6 weeks and PD-1 and PD-L1 expression in the surface of CD(+)4 and CD(+)8 T lymphocytes was also determined by flow cytometry. The data were statistically analyzed.

RESULTSThe percentage of PD-1 expression in CD(+)4 and CD(+)8 T lymphocytes of chronic periodontitis group[(16.7 ± 5.5)%,(20.8 ± 5.1)%]and chronic gingivitis group[(14.2 ± 6.1)%,(14.5 ± 4.3)%]were higher than that of healthy controls[(9.5 ± 2.1)%, (8.1 ± 1.9)%](P < 0.05). The percentage of PD-L1 expression in CD(+)4 and CD(+)8 T lymphocytes of chronic periodontitis group[(24.2 ± 7.1)%,(15.3 ± 6.8)%]and chronic gingivitis group[(12.4 ± 6.0)%,(11.2 ± 5.5)%]were higher than that of healthy controls[(4.7 ± 1.2)%, (3.2 ± 2.3)%] (P < 0.05). The percentage of PD-1/PD-L1 expression in CD(+)4 T lymphocytes and CD(+)8 T lymphocytes of the chronic periodontitis group were significantly decreased after initial therapy(P < 0.05).

CONCLUSIONSThe expression of PD-1 and PD-L1 in peripheral CD(+)4 T lymphocytes and CD(+)8 T lymphocyte of chronic periodontitis patients was up-regulated and was associated with periodontal condition. The initial therapy reduced the expression of PD-1 and PD-L1.

B7-H1 Antigen ; biosynthesis ; Case-Control Studies ; Chronic Periodontitis ; immunology ; metabolism ; Flow Cytometry ; Humans ; Programmed Cell Death 1 Receptor ; biosynthesis ; T-Lymphocytes ; Up-Regulation

Objective:To explore the diagnostic value of strain ultrasonic elastography (SUE) supported by Image Pro Plus (IPP) software in distinguishing benign and malignant Breast Imaging Reporting and Data System (BI-RADS) category 4 nodules.Methods:The clinical and ultrasound imaging data of 192 female patients with BI-RADS category 4 nodules diagnosed by breast ultrasound in Tianjin Medical University Cancer Institute and Hospital from January 2020 to January 2021 were retrospectively analyzed. One nodule was selected for each patient, and a total of 192 nodules were analyzed. The ultrasound images and SUE images of each nodule were acquired before surgery, followed by BI-RADS classification scoring and SUE scoring. The IPP software was applied to outline the region of interest of all nodules, and the software automatically counted the SUE area ratio (SUE-IPP-AR) of all nodules. Using pathological diagnosis as the gold standard, SUE-IPP scoring was performed based on the optimal cut-off value of SUE-IPP-AR for distinguishing benign and malignant nodules according to receiver operating characteristic (ROC) curve. The efficacy of BI-RADS classification, SUE score, SUE-IPP score, and SUE-IPP+BI-RADS combined score in the differentiation of benign and malignant breast nodules were analyzed by ROC curve. Kappa coefficient was used to assess inter-observer agreement for SUE and SUE-IPP-AR.Results:Of the 192 nodules, 58 were benign nodules and 134 were malignant nodules diagnosed by pathology. These nodules were classified by BI-RADS, with 46 nodules in BI-RADS category 4A, 57 nodules in BI-RADS category 4B and 89 nodules in BI-RADS category 4C. SUE images 1-6 level were 12, 14, 41, 51, 42, and 32 nodules, respectively. ROC curve analysis showed that the optimal cut-off value of SUE-IPP for determining benign and malignant BI-RADS category 4 breast nodules was 58% [area under the curve (AUC) = 0.729, sensitivity 73%, specificity 69%]. The AUC of SUE-IPP+BI-RADS combined score for determining benign and malignant nodules was the largest (0.871), which was higher than that of BI-RADS score (AUC = 0.829, Z = 2.51, P = 0.012), SUE-IPP score (AUC = 0.729, Z = 3.56, P < 0.001) and SUE score (AUC = 0.695, Z = 4.37, P < 0.001). The sensitivity of SUE-IPP+BI-RADS combined score ≥ 3 points for diagnosing malignant nodules was 86.6%, while the specificity was 82.8%. Therefore, SUE-IPP+ BI-RADS score had the best efficacy for determining benign and malignant nodules. There was good agreement between sonographer with more than 5 years of experience and those with less than 5 years of experience in applying SUE to diagnose breast malignant nodules (Kappa = 0.768, 95% CI 0.711-0.825), and very good diagnostic agreement in applying SUE-IPP (Kappa = 0.946, 95% CI 0.919-0.974). Conclusions:SUE-IPP can improve the diagnostic ability for BI-RADS category 4 breast malignant nodules and can be used as an adjunct to ultrasound diagnosis.

As one of the most important components of caveolae, caveolin-1 is involved in caveolae-mediated endocytosis and transcytosis pathways, and also plays a role in regulating the cell membrane cholesterol homeostasis and mediating signal transduction. In recent years, the relationship between the expression level of caveolin-1 in the tumor microenvironment and the prognostic effect of tumor treatment and drug treatment resistance has also been widely explored. In addition, the interplay between caveolin-1 and nano-drugs is bidirectional. Caveolin-1 could determine the intracellular biofate of specific nano-drugs, preventing from lysosomal degradation, and facilitate them penetrate into deeper site of tumors by transcytosis; while some nanocarriers could also affect caveolin-1 levels in tumor cells, thereby changing certain biophysical function of cells. This article reviews the role of caveolin-1 in tumor prognosis, chemotherapeutic drug resistance, antibody drug sensitivity, and nano-drug delivery, providing a reference for the further application of caveolin-1 in nano-drug delivery systems.

Conventional chemotherapy based on cytotoxic drugs is facing tough challenges recently following the advances of monoclonal antibodies and molecularly targeted drugs. It is critical to inspire new potential to remodel the value of this classical therapeutic strategy. Here, we fabricate bisphosphonate coordination lipid nanogranules (BC-LNPs) and load paclitaxel (PTX) to boost the chemo- and immuno-therapeutic synergism of cytotoxic drugs. Alendronate in BC-LNPs@PTX, a bisphosphonate to block mevalonate metabolism, works as both the structure and drug constituent in nanogranules, where alendronate coordinated with calcium ions to form the particle core. The synergy of alendronate enhances the efficacy of paclitaxel, suppresses tumor metastasis, and alters the cytotoxic mechanism. Differing from the paclitaxel-induced apoptosis, the involvement of alendronate inhibits the mevalonate metabolism, changes the mitochondrial morphology, disturbs the redox homeostasis, and causes the accumulation of mitochondrial ROS and lethal lipid peroxides (LPO). These factors finally trigger the ferroptosis of tumor cells, an immunogenic cell death mode, which remodels the suppressive tumor immune microenvironment and synergizes with immunotherapy. Therefore, by switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis, BC-LNPs@PTX provides new insight into the development of cytotoxic drugs and highlights the potential of metabolism regulation in cancer therapy.