[Effects of Dapagliflozin on contrast-induced acute kidney injury in patients with type 2 diabetes mellitus underwent percutaneous coronary intervention].

Objective: To investigate the effect of Dapagliflozin, sodium-glucose cotransporter 2 inhibitor (SGLT2i), on contrast-induced acute kidney injury (CIAKI) in patients with type 2 diabetes mellitus (T2DM) after percutaneous coronary intervention(PCI). Methods: A cohort study. The clinical data of 366 patients with coronary heart disease combined with T2DM who underwent PCI in the Department of Cardiology, Tianjin University Chest Hospital, from June 2021 to June 2022 were retrospectively analyzed, including 218 males and 148 females, aged (64.6±11.0) years old. According to whether the patients had used Dapagliflozin or not, the selected patients were divided into SGLT2i group(n=124) and control group(n=242). The changes in cardiac indicators, renal function, and inflammatory response indicators before and 72 hours after PCI treatment were analyzed and compared between the two groups. The incidence rate of CIAKI in the two groups was analyzed, and the influencing factors of CIAKI were analyzed by multivariate logistic regression. The major adverse cardiac events (MACE) were recorded during the follow-up period of the two groups, and Kaplan-Meier survival analysis and log-rank test were used to compare the differences in MACE occurrence between the two group. Results: The left ventricular ejection fraction (LVEF) of the SGLT2i group was lower than that of the control group, and the proportion of patients with LVEF<45% and CIAKI risk score were higher than those of the control group, with statistical significance (all P<0.05). 72 h after PCI treatment, ß-2 Microglobulin(ß-2MG), cystatin-C(Cys-C), and neutrophil gelatinase-associated lipocalin (NGAL) in both groups were all increased compared to those before PCI treatment, with statistical significance (all P<0.05).ß-2MG, Cys-C, and NGAL in SGLT2i group were all lower than those in the control group, with statistical significance(all P<0.05).The levels of interleukin-6(IL-6), hypersensitive C-reactive protein (hs-CRP), and malondialdehyde in both groups of patients increased compared to preoperative levels, while the levels of superoxide dismutase (SOD) decreased compared to preoperative levels, with statistical significance (all P<0.05). The levels of IL-6, hs-CRP, and malondialdehyde in the SGLT2i group were lower than those in the control group, while SOD was higher than that in the control group, with statistical significance (all P<0.05). Among all patients included, 34 cases experienced CIAKI (9.8%), and the incidence of CIAKI in the SGLT2i group was lower than that in the control group [4.8% (6/124) vs 11.6% (28/242),P=0.037]. Multivariate logistic regression analysis showed that the use of dapagliflozin was a protective factor for CIAKI in T2DM patients receiving PCI treatment (OR=0.321, 95%CI: 0.127-0.816, P=0.017). After a follow-up of 14.0 (12.0, 16.2) months, the incidence of MACE in SGLT2i group was lower than that in the control group (7.3% vs 12.8%, P=0.048). Conclusions: Dapagliflozin may reduce the risk of CIAKI and MACE in T2DM patients after PCI treatment. Its mechanism may be related to the anti-inflammatory and antioxidant effects of SGLT2i.

Glycosylated hemoglobin levels and the risk for contrast-induced nephropathy in diabetic patients undergoing coronary arteriography/percutaneous coronary intervention.

BACKGROUNDS: Diabetes mellitus is an independent risk factor for Contrast-induced nephropathy (CIN) in patients undergoing Coronary arteriography (CAG)/percutaneous coronary intervention (PCI). Glycosylated hemoglobin (HbA1c) is the gold standard to measure blood glucose control, which has important clinical significance for evaluating blood glucose control in diabetic patients in the past 3 months. This study aimed to assess whether preoperative HbA1c levels in diabetic patients who received CAG/PCI impacted the occurrence of postoperative CIN. METHODS: We reviewed the incidence of preoperative HbA1c and postoperative CIN in 670 patients with CAG/PCI from January 1, 2020 to October 30, 2020 and divided the preoperative HbA1c levels into 5 groups. Blood samples were collected at admission, 48 h and 72 h after operation to measure the Scr value of patients. Categorical variables were compared using a chi-square test, and continuous variables were compared using an analysis of variance. Fisher's exact test was used to compare the percentages when the expected frequency was less than 5. Univariable and multivariable logistic regression analysis was used to exclude the influence of confounding factors, and P for trend was used to analyze the trend between HbA1c levels and the increased risk of CIN. RESULTS: Patients with elevated HbA1c had higher BMI, FBG, and LDL-C, and they were more often on therapy with hypoglycemic agents, Insulin and PCI. They also had higher basal, 48 h and 72 h Scr. The incidence of CIN in the 5 groups of patients were: 9.8, 11.9, 15.2, 25.3, 48.1%. (p < 0.0001) The multivariate analysis confirmed that in the main high-risk subgroup, patients with elevated HbA1C levels (≥8.8%) had a higher risk of CIN disease. Trend test showed the change of OR (1.000,1.248,1.553,2.625,5.829). CONCLUSIONS: Studies have shown that in diabetic patients undergoing CAG/PCI, elevated HbA1c is independently associated with the risk of CIN, and when HbA1c > 9.5%, the incidence of CIN trends increase. Therefore, we should attach great importance to patients with elevated HbA1c at admission and take more active measures to prevent CIN.

Comparative efficacy of adjuvant trastuzumab-containing chemotherapies for patients with early HER2-positive primary breast cancer: a network meta-analysis.

BACKGROUND: Trastuzumab (H) with chemotherapy benefits patients with HER2+ breast cancer (BC); however, we lack head-to-head pairwise assessment of survival or cardiotoxicity for specific combinations. We sought to identify optimal combinations. METHODS: We searched PubMed, updated October 2017, using keywords "Breast Neoplasms/drug therapy," "Trastuzumab," and "Clinical Trial" and searched Cochrane Library. Our search included randomized trials of adjuvant H plus chemotherapy for early-stage HER2+ BC, and excluding trials of neoadjuvant therapy or without data to obtain hazard ratios (HRs) for outcomes. Following PRISMA guidelines, one investigator did initial search; two others independently confirmed and extracted information; and consensus with another investigator resolved disagreements. Before gathering data, we set outcomes of overall survival (OS), event-free survival (EFS), and severe cardiac adverse events (SCAEs). Analyzing 6 trials and 13,621 patients, we made direct and indirect comparisons using network meta-analysis on HR for OS or EFS and on odds ratio (OR) for SCAE; ranked therapy was done based on outcomes using p scores. RESULTS: Compared with anthracycline-cyclophosphamide with taxane (ACT), ACT with concurrent H (ACT+H) showed best OS (HR 0.63, 95% confidence interval [CI] 0.55, 0.72), followed by taxane and carboplatin (TC) with concurrent H (TC+H) (HR 0.77, 95% CI 0.59, 1) and ACT with sequential H (ACT-H) (HR 0.85, 95% CI 0.68, 1.05). Pairwise comparisons showed statistically significant OS benefit for ACT+H over others; similar results for EFS. TC+H showed statistically significant lower SCAE risk compared to ACT+H (OR 0.13, 95% CI 0.03, 0.61). CONCLUSIONS: Concurrent H with ACT or TC showed most clinical benefit for early-stage HER2+ BC; TC+H had lowest cardiotoxicity.

[Effect of probucol on preventing contrast-induced nephropathy in patients undergoing percutaneous coronary intervention].

Objective: To investigate the preventive effect, possible mechanism and safety of probucol on contrast-induced nephropathy (CIN) after percutaneous coronary intervention (PCI) in patients with coronary heart disease (CHD). Methods: A total of 641 patients with coronary heart disease were consecutively enrolled from Department of Cardiology, in Tianjin Chest Hospital, Tianjin TEDA International Cardiovascular Hospital, Tianjin First Central Hospital, Tianjin Fourth Central Hospital. They were randomly divided into probucol group (n=321) and control group (n=320). The probucol group was given oral probucol 500 mg twice daily for day 0 to day 3 after PCI; the control group was given only conventional therapy. All patients were given intravenous drip 0.9% sodium chloride solution before 12 to 24 hours of operation. The levels of serum creatinine (Scr), blood urea nitrogen (BUN), evaluate glomerular filtration rate (eGFR), cystatin C (Cys-C), and high-sensitivity C-reactive protein (hs-CRP), neutrophil gelatinase associated lipocalin (NGAL), superoxide dismutase (SOD) and glutathione (GSH) were measured before and 72 h after the PCI operation in both groups. The incidence rates of CIN, the adverse events during hospitalization and postoperative 14-day follow-up were recorded in two groups. Results: There was no statistically significantly difference in the levels of Scr, BUN, eGFR, Cys-C, hs-CRP, NGAL, SOD and GSH between the two groups before PCI (P>0.05). The levels of serum Scr, BUN, Cys-C, hs-CRP, NGAL, SOD and GSH after operation in the two groups were higher than those before the operation (P<0.05). The levels of hs-CRP and NGAL in the probucol group were lower than those in the control group [(10±4) vs (11±4)mg/L, (25±8)vs (34±7)U/ml, P<0.05]. The levels of eGFR, SOD and GSH in probucol group were higher than those in control group [(80±27) vs (72±26) ml·min(-1)·1.73 m(-2,) (67±9) vs (58±8)U/ml, (4.6±0.9) vs (3.9±0.8)U/ml, P<0.05]. The incidence of CIN was 4.0% in the probucol group and 10.9% in the control group, and the difference was statistically significant (P<0.05, χ(2)=-3.31). Multivariate Logistic regression analysis showed that probucol was an independent protective factor for CIN (OR=0.334, 95%CI 0.172-0.648, P=0.001). There were no adverse events such as myasthenia gravis, abnormal liver function and cardiovascular events during the hospitalization and 14-day follow-up. Conclusions: Probucol can reduce the incidence of contrast-induced nephropathy after PCI. The protection mechanism is related with its anti-inflammatory and anti-oxidative stress effects, and it has good safety.

[An interpretation of the AASLD practice guideline on the diagnosis and management of nonalcoholic fatty liver disease in 2017].

The American Association for the Study of Liver Diseases (AASLD) updated and published the Practice Guidance for the Diagnosis and Management of Nonalcoholic Fatty Liver Disease (NAFLD) in July 2017, which provides recommendations for the accurate diagnosis, treatment, and effective prevention of NAFLD. Related metabolic diseases should be considered during the initial evaluation of patients suspected of NAFLD. Noninvasive diagnostic techniques including transient elastography, magnetic resonance elastography, and serum biochemical models should be used to evaluate the development and progression of liver fibrosis in patients with NAFLD. Clinical liver pathology report should clearly differentiate between nonalcoholic fatty liver (NAFL), NAFL with inflammation, and nonalcoholic steatohepatitis (NASH) and identify the presence or absence of liver fibrosis and its degree. Early medication for NAFLD can only be used in patients with pathologically confirmed NASH and liver fibrosis, and it is not recommended to use pioglitazone and vitamin E as the first-line drugs for patients with NASH which has not been proven by biopsy or non-diabetic NASH patients. Foregut bariatric surgery can be considered for obese patients with NAFLD/NASH who meet related indications. It is emphasized that the risk factors for cardiovascular disease should be eliminated for NAFLD patients. Statins can be used for the treatment of dyslipidemia in patients with NAFLD/NASH, but they cannot be used in patients with decompensated liver cirrhosis. Routine screening or hepatocellular carcinoma surveillance is not recommended for NASH patients without liver cirrhosis. Cardiovascular disease should be taken seriously during liver transplantation evaluation. There is still no adequate clinical evidence for the treatment of NAFLD in children and adolescents, and intensive lifestyle intervention is recommended as the first-line therapy for such patients.

[Mechanism of action of Yiqi Huoxue Recipe in regulating autophagy and reversing liver fibrosis].

Objective: To investigate the role and mechanism of action of Yiqi Huoxue Recipe (YQHXR) in regulating autophagy and reversing liver fibrosis in rats with carbon tetrachloride (CCl4)-induced liver fibrosis. Methods: Healthy male Wistar rats were intraperitoneally injected with a mixture of CCl4 (30%) and olive oil (70%) twice a week for 8 weeks to establish a rat model of liver fibrosis. The rats administered normal diet were used as control group. Furthermore, YQHXR or Fuzheng Huayu Recipe (FZHYR) was intragastrically administered to the rats. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured using an automatic biochemical analyzer. Hematoxylin-eosin (HE) staining and Masson staining were performed to observe the degree of fibrosis in rat liver. The protein expression of α-smooth muscle actin (α-SMA) and type I collagen α1 chain (Col1A1) in liver tissue was measured by immunohistochemistry. Furthermore, the mRNA and protein expression of α-SMA, Col1A1, autophagy-related protein 7 (Atg7), microtubule-associated protein 1 light chain 3 (LC3), and ubiquitin-binding protein (SQSTM1/p62) were determined using qRT-PCR and Western blotting, respectively. Comparison between multiple groups was made by one-way analysis of variance, and comparison between any two groups was made using the LSD test. P < 0.05 was considered as statistically significant. Results: The YQHXR group and FZHYR group had significantly lower serum levels of ALT and AST than the model group (ALT: 66.8±10.42 U/L and 73.2±10.33 U/L vs 106.80±18.24 U/L, F = 31.672, P < 0.001; AST: 122.6±16.65 U/L and 125.4±16.92 U/L vs 278.4±66.14 U/L, F = 25.539, P < 0.001). The pathological grades of hepatic fibrosis were S5.64±0.22, S3.70±0.35, and S3.90±0.34 in the model group, YQHXR group, and FZHYR group, respectively (F = 362.188, P < 0.001). Compared with the control group, the YQHXR group and FZHYR group had significantly reduced mRNA and protein expression of α-SMA, Col1A1, Atg7, and LC3B and significantly increased expression of p62 (all P < 0.05), and the differences were greatest in the YQHXR group. Conclusion: YQHXR and FZHYR can prevent or reverse liver fibrosis by regulating hepatocyte autophagy and inhibiting hepatic stellate cell activation and collagen deposition.

Effect of a potential probiotics Lactococcus garvieae B301 on the growth performance, immune parameters and caecum microflora of broiler chickens.

In this study, a novel Lactococcus garvieae B301 was isolated from the intestinal tract of a healthy piglet. L. garvieae B301 was tolerant to acid pH, simulated gastric and small intestinal transit juices, indicating that it was capable of surviving in the gastrointestinal tract. L. garvieae B301 was safe and beneficial to broilers, as broiler chickens supplemented with L. garvieae B301 had lower diarrhoea incidence and mortality than the Control. Moreover, supplementation of broiler diets with L. garvieae B301 resulted in an increase in body weight and the number of caecum lactic acid bacteria and Bifidobacterium spp., and decrease in feed-to-gain ratio and the number of caecum coliforms. It also had a positive effect on the thymus index and bursa of Fabricius index and enhanced serum levels of immune globulins. All these results showed that L. garvieae B301 could enhance the growth performance of broiler chickens and improve their health. Thus, L. garvieae B301 could be a promising feed additive for broiler chickens.

Effects of ionic and nonionic surfactants on milk shell wettability during co-spray-drying of whole milk particles.

Mixing surfactants with whole milk feed before spray drying could be a commercially favorable approach to produce instant whole milk powders in a single step. Pure whole milk powders obtained directly from spray drying often have a high surface fat coverage (up to 98%), rendering them less stable during storage and less wettable upon reconstitution. Dairy industries often coat these powders with lecithin, a food-grade surfactant, in a secondary fluidized-bed drying stage to produce instant powders. This study investigated the changes in wetting behavior on the surface of a whole milk particle caused by the addition of surfactants before drying. Fresh whole milk was mixed with 0.1% (wt/wt) Tween 80 or 1% (wt/wt) lecithin (total solids), and the wetting behavior of the shell formed by each sample was captured using a single-droplet drying device at intermediate drying stages as the shell was forming. The addition of surfactants improved shell wettability from the beginning of shell formation, producing more wettable milk particles after drying. The increase in surfactant loading by 10 times reduced the wetting time from around 30s to <5s. At the same loading of 1% (wt/wt; total solids), milk particles with Tween 80 were much more wettable than those with lecithin (<5s compared with >30s). We proposed that Tween 80 could adsorb at the oil-water interface of fat globules, making the surface fat more wettable, whereas lecithin tends to combine with milk proteins to form a complex, which then competes for the air-water surface with fat globules. Spray-drying experiments confirmed the greatly improved wettability of whole milk powders by the addition of either 0.1% (wt/wt) Tween 80 or 1% (wt/wt) lecithin; wetting time was reduced from 35±4s to <15s. To the best of our knowledge, this is the first time that a dynamic droplet drying system has been used to elucidate the complex interactions between ionic or nonionic surfactants and milk components (both proteins and fat), as well as the resultant effect on the development of milk particle functionality during drying.

Characteristics of anaphylaxis-inducing IgG immune complexes triggering murine passive systemic anaphylaxis.

BACKGROUND: With the broad and increasing application of therapeutic monoclonal antibodies (mAbs) in clinical settings, IgG-induced allergic reactions, including passive systemic anaphylaxis (PSA), have attracted significant attention. However, it is not clear which types of IgG mAb-antigen complexes or IgG aggregates formed by antigen binding can trigger PSA, as not all immune complexes (ICs) are capable of triggering PSA. Here, we characterise mAb-antigen complexes capable of inducing murine PSA to evaluate and predict which ICs are able to induce PSA. METHODS: Thirty-six combinatory reactions with eight antigens and 27 corresponding mAbs were used to trigger PSA, which was defined by rectal temperature. Sandwich ELISA, passive cutaneous anaphylaxis (PCA) induction and flow cytometry analysis of CD16/32 (FcγRIII/II) expression were used to characterise the ICs. The dynamic concentrations of antigen in the peripheral blood were measured by ELISA. RESULTS: Only 14 of the 36 ICs could trigger PSA and thus be termed anaphylaxis-inducing immune complexes (Ai-ICs). The Ai-ICs could be characterised by constructing sandwich ELISA, inducing PCA and down-regulating CD16/32 (FcγRIII/II) expression on blood neutrophils in vitro and in vivo. Additionally, the occurrence and severity of PSA was found to be associated with the instantaneous concentration of antigen in the peripheral blood in the presence of antibody. CONCLUSIONS: Only Ai-ICs, not all ICs, could trigger IgG-mediated PSA, which could be characterised by the above simple methods. The occurrence and severity of PSA was associated with the instantaneous concentration of antigen in the peripheral blood in the presence of antibody.

Uniform amorphous lactose microspheres formed in simultaneous convective and dehydration antisolvent precipitation under atmospheric conditions.

A simultaneous convection-dehydration and antisolvent precipitation approach has been shown to produce uniform microsized lactose particles from aqueous droplet at atmospheric pressure. Microparticles with high uniformity having diameters of between 1.0 and 2.4 µm have been obtained. The precipitation of the microparticles is driven by a unique self-assembly mechanism that cannot be fully elucidated by supersaturation alone. Further analysis suggests that structural changes in the solvent/antisolvent mixture, due to hydrophobic hydration, could play a role in the precipitation process observed.

CC chemokine ligand 21 enhances the immunogenicity of the breast cancer cell line MCF-7 upon assistance of TLR2.

CC chemokine ligand 21 (CCL21) is a known attractant for CCR7-positive (CCR7+) cells, but its additional role in the immunogenicity of CCR7+ cells remains poorly understood. This study explored the effects of CCL21-CCR7 ligation on cancer immunogenicity and related antitumor immune response, in the presence and absence of mitomycin C (MMC) treatment. CCL21-CCR7 binding upregulated human leukocyte antigen class I-restricted tumor antigen presentation with increased expression of human leukocyte antigen class I and transporter associated with antigen processing-1. In addition, CCL21 restrained the tumor-derived immunosuppressive factors FasL and transforming growth factor-ß. Consequently, CCL21 facilitated cancer-educated lymphocytes reaction in vitro. In the tumor-bearing mouse, CCL21 inhibited tumor growth and prolonged mouse survival via lymphocytes, especially in CCR7+ cancer cells. Furthermore, Toll-like receptor 2 activation of lymphocytes assisted the tumor-suppression functions of CCL21, in vitro and in vivo. This study implies that CCL21 improved the immunogenicity of the CCR7+ breast cancer cell line even with MMC treatment and triggered antitumor response by lymphocytes. These findings provide a new insight into the research and application of CCL21-associated antitumor response.

MiR-100 suppresses inflammatory activation of microglia and neuronal apoptosis following spinal cord injury via TLR4/NF-κB pathway.

OBJECTIVE: This study aims to ascertain the effect of miR-100 on inflammation, apoptosis and functional rehabilitation after spinal cord injury (SCI) and the potential mechanism. MATERIALS AND METHODS: Firstly, microglia were extracted from 3-day-old neonatal rats and cultured for the purpose of inflammatory activation. Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was conducted to detect the levels of miR-100, toll-like receptors 4 (TLR4) and nuclear factor-κB (NF-κB). Moreover, proteins expressions of I-κB and induced-nitric oxide synthase (iNOS) and apoptosis-related genes were measured by Western blotting. In addition, SCI model was established in rats. Expressions of inflammatory factors in SCI rats were determined by enzyme-linked immunosorbent assay (ELISA) assay. Expression levels of TLR4/NF-κB pathway and miR-100 were determined by qRT-PCR. Immunofluorescence was conducted to measure activated microglia. Hindlimbs motor function in SCI rats was estimated via BBB 21-point rating scale. RESULTS: In activated microglia, miR-100 level decreased, while TLR4 and NF-κB levels increased. The protein level of I-κB decreased and iNOS increased. Transfection of miR-100 mimics reversed the above trends. Inflammatory factors were highly elevated in SCI rats and mRNA levels of the TLR4/NF-κB pathway and miR-100 were down-regulated, which were ameliorated in SCI rats overexpressing miR-100 in vivo. The amount of activated microglia was declined with the administration of miR-100 mimics compared with the untreated SCI rats. Furthermore, apoptosis-related proteins were down-regulated by miR-100 mimics injection. Motor function in the miR-100 mimics group was improved better than that in the SCI group. CONCLUSIONS: MiR-100 alleviates inflammation of microglia and neuronal tissue apoptosis, and improves motor function following SCI via inhibiting the TLR4/NF-κB pathway.

Tetraploid complementation proves pluripotency of induced pluripotent stem cells derived from adipose tissue.

OBJECTIVES: Recently, pluripotency of induced pluripotent stem (iPS) cells has been displayed after producing adult mice, in tetraploid complementation assays. These studies lead us to the last piece of the puzzle for reprogramming somatic cells into fully pluripotent cells which function as embryonic stem cells in most applications. However, in all of previous studies, skin fibroblasts were used as the starting population for reprogramming, raising questions as to whether the pluripotency of the iPS cells was dependent on the particular starting cell type. MATERIALS AND METHODS: Our iPS cell lines were prepared from murine adipose stem cells (ASCs). Their multi-potency was first tested by teratoma formation in nude mice. Then, tetraploid complementation was performed to generate progeny from them. RESULTS: We succeeded to the birth of viable and fertile adult mice derived entirely from reprogrammed ASC, indicating cell types other than fibroblasts can also be restored to the embryonic level of pluripotency. CONCLUSIONS: We also directed differentiation of iPS cells into chondrocytes, thus adipose-derived iPS cells can be used as models to study chondrogenic differentiation and cartilage regeneration.

Overexpression of cofilin 1 in prostate cancer and the corresponding clinical implications.

Cofilin 1 (CFL1) is a cytoskeletal protein and overexpression of the protein has been associated with aggressiveness in certain types of malignancies. The aim of the present study was to investigate the clinical implications of CFL1 expression in prostate cancer (PCa). Immunohistochemical analysis was performed using formalin-fixed paraffin-embedded tissue sections obtained from 111 patients with PCa and 47 patients with benign prostatic hyperplasia (BPH). In total, 78 (70.3%) out of 111 PCa tissues were found to express the CFL1 protein, while no expression was detected in BPH tissues. In addition, CFL1 was also observed to be significantly associated with the Gleason score (GS; <7 vs. ≥7; P<0.0001) and presence of lymph node metastasis (presence vs. absence; P<0.0001). However, there was no association between the expression of CFL1 and other clinicopathological variables, such as age (<69 years vs. ≥69 years; P=0.54), pre-operative prostate specific antigen level (<20 ng/ml vs. ≥20 ng/ml; P=0.45) and pathological stage (T2 vs. ≥T3a; P=0.055). In addition, 35 tissues (31.5%) were observed to possess a CFL1-positive mesenchyme. CFL1 expression was revealed to be an independent predictive factor for a high GS. The status of CFL1 expression in the mesenchyme also found to individually predict extraprostatic extension in PCa patients, based on multivariate analysis. The results of the present study indicated that CFL1 may specifically predict the development of PCa, and that the expression of CFL1 in the mesenchyme may be closely associated with the development of lymph node metastasis.

Serological surveillance for Penicillium marneffei infection in HIV-infected patients during 2004-2011 in Guangzhou, China.

Prevalence of disseminated Penicillium marneffei infection is not known in human immunodeficiency virus (HIV)-infected patients. This retrospective study aimed to evaluate the prevalence of and risk factors for disseminated P. marneffei infection in HIV-infected patients during 2004-11 in Guangzhou, China. We tested 8131 archived HIV-infected patient serum samples for P. marneffei-specific mannoprotein (Mp1p) antigen using a highly sensitive and specific ELISA that we previously established. The CD4 count of 2686 cases was determined by flow cytometry. Logistic regression was used to assess predictors of Mp1p antigenaemia. The overall prevalence of disseminated penicilliosis as detected by positive serum Mp1p antigen was 9.36% (761/8131), in good concordance with Platelia™ Aspergillus immunoassay. During 2004-11, the prevalence increased to a peak of 12.58% (158/1256) in 2010 and decreased in 2011. Penicilliosis was strongly associated with progression from HIV to AIDS (OR 4.66, 95% CI 3.94-5.51, p <0.001) and humidity (OR 1.02, 95% CI 1.01-1.03, p 0.002). Disseminated penicilliosis occurred mainly during the rainy seasons (p <0.001). For 2686 cases with known CD4 count, logistic regression showed that CD4 count of <200 cells/µL was a risk factor for penicilliosis (OR 2.90, 95% CI 1.10-7.66, p 0.032), especially when it was <50 cells/µL (OR 24.26, 95% CI 10.63-55.36, p <0.001) during which 28.06% of patients developed disseminated penicilliosis. In conclusion, approximately 9.36% of the HIV-infected patients in our study developed disseminated penicilliosis. Rapid diagnosis may be achieved by performing serological surveillance for Mp1p antigenaemia as a routine procedure for all HIV-infected patients with CD4 count of <50 cells/µL.

Photosensitization of mitochondrial adenosine-triphosphatase and adenylate kinase by hematoporphyrin derivative in vitro.

Mitochondrial ATPase and adenylate kinase activity of hepatoma cells were inhibited by hematoporphyrin derivative (HPD) followed by photoirradiation. Inhibition of ATPase activity was a dose- and time-related event. Malonaldehyde (MDA) content of mitochondrial membranes was markedly increased by HPD plus light. The content of mouse liver microsomal cytochrome P-450 was greatly increased after intraperitoneal injection of HPD for 4 days (5 mg/kg/day). The liver weight, and levels of liver microsomal G-6-phosphatase, MDA and triglyceride (TG) showed no difference in treated vs. control animals. The data presented here demonstrate that mitochondria may be a sensitive site of action of HPD photosensitization, and inactivation of ATPase and adenylate kinase may be an important contributing factor to tumor cell damage and death.

[Effect of hematoporphyrin derivative (HpD) on nucleoside transport and nucleoside kinase activity of cancer cells].

The HpD and dihematoporphyrin ethers (Photofrin II) at the dose of 5 micrograms/ml significantly inhibited the transport and uptake of thymidine and uridine in Ehrlich ascites carcinoma (EAC) cells. The 50% inhibiting doses (ID50) of HpD and Photofrin II II for thymidine uptake were 1.0 microgram/ml and 7.0 micrograms/ml, and for uridine were 1.2 micrograms/ml and 1.6 micrograms/ml, respectively. The uptake kinetics were greatly changed. The Km values were increased and the Vmax values decreased. The incorporation of 3H-TdR and 3H-UR into the acid-soluble and insoluble materials of EAC cells was depressed. HpD at the dose of 10 micrograms/ml did not influence the activity of thymidine kinase but the uridine kinase activity was mildly inhibited. These results show that the cell membrane may be the initial acting site by both drugs.

[Photodynamic effect of several hematoporphyrin derivatives and their production of singlet oxygen and retention in cancer cells].

Photodynamic effect of three hematoporphyrin derivatives (HpD) on cancer cells in Ehrlich ascites carcinoma (EAC) mice were tested both in vivo and in vitro. At the dose of 5 micrograms/ml, HpD-81 and HpD-83 plus light inhibited the increase of ascites at inhibition rates of 84.6% and 17.5%. Yet HpD-82 plus light showed no effect. Their capacity to retain themselves in cancer cells differed and was related to their photodynamic effect. HpD-81 had the greatest capacity and its distribution ratio was higher than the others. The accumulation of HpD in cancer cells was obviously decreased by the addition of serum in the medium. The production rate of singlet oxygen by HpD-81 was slightly greater than that of HpD-83, but this difference could hardly explain the difference in cytotoxic effect of these two HpD. We expect that the accumulation of HpD in cancer cells may be one of the determinants in the photodynamic effect of photosensitizers.

[Influencing factors in the leakage of liposome and arabinoside cytosine (ARA-C) entrapped in liposomes in treatment of L1210 mouse leukemia].

Ara-c entrapped into multilamella vesicles (MLV's) composed of PC:C (2:1) (phosphotidylcholine, cholesterol) or PC:SM (1:4) (sphingomyelin) was incubated in the simple salt medium at 37 degrees C for one hour. Its leakage from the liposomes was 5.6-17.6% but, in the presence of serum, the leakage was 35.7-49.1%. Having been incubated at 37 degrees C overnight, the leakage significantly increased but the leakage rate was the highest within the 1st hour. When ara-c entrapped into reverse evaporation vesicles (REV's) composed of PC:C (2:1) or PC:SM (1:4) was incubated in the simple salt medium at 37 degrees C for one hour, its leakage was 2.4-4.1% but, in the presence of serum, the leakage was 10.9-8.2%. When the liposomes were incubated at 37 degrees C overnight, the leakage gradually increased. Whether in the presence of serum or not, the leakage from REV's was much less than that from MLV's. There was no effect on the survival of L1210 leukemia mice when free ara-c was injected intraperitoneally once at the dose of 10 mg/kg, but when the same dose was given for five times, the increase rate in life span was 43.2--51.3%. When ara-c, entrapped into MLV's or REV's composed of PC:C (2:1) and PC:SM (1:4), was given at the dose of 10 mg/kg only once, the effect of intraperitoneal injection was more marked than that of intravenous injection. No effect was observed when free ara-c was continuously infused at the dose of 2 mg/kg once everyday for five days.(ABSTRACT TRUNCATED AT 250 WORDS)

[Effect and toxicity of entrapped polysiloxane 5-Fu polycondensate].

Entrapped 5-Fu polysiloxane polycondensate (DMS-Fu) and equivalent doses of 5-Fu were tested on S-180 mice. At the dose of 100 mg/kg, the inhibition potency of these two compounds on tumor was similar, but the inhibition on the body weight was more marked in 5-Fu treated mice. At the dose of 250 mg/kg, all mice treated with 5-Fu died of toxicity but the mice treated with DMS-Fu survived and showed no obvious toxic effect. At the dose of 150-200 mg/kg, the peripheral white blood cells and the bone marrow nucleated cells of 5-Fu treated mice were seriously reduced, which lasted for several days before recovery. In the DMS-Fu group, the inhibition was mild.