[Comparison of stratification methods for malignant risk of thyroid nodules].

Objective: To compare the diagnostic value of the 2015 American Thyroid Association(ATA) guidelines and the American College of Radiology Thyroid Imaging Reporting and Data System(ACR TI-RADS) classification for thyroid nodules. Method: Retrospective analysis of 340 cases of 386 thyroid nodules confirmed by surgery or pathology from November 2016 to November 2018 in Yan' an University Hospital was conducted, using 2015 ATA, ACR TI-RADS for classification. Histopathology or cytology was the gold standard, The receiver operating characteristic(ROC) curve was plotted, using χ test to compare the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the two methods. Result: Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of ACR TI-RADS were 961%, 741%, 645%, 974%, 813%, respectively, and the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the 2015 ATA guidelines was 937%, 733%, 632%, 960%, 801%,respectively. There was no statistically significant difference between the two groups. The area under ACR TI-RADS and 2015 ATA guide curve is 0851 and 0839, respectively. Conclusion: Both ACR TI-RADS and 2015 ATA guidelines have high diagnostic value. The two classification methods are equally effective in assessing the benign and malignant thyroid nodules.

Store depletion by caffeine/ryanodine activates capacitative Ca(2+) entry in nonexcitable A549 cells.

Capacitative Ca(2+) entry is essential for refilling intracellular Ca(2+) stores and is thought to be regulated primarily by inositol 1, 4,5-trisphosphate (IP(3))-sensitive stores in nonexcitable cells. In nonexcitable A549 cells, the application of caffeine or ryanodine induces Ca(2+) release in the absence of extracellular Ca(2+) similar to that induced by thapsigargin (Tg), and Ca(2+) entry occurs upon the readdition of extracellular Ca(2+). The channels thus activated are also permeable to Mn(2+). The channels responsible for this effect appear to be activated by the depletion of caffeine/ryanodine-sensitive stores per se, as evidenced by the activation even in the absence of increased intracellular Ca(2+) concentration. Tg pretreatment abrogates the response to caffeine/ryanodine, whereas Tg application subsequent to caffeine/ryanodine treatment induces further Ca(2+) release. The response to caffeine/ryanodine is also abolished by initial ATP application, whereas ATP added subsequent to caffeine/ryanodine induces additional Ca(2+) release. RT-PCR analyses showed the expression of a type 1 ryanodine receptor, two human homologues of transient receptor potential protein (hTrp1 and hTrp6), as well as all three types of the IP(3) receptor. These results suggest that in A549 cells, (i) capacitative Ca(2+) entry can also be regulated by caffeine/ryanodine-sensitive stores, and (ii) the RyR-gated stores interact functionally with those sensitive to IP(3), probably via Ca(2+)-induced Ca(2+) release.

Effect of erythromycin on ATP-induced intracellular calcium response in A549 cells.

ATP induced a biphasic increase in the intracellular Ca(2+)concentration ([Ca(2+)](i)), an initial spike, and a subsequent plateau in A549 cells. Erythromycin (EM) suppressed the ATP-induced [Ca(2+)](i) spike but only in the presence of extracellular calcium (Ca(2+)(o)). It was ineffective against ATP- and UTP-induced inositol 1,4,5-trisphosphate [Ins(1,4,5)P(3)] formation and UTP-induced [Ca(2+)](i) spike, implying that EM perturbs Ca(2+) influx from the extracellular space rather than Ca(2+)release from intracellular Ca(2+) stores via the G protein-phospholipase C-Ins(1,4,5)P(3) pathway. A verapamil-sensitive, KCl-induced increase in [Ca(2+)](i) and the Ca(2+) influx activated by Ca(2+) store depletion were insensitive to EM. 3'-O-(4-benzoylbenzoyl)-ATP evoked an Ca(2+)(o)-dependent [Ca(2+)](i) response even in the presence of verapamil or the absence of extracellular Na(+), and this response was almost completely abolished by EM pretreatment. RT-PCR analyses revealed that P2X(4) as well as P2Y(2), P2Y(4), and P2Y(6) are coexpressed in this cell line. These results suggest that in A549 cells 1) the coexpressed P2X(4) and P2Y(2)/P2Y(4) subtypes contribute to the ATP-induced [Ca(2+)](i) spike and 2) EM selectively inhibits Ca(2+) influx through the P2X channel. This action of EM may underlie its clinical efficacy in the treatment of airway inflammation.

Flux of the L-serine metabolism in rat liver. The predominant contribution of serine dehydratase.

L-Serine metabolism in rat liver was investigated, focusing on the relative contributions of the three pathways, one initiated by L-serine dehydratase (SDH), another by serine:pyruvate/alanine:glyoxylate aminotransferase (SPT/AGT), and the other involving serine hydroxymethyltransferase and the mitochondrial glycine cleavage enzyme system (GCS). Because serine hydroxymethyltransferase is responsible for the interconversion between serine and glycine, SDH, SPT/AGT, and GCS were considered to be the metabolic exits of the serine-glycine pool. In vitro, flux through SDH was predominant in both 24-h starved and glucagon-treated rats. Flux through SPT/AGT was enhanced by glucagon administration, but even after the induction, its contribution under quasi-physiological conditions (1 mM L-serine and 0.25 mM pyruvate) was about (1)/(10) of that through SDH. Flux through GCS accounted for only several percent of the amount of L-serine metabolized. Relative contributions of SDH and SPT/AGT to gluconeogenesis from L-serine were evaluated in vivo based on the principle that 3H at the 3 position of L-serine is mostly removed in the SDH pathway, whereas it is largely retained in the SPT/AGT pathway. The results showed that SPT/AGT contributed only 10-20% even after the enhancement of its activity by glucagon. These results suggested that SDH is the major metabolic exit of L-serine in rat liver.

[Studies on the isolation, structure identification and biological function of two tumor cell suppressors of human fetal liver origin].

Our previous work showed the existence of low molecular weight tumor suppressors in human fetal tissues. In this paper, two tumor cell suppressors were isolated and purified from methanol extract of human fetal liver by C18 reversed-phase medium pressure chromatography, gel filtration on Sephadex LH-20, and high-performance liquid chromatography, directed by suppression of growth of HL-60 cells. The structures of the suppressors were identified to be 7-ketocholesterol and 7-beta-hydroxycholesterol. Under the condition of in vitro agar plate culture, 7-ketocholesterol and 7-beta-hydroxycholesterol showed preferentially inhibitory effects on the growth of both human and murine leukemic cell lines including human HL-60 and murine S-180 cells, but less effective on the growth of normal human and murine bone marrow granulocyte-macrophage progenitors (CFU-GM).

A new pharmacological activity of dibutyl phthalate (DBP) on selective elimination of tumor cells from bone marrow.

DBP possesses a new pharmacological activity leading to selective deterioration of leukemic cells, with less harmful effect on the growth of normal hematopoietic progenitors.

[Effect of a human fetal liver factor in suppression of HL-60 cell growth in vitro].

Two kinds of HL-60 cell growth suppressors present in human fetal liver were studied. One is the known arginase which shows non-specific suppression on the growth of HL-60 cells and human granulocyte-macrophage progenitors (CFU-GM), and the other, a new species of suppressor with a lower molecular weight (less than 10,000 daltons), shows preferential suppression on HL-60 cell growth, but less suppressive effect on the growth of CFU-GM.

Studies of haemopoietic stem cells and microenvironment in chronic irradiated mice.

Mice were irradiated at a dose rate of 70 rad per day for 25 days. Changes in properties and functions of haemopoietic stem cells and microenvironment were observed through a period of 12 months after termination of continuous irradiation. It was shown that the radiation damage of haemopoietic stem cells played an important role in the radiation-induced damage of haemopoiesis. This was further supported by the fact that transplantation of syngeneic bone marrow cells immediately after termination of continuous irradiation at 70 rad per day for 25 days would greatly improve the haemopoietic function of the irradiated mice, including the total recovery of CFU-S and numbers in the bone marrow and cell counts in the peripheral blood.

The nature of radiation damage of haemopoietic stem cells under continuous irradiation at low dose rate.

Mice irradiated continuously at a low dose rate of 70 rad/day showed not only a drop of CFU-S content in the bone marrow but also an apparent functional disturbance of haemopoietic stem cells. With increase in accumulated dose of radiation, the damage of the haemopoietic microenvironment becomes evident. From the changes caused by chronical irradiation, it is believed that haemopoietic stem cells is more sensitive than haemopoietic microenvironment, and the radiation injury by hemopoiesis involves both damage of haemopoietic stem cells and microenvironment. Furthermore, in the course of recovery of hemopoietic injury, microenvironment plays as important role. In comparison of the growth curves of CFU-S from normal and irradiated bone marrow cells in irradiated recipient spleens or cultured in diffusion chambers, it is suggested that the nature of radiation damage of haemopoietic stem cells in continuous irradiation at low dose rate is mainly attributed to the deterioration of self replicative capacity of CFU-S.

Studies on the property and transplantation of haemopoietic stem cells from peripheral blood.

Comparative studies of the properties of murine haemopoietic stem cells from different sources revealed that the peripheral haemopoietic stem cell is relatively weaker than the haemopoietic stem cell from bone marrow in promoting the recovery of hemopoiesis in the irradiated animals. This is due to the heterogenity of stem cell population in which some aged cellsubpopulations are co-existing. The modified potential in proliferation and differentiation of haemopoietic stem cells in the peripheral blood seems to be irreversible under normal physiological conditions. In a preliminary experiment, the use of an anti-thymocyte immunoglobulin to eliminate immunocompetent cells proved effective in reducing the severity and incidence of secondary diseases and in increasing the number of survivors of lethally irradiated semi-isologous mice after transplantation of parental peripheral mononuclear cells.