[Normocalcemic with elevated post-operative parathormone in primary hyperpara-thyroidism: 9 case reports and literature review].

OBJECTIVE: To summarize and analyze the clinical characteristics of primary hyperpara-thyroidism (PHPT) with normocalcemic parathormone elevation (NPE) after surgical treatment, so as to improve the therapeutic ability and standardized post-operative follow-up of PHPT patients. METHODS: Nine patients who were diagnosed with PHPT in the Department of Endocrinology of China-Japan Friendship Hospital from August 2017 to November 2019 were selected as the subjects. They all developed NPE within 6 months after surgical treatment. The clinical features and outcomes were collected and analyzed retrospectively, in addition, the related literature was reviewed. RESULTS: Clinical features: among the 9 patients, 6 were middle-aged and elderly females and 3 were male. The main clinical manifestations were bone pain, kidney stones, nausea and fatigue except for one case of asymptomatic PHPT. Pre-operative examination showed high serum calcium [(3.33±0.48) mmol/L], low serum phosphorus [0.76 (0.74, 0.78) mmol/L], high 24-hour urinary calcium [8.1(7.8, 12.0) mmol/24 h], obviously elevated intact PTH [(546.1±257.7) ng/L], vitamin D deficiency [25-hydroxyvitamin D3 (21.0±5.7) nmol/L]. Serum levels of bone alkaline phosphatase [7 patients 41.3(38.6, 68.4) µg/L, 2 patients >90 µg/L] and N-terminal midcourse osteocalcin (>71.4 µg/L) were significantly elevated. The estimated glomerular filtration rate decreased in 2 patients. Imaging examination: 7 patients had osteoporosis. Renal calculi were found in 3 patients by renal ultrasound. Imaging examination of parathyroid glands found definite lesions in all the patients, including 2 cases of multiple lesions and 7 cases of single lesions. TREATMENT AND OUTCOME: two patients underwent parathyroidectomy, while other patients were treated with microwave thermal ablation. PTH increased 1 month after therapy [(255.0±101.4) ng/L], and no recurrent lesions were found by parathyroid ultrasound. After combined treatment with cal-cium and vitamin D for six months, PTH decreased significantly and the level of serum calcium remained normal at anytime during the follow-up period. CONCLUSION: The occurrence of postoperative NPE may be related to the higher pre-operative PTH, vitamin D deficiency and lower creatinine clearance. However, NPE may not predict recurrent hyperthyroidism or incomplete parathyroidectomy. Adequate calcium and vitamin D supplementation after surgery seems to be beneficial for patients with NPE. Post-operative follow-up of PHPT patients should be standardized to prevent and treat post-operative NPE.

[Investigation and clinical analysis of a family with germline CEBPA mutations in acute myeloid leukemia].

Objective: To investigate the clinical characteristics, etiology, and prognosis of familial acute myeloid leukemia (AML) with germline CEBPA mutation and improve the understanding of familial leukemia. Methods: The age of onset, clinical characteristics, outcome, and prognosis of a family of patients with AML were investigated, and the family tree of the cases was displayed. Bone marrow and oral mucosal cells were collected from the proband, and peripheral blood was collected from the relatives of the proband. Gene mutation was detected by gene sequencing technology. Results: A total of 10 patients in this family were diagnosed with acute leukemia, including 4 males and 6 females, with a median age of 9 (3-48) years. Of the 10 patients, six died. Among them, 4 patients did not receive treatment, 1 patient survived 3 years after chemotherapy and died of relapse, and one patient died 2 years after receiving traditional Chinese medicine and supportive treatment. Four patients are alive. One patient has survived 15 years through chemotherapy, and three patients have survived with chemotherapy combined with hematopoietic stem cell transplantation, and the survival time was 6, 9, and 28 months at the end of follow-up. Gene sequencing was performed on proband and 8 relatives of the proband, and 5 were found to have the germline CEBPA TAD p.G36Afs*124 mutation. Among the 5 individuals with confirmed CEBPA mutation, 4 were diagnosed with AML, and 1 had not developed disease during follow-up. Conclusion: AML with germline CEBPA gene mutation mostly occurs in children and young adults, with complete or nearly complete penetrance. With active treatment, most of the patients have a favorable prognosis.

[Effect of NCCN (2015) risk stratification on prognosis of patients with acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation].

Objective: To analyze the effect of NCCN (2015) risk stratification on prognosis of patients with acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Retrospective analysis of 258 patients with AML in CR (186 cases in CR(1), 72 cases in CR(2)) who underwent allogeneic HSCT in our hospital between April 2012 and March 2015 according to NCCN (2015) risk stratification. Of them, 63 cases were classified as low risk, 112 cases intermediate risk and 83 cases high risk. Results: ①With the median follow up of 18 (5-41) months, two-year disease free surviva (DFS) in 258 patients was 78.0% (95% CI 60.4%-96.6%) . Two-year DFS in AML after transplantation was 78.6% (95% CI 61.0%-96.2%) in low risk, 76.0% (95% CI 84.0%-93.6%) in intermediate risk and 80.3% (95% CI 62.7%-97.9%) (P=0.886) in high risk groups respectively. ②Univariate analysis showed that DFS has no significant difference in patient age, the median disease course before HSCT, the WBC number at the beginning of the disease, blood routine and chromosomes examination before transplantation, extramedullary disease before transplantation, disease status before transplantation, conditioning regimen, donor type, donor and recipient sex, recipient blood type, transfused MNC number, transfused CD34(+) cell number and transfused CD3(+) cell number. DFS was significant lower in primary AML than that in secondary AML (P=0.006) and also lower in MRD positive than that in MRD negative (P=0.003) . The accumulative relapse was significant higher in CR(2) compared to that in CR(1) (P=0.046) . Accumulative non-relapse mortality (NRM) was significanlyt higher in secondary AML compared to that in primary AML (P=0.004) and also higher in MRD positive compared to that in MRD negative (P=0.010) . ③Multivariate analysis showed that MRD positive was the only significant factor in DFS and NRM. Conclusion: Allo-HSCT treatment of AML CR patients could achieve a high efficacy, which is similar between CR(1) and CR(2) patients. There is no significant correlation between NCCN (2015) risk stratification and the prognosis of AML patients with allo-HSCT treatment. Pre-conditioning MRD status monitored by multiparameter flow cytometry was the only impact factor on DFS and NRM in allo-HSCT for CR-AML patients.

corticofugal regulation of excitatory and inhibitory frequency tuning curves of bat inferior collicular neurons.

Corticofugal regulation of excitatory and inhibitory frequency tuning curves (FTCs) of neurons in the central nucleus of bat inferior colliculus (ICc) was studied by electrical stimulation of the primary auditory cortex (AC stimulation) under free field stimulation conditions using a two-tone inhibition paradigm. AC stimulation narrowed the excitatory FTCs and asymmetrically expanded the lateral inhibitory FTCs of corticofugally inhibited ICc neurons. The opposite results were observed for excitatory and inhibitory FTCs of corticofugally facilitated ICc neurons. These data support previous reports that corticofugal systems work together with widespread lateral inhibition to regulate subcortical frequency processing.

Immunohistologic evaluation of mechanisms mediating hyperacute lung rejection, and the effect of treatment with K76-COOH, FUT-175, and anti-Gal column immunoadsorption.

Although most investigators agree that lung dysfunction occurs rapidly in various pig-to-primate hyperacute lung rejection (HALR) models, the basic mechanisms mediating this phenomenon remain in question. Here we describe an immunohistochemical method for assessment of mechanisms driving HALR. Using an established model wherein piglet lungs are perfused ex vivo with human blood, six experimental groups (K76 COOH; FUT-175; K76 with FUT; anti-alpha-Gal column adsorption; column with FUT; and column with K76) and two control groups (unmodified human blood; autologous pig blood) were studied. Each lung was biopsied serially during perfusion, and assessed using an immunohistochemical technique, with vWF staining as an internal control to quantitate binding of human IgM, IgG, C3, C5b-9, properdin, and C1q. The effect of each treatment and subsequent lung perfusion on IgG and IgM anti-alpha-Gal titers(by ELISA) and on pig endothelial cell cytotoxicity were correlated with histologic findings. We found that [1] the classical complement activation pathway was activated, as has been shown for other pig organs in primate or human blood environments [2]; alternative complement pathway activation is also seen, which has not been described for other organs in pig-to-primate models, but only in the context of classical pathway activation; and [3] anti-Gal column absorption, pharmacologic inhibition of complement, or combination therapy each was associated with histologic evidence of partial protection, consistent with what would be predicted for each intervention. Further, immunohistologic differences correlated with physiologic outcomes [8] and with antibody assay results, and revealed that treatments used were incompletely effective. Our data suggest that more complete inhibition of antibody- and complement-driven pathways than was achieved in these experiments will be necessary to prevent the antibody and complement-mediated facets of hyperacute lung rejection. This immunohistologic technique may also help us identify additional pathogenic mechanisms important to eventual clinical application of pig-to-human lung xenografts.

Brain neutral lipids and phospholipids are modified by long-term feeding of beef tallow vs. corn oil diets.

Previous studies examining the response of brain lipids to dietary fat modification have not quantified neutral lipids such as diacylglycerols (DG) and triacylglycerols (TG). In this study we measured the concentrations of neutral lipids and phospholipids, and their fatty acid profiles, in the cerebra of rats fed defined diets containing either beef tallow (BT) or corn oil (CO) at 12% or 37% of energy. The diets were fed to rat pups beginning at 18 d of age and continued for 31 wk. The proportion of brain linoleic acid [18:2(n-6)] in TG from CO-fed rats was two- to fourfold greater than in BT-fed rats. Although 18:2(n-6) levels were higher in serum and brain TG of rats fed CO, differences in other TG fatty acid concentrations in serum were not reflected in the brain. Rats fed CO diets had higher concentrations of 18:2(n-6) in brain phospholipids as well as neutral lipids compared with rats fed BT diets, and the differences were greater in rats fed 37% rather than 12% of energy as fat. Differences in other polyunsaturated fatty acids associated with dietary fat composition were also found among the brain phospholipids. Most notably, the concentration of docosapentaenoic acid [22:5(n-6)] in brain phospholipids was highest in rats fed diets containing the lowest concentrations of alpha-linolenic acid [18:3(n-3)]. A concentration of 0.1 mg 18:3(n-3)/g diet appeared to be adequate to prevent elevation of 22:5(n-6) in brain phospholipids. These results demonstrate that consumption of a low fat diet (12% of energy) primarily comprised of saturated fats may potentiate an 18:3(n-3) deficiency in brain of rats.

[Effect of xue guan tong on PDGF-A, PDGF-B and c-myc gene expression of vessel wall in atherosclerotic rabbits].

In this study, the effect of Xue Guan Tong (XGT) on platelet-derived growth factor-A (PDGF-A), PDGF-B and c-myc gene expression of vessel wall was explored with dot blot and in situ hybridization. The results shown that the expression of PDGF-A mRNA in atherosclerotic plaque of the model group was higher, PDGF-A gene hybridizations were mainly distributed in smooth muscle cell which located in newly emerging plaque and edge of atherosclerotic plaque. In contrast, level of PDGF-A mRNA in the XGT group was lower than that in the model group, which indicated that XGT could influence the level of PDGF-A mRNA. The c-myc oncogene expression in the model group was significantly enhanced than that in the normal group. However, the expression in XGT group decreased less than that in the model group. From the results shown above, it suggested that one of the effects of XGT on preventing VSMC proliferation was its influence on PDGF-A and c-myc mRNA expression level.

Antitumor activity and tumor necrosis factor production of Phytolacca acinosa polysaccharides I in mice.

The antitumor activities of Phytolacca acinosa polysaccharides I (PAP-I) and its effects on the induction of tumor necrosis factor (TNF) and immunological cytotoxicity of peritoneal macrophages were studied. PAP-I was given ip 5-20 mg.kg-1.d-1 x 7 d to ICR mice as priming agent with subsequent lipopolysaccharides (10 micrograms/mouse) iv for TNF production. TNF activity was measured by crystal violet staining assay using L929 cells. PAP-I showed priming activity for TNF production with hepto-splenic hyperplasia in a dose-dependent manner. The peritoneal macrophages treated with PAP-I 10 and 20 mg.kg-1 showed 67 and 74%, respectively, cytotoxicity (the control 34% cytotoxicity) against Meth A cells at effector:target = 40:1. PAP-I 10 and 20 mg.kg-1 prolonged the survival time of mice bearing ascites Meth A tumor from 21 +/- 4 to 32 +/- 10 and 38 +/- 8 d and inhibited the solid Meth A tumor growth with inhibition rate of 28.5 and 55.7%, respectively. These results suggested that the antitumor activities of PAP-I were based on the activation of macrophages and induction of TNF.

Effect of esculentoside H on release of tumor necrosis factor from mouse peritoneal macrophages.

Effect of esculentoside H (EH) on release of tumor necrosis factor (TNF) from murine peritoneal macrophage (Mphi) in vitro was studied. The results showed that EH (12.5-200 micrograms.ml-1) induced the thioglycolate-broth elicited peritoneal Mphi to release TNF into supernatants in a dose-dependent manner, and higher levels of TNF activity were detected in the supernatants from EH-stimulated calcimycin-primed Mø culture. EH-induced TNF release had a different type of kinetics compared with that of lipopolysaccharides (LPS). LPS-induced release of TNF increased rapidly until 6 h after LPS stimulation, then declined gradually, while EH-induced TNF release increased gradually after EH stimulation and reached its peak at approximately 24 h later. These results suggested that the anti-tumor mechanisms of Phytolaccaceae may be related to the capacity of EH for TNF release.

[Changes in leucocytic estrogen receptor levels in patients with climacteric syndrome and therapeutic effect of liuwei dihuang pills].

The numbers of estrogen receptor (ER) in human peripheral leucocytes in 22 women with climacteric syndrome were measured by radioligand method. The results were compared with those of 12 normal child-bearing-age women. It wat found that the contents of leucocytic ER in climacteric syndrome patients were significantly lower than normal child-bearing-age women. The authors used a Chinese prescription--Liuwei Dihuang Pills (LDP) to treat the patients for 2 months. The numbers of leucocytic ER were significantly increased after treatment. The data indicate that decrease of ER levels in cell may involve in the pathogenesis of climacteric syndrome. LDP not only increases plasma estradiol levels, but also increases the leucocytic ER levels. This may be the basis of the therapeutic effect on the disease.

[Effects of Phytolacca acinosa polysaccharides I on cytotoxicity of macrophages and its production of tumor necrosis factor and interleukin 1].

The in vivo effects of Phytolacca acinosa polysaccharides I (PEP-I) on immunologic cytotoxicity of mouse peritoneal macrophages and its production of tumor necrosis factor (TNF) and interleukin 1 (IL-1) were studied. PEP-I 80, 160 mg/kg was given ip twice every 4 d. Both doses were found to have significant enhancing activity on macrophages cytotoxicity against S180 sarcoma cells and malignant transformed fibroblast L929 cells. Peritoneal activated macrophages were incubated with LPS for 2 and 24 h to induce TNF and IL-1, respectively. The TNF and IL-1 activities were tested from cytotoxicity against L929 cells in an absorbance assay of enzymatic reaction and proliferation of thymocytes co-stimulated assay separately. The optimal time for TNF production was found on d 8. Significant increases in TNF and IL-1 were observed. In comparison of the effect of PEP-I on TNF with that of known priming agent BCG, there was no difference between these two, but PEP-I had a high effect on IL-1. These results suggest that cytotoxicity of macrophages primed by PEP-I is closely related to its TNF and IL-1 production.

[Experimental studies of hyperlipidemia in rats and mice given a hyperlipidemic diet].

Hyperlipidemia in rats and mice was induced by hyperlipidemic diet containing 1.5% cholesterol, 0.25% cholic acid, 7.5% lard and 90.75% essential diet. After feeding for 7 days, the serum cholesterol levels in the experimental group are about 5 times higher than that in the control group. It appears that there exist similarities between rats and mice and that these models may be used for screening tests of hypolipidemic drugs.