[Transient infantile hypertriglyceridemia caused by GPD1 deficiency: report of two cases and literature review].

Objective: To investigate the clinical phenotype and genotype of transient infantile hypertriglyceridemia (HTGTI). Methods: The clinical data of two HTGTI children, diagnosed at Children's Hospital of Fudan University from July 2019 to January 2020, were collected and analyzed retrospectively. The literature up to 25th January 2020 were searched in PubMed, CNKI and Wanfang databases with the key words of "hypertriglyceridemia" and "glycerol phosphate dehydrogenase-1 (GPD1)". Results: Two children, including a 5-month-old female and a 13-month-old male, who presented with hepatomegaly, hypertriglyceridemia, transaminase elevation and hepatic steatosis, were admitted to the hospital. Gene detection found compound heterozygous variation of GPD1. After a low-fat diet with enriched medium-chain fatty acids, their plasma triglyceride level were significantly decreased, and finally normalized in case 2. Literature review found 17 patients with GPD1 gene variation reported in 5 papers, including 16 HTGTI cases and one case of different phenotype. Most of the cases presented with hepatomegaly, hypertriglyceridemia and transaminase elevation, while some had developmental retardation, splenomegaly, hypoglycemia, obesity and insulin resistance. The c.361-1G>C was the most common variation of GPD1. Conclusions: HTGTI caused by GPD1 deficiency is mainly manifested with hepatomegaly, hypertriglyceridemia, transaminase elevation as well as hepatic steatosis and fibrosis. The most common variation of GPD1 is c.361-1G>C.

Facial artery musculomucosal flaps in oropharyngeal reconstruction following salvage transoral robotic surgery: a review of outcomes.

OBJECTIVE: There has been little reported on the transoral reconstructive options following salvage transoral robotic surgery. This paper describes the facial artery musculomucosal flap as a method to introduce vascularised tissue to a previously irradiated resection bed. METHODS: A facial artery musculomucosal flap was used to reconstruct the lateral pharyngeal wall in 13 patients undergoing salvage transoral robotic surgery for oropharyngeal squamous cell carcinoma. Outcomes recorded include flap and donor site complications, length of stay, and swallowing and speech outcomes. RESULTS: There were no immediate or late flap complications, or cases of delayed wound healing in this series. There were two facial artery musculomucosal related complications requiring surgical management: one bleed from the facial artery musculomucosal donor site and one minor surgical revision. Healing of the flap onto the resection bed was successful in all cases. CONCLUSION: The facial artery musculomucosal flap provides a suitable transoral local flap option for selected patients undergoing salvage transoral robotic surgery for oropharyngeal malignancies.

[Characteristics of renal cortical perfusion and its association with renal function among elderly patients with renal artery stenosis].

Objective: To evaluate the characteristics of renal cortical blood perfusion assessed by contrast-enhanced ultrasound (CEUS) in elderly patients with renal artery stenosis (RAS) and its relationship with renal function. Methods: Ninety-three elderly patients diagnosed with RAS, who were admitted in Beijing Hospital during June 2017 and December 2018, were retrospectively enrolled. According to the degree of RAS, 186 renal arteries were divided into normal renal artery group (n=79), mild RAS group (30% to 49%, n=59), moderate RAS group (50% to 70%, n=33), and severe RAS group (70% to 99%, n=15). Renal cortical blood perfusion and renal glomerular filtration rate (GFR) were measured by CEUS and radionuclide renal dynamic imaging. According to the renal GFR, 186 kidneys were divided into normal renal function group (GFR≥35 ml/min, n=42) and mild renal insufficiency group (35 ml/min>GFR≥25 ml/min, n=51), moderate renal insufficiency group (25 ml/min>GFR≥15 ml/min, n=75) and severe renal insufficiency group (GFR<15 ml/min, n=18). The renal cortical blood perfusion time-intensity curve (TIC) and related parameters were analyzed, including the area under the curve (AUC), the slope of the ascending branch (A), the peak intensity (PI), the peak time (TTP) and the mean transit time (MTT), the kidneys of different RAS groups and patients with different renal function groups were analyzed. Pearson correlation analysis was used to evaluate the correlation between renal cortical blood perfusion parameters and renal GFR. Results: (1) Renal cortical blood perfusion and GFR: CEUS showed that parameter A of TIC was significantly reduced, while TTP was prolonged in the mild renal artery stenosis group compared with the normal renal artery group (both P<0.05), GFP was similar between the two groups. Cortical perfusion parameters, such as AUC, A, PI and GFR were significantly lower, while TTP and MTT were significantly prolonged in the moderate and severe renal artery stenosis group than in the normal and mild stenosis groups (all P<0.05). Compared with the moderate stenosis group, AUC, A, PI and GFR were significantly lower while TTP, MTT were significantly prolonged in the severe renal artery stenosis group (all P<0.05). (2) TIC showed that the renal perfusion parameters, AUC, PI and A were significantly lower, while TTP was significantly longer in the mild renal dysfunction group than in the normal renal function group (all P<0.001). The changes aggravated in proportion with renal dysfunction. (3) Correlation between perfusion parameters and GFR: Pearson correlation analysis showed that the AUC (r=0.774, P<0.05), A (r=0.815, P<0.05) and PI (r=0.772, P<0.05) were positively correlated with GFR; serum creatinine level (r=-0.841, P<0.05), renal function grading (r=-0.731, P<0.05), TTP (r=-0.803, P<0.05) and MTT (r=-0.741, P<0.05) were negative correlated with GFR. The degree of stenosis was negatively correlated with GFR (r=-0.427, P<0.05). Conclusion: Cortical perfusion parameters differ significantly among patients with various degree of RAS and renal dysfunction. The renal cortical blood perfusion parameters are correlated with renal GFR.

A study of regulatory effects of TLR4 and NF-κB on primary biliary cholangitis.

OBJECTIVE: To investigate the regulatory effects of the Toll-like receptor 4 (TLR4) and the nuclear factor kappa-light-chain-enhancer of the activated B cells (NF-κB) on primary biliary cholangitis (PBC) and to analyze the possible mechanisms. MATERIALS AND METHODS: A total of 24 C57BL/6 mice were randomly divided into M group (n=12, intraperitoneally injected with polyinosinic acid-polycytidine acid (PolyI:C) for 12 consecutive weeks, 2 times/week) and C group (n=12, intraperitoneally injected with the same volume of normal saline). After 12 weeks, the mice were sacrificed to collect liver tissues. Then, an enzyme-linked immunosorbent assay (ELISA) kit was used to detect the content of interleukin-6 (IL-6), IL-10, and tumor necrosis factor-alpha (TNF-α) in liver tissues. Hematoxylin-eosin (HE) staining assay was performed to observe the pathological changes of liver tissues, and measure the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in peripheral blood of mice. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling (TUNEL) staining was applied to determine cell apoptosis in liver tissues. The relative messenger ribonucleic acid (mRNA) expression levels of TLR4 and NF-κB in liver tissues were detected by quantitative Polymerase Chain Reaction (qPCR). Western blotting was adopted to measure the protein expressions of TLR4, NF-κB, myeloid differentiation factor 88 (MyD88), B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax), and Caspase-3. RESULTS: Compared with that in C group, the content of IL-6 and TNF-α in liver tissues in M group was significantly increased (p<0.01), but the level of IL-10 was statistically downregulated (p<0.01). According to HE staining, liver damage of mice in M group was evidently severer than that in C group, and the levels of ALT and AST in M group were significantly higher than those in C group (p<0.01). The amount of TUNEL-positive cells in liver tissues in M group was significantly greater than that in C group (p<0.01). The levels of TLR4 and NF-κB mRNA in liver tissues from M group were significantly elevated in comparison with the C group (p<0.01). Compared with those in C group, the expressions of TLR4, NF-κB, MyD88, and Caspase-3 proteins in M group showed statistical increases in liver tissues (p<0.01), whereas that of Bcl-2/Bax was significantly declined (p<0.01). CONCLUSIONS: PBC activates the TLR4/MyD88/NF-κB signaling pathway, induces the release of inflammatory factors and produces a large number of apoptotic proteins, which results in liver damage and cell apoptosis in mice.

Association of NPR3 polymorphism with risk of essential hypertension in a Chinese population.

WHAT IS KNOWN AND OBJECTIVE: Essential hypertension (EH) is a common disease exhibiting large individual difference in occurrence, development and treatment response. Genetic factors are implicated in the development and progression of EH. This study aimed to explore the association between NPR3 single nucleotide polymorphism rs2270915 (A/G, Asn521Asp) and the risk of EH in a Chinese Han population by a case-control study. METHODS: The study was a single-centre, case-control trial, in which a total of 287 EH patients and 289 age- and sex-matched healthy controls were enrolled. The inclusion criteria were as follows: Han Chinese origin, male or female patients, systolic blood pressure (SBP) ≥140 mm Hg and/or diastolic blood pressure (DBP) ≥90 mm Hg. The healthy controls were subjects without histories of cardiovascular or cerebrovascular diseases. NPR3 rs2270915 polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In addition, primary human umbilical vein endothelial cells (HUVECs) were isolated from 19 fresh human umbilical cords and cultured. Atrial natriuretic peptide (ANP) concentration in cell medium was determined by enzyme-linked immunosorbent assay (ELISA). NPR3 mRNA expression was determined by real-time semi-quantitative PCR. RESULTS AND DISCUSSION: No significant difference in genotype distribution of NPR3 rs2270915 polymorphism was observed between cases and controls (P>.05). Patients carrying the rs2270915 G allele showed decreased SBP, and the difference was marginal. As compared with cells carrying the rs2270915 AA genotype, those with the AG genotype showed significantly lower NPR3 mRNA expression levels (P<.05) and lower medium ANP concentration (P<.001). WHAT IS NEW AND CONCLUSION: This study suggested that NPR3 rs2270915 polymorphism was associated with decreased SBP level marginally in EH patients in a Chinese Han population, and the polymorphism may function through decreasing NPR3 mRNA expression and ANP level.

A school outbreak of pandemic (H1N1) 2009 infection: assessment of secondary household transmission and the protective role of oseltamivir.

In mid-June 2009, an outbreak of pandemic (H1N1) 2009 (pH1N1) infection occurred in a secondary school in Hong Kong. We carried out an epidemiological investigation to delineate the characteristics of the outbreak, gauge the extent of secondary household transmission, and assess the protective role of oseltamivir in household contacts. We interviewed pH1N1-confirmed cases using a standardized questionnaire. Sixty-five of 511 students in the school were affected. Of the 205 household contacts identified, 12 were confirmed as cases. All cases recovered. The estimated secondary household attack rate was 5·9% (95% CI 2·7-9·1). Household contacts aged <18 years were about 15 times more likely to be infected than older contacts. Household contacts who had received oseltamivir prophylaxis were less likely to acquire a secondary infection than those who had not (odds ratio=0). The estimated mean household serial interval of pH1N1 virus was 2·8 days (95% CI 2·1-3·4 days).

Smoking and depressive symptoms in Chinese elderly in Hong Kong.

OBJECTIVE: To examine the association between smoking and depressive symptoms among Chinese elderly in Hong Kong. METHOD: Cross-sectional data on smoking and depressive symptoms from 56,167 Chinese elderly aged 65 or over in Hong Kong were analysed using logistic regression. RESULTS: Current smokers and former smokers were more likely to have depressive symptoms than never smokers. The adjusted odds ratios (OR) and 95% confidence interval (CI) in males and females respectively were 1.62 (1.34-1.96) and 1.43 (1.20-1.70) for current smokers, and were 1.18 (0.99-1.40) and 1.29 (1.12-1.47) for former smokers. Former smokers were less likely to have depressive symptoms than current smokers (OR = 0.80, 95% CI: 0.70-0.92). CONCLUSION: Smoking is positively associated with depressive symptoms in Chinese elderly. Health care workers should be vigilant about the detection of depressive symptoms in elderly smokers.

Modification of vesicle surfaces with amphiphilic sterols. Effect on permeability and in vivo tissue distribution.

In this paper, we describe the permeability of vesicles prepared with various synthetic cholesterol derivatives. Cholesterol derivatives with side-chains ending in hydroxyl groups reduced the permeability of unilamellar vesicles. However, addition of cholesterol derivatives with terminal amino groups makes the vesicles more permeable. Vesicles prepared with a short-chain amino-cholesterol derivative were found to be less permeable in phosphate-buffered saline, but not in bovine serum, while long-chain amino-cholesterol-containing vesicles were very permeable in both media. Studies in vivo indicate a rapid clearance rate for intravenously administered amino-cholesterol-containing vesicles with a concomitant increase in liver uptake. However, no difference was found in either the clearance or tissue distribution of control vesicles and the less permeable hydroxyl-cholesterol-containing vesicles.

The pharmacological efficacy of a rigid non-phospholipid liposome drug delivery system.

Hydration of an ethoxylate derivative of cholesterol, triethoxycholesterol, results in the formation of stable, rigid, bilayer-like structures capable of encapsulating polar compounds. Studies on the stability and tissue distribution of these liposomes in mice indicate that they are suitable as a drug delivery system. Intraperitoneal injection of triethoxycholesterol encapsulated methotrexate into mice bearing hepatoma ascites tumor results in a doubling of the survival time, relative to untreated mice and those receiving unencaptulated drug. These studies show that fluid, acyl chains are not required for the formation of pharmacologically useful vesicles and that such formulations need not be limited to phospholipid-containing systems.

Suppression of liver uptake of liposomes by dextran sulfate 500.

The effect of dextran sulfate (DS, 500,000 Mr) and multilamellar vesicles (MLV) as liver blockade agents has been investigated in mice. Intravenous injection of unlabeled MLV prior to radioactive MLV caused moderate reduction in the liver uptake and increased tibia, lung, and spleen uptake. More drastic differences were observed with intraperitoneal injection of DS. When tested in the range of 0-50 mg of DS per kg of body weight, maximal liver blockade occurred at a dose of 50 mg. By using 50 mg of DS per kg, maximal liver blockade occurred at 12 hr after DS injection. The liver blockade was temporary, ending within 48 hr. The intraperitoneal route of injection for DS was more effective for liver blockade than the intravenous route.

Steroid derivatives for electrophilic affinity labelling of glucocorticoid binding sites: interaction with the glucocorticoid receptor and biological activity.

To investigate the possible use of electrophilic affinity labelling for the characterization of glucocorticoid receptors, different chemically reactive derivatives of deoxycorticosterone (deoxycorticosterone 21-mesylate and deoxycorticosterone 21-(1-imidazole) carboxylate), dexamethasone (dexamethasone 21-mesylate, dexamethasone 21-iodoacetate and dexamethasone 21-bromoacetate) and progesterone (21-chloro progesterone) were tested for their ability to bind irreversibly to the glucocorticoid receptor from goat lactating mammary gland. Using partially purified receptor, only one of the steroids tested, dexamethasone 21-mesylate (DXM-M) was found more effective than dexamethasone (DXM) in preventing exchange of radioactive dexamethasone in the receptor binding site. The affinity of DXM-M for the glucocorticoid receptor, measured by competitive binding assay, was 1/15 that of DXM. Polyacrylamide gel electrophoresis in sodium dodecyl sulphate of the [3H]-DXM-M labeled glucocorticoid receptor revealed a specific covalently radiolabeled fraction corresponding to an apparent molecular weight of 75,000 to 80,000. The biological activity of DXM-M was studied in RPMI 3460-clone 6 Syrian hamster melanoma cells, a cell line which is sensitive to growth inhibition by glucocorticoids. Like DXM, DXM-M inhibits the growth of RPMI 3460-clone 6 cells and it acts as a slowly reversible glucocorticoid agonist at concentrations which correlate with the affinity of DXM-M for the glucocorticoid receptor in vitro.

Oxidative peptide (and amide) formation from Schiff base complexes.

One hypothesis of the origin of pre-modern forms of life is that the original replicating molecules were specific polypeptides which acted as templates for the assembly of poly-Schiff bases complementary to the template, and that these polymers were then oxidized to peptide linkages, probably by photo-produced oxidants. A double cycle of such anti-parallel complementary replication would yield the original peptide polymer. If this model were valid, the Schiff base between an N-acyl alpha amino aldehyde and an amino acid should yield a dipeptide in aqueous solution in the presence of an appropriate oxidant. In the present study it is shown that the substituted dipeptide, N-acetyl-tyrosyl-tyrosine, is produced in high yield in aqueous solution at pH 9 through the action of H2O2 on the Schiff-base complex between N-acetyl-tyrosinal and tyrosine and that a great variety of N-acyl amino acids are formed from amino acids and aliphatic aldehydes under similar conditions.

Hypertensive action of 18-hydroxydeoxycorticosterone.

18-Hydroxydeoxycorticosterone is an adrenal steroid hormone causing salt and water retention and is secreted in greatly increased amounts in response to the pituitary hormone adrenocorticotropic hormone. Its production is abnormally high in some forms of hypertension in man and rat. Direct proof that 18-hydroxydeoxycorticosterone is capable of causing hypertension is present. Daily subcutaneous injections of 200 micrograms, a low physiological dose, significantly increase the blood pressure of unilaterally nephrectomized saline-treated rats after 2 weeks. This strengthens the hypothesis that 18-hydroxydeoxycorticosterone contributes to the etiology of hypertension, possibly by a mechanism involving stressinduced release of adrenocorticotropic hormone.