Effects of effective antithyroid therapy on adiposity and skeletal muscle in patients with hyperthyroidism across gender and age groups.

OBJECTIVE: The study aimed to evaluate the effects of effective antithyroid therapy on adiposity and skeletal muscle in patients with hyperthyroidism across gender and age groups. PATIENTS AND METHODS: A total of 57 adult hyperthyroid patients (21 males and 36 females) who underwent effective antithyroid medication from January 2018 to January 2021 at Liuzhou People's Hospital and the First Affiliated Hospital of Guangxi Medical University were recruited and followed up for one year to observe the long-term efficacy of the antithyroid therapy. The eligible patients were divided by age and gender groups into male group A (males of <40 years old, n=12), female group A (females of <40 years old, n=19), male group B (males of 40-59 years old, n=8), female group B (female of 40-59 years old, n=13), and group C (patients of ≥60 years old, including one male and four females). A cohort of 57 healthy individuals was also recruited as controls. A Dual Energy X-ray (DXA) was performed to measure changes in fat and lean tissue mass and grip strength of the dominant hand before and after treatment and the body fat percentage (BFP). The whole-body skeletal muscle mass index (ASMI) was calculated to evaluate the long-term effects of antithyroid therapy. RESULTS: The eligible patients of all ages reported significantly increased total fat mass, body fat percentage, and body mass index (p<0.05). The total lean tissue mass was markedly increased in male and female group A (p<0.05), showed no significant changes in male and female group B (p>0.05), and exhibited a marked decline in group C (p<0.05). Significantly elevated ASMI after treatment was observed in male and female group A (p<0.05), while no significant changes were detected in ASMI after treatment in groups B and C (p>0.05). All patients in groups A and B exhibited enhanced grip strength, while the enhancement of grip strength in patients of group C was poor (p>0.05). CONCLUSIONS: Effective anti-hyperthyroidism therapy improves fat mass and body fat percentage in patients of all ages. However, gender and age differences exist in the effectiveness of improvements in total muscle mass and ASMI. Suboptimal muscle mass recovery was reported in patients over 40 years after effective anti-hyperthyroid therapy.

Expanding the phenotypic and genetic spectrum of Chinese patients with congenital absence of vas deferens bearing CFTR and ADGRG2 alleles.

BACKGROUND: Congenital absence of vas deferens (CAVD) is a major cause of obstructive azoospermia. Mutations in CFTR and ADGRG2 are responsible for this disease. However, until now the genetic spectrum of the CFTR and ADGRG2 genes in Chinese population and the reasons of the differences from Caucasian cohorts were not clear. OBJECTIVES: (i) To study the characteristic and functional consequences of CFTR and ADGRG2 mutations in Chinese CAVD patients. (ii) To describe the genetic spectrum of Chinese CAVD patients and explain the reasons of the differences from Caucasian cohorts and Chinese cystic fibrosis (CF) patients. MATERIALS AND METHODS: Patients were screened for mutations in CFTR by Sanger sequencing. Patients with only one or no mutations were further investigated by multiplex ligation-dependent probe amplification analysis and direct sequencing of ADGRG2 gene. Bioinformatic analysis and structural modeling of proteins were performed. RESULTS: A total of 28 mutations in CFTR were identified in 72 patients, of which five mutations were novel. Fifty-five patients (76.39%) had CFTR mutations but no indels, among which 80.00% CBAVD patients have at least one CFTR mutation and 66.67% CUAVD have at least one CFTR mutation. Two novel mutations (p.Lys818* and p.Arg1008Gln) in ADGRG2 were detected. These novel mutations were predicted to be damaging by bioinformatics and were absent or extremely low frequency among our controls and databases. The genetic spectrum of Chinese CAVD patients revealed that the most common mutations were c.1210-12T[5], p.Ile556Val and p.Gln1352His, the last two of which were predicted to reduce the domains' contacts and weaken adenosine triphosphate binding. DISCUSSION AND CONCLUSION: This study illustrates the significance of all exon sequencing in CFTR and ADGRG2. A picture of the genetic spectrum of Chinese CAVD patients and the most common mutations can be described, which are different from Caucasian cohorts and Chinese CF patients.

Correlation between blood asymmetric dimethylarginine level and the complications of patients with cardiovascular diseases.

This study aimed to investigate the correlation between blood asymmetric dimethylarginine (ADMA) and the complications of patients with cardiovascular diseases through studying the level changes of ADMA, endothelial nitric oxide synthase (eNOS) and NO. Two hundred research subjects with small differences in gender ratio and age, including 50 patients with hypertension combined with myocardial infarction, 50 patients with hypertension, 50 patients with myocardial infarction and 50 healthy normal controls, were enrolled. Relevant basic indexes were measured and recorded; the blood ADMA levels of all the research subjects were detected using high pressure liquid chromatography (HPLC) within the required time. Furthermore, the levels of eNOS and NO were detected using enzyme-linked immunosorbent assay and the relevant information, such as blood pressure, was recorded. The comparison and analysis results of data obtained through detection demonstrated that the subjects in the four groups were well comparable. It was found that the myocardial infarction combined with hypertension group had a much higher serum ADMA level and relatively low levels of eNOS and NO compared to those of the other three groups; the myocardial infarction group and the hypertension group had a much higher serum ADMA level compared to that of the healthy control group and the two groups had much lower levels of eNOS and NO. Moreover, the serum ADMA level was in a positive correlation with the severity of cardiovascular diseases and it showed a significant difference in patients with different severity of hypertension. The change of blood ADMA level can induce acute myocardial infarction as well as the occurrence of cardiovascular disease-associated complications.

Clinical significance and levels of blood brain natriuretic peptides in patients with persistent atrial fibrillation before and after catheter ablation.

The aim of this study was to observe levels of blood brain natriuretic peptides (BNPs) in patients with persistent atrial fibril-lation (AF) before and after catheter ablation. Thirty-six patients with persistent AF (28 successful surgeries and eight recurrent cases) and 36 healthy controls with normal sinus rhythm were recruited for this study. BNP levels in the AF and control groups were measured before and after catheter ablation. BNP levels before surgery were significantly higher in the persistent AF group than in the control group (P < 0.01). The successful surgery group had distinctly lower BNP levels before ablation than the recurrent group (P < 0.01). In the recurrent group, BNP levels 2 h after ablation were significantly lower than those be-fore ablation (P < 0.01); these levels increased after AF recurrence (P < 0.01) and were comparable with those before ablation (P < 0.01). Logistic regression analysis indicated that the BNP level was an inde-pendent factor for and predictor of AF recurrence (P < 0.01). The BNP level in patients with persistent AF is clinically important in predicting and evaluating AF recurrence after ablation.

Safety and efficacy of intracoronary tirofiban administration in patients with serious thrombus burden and ST-elevation myocardial infarction undergoing percutaneous coronary intervention.

OBJECTIVE: This work aims to explore the safety and efficacy of intracoronary tirofiban administration in patients with serious thrombus burden and ST-elevation myocardial infarction (STEMI) undergoing emergency percutaneous coronary intervention (PCI). PATIENTS AND METHODS: A total of 104 patients with serious thrombus burden and acute STEMI were randomly divided into treatment (intracoronary tirofiban administration, 56 cases) and control (48 cases) groups. Comparison of coronary blood flow, ST-segment resolution (STR), duration of hospital stay, 30-day major adverse cardiac events (MACE) and complications such as hemorrhage was conducted. RESULTS: In treatment group, the percentage of thrombolysis in myocardial infarction-3 (TIMI-3) flow in the infarct-related artery (IRA) increased (89.3% to 85.4, p < 0.05), blood flow in the IRA calculated with TIMI frame count method enhanced [(1.68 ± 0.23) ml/s to (1.42 ± 0.31) ml/s, p < 0.05], STR on electrocardiogram (ECG) enlarged [(64.3 ± 7.84)% to (48.6 ± 6.47)%, p < 0.05)] and the prevalence of MACE decreased (10.7% to 18.8%, p < 0.05), all of which were significantly different from those of control group, but no statistical difference in complications was observed between two groups (p > 0.05). CONCLUSIONS: It was simple, safe and effective to perform intracoronary tirofiban administration in patients with serious thrombus burden and STEMI when undergoing emergency PCI.

An oligopeptide ligand-mediated therapeutic gene nanocomplex for liver cancer-targeted therapy.

The epidermal growth factor receptor (EGFR) is over-expressed in a wide variety of epithelial-derived cancer cells. In this study, EGFR-targeted gene carriers were designed to complex the therapeutic acetylcholinesterase gene (AChE gene), which suppresses cell proliferation via inactivating mitogen-activated protein kinase and PI3K/Akt pathways in cells, for treatment of EGFR-positive liver cancers. Different amounts of target ligand YC21 (an oligopeptide composed of 21 amino acid units) were coupled with the PEI(600)-CD (PC) vectors composed of ß-cyclodextrin (ß-CD) and low-molecular-weight polyethylenimine (PEI, Mw 600) to form the EGFR-targeted gene vectors (termed as YPCs). The YPC vectors possessed the highly efficient gene delivery ability to the EGFR-positive liver cancer cells. YPCs could effectively promote AChE gene expression. The YPC/AChE complexes produced excellent gene transfection abilities in EGFR-positive liver cancer cells in vitro and in vivo.

Concomitant irritable bowel syndrome is associated with failure of step-down on-demand proton pump inhibitor treatment in patients with gastro-esophageal reflux disease.

BACKGROUND: The predictors for treatment failure of on-demand proton pump inhibitor (PPI) therapy in gastro-esophageal reflux disease (GERD) patients are unclear. We studied the efficacy and predictors for treatment failure of step-down on-demand PPI therapy in patients with non-erosive reflux disease (NERD) and those with low grade erosive esophagitis. METHODS: Consecutive symptomatic GERD patients who had positive esophageal pH studies and complete symptom resolution with initial treatment of esomeprazole were given step-down on-demand esomeprazole for 26 weeks. Patients with esophagitis of Los Angeles (LA) grade C or above and recent use of PPI were excluded. Treatment failure was defined as an inadequate relief of reflux symptoms using global symptom assessment. Potential predictors of treatment failure were determined using multivariate analysis. KEY RESULTS: One hundred and sixty three NERD and 102 esophagitis patients were studied. The 26-week probability of treatment failure was 36.2% (95% CI: 23.9-46.5%) in NERD group and 20.1% (95% CI: 10.9-28.3%) in esophagitis group, respectively (P = 0.021). Irritable bowel syndrome (adjusted HR: 2.1, 95% CI: 1.5-3.8, P = 0.01), in addition to daily reflux symptom (adjusted hazard ratio: 2.7, 95% CI: 1.9-4.2, P = 0.001) and concomitant dyspepsia (adjusted hazard ratio: 1.7, 95% CI: 1.1-2.8, P = 0.04), were independent predictors for treatment failure. CONCLUSIONS & INFERENCES: Compared to patients with esophagitis, NERD patients have higher failure rate of on-demand PPI therapy. Concomitant irritable bowel syndrome, in addition to daily reflux symptom and dyspepsia, is associated with the failure of on-demand PPI in these patients.

Endoscopic ultrasonography-guided fine-needle aspiration in the management of mediastinal diseases: local experience of a novel investigation.

OBJECTIVE: To study the efficacy and safety of endoscopic ultrasonography-guided fine-needle aspiration in the management of mediastinal diseases in Hong Kong. DESIGN: Retrospective review of prospectively collected data. SETTING: University teaching hospital, Hong Kong. PATIENTS: A total of 125 consecutive patients with various mediastinal and pulmonary lesions that underwent trans-oesophageal endoscopic ultrasonography-guided fine-needle aspiration from July 1998 to June 2007. MAIN OUTCOME MEASURES: The diagnostic accuracy and safety of the procedure and its influence in patient management. RESULTS: Malignancy was confirmed in 62 (50%) of the patients and excluded in 42 (34%). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of endoscopic ultrasonography-guided fine-needle aspiration in diagnosing mediastinal malignancies were 75% (95% confidence interval, 64-83%), 100% (90-100%), 100% (93-100%), 67% (54-78%), and 83%, respectively. Eighty-six (69%) of the patients had their initial plan of invasive investigations changed. Only one (0.8%) patient developed a septic complication in a mediastinal cyst after puncturing, and was treated surgically. CONCLUSIONS: Trans-oesophageal endoscopic ultrasonography-guided fine-needle aspiration is a minimally invasive, effective, and safe method of diagnosing malignant mediastinal disease. It may reduce the need for other invasive investigations.

A novel glioblastoma cancer gene therapy using AAV-mediated long-term expression of human TERT C-terminal polypeptide.

Glioblastoma multiforme is the most aggressive form of human brain tumor, which has no effective cure. Previously, we have demonstrated that overexpression of the C-terminal fragment of the human telomerase reverse transcriptase (hTERTC27) inhibits the growth and tumorigenicity of human cervical cancer HeLa cells. In this study, the therapeutic effect and molecular mechanisms of hTERTC27-mediated cancer gene therapy were further explored in vivo in established human glioblastoma xenografts in nude mice. We showed that intratumoral injection of adeno-associated virus carrying hTERTC27 (rAAV-hTERTC27) is highly effective in reducing the growth of the subcutaneously transplanted glioblastoma tumors. Histological analyses showed that rAAV-hTERTC27 treatment leads to profound necrosis, apoptosis, infiltration of polymorphonuclear neutrophils and reduced microvessel density in the tumor samples. To study the molecular mechanism of rAAV-hTERTC27-mediated antitumor effects, we analyzed the global gene expression profiles of the rAAV-hTERTC27-treated tumor tissues and cell line as compared with that of the control rAAV-green fluorescent protein-treated samples by DNA microarray. Our results suggest that hTERTC27 exerts its effect through complex mechanisms, which involve genes regulating apoptosis, cell adhesion, cell cycle, immune responses, metabolism, signal transduction, transport, transcription and telomere maintenance.

Cyclization of several linear penta- and heptapeptides with different metal ions studied by CD spectroscopy.

A cyclic pentapeptide c(Tyr-Leu-Ala-Gly-Pro) (I), which was isolated and identified from Pseudostellaria heterophylla medicinal herbs, and two cyclic heptapeptides, c(Gly-Tyr-Gly-Gly-Pro-Phe-Pro) (II) and c(Gly-Ile-Pro-Tyr-Ile-Ala-Ala) (III), which were isolated and identified from Stellaria yunnanensis Franch (M), were synthesized by using 3-(diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3 H)-one (DEPBT) as a coupling reagent in solution, and mediated by different metal ions, from their linear peptide precursors H-Tyr-Leu-Ala-Gly-Pro-OH (I-1) and H-Ala-Gly-Pro-Tyr-Leu-OH (I-2), H-Gly-Tyr-Gly-Gly-Pro-Phe-Pro-OH (II-1) and H-Gly-Ile-Pro-Tyr-Ile-Ala-Ala-OH (III-1), respectively. The results show that alkali metal ions can improve the cyclization yields and/or the cyclization rates of linear peptide precursors, such as Na(+) ion is favorable for the cyclization of linear pentapeptides and Cs(+) ion is favorable for the cyclization of linear heptapeptides, while some bivalent and trivalent metal ions, such as Mg(2+), Ca(2+), Zn(2+), Fe(2+), Ni(2+) and Cr(3+) reduced/inhibited both the cyclization yields and the cyclization rates of the linear peptide precursors. The circular dichroism spectra of I-1, II-1 and III-1 with different metal ions were studied to elucidate the changes in their secondary structures. It is shown that Cs(+) can induce and stabilize the type I beta-turn conformation in the linear heptapeptide II-1 and the type II beta-turn conformation in the linear heptapeptide III-1.

Structure-activity relationship of memory enhancing peptide ZNC (C) PR analogs.

ZNC(C)PR has been found to be a new neuropeptide in rat brain as a significant enhancer of learning and memory. In this work, the structure-activity relationship of ZNC(C)PR was studied. First, the roles of every residue in ZNC(C)PR were investigated theoretically and analogs were designed according to the predicted conformational properties. Five analogs were synthesized following the design. Passive avoidance behavior tests in rats showed that NIPR, NVPR, and NAPR have positive effects to facilitate memory, while NSPR has no effect, and DLPR has somewhat inhibitory effect. As the experimental results are in good agreement with that of theoretical calculations, it is suggested that further research may help us to understand more details on the structure-activity relationship of ZNC(C)PR and provides a way for further design of potent agonist, antagonist and possible nonpeptide mimetics of ZNC(C)PR.

Phyletic relationships of protein structures based on spatial preference of residues.

A structure-based scoring matrix MDPRE was derived from amino acid spatial preferences in protein structures. Sequence alignment and evolutionary studies by using MDPRE matrix gave similar results as those from ordinary sequence and structure alignments. It is interesting that a matrix derived from structure data solely could give comparable alignment results, strongly indicating the intimate connection between protein sequences and structures. The branch order and length from this approach were close to those obtained by a structure comparison method. Thus, by applying this structure-based matrix, the trees obtained should reflect evolutionary characteristics of protein structure. This approach takes advantage over a direct structure comparison in that (1) only a sequence and MDPRE matrix are needed, making it simple and widely applicable (especially in the absence of 3-dimensional protein structure data); (2) an established algorithm for sequence alignment and tree building could be employed, providing opportunities for direct comparison between matrices from different methodologies. One of the most striking features of this method is its capability to detect protein structure homologies when the sequence identities are low. This was well reflected in the given examples of the alignment of dinucleotide-binding domains.

[Clinical study of Urocit-K: a slow releasing potassium citrate].

Citrate is recognized as one of the inhibitors of urinary stone formation. If the urinary citrate and pH could be elevated by the supply of potassium citrate, the recurrence of stone formation would hopefully be prevented. Urocit-K is a kind of slow releasing preparation of potassium citrate. The pharmacokinetics of Urocit-K is investigated in this study, which included two groups: 1) the hypocitraturia group consisting of twenty patients and 2) the normal volunteer group consisting of ten persons. Urokit-K was administered to patients in 10 mEq doses, t.i.d. for 2 weeks. Comparison of urinary biochemistry was done prior to, and one week after administration of the Urocit-K. In the normal volunteer group, the pharmacokinetics of Urocit-K was determined by urinary pH, K, and citrate. Determinations were made six times a day (every 2-hours for first 8 hours, 7- and 9- hours for the last 16 hours) with Urocit-K for comparison. This study indicated that Urocit-K increases urinary pH, K, and citrate in hypocitraturic patients. In the normal volunteer group, Urocit-K deserves its slow-releasing property shown by a constant increase of urinary pH and K for the first 8 hours; and urinary citrate for almost 24 hours. No apparent complications, such as gastrointestinal upset or cardiopulmonary discomfort were observed. In conclusion, Urocit-K is an excellent preparation of potassium citrate and a good choice for prevention of stone recurrence.

The structural basis of the poor fibrin specificity of urokinase(I)--knowledge-based prediction of kringle structures of urokinase and its related proteins.

The Kringle-1 structure of plasminogen (PGK-1), the Kringle-2 structure of tissue plasminogen activator (PAK-2) and the Kringle structure of prourokinase (UKK) has been modeled on the basis of the three-dimensional structure of Kringle-1 of prothrombin (PTK-1) at 2.8 A resolution. The predicted three-dimensional structure of these Kringles shows that the binding site of PGK-1 is characterized by an apparent dipolar site, the polar parts of which are separated by a hydrophobic region. PAK-2 possesses the anionic center but has not a cationic binding center which might be provided by a guanidinium group from Arg-69 located adjacent to the Arg-71 position. UKK possesses neither the anionic binding center nor the cationic center which are probably the main reason for the poor fibrin specificity of urokinase.