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Biomedical subjects

H P Zhang

Publications and source records attributed to H P Zhang.

At least 19 recordsLinked to original sources

[Efficacy and safety of acute-phase transcutaneous auricular vagus nerve stimulation for herpes zoster-related pain in middle-aged and elderly patients with comorbid depression and anxiety].

Objective: To evaluate the efficacy and safety of transcutaneous auricular vagus nerve stimulation (taVNS) during the acute phase in middle-aged and elderly patients with herpes zoster (HZ) comorbid depressive and anxiety states. Methods: This was a randomized controlled trial. Forty middle-aged and elderly patients with acute-phase HZ who attended the Department of Dermatology at Xuanwu Hospital, Capital Medical University, from June 2024 to June 2025 were enrolled and randomly assigned in a 1&#x2236;1 ratio using a random number table to receive either taVNS (n=20) or sham stimulation (n=20) for 5 consecutive days. Both groups received antiviral therapy and on-demand rescue analgesia. Pain, anxiety/depression, and sleep quality were evaluated using the Visual Analog Scale (VAS), the 4-item Patient Health Questionnaire (PHQ-4), and the Insomnia Severity Index (ISI), respectively. The primary outcome was the incidence of subacute pain at 30 days post-rash onset. Secondary outcomes included cumulative analgesic consumption at 1 and 2 weeks after treatment, the changes from baseline (&#x394; values) in PHQ-4 and ISI scores at 2 weeks, and the incidence of postherpetic neuralgia (PHN) at 90 days post-rash onset. Results: In the taVNS group, 7 patients (35%) were female, with a mean age of (64.1&#xb1;9.7) years; in the sham group, 10 patients (50%) were female, with a mean age of (61.5&#xb1;8.5) years. There were no statistically significant differences between the two groups in baseline VAS, PHQ-4, or ISI scores (all P>0.05). The incidence of subacute pain was significantly lower in the taVNS group than in the sham group [5% (1/20) vs 35% (7/20), RD=-30.0% (95%CI:-52.1%--4.9%); RR=0.14 (95%CI: 0.02-1.06); P=0.044]. At 2 weeks after treatment, the &#x394; values of PHQ-4 and ISI in the taVNS group were significantly greater than those in the sham group. The proportion of patients taking Lofentadine and the cumulative Lofentadine consumption at weeks 1 and 2 were both lower in the taVNS group than in the sham group (all P<0.05). No serious adverse events occurred in either group, and the difference in PHN incidence between groups was not statistically significant (P>0.05). Conclusions: Acute-phase taVNS appears to be feasible and safe in middle-aged and elderly patients with HZ and comorbid depressive and anxiety, effectively reducing subacute pain and improving emotional and sleep outcomes.

Humans↗

Quantitative comparison of ohmefentanyl isomers induced conditioning place preference in mice.

Differences of analgesia and withdrawal response among ohmefentanyl stereoisomers have been studied. In the present study, Quantitative comparison of reinforcing effects of ohmefentanyl stereoisomers and morphine was performed by using a conditioned place preference design in mice. Results showed that morphine and ohmefentanyl stereoisomers were able to increase significantly the time spent in the drug-paired side with respect to vehicle treated animals. A good linear correlation between doses of drugs and number of mice with place preference was found within a given dose range. On the basis of the dose-response curve analysis, ohmefentanyl stereoisomers displayed a significant difference in place preference ED50. The addictive index (analgesic ED50/place preference ED50) was used to assess the addictive potential of drugs. It was demonstrated that the addictive potential of ohmefentanyl stereoisomers did not exhibit a large difference as addictive index. Among these stereoisomers, the addictive potential of compound F9208 was markedly lower than that of morphine.

Analgesics, Opioid↗

The propeptide of the transforming growth factor-beta superfamily member, macrophage inhibitory cytokine-1 (MIC-1), is a multifunctional domain that can facilitate protein folding and secretion.

Macrophage inhibitory cytokine-1 (MIC-1) is a divergent member of the transforming growth factor-beta (TGF-beta) superfamily. While it is synthesized in a pre-pro form, it is unique among superfamily members because it does not require its propeptide for correct folding or secretion of the mature peptide. To investigate factors that enable these propeptide independent events to occur, we constructed MIC-1/TGF-beta1 chimeras, both with and without a propeptide. All chimeras without a propeptide secreted less efficiently compared with the corresponding constructs with propeptide. Folding and secretion were most affected after replacement of the predicted major alpha-helix in the mature protein, residues 56-68. Exchanging the human propeptide in this chimera with either the murine MIC-1 or TGF-beta1 propeptide resulted in secretion of the unprocessed, monomeric chimera, suggesting a specific interaction between the human MIC-1 propeptide and mature peptide. Propeptide deletion mutants enabled identification of a region between residues 56 and 78, which is important for the interaction between the propeptide and the mature peptide. Cotransfection experiments demonstrated that the propeptide must be in cis with the mature peptide for this phenomenon to occur. These results suggest a model for TGF-beta superfamily protein folding.

Activins↗

Epitope mapping of the transforming growth factor-beta superfamily protein, macrophage inhibitory cytokine-1 (MIC-1): identification of at least five distinct epitope specificities.

Macrophage inhibitory cytokine-1 (MIC-1) is a divergent member of the transforming growth factor-beta (TGF-beta) superfamily whose increased expression is associated with macrophage activation and which is expressed highly in placenta as compared to other tissues. There are two known allelic forms of human MIC-1 due an amino acid substitution at position 6 of the mature protein. We have raised four monoclonal antibodies (MAbs) and one polyclonal antiserum to the mature protein region of human MIC-1 and have used an extensive panel of MIC-1 relatives, mutants, and chimeras to map their epitopes. None of the MAbs were able to cross-react with either the murine homologue of MIC-1 or with hTGF-beta1, and all of the MAb epitopes were conformation-dependent. A distinct cross-reactivity pattern with the various antigens was observed for each of the monoclonal and polyclonal antibodies suggesting the presence of at least five immunogenic regions on the MIC-1 surface. One of the MAbs is directed against the amino terminus of the protein and can distinguish between the two allelic forms of MIC-1. The epitopes for the other three MAbs were located near the tips of the so-called "fingers" of the protein and appeared to be partially overlapping as each involved amino acids in the region 24-37. In one case, it was possible to mutate murine MIC-1 so that it could be recognized by one of the MAbs. Finally, the use of another mutant in which Cys 77 was replaced by serine enabled confirmation of the location of the MIC-1 interchain disulfide bond.

Amino Acid Sequence↗

The propeptide of macrophage inhibitory cytokine (MIC-1), a TGF-beta superfamily member, acts as a quality control determinant for correctly folded MIC-1.

Macrophage inhibitory cytokine (MIC-1), a divergent member of the transforming growth factor-beta (TGF-beta) superfamily and activation associated cytokine, is secreted as a 28 kDa dimer. To understand its secretion, we examined its processing in MIC-1-transfected Chinese hamster ovary cells. Mature MIC-1 dimer arises post-endoplasmic reticulum (ER) by proteolytic cleavage of dimeric pro-MIC-1 precursor at a furin-like site. Unlike previously characterized TGF-beta superfamily members, MIC-1 dimers are also secreted in constructs lacking the propeptide. A clue to the function of the propeptide came from the observation that a range of proteasome inhibitors, including lactacystin and MG132, cause major increases in levels of undimerized pro-MIC-1 precursor. There was no effect of proteasome inhibitors on cells expressing mature MIC-1 without the propeptide, suggesting that the propeptide can signal misfolding of MIC-1, leading to proteasomal degradation. Deletion mutagenesis showed the N-terminal 28 amino acids of the propeptide are necessary for proteasomal degradation. This is the first demonstration, to our knowledge, of a quality control function in a propeptide domain of a secretory protein and represents an additional mechanism to ensure correct folding of proteins leaving the ER.

Animals↗

Factors determining normalization of pulmonary vascular resistance following successful balloon mitral valvotomy.

Balloon mitral valvotomy (BMV) provides improvement in pulmonary vascular resistance (PVR) in patients with severe mitral stenosis. Its normalization, however, remains questionable. We evaluated PVR before, after BMV, and at follow-up in 37 patients who had a previous successful BMV. Patients were divided into 2 groups: group 1 had 21 patients with normalized PVR (<125 dynes/s/cm5) either after BMV or at follow-up, and group 2 had 16 patients with persistently abnormal PVR. Patients in group 2 were older than patients in group 1 (55+/-13 vs 43+/-14 years, p = 0.01) and had atrial fibrillation more frequently (10 [63%] vs 6 [29%], p = 0.04). Age, cardiac rhythm, mitral valve area, pulmonary bed gradient, pulmonary artery pressure, and PVR before the procedure were significant univariate predictors for normalization of PVR. Age, echocardiographic score, systolic pulmonary artery pressure, and mitral regurgitation were all independent determinants of normalization of PVR in a multivariate logistic regression model. We conclude that PVR failed to return to normal in 16 patients (43%) after successful BMV; this can be predicted by baseline clinical and hemodynamic parameters.

Adult↗

MIC-1 is a novel TGF-beta superfamily cytokine associated with macrophage activation.

As part of a study to identify novel genes associated with macrophage activation, we have cloned a new member of the transforming growth factor beta (TGF-beta) superfamily designated macrophage inhibitory cytokine 1 (MIC-1). MIC-1 is synthesized as a 62-kDa intracellular protein, which, after cleavage by a furin like protease, is secreted as a 25-kDa disulfide-linked dimeric protein. Sequence analysis indicates that it does not cluster within any existing TGF-beta families, suggesting it may be the first member of a new grouping within the TGF-beta superfamily. Tissue Northern blots show that MIC-1 transcripts are only found abundantly in placenta, although smaller amounts are seen in a limited number of other adult and fetal tissues. MIC-1 is not expressed in resting macrophages but is induced by a number of different activation agents, including phorbol myristate acetate, interleukin 1, tumor necrosis factor alpha, and macrophage colony-stimulating factor but not by lipopolysaccharide or interferon-gamma. We have hypothesized that it may be an autocrine inhibitor of macrophage activation but its major biological role is still uncertain.

Amino Acid Sequence↗

Comparison of late results of balloon valvotomy in mitral stenosis with versus without mitral regurgitation.

Balloon mitral valvotomy (BMV) is safe and effective in patients with mitral stenosis (MS) and coexisting mild mitral regurgitation (MR). Influence of preexisting MR on late outcome of BMV is under evaluation. We included 77 patients without MR and 72 with MR in this study, and compared their immediate and late results in a mean follow-up of 33 +/- 24 months after BMV. Patients with coexisting MR were older and more frequently had significant valvular calcium and atrial fibrillation than patients without MR. After BMV, mitral valve gradient decreased, and cardiac output and mitral valve area by planimetry increased significantly (all p = 0.0001) in both groups. There was no difference in values of mitral valve gradient and cardiac output after BMV between the groups. Mitral valve area was significantly smaller in patients with preexisting MR. During follow-up, there were 11 patients (14%) in the group without MR and 24 (33%) in the group with MR developed cardiac events (p = 0.006). Cumulative event-free survival was 90% at the second year, 87% at the fourth year, and 69% at the sixth year, respectively, in the group without MR versus 78%, 62%, and 37%, respectively, in the group with MR (p = 0.0014). Cox regression showed that preexisting MR was a significant predictor for late cardiac events with a threefold increased hazard risk (p = 0.0025), but age, valvular calcium, echocardiographic score, and cardiac rhythm also played a culpable role. We conclude that preexisting MR is an important risk factor for poor, late outcome of BMV.

Adolescent↗

Dihydropteridine reductase deficiency: physical structure of the QDPR gene, identification of two new mutations and genotype-phenotype correlations.

Dihydropteridine reductase (DHPR) is an enzyme involved in recycling of tetrahydrobiopterin (BH4), the cofactor of the aromatic amino acid hydroxylases. Its deficiency is characterized by hyperphenylalaninemia due to the secondary defect of phenylalanine hydroxylase and depletion of the neurotransmitters dopamine and serotonin, whose syntheses are controlled by tryptophan and tyrosine hydroxylases. The DHPR cDNA has been cloned and mapped on 4p15.3. In the present study we report the genomic structure of the DHPR gene (QDPR). This gene includes seven exons within a range of 84-564 bp; the corresponding introns are flanked by canonic splice junctions. We also present a panel of PCR primers complementary to intronic sequences that greatly facilitates amplification of the gene and provides a genomic DNA approach for mutation detection. We have used this approach to study six patients with DHPR deficiency. Four known mutations (G23D, H158Y, IVS5G+ 1A, R221X) and two new mutations (Y150C and G218ins9bp) were found. The Y150C mutation was found in compound heterozygosity with G23D, a mutation always associated with a severe phenotype in homozygous patients. This patient has an intermediate phenotype (good response to monotherapy with BH4). The mutant enzyme for Y150C was expressed in an E. coli system. Comparison of its kinetic parameters with those of the G23D mutant enzyme showed that it is not as effective as the wild-type enzyme, but is more active than the G23D mutant. This patient's intermediate phenotype is thus due to the mild DHPR mutation Y150C. Correlations between genotypes and phenotypes were also found for the other mutations.

Alleles↗

Effects of three stimulus parameters on eye position in cerebral palsied adults.

Bilateral eye position was measured in 6 cerebral palsied adults to assess the effects of stimulus dimensions (horizontal, vertical), amplitude (+/- 4 degrees, +/- 6 degrees, +/- 8 degrees), and frequency (0.3, 0.5, 0.7 Hz) on saccadic and pursuit movements. The head-free, corneal reflection method was used for 54 10-sec. trials of square, triangle, and sine wave stimuli. Shared variance between each eye's position and the stimulus was tested by Wilcoxon T (dimension) and Friedman analysis of variance (amplitude, frequency) showing that the effects of saccadic and pursuit dimension and amplitude were individualized with regard to subject and right and left eye positions. The bilateral eye position of 5 of 6 subjects was affected by saccadic frequency; pursuit frequency affected bilateral eye position of 4 of 6 subjects. The lowest shared variance (critical difference in ranks) was at 0.7 Hz. The results are discussed with regard to subjects' disability, stimulus velocity, and frequency of directional reversal. Reversal may be the most critical stimulus property.

Adult↗

MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-beta superfamily.

Macrophages play a key role in both normal and pathological processes involving immune and inflammatory responses, to a large extent through their capacity to secrete a wide range of biologically active molecules. To identify some of these as yet not characterized molecules, we have used a subtraction cloning approach designed to identify genes expressed in association with macrophage activation. One of these genes, designated macrophage inhibitory cytokine 1 (MIC-1), encodes a protein that bears the structural characteristics of a transforming growth factor beta (TGF-beta) superfamily cytokine. Although it belongs to this superfamily, it has no strong homology to existing families, indicating that it is a divergent member that may represent the first of a new family within this grouping. Expression of MIC-1 mRNA in monocytoid cells is up-regulated by a variety of stimuli associated with activation, including interleukin 1beta, tumor necrosis factor alpha (TNF-alpha), interleukin 2, and macrophage colony-stimulating factor but not interferon gamma, or lipopolysaccharide (LPS). Its expression is also increased by TGF-beta. Expression of MIC-1 in CHO cells results in the proteolytic cleavage of the propeptide and secretion of a cysteine-rich dimeric protein of Mr 25 kDa. Purified recombinant MIC-1 is able to inhibit lipopolysaccharide -induced macrophage TNF-alpha production, suggesting that MIC-1 acts in macrophages as an autocrine regulatory molecule. Its production in response to secreted proinflammatory cytokines and TGF-beta may serve to limit the later phases of macrophage activation.

Amino Acid Sequence↗

Percutaneous treatment of abdominal aortic aneurysm in a swine model: understanding the behavior of aortic aneurysm closure through a serial histopathological analysis.

BACKGROUND: Previous studies used covered stent grafts to treat abdominal aortic aneurysms; however, such devices block flow into aortic side branches. We used uncovered stents with and without additional embolization coils to treat abdominal aortic aneurysm in a swine model and examined serial histological changes in the aneurysms over a 6-month period. METHODS AND RESULTS: We examined aneurysms in 9 control and 9 treated pigs (5 received stents alone and 4 received stents and coils). Aneurysms were surgically created with abdominal fascia. Three days later, we percutaneously placed a self-expandable uncovered stent across the aneurysm. Coils were implanted through the stent into the aneurysm lumen. An aortogram immediately after stent placement showed no significant change in aneurysm lumen; however, in pigs that had aortograms between 6 weeks and 6 months after treatment, the diameter decreased (28% to 65%) in 4 of 5 pigs, and 1 had no discernible aneurysm. Three treated pigs died, but only 1 from rupture. In contrast, 7 untreated aneurysms ruptured (2 pigs died of other causes). Histological examination revealed that the aneurysm lumen was reduced after treatment by collagen production. This healing process was accelerated in aneurysms treated with both stents and coils. In contrast, only limited amounts of new collagen were found in untreated, ruptured aneurysms. Instead, the fascia was disrupted and there was evidence of collagen degradation. CONCLUSIONS: We found that uncovered stents reduce the likelihood of aneurysm rupture in a swine model without blocking arterial branches. The presence of coils enhanced filling of the lumen by collagen.

Aneurysm, Ruptured↗

A novel prognostic scoring system to predict late outcome after percutaneous balloon valvotomy in patients with severe mitral stenosis.

We developed a prognostic scoring system to predict the outcome of follow-up after balloon mitral valvotomy. The system incorporates seven variables before valvotomy: age, New York Heart Association class, fluoroscopic calcification, echocardiographic score, cardiac rhythm, mitral regurgitation, and mitral valve area. Each variable was coded with either 0 or 1 and a total score was between 0 and 7. The study included 150 patients with a mean follow-up of 33 +/- 24 months. In patients with scores of 0-1, 2-3, 4-5, and 6-7, the estimated cardiac event-free survival rate was 97%, 94%, 86%, and 68%, respectively, at 1 year; 95%, 88%, 74%, and 47%, respectively, at 3 years; and 92%, 82%, 61%, and 30%, respectively, 5 years after valvotomy (p = 0.0001). The hazard risk ratio for cardiac events was 1.7 times greater for every step up of the score (p = 0.0001). Our scoring system provides a simple but effective method to predict late outcome of balloon mitral valvotomy.

Catheterization↗

Non-surgical treatment of abdominal aortic aneurysms.

Percutaneous placement of an endovascular stent, with and without coils, in the treatment of large AAA in animal models is feasible, safe and effective. The covered stent sealed off AAA immediately after stent placement, however, it interrupted blood flow into arteries in the area covered by the stent. The uncovered stent prevented further expansion of the aneurysm and also significantly decreased the incidence of rupture. The long-term patency of branch arteries by the uncovered stent supported the possibility of safely using this approach in humans. Furthermore, either covered stent or uncovered stent with additional coils have the potential for treatment of acute aneurysm rupture or leaking. Most importantly, the aneurysm lumen in our model was gradually replaced by collagen after stent placement which further reduces the risk of aneurysm rupture: and this healing process was enhanced by the addition of coils. If proven safe and effective for humans as well, this technique has the potential for substantially reducing the morbidity and mortality associated with AAA.

Animals↗