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H Zhou

Publications and source records attributed to H Zhou.

At least 19 recordsLinked to original sources
PubMed2026

[Analysis of clinical spectrum and genotype characteristics of 9 cases of Fabry disease].

Objective: To investigate the genetic characteristics and clinical phenotypes across different genotypes in patients with Fabry disease. Methods: Clinical data of 9 confirmed FD patients treated from June 2019 to December 2025 at the Affiliated Huai'an No.1 people's Hospital of Nanjing Medical University were retrospectively analyzed. The diagnostic criteria for FD included α-galactosidase A (α-GalA) activity, GLA gene sequencing, globotriaosylsphingosine levels, and renal biopsy findings, supplemented by clinical symptoms and signs. Genetic testing was performed on both the proband and their family members. Proband underwent next-generation sequencing of the GLA gene using the long-range PCR. Family members were verified by conventional PCR combined with Sanger sequencing. Variants were classified according to the 2015 American College of Medical Genetics and Genomics guidelines for sequence variation interpretation. Results: Of the 9 patients, 4 were males and 5 were females. The mean α-Gal A activity was (0.47±0.13) μmol·L-1·h-1 in males and (2.38±0.91) μmol·L-1·h-1 in females. The mean age at diagnosis was (43.0±16.7) years. The main clinical manifestations included renal impairment in 7 cases (proteinuria, chronic kidney disease, or end-stage renal disease), cardiac involvement in 8 cases (myocardial hypertrophy, arrhythmia, etc.), and autonomic nervous system symptoms in 6 cases (hypohidrosis). Pathogenic or likely pathogenic GLA variants were identified in all 9 patients, of which 8 were classified as pathogenic and 1 as a variant of uncertain significance. Three patients underwent family screening: in one case, the variant was possibly inherited from the maternal grandmother; one case was confirmed as a de novo mutation; and in one case, paternal inheritance could not be excluded. Renal biopsy in one patient revealed characteristic myeloid bodies and zebra bodies. Among the 9 patients, 1 received agalsidase α and 8 received agalsidase β, with one case developing infusion-associated reactions after 12 infusions. During the follow-up period, one patient died due to cardiac complications. Conclusions: FD patients exhibit a broad clinical spectrum and diverse genotypes. Atypical presentations should be closely monitored to enable early diagnosis and treatment, thereby improving prognosis.

Humans↗
PubMed2006

Hybrid atomistic-coarse-grained treatment of multiscale processes in heterogeneous materials: a self-consistent-field approach.

A treatment of multiscale quasistatic processes that combines an atomistic description of microscopic heterogeneous ("near") regions of a material with a coarse-grained (quasicontinuum) description of macroscopic homogeneous ("far") regions is presented. The hybrid description yields a reduced system consisting of the original atoms of the near regions plus pseudoatoms (nodes of the coarse-graining mesh) of the far regions, which interact through an effective many-body potential energy V(eff) that depends on the thermodynamic state. The approximate nature of V(eff) gives rise to "ghost forces," which are reflected in spurious heterogeneities close to interfaces between near and far regions. The impact of ghost forces, which afflict all previous hybrid schemes, is greatly diminished by a self-consistent-field hybrid atomistic-coarse-grained (SCF-HACG) methodology. Tests of the SCF-HACG technique on a fully three-dimensional prototypal model [Lennard-Jones (12,6) crystal] yield thermomechanical properties (e.g., local stress) in good agreement with "exact" properties computed in the fully atomistic limit. The SCF-HACG method is also successfully used to characterize the grain boundary in a Lennard-Jones bicrystal.

Journal Article↗
PubMed2006

On the human CYP2C9*13 variant activity reduction: a molecular dynamics simulation and docking study.

Cytochrome P450 2C9 (CYP2C9) plays a key role in the metabolism of clinical drugs. CYP2C9 is a genetically polymorphic enzyme and some of its allelic variants have less activity compared to the wild-type form. Drugs with a narrow therapeutic index may cause serious toxicity to the individuals who carry such allele. CYP2C9*13, firstly identified by some of the present authors in a Chinese poor metabolizer of lornoxicam, is characterized by mutation encoding Leu90Pro substitution. Kinetic experiments show that CYP2C9*13 has less catalytic activity in elimination of diclofenac and lornoxicam in vitro. In order to explore the structure-activity relationship of CYP2C9*13, the three-dimensional structure models of the substrate-free CYP2C9*1 and its variant CYP2C9*13 are constructed on the basis of the X-ray crystal structure of human CYP2C9*1 (PDB code 1R9O) by molecular dynamics simulations. The structure change caused by Leu90Pro replacement is revealed and used to explain the dramatic decrease of the enzymatic activity in clearance of the two CYP2C9 substrates: diclofenac and lornoxicam. The trans configuration of the bond between Pro90 and Asp89 in CYP2C9*13 is firstly identified. The backbone of residues 106-108 in CYP2C9*13 turns over and their side chains block the entrance for substrates accessing so that the entrance of *13 shrinks greatly than that in the wild-type, which is believed to be the dominant mechanism of the catalytic activity reduction. Consequent docking study which is consistent with the results of the kinetic experiments by Guo et al. identifies the most important residues for enzyme-substrate complexes.

Amino Acid Substitution↗
PubMed2006

The comparative study of Sprague-Dawley and Lewis rats in adjuvant-induced arthritis.

The outbred Sprague-Dawley (SD) rats, similar to the inbred Lewis (LEW) rats, have been recently demonstrated to be highly susceptible to adjuvant-induced arthritis (AIA). We herein compared AIA in SD and LEW rats in terms of clinical, histological, radiological, and immuno-inflammatory features. The results showed that, following inoculation with a ground Mycobacterium tuberculosis (MT) suspension, SD and LEW rats manifested closely similar disease progression, with 100% incidence and similar severity. The development of arthritis was accompanied by significantly higher erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels than in control rats. Radiographic examination of the hind paws showed that both SD and LEW AIA rats manifested conspicuous soft tissue swelling, bone matrix resorption, periosteal new bone formation and bone erosion, while histopathological analysis of the synovial joints revealed marked cellular infiltration, angiogenesis, synovial hyperplasia, pannus formation, narrowing of joint space, and cartilage and bone destruction. Moreover, in relation to disease progression, serum tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-6 levels were markedly overexpressed in both SD and LEW AIA versus control rats, and SD and LEW AIA rats exhibited divergent profiles for the expression of TNF-alpha and IL-1beta. Taken together, these results demonstrated that the SD rat AIA model shares several arthritic features with the comparable model in LEW rats. Hence, given the more favorable characteristics of SD rats than LEW rats (i.e., lower cost, wider availability, and heterogenic background), this SD rat AIA model is more cost effective and advantageous for screening and testing novel anti-arthritic agents.

Animals↗
PubMed2006

The association of CAG repeat length with clinical progression in Huntington disease.

OBJECTIVE: To determine whether the rate of clinical progression in Huntington disease (HD) is influenced by the size of the CAG expansion. METHODS: The dataset consisted of 3,402 examinations of 512 subjects seen through the Baltimore Huntington's Disease Center. Subjects were seen for a mean of 6.64 visits, with mean follow-up of 6.74 years. Subjects were administered the Quantified Neurological Examination, with its subsets the Motor Impairment and Chorea Scores, the Mini-Mental State Examination, and the HD Activities of Daily Living (ADL) Scale. RESULTS: In an analysis based on the Random Effects Model, CAG length was significantly associated with the rate of progression of all measures except chorea and ADL. There was a significant interaction term between CAG length and disease duration for all measures except chorea. Further graphical exploration of the data supported these linear models and suggested that subjects at the low end of the expanded CAG repeat range may experience a more benign late course. CONCLUSIONS: CAG repeat length has a small effect on rate of progression that may be clinically important over time. Individuals with the shortest expansions appear to have the best prognosis. These effects of the CAG length may be relevant in the analysis of clinical trials.

Baltimore↗
PubMed2006

Cell therapy of pain: Characterization of human fetal chromaffin cells at early adrenal medulla development.

Adult adrenal chromaffin cells are being utilized for therapeutic transplantation. With the prospect of using fetal chromaffin cells in pain therapy, we studied their phenotype, proliferative power, function, and growth in vitro and in situ in order to determine the optimal time for implantation. Between 7 and 10 gestational weeks (GW), we isolated, in vitro, two types of chromaffin cells with a noradrenergic phenotype akin to that observed, in situ. Among the adherent chromaffin cells first observed in vitro, only a few samples expressed met-enkephalin, whereas almost all the neurosphere-like colonies, which appeared later, expressed it. However, neither of the two types of populations expressed an adrenergic phenotype in line with that observed in situ. At the upper limits of the voluntary abortion period authorized in France, this phenotype (12 GW) and met-enkephalin expression (13 GW) were evidenced in situ. For the first time in man, we demonstrate the secretion of noradrenaline in vitro by the two populations of cells. Consistent with this result, we also noted dopamine beta hydroxylase (DbetaH) mRNA expression in vitro and in situ within this period. These observations on the expression of these biological factors indicate that 9-10 GW would be the best stage for sampling these cells for preclinical transplantation experiments.

Adrenal Medulla↗
PubMed2006

CD56 expression aids in the differential diagnosis of cholangiocarcinomas and benign cholangiocellular lesions.

CD56 (neuronal cell adhesion molecule, N-CAM) has been reported in neuroendocrine tumours and as a marker of reactive biliary epithelial cells. However, up to date, it is not used to distinguish malignant from non-malignant biliary lesions. In this study, we systematically examined CD56 expression on 98 tumours arising from the biliary tree as well as intrahepatic conditions with reactive neoductules. When neuroendocrine carcinomas are excluded, only 4 of 32 (12.5%) cholangiocarcinomas expressed CD56, 2 of which showed clear cell morphology. Reactive bile ductules adjacent to cirrhotic nodules as well as in focal nodular hyperplasia were CD56 positive. Twelve of 17 (70.5%) bile duct adenomas were CD56 positive, whereas von Meyenburg complexes expressed CD56 only very focally in less than 5% of lesional cells. Bile duct cysts were negative for CD56 with the exception of focally interspersed neuroendocrine cells, similar to that seen in segmental bile ducts. Thus, if van Meyenburg complexes are excluded, CD56 can be used to differentiate intrahepatic non-neoplastic from neoplastic proliferations, which is a helpful diagnostic tool in small liver biopsies.

Adenocarcinoma↗
PubMed2006

[Nodular lesions of liver parenchyma caused by pathological vascularisation/perfusion].

Nodular regenerative hyperplasia (NRH) is characterized by a non-cirrhotic micronodular transformation of the liver parenchyma. It is based on the obliteration of small portal veins. Macroregenerative nodules (MRN) develop in areas of favourable blood flow in otherwise hypoperfused liver tissue. Hypoperfusion is caused by obliteration of liver veins and/or large portal veins with the subsequent atrophy or extinction of parenchyma. The hyperperfused and sometimes rapidly growing MRN might simulate a malignant tumor in CT and MRT. Morphologically, MRN resemble FNH. In contrast to hepatocellular adenoma, they show a more or less nodular architecture with fibrous septa and ductular structures. NRH and cases of MRN without cirrhosis can indicate an extrahepatic/systemic disease causing altered liver perfusion. MRN in liver cirrhosis must be differentiated from dysplastic nodules and highly differentiated hepatocellular carcinoma by cytological and microarchitectural criteria. Focal nodular hyperplasia (FNH) can imitate liver cirrhosis, steatohepatitis, cholangitis or chronic hepatitis, if biopsy material does not include normal perilesional liver tissue. Telangiectatic FNH might resemble classic hepatocellular adenoma. Neoductular structures and septation argue for this rare subtype of FNH. Neoductular transformation of hypoperfused liver parenchyma might imitate cholangioma or cholangiocarcinoma.

Humans↗
PubMed2006

Collection, storage, preservation, and normalization of human urinary exosomes for biomarker discovery.

Urinary exosomes containing apical membrane and intracellular fluid are normally secreted into the urine from all nephron segments, and may carry protein markers of renal dysfunction and structural injury. We studied methods for collection, storage, and preservation of urinary exosomal proteins. We collected urine from healthy volunteers, added protease inhibitors, and stored urine samples at 4, -20, and -80 degrees C for 1 week or 7 months. Samples were thawed with and without extensive vortexing, and three fractions were isolated: urinary sediment, supernatant, and exosome fraction. Protein concentration, electrophoresis patterns, and abundance of seven exosome-associated proteins were measured. Exosome-associated proteins were not detected in sediment or supernatant fractions. Protease inhibitors prevented degradation of exosome-associated proteins. Freezing at -20 degrees C caused a major loss in exosomes compared to fresh urine. In contrast, recovery after freezing at -80 degrees C was almost complete. Extensive vortexing after thawing markedly increased exosome recovery in urine frozen at -20 or -80 degrees C, even if frozen for 7 months. The recovery from first and second morning urine was similar. The abundance of cytosolic exosome-associated proteins did not decrease during long-term storage. We concluded: (1) protease inhibitors are essential for preservation; (2) storage at -80 degrees C with extensive vortexing after thawing maximizes the recovery of urinary exosomes; (3) the difference between first and second morning urine exosome-associated protein was small, suggesting minimal protein degradation in the urinary tract/bladder; (4) urinary exosomes remain intact during long-term storage. These urine collection, storage, and processing conditions may be useful for future biomarker discovery efforts.

Biomarkers↗
PubMed2006

Simvastatin improves sepsis-induced mortality and acute kidney injury via renal vascular effects.

Acute kidney injury (AKI) occurs in about half of patients in septic shock and the mortality of AKI with sepsis is extremely high. An effective therapeutic intervention is urgently required. Statins are 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors that also have pleiotropic actions. They have been reported to increase the survival of septic or infectious patients. But the effect of simvastatin, a widely used statin, on sepsis-induced AKI is unknown. The effects of simvastatin and tumor necrosis factor (TNF)-alpha neutralizing antibody were studied in a clinically relevant model of sepsis-induced AKI using cecal ligation and puncture (CLP) in elderly mice. Simvastatin significantly improved CLP-induced mortality and AKI. Simvastatin attenuated CLP-induced tubular damage and reversed CLP-induced reduction of intrarenal microvascular perfusion and renal tubular hypoxia at 24 h. Simvastatin also restored towards normal CLP-induced renal vascular protein leak and serum TNF-alpha. Neither delayed simvastatin therapy nor TNF-alpha neutralizing antibody improved CLP-induced AKI. Simvastatin improved sepsis-induced AKI by direct effects on the renal vasculature, reversal of tubular hypoxia, and had a systemic anti-inflammatory effect.

Acute Kidney Injury↗
PubMed2006

Marek's disease virus-induced transient paralysis is associated with cytokine gene expression in the nervous system.

Marek's disease (MD)-associated transient paralysis (TP) was experimentally induced in chickens by intraperitoneal inoculation of RB1B strain of Marek's disease virus (MDV). Between 7 and 11 days post-infection (d.p.i.), neck and limb paralysis was observed in 18% of infected chickens, which was associated with various degrees of edema, vacuolation, perivascular cuffing of mononuclear cells, and glial cell infiltration mainly in the cerebrum, cerebellum, and brain stem. The chickens that were infected but did not progress to develop TP until 12 d.p.i. also had similar lesions suggestive of encephalitis in the cerebrum, cerebellum, and brain stem. Chickens infected with MDV had more interleukin (IL)-6, IL-12, and interferon (IFN)-gamma in their brain tissues compared to uninfected chickens. Moreover, IL-18 was significantly increased in brain tissues of birds showing clinical signs of TP compared to uninfected birds. Importantly, the expression of IL-6, IL-18, and IFN- gamma in brain tissues of MDV-infected chickens with signs of TP was significantly increased compared to that in asymptomatic MDV-infected birds. MDV genome load in the brain of chickens showing clinical signs of TP was higher than that in asymptomatic MDV-infected chickens but was not statistically significant. The lesions in the cervical, thoracic, and lumbar spinal cord segments in MDVinfected chickens were characterized mainly by perivascular cuffing of mononuclear cells irrespective of the group. The expression of mRNA for IL-18 and IFN-gamma genes was not significantly different in spinal cord tissues of chickens with TP compared to clinically normal, MDV-infected and noninfected chickens. These results suggest possible underlying immunologic mechanisms for MDV-induced TP.

Animals↗
PubMed2006

Diagnostic value of markers M2A, OCT3/4, AP-2gamma, PLAP and c-KIT in the detection of extragonadal seminomas.

AIMS: To compare the suitability of new seminoma markers including transcription factors AP-2gamma, OCT3/4 and M2A for detection of metastatic and extragonadal seminomas with the two well-known markers c-KIT and PLAP. MATERIALS AND METHODS: The immunohistochemical distribution of PLAP, c-KIT, M2A, AP-2gamma and OCT3/4 was examined in two pineal germinomas, 28 metastatic seminomas and 10 of their testicular primaries. Evaluation of specificity was achieved by additional tissue array studies on 75 malignancies other than germ cell tumours (GCT). Clinical data including serum PLAP were available in 18 patients. RESULTS: Compared with other markers, significantly better staining results were observed with antibodies to M2A and AP-2gamma in all seminomatous GCT. In contrast, the staining pattern with antibodies to c-KIT, PLAP and OCT3/4 was variable or absent. The lowest specificity was obtained with c-KIT, which was expressed in a variety of non-GCT. The only M2A+ mesothelioma expressed no other seminoma markers. No correlation between serum PLAP level and tissue PLAP expression was found. CONCLUSIONS: M2A and AP-2gamma are the most sensitive markers for seminoma metastases or primary extragonadal seminomas. Combination of these markers provides highly specific and clear results for detection of a seminomatous GCT.

Adult↗
PubMed2005

Minicore myopathy with ophthalmoplegia caused by mutations in the ryanodine receptor type 1 gene.

BACKGROUND: Minicore myopathy (multi-minicore disease [MmD]) is a congenital myopathy characterized by multifocal areas with loss of oxidative activity on muscle biopsy. MmD is clinically heterogeneous and distinct phenotypes have been associated with recessive mutations in either the selenoprotein N (SEPN1) or the skeletal muscle ryanodine receptor (RYR1) gene, also implicated in central core disease and malignant hyperthermia. External ophthalmoplegia is an additional finding in a subset of patients with MmD. OBJECTIVE: To clinically and genetically examine families with MmD and external ophthalmoplegia. METHODS: The authors investigated 11 affected individuals from 5 unrelated families. Clinical, histopathologic, and imaging studies were performed and RYR1 haplotyping and mutational analysis were carried out. RESULTS: All patients had multiple cores involving the entire fiber diameter on longitudinal sections. Weakness and wasting in the shoulder girdle, scoliosis, moderate respiratory impairment, and feeding difficulties were prominent. In contrast to SEPN1-related myopathies, soleus was more severely affected than gastrocnemius on muscle MRI. Haplotyping suggested linkage to the RYR1 locus in informative families and mutational screening revealed four novel RYR1 mutations in three unrelated families; in addition, functional haploinsufficiency was found in one allele of two recessive cases. CONCLUSION: These findings expand the phenotypic spectrum associated with mutations in the skeletal muscle ryanodine receptor (RYR1) gene. Recessive mutations of domains commonly affected in malignant hyperthermia appear to be particularly prevalent in multi-minicore disease with external ophthalmoplegia and might suggest a different pathomechanism from that involved in central core disease.

Adolescent↗