Clinically being applied treatment against chronic hepatitis has three limitations: low response rates, severe adverse effects and a high rate of drug resistance. Hence, novel targets for antiviral therapy need to be developed so as to provide an armory of different strategies. During the replication of hepatitis B virus, the interaction of viral polymerase (P protein, also called P) and epsilonRNA is indispensable for the initiation of reverse transcription via protein priming and the pregenome RNA (pgRNA) packaging. Three strategies are currently developed for blocking P-epsilon interaction: heat shock protein inhibitors, epsilonaptamers and chemical compounds for blocking formation of P-epsilon complex. Previously, our group has for the first time worldwide in vitro screened several aptamers, which are able to interfere with the P-epsilon interaction. A strong inhibition against HBV was observed in vitro and in vivo experiments, respectively. In conclusion, the so far developed chemicals suppressing the P-epsilon interaction may bypass or overcome the viral resistance problems during clinic treatment and represent a highly attractive option for therapeutic intervention.
Animals ; Gene Expression Regulation, Viral ; Gene Products, pol ; antagonists & inhibitors ; genetics ; metabolism ; Hepatitis B ; therapy ; virology ; Hepatitis B virus ; enzymology ; genetics ; physiology ; Humans ; RNA, Viral ; genetics ; metabolism ; Virus Replication

Adolescent ; Adult ; Aged ; Endoscopy ; Female ; Humans ; Male ; Middle Aged ; Neck ; surgery ; Thyroidectomy ; methods ; Young Adult

Objective Discuss the nursing interventions for reducing the VAP incidence for aged critical patients. Methods The clinical data of 148 patients of more than 65 years with mechanical ventilation (MV) were analyzed retrospectively. The incidence of VAP and the fatality rate were observed. Results 43 cases were confirmed with VAP in 148 patients, the incidence rate was 29.1%. 24 patients died from severe primary diseases or/and multiple organ failure. Conclusions For patients with mechanical ventilation, strict procedure, micromesh basic nursing were vital for prevention and reduction of the incidence of VAP.

Objective To analyse the clinical and pathological characteristics of congenital adrenal hyperplasia (CAH) with adrenal myelolipoma (AML),and to improve the awareness of CAH.Methods The P450c17a gene in a pedigree with CAH and the clinical and pathological characteristics of three sisters of the pedigree with CAH and adrenal myelolipoma were studied;and the pertinent literatures reported abroad were analyzed and summarized.Results (1) A heterozygous point mutation 1178 base A to T in exon 6,and a heterozygous deletion mutation 1 457-1 465 bases TCGACTCTT of exon 8 were detected in P450c17 (CYP17) gene of three sisters of the pedigree with CAH.(2) The clinical characteristics of three sisters were hypertension,hypokalemia,primary amenorrhea,and gonadal dysgenesis.Without regular treatment after the diagnosis of CAH,the three sisters experienced many years of elevated serum ACTH levels,and developed AML.Conclusion The long-term high ACTH level plays an important role in the development of AML,although the exact mechanism of CAH with adrenal myelolipoma remains still unclear.CAH patients require long-term regular treatment.

To study the MEN1 gene mutations in a multiple endocrine neoplasia type 1 ( MEN 1 ) family,and determine the possible mechanism of disease induced by the mutations.Genomic DNA was isolated from peripheral blood leukocytes and the MEN1-related tumor tissues of the patient and the family members,then the coding exons and exon/intron boundaries of the MEN1 gene were amplified by polymerase chain reaction (PCR) and sequenced.Subclone sequencing was performed to identify the heterozygosity.Further immunohistochemistry was performed to observe menin protein expression in the tumor tissues.We identified a heterozygous deletion mutation of intron 9 ( IVS9+ 1_11 delGTGAGGGACAG) in the proband and two family menbers.We also demonstrated for the first time that the expression of menin protein is absent in the parathyroid adenoma tissue.The heterozygous mutation in the initial of intron 9,IVS9+ 1_11 delGTGAGGGACAG is a new type of MEN1 gene mutations in China.This mutation may produce an aberrant splicing of MEN1 mRNA,generating easily degradation and loss of expression of menin protein and resulting eventually in the disease.

It is very important to probe into the axonal regeneration and functional recovery of central nervous system (CNS) after implantation of cells into cerebrospinal fluid (CSF) for spinal cord injury (SCI). Transplantation of cells via CSF poses great potentials for SCI in clinic. Studies on administration of cells via CSF indicate that the method is safe and convenient. The method is more suitable to treating multiple lesions of the CNS since it does not produce open lesions. However, there are disputes over its promotion effects on axonal regeneration and functional recovery of spinal cord after injury; and some questions, such as the mechanisms of functional recovery of spinal cord, the proper time window of cell transplantation, and cell types of transplantation, still need to be handled. This review summarized the method of cell transplantation via CSF for treatment of SCI.
Animals ; Cell Transplantation ; methods ; Cerebrospinal Fluid ; cytology ; physiology ; Humans ; Nerve Regeneration ; physiology ; Spinal Cord Injuries ; pathology ; surgery

It has been extensively confirmed that fetal ventral mesencephalic cell (VMC) transplantation can ameliorate the symptoms of Parkinson's disease (PD). But there are still several problems to be resolved before the extensive clinical application of this technology. The major limitations are the poor survival of grafted dopamine (DA) neurons and restricted dopaminergic reinnervation of host striatum. Some attempts have been made to solve these problems including use of some trophic factor and co-transplantation with neural/paraneural origins. The purpose of this review is to overview advances of the means improving the survival of grafts and their current limitations.
Animals ; Brain Tissue Transplantation ; methods ; Fetal Stem Cells ; transplantation ; Fetal Tissue Transplantation ; methods ; Graft Survival ; Humans ; Mesencephalon ; embryology ; transplantation ; Parkinson Disease ; therapy

Adult ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Lead ; blood ; Lead Poisoning ; blood ; epidemiology ; Middle Aged

OBJECTIVETo observe the characteristics of sperm single-stranded DNA breaks (SSB) and double-stranded DNA breaks (DSB) in infertile men, explore the association of DSB with male infertility, and provide a new observation index and idea for the diagnosis and treatment of the disease.

METHODSThis study involved 60 infertile men (infertility group) and 30 normal healthy males with infertile wives (control group). We comparatively analyzed the seminal parameters of the two groups, determined sperm concentration and viability using the computer aided sperm analysis system, measured the sperm survival rate by hypoosmotic swelling (HOS) test, examined sperm morphology by Diff-Quick staining, and detected sperm DNA damage by two-tail comet assay.

RESULTSNine two-tail comet models were established for detecting sperm DNA integrity. Comparisons between the fertility and control groups showed that the sperm DNA fragmentation index (DFI) was (33.8 ± 13.1) vs (16.3 ± 7.9)% (P < 0.01), the SSB-DFI was (19.2 ± 11.4) vs (14.9 ± 7.6)% (P > 0.05), the SSB-DFI/DFI was (56.8 ± 32.4) vs (91.4 ± 27.8)% (P < 0.01), the DSB-DFI was (23.9 +13.4) vs (6.1 ± 2.7)% (P < 0.01), and the DSB-DFI/DFI was (70.8 ± 19.5) vs (37.4 ± 11.3)% (P < 0.01). The optimal cut-off value of DSB-DFI/DFI in the diagnosis of male infertility was 39.5%, with the AUG, sensitivity, and specificity of 0.969, 98.3%, and 90%; that of DSB-DFI was 15.85%, with the AUC, sensitivity, and specificity of 0.912, 86.7%, and 80%; and that of DFI was 18.65%; with the AUC, sensitivity, and specificity of 0.861, 90%, 70%, respectively. In the infertile men, neither SSB-DFI nor SSB-DFI/DFI exhibited any correlation with semen parameters (P > 0.05); DFI was correlated negatively with the percentage of progressively motile sperm, sperm survival rate, and the percentage of morphologically normal sperm (P < 0.05 or P < 0.01), but not correlated with sperm concentration (P > 0.05); both DSB-DFI and DSB-DFI/DFI showed a negative correlation with sperm concentration, sperm survival rate, and the percentages of progressively motile sperm and morphologically normal sperm (P < 0.05 or P < 0.01).

CONCLUSIONDouble-stranded, rather than single-stranded DNA breaks, may be a factor inducing male infertility. The type of sperm DNA strand damage is of much reference value for the assessment of male fertility.

Case-Control Studies ; Comet Assay ; DNA Breaks, Double-Stranded ; DNA Breaks, Single-Stranded ; DNA Fragmentation ; Fertility ; Humans ; Infertility, Male ; diagnosis ; genetics ; Male ; Semen Analysis ; Sensitivity and Specificity ; Sperm Count ; Spermatozoa ; Staining and Labeling