Chromosomes, Human, Y ; Deleted in Azoospermia 1 Protein ; Gene Deletion ; Humans ; Infertility, Male ; genetics ; Male ; RNA-Binding Proteins ; genetics

OBJECTIVETo investigate the correlation of male infertility with abnormality of chromosomal quantity and construction and with the deletion of DAZ gene copy in the AZFc region of Y chromosome.

METHODSIncluded in the study were 247 azoospermic and 206 severe oligozoospermic patients, as well as 210 fertile men as controls. Multi-PCR and PCR-RFLP were used to analyze the deletion of DAZ gene copies in the AZFc region of Y chromosome. Chromosomal quantity and construction were detected by G-band in the 453 patients.

RESULTSIn the azoospermic and severe oligozoospermic patients, the incidences of chromosomal abnormality were 12.6% and 8.3%; the rates of complete DAZ deletion were 7.7% and 11.2%, and the rates of DAZ1/DAZ2 deletion were 7.3% and 4.9% respectively, but no deletion was detected in the controls.

CONCLUSIONThere is a high frequency of chromosomal abnormality and DAZ gene copy deletion in patients with azoospermia and oligospermia, which suggests that chromosomal abnormality and partial and complete deletion of DAZ gene copy might be important genetic causes of Chinese male infertility.

China ; epidemiology ; Chromosome Deletion ; Chromosomes, Human, Y ; genetics ; Deleted in Azoospermia 1 Protein ; Gene Dosage ; Humans ; Infertility, Male ; epidemiology ; genetics ; Male ; Oligospermia ; epidemiology ; genetics ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; RNA-Binding Proteins ; genetics ; Sex Chromosome Aberrations

To investigate the effects of 2-(4-methoxycarbonyl-2-tetradecyloxyphenyl)carbamoylbenzoic acid (CX09040) on protecting pancreatic β cells, the β cell dysfunction model mice were induced by injection of alloxan into the caudal vein of ICR mice, and were treated with compound CX09040. Liraglutide was used as the positive control drug. The amount and the size of islets observed in pathological sections were calculated to evaluate the β cell mass; the glucose stimulated insulin secretion (GSIS) test was applied to estimate the β cell secretary function; the oral glucose tolerance test (OGTT) was taken to observe the glucose metabolism in mice; the expressions of protein in pancreas were detected by Western blotting. The effects on the target protein tyrosine phosphatase 1B (PTP1B) were assessed by the PTP1B activities of both recombinant protein and the intracellular enzyme, and by the PTP1B expression in the pancreas of mice, separately. As the results, with the treatment of CX09040 in alloxan-induced β cell dysfunction mice, the islet amount (P<0.05) and size (P<0.05) increased significantly, the changes of serum insulin in GSIS (P<0.01) and the values of acute insulin response (AIR, P<0.01) were enhanced, compared to those in model group; the impaired glucose tolerance was also ameliorated by CX09040 with the decrease of the values of area under curve (AUC, P<0.01). The activation of the signaling pathways related to β cell proliferation was enhanced by increasing the levels of p-Akt/Akt (P<0.01), p-FoxO1/FoxOl (P<0.001) and PDX-1 (P<0.01). The effects of CX09040 on PTP1B were observed by inhibiting the recombinant hPTP1B activity with IC50 value of 2.78x 10(-7) mol.L-1, reducing the intracellular PTP1B activity of 72.8% (P<0.001), suppressing the PTP1B expression (P<0.001) and up-regulating p-IRβ/IRβ (P<0.01) in pancreas of the β cell dysfunction mice, separately. In conclusion, compound CX09040 showed significant protection effects against the dysfunction of β cell of mice by enlarging the pancreatic β cell mass and increasing the glucose-induced insulin secretion; its major mechanism may be the inhibition on target PTP1B and the succedent up-regulation of β cell proliferation.
Alloxan ; Animals ; Benzoates ; pharmacology ; Biological Assay ; Disease Models, Animal ; Glucose ; metabolism ; Glucose Tolerance Test ; Insulin ; secretion ; Insulin Resistance ; Insulin-Secreting Cells ; drug effects ; Liraglutide ; pharmacology ; Mice ; Mice, Inbred ICR ; Molecular Weight ; Pancreas ; drug effects ; enzymology ; Protein Tyrosine Phosphatase, Non-Receptor Type 1 ; antagonists & inhibitors ; Signal Transduction

Cloning, Molecular ; DNA ; genetics ; DNA-Binding Proteins ; genetics ; Humans ; Proteins ; genetics ; Sequence Analysis, DNA ; Two-Hybrid System Techniques ; Yeasts ; genetics

Objective To observe the improving effect in joint function of moderate skeletal fluorosis treated by traditional Chinese medication(main ingredient was Strychnine).MethodsFrom December 2007 to July 2009,120 moderate skeletal fluorosis patients met the inclusion criteria were divided into the treatment group(60 cases)and the control group(60 cases)in the skeletal fluorosis hospital of Xinzhou,the treatment group was given basic treatment and traditional Chinese medication,the control group wa8 given basic treatment and placebo.The treatment lasted 12 weeks,follow up 24 weeks.Before treatment,after treatment 4 weeks,8 weeks,12 weeks,36 weeks,a third party evaluate comprehensive function of both upper and lower limb and joint dysfunction.Results The main effect of both drugs was statistically significance in the scores of the upper forearm in the finger by touching the posterior contralateral ear, upper arm touched by the finger back in the opposite corner subscapularis function, lower limb function and single-joint dysfunction(F values were 4.08,14.32,35.81,13.02, all P<0.05), the main effect of time also was significant (F values were 82.63,72.82,277.33,328.16, all P<0.05),①the upper forearm in the finger by touching the posterior contralateral ear functions:At the time of 8,12 weeks,scores of the treatment group were lower than those of before treatment and control group (all P<0.05);At the time of 36 weeks,scores of the treatment group were lower than that 12 weeks(all P<0.05);At the time of 8,12,36 weeks, scores of the control group were lower than those of before treatment(all P < 0.05);②upper arm function, namely fingers touching the opposite corner subscapularis:At the time of 4,8,12 weeks, scores of the treatment group were lower than those of before treatment(all P<0.05); At the time of 36 weeks, scores of the treatment group were lower than that 12 weeks(all P<0.05); At the time of 8,12,36 weeks, scores of the treatment group were lower than those of the control group (all P<0.05);③Lower extremity functions: At the time of 8,12 weeks,scores of the treatment group were lower than those of before treatment and control group (all P<0.05);At the time of 36 weeks, scores of the treatment group were lower than that 12 weeks(all P<0.05) ; At the time of 8,12,36 weeks, scores of the control group were lower than those of before treatment (all P<0.05);④single joint functions:At the time of 4,8,12 weeks,scores of the treatment group were lower than those of before treatment(all P<0.05); At the time of 36 weeks,scores of the treatment group were lower than that 12 weeks(all P<0.05) ; At the time of 8,12,36 weeks, scores of the control group were lower than those of before treatment(all P<0.05);At the time of 4,8,12,36 weeks, scores of the treatment group were lower than those of control group(all P<0.05);⑤At the end of treatment and follow-up,the improvement rate in joint functions in the treatment group were 88.33% (53/60),93.33% (56/60); the control group were 28.07%(16/57),40.35%(23/57), (Fisher test, P<0.01,X2=56.21, P<0.01). ConclusionTraditional Chinese medication(its main ingredient is Strychnine), an effective drug for improving joint dysfunction in patients suffering from moderate skeletal fluorosis, is simple and effective.

OBJECTIVETo evaluate the efficiency of the BIOMED-2 PCR assay and its implication in the diagnosis of mature B-cell non-Hodgkin's lymphomas.

METHODSClinical, morphological and immunohistochemical features of 72 cases of non-Hodgkin's lymphomas were studied, including 25 reactive lymphoid hyperplasia, 37 diffuse large B cell lymphomas (DLBCL) and 35 extranodal marginal zone lymphomas of mucosa associated lymphoid tissues (MALT lymphoma and in addition, 25 cases of reactive lymphoid hyperplasia were used as the controls). DNA was exacted from the paraffin embedded formalin fixed tissue blocks and the quality of DNA was assessed using the BIOMED-2 specimen control reaction. Adequate samples were then analyzed by BIOMED-2 for immunoglobulin heavy and kappa light chain rearrangements.

RESULTSAdequate DNA was obtained in 83 of 97 samples, including 60 mature B cell lymphomas and 23 reactive lymphoid hyperplasia. Clonal B-cell gene rearrangements were detected in 57 of 60 (95%) lymphomas. In contrast, clonal Ig gene rearrangements were not detected in any of the 23 cases of reactive lymphoid hyperplasia.

CONCLUSIONBIOMED-2 assay is highly sensitive and specific for the detection of clonal B cell gene rearrangement using routine paraffin embedded formalin fixed specimens.

Antigens, CD20 ; metabolism ; CD79 Antigens ; metabolism ; DNA, Neoplasm ; genetics ; Gene Rearrangement, B-Lymphocyte ; genetics ; Gene Rearrangement, B-Lymphocyte, Heavy Chain ; genetics ; Gene Rearrangement, B-Lymphocyte, Light Chain ; genetics ; Genes, Immunoglobulin ; Humans ; Immunophenotyping ; Lymphoma, B-Cell ; genetics ; immunology ; pathology ; Lymphoma, B-Cell, Marginal Zone ; genetics ; immunology ; pathology ; Lymphoma, Large B-Cell, Diffuse ; genetics ; immunology ; pathology ; Paraffin Embedding ; Pseudolymphoma ; genetics ; immunology ; pathology ; Sensitivity and Specificity

OBJECTIVETo investigate the possible association between ZNF230 gene and azoospermia.

METHODSScreening for mutation of all 6 exons of ZNF230 gene was performed by denaturing high performance liquid chromatography(DHPLC) in 99 patients with azoospermia and in 115 healthy men as controls.

RESULTSAn A-->G transition at nucleotide 316 in exon 6 was identified. There were significant differences in the distribution profiles of both allele and genotype frequencies between patient group and control group (P < 0.01 and P < 0.05, respectively). In addition,there was a statistically significant difference in the serum follicle stimulating hormone (FSH) level between the patients with GG/GA genotype and those with AA genotype (P < 0.05).

CONCLUSIONZNF230 gene may be associated with azoospermia, and the A316G mutation may be correlated with the serum FSH level.

Adult ; Azoospermia ; diagnosis ; genetics ; Base Sequence ; Chromatography, High Pressure Liquid ; DNA Mutational Analysis ; DNA-Binding Proteins ; genetics ; Gene Frequency ; Genetic Testing ; Genotype ; Humans ; Male ; Mutation ; Polymerase Chain Reaction ; Transcription Factors ; genetics ; Young Adult

OBJECTIVE Tissue plasminogen activator (tPA) is the only approved pharmaco-logical therapy for acute brain ischaemia;however,a major limitation of tPA is the haemorrhagic trans-formation that follows tPA treatment. Here, we determined whether nicotinamide mononucleotide (NMN), a key intermediate of nicotinamide adenine dinucleotide biosynthesis, affects tPA-induced haemorrhagic transformation. METHODS Middle cerebral artery occlusion (MCAO) was achieved in CD1 mice by introducing a filament to the left MCA for 5 h.When the filament was removed for reperfusion, tPA was infused via the tail vein.A single dose of NMN was injected i.p.(300 mg·kg-1).Mice were killed at 24 h post ischaemia, and their brains were evaluated for brain infarction, oedema, haemoglobin content, apoptosis, neuroinflammation, blood-brain barrier (BBB) permeability, the expression of tight junction proteins(TJPs)and the activity/expression of MMPs. RESULTS In the mice infused with tPA at 5 h post ischaemia, there were significant increases in mortality, brain infarction, brain oedema, brain haemoglobin level, neural apoptosis, Iba-1 staining (microglia activation) and myeloperoxidase staining (neutrophil infiltration). All these tPA-induced alterations were significantly prevented by NMN administration. Mechanistically, the delayed tPA treatment increased BBB permeability by down-regulating TJPs, including claudin-1, occludin and zonula occludens-1,and enhancing the activities and protein expression of MMP9 and MMP2. Similarly, NMN administration partly blocked these tPA-induced molecular changes. CONCLUSION Our results demonstrate that NMN ameliorates tPA-induced haemorrhagic transformation in brain ischaemia by maintaining the integrity of the BBB.

The“two-hit”theory which underlies the mechanism of non-alcoholic fatty liver disease (NAFLD) is difficult to explain the progress of NAFLD from liver lipid accumulation to steatohepatitis, liver fibrosis and the gradually aggravated diseases.Recently the“multiple-hit”theory emphasizes the significance of endoplasmic reticulum stress (ERS) in the progression of NAFLD. The endoplasmic reticulum is a cytoplasmic organella for protein and lipid synthesis. ERS, which can be induced by the unbalance of endoplasmic reticulum homeostasis, plays a critical role in hepatocyte lipid metabolic disorders, Apoptosis and the progression of NAFLD. In this paper, the relevance of ERS and non-alcoholic liver lipid accumulation, steatohepatitis and hepatocyte apoptosis is reviewed.

Objective: Patients with late life depression sometimes refuse to receive electroconvulsive therapy (ECT) owing to its adverse reactions. To alleviate patient’s resistance, a novel ECT stimulation strategy named mixed-strategy ECT (msECT) was designed in which patients are administered conventional ECT during the first three sessions, followed by low energy stimulation during the subsequent sessions. However, whether low energy electrical stimulation in the subsequent stage of therapy affect its efficacy and reduce adverse reactions in patients with late life depression remains unknown. To explore differences between msECT and regular ECT(RECT) with respect to clinical efficacy and side effects Methods: This randomized, controlled trial was conducted from 2019 to 2021 on 60 patients with late life depression who were randomly assigned to two groups: RECT or msECT. A generalized estimating equation (GEE) was used to compare the two stimulation strategies regarding their efficacy and side effects on cognition. Chi-squared test was used to compare side effects in the two strategies. Results: In the intent-to-treat group, the GEE model suggested no differences between-group difference in Hamilton Depression Rating Scale-17 score over time (Wald χ2=7.275, p=0.064), whereas the comparison of side effects in the two strategies favored msECT (Wald χ2=8.463, p=0.015) as fewer patients had adverse events during the second phase of treatment with msECT (χ2 =13.467, p=0.004). Conclusion msECT presents its similar efficacy to RECT. msECT may have milder side effects on cognition.