[Intracytoplasmic sperm injection for patients with special types of teratozoospermia: Analysis of outcomes].

OBJECTIVE: To investigate the outcomes of intracytoplasmic sperm injection (ICSI) in the treatment of special types of teratozoospermia such as globozoospermia, acephalic spermatozoa syndrome (ASS) and multiple morphological abnormalities of sperm flagella (MMAF). METHODS: We retrospectively analyzed the clinical data on 7 cases of globozoospermia (group A), 6 cases of ASS (group B) and 21 cases of MMAF (group C) treated by ICSI from January 2011 to January 2021, all confirmed with pathogenic or likely pathogenic gene variations. We compared the age, body mass index (BMI), sperm parameters, number of mature oocytes, and rates of fertilization, high-quality embryos, clinical pregnancy, live birth and spontaneous abortion among the three groups of patients. RESULTS: There were no statistically significant differences in the age, BMI and number of metaphase Ⅱ (MⅡ) oocytes among the three groups (P > 0.05). Sperm concentration and motility were dramatically higher (P < 0.01) while the rates of fertilization, clinical pregnancy and live birth remarkably lower in group A than in B and C (P < 0.01). No statistically significant difference was observed in the spontaneous abortion rate among the three groups (P > 0.05). CONCLUSION: ICSI can achieve relatively satisfactory outcomes of clinical pregnancy in patients with ASS or MMAF, but only a low fertilization rate or no fertilization at all in those with globozoospermia even if treated by artificial oocyte activation.

[Effect of complete Y chromosome AZFc microdeletion on embryo euploidy].

OBJECTIVE: Preimplantation genetic testing (PGT) was performed to analyze the embryo euploidy in patients with complete Y chromosome AZFc microdeletion. METHODS: The clinical data of complete AZFc microdeletion underwent PGT from January 2013 to December 2021 in Reproductive Medicine Center of the First Affiliated Hospital of Nanjing Medical University were retrospectively analyzed. The patients with monogenic disease who underwent PGT during the same period were set as the control group. The basic characteristics, fertilization rate, Day 3 high quality embryo rate, blastocyst formation rate, embryo euploid rate, 45, X embryo ratio was compared between the two groups. RESULTS: A total of 220 patients were included, including 91 patients with complete AZFc microdeletion and 129 patients with monogenic disease. There was no significant difference in age between the two groups. In semen parameters, the sperm concentration, total sperm count and progressive motility in AZFc microdeletion group were lower than those in monogenic disease group, and the differences were statistically significant (P=0.001). The fertilization rate of AZFc microdeletion group was lower than that in monogenic disease group (P=0.012), and there was no significant difference in the number of MII oocytes, Day 3 high-quality embryo rate and blastocyst formation rate. A total of 933 blastocysts were successfully tested, including 496 blastocysts in AZFc deletion group and 437 blastocysts in monogenic disease group. The euploid, aneuploid and mosaic rates of the AZFc microdeletion group were 57.26%, 24.60% and 18.14%, respectively, while those of the monogenic disease group were 66.13%, 23.80% and 10.07%, with statistically significant differences between the two groups (P=0.001). Further analysis of the two groups of aneuploid embryos showed that aberrations occurred most commonly in chromosome16 (3.87%), X (3.46%), 13 (2.44%), 22 (2.24%) and 19 (2.03%) in AZFc microdeletion group, respectively, while the monogenic disease group was 22 (4.35%), 16 (2.97%), 7 (2.74%), 15(1.60%) and 2(1.60%), respectively. The proportion of sex chromosome abnormality in AZFc microdeletion group was higher than that in monogenic disease group (P=0.039), and there was no significant difference in the proportion of 45,X between the two groups. CONCLUSION: Compared with monogenic disease group, The embryo euploid rate in AZFc microdeletion patients decreased and the proportion of 45, X embryos did not increase significantly. It is recommended to select euploid female embryos by PGT, which not only avoids vertical transmission of AZFc microdeletion, but also reduces the risk of miscarriage due to aneuploid embryos.

Congenital absence of the vas deferens with hypospadias or without hypospadias: Phenotypic findings and genetic considerations.

Congenital absence of the vas deferens (CAVD) is a major cause of obstructive azoospermia. Mutations of CFTR and ADGRG2 cause the majority of CAVD. Despite this, 10%-20% of CAVD patients remain without a clear genetic diagnosis. Herein, the CFTR and ADGRG2 genes were first sequenced using Sanger sequencing in 50 CAVD patients. Whole-exome sequencing (WES) was used to further identify potential novel genetic causes in CAVD with hypospadias. In total, 29 of 50 CAVD patients carried at least one CFTR mutation, but no ADGRG2 mutation was found. 5T was found to be the most frequent variant in our CAVD populations. Seven CAVD patients with hypospadias were further analyzed using WES. No homozygous or compound heterozygous mutations related to disorders of sex development (DSDs) or male infertility were identified by WES. CAVD with hypospadias presented lower testicular volume (9.71 ± 2.14 ml vs. 14.45 ± 2.93 ml, p < 0.001) and higher FSH level (FSH: 7.28 ± 3.91 IU/L vs. 4.24 ± 1.96 IU/L, p = 0.027) than CAVD without hypospadias. It is worth noting that neither CFTR or ADGRG2 mutation nor homozygous or compound heterozygous gene mutations were identified in seven CAVD cases with hypospadias. However, nine heterozygous or hemizygous mutations were selected as potential pathogenic genes in CAVD with hypospadias. In conclusion, CFTR variants, especially 5T, play a major role in the Chinese CAVD population. CAVD with hypospadias shows relatively lower testicular spermatogenesis, suggesting a different genetic basis or pathogenic factor from cystic fibrosis/CAVD or unilateral renal agenesis/CAVD.

A novel mutation of AMHR2 in two brothers with persistent Müllerian duct syndrome and their intracytoplasmic sperm injection outcome.

BACKGROUND: Persistent Müllerian duct syndrome (PMDS) is defined as the presence of Müllerian duct derivatives in an otherwise normally virilized 46, XY male. It is usually caused by homozygous or compound heterozygous mutations in either the anti-Müllerian hormone (AMH) or AMH receptor type 2 (AMHR2) genes. The main purpose of the study is to determine the novel mutations of AMHR2 in PMDS patients and their intracytoplasmic sperm injection outcomes (ICSI). METHODS: Whole-exome sequencing (WES) was carried out. Sanger sequencing was used to detect mutations in AMHR2. The pathogenicity of the identified variant and its possible effects on the protein were evaluated with in silico tools. The expression level of AMHR2 was determined by Western blotting. The spermatogenic function was evaluated by testicular sperm aspiration and histopathologic examination. The ICSI outcomes were recorded. RESULTS: We present two brothers with a history of bilateral cryptorchidism with orchidopexy and infertility due to azoospermia. A novel compound heterozygous mutation of c.1219C>T [p.R407X] and c.1387C>T [p.R463C] in exons 9 and 10 of AMHR2 (NM_020547.2) was detected by whole-exome sequencing (WES). Spermatozoon could be retrieved from the two patients by testicular aspiration following intracytoplasmic sperm injection (ICSI) due to azoospermia. Finally, patient 1 had two healthy boys and patient 2 failed to conceive after three ICSI attempts. CONCLUSION: The spermatozoa could obtain from PMDS patients due to azoospermia. For patients with bilateral cryptorchidism, PMDS should be included in the differential diagnosis and that genetic counseling needs to be considered when they seek reproductive help.

Intracytoplasmic sperm injection outcomes in patients with orgasmic dysfunction and anejaculation by percutaneous epididymal sperm aspiration (PESA).

BACKGROUND: Orgasmic dysfunction and anejaculation are two uncommon yet powerful factors of male infertility. The treatment of orgasmic dysfunction and anejaculation is especially important for men who desire paternity, who otherwise would have to undergo surgical sperm retrieval for use with intracytoplasmic sperm injection (ICSI). We evaluated the reproductive outcomes of percutaneous epididymal sperm aspiration (PESA) for ICSI in a cohort of infertile patients who had presented with orgasmic dysfunction and anejaculation in the past five years. METHODS: We conducted a retrospective study of 41 patients with orgasmic dysfunction and 55 patients with anejaculation who underwent surgical sperm retrieval for ICSI. The sperm was firstly aspirated from the cauda epididymis, and then from the caput of the epididymis. If aspiration attempts failed at both locations, testicular sperm aspiration (TESA) was performed. The ICSI outcomes following these collection methods were compared with those of patients with congenital bilateral absence of the vas deferens (CBAVD). The ICSI outcomes of PESA (fertilization rate, high-quality embryo rate, clinical pregnancy, and live birth rate) were recorded. RESULTS: Of all 96 participants, PESA was successfully performed in 91 patients (94.8%), and TESA was necessary for only 5 patients (5.2%). Of the 91 patients who received PESA, 90 succeeded in retrieving sperm from the cauda epididymis, and just 1 from the caput. Among the patients with anejaculation, there were 28 cases (28/55, 50.9%) of diabetes mellitus (DM). In 56 fresh transfer cycles, the clinical pregnancy rate and live birth rate were 57.1% and 51.8%, respectively, both similar to those of CBAVD (53.47% vs. 63.4%, P=0.483, 47.2% vs. 53.5%, P=0.393, respectively). The fertilization rate, transferable embryo rate, high-quality embryo rate, clinical pregnancy, early pregnancy loss, and the live birth rate did not show differences resulting from using fresh or frozen sperm in the two groups. The fertilization rate and high-quality embryo rate in patients with DM were lower than those of patients without DM (75.0% vs. 86.7%, P=0.002; 50.4% vs. 77.4%, P=0.028, respectively). CONCLUSIONS: Like TESA, PESA is an appropriate and convenient way to obtain sperm for ICSI for patients with orgasmic dysfunction and anejaculation. Performing ICSI with sperm from the cauda epididymis can achieve favorable clinical pregnancy and live birth rates in patients with orgasmic dysfunction and anejaculation.

Patients with acephalic spermatozoa syndrome linked to SUN5 mutations have a favorable pregnancy outcome from ICSI.

STUDY QUESTION: Are Sad1 and UNC84 domain containing 5 (SUN5) mutations associated with the outcomes of ICSI in patients with acephalic spermatozoa syndrome (ASS)? SUMMARY ANSWER: Despite highly abnormal sperm morphology, ASS patients with SUN5 mutations have a favorable pregnancy outcome following ICSI. WHAT IS KNOWN ALREADY: ASS is a rare cause of infertility characterized by the production of a majority of headless spermatozoa, along with a small proportion of intact spermatozoa with an abnormal head-tail junction. Previous studies have demonstrated that SUN5 mutations may cause ASS. Several studies showed that ICSI could help patients with ASS father children. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study included 11 infertile ASS males with SUN5 mutations. Five of them underwent five ICSI cycles. Their ICSI results were compared to men with ASS without SUN5 mutations (n = 3) and to men with multiple morphological abnormalities of the sperm flagella (MMAF) (n = 9). All ICSI treatments were completed between Jan 2011 and May 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: Sanger DNA sequencing was used to detect mutations in SUN5. Clinical and biological data were collected from patients at the fertility center. MAIN RESULTS AND THE ROLE OF CHANCE: Sanger sequencing validated 11 patients with SUN5 mutations. Three novel mutations in SUN5 (c.829C>T [p.Q277*]; c.1067G>A [p.R356H]; c.211+1 insGT [p.S71Cfs11*]) were identified in three patients. The rates of fertilization, good-quality embryos and pregnancy for five patients with SUN5 mutations following ICSI were 81.5%, 81.8% and 100%, respectively. The rates of fertilization and good-quality embryos in patients with MMAF were significantly lower compared with ASS patients (65.6 versus 82.4%, P = 0.039 and 53.6 versus 85.2%, P = 0.031, respectively). There were no differences in ICSI results between ASS patients with and without SUN5 mutations. LIMITATIONS, REASONS FOR CAUTION: Only a small number patients with SUN5 mutations was available because of its rare incidence. WIDER IMPLICATIONS OF THE FINDINGS: Patients with ASS can be effectively treated with ICSI. SUN5 mutations may be one of the genetic causes of ASS. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the National Natural Science Foundation of China (81401251, 81370754, and 81170559), the Jiangsu Province Special Program of Medical Science (BL2012009, ZX201110, FXK201221) and a project funded by PAPD of the Priority Academic Program Development of Jiangsu High Education Institutions (JX10231802). None of the authors have any competing interests.

Abnormal Hypermethylation of the VDAC2 Promoter is a Potential Cause of Idiopathic Asthenospermia in Men.

This study aimed to explore the association between the methylation status of the VDAC2 gene promoter region and idiopathic asthenospermia (IAS). Twenty-five IAS patients and 27 fertile normozoospermia (NZ) were involved. GC-2spd cells were treated with different concentrations of 5-aza-2'-deoxycytidine (5-Aza-CdR) for 24 h and 48 h. qRT-PCR was conducted to reveal whether or not VDAC2 expression was regulated by methylated modification. A dual-luciferase activity detection was used to verify VDAC2 promoter activity in GC-2spd cells. Bisulphite genomic sequence was used to analyse DNA methylation of the VDAC2 promoter. The results showed that VDAC2 expression was significantly increased after treated with 5-Aza-CdR. A strong activity of the promoter (-2000 bp to +1000 bp) was detected by dual-luciferase activity detection (P < 0.05). The bisulphite genomic sequencing and correlation analysis showed that sperm motility was positively associated with the methylation pattern of uncomplete methylation and mild hypermethylation, and negatively related to the percentage of moderate methylation. In conclusion, high methylation of the VDAC2 promoter CpGs could be positively correlated with low sperm motility. Abnormal methylation of VDAC2 promoter may be a potential cause to idiopathic asthenospermia.

Galangin inhibits cell invasion by suppressing the epithelial-mesenchymal transition and inducing apoptosis in renal cell carcinoma.

Galangin, a flavonoid extracted from the root of the Alpinia officinarum Hence, has been shown to have anticancer properties against several types of cancer cells. However, the influence of galangin on human renal cancer cells remains to be elucidated. In the present study, proliferation of 786­0 and Caki­1 cells was suppressed following exposure to various doses of galangin. Cell invasion and wound healing assays were used to observe the effect of galangin on invasion and migration. The results demonstrated that Galangin inhibited cell invasion by suppressing the epithelial mesenchymal transition (EMT), with an increase in the expression of E­cadherin and decreased expression levels of N­cadherin and vimentin. The apoptosis induced by galangin was analyzed by flow cytometry. The results revealed that galangin induced apoptosis in a dose­dependent manner. The accumulation of reactive oxygen species (ROS) is an important contributing factor for the apoptosis of various types of cancer cell. The dichlorofluorescein-diacetate method was used to determine the level of ROS. Galangin induced the accumulation of intracellular ROS and malondialdehyde, and decreased the activities of total antioxidant and superoxide dismutase in renal cell carcinoma cells. Galangin exerted an antiproliferative effect and inhibited renal cell carcinoma invasion by suppressing the EMT. This treatment also induced apoptosis, accompanied by the production of ROS. Therefore, the present data suggested that galangin may have beneficial effects by preventing renal cell carcinoma growth, inhibiting cell invasion via the EMT and inducing cell apoptosis.

H19-derived miR-675 contributes to bladder cancer cell proliferation by regulating p53 activation.

Long noncoding RNA 19 (H19) has been shown to promote bladder cancer cell proliferation and metastasis. However, little is known about how miR-675, mature product of H19, contributes to bladder cancer cell proliferation. In this study, we first evaluated the expression of miR-675 in bladder cancer tissues by quantitative real-time PCR (qRT-PCR) and defined its biological functions by flow cytometry and Western blotting. We found that miR-675 expression levels were remarkably increased in bladder cancer tissues as compared with adjacent noncancerous tissues or normal bladder tissue from health donors; moreover, enhanced miR-675 expression was also observed in bladder cancer cell lines. Ectopic expression of H19 significantly increased bladder cancer cell proliferation and miR-675 expression in vitro. Furthermore, overexpression of miR-675 promoted bladder cancer cell proliferation, while suppression of miR-675 induced G1 phase cell cycle arrest and promoted cell apoptosis. Western blotting analysis further identified that miR-675 inhibited p53 activation, decreased the ratio of Bax/Bcl-2 and cyclin D1 expression in bladder cancer cells; those effects may result in the abnormal proliferation of bladder cancer cells. In conclusion, abnormal enhanced miR-675 expression increases bladder cancer growth by regulating p53 activation, and thus may be helpful in the development of effective treatment strategies for bladder cancer.

Downregulation of tNASP inhibits proliferation through regulating cell cycle-related proteins and inactive ERK/MAPK signal pathway in renal cell carcinoma cells.

Nuclear auto-antigenic sperm protein (NASP), initially described as a highly auto-immunogenic testis and sperm-specific protein, is a histone chaperone that is proved to present in all dividing cells. NASP has two splice variants: testicular NASP (tNASP) and somatic form of NASP (sNASP). Only cancer, germ, transformed, and embryonic cells have a high level of expression of the tNASP. Up to now, little has been known about tNASP in renal cell carcinoma (RCC). In the present study, the molecular mechanism of tNASP in RCC was explored. The expression level of tNASP in 16 paired human RCC specimens was determined. Downregulation of tNASP by small interfering RNA (siRNA) was transfected in RCC cell lines. The effect of downregulation of tNASP by siRNA on cell colony formation and proliferation was examined by colony formation assay and CCK-8 assay, cell cycle was analyzed by flow cytometry, and the expression of cyclin D1 and P21 were detected by Western blotting. ERK/MAPK signaling was also analyzed. tNASP has a relative high expression level in human RCC tissues. Via upregulation of P21 and downregulation of cyclinD1, silence of tNASP can inhibit cell proliferation, which induces cell cycle arrest. Furthermore, ERK signaling pathway is confirmed to mediate the regulation of cell cycle-related proteins caused by silence of tNASP. Our research demonstrates that knockdown of tNASP effectively inhibits the proliferation and causes G1 phase arrest through ERK/MAPK signal pathway.

Seminal plasma protein in renal cell carcinoma: expression of semenogelin I is a predictor for cancer progression and prognosis.

The incidence of renal cell carcinoma (RCC) has been steadily rising each year. There are currently few recognized biomarkers for the diagnosis and prognosis of RCC. We investigated semenogelin I (Sg I) expression and its clinical significance in patients with RCC. The expression levels of Sg I and its protein were measured by qPCR and Western blotting, respectively. Immunohistochemistry was used to investigate the protein expression of Sg I in RCC and normal renal tissue from 53 patients. The Kaplan-Meier method and log-rank test were used to evaluate the data. By qRCR (p < 0.01) and Western blot, the level of Sg I expression in benign tissues was higher than that in RCC tissues. Expression of Sg I was observed in 30 (57 %) RCC cases, which was significantly lower than that observed in benign renal tissues from the same patients [Sg I positive in 53 (100 %) cases (p < 0.0001)] by immunohistochemistry. There was an inverse relation between Sg I expression and clinical stage (pT1-2 vs pT3-4, p < 0.0001). Patients with Sg I-negative tumor had a significantly higher risk of recurrence (Kaplan-Meier and log-rank tests, p < 0.0001). There was low Sg I expression in RCC. Sg I expression has potential value in predicting cancer progression and prognosis. These findings support the use of Sg I as a novel biomarker for RCC.

Proteomic characteristics of human sperm cryopreservation.

Human sperm cryopreservation in assisted reproductive technology is the only proven method that enables infertile men to father their own children. However, freezing and thawing reduces spermatozoon motility, viability, and fertilizing ability. An association between dysfunctional spermatozoa due to cryoinjury and protein changes has not been established. We investigated through proteomic analysis the differential protein characteristics between freeze-thawed and fresh sperm samples obtained from nine normozoospermic donors. Twenty-seven proteins differed in abundance between the two groups, and results were verified for four proteins via Western blot and immunofluorescent staining. These proteins are putatively involved in sperm motility, viability, acrosomal integrity, ATP and isocitrate content, mitochondrial membrane potential, capacitation, acrosome reaction, and intracellular calcium concentration. These marked differences suggest that dysfunctional spermatozoon after cryopreservation may be due to protein degradation and protein phosphorylation.

The Cytochrome P4501A1 gene polymorphisms and idiopathic male infertility risk: a meta-analysis.

Studies of the relationship between male infertility and CYP1A1 polymorphisms are inconclusive. To drive a more precise estimation, we performed a meta-analysis based on 1060 cases and 1225 controls from 7 published case-control studies. PubMed and CNKI literature search were conducted to identify all eligible studies investigating such a relationship. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association in the additive model, dominant model, recessive model, and allele-frequency genetic model. In the overall analysis, the frequency of CYP1A12A genotype was significantly associated with susceptibility to idiopathic male infertility. Further stratified analysis by ethnicity showed notable association between the polymorphism and the risk of idiopathic male infertility in Asians. In conclusion, these results support that the CYP1A1 2A genotype polymorphism mainly contributes to idiopathic male infertility susceptibility in Asians but not in Caucasians.

Correlation of epididymal protease inhibitor and fibronectin in human semen.

OBJECTIVE: Epididymal protease inhibitor (Eppin) was located on the surface of spermatozoa and modulates the liquefaction of human semen. Here, we identify the correlative protein partner of Eppin to explore the molecular mechanism of liquefaction of human semen. METHODS: (1) Human seminal vesicle proteins were transferred on the membrane by Western blotting and separated by 2-D electrophoresis and incubated in recombinant Eppin. The correlative protein was identified by Mass Spectrometry (MS) (2). Western blotting was used to determine the relation of rEppin and rFibronectin(Fn); (3) Co-localization in spermatozoa were detected using immunofluorescence; (4) Correalation of Eppin and Fn was proved by co-immunoprecipitation. RESULTS: Fn was identified as the binding partner of recombinant Eppin by MS. Recombinant of Eppin was made and demonstrated that the Eppin fragment binds the fn 607-1265 fragment. The Eppin-Fn complex presents on the sperm tail and particularly in the midpiece region of human ejaculated spermatozoa. Immunoprecipitation indicated that Eppin in the spermatozoa lysates was complexed with Fn. CONCLUSIONS: Our study demonstrates that Eppin and Fn bind to each other in human semen and on human ejaculated spermatozoa. Eppin-Fn complex may involve in semen coagulation, liquefaction and the survival and preparation of spermatozoa for fertility in the female reproductive tract.

Association of the glutathione s-transferase m1, t1 polymorphisms with cancer: evidence from a meta-analysis.

BACKGROUND: Glutathione S-transferases (GSTs) are a family of multifunctional enzymes that are involved in the metabolism of many xenobiotics, including a wide range of environmental carcinogens. While the null genotypes in GSTM1 and GSTT1 have been implicated in tumorigenesis, it remains inconsistent and inconclusive. Herein, we aimed to assess the possible associations of the GSTM1 and GSTT1 null genotype in cancer risks. METHODS: A meta-analysis based on 506 case-control studies was performed. Odds ratios (OR) with corresponding 95% confidence intervals (CIs) were used to assess the association. RESULTS: The null genotypes of GSTM1 and GSTT1 polymorphisms were associated with a significantly increased risk in cancer (for GSTM1: OR = 1.17; 95%CI = 1.14-1.21; for GSTT1: OR = 1.16; 95%CI = 1.11-1.21, respectively). When the analysis was performed based on their smoking history, the risk associated of GSTM1 null and GSTT1 null genotypes with cancer is further increased (for GSTM1: OR = 2.66; 95%CI = 2.19-3.24; for GSTT1: OR = 2.46; 95%CI = 1.83-3.32, respectively). CONCLUSIONS: These findings indicate that GSTM1 and GSTT1 polymorphisms may play critical roles in the development of cancer, especially in smokers.

PAI-1 4G/5G polymorphism contributes to cancer susceptibility: evidence from meta-analysis.

BACKGROUND: The plasminogen activator inhibitor-1 (PAI-1) is expressed in many cancer cell types and allows the modulation of cancer growth, invasion and angiogenesis. To date, studies investigated the association between a functional polymorphism in PAI-1 (4G/5G) and risk of cancer have shown inclusive results. METHODS: A meta-analysis based on 25 case-control studies was performed to address this issue. Odds ratios (OR) with corresponding 95% confidence intervals (CIs) were used to assess the association. The statistical heterogeneity across studies was examined with I(2) test. RESULTS: Overall, a significant increased risk of cancer was associated with the PAI-1 4G/4G polymorphism for the allele contrast (4G vs. 5G: OR = 1.10, CI = 1.03-1.18, I(2) = 49.5%), the additive genetic model (4G/4G vs. 5G/5G: OR = 1.21, CI = 1.06-1.39, I(2) = 51.9%), the recessive genetic model (4G/4G vs. 4G/5G+5G/5G: OR = 1.11, CI = 1.04-1.18, I(2) = 20.8%). In the subgroup analysis by ethnicity, the results indicated that individuals with 4G/4G genotype had a significantly higher cancer risk among Caucasians (4G/4G vs. 5G/5G: OR = 1.31, 95%CI = 1.09-1.59, I(2) = 59.6%; 4G/4G vs. 4G/5G: OR = 1.12, 95%CI = 1.04-1.21, I(2) = 3.6%; recessive model: OR = 1.12, 95%CI = 1.05-1.21, I(2) = 25.3%). CONCLUSIONS: The results of the present meta-analysis support an association between the PAI-1 4G/5G polymorphism and increasing cancer risk, especially among Caucasians, and those with 4G allele have a high risk to develop colorectal cancer and endometrial cancer.

[Effect of simvastatin on the proliferation of human omental preadipocytes and caspase-3 expression].

OBJECTIVE: To explore the effect of simvastatin on the cell cycle and caspase-3 expression in human omental preadipocytes. METHODS: The preadipocytes were randomly divided into a blank group, a 10(-5) mol/L simvastatin group, and a 10(-4) mol/L simvastatin group. Each group was incubated with different concentrations of simvastatin for 48 hours. MTT method was used to analyze the effect of simvastatin on the proliferation. Distribution of the cell cycle was measured by flow cytometric. Caspase-3 expression was examined by cyto- immunochemistry. RESULTS: After being induced to differentiate for 16 days the human omental preadipocytes developed to mature adipocyte penotypes with lipid droplet. Simvastatin 10(-4) mol/L had significant anti-proliferation effect. Flow cytometric analysis showed the cell cycle was blocked in G0/G1 phase and caspase-3 positive cells increased dramatically. CONCLUSION: Simvastatin may block the cells in G0/G1 phase, and induce caspase-3 expression, which may trigger apoptosis.