Bioinformatic Analysis of the Significance of the KIR2DL4 Gene in Recurrent Implantation Failure.

Related studies have pointed out that Killer immunoglobulin-like receptor 2DL4 (KIR2DL4) was associated with vascular remodeling in early pregnancy, and it might play an important role in immunity. In this study, recurrent implantation failure (RIF)-related GSE58144 dataset was extracted from the Gene Expression Omnibus (GEO) database. Firstly, the immune micro-environment analyses were conducted to analyze the pathogenesis of KIR2DL4 in RIF. Then, the gene set enrichment analysis (GSEA) was performed to investigate the function of KIR2DL4. Moreover, the TF-mRNA-miRNA and the co-expression networks were constructed to reveal the potential regulation of KIR2DL4. Furthermore, the genes that were associated with KIR2DL4 and differentially expressed in RIF were obtained and defined as key genes, and the functions of these genes were further explored. KIR2DL4 could be used for clinical diagnosis of RIF, and it was correlated with the changes in the immune micro-environment in RIF. From the perspective of function, KIR2DL4 was associated with complement and coagulation cascades, natural killer cell-mediated cytotoxicity, etc. Moreover, the TF-mRNA-miRNA regulatory network was constructed with KIR2DL4, 9 TFs, and 29 miRNAs. Furthermore, KIR2DL4, ACSM1, IL2RB, and PTPN11 were screened as key genes, which were associated with immune-related functions. This study deeply analyzed the function of KIR2DL4 and its role in RIF, and we found that STAT1 might up-regulate KIR2DL4 by INF-γ/JAK2/STAT1 signaling pathway. Besides, over-expressed KIR2DL4 in the mid-luteal endometrium might influence embryo implantation by affecting the embryo implantation microenvironment, which might help deepen the understanding of the molecular mechanism of RIF.

Pregnancy outcome and follow-up of offspring of donor oocytes recipient from PCOS patients.

BACKGROUND: The use of donated oocytes (DO) for in vitro fertilization(IVF) treatment in patients with infertility is generally recognized, and females with polycystic ovarian syndrome (PCOS) can participate in oocyte donation programs as donor patients. However, the pregnancy outcomes and offspring follow-up in patients with PCOS as the recipients are unclear. This study was to compare the pregnancy outcomes and follow-up of offspring in PCOS and non-PCOS receptor. METHODS: This was a retrospective cohort study of 62 patients undergoing the oocyte reception program were separated into 2 groups: Group I, PCOS oocyte recipients (n = 30); Group II, non-PCOS recipients (n = 32). Medical records were reviewed, and rates of fertilization, cleavage, high-quality embryos and blastocysts were compared between PCOS and non-PCOS groups. Rates of implantation, pregnancy, ectopic pregnancy, early abortion, multiple pregnancies, and offspring outcomes were calculated using the first single vitrified-warmed blastocyst transfer (SVBT) analysis between the groups. RESULTS: The average recipient age and body mass index (BMI) of PCOS and non-PCOS patients was (36.3 ± 2.6 vs. 36.2 ± 2.8, and 23.4 ± 3.9 vs. 23.7 ± 4.0), respectively (P > 0.05). The fertilization, cleavage, high-quality embryos and blastocyst rates were not significantly different between the PCOS and non-PCOS groups. Rates of implantation, pregnancy, ectopic pregnancy, early abortion, and multiple pregnancies were not significantly different in SVBT between the PCOS and non-PCOS groups. The incidence of complications, such as pre-eclampsia or gestational diabetes, between PCOS and non-PCOS groups was similar (11.8% vs.11.1%, 5.9% vs.5.5%; P > 0.05). Preterm births were also similar (11.8% vs.16.7%, P > 0.05). Donor oocytes are more likely to be delivered via cesarean Sect. (80.0% vs. 86.7%: P > 0.05). The mean gestational age, birth weight, and height were comparable between the 2 groups during full-term delivery. CONCLUSION: There was no difference in the pregnancy outcomes and follow-up of the offspring between the PCOS and non-PCOS groups.

Structural Characterization and In Vitro Antioxidant Activity of Metallothionein from Oratosquilla oratoria.

We report here the purification of a novel metal-binding protein from Oratosquilla oratoria (O. oratoria MT-1) by gel and ion-exchange chromatography. SDS-PAGE and MALDI-TOF analyses demonstrated that isolated O. oratoria MT-1 was of high purity with a molecular weight of 12.4 kDa. The fluorescence response to SBD-F derivatives revealed that O. oratoria MT-1 contained a large number of sulfhydryl groups, which is a general property of metallothioneins. Zn and Cu metal stoichiometries for O. oratoria MT-1 were 3.97:1 and 0.55:1, respectively. The proportion of cysteine (Cys) residues in the amino acid composition was 32.69%, and aromatic amino acids were absent. The peptide sequence coverage with Macrobrachium rosenbergii calmodulin (accession AOA3S8FSK5) was 60%. Infrared spectroscopy of O. oratoria MT-1 revealed two obvious peaks at absorption frequencies for the amide I band and the amide II band. CD spectra revealed that the secondary structure was mainly composed of random coil (57.6%) and ß-sheet (39.9%). An evaluation of in vitro antioxidant activity revealed that isolated O. oratoria MT-1 has strong reducing activities, exhibiting scavenging rates for DPPH and OH of 77.8% and 75.8%, respectively (IC50 values 0.57 mg/mL and 1.1 mg/mL). O. oratoria MT-1 may be used as a functional additive in cosmetics, health foods, and medical products, as well as a reference material for quantitative analysis of metallothionein in such products.

Does the additional use of clomiphene citrate or letrozole for in vitro fertilization deserve more attention?

BACKGROUND: Adding clomiphene citrate (CC) and/or letrozole (LE) to in vitro fertilization (IVF) cycles for mild ovarian stimulation is a general approach. Although lots of researches have demonstrated partial benefits of the strategy, all-around effects of oral medications remained deficient. This paper aims to assess whether an addition of oral medication will result in considerable outcomes on T-Gn (total dose of gonadotropin), Gn days, total retrieved ova, high quality embryos, blastocyst number, ovarian hyperstimulation syndrome (OHSS) rate, clinical pregnancy rate and cumulative pregnancy rate, even if it was not conventional mild/minimal stimulations. RESULTS: Participants were categorized to three diverse populations as high responders, normal responders and poor responders according to basal antral follicle count. T-Gn in patients treated with CC/LE distinctly decreased from 2496.96 IU/d to 1827.68 IU/d, from 2860.28 IU/d to 2119.99 IU/d, and from 3182.15 IU/d to 1802.84 IU/d, respectively. For high ovary responders and normal responders, the OHSS incidence rate also declined from 29.2 to 4.3% (P < 0.001) and from 1.1 to 0.0% (P = 0.090). Other, there was no statistical difference with respect to the T-retrieved ova (total retrieved ova), high quality embryos, cultured blastocyst and blastocyst number in high responders. For normal responders and poor ovary responders, T-Gn, Gn days, T-retrieved ova, high quality embryos, cultured blastocyst and blastocysts number in oral medications group all apparently decreased. Clinical pregnancy rate per fresh cycle of poor responders with prior oral medications was significantly decreased (25.7% vs. 50.8%, P = 0.005), and no significant differences in high responders and normal responders were expressed (52.5% vs. 44.2%, P = 0.310; 51.9% vs. 42.4%, P = 0.163) between two groups of participants. The numbers of cumulative pregnancy rates were lower in the conventional group compared to the add group for high (75.90% versus 81.03%, P = 0.279), normal (62.69% versus 71.36%, P = 0.016) and poor (39.74% versus 68.21%, P < 0.001) responders. CONCLUSIONS: The addition of CC/LE to the ovulation induction during IVF has certain efficacy in terms of low cost, low OHSS incidence. CC/LE deserves more recommendations as a responsible strategy in high responders due to advantageous pregnancy outcomes. For normal responders, the strategy needs to be considered with more comprehensive factors.

Changes and correlations of anti-Müllerian hormone and stem-cell factors in different ovarian reserve patients during GnRH-antagonist protocol and the effects on controlled ovarian hyperstimulation outcomes.

PURPOSE: To explore the changes and correlations of anti-Müllerian hormone (AMH) and stem-cell factors (SCF) in different ovarian reserve patients during controlled ovarian hyperstimulation (COH) and the effects on COH outcomes. METHODS: Serum at six different timepoints during GnRH-antagonist protocol and follicular fluid (FF) on oocyte retrieval day of 52 patients with polycystic ovary syndrome (PCOS), 61 patients with normal ovarian reserve (NOR) and 42 patients with diminished ovarian reserve (DOR) were collected. AMH and SCF were assessed using enzyme-linked immunosorbent assay. RESULTS: During COH, AMH in the PCOS group was the highest, but SCF did the opposite, and serum AMH gradually decreased, while SCF inversely increased. In the PCOS group, SCF on the first and fourth days of gonadotropin (Gn) administration was negative with Gn dosage (r = - 0.362, P < 0.05; r = - 0.344, P < 0.05). In the NOR group, the basal AMH was also negative with Gn dosage (r = - 0.297, P < 0.05) and positive with COH outcomes (number of retrieved oocytes, MII oocytes, and 2PN fertilization) as well as serum SCF after Gn administration. In the DOR group, both AMH and SCF were significantly associated with COH outcomes. Serum AMH in the DOR group after Gn administration and FF AMH showed a negative correlation with SCF. CONCLUSIONS: Serum AMH decreased, while SCF increased during COH. AMH and SCF are effective for Gn time and dosage adjustment and predicting COH outcomes for NOR and DOR patients. In addition, serum AMH in DOR patients after Gn administration and FF AMH has a negative effect on SCF.

Characteristics of women with mixed mass formation after evacuation following uterine artery chemoembolization for cesarean scar pregnancy.

PURPOSE: To explore the efficacy of treatment for early cesarean scar pregnancy (CSP) and to evaluate the characteristics of women with subsequent mixed mass formation. METHODS: Women with CSP, who received UACE followed by evacuation, were retrospectively analyzed. Clinical/sonographic characteristics in patients with or without mixed mass formation were compared. RESULTS: From a total of 395 cases, 105 cases had a pregnancy residual with mixed mass formation. Blood loss and subsequent salvage intervention were significantly lower in patients without mixed mass, although all women retained their uteri. It required 50 days for the mass to resolve, 40 days for ß-hCG concentrations to drop back to normal, and 61 days for menses to be restored; all of which were significantly longer than the same indices in women without a mixed mass. Clinical/sonographic characteristics predicting residual mass formation were maximal diameter of gestational sac (OR = 1.05, P = 0.001, with a sensitivity and specificity of 68.6 and 80.3%, respectively), presence of a fetal heart beat (OR = 2.63, P = 0.002, with a sensitivity and specificity of 62.9 and 67.2%, respectively), remnant myometrial thickness (OR = 108.91, P = 0.001 when thickness was less than 1 mm, with a sensitivity and specificity of 42.9% and 96.6%), location of gestational sac (OR = 59.20, P = 0.01 for complete type, with a sensitivity and specificity of 99.0 and 36.9%), and Doppler signal grading (OR = 8.08, P = 0.013 for Grade III, with a sensitivity and specificity of 83.8 and 51.0%). CONCLUSIONS: UACE followed by evacuation was effective for CSP and subsequent mixed mass formation could be predicted by some clinical/sonographic characteristics.

Naringenin enhances the efficacy of human embryonic stem cell-derived pancreatic endoderm in treating gestational diabetes mellitus mice.

Gestational diabetes mellitus (GDM) is a disease commonly occurs during mid to late pregnancy with pathologies such as hyperglycemia, hyperinsulinemia and mal-development of fetus. We have previously demonstrated that pancreatic endoderm (PE) derived from human embryonic stem cells (hESCs) effectively alleviated diabetic symptoms in a mouse model of GDM, although the clinical efficacy was limited due to oxidative stress. In this study, using the anti-oxidant agent naringenin, we aimed to further enhance the efficacy of hESC-derived PE transplant. Insulin-secreting PE was differentiated from hESCs, which were then transplanted into GDM mice. Naringenin was administered to mice receiving the PE transplant, with sham operated mice serving as negative control, to assess its effect on alleviation of GDM symptoms. We found that naringenin supplement further improved insulin response, glucose metabolism and reproductive outcome of the PE-transplanted female mice. Our new findings further potentiates the feasibility of using differentiated hESCs to treat GDM, in which anti-oxidative agent such as naringenin could greatly enhance the clinical efficacy of stem cell based therapies.

Self-expandable metallic stent as a bridge to elective surgery versus emergency surgery for acute malignant colorectal obstruction.

BACKGROUD: The efficacy and safety of self-expandable metallic stents (SEMSs) as a bridge for patients with acute malignant colorectal obstructions (AMCOs) are still controversial. We conducted this study to evaluate the outcomes of patients with AMCOs treated by different strategies. METHODS: From January 2010 to March 2014, a total of 171 patients with AMCOs from Zhongshan Hospital were retrospectively enrolled in this study. One hundred twenty patients successfully received stent placement followed by one-stage laparoscopic or open resection in the stent group, and 51 patients received emergency operations in the emergency group. RESULTS: The operation duration and postoperative hospital stay were significantly shorter in the stent group (114.51 ± 28.65 vs. 160.39 ± 58.94 min, P < 0.001; 8.00 ± 3.97 vs. 12.59 ± 9.07 days, P = 0.001). The stent group also had significantly reduced intraoperative blood loss and the incidence of postoperative complications compared with the emergency group (61.00 ± 43.70 vs. 121.18 ± 85.90 ml, P < 0.001; 16.7 vs. 37.3%, P = 0.003). Kaplan-Meier survival curves showed that the median survival time in the stent group was significantly longer than that in the emergency group (53 vs. 41 months, P = 0.034). In subgroup analysis of stent group, the stent laparoscopy group had significantly decreased postoperative complications (P = 0.025), and similar long-term survival (P = 0.81). CONCLUSIONS: Stent placement as a bridge to surgery is a safe and feasible procedure and provides significant advantages in terms of short-term outcomes and favorable prognoses for patients with AMCOs. Laparoscopic surgery could be considered as an optimal treatment after stent placement.

[Refractive development and form-deprivation induced myopic refractive error in CBA/CaJ mice].

Due to the advantages in genetic manipulation, mice have become one of the most commonly used mammalian models for the study of mechanisms underlying myopia development. However, the vast majority of laboratory mouse strains are incapable of synthesizing melatonin, a neurohormone that may play an important role in myopia generation in humans. The present study investigated refractive development profiles in the CBA/CaJ mouse, a strain proficient in melatonin, and determined whether and how its refractive development could be affected by form-deprivation. Eccentric infrared photoretinoscopy revealed that this animal could be stably refracted, and the refractive error underwent developmental changes, which increased with age in the hyperopic direction and eventually got stable approximately 9 weeks after birth. The absolute values of refractive error in CBA/CaJ mice were larger than those of age-matched C57BL/6 mice, whereas the time points when refractive error reached steady state were similar between the two strains. Five weeks of form-deprivation applied to 3-week-old CBA/CaJ mice by translucent occluder wear caused a significant myopic shift in refractive error, indicating that this strain could be adequately used as a myopia model.

Checkpoint inhibitors in immunotherapy of ovarian cancer.

The treatment of ovarian cancer is a major challenge in oncology as mortality from ovarian cancer remains very high. The immune system plays a critical role in controlling cancer through a dynamic relationship with cancer cells. Immunotherapy can establish a sustained immune system response against recurring cancer cells leading to long-term remissions for ovarian cancer patient. The use of immune checkpoint inhibitors, which work by targeting molecules that serve as checks and balances in the regulation of immune responses, might be a promising avenue of immunotherapeutic research in ovarian cancer. In this review, we have focused on the potential of certain immune checkpoint inhibitors, such as anti-cytotoxic T lymphocyte antigens, anti-programmed death agents, and anti-program death ligands against ovarian cancer, with their mechanism of actions. Also, the problems arising due to checkpoint inhibitor immunotherapy have been discussed in this review. Checkpoint inhibitor immunotherapy is still in early-phase testing for ovarian cancer. Understanding the pivotal role of the tumor microenvironment in suppressing anticancer immunity, the unique adverse effects profiles of these agents, and the exploration of combinatorial treatment regimens will ultimately lead to enhance the efficacy of ovarian cancer immunotherapies and improved patient care.

Research on the comprehensive child life intervention program (CCLIP) for adjusting medical fear in children with central nervous system (CNS) cancers: a randomized controlled trial study protocol.

BACKGROUND: Medical fear is a common psychological reaction in hospitalized children, especially during radiotherapy for central nervous system (CNS) cancers. This fear not only causes negative emotions such as anxiety and depression but also affects children's quality of life and treatment outcomes. It is exacerbated by factors such as unfamiliar environments during radiation therapy and separation from parents. Child Life, as a professional service, offers physical and mental support to children through medical understanding and psychological preparation, addressing their social and psychological needs, among other things. This study aims to construct a comprehensive Child Life intervention program (CCLIP), consisting of four key components: psychological adjustment and preparation, therapeutic play, pain management and coping strategies, and family support. The integration of effective intervention methods aims to reduce medical fear in children undergoing radiotherapy, promote psychological well-being, improve treatment compliance, and enhance quality of life. METHODS: This study is a protocol for a randomized controlled trial. Using a random number table method, we plan to recruit 38 eligible children who meet the inclusion criteria and then randomize them into two distinct groups: the intervention group and the control group. The intervention group will receive the CCLIP, and the control group will receive standardized care. Data will be collected through questionnaires and on-site assessments during the one-month intervention period at four distinct time points: the day of admission (T0), the first radiotherapy positioning (T1), mid-radiotherapy (T2), and postradiotherapy (T3). The primary outcome measure is the effectiveness of the CCLIP in reducing medical fear among children receiving radiation treatment for CNS cancers. Secondary outcomes include anxiety, depression, radiation adherence, quality of life among children, and parental satisfaction. DISCUSSION: This study aims to alleviate medical fear among children with CNS tumors undergoing radiotherapy through the implementation of the CCLIP while enhancing their mental health and quality of life. The expected outcomes of this research include providing effective intervention strategies for clinical practice, improving the treatment experience and long-term prognosis of children, and having positive impacts on children and their families. TRIAL REGISTRATION: This study is registered at the Chinese Clinical Trial Registry, ChiCTR2400082622. Registered 2 April, 2024.

Global burden and health inequality of nutritional deficiencies from 1990 to 2019.

Introduction: Nutritional deficiencies (NDs) manifest in various forms and are widespread globally. However, a systematic evaluation of the epidemiology of NDs across all causes and age groups in different countries and regions has not been conducted. Materials and methods: This study aimed to utilize data from the 2019 Global Burden of Disease (GBD) study to assess the burden and trends of NDs, including their incidence, prevalence, mortality, and disability-adjusted life years (DALYs). Additionally, the study evaluated health inequalities at global, regional, and national levels from 1990 to 2019. Result: In 2019, the age-standardized incidence rate of NDs was 2,207.71 per 100,000 individuals (95% UI 1,863.04-2,604.67), and the age-standardized DALYs (ASR-DALYs) was 680.12 per 100,000 individuals (95% UI 507.21-894.89). Among the causes of NDs, dietary iron deficiency had the highest ASR-DALYs and exhibited minimal variation. Children under the age of 5 years faced the greatest risk of NDs. Sex disparity was evident, with males having lower rates than females. Although the gap in the burden of NDs between regions classified as poor and wealthy decreased, disparities persist. Conclusion: These findings provide critical insights for the development of global health strategies aimed at mitigating NDs and may guide policymakers in implementing effective and economically viable interventions.

Synthesis, preliminary structure-activity relationships, and in vitro biological evaluation of 6-aryl-3-amino-thieno[2,3-b]pyridine derivatives as potential anti-inflammatory agents.

In our previous study, a series of 6-aryl-3-amino-thieno[2,3-b]pyridine derivatives exhibited potent antiproliferative activities and an unique hepatocellular carcinoma (HCC)-specific anticancer activity was also observed. In further anti-inflammatory research, thienopyridine derivative 1a showed potent inhibition of nitric oxide (NO) production. So a series of thienopyridine analogues of 1a were synthesized and evaluated for anti-inflammatory activities. The structure-activity relationships (SARs) revealed that the most potent analogues 1f and 1o were identified as potent inhibitors of NO production with IC50 values of 3.30 and 3.24 µM, respectively. These results suggest that these 6-aryl-3-amino-thieno[2,3-b]pyridine derivatives might potentially constitute a novel class of anti-inflammatory agents, which require further studies.

[Relationship between chemokine axis CXCL12-CXCR4 and epithelial ovarian cancer].

OBJECTIVE: To explore the relationship between chemokine axis CXCL12-CXCR4 and the pathogenesis and severity of epithelial ovarian cancer. METHODS: SKOV3 transfected with plasmid, SKOV3 transfected with vector and SKOV3 were cultured in vitro. Methyl thiazolyl tetrazolium (MTT) was used to analyze the effects of different concentrations of CXCL12 on the proliferation, migration and invasion of three cell lines and examine the inhibition of neutralizing CXCR4 antibody or antagonist AMD3100. And the load and weight of acquired tumor were determined at different concentrations of CXCL12. RESULTS: CXCL12 could promote the proliferation, migration and invasion of SKOV3/CXCR4 cells in a dose-dependent fashion (P < 0.05). The effect on CXCL12 tumorigenesis could be inhibited by neutralizing CXCR4 antibody or antagonist AMD3100 (P < 0.05). Significant differences existed in the mean survival time, load and weight of metastatic tumors among the three nude mice. CONCLUSION: A close correlation exists between chemokine axis CXCL12-CXCR4 and the pathogenesis, metastasis of epithelial ovarian cancer. The above axis may be an important pathogenic factor of epithelial ovarian cancer. And the antibody of CXCL12-CXCR4 is probably effective in its management.

[Extended-field intensity modulated radiation therapy and intra-cavitary brachytherapy combined with chemotherapy for stage Ib1-IVa cervical cancer with positive para-aortic lymph nodes].

OBJECTIVE: To investigate the treatment effects and toxicities of extended-field intensity modulated radiation therapy (EF-IMRT) and intra-cavitary brachytherapy combined with chemotherapy for stageIb1-IVa cervical cancer with positive para-aortic lymph nodes. METHODS: A total of 46 stage Ib1-IVa cervical cancer patients with positive para-aortic lymph nodes treated at Fudan University Shanghai Cancer Center between 2009 and 2011 were reviewed. Neoadjuvant, concomitant and adjuvant chemotherapy with paclitaxel and carboplatin were administrated for one cycle before radiation therapy, two cycles during radiation therapy or three cycles after radiation therapy. All patients received EF-IMRT and intra-cavitary brachytherapy. The positive lymph nodes received an additional boost dose. RESULTS: All patients received EF-IMRT to 50.4 Gy (1.8 Gy per fraction). Twenty-six patients was treated with boost dose of 6.0-8.0 Gy in 2.0 Gy per fraction to positive para-aortic lymph nodes. Thirty-seven patients received a positive para-aortic lymph nodes boost or (and) parametrial boost. All patient also received a high-dose-rate intra-cavitary brachytherapy at the point "A" dose of 20.0-30.0 Gy in 5.0 Gy per fraction. Total chemotherapy cycles were 189, and the average patient received 4.1 courses. Two cases (4%, 2/46) experienced grade III gastrointestinal toxicities, no patients suffered grade IV gastrointestinal toxicities. Fifteen cases (33%, 15/46) experienced grade III hematological toxicities, and 3(7%, 3/46) experienced grade IV hematological toxicities.Late grade III-IV toxicity was seen in 3 cases (7%, 3/46). The 3 year progression- free survival rate was 46.2%, and the 3 years overall survival rate was 61.2%. CONCLUSION: EF-IMRT and intra-cavitary brachytherapy combined with chemotherapy is safe and effective for stageIb1-IVa cervical cancer with positive para-aortic lymph nodes.

Decreased CD56+CD16-CD94+uNK cells in the mid-luteal phase in women with recurrent implantation failure are associated with IL-15 deficiency.

PROBLEM: Whether the abnormal development of uterine natural killer (uNK) cells contributes to women with recurrent implantation failure (RIF) remains unclear. METHOD OF STUDY: We characterized the development of uNK cells and peripheral blood NK cells (pbNK) in the mid-luteal phase in women with RIF (n = 31) and controls (n = 14) by flow cytometry. Endometrial IL-15 mRNA expression was studied by quantitative reverse transcription-PCR. The GSE58144 dataset was used to validate the correlation results. RESULTS: We found decreased proportions of stage 4 CD56+CD16-CD94+ uNK cells (median: 9.56% vs. 17.78%, P .014) and increased proportions of stage 6 CD56+CD16+CD57+ uNK cells (median: 1.54% vs. 0.74%, P = .020) in the mid-luteal endometrium of women with RIF compared to fertile women. We also found that there was no quantitative correlation between uNK cells and the corresponding pbNK cell subpopulations (P > .05). In addition, IL-15 mRNA levels in the mid-luteal endometrium were positively correlated with the proportion of CD56+ uNK cells (r = .392, P = .008), especially with stage 4 uNK cell populations (r = .408, P = .005). CONCLUSIONS: We showed that the proportion of stage 4 uNK cells decreased in the RIF group compared to controls, and the decrease in stage 4 uNK cells correlated positively with low IL-15 mRNA expression. We suggest that the reduced stage 4 uNK cells in women with RIF are associated with IL-15 deficiency.

Comparing the pregnancy outcomes of Re­ICSI and ICSI embryos in fresh ET and FET cycles.

Early rescue intracytoplasmic sperm injection (Re-ICSI) can prevent total fertilization failure (TFF) during conventional in vitro fertilization (IVF). However, the implantation rate of Re-ICSI embryos is lower than that of direct ICSI during fresh embryo transfer (ET). The aim of the present study was to investigate the effect of frozen ET (FET) after Re-ICSI. In the present retrospective study, primary infertility patients that underwent the first Re-ICSI and ICSI treatment, were studied. The clinical pregnancy rate, implantation rate, ectopic pregnancy, abortion rate and live birth rate were analyzed between the Re-ICSI and ICSI groups in fresh ET and FET cycles. The average age of patients between Re-ICSI and ICSI groups in fresh ET and FET cycles was (29.0±3.2 vs. 29.1±3.1, and 29.1±3.3 vs. 28.9±3.0), respectively (P>0.05). Compared with ICSI embryos, the clinical pregnancy, implantation and live birth rates of Re-ICSI embryos were lower in fresh ET cycles. By contrast, there were no significant differences in the pregnancy, implantation and live birth rates between the Re-ICSI and ICSI embryos during the FET cycles. Re-ICSI coupled with FET may overcome the impaired outcomes in fresh ET.

Knockdown of Porf-2 restores visual function after optic nerve crush injury.

Retinal ganglion cells (RGCs), the sole output neurons in the eyes, are vulnerable to diverse insults in many pathological conditions, which can lead to permanent vision dysfunction. However, the molecular and cellular mechanisms that contribute to protecting RGCs and their axons from injuries are not completely known. Here, we identify that Porf-2, a member of the Rho GTPase activating protein gene group, is upregulated in RGCs after optic nerve crush. Knockdown of Porf-2 protects RGCs from apoptosis and promotes long-distance optic nerve regeneration after crush injury in both young and aged mice in vivo. In vitro, we find that inhibition of Porf-2 induces axon growth and growth cone formation in retinal explants. Inhibition of Porf-2 provides long-term and post-injury protection to RGCs and eventually promotes the recovery of visual function after crush injury in mice. These findings reveal a neuroprotective impact of the inhibition of Porf-2 on RGC survival and axon regeneration after optic nerve injury, providing a potential therapeutic strategy for vision restoration in patients with traumatic optic neuropathy.

A strategy to control transmission of Schistosoma japonicum in China.

BACKGROUND: Schistosoma japonicum causes an infection involving humans, livestock, and snails and is a significant cause of morbidity in China. METHODS: We evaluated a comprehensive control strategy in two intervention villages and two control villages along Poyang Lake in the southeastern province of Jiangxi, where annual synchronous chemotherapy is routinely used. New interventions, implemented from 2005 through 2007, included removing cattle from snail-infested grasslands, providing farmers with mechanized farm equipment, improving sanitation by supplying tap water and building lavatories and latrines, providing boats with fecal-matter containers, and implementing an intensive health-education program. During the intervention period, we observed changes in S. japonicum infection in humans, measured the rate of infection in snails, and tested the infectivity of lake water in mice. RESULTS: After three transmission seasons, the rate of infection in humans decreased to less than 1.0% in the intervention villages, from 11.3% to 0.7% in one village and from 4.0% to 0.9% in the other (P<0.001 for both comparisons). The rate of infection in humans in control villages fluctuated but remained at baseline levels. In intervention villages, the percentage of sampling sites with infected snails decreased from 2.2% to 0.1% in one grassland area and from 0.3% to no infection in the other (P<0.001 for both comparisons). The rate of infection in mice after exposure to lake water decreased from 79% to no infection (P<0.001). CONCLUSIONS: A comprehensive control strategy based on interventions to reduce the rate of transmission of S. japonicum infection from cattle and humans to snails was highly effective. These interventions have been adopted as the national strategy to control schistosomiasis in China.

Genotypic differences in pod wall and seed growth relate to invertase activities and assimilate transport pathways in asparagus bean.

BACKGROUND AND AIMS: Coordination of sugar transport and metabolism between developing seeds and their enclosing fruit tissues is little understood. In this study the physiological mechanism is examined using two genotypes of asparagus bean (Vigna unguiculata ssp. sesquipedialis) differing in pod wall and seed growth rates. Pod growth dominates over seed growth in genotype 'Zhijiang 121' but not in 'Zhijiang 282' in which a 'bulging pod' phenotype is apparent from 8 d post-anthesis (dpa) onward. METHODS: Seed and pod wall growth rates and degree of pod-bulging were measured in the two genotypes together with assays of activities of sucrose-degrading enzymes and sugar content in pod wall and seed and evaluation of cellular pathways of phloem unloading in seed coat using a symplasmic fluorescent dye, 5(6)-carboxyfluorescein (CF). KEY RESULTS: Activities of cell wall, cytoplasmic and vacuolar invertases (CWIN, CIN and VIN) were significantly smaller in pod walls of '282' than in '121' at 10 dpa onwards. Low INV activities were associated with weak pod wall growth of '282'. In seed coats, CF was confined within the vasculature in '282' but moved beyond the vasculature in '121', indicating apoplasmic and symplasmic phloem unloading, respectively. Higher CWIN activity in '282' seed coats at 6-8 dpa correlated with high hexose concentration in embryos and enhanced early seed growth. However, CWIN activity in '282' decreased significantly compared with '121' from 10 dpa onwards, coinciding with earlier commencement of nuclei endoreduplication in their embryos. CONCLUSIONS: The study shows genotypic differences between 'bulging pod' and 'non-bulging' phenotypes of asparagus bean in sucrose metabolism in relation to the pathway of phloem unloading in developing seed coats, and to pod and seed growth. Low INV activity in pod wall corresponds to its shortened and weak growth period; by contrast, the apoplasmic path in the seed coat is associated with high CWIN activity and strong early seed growth.