Maternal and neonatal complications after IVF/ICSI-fresh embryo transfer in low-prognosis women under the POSEIDON criteria: a retrospective cohort study.

BACKGROUND: Several studies on pregnancy complications of poor ovarian response (POR) patients did not draw a consistent conclusion. The POSEIDON criteria introduces the concept of "low prognosis" and divides POR patients into four groups based on age, AFC and AMH for individualized management. We analyzed low-prognosis population and patients with regular ovarian response, compared maternal and neonatal complications and discussed the relevant risk factors. METHODS: A retrospective cohort study was conducted of females who achieved a singleton clinical pregnancy after IVF / ICSI-fresh embryo transfer in a single center from January 2014 to March 2019. Participants with low prognosis, as defined by the POSEIDON criteria, were enrolled in the study groups. The controls were defined as AFC ≥ five and number of retrieved oocytes > nine. Maternal and neonatal complications were compared among those groups. RESULTS: There were 2554 cycles in POSEIDON group 1, 971 in POSEIDON group 2, 141 in POSEIDON group 3, 142 in POSEIDON group 4, and 3820 in Control. Univariate analysis roughly showed that Groups 2 and 4 had an increased tendency of pregnancy complications. Multi-variable generalized estimating equations (GEE) analysis showed that the risks of GDM, total pregnancy loss, and first-trimester pregnancy loss in Groups 2 and 4 were significantly higher than in Control. The risk of hypertensive disorders of pregnancy (HDP) in Groups 2 and 3 increased, and Group 4 had an increased tendency without statistical significance. After classification by age, GEE analysis showed no significant difference in risks of all complications among groups ≥ 35 years. In patients < 35 years, the risk of HDP in POSEIDON group 3 was significantly higher than in controls (< 35 years), and there was no significant increase in the risk of other complications. CONCLUSION: Compared to patients with regular ovarian response, low-prognosis population have increased tendency of maternal and neonatal complications. In low-prognosis patients, advanced age (≥ 35 years) might be the predominant risk factor for pregnancy complications. In those < 35 years, poor ovarian reserve could contribute to HDP.

Effect of dehydroepiandrosterone administration before in vitro fertilization on the live birth rate in poor ovarian responders according to the Bologna criteria: A randomised controlled trial.

OBJECTIVE: To evaluate the effect of dehydroepiandrosterone (DHEA) pre-treatment before in vitro fertilization and embryo transfer (IVF-ET) on the live birth rate in infertile women with poor ovarian response (POR) defined according to the Bologna criteria. DESIGN: A randomized, double-blind, placebo-controlled trial. SETTING: Nine reproductive medical centers in China. POPULATION: A total of 821 participants with POR defined according to the Bologna criteria were enrolled in the study between April 2016 and December 2018. METHODS: Eligible participants were randomly assigned to receive either DHEA (n = 410) or placebo (n = 411) treatments for 4-12 weeks prior to IVF-ET, in a 1:1 ratio. MAIN OUTCOME MEASURES: Live birth rate after the first embryo transfer. RESULTS: Thirty-six (8.8%) of 410 women in the DHEA group and 37 (9.0%) of 411 women in the placebo group had a live birth, with no significant difference observed between groups (relative risk, 0.98, 95% CI, 0.63-1.51; p = 0.911). There were no significant differences in the number of retrieved oocytes, and the rates of clinical pregnancy, pregnancy loss, and cumulative live births between the two groups. CONCLUSIONS: DHEA administration prior to IVF-ET had no beneficial effect on the live birth rate relative to placebo in women with POR defined according to the Bologna criteria. TWEETABLE ABSTRACT: No benefit was found in poor ovarian responders who received DHEA administration prior to IVF.

Two New Types of Homodiploid Fish and Polyploid Hybrids Derived from the Distant Hybridization of Female Koi Carp and Male Bighead Carp.

Bighead carps  (Hypophthalmichthys nobilis) and silver carps (Hypophthalmichthys molitrix) represent an important component of freshwater ichthiofauna in its native range, though they might become mass propagation in other systems (North America) and the reason of concern for fisheries management. Therefore, understanding their reproductive traits and particularly in the context of hybridization with other cyprinids was of value to explain their rapid propagation as well as potential benefits for aquaculture due to their unique diet, behavior, growth potential, and tolerance to deteriorating environmental conditions in freshwater ecosystems. Distant hybridization is an effective tool to create different ploidy offspring with changed phenotypes and genotypes. In this study, we reported distant hybridization of female koi carp (Cyprinus carpio haematopterus, KOC, 2n = 100) × male bighead carp (Hypophthalmichthys nobilis, BIC, 2n = 48) and the spontaneous occurrence of two new "crucian" carp-like homodiploid fish (2nGCC-L; 2nCCC-L; 2n = 100), a new type of triploid hybrid (3nKB, 3n = 124), and a new type of tetraploid hybrid (4nKB, 4n = 148). The body color of 2nGCC-L and 2nCCC-L were gray and multicolor, respectively. Both phenotypes were similar to the crucian carp (Carassius auratus). The difference was that their heads were rounder than those of the crucian carp and they had higher backs. Compared with the KOC with two pairs of barbels and BIC without barbel, 2nGCC-L, 2nCCC-L, and 4nKB had no barbel, but 3nKB had one pair of barbels. Microsatellite patterns and 5S rDNA sequences confirmed that 2nGCC-L, 2nCCC-L, and 3nKB were of hybrid origin. In regard to feeding, KOC was omnivorous and BIC was a typical filter-feeder. However, the 2nGCC-L, 2nCCC-L, and 3nKB were omnivorous. The formation of four kinds of new offspring is a groundbreaking finding in fish genetic breeding and evolutionary biology.

Hox genes reveal variations in the genomic DNA of allotetraploid hybrids derived from Carassius auratus red var. (female) × Cyprinus carpio L. (male).

BACKGROUND: Hox transcription factors are master regulators of animal development. Although highly conserved, they can contribute to the formation of novel biological characteristics when modified, such as during the generation of hybrid species, thus potentially serving as species-specific molecular markers. Here, we systematically studied the evolution of genomic sequences of Hox loci in an artificial allotetraploid lineage (4nAT, 4n = 200) derived from a red crucian carp (♀, RCC, 2n = 100) × common carp (♂, CC, 2n = 100) cross and its parents (RCC and CC). RESULTS: PCR amplification yielded 23 distinct Hox gene fragments from 160 clones in 4nAT, 22 fragments from 90 clones in RCC, and 19 fragments from 90 clones in CC. Sequence alignment of the HoxA3a and HoxC10a genes indicated both the inheritance and loss of paternal genomic DNA in 4nAT. The HoxA5a gene from 4nAT consisted of two subtypes from RCC and two subtypes from CC, indicating that homologous recombination occurred in the 4nAT hybrid genome. Moreover, 4nAT carried genomic pseudogenization in the HoxA10b and HoxC13a loci. Interestingly, a new type of HoxC9a gene was found in 4nAT as a hybrid sequence of CC and RCC by recombination in the intronic region. CONCLUSION: The results revealed the influence of Hox genes during polyploidization in hybrid fish. The data provided insight into the evolution of vertebrate genomes and might be benefit for artificial breeding programs.

The Hybrid Genome of a New Goldfish-Like Fish Lineage Provides Insights Into the Origin of the Goldfish.

Distant hybridization leads to obvious changes in genotypes and phenotypes, giving rise to species with novel capabilities. However, the fusion of distinct genomes also polymerizes the DNA or gene variations that occur during the course of evolution. Knowledge of the early stages of post-hybridization evolution is particularly important. Here, we investigated the full-length (FL) transcriptomes and the sequences resulting from the genome resequencing of the red crucian carp-like homodiploid fish (RCC-L) and goldfish-like homodiploid fish (GF-L) derived from the interspecific hybridization of koi carp (KOC) and blunt snout bream (BSB) to provide molecular evidence for the hybrid origin of the goldfish (GF). We compared the orthologous genes in the transcriptomes of RCC-L and GF-L with those of KOC and BSB. We also mapped the orthologous genes to the common carp (CC) and BSB genomes and classified them into eight gene patterns in three categories (chimaera, mutant, and biparental origin genes). The results showed that 48.20% and 46.50% of the genes were chimaera and that 3.70% and 8.30% of the genes were mutations of orthologous genes in RCC-L and GF-L, respectively. In RCC-L and GF-L, 63.70% and 68.20% of the genetic materials were from KOC, and 12.30% and 11.90% of the genetic materials were from BSB. The sequences from the genome resequencing of RCC-L and GF-L were mapped to the genome sequences of CC and BSB, revealing that the similarities of both RCC-L and GF-L to the CC genome (92.52%, 90.18%) were obviously higher than to the BSB genome (50.33%, 49.18%), supporting the suggestion that the genomes of both RCC-L and GF-L were mainly inherited from KOC but had some DNA fragments from BSB. Overall, our results provide molecular biological evidence for the hybrid origin of red crucian carp (RCC) and GF.

Variations in the Mitochondrial Genome of a Goldfish-Like Hybrid [Koi Carp (♀) × Blunt Snout Bream (♂)] Indicate Paternal Leakage.

Previously, a homodiploid goldfish-like fish (2n = 100; GF-L) was spontaneously generated by self-crossing a homodiploid red crucian carp-like fish (2n = 100; RCC-L), which was in turn produced via the distant hybridization of female koi carp (Cyprinus carpio haematopterus, KOC, 2n = 100) and male blunt snout bream (Megalobrama amblycephala, BSB, 2n = 48). The phenotypes and genotypes of RCC-L and GF-L differed from those of the parental species but were similar to diploid red crucian carp (2n = 100; RCC) and goldfish (2n = 100; GF), respectively. We sequenced the complete mitochondrial DNAs (mtDNAs) of the KOC, BSB, RCC-L, GF-L, and subsequent generations produced by self-crossing [the self-mating offspring of RCC-L (RCC-L-F2) to the self-mating offspring of RCC-L-F2 (RCC-L-F3) and the self-mating offspring of GF-L (GF-L-F2)]. Paternal mtDNA fragments were stably embedded in the mtDNAs of both lineages, forming chimeric DNA fragments. In addition to these chimeras, several nucleotide positions in the RCC-L and GF-L lineages differed from the parental bases, and were instead identical with RCC and GF, respectively. Moreover, RCC-L and GF-L mtDNA organization and nucleotide composition were more similar to those of RCC and GF, respectively, compared to parental mtDNA. Finally, phylogenetic analyses indicated that RCC-L and GF-L clustered with RCC and GF, not with the parental species. The molecular dating time shows that the divergence time of KOC and GF was about 21.26 Mya [95% highest posterior density (HPD): 24.41-16.67 Mya], which fell within the period of recent. The heritable chimeric DNA fragments and mutant loci identified in the mtDNA of the RCC-L and GF-L lineages provided important evidence that hybridizations might lead to changes in the mtDNA and the subsequent generation of new lineages. Our findings also demonstrated for the first time that the paternal mtDNA was transmitted into the mtDNA of homodiploid lineages (RCC-L and GF-L), which provided evidence that paternal DNA plays a role in inherited mtDNA. These evolutionary analyses in mtDNA suggest that GF might have diverged from RCC after RCC diverged from koi carp.

Krüppel-like factor 2 inhibits hepatocarcinogenesis through negative regulation of the Hedgehog pathway.

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. The most important reason for the occurrence of HCC is hepatitis C or B infection. Moreover, genetic factors play an important role in the tumorigenesis of HCC. Here, we demonstrated that Krüppel-like factor 2 (KLF2) expression was downregulated in HCC samples compared with adjacent tissues. Additionally, KLF2 was shown to inhibit the growth, migration and colony-formation ability of liver cancer cells. Further mechanistic studies revealed that KLF2 can compete with Gli1 for interaction with HDAC1 and restrains Hedgehog signal activation. Together, our results suggest that KLF2 has potential as a diagnostic biomarker and therapeutic target for the treatment of HCC.

Use of Walnut Shell Powder to Inhibit Expression of Fe(2+)-Oxidizing Genes of Acidithiobacillus Ferrooxidans.

Acidithiobacillus ferrooxidans is a Gram-negative bacterium that obtains energy by oxidizing Fe(2+) or reduced sulfur compounds. This bacterium contributes to the formation of acid mine drainage (AMD). This study determined whether walnut shell powder inhibits the growth of A. ferrooxidans. First, the effects of walnut shell powder on Fe(2+) oxidization and H⁺ production were evaluated. Second, the chemical constituents of walnut shell were isolated to determine the active ingredient(s). Third, the expression of Fe(2+)-oxidizing genes and rus operon genes was investigated using real-time polymerase chain reaction. Finally, growth curves were plotted, and a bioleaching experiment was performed to confirm the active ingredient(s) in walnut shells. The results indicated that both walnut shell powder and the phenolic fraction exert high inhibitory effects on Fe(2+) oxidation and H⁺ production by A. ferrooxidans cultured in standard 9K medium. The phenolic components exert their inhibitory effects by down-regulating the expression of Fe(2+)-oxidizing genes and rus operon genes, which significantly decreased the growth of A. ferrooxidans. This study revealed walnut shell powder to be a promising substance for controlling AMD.

[Observation of the efficacy of allergen blocking nasal spray in patients with rhinitis sicca].

OBJECTIVE: To observe the efficacy of allergen blocking nasal spray (ABNS) , combined with seawater spray (SS) and myrtol standardized capsules (MSS), in patients with rhinitis sicca. METHOD: Patients diagnosed as rhinitis sicca were randomly divided into 2 groups: ABNS+SS group and SS group. In ABNS+SS group, patients used ABNS and SS four times per day and MSS twice per day. In SS group, patients used the same medicine except ABNS. Both group were observed for 14 days. The visual analog scale (VAS) of dryness, the endoscopy evaluation score (EES) and the tolerability of the spray were compared between the 2 groups. RESULT: There were 30 patients included in each group. The VAS and EES were improved in both groups after 2 weeks' treatment. The improvement of VAS and EES in ABNS+SS group was significantly superior to SS group (VAS: P < 0.01, EES: P < 0.05). There were only 2 patients complaint of slight discomfort when using ABNS, which did not disturb the treatment. CONCLUSION: There is good efficacy of allergen blocking nasal spray (ABNS), combined with seawater spray (SS) and myrtol standardized capsules (MSS), in patients with rhinitis sicca.

[Health economics analysis of specific immunotherapy in allergic rhinitis accompanied with asthma].

OBJECTIVE: To investigate the cost-effectiveness of standardized specific immunotherapy (SIT) for allergic rhinitis patients accompanied with asthma (ARAS) in China. METHOD: Forty ARAS patients sensitized with house dust mite (HDM) were administered with SIT (SIT group) or merely medicine treatment (control group). Alutard dermatophagoides pteronyssinus vaccine from ALK company was used for immunotherapy. The usage of symptom control medicine was according to the ARIA and GINA guideline. Cost-effectiveness ratio (CER) and Incremental cost-effectiveness ratio(ICER) analysis was conducted. The effectiveness was measured in terms of symptom scores, quality of life, objective improvement of rhinitis and asthma. Sensitive analysis was conducted to verify the stability of the results. RESULT: The cost of SIT group for 1 year (6578 yuan) was higher than that of control group (1733.3 yuan), while the cost-effectiveness ratio and incremental cost-effectiveness ratio of SIT group were significant better than that of control group in all items. CER was 1686.7 yuan in SIT group compared with 3466.6 yuan in control group for nasal symptom scores, 4698.6 yuan in SIT group compared with 5777.8 yuan in control group for asthma symptom scores, 3462.1 yuan in SIT group compared with 8666.7 yuan in control group. The sensitive analysis of the price 10 percent higher or lower showed the same results. CONCLUSION: The cost-effectiveness of specific immunotherapy (SIT) for mite sensitized ARAS patients was better than that of merely medicine treatment.

[Efficacy evaluation of specific immunotherapy with standardized dermatophagoides pteronyssinus extract for allergic rhinitis accompanied with asthma].

OBJECTIVE: To evaluate the efficacy of specific immunotherapy (SIT) with standardized dermatophagoides pteronyssinus extract for allergic rhinitis (AR)accompanied with asthma. METHOD: One hundred and fifty-five patients (40 AR with asthma, AR & asthma) in accordance with the inclusion criteria of SIT, were allocated to receive standardized Dermatophagoides pteronyssinus extract (SIT group, n = 89) or medical treatment (control group, n = 66). AR with or without asthma was observed separately. Symptom and medicine scores, quality of life were recorded and analyzed before and after 1 year treatment. Side effects were registered. Subjective evaluation of symptoms was made by the patients. RESULT: Rhinitis and asthma symptom scores, medicine scores and quality of life were greatly improved in SIT group of AR & asthma after 1 year, which were not significant changed in control group except for medicine scores. The subjective evaluation of symptoms was also significantly improved in SIT group. In patients of AR without asthma, the symptom scores, medicine scores and quality of life were both improved. The SIT group improved greater than that of control group. CONCLUSION: The clinical efficacy of patients with AR & asthma was not good with simple medical treatment, while great clinical efficacy could be acquired with SIT.

[Age features of the allergens in allergic rhinitis patients of different age in Hubei area].

OBJECTIVE: To investigate the distribution of positive allergens in patients with allergic rhinitis and the discrepancy among different age group. METHOD: Skin prick tests were done to 2 808 allergic rhinitis patients, the major allergens of local area were tested with standard allergens. Data was analyzed with age and allergens. RESULT: Dermatophagoides pteronyssinus and dermatophagoides farinae had the highest positivity among all allergens (91.03%, 86.47%). Other important allergens were cockroach (19.55%), ragweed (15.63%) and mugwort (14.13%) subsequently. The distribution of major allergens was variable among different age group. The positivity of mold mixture I was much higher in 3-9 years old group than other age group. Positive percentage of ragweed and mugwort allergens were increased with age growing. Positive ratio of cockroach which was higher in the elder than that in the younger, was highest in 30-39 years old group. Ratio in patients with single allergen positive decreased with age growing. CONCLUSION: House dust mite was the most important allergen of the local area, the distribution of positive allergens was variable in different age group.

[Efficacy evaluation of polysaccharide nucleic acid-fraction of BCG on vasomotor rhinitis].

OBJECTIVE: To investigate the efficacy and safety of polysaccharide nucleic acid-fraction (BCG-PSN) in the treatment of vasomotor rhinitis. METHOD: Sixty patients were randomly divided into BCG-PSN group (n = 30) and control group (n = 30). The patients in BCG-PSN group were administered with BCG-PSN 1.0 mg twice a week for two months, and intranasal azelastine was used if needed. The patients in control group were administered with intranasal azelastine solely twice a day, which could be decreased with the symptom relief. Follow-up was 6 months. Symptom and medication scores were recorded. Side effects were registered. RESULT: The symptom and medication scores of BCG-PSN group were significantly lower than that of control group (P < 0.01) after BCG-PSN treatment. There was no significant difference in symptom score between the two groups at 6 months after BCG-PSN treatment (P > 0.05), while the medication score of BCG-PSN group was still much lower than that of control group (P < 0.01). No serious adverse events were reported in BCG-PSN group except for local pain on the injection place in one patient. CONCLUSION: BCG-PSN is effective and safe in the treatment of vasomotor rhinitis.

[The expression of serum IL-10,12,13,16 in patients with allergic rhinitis and vasomotor rhinitis].

OBJECTIVE: To study the role of serum IL-10, 12, 13, 16 in patients with allergic rhinitis and vasomotor rhinitis. METHOD: The serum levels of IL-10, 12, 13, 16 were measured by ELISA in 30 cases of allergic rhinitis, 25 cases of vasomotor rhinitis and 20 healthy people. RESULT: The level of IL-12 in allergic rhinitis was (170.33 +/- 90.58) ng/L, which was significantly lower than that of normal controls [(376.69 +/- 140.70) ng/L, P < 0.01]. The levels of IL-13 and IL-16 in allergic rhinitis were (408.51 +/- 189.68) ng/L and (151.53 +/- 63.56) ng/L, which were significantly higher than those of normal controls [(151.92 +/- 85.08) ng/L, (60.65 +/- 32.45) ng/L, P < 0.01]. There were no significant difference of levels of IL-10, 13, 16 between vasomotor rhinitis and normal controls, while the level of IL-12 in vasomotor rhinitis was lower than that of normal controls [(196.03 +/- 96.31) ng/L vs. (376.69 +/- 140.70) ng/L, P < 0.01]. It was suggested that IL-10 had positive correlation with IL-12 (r = 0.73, P < 0.01), and IL-13 had positive correlation with IL-16 (r = 0.94, P < 0.01). CONCLUSION: The imbalance of IL-12, IL-13 and IL-16 play crucial roles of regulation in the onset and developing of allergic rhinitis. Further research is needed on the role of IL-12 in vasomotor rhinitis.

[Safety analysis of Allergovit immunotherapy in patients of allergic rhinitis].

OBJECTIVE: To analyse the safety of Allergovit immunotherapy in patients of allergic rhinitis. METHOD: Two hundred and fifty-six patients with allergic rhinitis received Allergovit immunotherapy, their local and systemic side-effect were observed, recorded and analyzed during the treatment. RESULT: The number of patients who got local side-effect was 84 cases, the percent of local side-effect was 4.45%; the number of patients who got systemic side-effect were 21 cases, the percent of systemic side-effect was 0.31%. Both side-effects were slight. CONCLUSION: Allergovit immunotherapy is a safe and feasible choice for allergic rhinitis. While the schedule fit for Chinese or individually is needed to be mended in practice.

[The study of the relationship between obstructive sleep apnea syndrome and positional nasal resistance].

OBJECTIVE: To study the nasal resistance in different position and its possible relationship to obstructive sleep apnea syndrome (OSAS). METHOD: The positional rhinomanometry and the detection of polysomnography were performed in 14 normal subjects, 20 snoring patients and 40 patients with OSAS. RESULT: The study reveals that: 1. the nasal resistance in seated position and in supine position of the patients with OSAS but without nasal diseases or snoring patients without nasal disease were higher than that of the normal group (P < 0.05). 2. The nasal resistance in seated position and in supine position of the patients with both OSAS and nasal disease were higher than that of the snoring patients with nasal disease (P < 0.05). 3. The nasal resistance in supine position was higher than the nasal resistance in seated position in all the groups (P < 0.05), even in the patients with OSAS (P < 0.01). 4. The AHI, waken intervals, snoring index of the patients both with OSAS and nasal disease were higher than those of the patients only with OSAS. CONCLUSION: Nasal resistance increased in the patients with snoring or OSAS and increased more in the supine position. Nasal resistance may be an important factor in the pathogenesis of OSAS.

[Choice of the methods for inferior turbinectomy].

OBJECTIVE: To make clear the indications for each kind of inferior turbinectomy and to find out the best way of inferior turbinectomy. METHOD: The nasal resistances in pre-operation and post-operation were examined with rhinomanometer in 97 cases. The time of recovery, the symptoms remained and the complications after operation were recorded. RESULT: "Functional" inferior turbinectomy is characterized for its mild postoperation reaction, quick recovery and good therapeutic effect whereas the partial inferior turbinectomy is characterized for its serious reaction, bleeding and dryness after operation. CONCLUSION: There is a definite indication for each kind of inferior turbinectomy, but the indication of " functional" inferior turbinectomy is wide.