Impact of Recombinant Human Granulocyte Colony-Stimulating Factor Combined with Aspirin on Clinical Pregnancy Outcomes and Endometrial Receptivity in Patients with Recurrent Abortion: A Retrospective Study.

Objective: This study investigates the impact of recombinant human granulocyte colony-stimulating factor (rhG-CSF) and aspirin on endometrial receptivity and clinical pregnancy outcomes in individuals with a history of recurrent abortions. Methods: In this retrospective study, 131 individuals with recurrent abortions treated at our facility from July 2019 to December 2020 were split into two groups: mixed therapy and control. The mixed therapy group received aspirin and rhG-CSF, while the control group had no specific treatment. Primary endpoint: live birth rate; secondary: pregnancy rate at 20 weeks. We also evaluated abortion rates, newborn weight, pre-eclampsia, premature delivery, fetal/newborn congenital malformations, and maternal drug adverse reactions. Additionally, we analyzed endometrial blood flow three weeks post-treatment. Results: The analysis encompassed 131 individuals, with 65 in the control group and 66 in the mixed therapy group. Notably, the mixed therapy group (n = 54) exhibited a markedly higher live birth rate than the control group (P < .05). In terms of medication-related side effects, the control group showed no adverse reactions, while the mixed therapy group reported mild effects (skin itching in three cases, leukocytosis in seven, and bone pain in one case) that did not significantly impact outcomes. Pre-treatment, the mixed therapy group had a notably lower resistive index, pulsatility index, and systolic-to-diastolic ratio compared to the control group, with statistical significance (P < .05). The control group's indices remained unchanged (P > .05). Conclusions: In women with a history of recurrent abortions, the administration of recombinant human granulocyte colony-stimulating factor and aspirin can effectively and safely improve live birth rates. This improvement may be associated with enhanced endometrial receptivity.

Comprehensive Serial Treatment of Treacher Collins Syndrome.

OBJECTIVE: To discuss and summarize the comprehensive serial surgical treatment of Treacher Collins syndrome. MATERIALS AND METHODS: From September 2012 to January 2020, 12 patients with Treacher Collins syndrome were treated by autologous fat graft, mandibular distraction osteogenesis, orbitozygomatic reconstruction with calvarial external lamina, orthognathic surgery combined with postoperative orthodontics, transplantation of upper eyelid orbicularis myocutaneous flap, lateral canthal ligament reduction, and other methods. The authors evaluated the postoperative improvement, summarized experiences, and reviewed literatures about the comprehensive serial treatment of Treacher Collins syndrome. RESULTS: All patients showed significant improvement in appearance and function, and no complications were found during the follow-up period of 5 months to 3 years. CONCLUSIONS: The deformities of Treacher Collins syndrome involves multiple craniofacial region, and only by formulating comprehensive serial treatment strategies according to the malformation characteristics of different patients can the best effect be achieved.

Application and Accuracy of Craniomaxillofacial Plastic Surgery Robot in Congenital Craniosynostosis Surgery.

OBJECTIVE: The objective of this study was to observe the accuracy and security of the craniomaxillofacial plastic surgery robot in congenital craniosynostosis surgery and to enhance and improve its performance. MATERIALS AND METHODS: We performed model surgical experiments on computed tomography data of 5 children with congenital craniosynostosis who were diagnosed and treated in our hospital, and model surgical experiments and animal experiments on the skulls of 3 Bama minipigs. RESULTS: There was no statistically significant difference shown either in model experiments or animal experiments in comparing the actual operation with the surgical simulation and inside the groups ( P >0.05). CONCLUSIONS: The craniomaxillofacial plastic surgery robot has achieved good security and accuracy in model surgery and animal experiments. Further studies are needed to be conducted to confirm its security and accuracy and to continuously improve and refine the robot's performance.

A Novel and Simplified Parameter for Mandible Angle Asymmetry Evaluation in Chinese Females.

AIM: To develop a novel and simplified parameter for mandible angle asymmetry (MAA) evaluation for facial countering surgeries in Chinese females. MATERIALS AND METHODS: A total of 250 craniofacial computer tomography of healthy Chinese individuals were collected in this retrospective study. Mimics 21.0 was applied for 3-dimensional anthropometry. The Frankfort and Green planes were set as referenced vertical and horizontal planes for measuring the distances to gonions. The differences in both orientations were analyzed to verify the symmetry. Mandible angle asymmetry (∠Go-N-ANS, MAA) which comprehensively represented horizontal and vertical placements was defined qas the novel parameter for asymmetric evaluation and quantitative analysis was conducted to generate referenced materials. RESULTS: Mandible angle asymmetry was divided into horizontal and vertical asymmetry. No significant differences were found in either horizontal or vertical orientations. The horizontal difference was 3.09±2.52 mm, the reference range was (0.28, 7.54) mm, whereas the±ertical difference was 2.59±2.48 mm, the reference range was (0.12, 6.34) mm. The difference of MAA was 1.74±1.30 degrees, and the reference range was (0.10,4.32）degrees. CONCLUSION: This study provided a novel parameter for asymmetric evaluation in the mandible angle region through quantitative 3-dimensional anthropometry, arousing plastic surgeons' attention to both aesthetics and symmetry in facial contouring surgery.

Accuracy and Security Analysis of a Cranio-Maxillofacial Plastic Surgery Robot Equipped with Piezosurgery in Genioplasty.

ABSTRACT: This study aims to verify that the craniofacial plastic surgery robot with piezosurgery is more accurate and safer than traditional operations in genioplasty. This study chose data from the Digital Plastic Surgery of Plastic Surgery Hospital in the Chinese Academy of Medical Sciences and Peking Union Medical College. The CT data of the patient's skull were reconstructed in the software, and the authors designed the measurement index. The surgical plan was designed as an ideal scheme (control group). Patients underwent traditional surgery according to the preoperative surgery plan (clinical group). Guided by surgical navigation, the osteotomy was operated on patients' same size plaster model using the surgery robot equipped with a piezosurgery (robot group). At last, the accuracy was calculated by CT data. There was no significant difference between the robotic group and control groups in the postoperative measurement index (P < 0.05). There was no significant difference between the robotic group and the control group (P > 0.05) in the line of osteotomy, but there was a significant difference between the clinical group and the control group in the line of the osteotomy.

Chromosome aneuploidy analysis in embryos derived from in vivo and in vitro matured human oocytes.

BACKGROUND: In vitro oocyte maturation (IVM) is being increasingly approached in assisted reproductive technology (ART). This study aimed to evaluate the quality of embryos generated by in-vitro matured immature follicles, as a guideline for further clinical decision-making. METHODS: A total of 52 couples with normal karyotypes underwent in vitro fertilization, and 162 embryos were donated for genetic screening. Embryos in IVF group were generated by mature follicles retrieved during gonadotrophin-stimulated in vitro fertilization (IVF) cycles. And embryos in IVM group were fertilized from IVM immature oocytes. RESULTS: The average age of the women was 30.50 ± 4.55 years (range 21-42 years) with 87 embryos from IVF group and 75 embryos from IVM group. The rate of aneuploid with 28 of the 87 (32.2%) embryos from IVF group and 21 of the 75 (28%) embryos from IVM group, with no significant difference. The frequency of aneuploid embryos was lowest in the youngest age and increased gradually with women's age, whether in IVF group or IVM group and risen significantly over 35 years old. The embryos with morphological grade 1 have the lowest aneuploidy frequency (16.6%), and increase by the grade, especially in IVF group. In grade 3, embryos in IVM group were more likely to be euploid than IVF group (60% vs 40%, respectively). CONCLUSIONS: IVM does not affect the quality of embryos and does not increase the aneuploidy rate of embryos. It is clinically recommended that women more than 35 years have a high aneuploidy rate and recommended to test by PGS (strongly recommended to screened by PGS for women more than 40 years). Women aged less than 35 years old for PGS according to their physical and economic conditions. Embryo with poor quality is also recommended to test by PGS, especially for grade III embryos.

One-Half Wedge Osteotomy Genioplasty for Correction of Chin Deviation Based on Three-Dimensional Computed Tomography Measurements and Simulation.

ABSTRACT: Conventional operations correcting chin deviations mainly rely on the observation and experience of the surgeons during the operation. We have created a new surgical method, one-half wedge osteotomy genioplasty (1/2WOG), that combines three-dimensional computed tomography measurements and simulation. This study evaluated the clinical effect of chin deviation correction with the 1/2WOG method. A total of 38 patients (15 men and 23 women) who underwent 1/2WOG between October 2019 and October 2014 were evaluated. The chin deviation angle and distance, and partial chin deformity were measured preoperatively using three-dimensional computed tomography data. Precise calculations and osteotomy lines were achieved by preoperative simulation. All patients underwent the same surgery by the same surgical team. The clinical effect of 1/2WOG was evaluated according to the preoperative and postoperative data and patient satisfaction. All 38 patients achieved satisfactory aesthetic results without major complications such as chin nerve injury or bone nonunion. Eight patients occured numbness of the lower lip after surgery; at 6-month follow-up, the numbness was reduced in 2 patients and disappeared in 6 patients. Compared with preoperative data, the chin deviation angle, chin deviation distance, and gonion-menton difference were significantly reduced postoperatively. During the 12-month follow-up, the patient satisfaction rate reached 90%. We conclude that chin deviation can be improved by 1/2WOG. The combination of digital technology measurements and simulation can increase the accuracy of the osteotomy line design, thus reducing surgical trauma and increasing patient satisfaction, which is worthy of clinical promotion.

Protective effects of melatonin on male fertility preservation and reproductive system.

Melatonin is a ubiquitous indoleamine hormone synthesized primarily by the pineal gland. Diverse biological actions of melatonin involve quite complex mechanisms via its membrane receptors. More recently, studies have focused on the role of melatonin in male fertility preservation and male reproductive system. The protective effects of melatonin on immature testicular tissue freshness and activity maintenance and the preservation of sperm and spermatogonial stem cells (SSCs) have attracted considerable attention in recent years. Furthermore, since melatonin has strong antioxidant and anti-apoptotic properties, researchers have examined its potential role in male reproductive system. In this article, recent progress regarding melatonin's effects on male fertility preservation and its potential role is reviewed.

Regulation of blood-testis barrier assembly in vivo by germ cells.

The assembly of the blood-testis barrier (BTB) during postnatal development is crucial to support meiosis. However, the role of germ cells in BTB assembly remains unclear. Herein, KitW/KitWV mice were used as a study model. These mice were infertile, failing to establish a functional BTB to support meiosis due to c-Kit mutation. Transplantation of undifferentiated spermatogonia derived from normal mice into the testis of KitW/KitWV mice triggered functional BTB assembly, displaying cyclic remodeling during the epithelial cycle. Also, transplanted germ cells were capable of inducing Leydig cell testosterone production, which could enhance the expression of integral membrane protein claudin 3 in Sertoli cells. Early spermatocytes were shown to play a vital role in directing BTB assembly by expressing claudin 3, which likely created a transient adhesion structure to mediate BTB and cytoskeleton assembly in adjacent Sertoli cells. In summary, the positive modulation of germ cells on somatic cell function provides useful information regarding somatic-germ cell interactions.-Li, X.-Y., Zhang, Y., Wang, X.-X., Jin, C., Wang, Y.-Q., Sun, T.-C., Li, J., Tang, J.-X., Batool, A., Deng, S.-L., Chen, S.-R., Cheng, C. Y., Liu, Y.-X. Regulation of blood-testis barrier assembly in vivo by germ cells.

Melatonin Regulates the Synthesis of Steroid Hormones on Male Reproduction: A Review.

Melatonin is a ubiquitous molecule and exhibits different effects in long-day and short-day breeding animals. Testosterone, the main resource of androgens in the testis, is produced by Leydig cells but regulated mainly by cytokine secreted by Sertoli cells. Melatonin acts as a local modulator of the endocrine activity in Leydig cells. In Sertoli cells, melatonin influences cellular proliferation and energy metabolism and, consequently, can regulate steroidogenesis. These suggest melatonin as a key player in the regulation of steroidogenesis. However, the melatonin-induced regulation of steroid hormones may differ among species, and the literature data indicate that melatonin has important effects on steroidogenesis and male reproduction.

EZH2 deletion promotes spermatogonial differentiation and apoptosis.

Spermatogenesis is crucial for male fertility and is therefore tightly controlled by a variety of epigenetic regulators. However, the function of enhancer of zeste homolog 2 (EZH2) in spermatogenesis and the molecular mechanisms underlying its activity remain poorly defined. Here, we demonstrate that deleting EZH2 promoted spermatogonial differentiation and apoptosis. EZH2 is expressed in spermatogonia, spermatocytes and round and elongated spermatids from stage 9 to 11 but not in leptotene and zygotene spermatocytes. Knocking down Ezh2 in vitro using a lentivirus impaired self-renewal in spermatogonial stem cells (SSCs), and the conditional knockout of Ezh2 in spermatogonial progenitors promoted precocious spermatogonial differentiation. EZH2 functions to balance self-renewal and differentiation in spermatogonia by suppressing NEUROG3 and KIT via a direct interaction that is independent of its histone methyltransferase activity. Moreover, deleting Ezh2 enhanced the activation of CASP3 in spermatids, resulting in reduced spermatozoa production. Collectively, these data demonstrate that EZH2 plays a nonclassical role in the regulation of spermatogonial differentiation and apoptosis in murine spermatogenesis.

Electron transfer and microbial mechanism of synergistic degradation of lignocellulose by hydrochar and aerobic fermentation.

In response to the problem of asynchronous fermentation between lignocellulose and perishable materials in compost, the combined technology of low-temperature hydrochar and compost has been studied. Hydrochar was prepared through low-temperature hydrothermal reactions and applied to aerobic fermentation. The response relationship between lignocellulose content, electron transfer capability, and microbes was explored. The results showed that a pore structure with oxygen-containing functional groups was formed in hydrochar, promoting electron transfer during composting. With the rapid increase in composting temperature, the lignocellulose content decreased by 64.36 mg/g. Oceanobacillus, Cerasibacillus, Marinimicrobium, and Gracilibacillus promoted the degradation of lignocellulose and the carbon/nitrogen cycle during aerobic fermentation, and there was a significant response relationship between electron transfer capability and functional microbes. The combined application of hydrochar and aerobic fermentation accelerated the degradation of lignocellulose. This study provides technical support for the treatment of heterogeneous organic waste.

[Nuclear matrix proteins differentially expressed in human prostate cancer cell lines and benign prostatic hyperplasia epithelial cell line].

OBJECTIVE: To compare the expression of nuclear matrix proteins (NMPs) in benign prostatic hyperplasia (BPH) epithelial cell line BPH-1 versus those in androgen-dependent human prostate cancer cell line LNCap and androgen-independent prostate cancer cell line PC-3. METHODS: We isolated NMPs from the BPH-1, LNCap and PC-3 cell lines by 2-dimensional electrophoresis (2-DE), analyzed the differentially expressed proteins by matrix-assisted laser desorption / ionization time of flight mass spectrometry (MALDI-TOF-MS), and identified them by peptide mass fingerprint and database searching. RESULTS: We successfully obtained well-resolved reproducible 2-DE patterns of NMPs in human prostate cancer cell lines, identified 12 differentially expressed NMPs including enzymes, regulatory proteins, RNA-binding protein and various other factors, 3 up-regulated and 9 down-regulated in prostate cancer cell lines. CONCLUSION: There are obvious differences in the expressions of NMPs between human prostate cancer cell lines and benign prostatic hyperplasia epithelial cell line.

The Predictive Levels of Serum Anti-Müllerian Hormone and the Combined Index of the Number of Retrieved Oocytes and Good-Quality Embryos in Advanced-Age Infertile Women.

The primary objective of the study was to assess the values of serum anti-Müllerian hormone (AMH) levels and the combined index for the prediction of number of oocytes retrieved (NOR) and number of good-quality embryos (GQE) in infertile women undergoing IVF/ICSI treatment. A group of 521 infertile women aged 21-46 years were recruited as subject in this study. Serum AMH, hormones, and antral follicle count (AFC) were measured. The infertile women were categorized into three groups: 21-34 years (reproductive age), 35-39 years (reproductive age), and 40-46 years (advanced-age infertile). The predictive accuracy of variables was analyzed by the receiver operating characteristic (ROC) curve. AFC, AFC/age ratio, AMH/age ratio, and ovarian response prediction index (ORPI) decreased gradually, while AMH decreased significantly with increase in age. Moreover, NOR and GQE were positively correlated with AFC, AMH, AFC/age ratio, AMH/age ratio, and ORPI (P < 0.001). A statistical significance was observed in predicted oocyte retrieval including AMH, AMH/age ratio, and ORPI between 21-34 years and 35-46 years; especially in the 35-46 years group, these variables reached a "high" grade in the diagnostic accuracy because area under curve (AUC) ranged from 0.982 to 0.988 significantly. No statistical significance was observed for FSH, AMH, AFC, and related combined index predicting GQE. The predictive value of AFC and AFC/age ratio was limited regarding oocyte retrieval; however, AMH, AMH/age ratio, and ORPI concurrently had an excellent value for predicting NOR in reproductive-age women, especially in advanced-age infertile women.

The status and comparison of ovarian reserve between fertile and infertile healthy Chinese women of reproductive age.

ABSTRACT: We aimed to investigate ovarian reserve status, and explore differences in ovarian reserve between fertile and infertile healthy Chinese women of reproductive age.We recruited 442 fertile women aged 23 to 49 years (mean: 35.22 ±â€Š4.91 years) as subjects, and 196 infertile women aged 23 to 46 years (mean: 32.34 ±â€Š4.34 years) as controls. For all participants, a number of parameters were tested on days 2 to 4 of a spontaneous cycle, including basal serum follicle-stimulating hormone (FSH), estradiol (E2), luteinizing hormone (LH), total testosterone, anti-Müllerian hormone (AMH), ovarian response prediction index (ORPI), and antral follicle count (AFC).There were significant differences in terms of AFC, serum AMH levels, and ORPI among subject subgroups (10.58 ±â€Š5.80; 2.533 ±â€Š2.146 ng/mL; 1.28 ±â€Š1.87; respectively), and among control subgroups (12.44 ±â€Š5.69; 3.189 ±â€Š2.551 ng/mL; 1.88 ±â€Š2.68; respectively) (P < .01 for all). For both subjects and controls, AFC, AMH levels, and ORPI decreased gradually with increasing age, and presented with similar age-related trends; there were positive correlations between AMH and AFC (P < .001), and negative correlations between age and AFC, AMH, ORPI (P < .05 for all). There was a significant difference in age (P < .001), serum E2 (P < .01), and AMH (P < .01) levels between subjects and controls; however, when controlling for confounding factors (age, body mass index, total testosterone, and LH), we found no differences between the 2 groups with regards to the serum levels of AMH, FSH, E2, and AFC (P > .05 for all). Moreover, receiver operating characteristic curve analysis indicated that the significant variables of subjects and controls for evaluating ovarian reserve included age, AMH and ORPI, and ORPI was more valuable than other variables.A diminished ovarian reserve was one of the manifestations caused by female aging. When confounding factors were controlled for, we found no differences in ovarian reserve when compared between fertile and infertile women, and no correlation with infertility.

LncRNAs induce oxidative stress and spermatogenesis by regulating endoplasmic reticulum genes and pathways.

Oligozoospermia or low sperm count is a leading cause of male infertility worldwide. Despite decades of work on non-coding RNAs (ncRNAs) as regulators of spermatogenesis, fertilization, and male fertility, the literature on the function of long non-coding RNAs (lncRNAs) in human oligozoospermia is scarce. We integrated lncRNA and mRNA sequencing data from 12 human normozoospermic and oligozoospermic samples and comprehensively analyzed the function of differentially expressed lncRNAs (DE lncRNAs) and mRNAs (DE mRNAs) in male infertility. The target genes of DE lncRNAs were identified using a Gaussian graphical model. Gene ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways were primarily enriched in protein transport and localization to the endoplasmic reticulum (ER). The lncRNA-mRNA co-expression network revealed cis- and trans-regulated target genes of lncRNAs. The transcriptome data implicated DE lncRNAs and DE mRNAs and their target genes in the accumulation of unfolded proteins in sperm ER, PERK-EIF2 pathway-induced ER stress, oxidative stress, and sperm cell apoptosis in individuals with oligozoospermia. These findings suggest that the identified lncRNAs and pathways could serve as effective therapeutic targets for male infertility.

High anti-Müllerian hormone levels might not reflect the likelihood of clinical pregnancy rate in IVF/ICSI treatment.

OBJECTIVE: To investigate if high anti-Müllerian hormone (AMH) concentration is a useful tool to predict the outcome of assisted reproductive treatment. METHODS: Retrospective cohort study involving 520 patients who underwent IVF/ICSI procedures in a university hospital. We measured the serum AMH level on day 3 of the menstrual cycle. Based on AMH levels, we divided the patients into three groups as follows: low (<25th percentile) AMH group, average (25th to 75th percentile) AMH group and high (>75th percentile) AMH group. We recorded the fertilization rate (FR), the number of oocytes retrieved, the number of good quality embryos (GQEs) and the clinical pregnancy rate (CPR). RESULTS: There was no difference between the three AMH groups in terms of maternal age, body mass index (BMI), follicle-stimulating hormone (FSH), estradiol (E2), luteinizing hormone (LH) and testosterone (T) in the IVF/ICSI cycles. The women in the high serum AMH group had a higher number of retrieved oocytes than those in the low or average AMH groups (p < 0.01) in the IVF/ICSI cycles. Compared with the low or average AMH groups, the women with high AMH levels had a higher number of good quality embryos (GQEs) in the IVF/ICSI cycles (p < 0.01). However, high AMH women had no significantly higher clinical pregnancy rate (CPR) compared to the women in the low or average AMH groups. In addition, for the prediction of CPR, the AMH levels alone were not an independent predictor of CPR for IVF and ICSI cycles in the ROC curve analysis. CONCLUSIONS: High anti-Müllerian hormone levels are an independent predictor of the number of retrieved oocytes and good quality embryos (GQEs), but might not reflect the likelihood of higher clinical pregnancy rates (CPR) in IVF/ICSI treatment.

Restore natural fertility of Kitw/Kitwv mouse with nonobstructive azoospermia through gene editing on SSCs mediated by CRISPR-Cas9.

BACKGROUND: Male infertility is a serious social problem in modern society. Nonobstructive azoospermia (NOA) caused by germ cell gene defects is an important reason for male infertility, but effective clinical treatment for this disease has not been established. METHODS: We choose Kitw/Kitwv mouse as a research model and try to develop a new treatment strategy and "cure" its infertility. Mutant spermatogonial stem cells (SSCs) were isolated from one single unilateral testis of a 14-day-old Kitw/Kitwv mouse and propagated in vitro. The C to T point mutation on Kitwv site of these SSCs was corrected through CRISPR-Cas9-mediated homology-directed repair (HDR) in vitro. Then, the repaired SSCs were screened out, proliferated, and transplanted into the remaining testis, and complete spermatogenesis was established in the recipient testis. RESULTS: Healthy offsprings with wild type Kit gene or Kitw mutation were obtained through natural mating 4 months after SSC transplantation. CONCLUSION: In this study, we established an effective new treatment strategy for NOA caused by germ cell gene defects through a combination of SSC isolation, CRISPR-Cas9-mediated gene editing, and SSC transplantation, which brought hope for these NOA patients to restore their natural fertility.

Effects of sperm proteins on fertilization in the female reproductive tract.

Mammalian fertilization that culminates by fusion of the male and female gametes is intricately regulated within the female reproductive tract. To become competent to fertilize an egg, the mammalian spermatozoa that enter the female reproductive tract must undergo a series of physiological changes, including hyperactivation, and capacitation. For reaching full competency, the acrosome, a specialized membrane-bound organelle that covers the anterior part of the sperm head, must undergo an acrosome reaction. For becoming competent to bind an ovum, and to penetrate the zona pellucida and cumulus, many sperm proteins are released in the course of the acrosome reaction. Ultimately, the acrosome binds to the oolemma and fusion of sperm and egg occurs. In this review, we outline current understanding of the roles and effects of some essential sperm proteins and their functions during fertilization in the female reproductive tract.