Intracytoplasmic sperm injection versus conventional in-vitro fertilisation for couples with infertility with non-severe male factor: a multicentre, open-label, randomised controlled trial.

BACKGROUND: Introduced in 1992, intracytoplasmic sperm injection (ICSI) was initially indicated for severe male infertility; however, its use has since been expanded to non-severe male infertility. We aimed to compare the efficacy and safety of ICSI versus conventional in-vitro fertilisation (IVF) in couples with infertility with non-severe male factor. METHODS: We conducted an investigator-initiated, multicentre, open-label, randomised controlled trial in ten reproductive medicine centres across China. Couples with infertility with non-severe male factor without a history of poor fertilisation were randomly assigned (1:1) to undergo either ICSI or conventional IVF. The primary outcome was live birth after first embryo transfer. We performed the primary analysis in the intention-to-treat population using log-binomial regression models for categorical outcomes or linear regression models for continuous outcomes, adjusting for centre. This trial is registered with Clinicaltrials.gov, NCT03298633, and is completed. FINDINGS: Between April 4, 2018, and Nov 15, 2021, 3879 couples were screened, of whom 2387 (61·5%) couples were randomly assigned (1184 [49·6%] to the ICSI group and 1203 [50·4%] to the conventional IVF group). After excluding couples who were ineligible, randomised twice, or withdrew consent, 1154 (97·5%) in the ICSI group and 1175 (97·7%) in the conventional IVF group were included in the primary analysis. Live birth after first embryo transfer occurred in 390 (33·8%) couples in the ICSI group and in 430 (36·6%) couples in the conventional IVF group (adjusted risk ratio [RR] 0·92 [95% CI 0·83-1·03]; p=0·16). Two (0·2%) neonatal deaths were reported in the ICSI group and one (0·1%) in the conventional IVF group. INTERPRETATION: In couples with infertility with non-severe male factor, ICSI did not improve live birth rate compared with conventional IVF. Given that ICSI is an invasive procedure associated with additional costs and potential increased risks to offspring health, routine use is not recommended in this population. FUNDING: National Natural Science Foundation of China, National Key Research and Development Program, Beijing Municipal Science & Technology Commission, and Peking University Third Hospital.

Characteristics of broadband OPCPA based on DKDP crystals with different deuterations for the SEL-100 PW laser system.

We present the performances of a broadband optical parametric chirped pulse amplification (OPCPA) using partially deuterated potassium dihydrogen phosphate (DKDP) crystals with deuteration levels of 70% and 98%. When pumped by a Nd:glass double frequency laser, the OPCPA system using the 98% deuterated DKDP crystal achieves a broad bandwidth of 189 nm (full width at 1/e2 maximum) from 836 nm to 1025 nm. For the DKDP crystal with length of 43 mm, the pump-to-signal conversion efficiency reaches 28.4% and the compressed pulse duration is 13.7 fs. For a 70% deuterated DKDP crystal with a length of 30 mm, the amplified spectrum ranges from 846-1021 nm, the compressed pulse duration is 15.7 fs, and the conversion efficiency is 25.5%. These results demonstrate the potential of DKDP crystals with higher deuteration as promising nonlinear crystals for use as final amplifiers in 100 Petawatt (PW) laser systems, supporting compression pulse duration shorter than 15 fs.

SESAM mode-locked Yb:GdScO3 laser.

We report on the investigation of continuous-wave (CW) and SEmiconductor Saturable Absorber Mirror (SESAM) mode-locked operation of a Yb:GdScO3 laser. Using a single-transverse-mode, fiber-coupled InGaAs laser diode at 976 nm as a pump source, the Yb:GdScO3 laser delivers 343 mW output power at 1062 nm in the CW regime, which corresponds to a slope efficiency of 52%. Continuous tuning is possible across a wavelength range of 84 nm (1027-1111 nm). Using a commercial SESAM to initiate mode-locking and stabilize soliton-type pulse shaping, the Yb:GdScO3 laser produces pulses as short as 42 fs at 1065.9 nm, with an average output power of 40 mW at 66.89 MHz. To the best of our knowledge, this is the first demonstration of passively mode-locking with Yb:GdScO3 crystal.

Association between pre-gravid body mass index and clinical outcomes in in vitro fertilization: a multicentered retrospective cohort study.

BACKGROUND: With the increasing incidence of obesity and the childbearing-age delay among women, a debate over obesity's impacts on pregnancy and neonatal outcomes becomes hot. The potential negative effects of obesity and aging on fertility lead to an idea, whether an obese female pursuing IVF treatment can benefit from an ideal BMI achieved over a long-time weight loss process at the cost of aging? We aimed to assess the association between body mass index (BMI) and clinical or neonatal outcomes in patients undergoing in vitro fertilization (IVF) treatment, for answering whether it is necessary to lose weight first for obese patients, particularly those at advanced age. METHODS: A retrospective cohort study was performed using multicentered data from China. The women were stratified into 5 groups in terms of pre-gravid BMI (kg/m2) with the WHO obesity standard (group 1: BMI < 18.5; group 2: 18.5 ≤ BMI < 23.0; group 3: 23.0 ≤ BMI < 25.0; group 4: 25.0 ≤ BMI < 30.0; group 5: BMI ≥ 30.0). The primary outcome was cumulative live birth rate (CLBR), and other clinical and neonatal outcomes were weighed as secondary outcomes. Multivariate logistic regression analyses were carried to evaluate the association between BMI and the CLBR, or between BMI and some neonatal outcomes. Furthermore, we implemented a machine-learning algorithm to predict the CLBR based on age and BMI. RESULTS: A total of 115,287 women who underwent first IVF cycles with autologous oocytes from January 2013 to December 2017 were included in our study. The difference in the CLBR among the five groups was statistically significant (P < 0.001). The multivariate logistic regression analysis showed that BMI had no significant impact on the CLBR, while women's age associated with the CLBR negatively. Further, the calculation of the CLBR in different age stratifications among the five groups revealed that the CLBR lowered with age increasing, quantitatively, it decreased by approximately 2% for each one-year increment after 35 years old, while little difference observed in the CLBR corresponding to the five groups at the same age stratification. The machine-learning algorithm derived model showed that BMI's effect on the CLBR in each age stratification was negligible, but age's impact on the CLBR was overwhelming. The multivariate logistic regression analysis showed that BMI did not affect preterm birth, low birth weight infant, small for gestational age (SGA) and large for gestational age (LGA), while BMI was an independent risk factor for fetal macrosomia, which was positively associated with BMI. CONCLUSIONS: Maternal pre-gravid BMI had no association with the CLBR and neonatal outcomes, except for fetal macrosomia. While the CLBR was lowered with age increasing. For the IVF-pursuing women with obesity plus advanced age, rather than losing weight first, the sooner the treatment starts, the better. A multicentered prospective study with a large size of samples is needed to confirm this conclusion in the future.

Development of a machine learning-based prediction model for clinical pregnancy of intrauterine insemination in a large Chinese population.

PURPOSE: This study aimed to evaluate the effectiveness of a random forest (RF) model in predicting clinical pregnancy outcomes from intrauterine insemination (IUI) and identifying significant factors affecting IUI pregnancy in a large Chinese population. METHODS: RESULTS: A total of 11 variables, including eight from female (age, body mass index, duration of infertility, prior miscarriage, and spontaneous abortion), hormone levels (anti-Müllerian hormone, follicle-stimulating hormone, luteinizing hormone), and three from male (smoking, semen volume, and sperm concentration), were identified as the significant variables associated with IUI clinical pregnancy in our Chinese dataset. The RF-based prediction model presents an area under the receiver operating characteristic curve (AUC) of 0.716 (95% confidence interval, 0.6914-0.7406), an accuracy rate of 0.6081, a sensitivity rate of 0.7113, and a specificity rate of 0.505. Importance analysis indicated that semen volume was the most vital variable in predicting IUI clinical pregnancy. CONCLUSIONS: The machine learning-based IUI clinical pregnancy prediction model showed a promising predictive efficacy that could provide a potent tool to guide selecting targeted infertile couples beneficial from IUI treatment, and also identify which parameters are most relevant in IUI clinical pregnancy.

The relationship between servant leadership and nurses' in-role performance: The sequential mediating effects of job autonomy and emotional exhaustion.

AIMS: Drawing on the conservation of resources theory, this study examines the underlying process through which servant leadership is associated with nurses' in-role performance. Specifically, we test the indirect effect of servant leadership on in-role performance via a sequential mediating mechanism of job autonomy and emotional exhaustion. DESIGN: A time-lagged design was implemented using data gathered from two-wave online surveys (1 week apart) of registered nurses from Jiangsu Province, China. METHODS: Between September 2022 and February 2023, we used Wenjuanxing and Credma, which are two powerful and user-friendly data collection platforms, to distribute online surveys to potential participants. We received a total of 220 usable responses and employed the PROCESS Model 4 and Model 6 to assess our proposed hypotheses. RESULTS: Our proposed model was supported. Servant leadership has a positive indirect effect on nurses' in-role performance through job autonomy and emotional exhaustion. Job autonomy has a negative effect on emotional exhaustion. Additionally, job autonomy mediates the negative relationship between servant leadership and emotional exhaustion. CONCLUSION: The present research extends existing nursing studies by unravelling the complex mechanisms underlying the relationship between servant leadership and nurses' in-role performance. Our study also identifies the underlying mechanism of how servant leadership mitigates emotional exhaustion by supporting nurses' job autonomy. IMPACT: The sequential mediation results provide us with a more fine-grained understanding of the relationship between servant leadership and nurses' in-role performance. It further promotes job autonomy and decreases emotional exhaustion, which supports the UN Sustainable Development Goal #3 (Good Health and Well-being). PATIENT OR PUBLIC CONTRIBUTION: This study addresses the UN Sustainable Development Goal #3: 'To ensure healthy lives and promote well-being for all at all ages' and the healthcare providers will benefit from our study. Therefore, the study contributes to a more sustainable organization and society.

Cardiometabolic multimorbidity, peripheral biomarkers, and dementia in rural older adults: The MIND-China study.

INTRODUCTION: Evidence has emerged that cardiometabolic multimorbidity (CMM) is associated with dementia, but the underlying mechanisms are poorly understood. METHODS: This population-based study included 5704 older adults. Of these, data were available in 1439 persons for plasma amyloid-ß (Aß), total tau, and neurofilament light chain (NfL) and in 1809 persons for serum cytokines. We defined CMM following two common definitions used in previous studies. Data were analyzed using general linear, logistic, and mediation models. RESULTS: The presence of CMM was significantly associated with an increased likelihood of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) (p < 0.05). CMM was significantly associated with increased plasma Aß40, Aß42, and NfL, whereas CMM that included visceral obesity was associated with increased serum cytokines. The mediation analysis suggested that plasma NfL significantly mediated the association of CMM with AD. DISCUSSION: CMM is associated with dementia, AD, and VaD in older adults. The neurodegenerative pathway is involved in the association of CMM with AD. HIGHLIGHTS: The presence of CMM was associated with increased likelihoods of dementia, AD, and VaD in older adults. CMM was associated with increased AD-related plasma biomarkers and serum inflammatory cytokines. Neurodegenerative pathway was partly involved in the association of CMM with AD.

Designing salt stress-resilient crops: Current progress and future challenges.

Excess soil salinity affects large regions of land and is a major hindrance to crop production worldwide. Therefore, understanding the molecular mechanisms of plant salt tolerance has scientific importance and practical significance. In recent decades, studies have characterized hundreds of genes associated with plant responses to salt stress in different plant species. These studies have substantially advanced our molecular and genetic understanding of salt tolerance in plants and have introduced an era of molecular design breeding of salt-tolerant crops. This review summarizes our current knowledge of plant salt tolerance, emphasizing advances in elucidating the molecular mechanisms of osmotic stress tolerance, salt-ion transport and compartmentalization, oxidative stress tolerance, alkaline stress tolerance, and the trade-off between growth and salt tolerance. We also examine recent advances in understanding natural variation in the salt tolerance of crops and discuss possible strategies and challenges for designing salt stress-resilient crops. We focus on the model plant Arabidopsis (Arabidopsis thaliana) and the four most-studied crops: rice (Oryza sativa), wheat (Triticum aestivum), maize (Zea mays), and soybean (Glycine max).

Tumor Necrosis Factor α-Dependent Lung Inflammation Promotes the Progression of Lung Adenocarcinoma Originating From Alveolar Type II Cells by Upregulating MIF-CD74.

Lung adenocarcinoma is the most common type of lung cancer. We recently reported that inflammation-driven lung adenocarcinoma (IDLA) originates from alveolar type (AT)-II cells, which depend on major histocompatibility complex (MHC) class II to promote the expansion of regulatory T cells. The MHC class II-associated invariant chain (CD74) binds to the macrophage migration inhibitory factor (MIF), which is associated with promoting tumor growth and invasion. However, the role of MIF-CD74 in the progression of lung adenocarcinoma and the underlying mechanisms remain unclear. We aimed to explore the role of MIF-CD74 in the progression of lung adenocarcinoma and elucidate the mechanisms by which tumor necrosis (TNF)-α-mediated inflammation regulates CD74 and MIF expression in IDLA. In human lung adenocarcinoma, CD74 was upregulated on the surface of tumor cells originating from AT-II cells, which correlated positively with lymph node metastasis, tumor origin/nodal involvement/metastasis stage, and TNF-α expression. MIF interaction with CD74 promoted the proliferation and migration of A549 and H1299 cells in vitro. Using a urethane-induced IDLA mouse model, we observed that CD74 was upregulated in tumor cells and macrophages. MIF expression was upregulated in macrophages in IDLA. Blocking TNF-α-dependent inflammation downregulated CD74 expression in tumor cells and CD74 and MIF expression in macrophages in IDLA. Conditioned medium from A549 cells or activated mouse AT-II cells upregulated MIF in macrophages by secreting TNF-α. TNF-α-dependent lung inflammation contributes to the progression of lung adenocarcinoma by upregulating CD74 and MIF expression, and AT-II cells upregulate MIF expression in macrophages by secreting TNF-α. This study provides novel insights into the function of CD74 in the progression of IDLA.

An Enhancer-Driven Stem Cell-Like Program Mediated by SOX9 Blocks Intestinal Differentiation in Colorectal Cancer.

BACKGROUND AND AIMS: Genomic alterations that encourage stem cell activity and hinder proper maturation are central to the development of colorectal cancer (CRC). Key molecular mediators that promote these malignant properties require further elucidation to galvanize translational advances. We therefore aimed to characterize a key factor that blocks intestinal differentiation, define its transcriptional and epigenetic program, and provide preclinical evidence for therapeutic targeting in CRC. METHODS: Intestinal tissue from transgenic mice and patients were analyzed by means of histopathology and immunostaining. Human CRC cells and neoplastic murine organoids were genetically manipulated for functional studies. Gene expression profiling was obtained through RNA sequencing. Histone modifications and transcription factor binding were determined with the use of chromatin immunoprecipitation sequencing. RESULTS: We demonstrate that SRY-box transcription factor 9 (SOX9) promotes CRC by activating a stem cell-like program that hinders intestinal differentiation. Intestinal adenomas and colorectal adenocarcinomas from mouse models and patients demonstrate ectopic and elevated expression of SOX9. Functional experiments indicate a requirement for SOX9 in human CRC cell lines and engineered neoplastic organoids. Disrupting SOX9 activity impairs primary CRC tumor growth by inducing intestinal differentiation. By binding to genome wide enhancers, SOX9 directly activates genes associated with Paneth and stem cell activity, including prominin 1 (PROM1). SOX9 up-regulates PROM1 via a Wnt-responsive intronic enhancer. A pentaspan transmembrane protein, PROM1 uses its first intracellular domain to support stem cell signaling, at least in part through SOX9, reinforcing a PROM1-SOX9 positive feedback loop. CONCLUSIONS: These studies establish SOX9 as a central regulator of an enhancer-driven stem cell-like program and carry important implications for developing therapeutics directed at overcoming differentiation defects in CRC.

A teosinte-derived allele of an HKT1 family sodium transporter improves salt tolerance in maize.

The sodium cation (Na+ ) is the predominant cation with deleterious effects on crops in salt-affected agricultural areas. Salt tolerance of crop can be improved by increasing shoot Na+ exclusion. Therefore, it is crucial to identify and use genetic variants of various crops that promote shoot Na+ exclusion. Here, we show that a HKT1 family gene ZmNC3 (Zea mays L. Na+ Content 3; designated ZmHKT1;2) confers natural variability in shoot-Na+ accumulation and salt tolerance in maize. ZmHKT1;2 encodes a Na+ -preferential transporter localized in the plasma membrane, which mediates shoot Na+ exclusion, likely by withdrawing Na+ from the root xylem flow. A naturally occurring nonsynonymous SNP (SNP947-G) increases the Na+ transport activity of ZmHKT1;2, promoting shoot Na+ exclusion and salt tolerance in maize. SNP947-G first occurred in the wild grass teosinte (at a allele frequency of 43%) and has become a minor allele in the maize population (allele frequency 6.1%), suggesting that SNP947-G is derived from teosinte and that the genomic region flanking SNP947 likely has undergone selection during domestication or post-domestication dispersal of maize. Moreover, we demonstrate that introgression of the SNP947-G ZmHKT1;2 allele into elite maize germplasms reduces shoot Na+ content by up to 80% and promotes salt tolerance. Taken together, ZmNC3/ZmHKT1;2 was identified as an important QTL promoting shoot Na+ exclusion, and its favourable allele provides an effective tool for developing salt-tolerant maize varieties.

Spatio-temporal characterization of tightly focused femtosecond laser fields formed by paraboloidal mirrors with different F-numbers.

The focusing spatiotemporal property of a femtosecond laser pulse is presented under tight focusing conditions by using the frequency-resolved incident electric field and vector diffraction formulas with the wavefront correction term. In the ideal case, the focused laser intensity reaches its maximum at the F-number of ∼0.35 due to the strong diffraction effect under extremely tight focusing conditions. In spatio-temporal coupling distortion cases, their spatiotemporal Strehl ratios show a trend of improvement as the F-number decreases and this phenomenon is mainly concentrated along the y-direction. Based on the numerical calculation method used in this work, the precise information of tightly focused ultra-intense femtosecond laser fields can be obtained, which is crucial for assessing a focused intensity and describing the motion of charged particles under an extremely strong electric field. Moreover, the evolution law of focal fields with spatiotemporal distortions found in this paper can offer some theoretical guidance for realizing ultrahigh laser intensity in the near future.

Efficient high-power orthogonal dual-slab Yb:KGd(WO4)2 laser oscillator with a TEM00 mode.

We demonstrated a TEM00 mode orthogonal dual-slab Yb:KG(WO4)2(Yb:KGW) laser oscillator with high average power. Polarization anisotropy of thermal lenses was investigated and alleviating the astigmatism based on orthogonal dual-slab. In addition, the laser polarization was directly controlled by adjusting the net gain of the two crystals. The maximum output power was highly enhanced compared with single crystal due to effective thermal distribution. For an absorbed pump power of 52.4 W, this oscillator delivered an average power of 26.5 W, corresponding to an optical-to-optical conversion efficiency of 50.6%. Meanwhile, the ellipticity of the output laser was optimized to 0.940. Nearly diffraction-limited beam quality was measured to be M x2 = 1.19 and M y2=1.18.

417†W, 2.38†mJ Innoslab amplifier compressible to a high pulse quality of 406†fs.

We demonstrate a 417 W, 175 kHz Innoslab chirped pulse amplification laser compressible to short and clean 406 fs pulse duration. A spectral bandwidth (full width at half maximum, FWHM) of ∼3 nm was maintained at full pump power, and the pulses exhibited good pulse quality in a wide tunable pulse energy range from 1.7 mJ to a maximum of 2.38 mJ. At the maximum output power, the compressed pulses were nearly pedestal free. The comprehensive effects of residual high-order dispersion from the front end, the gain shaping effects of the amplifier, and the slight mismatch of third-order dispersion (TOD) between the stretcher (CFBG) and the gating compressor, along with the small nonlinear phase shift accumulated in the amplifier, could have facilitated the high pulse quality. To the best of our knowledge, this is the shortest pulse duration from the Innoslab amplifiers at hundreds of watts average power in the millijoule energy regime.

Dual-slab Yb:KGd(WO4)2 regenerative amplifier for spectral shaping and high-power output.

A high-power regenerative amplifier (RA) based on dual-slab Yb:KGd(WO4)2 (Yb:KGW) was demonstrated, which provided a maximum average power of 33.7 W at a repetition rate of 75-200 kHz before compression with a central wavelength of 1039 nm, corresponding to an optical-to-optical conversion efficiency of 51.4%. To the best of our knowledge, this is the highest average power from the Yb:KGW solid-state RA. The compressed pulse duration of 205 fs was realized under the maximum output power. By adjusting the gain of the crystals, respectively, the spectral shaping can be achieved. A combination spectrum with root-mean-square (RMS) bandwidth of 4.5 nm was generated with a central wavelength of 1035 nm at an output power of 20 W, the compressed pulse duration was 159 fs. Meanwhile, effective mitigation of thermal effects by dual-slab configuration guaranteed the nearly diffraction-limited beam quality: M x2 = 1.17 and M y2 = 1.20.

A novel variant in the FBP1 gene causes fructose-1,6-bisphosphatase deficiency through increased ubiquitination.

Fructose-1,6-bisphosphatase (FBPase) deficiency is an autosomal recessive disorder characterized by impaired gluconeogenesis caused by mutations in the fructose-1,6-bisphosphatase 1 (FBP1) gene. The molecular mechanisms underlying FBPase deficiency caused by FBP1 mutations require investigation. Herein, we report the case of a Chinese boy with FBPase deficiency who presented with hypoglycemia, ketonuria, metabolic acidosis, and repeated episodes of generalized seizures that progressed to epileptic encephalopathy. Whole-exome sequencing revealed compound heterozygous variants, c.761 A > G (H254R) and c.962C > T (S321F), in FBP1. The variants, especially the novel H254R, reduced protein stability and enzymatic activity in patient-derived leukocytes and transfected HepG2 and U251 cells. Mutant FBP1 undergoes enhanced ubiquitination and proteasomal degradation. NEDD4-2 was identified as an E3 ligase for FBP1 ubiquitination in transfected cells and the liver and brain of Nedd4-2 knockout mice. The H254R mutant FBP1 interacted with NEDD4-2 at significantly higher levels than the wild-type control. Our study identified a novel H254R variant of FBP1 underlying FBPase deficiency and elucidated the molecular mechanism underlying the enhanced NEDD4-2-mediated ubiquitination and proteasomal degradation of mutant FBP1.

Artificial oocyte activation with ionomycin compared with A23187 among patients at risk of failed or impaired fertilization.

RESEARCH QUESTION: Do fertilization rates differ between intracytoplasmic sperm injection (ICSI) cycles treated with artificial oocyte activation (AOA) using 10 µmol/l ionomycin or commercial A23187 in women at risk of failed or impaired fertilization? DESIGN: This single-centre, 7-year retrospective cohort study included 157 couples with a history of total fertilization failure (TFF, 0%) or low fertilization (<30%) after ICSI, or with severe oligo-astheno-teratozoospermia (OAT) in the male partner. Couples and underwent 171 ICSI-AOA cycles using either 10 µmol/l ionomycin or commercial A23187. The embryological and clinical outcomes were compared. RESULTS: Fertilization rates in the ionomycin group were significantly higher than those in the A23187 group for all three subgroups (TFF, 46.9% versus 28.4%, P = 0.002; low fertilization, 67.7% versus 49.2%, P < 0.001; severe OAT, 66.4% versus 31.6%, P < 0.001). AOA with ionomycin significantly increased the day 3 cleavage rate (P = 0.009) when compared with A23187 in the low fertilization group, but not in the TFF or severe OAT group (both P > 0.05). The rates of day 3 good-quality embryos, clinical pregnancy, implantation and live birth, and the cumulative live birth, did not differ between the two groups (all P > 0.05). A total of 64 live births resulted in 72 healthy babies born. CONCLUSIONS: AOA with 10 µmol/l ionomycin may be more effective than commercial A23187 in improving oocyte activation in patients at risk of failed or impaired fertilization, especially in cases of sperm-related defects.

Comparison of recombinant human FSH biosimilar QL1012 with Gonal-f® for ovarian stimulation: a phase-three trial.

RESEARCH QUESTION: Are QL1012 and Gonal-f® equivalent in women undergoing ovarian stimulation for assisted reproductive technology (ART)? DESIGN: This multicentre, randomized, assessor-blinded, phase-three trial was conducted at 13 centres in China. Eligible patients were infertile women; age 20-39 years; body mass index 18-30 kg/m2; regular menstrual cycles; and indication for ART. After successful pituitary downregulation, patients were randomly assigned (1:1) to receive QL1012 or Gonal-f®, stratified by age (initial dose of 75-150 IU for women younger than 30 years, 150-225 IU for women aged 30-34 years and 225-300 IU for women aged ≥35 years, subcutaneously, once daily). The primary end point was the number of oocytes retrieved. RESULTS: Between October 2018, and June 2019, 341 patients were included in the per-protocol set. The mean numbers of oocytes retrieved were 14.7 ± 7.0 in the QL1012 group (n = 169) and 13.4 ± 6.1 in the Gonal-f® group (n = 172). Adjusted by analysis of covariance model, the least-squares mean difference was 1.3 oocytes (95% CI -0.1 to 2.7; P = 0.0650), within the pre-defined equivalence margins of ±3.0. Similar results were observed in the full analysis set. Additionally, no statistical differences were found in secondary end points except oestradiol concentration (median 3948.0 pg/ml versus 3545.3 pg/ml; P = 0.0015). Ovarian hyperstimulation syndrome (12.4% versus 13.1 %) and other adverse events were similar between the two groups. CONCLUSIONS: Therapeutic equivalence and similar safety profiles were demonstrated between QL1012 and Gonal-f® in women undergoing ovarian stimulation for ART.

Effect of recombinant human thrombopoietin on IL-2, IL-4 and platelet parameters in thrombocytopenic purpura.

The objective of this study was to observe the effect of recombinant human thrombopoietin on IL-2, IL-4 and platelet parameters in thrombocytopenic purpura. For this purpose, a convenient sampling method was used to select 84 patients with thrombocytopenic purpura who visited the hospital from January 2018 to December 2022. The patients were divided into the norm group and rhTPO group with 42 cases each by random number table. The norm group was treated with routine treatment, while the rhTPO group was treated with recombinant thrombopoietin based on routine treatment. The changes in IL-2, IL-4, platelet parameters, immune recovery and treatment efficiency of the two groups were compared before and after treatment. Findings suggested that the levels of IL-2 and IL-4 in both groups decreased after treatment compared with those before treatment. However, the level of IL-2 in the rhTPO group after treatment was lower than that in the norm group, and the level of IL-4 in the rhTPO group after treatment was higher than that in the norm group (P<0.05). The levels of platelet parameters PLT and PCT in the two groups after treatment were higher than those before treatment, but the levels of PLT and PCT in the rhTPO group after treatment were higher than those in the norm group (P<0.05). The PLT of the rhTPO group was (69.57±6.73)×109/L after 7 days of treatment, which was higher than that in the norm group (62.05 ± 8.52)×109/L (P<0.05). The levels of PDW and MPV in the two groups after treatment decreased compared with those before treatment, but the levels of PDW and MPV in the rhTPO group after treatment were lower than those in the norm group (P<0.05). The overall immune recovery and treatment effectiveness of the rhTPO group were significantly better than those of the norm group. In summary, recombinant human thrombopoietin used in patients with thrombocytopenic purpura can maintain the balance between T cell activation and inhibition homeostasis, and promote faster recovery of platelet parameters.

Transcriptome profiling reveals multiple regulatory pathways of Tamarix chinensis in response to salt stress.

KEY MESSAGE: Multiple regulatory pathways of T. chinensis to salt stress were identified through transcriptome data analysis. Tamarix chinensis (Tamarix chinensis Lour.) is a typical halophyte capable of completing its life cycle in soils with medium to high salinity. However, the mechanisms underlying its resistance to high salt stress are still largely unclear. In this study, transcriptome profiling analyses in different organs of T. chinensis plants in response to salt stress were carried out. A total number of 2280, 689, and 489 differentially expressed genes (DEGs) were, respectively, identified in roots, stems, and leaves, with more DEGs detected in roots than in stems and leaves. Gene Ontology (GO) term analysis revealed that they were significantly enriched in "biological processes" and "molecular functions". Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that "Beta-alanine metabolism" was the most differentially enriched pathway in roots, stems, and leaves. In pair-to-pair comparison of the most differentially enriched pathways, a total of 14 pathways, including 5 pathways in roots and leaves, 6 pathways in roots and stems, and 3 pathways in leaves and stems, were identified. Furthermore, genes encoding transcription factor, such as bHLH, bZIP, HD-Zip, MYB, NAC, WRKY, and genes associated with oxidative stress, starch and sucrose metabolism, and ion homeostasis, were differentially expressed with distinct organ specificity in roots, stems, and leaves. Our findings in this research provide a novel approach for exploring the salt tolerance mechanism of halophytes and identifying new gene targets for the genetic breeding of new plant cultivars with improved resistance to salt stress.