Decreased LONP1 expression contributes to DNA damage and meiotic defects in oocytes.

Meiotic defects in oocytes are the primary reason for decreased female fertility with advanced maternal age. In this study, we revealed that decreased expression of ATP-dependent Lon peptidase 1 (LONP1) in aged oocytes and oocyte-specific depletion of LONP1 disrupt oocyte meiotic progression accompanying with mitochondrial dysfunction. In addition, LONP1 downregulation increased oocyte DNA damage. Moreover, we demonstrated that splicing factor proline and glutamine rich directly interacts with LONP1 and mediate the effect of LONP1 depletion on meiotic progression in oocytes. In summary, our data suggest that decreased expression of LONP1 is involved in advanced maternal age-related meiosis defects and that LONP1 represents a new therapeutic target to improve aged oocyte quality.

Plasma Circulating Tumor Necrosis Factor Receptors at Multiple Time Points Can Predict the Outcome of Severe Acute Kidney Injury.

INTRODUCTION: This prospective cohort study investigated the clinical role of circulating tumor necrosis factor receptor (cTNFR) levels as prognostic biomarkers in severe acute kidney injury (AKI) patients requiring continuous renal replacement therapy (CRRT). METHODS: We enrolled 136 patients from 7 hospitals participating in the VENUS (VolumE maNagement Under body composition monitoring in critically ill patientS on CRRT) trial from July 2017 to October 2019. The levels of cTNFR1 and cTNFR2 were measured using plasma samples collected on days 0 (D0), 2 (D2), and 7 (D7). Patients were divided into high- and low-cTNFR groups based on their receptor concentrations. RESULTS: D0 concentrations of cTNFR1 and cTNFR2 were positively correlated with one another (R2 = 0.37, p < 0.001). The high-cTNFR1 group displayed a higher in-hospital mortality rate than the low-TNFR1 group (p = 0.002). Moreover, the mortality rate was significantly higher in the high-TNFR1 group than in the low-TNFR1 group after adjusting for age, sex, and acute physiology, and chronic health evaluation II scores (hazard ratio 1.82, 95% confidence interval 1.09-3.03, p = 0.025). D2 and D7 cTNFR1 levels were also associated with in-hospital mortality; contrastingly, cTNFR2 levels were not associated with this outcome. Additionally, patients were divided into three groups according to the change in cTNFR levels from D0 to D2 (ΔcTNFR). Those in the highest ΔcTNFR tertile had a higher mortality rate than the remaining patients (p = 0.033 for ΔcTNFR1; p = 0.025 for ΔcTNFR2). Patients who underwent AKI-to-chronic kidney disease transition had higher concentrations of cTNFR1 (p = 0.014). DISCUSSION/CONCLUSION: Plasma cTNFR1 concentrations at CRRT initiation and changes in cTNFR1 and 2 levels immediately following CRRT initiation are significant biomarkers for predicting the outcomes of patients with severe AKI.

[The application study of Electrophysiological appropriate technology in perioperative nursing of patients undergoing microdissection testicular sperm extraction].

Obstract: To explore the application of electrophysiological appropriate technology in perioperative nursing of patients undergoing microdissection testicular sperm extraction. METHODS: A retrospective analysis was conducted on the medical records of 108 patients who underwent testicular incision and sperm extraction under a microscope at our center from May 2022 to June 2023. Among them, 51 patients received routine care and 57 patients received electrophysiological treatment. Evaluate the perioperative nursing effects of appropriate electrophysiological techniques through VAS pain score, Self Rating Anxiety Scale (SAS) score, Pittsburgh Sleep Quality Score, and Kolcaba Comfort Scale. RESULT: Patients who received appropriate electrophysiological interventions had lower VAS pain scores (2.36 ± 1.37 vs 4.16 ± 1.38, P<0.001) than the control group, and higher KOLCABA comfort scale scores than the control group (70.73 ± 19.46 vs 52.06 ± 17.50, P<0.001); There was no statistically significant difference in the Self Rating Anxiety Scale (SAS) score and Pittsburgh Sleep Quality Score. CONCLUSION: Electrophysiological techniques can effectively improve postoperative pain and comfort in patients undergoing testicular incision and sperm extraction under a microscope, and have clinical application value.

[Nursing cooperation in surgical collection of testis tissues from prepubertal male patients for cryopreservation: A study of 4 cases].

OBJECTIVE: To explore nursing cooperation in surgical collection of the testis tissue from prepubertal male patients for cryopreservation. METHODS: We retrospectively analyzed the methods and effects of perioperative nursing in surgical collection of the testis tissue from 4 prepubertal male patients for cryopreservation in our Center of Reproductive Medicine. Before, during and after operation, we took strict measures in making sterilized ice containers, intraoperative nursing cooperation, protection of the isolated testis tissues and transferring of the samples. RESULTS: Testis tissues were successfully collected from all the 4 prepubertal males, 31, 31, 20 and 34 samples from each case respectively, well protected and subjected to slow cryopreservation after standard processing in the embryo laboratory. CONCLUSION: In surgical collection of the testis tissue for cryopreservation, preparation of sterilized ice containers, intraoperative nursing cooperation and protection and transferring of the samples are essential for standard processing and cryopreservation of the testis tissue in the embryo laboratory.

cMet agonistic antibody prevents acute kidney injury to chronic kidney disease transition by suppressing Smurf1 and activating Smad7.

We aimed to investigate the role of cMet agonistic antibody (cMet Ab) in preventing kidney fibrosis during acute kidney injury (AKI) to chronic kidney disease (CKD) transition. Additionally, we explored the effect of cMet Ab on TGF-ß1/Smad pathway during the pathogenesis of kidney fibrosis. A unilateral ischemia-reperfusion injury (UIRI) mouse model was established to induce AKI-to-CKD transition. Furthermore, we incubated human proximal tubular epithelial cells (hPTECs) under hypoxic conditions as in vitro model of kidney fibrosis. We analyzed the soluble plasma cMet level in patients with AKI requiring dialysis. Patients who did not recover kidney function and progressed to CKD presented a higher increase in the cMet level. The kidneys of mice treated with cMet Ab showed fewer contractions and weighed more than the controls. The mice in the cMet Ab-treated group showed reduced fibrosis and significantly decreased expression of fibronectin and α-smooth muscle actin. cMet Ab treatment decreased inflammatory markers (MCP-1, TNF-α, and IL-1ß) expression, reduced Smurf1 and Smad2/3 level, and increased Smad7 expressions. cMet Ab treatment increased cMet expression and reduced the hypoxia-induced increase in collagen-1 and ICAM-1 expression, thereby reducing apoptosis in the in vitro cell model. After cMet Ab treatment, hypoxia-induced expression of Smurf1, Smad2/3, and TGF-ß1 was reduced, and suppressed Smad7 was activated. Down-regulation of Smurf1 resulted in suppression of hypoxia-induced fibronectin expression, whereas treatment with cMet Ab showed synergistic effects. cMet Ab can successfully prevent fibrosis response in UIRI models of kidney fibrosis by decreasing inflammatory response and inhibiting the TGF-ß1/Smad pathway.

Urinary cMet as a prognostic marker in immunoglobulin A nephropathy.

The prediction of prognosis in patients with immunoglobulin A nephropathy (IgAN) is challenging. We investigated the correlation between urinary cMet (ucMet) levels and clinical parameters and examined the effects of cMet agonistic antibody (cMet Ab) in an in vitro IgAN model. Patients diagnosed with IgAN (n = 194) were divided into three groups representing undetectable (Group 1), below-median (Group 2) and above-median (Group 3) levels of ucMet/creatinine (ucMet/Cr). Stained kidney biopsy samples were graded according to cMet intensity. Primary-cultured human mesangial cells were stimulated with recombinant tumour necrosis factor (TNF)-α and treated with cMet Ab. Our results showed that ucMet/Cr levels positively correlated with proteinuria (P < .001). During the follow-up, patients in Group 3 showed a significantly lower probability of complete remission (CR; uPCr < 300 mg/g) than those in groups 1 and 2, after adjusting for blood pressure, estimated glomerular filtration rate, and proteinuria, which influence clinical prognosis (HR 0.60, P = .038); moreover, ucMet/Cr levels were also associated with glomerular cMet expression. After TNF-α treatment, the proliferation of mesangial cells and increased interleukin-8 and intercellular adhesion molecule-1 expression were markedly reduced by cMet Ab in vitro. In conclusion, ucMet/Cr levels significantly correlated with proteinuria, glomerular cMet expression, and the probability of CR. Further, cMet Ab treatment alleviated the inflammation and proliferation of mesangial cells. Hence, ucMet could serve as a clinically significant marker for treating IgAN.

cMet agonistic antibody attenuates apoptosis in ischaemia-reperfusion-induced kidney injury.

Acute kidney injury (AKI) is a very common complication with high morbidity and mortality rates and no fundamental treatment. In this study, we investigated whether the hepatocyte growth factor (HGF)/cMet pathway is associated with the development of AKI and how the administration of a cMet agonistic antibody (Ab) affects an AKI model. In the analysis using human blood samples, cMet and HGF levels were found to be significantly increased in the AKI group, regardless of underlying renal function. The administration of a cMet agonistic Ab improved the functional and histological changes after bilateral ischaemia-reperfusion injury. TUNEL-positive cells and Bax/Bcl-2 ratio were also reduced by cMet agonistic Ab treatment. In addition, cMet agonistic Ab treatment significantly increased the levels of PI3K, Akt and mTOR. Furthermore, after 24 hours of hypoxia induction in human proximal tubular epithelial cells, treatment with the cMet agonistic Ab also showed dose-dependent antiapoptotic effects similar to those of the recombinant HGF treatment. Even when the HGF axis was blocked with a HGF-blocking Ab, the cMet agonistic Ab showed an independent dose-dependent antiapoptotic effect. In conclusion, cMet expression is associated with the occurrence of AKI. cMet agonistic Ab treatment attenuates the severity of AKI through the PI3K/Akt/mTOR pathway and improves apoptosis. cMet agonistic Ab may have important significance for the treatment of AKI.

Reduced and delayed expression of GDF9 and BMP15 in ovarian tissues from women with polycystic ovary syndrome.

PURPOSE: Growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) play crucial roles in follicular development and oocyte maturation. This study aimed to investigate and compare the expression of these proteins in ovarian tissues of women with and without polycystic ovary syndrome (PCOS). METHODS: Ovarian tissues from 28 patients with PCOS and 26 normal ovulatory women were collected, and the expression of GDF9 and BMP15 in oocytes and granulosa cells was evaluated via immunohistochemical staining. RESULTS: GDF9 and BMP15 were first expressed in primordial follicles at very low levels, and their expression increased gradually with follicular development, reaching the highest levels in Graafian follicles. However, less GDF9 and BMP15 expression was observed in primordial, primary, and secondary follicles in ovarian tissues of PCOS patients compared with levels in the control tissues (P < 0.05). In Graafian follicles, GDF9 and BMP15 expression reached comparable levels in the PCOS and control groups (P > 0.05). CONCLUSIONS: The expression of GDF9 and BMP15 in ovarian tissues varies among the developmental stages in both oocytes and granulosa cells in human ovarian tissues. The expression of these proteins is reduced and delayed in the early follicular stage in PCOS ovarian tissues, and these differences in expression may be associated with aberrant follicular development in patients with PCOS.

[Array comparative genomic hybridization analysis of early-stage arrested human embryos].

OBJECTIVE: To investigate chromosomal euploidies in early-stage arrested human embryos. METHODS: To determine the euploidy status of the 24 chromosomes, 13 embryos were analyzed, which included 5 arrested at 4-cell stage, 4 arrested at 8-cell stage, and 4 embryos at blastocyst stage regardless of their morphological scores. All embryos were subjected to biopsy, whole genome amplification, and array comparative genome hybridization analysis. RESULTS: Chromosome euploidies of the arrested embryos can be normal, aberrant and chaotic. Mosaicism is prevalent in early stage cleavage, whilst most of the blastocysts, even with poor morphology, are normal diploid. CONCLUSION: Arrested embryo may have normal chromosomes euploidy. Mosaicism is common in cleavage stage embryos. Early stage embryo arrest may not be solely attributable to chromosomal aneuploidies and needs further research.

Renalase rs2296545 variant improve hypertension susceptibility by modifying binding affinity to catecholamines in obstructive sleep apnea.

Obstructive sleep apnea (OSA), a condition often linked with hypertension, has an undefined relationship with renalase, a protein known for regulating blood pressure. This study aimed to investigate the relationship between serum renalase levels as well as renalase functional single nucleotide polymorphism (SNP) rs2296545 variant and hypertension in a Han Chinese OSA population. 126 subjects underwent serum renalase detection, with linear regression being performed to evaluate the relationship between serum renalase levels and OSA-related traits. Additional 4275 subjects were obtained rs2296545 genotype information by SNP microarray. And binary logistic regression was used to assess the effect of rs2296545 on hypertension risk. Molecular dynamics simulation and molecular docking were utilized to access the protein structures and the interplay between protein and catecholamines of wild-type and rs2296545 mutant renalase. The results showed that serum renalase levels were significantly higher in the severe OSA group. Further analysis showed renalase levels were positively correlated with blood pressure in the non-OSA group and negatively correlated in the severe OSA group. For rs2296545 polymorphism analysis, the hypertension risk significantly increased for the recessive model CC/GG + CG (OR = 1.211, 95% CI: 1.025-1.431) and the additive model CC/CG (OR = 1.223, 95% CI: 1.025-1.458) in the severe OSA. The rs2296545 polymorphism affected protein structure, and led to increase binding free energy, weakening interactions between renalase and catecholamines. In conclusion, serum renalase levels had independent association with blood pressure. And rs2296545 polymorphism may influence on susceptibility to hypertension by altering protein ability to bind to catecholamines, which might contribute to the intervention of hypertension in the OSA population.

Integrated test system for interfacial strength and morphology of multi-type hydrate-bearing sediments.

Predicting the strength parameters of multi-type sediments containing hydrates is the basis and precondition for the safe and efficient development of natural gas hydrates. However, studies on the shear mechanical behavior and morphology of multi-type hydrate-bearing sediments (HBS) are still insufficient. Herein, this study presents an integrated test system that can be used to measure the interfacial strength and morphology of multi-type sediments containing hydrates. This device integrates specimen preparation, shear test, morphology observation, and data analysis, which is helpful to comprehensively evaluate interfacial strength, roughness, and morphology. The propagation and development characteristics of microfractures of HBS during shearing can be obtained, which is favorable for identifying the damage and failure modes. Preliminary validation experiments have been conducted on massive pure hydrate, hydrate-sediment interface, and homogenous HBS to verify the applicability of the device for multi-type HBS. The device and corresponding analysis method are expected to support the evaluation of interfacial strength and morphology, thereby promoting a deeper understanding of hydrate-sediment interactions and failure mechanisms of hydrate reservoirs.

A signature based on circadian rhythm-associated genes for the evaluation of prognosis and the tumour microenvironment in HNSCC.

The morbidity and mortality rates of head and neck squamous cell carcinoma (HNSCC) remain high worldwide. Therefore, there is an urgent need to identify a new prognostic biomarker to guide the personalized treatment of HNSCC patients. Increasing evidence suggests that circadian rhythm genes play an important role in the development and progression of cancer. We aimed to explore the value of circadian rhythm genes in predicting prognosis and guiding the treatment of HNSCC. We first obtained a list of circadian rhythm genes from previous research. The sequencing data were retrieved from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Finally, univariate Cox proportional hazard analysis, least absolute shrinkage and selection operator (LASSO) regression, and multivariate Cox proportional hazard analysis were performed to develop a prognostic signature (Circadian Rhythm-Related Gene Prognostic Index, CRRGPI) consisting of nine circadian rhythm genes. The signature exhibited good performance in predicting overall survival. Patients with low CRRGPI scores had lower metabolic activities and an active antitumour immunity ability. Additionally, a clinical cohort was used to further evaluate the ability of the CRRGPI to predict the efficacy of immune checkpoint inhibitors. In conclusion, the novel circadian rhythm-related gene signature can provide a precise prognostic evaluation with the potential capacity to guide individualized treatment regimens for HNSCC patients.

Phosphate-to-alanine ratio and bilirubin-to-androsterone glucuronide ratio are the hub metabolites in upper gastrointestinal cancers: a Mendelian randomisation (MR) study.

Objective: Upper gastrointestinal (UGI) cancers, particularly esophageal cancer (EC) and gastric cancer (GC) represent a significant health burden with complex etiologies. Metabolic alterations are known to play a crucial role in cancer development and progression. Identifying key metabolic biomarkers may offer insights into the pathophysiology of UGI cancers and potential therapeutic targets. This study aimed to investigate the causal associations between 1,400 types of metabolites, specifically phosphate-to-alanine and bilirubin-to-androsterone glucuronide, and the risk of developing UGI cancers using Mendelian randomisation (MR) analysis. Method: We conducted a two-sample MR study utilising genetic instruments identified from large-scale genome-wide association studies (GWASs) for metabolic traits. The outcomes were derived from GWAS datasets of UGI cancer patients, including EC and GC. Several MR methods were employed to ensure the robustness of the findings, including inverse variance weighted (IVW), MR-Egger and weighted median approaches. Results: Our analysis found a total of 44 metabolites associated with EC and 15 metabolites associated with GC. The MR analyses revealed a significant causal relationship between the phosphate-to-alanine ratio (EC: OR = 1.002,95% CI = 1.00034-1.0037, p = 0.0037; GC: OR = 1.24,95% CI = 1.046-1.476, p = 0.01) and increased risk of UGI cancers. In contrast, the bilirubin-to-androsterone glucuronide ratio (EC: OR = 0.998,95% CI = 0.997-0.999, p = 0.03; GC: OR = 0.80,95% CI = 0.656-0.991, p = 0.04) was inversely associated with the risk, suggesting a potential protective effect. Conclusion: Our findings suggest that the phosphate-to-alanine ratio and bilirubin-to-androsterone glucuronide ratio are key hub metabolites in the etiology of UGI cancers. These metabolic ratios could serve as potential biomarkers for early detection or targets for therapeutic intervention. Further research is warranted to elucidate the underlying biological mechanisms and to validate the clinical utility of these associations.

Antioxidative effects of molybdenum and its association with reduced prevalence of hyperuricemia in the adult population.

The relationship between molybdenum and kidney-related disease outcomes, including hyperuricemia, is not well investigated. This study aims to determine whether molybdenum and its antioxidative property are associated with systemic inflammation and kidney-related disease parameters including hyperuricemia. Urinary molybdenum's epidemiological relationship to hyperuricemia and kidney-disease related outcomes was evaluated in 15,370 adult participants in the National Health and Nutrition Examination Survey (NHANES) collected between 1999 and 2016. Individuals' urinary molybdenum levels were corrected to their urinary creatinine concentrations. The association between urinary molybdenum-to-creatinine ratio and kidney-disease related outcomes were assessed by multivariable linear and logistic regression analyses, adjusting for covariates including age, sex, ethnicity, diabetes mellitus, hypertension, body mass index, and estimated glomerular filtration rate. Antimony and tungsten were used as control trace metals. Experimentally, HK-2 cell was used to assess molybdenum's antioxidative properties. HK-2 cells were challenged with H2O2-induced oxidative stress. Oxidative stress was measured using a fluorescent microplate assay for reactive oxygen species (ROS) and antioxidation levels were assessed by measuring the expression of manganese superoxide dismutase. In the adult NHANES population, urinary molybdenum-to-creatinine ratio was significantly associated with decreased serum uric acid (ß, -0.119; 95% CI, -0.148 to -0.090) concentrations, and decreased prevalence of hyperuricemia (OR, 0.73; 95% CI, 0.64-0.83) and gout (OR, 0.71; 95% CI, 0.52-0.94). Higher urinary molybdenum levels were associated with lower levels of systemic oxidative stress (gamma-glutamyltransferase levels; ß, -0.052; 95% CI, -0.067 to -0.037) and inflammation (C-reactive protein levels; ß, -0.184; 95% CI, -0.220 to -0.148). In HK-2 cells under H2O2-induced oxidative stress, molybdenum upregulated manganese superoxide dismutase expression and decreased oxidative stress. Urinary molybdenum levels are associated with decreased prevalence of hyperuricemia and gout in adult population. Molybdenum's antioxidative properties might have acted as an important mechanism for the reduction of systemic inflammation, ROS, and uric acid levels.

Day-2 and day-3 sequential transfer improves pregnancy rate in patients with repeated IVF-embryo transfer failure: a retrospective case-control study.

The purpose of this study was to evaluate the effect of sequential embryo transfer in patients with repeated IVF failure. A retrospective matched case-control study was conducted and the outcomes of 213 patients with a history of repeated IVF-embryo transfer failure were analysed, of which 33 women underwent sequential embryo transfer on day 2 and day 3 (D2/D3 group), 66 women on day 3 and day 5 (D3/D5 group), 85 women underwent day-3 embryo transfer only (D3 control group) and 29 women underwent day-5 embryo transfer only (D5 control group) in the assisted reproduction centre of the Sixth Affiliated Hospital of Sun Yat-sen University from August 2010 to December 2011. The results showed that the clinical pregnancy rate of the D2/D3 group was higher than that of the D3 group (48.5% versus 22.4%, P=0.006) while the clinical pregnancy rates of the D3/D5 and D5 groups were not significantly different (50.9% versus 45.8%). Day-2 and day-3 sequential embryo transfer may improve the clinical outcomes for patients with repeated IVF-embryo transfer failures. The purpose of this study was to evaluate the effect of sequential embryo transfer in patients with repeated IVF failure. A retrospective matched case-control study was conducted and the outcomes of 213 patients with a history of repeated IVF-embryo transfer failure were analysed, of which 33 women underwent sequential embryo transfer on day 2 and day 3 (D2/D3 group), 66 women on day 3 and day 5 (D3/D5 group), 85 women underwent day-3 embryo transfer only (D3 control group) and 29 women underwent day-5 embryo transfer only (D5 control group) in the assisted reproduction centre of the Sixth Affiliated Hospital of Sun Yat-sen University from August 2010 to December 2011. The results showed that the clinical pregnancy rate of the D2/D3 group was higher than that of the D3 group (48.5% versus 22.4%, P=0.006) while the clinical pregnancy rates of the D3/D5 and D5 groups were not significantly different (50.9% versus 45.8%). Day-2 and day-3 sequential embryo transfer may improve the clinical outcomes for patients with repeated IVF-embryo transfer failures.

Comparison of amino acid metabolism in frozen-thawed and fresh early-stage human embryos.

AIMS: To compare the amino acid differences of changes of frozen-thawed early-stage human embryos and fresh cultured early-stage human embryos. MATERIAL AND METHODS: Discarded embryos and their in vitro culture medium of patients who underwent in vitro fertilization-embryo transfer (IVF-ET) at the Research Center for Reproductive Medicine, the Sixth Affiliated Hospital of Sun Yat-sen University, from September 2010 to April 2011 were collected. Amino acid levels were determined by high performance liquid chromatography. RESULTS: The amino acid differences of changes in the culture medium of fresh embryos (661.50 µmol/L) were significantly higher than in the medium of post-thawed embryos (232.00 µmol/L) at 0.5 h (P < 0.001). At 1 and 2 h, no significant difference of change was found in all amino acids. Differences in the concentration of amino acids between post-thawed embryos and blank control medium were already present beginning at 1 h. CONCLUSIONS: The level of amino acid metabolism of frozen-thawed early-stage human embryos has already recovered from the state of metabolic stagnation during cryopreservation at 1 h of incubation after thawing, and the amino acid metabolism level at that time approximates that in fresh embryos before freezing. This may be established as the optimal embryo transfer time in IVF-ET.

Inhibitory effects of controlled ovarian stimulation on the expression of GDF9 and BMP15 in oocytes from women with PCOS.

PURPOSE: To explore the effects of controlled ovarian stimulation (COS) on the expression of growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) in oocytes and granulosa cells from patients with or without polycystic ovary syndrome (PCOS). METHODS: This case-control study was conducted in the university affiliated hospital. The study comprised four groups of patients: eighteen PCOS patients with COS (stimulated-PCOS) and twenty-two PCOS patients without COS (unstimulated-PCOS), twenty-nine normal ovulatory women with COS (stimulated-control) and twenty-eight normal ovulatory women without COS (unstimulated-control). The oocytes and granulosa cells were collected and the abundance of GDF9 and BMP15 mRNA in the cells were detected by nested quantitative real-time PCR. RESULTS: The abundance of GDF9 and BMP15 mRNA was significantly higher both in oocytes (P < 0.01, P < 0.001, respectively) and GCs (P < 0.01, P < 0.05, respectively) from stimulated-control group than in unstimulated-control group. However, there was no significant difference for GDF9 or BMP15 mRNA in oocytes from stimulated-PCOS goup compared with unstimulated-PCOS group (P > 0.05, P > 0.05, respectively). The abundance of GDF9 mRNA was significantly lower (P < 0.01) while the abundance of BMP15 mRNA was significantly higher (P < 0.001) in GCs from stimulated-PCOS group than in unstimulated-PCOS group. CONCLUSIONS: The controlled ovarian stimulation can promote the expression of GDF9 and BMP15 both in oocytes and GCs from normal ovulatory women. However, the stimulating effects may be inhibited in oocytes from PCOS patients, which subsequently impair cytoplasm maturation and lead to poor oocyte quality.

Progress and expectation of stem cell therapy for diabetic wound healing.

Impaired wound healing presents great health risks to diabetics. Encouragingly, the current clinical successfully found out meaningful method to repair wound tissue, and stem cell therapy could be an effective method for diabetic wound healing with its ability to accelerate wound closure and avoid amputation. This minireview aims at introducing stem cell therapy for facilitating tissue repair in diabetic wounds, discussing the possible therapeutic mechanism and clinical application status and problems.

Canthaxanthin Attenuates the Vascular Aging or Endothelial Cell Senescence by Inhibiting Inflammation and Oxidative Stress in Mice.

BACKGROUND: Vascular endothelial dysfunction is an early phenotype of aging-related vascular dysfunction. Delaying vascular aging and preventing cardiovascular disease are major public health problems that urgently need to be solved. Scientists have studied various drugs to prevent the occurrence and progress of cardiovascular disease, but progress has been slow. Here, the antisenescence and anti-endothelial damage of canthaxanthin (CX, which is an active molecule from food) has been studied. METHODS: This study was performed by adding CX to a model of cell senescence and oxidative damage induced by hydrogen peroxide. Cellular senescence markers (e.g., p16, p21, and p53) and oxidative damage markers (e.g., reactive oxygen species, nitric oxide, malondialdehyde, superoxide dismutase) were evaluated by the enzyme-linked immunosorbent assay, laser scanning confocal microscopy, and Western blotting. RESULTS: We found that CX downregulated the expression level of senescence-associated molecules, and significantly reduced the oxidative damage of vascular endothelial cells. These observations showed that CX effectively alleviated the senescence of vascular endothelial cells. Furthermore, CX treatment reduced the expression levels of interleukin-6 (IL-6), tumor necrosis factor alpha, and IL-1ß. Finally, in vivo, CX significantly alleviated vascular senescence. CONCLUSIONS: The current study shows that CX has potential application value for treating vascular aging or endothelial cell senescence.

A Meta-analysis of Total Neoadjuvant Therapies Combining Chemoradiotherapy with Induction or Consolidated Chemotherapy for Locally Advanced Rectal Cancer.

OBJECTIVE: Total neoadjuvant therapy (TNT) combining chemoradiotherapy (CRT) with chemotherapy (CT) was a novel pre-surgical approach to cancer treatment. This meta-analysis aimed to compare the clinical outcomes between neoadjuvant CRT (nCRT) with induction CT and nCRT with consolidated CT in locally advanced rectal cancer (LARC) patients. METHOD: In July 2022, a literature search was conducted using the following public databases: PubMed, MEDLINE, Embase, the Cochrane Library, and Web of Science, retrieved all relevant articles comparing nCRT-combining induction CT with nCRT-combining-consolidated CT treatments for LARC patients. RESULTS: Four eligible studies were identified, including a total of 995 LARC patients: 473 in the nCRT with consolidated CT group and 522 in the nCRT with induction CT group. The organ preservation (OP) rate of the nCRT with consolidated CT group was higher than that of the nCRT with induction CT group (RR [relative risk]: 1.53; 95% CI (confidence interval): 1.09-2.14). The pathological complete response (PCR, RR: 1.22; 95% CI 0.37-2.17), the 3-year disease-free survival (DFS, RR 1.02; 95% CI 0.71-1.46), the local recurrence (LR, RR 0.98; 95% CI 0.52-1.85), rates of R0 resection (RR 0.74; 95% CI 0.55-1.10), compliance (RR 0.52; 95% CI 0.12-2.26), and grade 3--4 toxicities (RR 0.78; 95% CI 0.57-1.06) were all similar between the two groups. CONCLUSION: In this meta-analysis of TNT regimens for rectal cancer, consolidative CT following nCRT was associated with similar PCR, 3-year DFS, LR, R0 resection, compliance, and grade 3-4 toxicities compared to induction CT prior to nCRT but a higher rate of organ preservation.