Impact of mobile application and outpatient follow-up on renal endpoints and physiological indices in patients with chronic kidney disease: a retrospective cohort study in Southwest China.

BACKGROUND: Chronic kidney disease (CKD) is a significant public health concern, and patient self-management is an effective approach to manage the condition. Mobile applications have been used as tools to assist in improving patient self-management, but their effectiveness in long-term outpatient follow-up management of patients with CKD remains to be validated. This study aimed to investigate whether using a mobile application combined with traditional outpatient follow-up can improve health outcomes of patients with CKD . METHODS: This retrospective cohort study recruited CKD patients with stage 1-5 who were not receiving renal replacement therapy from a CKD management center. Two groups were established: the APP + outpatient follow-up group and the traditional outpatient follow-up group. Baseline data was collected from January 2015 to December 2019, followed by a three-year long-term follow-up until December 2022. Laboratory data, all-cause mortality, and renal replacement treatment were then collected and compared between the two groups. RESULTS: 5326 patients were included in the study, including 2492 in the APP + outpatient group and 2834 in the traditional outpatient group. After IPTW virtualization matching, the final matched the APP + outpatient group consisted of 2489 cases (IQR, 33-55) and 2850 (IQR, 33-55) in the traditional outpatient group. By the end of the study, it was observed that the laboratory data of Phosphorus, Sodium, Triglyceride, Hemoglobin showed significant improvements, Furthermore the APP + outpatient group demonstrated superior results compared to the traditional outpatient group (P < .05). And it was observed that there were 34 deaths (1.4%) in the APP + outpatient group and 46 deaths (1.6%) in the traditional outpatient group(P = .49). After matching for renal replacement therapy outcomes, the two groups were found to be comparable (95% CI [0.72-1.08], P = .23), with no significant difference. However, it was noted that the traditional outpatient group had a lower incidence of using temporary catheters during initial hemodialysis (95% CI [8.4-29.8%], P < .001). CONCLUSION: The development and application of an app combined with outpatient follow-up management can improve patient health outcomes. However, to ensure optimal preparation for kidney replacement therapy, patients in CKD stages 4-5 may require more frequent traditional outpatient follow-ups, and further develop an information-based decision-making support tool for renal replacement therapy.

The gene AccCyclin H mitigates oxidative stress by influencing trehalose metabolism in Apis cerana cerana.

BACKGROUND: Environmental stress can induce oxidative stress in Apis cerana cerana, leading to cellular oxidative damage, reduced vitality, and even death. Currently, owing to an incomplete understanding of the molecular mechanisms by which A. cerana cerana resists oxidative damage, there is no available method to mitigate the risk of this type of damage. Cyclin plays an important role in cell stress resistance. The aim of this study was to explore the in vivo protection of cyclin H against oxidative damage induced by abiotic stress in A. cerana cerana and clarify the mechanism of action. We isolated and identified the AccCyclin H gene in A. cerana cerana and analysed its responses to different exogenous stresses. RESULTS: The results showed that different oxidative stressors can induce or inhibit the expression of AccCyclin H. After RNA-interference-mediated AccCyclin H silencing, the activity of antioxidant-related genes and related enzymes was inhibited, and trehalose metabolism was reduced. AccCyclin H gene silencing reduced A. cerana cerana high-temperature tolerance. Exogenous trehalose supplementation enhanced the total antioxidant capacity of A. cerana cerana, reduced the accumulation of oxidants, and improved the viability of A. cerana cerana under high-temperature stress. CONCLUSION: Our findings suggest that trehalose can alleviate adverse stress and that AccCyclin H may participate in oxidative stress reactions by regulating trehalose metabolism. © 2023 Society of Chemical Industry.

Preimplantation genetic testing for aneuploidy helps to achieve a live birth with fewer transfer cycles for the blastocyst FET patients with unexplained recurrent implantation failure.

PURPOSE: This retrospective cohort study aimed to investigate the value of preimplantation genetic testing for aneuploidy (PGT-A) as a screening test for patients suffering from unexplained recurrent implantation failure (RIF). METHODS: After screening patients in one reproductive medicine center, twenty-nine, forty-nine and thirty-eight women (< 40 years old) who had suffered unexplained RIF with PGT-A, or RIF without PGT-A, or no RIF with PGT-A were included. The clinical pregnancy rate and live birth rate per transfer, the conservative and optimal cumulative clinical pregnancy rates (CCPR) and live birth rates (CLBR) after three blastocyst FETs were analyzed. RESULTS: The live birth rate per transfer was significantly higher in the RIF + PGT-A group than that in the RIF + NO PGT-A group (47.6% vs. 24.6%, p = 0.014). After 3 cycles of FET, RIF + PGT-A group had significantly higher conservative CLBR and optimal CLBR compared to the RIF + NO PGT-A group (69.0% vs. 32.7%, p = 0.002 and 73.7% vs. 57.5%, p = 0.016), but had similar conservative and optimal CLBRs compared to the NO RIF + PGT-A group. The number of FET cycles required when half women achieved a live birth was 1 in the PGT-A group and 3 in RIF + NO PGT-A group. The miscarriage rates were not different between the RIF + PGT-A and RIF + NO PGT-A, RIF + PGT-A and NO RIF + PGT-A groups. CONCLUSION: PGT-A did be superior in reducing the number of transfer cycles required to achieve a similar live birth rate. Further studies to identify the RIF patients who would benefit most from PGT-A are necessary.

Risk factors for early neurological deterioration in acute isolated pontine infarction without any causative artery stenosis.

BACKGROUND: This study aimed to investigate the risk predictors for early neurological deterioration (END) in isolated acute pontine infarction without any causative artery stenosis. METHODS: In this retrospective study, patients with isolated acute pontine infarction within 72 h of symptom onset were enrolled between October 2017 and December 2021. END was defined as an increase in the National Institutes of Health Stroke Scale (NIHSS) score ≥ 2 points within the first week postadmission. Patients were divided into the END and the non-END groups. Multiple logistic regression analysis was used to evaluate independent predictors of END in patients with isolated acute pontine infarction. RESULTS: A total of 153 patients were included in the final study (62 females; mean age, 67.27 ± 11.35 years), of whom 28.7% (47 of 153) experienced END. Multiple logistic regression analyses showed that infarct volume (adjusted odds ratio [aOR], 1.003; 95% CI, 1.001-1.005; P = 0.002) and basilar artery branch disease  (aOR, 3.388; 95% CI, 1.102-10.417; P = 0.033) were associated with END. The combined ROC analysis of the infarct volume and basilar artery branch disease for predicting END showed that the sensitivity and specificity were 80.9% and 72.6%, respectively. CONCLUSION: Basilar artery branch disease and infarct volume were associated with END in acute isolated pontine infarction and may be useful prognostic factors for neurological progression.

Distribution and identification of Mycobacterium tuberculosis lineage in Kashgar prefecture.

OBJECTIVES: Kashgar prefecture is an important transportation and trade hub with a high incidence of tuberculosis. The following study analyzed the composition and differences in Mycobacterium tuberculosis (M.tb) lineage and specific tags to distinguish the lineage of the M.tb in Kashgar prefecture, thus providing a basis for the classification and diagnosis of tuberculosis in this area. METHODS: Whole-genome sequencing (WGS) of 161 M.tb clinical strains was performed. The phylogenetic tree was constructed using Maximum Likelihood (ML) based on single nucleotide polymorphisms (SNPs) and verified through principal component analysis (PCA). The composition structure of M.tb in different regions was analyzed by combining geographic information. RESULTS: M.tb clinical strains were composed of lineage 2 (73/161, 45.34%), lineage 3 (52/161, 32.30%) and lineage 4 (36/161, 22.36%). Moreover, the 3 lineages were subdivided into 11 sublineages, among which lineage 2 included lineage 2.2.2/Asia Ancestral 1 (9/73, 12.33%), lineage 2.2.1-Asia Ancestral 2 (9/73, 12.33%), lineage 2.2.1-Asia Ancestral 3 (18/73, 24.66%), and lineage 2.2.1-Modern Beijing (39/73, 53.42%). Lineage 3 included lineage 3.2 (14/52, 26.92%) and lineage 3.3 (38/52, 73.08%), while lineage 4 included lineage 4.1 (3/36, 8.33%), lineage 4.2 (2/36, 5.66%), lineage 4.4.2 (1/36, 2.78%), lineage 4.5 (28/36, 77.78%) and lineage 4.8 (2/36, 5.66%), all of which were consistent with the PCA results. One hundred thirty-six markers were proposed for discriminating known circulating strains. Reconstruction of a phylogenetic tree using the 136 SNPs resulted in a tree with the same number of delineated clades. Based on geographical location analysis, the composition of Lineage 2 in Kashgar prefecture (45.34%) was lower compared to other regions in China (54.35%-90.27%), while the composition of Lineage 3 (32.30%) was much higher than in other regions of China (0.92%-2.01%), but lower compared to the bordering Pakistan (70.40%). CONCLUSION: Three lineages were identified in M.tb clinical strains from Kashgar prefecture, with 136 branch-specific SNP. Kashgar borders with countries that have a high incidence of tuberculosis, such as Pakistan and India, which results in a large difference between the M.tb lineage and sublineage distribution in this region and other provinces of China.

Daily Walking Dose and Health-related Quality of Life in Patients With Chronic Kidney Disease.

OBJECTIVE: Exercise, like daily walking, may improve overall health and impede progression of chronic kidney disease (CKD); however, no specific walking dose has been recommended for patients with CKD. We aimed to investigate the association between daily walking steps and health-related quality of life (HRQOL) in adults with CKD. DESIGN AND METHODS: The walking steps of patients with CKD were extracted from the We Run mobile application. Their average daily walking steps were calculated and subdivided into the low-, middle-, and high-level groups. HRQOL was assessed using the physical component summary (PCS) and mental component summary (MCS) of the MOS 36 Short Form Health Survey (SF-36). RESULTS: A total of 558 adults (50.5%, men) with an average age of 40.2 (±13.8) years were enrolled. The median daily step count was 7,404 steps. The daily walking step count demonstrated an inverse U-shaped relationship with the SF-36 and subscale scores. Participants with daily walking steps between 7,000 and 12,000 have the highest PCS (68.1 ± 12.2) and MCS scores (70.0 ± 19.5). The multiple linear regression model showed that compared with patients with a daily step count of 7,000 to 12,000, patients with a daily step count >12,000 had a significantly lower MCS score (P < .001), while patients with a daily step count <7,000 had significantly lower PCS (P < .001) and MCS scores (P = .034). Moreover, the multivariable logistic regression model showed that patients with a daily step count >12,000 had significantly lower mental health-related quality (odds ratio [OR], 2.188; 95% confidence interval [CI], 1.079-1.439 for low MCS), while those with a daily step count <7,000 had a significantly lower HRQOL than the 7,000 to 12,000 daily step count group (OR, 2.113; 95% CI, 1.203-3.711 for low PCS; OR, 2.099; 95% CI, 1.210-3.643 for low MCS). CONCLUSIONS: These findings suggest that daily walking steps between 7,000 and 12,000 are associated with high HRQOL in adults with CKD.

Tß4-Ac-SDKP pathway: Any relevance for the cardiovascular system?

The last 20 years witnessed the emergence of the thymosin ß4 (Tß4)-N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) pathway as a new source of future therapeutic tools to treat cardiovascular and renal diseases. In this review article, we attempted to shed light on the numerous experimental findings pertaining to the many promising cardiovascular therapeutic avenues for Tß4 and (or) its N-terminal derivative, Ac-SDKP. Specifically, Ac-SDKP is endogenously produced from the 43-amino acid Tß4 by 2 successive enzymes, meprin α and prolyl oligopeptidase. We also discussed the possible mechanisms involved in the Tß4-Ac-SDKP-associated cardiovascular biological effects. In infarcted myocardium, Tß4 and Ac-SDKP facilitate cardiac repair after infarction by promoting endothelial cell migration and myocyte survival. Additionally, Tß4 and Ac-SDKP have antifibrotic and anti-inflammatory properties in the arteries, heart, lungs, and kidneys, and stimulate both in vitro and in vivo angiogenesis. The effects of Tß4 can be mediated directly through a putative receptor (Ku80) or via its enzymatically released N-terminal derivative Ac-SDKP. Despite the localization and characterization of Ac-SDKP binding sites in myocardium, more studies are needed to fully identify and clone Ac-SDKP receptors. It remains promising that Ac-SDKP or its degradation-resistant analogs could serve as new therapeutic tools to treat cardiac, vascular, and renal injury and dysfunction to be used alone or in combination with the already established pharmacotherapy for cardiovascular diseases.

N-acetyl-seryl-aspartyl-lysyl-proline treatment protects heart against excessive myocardial injury and heart failure in mice.

Myocardial infarction (MI) in mice results in cardiac rupture at 4-7 days after MI, whereas cardiac fibrosis and dysfunction occur later. N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) has anti-inflammatory, anti-fibrotic, and pro-angiogenic properties. We hypothesized that Ac-SDKP reduces cardiac rupture and adverse cardiac remodeling, and improves function by promoting angiogenesis and inhibiting detrimental reactive fibrosis and inflammation after MI. C57BL/6J mice were subjected to MI and treated with Ac-SDKP (1.6 mg/kg per day) for 1 or 5 weeks. We analyzed (1) intercellular adhesion molecule-1 (ICAM-1) expression; (2) inflammatory cell infiltration and angiogenesis; (3) gelatinolytic activity; (4) incidence of cardiac rupture; (5) p53, the endoplasmic reticulum stress marker CCAAT/enhancer binding protein homology protein (CHOP), and cardiomyocyte apoptosis; (6) sarcoplasmic reticulum Ca2+ ATPase (SERCA2) expression; (7) interstitial collagen fraction and capillary density; and (8) cardiac remodeling and function. Acutely, Ac-SDKP reduced cardiac rupture, decreased ICAM-1 expression and the number of infiltrating macrophages, decreased gelatinolytic activity, p53 expression, and myocyte apoptosis, but increased capillary density in the infarction border. Chronically, Ac-SDKP improved cardiac structures and function, reduced CHOP expression and interstitial collagen fraction, and preserved myocardium SERCA2 expression. Thus, Ac-SDKP decreased cardiac rupture, ameliorated adverse cardiac remodeling, and improved cardiac function after MI, likely through preserved SERCA2 expression and inhibition of endoplasmic reticulum stress.

Chromosome constitution of equal-sized three-cell embryos using next-generation sequencing technology.

PURPOSE: To study the chromosome constitution of equal-sized three-cell embryo. METHODS: We determined the chromosome constitution of 105 blastomeres from 35 embryos using multiple annealing and looping-based amplification cycles (MALBAC) together with NGS sequencing technology. Chromosomal copy number variation (CNV) analysis was successfully performed in 27 embryos. We also analyzed radius, perimeter, area, and volume of each blastomere to explore the possibility of selecting the normal embryos. RESULTS: Majority of the embryos (77.8%, 21/27) studied were mosaic or aneuploid, and only 22.2% (6/27) had normal chromosome numbers. The aneuploid chromosomes spread across all chromosomes and the most frequent aneuploidies were for chromosomes 1, 16, and 18 followed by 13, 19, and 21. Statistical analyses showed no significant difference between euploid and aneuploid embryos regarding radius, perimeter, area, and volume of their blastomeres. CONCLUSIONS: Our results showed that majority of the equal-sized three-cell embryos were chromosomally abnormal and could not be distinguished by morphology observation, so they should be given lower priority at selection for transfer.

Thymosin-ß4 prevents cardiac rupture and improves cardiac function in mice with myocardial infarction.

Thymosin-ß4 (Tß4) promotes cell survival, angiogenesis, and tissue regeneration and reduces inflammation. Cardiac rupture after myocardial infarction (MI) is mainly the consequence of excessive regional inflammation, whereas cardiac dysfunction after MI results from a massive cardiomyocyte loss and cardiac fibrosis. It is possible that Tß4 reduces the incidence of cardiac rupture post-MI via anti-inflammatory actions and that it decreases adverse cardiac remodeling and improves cardiac function by promoting cardiac cell survival and cardiac repair. C57BL/6 mice were subjected to MI and treated with either vehicle or Tß4 (1.6 mg·kg(-1)·day(-1) ip via osmotic minipump) for 7 days or 5 wk. Mice were assessed for 1) cardiac remodeling and function by echocardiography; 2) inflammatory cell infiltration, capillary density, myocyte apoptosis, and interstitial collagen fraction histopathologically; 3) gelatinolytic activity by in situ zymography; and 4) expression of ICAM-1 and p53 by immunoblot analysis. Tß4 reduced cardiac rupture that was associated with a decrease in the numbers of infiltrating inflammatory cells and apoptotic myocytes, a decrease in gelatinolytic activity and ICAM-1 and p53 expression, and an increase in the numbers of CD31-positive cells. Five-week treatment with Tß4 ameliorated left ventricular dilation, improved cardiac function, markedly reduced interstitial collagen fraction, and increased capillary density. In a murine model of acute MI, Tß4 not only decreased mortality rate as a result of cardiac rupture but also significantly improved cardiac function after MI. Thus, the use of Tß4 could be explored as an alternative therapy in preventing cardiac rupture and restoring cardiac function in patients with MI.

Development and validation of the patient-reported outcome scale for chronic kidney disease.

PURPOSE: The patient-reported outcomes (PROs) measuring patient's experience and perception of disease are important components of approach to care. However, no tools are available to assess the PROs of chronic kidney disease (CKD). This study aims to develop and verify a PROs scale to evaluate clinical outcomes in CKD patients. METHODS: The theoretical structure model and original item pool were formed through a literature review, patient interviews and references to relevant scales. The Delphi method, classical test theory methods and item response theory method were used to select items and adjust dimensions to form the final scale. Altogether 360 CKD patients were recruited through convenience sampling. CKD-PROs could be evaluated from four aspects, namely reliability, content validity, construct validity, responsibility, and feasibility. RESULTS: The CKD-PROs scale covers 4 domains, including the physiological, psychological, social, and therapeutic domain, and 12 dimensions, 54 items. The Cronbach's α is 0.939, the split reliability coefficient is 0.945, and the correlation of the scores each item and domain's coefficients range from 0.413 to 0.669. The results of structure validity, content validity and reactivity showed that the multidimensional measurement of the scale met professional expectations. The recovery rate and effective rate of the scale were over 99%. CONCLUSION: The CKD-PROs scale has great reliability, validity, reactivity, acceptability and is capable of being used as one of the evaluation tools for the clinical outcomes of CKD patients.

Ac-SDKP attenuates ER stress-stimulated collagen production in cardiac fibroblasts by inhibiting CHOP-mediated NF-κB expression.

Inflammation and cardiac fibrosis are prevalent pathophysiologic conditions associated with hypertension, cardiac remodeling, and heart failure. Endoplasmic reticulum (ER) stress triggers the cells to activate unfolded protein responses (UPRs) and upregulate the ER stress chaperon, enzymes, and downstream transcription factors to restore normal ER function. The mechanisms that link ER stress-induced UPRs upregulation and NF-κB activation that results in cardiac inflammation and collagen production remain elusive. N-Acetyl-Ser-Asp-Lys-Pro (Ac-SDKP), a natural tetrapeptide that negatively regulates inflammation and fibrosis, has been reported. Whether it can inhibit ER stress-induced collagen production in cardiac fibroblasts remains unclear. Thus, we hypothesized that Ac-SDKP attenuates ER stress-stimulated collagen production in cardiac fibroblasts by inhibiting CHOP-mediated NF-κB expression. We aimed to study whether Ac-SDKP inhibits tunicamycin (TM)-induced ER stress signaling, NF-κB signaling, the release of inflammatory cytokine interleukin-6, and collagen production in human cardiac fibroblasts (HCFs). HCFs were pre-treated with Ac-SDKP (10 nM) and then stimulated with TM (0.25 µg/mL). We found that Ac-SDKP inhibits TM-induced collagen production by attenuating ER stress-induced UPRs upregulation and CHOP/NF-κB transcriptional signaling pathways. CHOP deletion by specific shRNA maintains the inhibitory effect of Ac-SDKP on NF-κB and type-1 collagen (Col-1) expression at both protein and mRNA levels. Attenuating ER stress-induced UPR sensor signaling by Ac-SDKP seems a promising therapeutic strategy to combat detrimental cardiac inflammation and fibrosis.

Development of standardized nursing terminology for the process documentation of patients with chronic kidney disease.

Introduction: European Nursing care Pathways (ENP) is a professional care language that utilizes software to map care processes and utilize the data for research purposes, process control, and personnel requirement calculations. However, there is a lack of internationally developed terminology systems and subset specifically designed for the nutritional management of CKD. The aim of this study was to create a subset of the standardized nursing terminology for nutrition management in patients with chronic kidney disease (CKD). Materials and methods: According to the guidelines for subset development, four research steps were carried out: (i) Translation of version 3.2 of the ENP (chapter on kidney diseases) and understanding of the framework structure and coding rules of the ENP; (ii) Identification of relevant six-dimensional nursing terms; (iii) Creation of a framework for the subset; (iv) Review and validation by experts. Results: A subset for CKD nutritional care was created as part of this project, comprising 630 terms, with 17 causal relationships related to nursing diagnoses, 115 symptoms, 31 causes, 34 goals/outcomes, 420 intervention specifications and 13 resources, including newly developed care terms. All terms within the subset have been created using a six-step maintenance procedure and a clinical standard pathway for nutrition management in the SAPIM mode. Implications for nursing practice: This terminology subset can facilitate standardized care reports in CKD nutrition management, which is used to standardize nursing practice, quantify nursing, services, guidance on care decisions, promoting the exchange and use of CKD nutrition data and serve as a reference for the creation of standardized subset of nursing terminology in China.

In Vitro Screening of Trehalose Synbiotics and Their Effects on Early-Lactating Females and Offspring Mice.

Activities such as childbirth and breastfeeding can cause severe oxidative stress and inflammatory damage to the mother during early lactation, and can affect animal milk production, and the growth and development of offspring. Trehalose alleviates damage to the body by endowing it with stress resistance. In this study, we used trehalose combined with Lactobacillus plantarum, Bifidobacterium longum, Bacillus subtilis, and Saccharomyces cerevisiae to explore whether dietary intervention can alleviate oxidative stress and inflammatory damage in early lactation and to evaluate the growth ability, acid production ability, antioxidant ability, non-specific adhesion ability, antibacterial ability, and other parameters to determine the optimal combinations and proportions. The results showed that the synbiotics composed of 2.5% trehalose and 1 × 107 cfu/g of Bifidobacterium longum could regulate the gut microbiota, and promote mammary gland development in dams by reducing progesterone (PROG) content in the blood, increasing prolactin (PRL) and insulin-like growth factor-1 (IGF-1) content, enhancing their antioxidant and immune abilities, and effectively increasing the weight and lactation of early lactating dams. In addition, it can also affect the growth of offspring and the development of the intestinal barrier. These results indicate that trehalose synbiotics have great potential in alleviating oxidative stress and inflammatory damage in early lactation.

Exploring the role of coagulation-related genes in renal cell carcinoma: Implications for tumor microenvironment and prognostic biomarkers.

PURPOSE: Clear cell renal cell carcinoma (ccRCC) frequently progresses to advanced stages due to tumor thrombus (TTs) formation. In this study, we aimed to investigate the role of coagulation-related pathway activation in the progression of ccRCC. METHODS: Consensus clustering was used to identify coagulation-related molecular clusters of ccRCC patients from The Cancer Genome Atlas Program (TCGA) database. The function of coagulation and its correlation with the immune microenvironment were investigated. Protein-protein interactions and differential expression analysis were used to identify the key gene, which was verified by external experiments. The coagulation-associated risk score was constructed by cox proportional hazards regression. RESULTS: Notable disparities were detected in immune characteristics, prognostic differentiation and drug sensitivity between two coagulation-related clusters. Through the integration of clinical stage significance and protein-protein interactions, the key gene MMP9 was screened and it was significantly correlated with CD4+T cells, CD8+T cells and Treg cells. A coagulation-related risk score prognostic model was developed in the Cancer Genome Atlas (TCGA) cohort for risk stratification and prognosis prediction. The prognostic predictive values of the coagulation-related risk score were further authenticated in both TCGA-KIRC and E-MTAB-1980 cohorts. CONCLUSION: There is an obvious correlation between the coagulation and the tumor microenvironment in ccRCC. As a key coagulation-related gene, MMP9 may promote the progression of renal cell carcinoma by influencing immune infiltration of CD8+T cells and Treg cells. Additionally, the risk score could be used as a durable prognostic biomarker, which could assist in clinical decision making for ccRCC patients.

N-acetyl-Ser-Asp-Lys-Pro inhibits interleukin-1ß-mediated matrix metalloproteinase activation in cardiac fibroblasts.

Myocardial matrix turnover involves a dynamic balance between collagen synthesis and degradation, which is regulated by matrix metalloproteinases (MMPs). N-acetyl-Ser-Asp-Lys-Pro (Ac-SDKP) is a small peptide that inhibits cardiac inflammation and fibrosis. However, its role in MMP regulation is not known. Thus, we hypothesized that Ac-SDKP promotes MMP activation in cardiac fibroblasts and decreases collagen deposition via this mechanism. To that end, we tested the effects of Ac-SDKP on interleukin-1ß (IL-1ß; 5 ng/ml)-stimulated adult rat cardiac fibroblasts. We measured total collagenase activity, MMP-2, MMP-9, and MMP-13 expressions, and activity along with their inhibitors, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2. In order to examine the effects of Ac-SDKP on the signaling pathway that controls MMP transcription, we also measured nuclear factor-κB (NFκB) and p42/44 mitogen-activated protein kinase (MAPK) activation. Ac-SDKP did not alter collagenase or gelatinase activity in cardiac fibroblasts under basal conditions, but blunted the IL-1ß-induced increase in total collagenase activity. Similarly, Ac-SDKP normalized the IL-1ß-mediated increase in MMP-2 and MMP-9 activities and MMP-13 expression. Inhibition of MMPs by Ac-SDKP was associated with increased TIMP-1 and TIMP-2 expressions. Collagen production was not affected by Ac-SDKP, IL-1ß, or a combination of both agents. Ac-SDKP blocked IL-1ß-induced p42/44 phosphorylation and NFκB activation in cardiac fibroblasts. We concluded that the Ac-SDKP-inhibited collagenase expression and activation was associated with increased expression of TIMP-1 and TIMP-2. These pharmacological effects of Ac-SDKP may be linked to the inhibition of MAPK and NFκB pathway.

A study of application effects of next-generation sequencing based preimplantation genetic testing for aneuploidies in advanced maternal age women.

OBJECTIVE: To investigate if next-generation sequencing-based preimplantation genetic testing for aneuploidies could improve pregnancy outcomes in women of advanced maternal age. MATERIALS AND METHODS: A retrospective analysis. The clinical data of 1099 couples treated in the First Medical Center of the Chinese PLA General Hospital from January 2019 to December 2021 were analyzed. They were divided into two groups based on whether they underwent a Next-generation sequencing-based preimplantation genetic test for aneuploidies. We analyzed and compared the biochemical pregnancy rate, clinical pregnancy rate, abortion rate, and live birth rate between the two groups. RESULTS: The Preimplantation genetic testing for aneuploidies (PGT-A) group was associated with higher rate of biochemical pregnancy and clinical pregnancy than the non-PGT-A group, which were 63.9% vs. 56.4% (P = 0.009) and 54.4% vs. 45.6% (P < 0.001), respectively. The abortion rate was significantly lower in the PGT-A group compared to the non-PGT-A group (2.3% vs. 14.7%, P < 0.001). In addition, the live birth rate was significantly higher in the PGT-A group compared to the non-PGT-A group (52.1% and 30.9%, respectively, P < 0.001). CONCLUSION: Next-generation sequencing-based preimplantation genetic testing for aneuploidies significantly improved the pregnancy outcomes in women of advanced maternal age.

Knockout of ACE-N facilitates improved cardiac function after myocardial infarction.

Angiotensin-converting enzyme (ACE) hydrolyzes N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) into inactive fragments through its N-terminal site (ACE-N). We previously showed that Ac-SDKP mediates ACE inhibitors' cardiac effects. Whether increased bioavailability of endogenous Ac-SDKP caused by knocking out ACE-N also improves cardiac function in myocardial infarction (MI)-induced heart failure (HF) is unknown. Wild-type (WT) and ACE-N knockout (ACE-NKO) mice were subjected to MI by ligating the left anterior descending artery and treated with vehicle or Ac-SDKP (1.6 mg/kg/day, s.c.) for 5 weeks, after which echocardiography was performed and left ventricles (LV) were harvested for histology and molecular biology studies. ACE-NKO mice showed increased plasma Ac-SDKP concentrations in both sham and MI group compared to WT. Exogenous Ac-SDKP further increased its circulating concentrations in WT and ACE-NKO. Shortening (SF) and ejection (EF) fractions were significantly decreased in both WT and ACE-NKO mice post-MI, but ACE-NKO mice exhibited significantly lesser decrease. Exogenous Ac-SDKP ameliorated cardiac function post-MI only in WT but failed to show any additive improvement in ACE-NKO mice. Sarcoendoplasmic reticulum calcium transport ATPase (SERCA2), a marker of cardiac function and calcium homeostasis, was significantly decreased in WT post-MI but rescued with Ac-SDKP, whereas ACE-NKO mice displayed less loss of SERCA2 expression. Our study demonstrates that gene deletion of ACE-N resulted in improved LV cardiac function in mice post-MI, which is likely mediated by increased circulating Ac-SDKP and minimally reduced expression of SERCA2. Thus, future development of specific and selective inhibitors for ACE-N could represent a novel approach to increase endogenous Ac-SDKP toward protecting the heart from post-MI remodeling.

Clinical Application of Double Ovulation Stimulation in Patients with Diminished Ovarian Reserve and Asynchronous Follicular Development Undergoing Assisted Reproduction Technology.

OBJECTIVE: This study aimed to compare the clinical effects of double ovulation stimulation (DouStim) applied during the follicular and luteal phases with the antagonist protocol in patients with diminished ovarian reserve (DOR) and asynchronous follicular development undergoing assisted reproductive technology (ART). METHODS: The clinical data of patients with DOR and asynchronous follicular development receiving ART from January 2020 to December 2021 were retrospectively analyzed. The patients were divided into two groups according to their ovulation stimulation protocol: DouStim group (n=30) and antagonist group (n=62). Assisted reproduction and clinical pregnancy outcomes were compared between the two groups. RESULTS: In the DouStim group, the number of oocytes retrieved, metaphase II (MII) oocytes, two-pronuclei (2PN), day 3 (D3) embryos, D3 high-quality embryos as well as blastocyst formation, implantation, and human chorionic gonadotropin-positive rates were significantly greater than those in the antagonist group (all P<0.05). No significant differences were found in MII, fertilization, or continued pregnancy rates at the first frozen embryo transfer (FET), in-vitro fertilization (IVF) cancellation, or early medical abortion rates between the groups (all P>0.05). Except for the early medical abortion rate, the DouStim group generally had favorable outcomes. In the DouStim group, the dosage and duration of gonadotropin and the fertilization rate were significantly greater in the first ovulation stimulation induction than in the second ovulation stimulation induction (P<0.05). CONCLUSION: The DouStim protocol efficiently and economically obtained more mature oocytes and high-quality embryos for patients with DOR and asynchronous follicular development.

MiR-23a Regulates Skin Langerhans Cell Phagocytosis and Inflammation-Induced Langerhans Cell Repopulation.

Langerhans cells (LCs) are skin-resident macrophage that act similarly to dendritic cells for controlling adaptive immunity and immune tolerance in the skin, and they are key players in the development of numerous skin diseases. While TGF-ß and related downstream signaling pathways are known to control numerous aspects of LC biology, little is known about the epigenetic signals that coordinate cell signaling during LC ontogeny, maintenance, and function. Our previous studies in a total miRNA deletion mouse model showed that miRNAs are critically involved in embryonic LC development and postnatal LC homeostasis; however, the specific miRNA(s) that regulate LCs remain unknown. miR-23a is the first member of the miR-23a-27a-24-2 cluster, a direct downstream target of PU.1 and TGF-b, which regulate the determination of myeloid versus lymphoid fates. Therefore, we used a myeloid-specific miR-23a deletion mouse model to explore whether and how miR-23a affects LC ontogeny and function in the skin. We observed the indispensable role of miR-23a in LC antigen uptake and inflammation-induced LC epidermal repopulation; however, embryonic LC development and postnatal homeostasis were not affected by cells lacking miR23a. Our results suggest that miR-23a controls LC phagocytosis by targeting molecules that regulate efferocytosis and endocytosis, whereas miR-23a promotes homeostasis in bone marrow-derived LCs that repopulate the skin after inflammatory insult by targeting Fas and Bcl-2 family proapoptotic molecules. Collectively, the context-dependent regulatory role of miR-23a in LCs represents an extra-epigenetic layer that incorporates TGF-b- and PU.1-mediated regulation during steady-state and inflammation-induced repopulation.