Effects of cluster nursing strategy on neurological and motor functions in patients with moderate to severe traumatic brain injury.

OBJECTIVES: This study aimed to explore the effects of the cluster nursing strategy applied to traumatic brain injury (TBI) patients. Ninety-eight TBI patients admitted to the hospital were selected as the study subjects. METHODS: They were randomized into two groups: the control group and the cluster group, with 49 cases in each group. The control group received routine nursing methods, while the cluster group received cluster nursing strategy. The intervention effects were compared between the two groups. RESULTS: After three months, the total occurrence of complications in the cluster group was significantly lower than that in the control group. Post-intervention, the cluster group had a significantly lower National Institutes of Health Stroke Scale (NIHSS) score and significantly higher Fugl-Meyer score and Loewenstein Occupational Therapy Cognitive Assessment (LOTCA) score compared to the control group. The serum level of glial fibrillary acidic protein (GFAP) in the control group was significantly higher than that in the cluster group, while the serum level of brain-derived neurotrophic factor (BDNF) was significantly lower. CONCLUSIONS: The application of the cluster nursing strategy in the care of TBI patients could effectively reduce the risk of complications and improve neurological, motor, and cognitive functions.

Identification and characterization of whole blood gene expression and splicing quantitative trait loci during early to mid-lactation of dairy cattle.

BACKGROUND: Characterization of regulatory variants (e.g., gene expression quantitative trait loci, eQTL; gene splicing QTL, sQTL) is crucial for biologically interpreting molecular mechanisms underlying loci associated with complex traits. However, regulatory variants in dairy cattle, particularly in specific biological contexts (e.g., distinct lactation stages), remain largely unknown. In this study, we explored regulatory variants in whole blood samples collected during early to mid-lactation (22-150 days after calving) of 101 Holstein cows and analyzed them to decipher the regulatory mechanisms underlying complex traits in dairy cattle. RESULTS: We identified 14,303 genes and 227,705 intron clusters expressed in the white blood cells of 101 cattle. The average heritability of gene expression and intron excision ratio explained by cis-SNPs is 0.28 ± 0.13 and 0.25 ± 0.13, respectively. We identified 23,485 SNP-gene expression pairs and 18,166 SNP-intron cluster pairs in dairy cattle during early to mid-lactation. Compared with the 2,380,457 cis-eQTLs reported to be present in blood in the Cattle Genotype-Tissue Expression atlas (CattleGTEx), only 6,114 cis-eQTLs (P < 0.05) were detected in the present study. By conducting colocalization analysis between cis-e/sQTL and the results of genome-wide association studies (GWAS) from four traits, we identified a cis-e/sQTL (rs109421300) of the DGAT1 gene that might be a key marker in early to mid-lactation for milk yield, fat yield, protein yield, and somatic cell score (PP4 > 0.6). Finally, transcriptome-wide association studies (TWAS) revealed certain genes (e.g., FAM83H and TBC1D17) whose expression in white blood cells was significantly (P < 0.05) associated with complex traits. CONCLUSIONS: This study investigated the genetic regulation of gene expression and alternative splicing in dairy cows during early to mid-lactation and provided new insights into the regulatory mechanisms underlying complex traits of economic importance.

Molecular subtyping and the construction of a predictive model of colorectal cancer based on ion channel genes.

PURPOSE: Colorectal cancer (CRC) is a highly heterogeneous malignancy with an unfavorable prognosis. The purpose of this study was to address the heterogeneity of CRC by categorizing it into ion channel subtypes, and to develop a predictive modeling based on ion channel genes to predict the survival and immunological states of patients with CRC. The model will provide guidance for personalized immunotherapy and drug treatment. METHODS: A consistent clustering method was used to classify 619 CRC samples based on the expression of 279 ion channel genes. Such a method was allowed to investigate the relationship between molecular subtypes, prognosis, and immune infiltration. Furthermore, a predictive modeling was constructed for ion channels to evaluate the ion channel properties of individual tumors using the least absolute shrinkage and selection operator. The expression patterns of the characteristic genes were validated through molecular biology experiments. The effect of potassium channel tetramerization domain containing 9 (KCTD9) on CRC was verified by cellular functional experiments. RESULTS: Four distinct ion channel subtypes were identified in CRC, each characterized by unique prognosis and immune infiltration patterns. Notably, Ion Cluster3 exhibited high levels of immune infiltration and a favorable prognosis, while Ion Cluster4 showed relatively lower levels of immune infiltration and a poorer prognosis. The ion channel score could predict overall survival, with lower scores correlated with longer survival. This score served as an independent prognostic factor and presented an excellent predictive efficacy in the nomogram. In addition, the score was closely related to immune infiltration, immunotherapy response, and chemotherapy sensitivity. Experimental evidence further confirmed that low expression of KCTD9 in tumor tissues was associated with an unfavorable prognosis in patients with CRC. The cellular functional experiments demonstrated that KCTD9 inhibited the proliferation, migration and invasion capabilities of LOVO cells. CONCLUSIONS: Ion channel subtyping and scoring can effectively predict the prognosis and evaluate the immune microenvironment, immunotherapy response, and drug sensitivity in patients with CRC.

A retrospective study of the effects of uterine manipulators on prognosis in patients with cervical cancer.

OBJECTIVE: This retrospective study investigated the effects of uterine manipulator use during minimally invasive radical hysterectomy on prognosis in patients with cervical cancer. METHODS: We collected clinical data on 762 patients with stage IA2 to IIB cervical cancer who underwent radical hysterectomy and pelvic lymphadenectomy in Chinese PLA General Hospital from 2009 to 2019. Kaplan-Meier analysis and log-rank tests were used to compare the 5-year overall survival rates between patients treated with and without a uterine manipulator. RESULTS: Patient demographics did not differ between the two groups. In addition, the incidence of lymphovascular space invasion, tumor size, pathologic types, the International Federation of Gynecology and Obstetrics stage, the histologic grade, and the rate of lymphatic metastases did not differ between the groups. Meanwhile, perioperative clinical indicators were similar in the groups. Furthermore, no significant differences in 5-year survival rates and survival curves were recorded between the groups among both all patients (84.5% vs. 85.6%) and early-stage patients (89.1% vs. 89.2%). CONCLUSIONS: The use of uterine manipulators during minimally invasive radical hysterectomy for cervical cancer did not affect clinicopathological markers or increase the risk of death.

Cross-Species Comparative DNA Methylation Reveals Novel Insights into Complex Trait Genetics among Cattle, Sheep, and Goats.

The cross-species characterization of evolutionary changes in the functional genome can facilitate the translation of genetic findings across species and the interpretation of the evolutionary basis underlying complex phenotypes. Yet, this has not been fully explored between cattle, sheep, goats, and other mammals. Here, we systematically characterized the evolutionary dynamics of DNA methylation and gene expression in 3 somatic tissues (i.e. brain, liver, and skeletal muscle) and sperm across 7 mammalian species, including 3 ruminant livestock species (cattle, sheep, and goats), humans, pigs, mice, and dogs, by generating and integrating 160 DNA methylation and transcriptomic data sets. We demonstrate dynamic changes of DNA hypomethylated regions and hypermethylated regions in tissue-type manner across cattle, sheep, and goats. Specifically, based on the phylo-epigenetic model of DNA methylome, we identified a total of 25,074 hypomethylated region extension events specific to cattle, which participated in rewiring tissue-specific regulatory network. Furthermore, by integrating genome-wide association studies of 50 cattle traits, we provided novel insights into the genetic and evolutionary basis of complex phenotypes in cattle. Overall, our study provides a valuable resource for exploring the evolutionary dynamics of the functional genome and highlights the importance of cross-species characterization of multiomics data sets for the evolutionary interpretation of complex phenotypes in cattle livestock.

Circ_0027446 promotes malignant development of glioblastoma by interacting with miR-346 to up-regulate PGK1.

Circular RNAs (circRNAs) can play essential roles in tumor development, including glioblastoma (GBM). The current study was performed to explore the function and mechanism of circ_0027446 in GBM progression. Circ_0027446, microRNA-346 (miR-346) and Phosphoglycerate kinase 1 (PGK1) levels were detected using reverse transcription-quantitative polymerase chain reaction assay. Cell behaviors were examined using Cell Counting Kit-8 assay, colony formation assay, EdU assay, flow cytometry, and transwell assay. Glycolytic metabolism was analyzed by commercial kits. The protein level was determined via western blot. The target interaction was analyzed by dual-luciferase reporter assay. Circ_0027446 function in vivo was explored by tumor xenograft assay. Circ_0027446 expression was significantly up-regulated in GBM samples and cells. Circ_0027446 down-regulation suppressed proliferation, invasion, glycolytic metabolism and enhanced apoptosis of GBM cells. MiR-346 was a target of circ_0027446, and circ_0027446 promoted GBM progression by sponging miR-346. PGK1 acted as a target gene of miR-346, and circ_0027446 interacted with miR-346 to regulate PGK1 expression. Overexpression of miR-346 inhibited malignant behaviors of GBM cells through down-regulating PGK1. Circ_0027446 contributed to tumor growth in vivo via miR-346/PGK1 axis. The current evidences demonstrated that circ_0027446 facilitated malignant progression of GBM through binding to miR-346 to up-regulate PGK1.

Gallic acid exerts protective effects in spinal cord injured rats through modulating microglial polarization.

BACKGROUND: Spinal cord injury (SCI) is a highly traumatic injury that causes mechanical damage to the spinal cord. Our study aimed to investigate whether gallic acid has protective effects against SCI injury. METHODS: Adult male rats were subjected to contusive spinal cord injuries. For behavioural evaluation, the rats were given gallic acid by i.p. injection at the doses of 10, 50 or 100 mg/kg immediately after SCI once daily for consecutive 28 days. Behavioral tests were used to evaluate locomotor functions, mechanical sensitivity and nerve conduction functions. For biochemical experiments, the rats were randomly divided into three groups: sham group, SCI group and SCI+gallic acid group. The rats in the SCI+gallic acid group were given gallic acid at the dose of 100 mg/kg immediately after SCI once daily for consecutive 14 days. The levels of inflammatory factors were evaluated. RESULTS: Gallic acid treatment could improve locomotive and sensory function and reduce the functional impairments in SCI rats. The effects were more effective with increasing gallic acid dose. The levels of M1 markers (inducible nitric oxide synthase and cyclooxygenase-2) were decreased in gallic acid-treated SCI rats, whereas the levels of M2 markers (arginase 1 and cluster of differentiation 206) were increased in response to gallic acid administration. Gallic acid treatment resulted in a significant reduction in pro-inflammatory cytokines and an increase in anti-inflammatory cytokine levels. CONCLUSION: Gallic acid enhances the recovery in SCI rats by regulating microglial polarization. The underlying mechanism may involve the promotion of M2 polarization and the suppression of M1 polarization in microglia.

Green credit and low-carbon development in China: Fresh evidence on spatial spillover insights.

The promulgation and execution of green credit (GC) policies have had a significant influence on the development of the economy and society, and their impact on low-carbon development (LCD) needs to be taken seriously. On the basis of elaborating the mechanism of the role of GC on LCD, this study constructs a panel fixed effects (FE) model to test the direct impact of GC on LCD by using Chinese provincial-level data from 2007 to 2020. An intermediary effect model is constructed to investigate its indirect effects. A dynamic SDM is further constructed to examine the spatial effects of GC on LCD in neighbouring regions. The results show that GC is helping China to achieve LCD. GC can promote LCD through promoting green innovation, optimizing energy structure and upgrading industrial structure. It is crucial to acknowledge that all three pathways are essential channels of influence and should not be disregarded. GC not only fosters LCD in the local areas, but also has a positive spatial spillover effect in adjacent regions. Based on the above conclusions, this study proposes policy recommendations such as increasing support for GC, smoothing the transmission channel from GC to LCD, and establishing a synergistic linkage mechanism between interregional credit and environmental governance. This study provides valuable insights for China to realize LCD, as well as for other countries to actively engage in energy conservation and emission reduction efforts.

Risk factors and a prediction model for unruptured intracranial aneurysms in patients with ischemic stroke using carotid intima-media thickness and systemic atherosclerosis.

Background: Systemic atherosclerosis and carotid intima-media thickness (IMT) have been widely used in clinical practice for ischemic stroke; however, little is known about the risk factors for unruptured intracranial aneurysms (UIAs) in patients with ischemic stroke (IS). Therefore, we performed this study to identify the risk factors and construct a prediction model for UIA in patients with IS. Methods: Data were retrospectively collected from patients with IS from 2015 to 2022 at the First Hospital of Quanzhou City, Quanzhou, Fujian, China. Risk factors for UIA in patients with IS were identified using a multivariate logistic regression model, and a receiver operating characteristic (ROC) curve was applied to construct the prediction model. Results: Out of the 122 patients with IS, 52 who presented with UIA (ISUIA) were categorized into the study group and the remaining 70 IS patients without UIA into the control group. Patients in the ISUIA group had lower carotid IMT and carotid artery plaque scores than those in the IS group (P < 0.05). Multivariate analyses found that aspirin use (OR: 12.987; P = 0.031), elevated C-reactive protein (CRP) level (OR: 1.019; P = 0.004), and carotid IMT > 0.09 mm (OR: 0.218; P < 0.001) were significantly associated with the risk of UIA in patients with IS. However, UIA in patients with IS was unaffected by the carotid artery plaque score (P = 0.114). The constricted prediction model based on the abovementioned factors for UIA in IS patients was 0.79 (95% CI: 0.71-0.87). Conclusion: The findings revealed that the risk factors for UIA in patients with IS included aspirin use, elevated CRP level, and smaller carotid IMT, and the predictive value of the prediction model was relatively better.

Molecular regulatory mechanism of key LncRNAs in subclinical mastitic cows with folic acid supplementation.

BACKGROUND: Folic acid is a water-soluble B vitamin (B9), which is closely related to the body's immune and other metabolic pathways. The folic acid synthesized by rumen microbes has been unable to meet the needs of high-yielding dairy cows. The incidence rate of subclinical mastitis in dairy herds worldwide ranged between 25%~65% with no obvious symptoms, but it significantly causes a decrease in lactation and milk quality. Therefore, this study aims at exploring the effects of folic acid supplementation on the expression profile of lncRNAs, exploring the molecular mechanism by which lncRNAs regulate immunity in subclinical mastitic dairy cows. RESULTS: The analysis identified a total of 4384 lncRNA transcripts. Subsequently, differentially expressed lncRNAs in the comparison of two groups (SF vs. SC, HF vs. HC) were identified to be 84 and 55 respectively. Furthermore, the weighted gene co-expression network analysis (WGCNA) and the KEGG enrichment analysis result showed that folic acid supplementation affects inflammation and immune response-related pathways. The two groups have few pathways in common. One important lncRNA MSTRG.11108.1 and its target genes (ICAM1, CCL3, CCL4, etc.) were involved in immune-related pathways. Finally, through integrated analysis of lncRNAs with GWAS data and animal QTL database, we found that differential lncRNA and its target genes could be significantly enriched in SNPs and QTLs related to somatic cell count (SCC) and mastitis, such as MSTRG.11108.1 and its target gene ICAM1, CXCL3, GRO1. CONCLUSIONS: For subclinical mastitic cows, folic acid supplementation can significantly affect the expression of immune-related pathway genes such as ICAM1 by regulating lncRNAs MSTRG.11108.1, thereby affecting related immune phenotypes. Our findings laid a ground foundation for theoretical and practical application for feeding folic acid supplementation in subclinical mastitic cows.

Human leukocyte antigen-G in gynaecological tumours.

Gynaecological tumours that threaten the health of women, especially when advanced and recurrent, have remained mostly intractable to existing treatments. Therefore, new therapeutic targets are urgently needed. Human leukocyte antigen-G (HLA-G) is a nonclassical major histocompatibility complex class I molecule typically expressed in foetuses for protection against destruction by the maternal immune system. HLA-G is also expressed under pathological conditions, such as in solid tumours, and may participate in tumour development and serve as a novel immune checkpoint in cancer. Furthermore, it is expressed in most gynaecological tumours. Therefore, inhibiting HLA-G and its receptors to block the immune escape pathway could represent a new strategy in cancer immunotherapy. To the best of our knowledge, this review is the first to summarize recent research findings on HLA-G in gynaecological oncology. We highlight the fact that HLA-G is expressed in gynaecological tumour tissues, wherein it inactivates immune effectors involved in tumour progression. Further studies on HLA-G in gynaecological oncology are needed to incorporate HLA-G into the design and evaluation of immunotherapy for malignant gynaecological diseases.

Comparison of the efficacy of low-molecular-weight heparin and fondaparinux sodium after total knee arthroplasty: a retrospective cohort study.

BACKGROUND: Low-molecular-weight heparin (LMWH) and fondaparinux sodium (FPX) are routinely used to prevent deep vein thrombosis (DVT) after total knee arthroplasty (TKA). In this study, we compared the effects of these agents in preventing post-TKA DVT. METHODS: Clinical data of patients who underwent unilateral TKA for unicompartmental knee osteoarthritis at the Ningxia Medical University General Hospital between September 2021 and June 2022 were retrospectively analyzed. Based on the anticoagulation agent used, the patients were divided into LMWH and FPX groups (34 and 37 patients, respectively). Changes in perioperative coagulation-related indicators, d-dimer and platelet count, perioperative complete blood count, amount of blood loss, lower-limb DVT, pulmonary embolism, and allogeneic blood transfusion were determined. RESULTS: Intergroup differences in d-dimer or fibrinogen (FBG) levels before and 1 or 3 days after surgery were not significant (all p > 0.05); within-group pairwise comparisons indicated significant differences (all, p < 0.05). Intergroup differences in preoperative prothrombin time (PT), thrombin time, activated partial PT, and international normalized ratio were not significant (all p > 0.05), whereas significant differences were detected on postoperative days 1 and 3 (all p < 0.05). Intergroup differences in platelet counts before and 1 or 3 days after surgery were not significantly different (all p > 0.05). Pairwise comparisons of hemoglobin and hematocrit levels between patients in the same group before and 1 or 3 days after surgery revealed significant differences in both groups (all p < 0.05); however, intergroup differences were not significant (all p > 0.05). Although intergroup differences in visual analog scale (VAS) scores before and 1 or 3 days after surgery were not significant (p > 0.05), we detected significant intragroup differences in VAS scores before and 1 or 3 days after surgery (p < 0.05). The treatment cost ratio was significantly lower in the LMWH group than in the FPX group (p < 0.05). CONCLUSION: Both LMWH and FPX can effectively prevent DVT after TKA. There are some suggestive signals that FPX may have more beneficial pharmacological effects and clinical significance, while LMWH is cheaper and therefore more economical.

The DNA methylation status of the serotonin metabolic pathway associated with reproductive inactivation induced by long-light exposure in Magang geese.

BACKGROUND: Domestic geese are seasonal breeders and have the lowest reproductive capacity among all poultry species. Magang geese is a topical short-day breeder, short photoperiod exposure stimulates its reproductive activity while long photoperiod inhibits. To explore epigenetic change that could influence reproductive activity, we performed whole genome bisulfite sequencing and transcriptome sequencing in the hypothalamus at three reproductive stages during long-light exposure in male Magang geese. RESULTS: A total number of 10,602 differentially methylated regions (DMRs) were identified among three comparison groups. We observed that the vast majority of DMRs were enriched in intron regions. By integrating the BS-sequencing and RNA-seq data, the correlation between methylation changes of CG DMRs and expression changes of their associated genes was significant only for genes containing CG DMRs in their intron. A total of 278 DMR-associated DEGs were obtained among the three stages. KEGG analysis revealed that the DMR-associated DEGs were mainly involved in 11 pathways. Among them, the neuroactive ligand-receptor interaction pathway was significantly enriched in both two comparisons (RA vs.RD and RD vs.RI); the Wnt signaling pathway, apelin signaling pathway, melanogenesis, calcium signaling pathway, focal adhesion, and adherens junction were significantly enriched in the RA vs. RI comparison. In addition, the expression level of two serotonin-metabolic genes was significantly altered during reproductive axis inactivation by the methylation status of their promoter region (TPH2) and intron region (SLC18A2), respectively. These results were confirmed by Bisulfite sequencing PCR (BSP), pyrosequencing, and real-time qPCR, indicating that serotonin metabolic signaling may play a key role in decreasing the reproductive activity of Magang geese induced by long-light exposure. Furthermore, we performed a metabolomics approach to investigate the concentration of neurotransmitters among the three stages, and found that 5-HIAA, the last product of the serotonin metabolic pathway, was significantly decreased in the hypothalamus during RI. CONCLUSIONS: Our study reveals that the methylation status of the serotonin metabolic pathway in the hypothalamus is associated with reproductive inactivation, and provided new insight into the effect of DNA methylation on the reproductive regulation of the hypothalamus in Magang geese.

Integrating sperm cell transcriptome and seminal plasma metabolome to analyze the molecular regulatory mechanism of sperm motility in Holstein stud bulls.

Considering that artificial insemination is the most widely used assisted reproductive technique in the dairy industry, the semen quality of bulls is very important for selecting excellent stud bulls. Sperm motility is one of the important traits of semen quality, and related genes may be regulated by environmental factors. Seminal plasma can affect sperm cell transcriptome and further affect sperm motility through exosome or other processes. However, the molecular regulation mechanism of bull sperm motility has not been studied by combining the sperm cell transcriptome with seminal plasma metabolome. The number of motile sperm per ejaculate (NMSPE) is an integrated indicator for assessing sperm motility in stud bulls. In the present study, we selected 7 bulls with higher NMSPE (5,698.55 million +/- 945.40 million) as group H and 7 bulls with lower NMSPE (2,279.76 million +/- 1,305.69 million) as group L from 53 Holstein stud bulls. The differentially expressed genes (DEGs) in sperm cells were evaluated between the two groups (H vs. L). We conducted gene co-expression network analysis (WGCNA) on H and L groups of bulls, as well as two monozygotic twin Holstein bulls with different NMSPE values, to screen candidate genes for NMSPE. The regulatory effect of seminal plasma metabolome on the candidate genes of NMSPE was also investigated. A total of 1,099 DEGs were identified in the sperm cells of H and L groups. These DEGs were primarily concentrated in energy metabolism and sperm cell transcription. The significantly enriched Kyoto encyclopedia of genes and genomes (KEGG) pathways of the 57 differential metabolites were the aminoacyl-tRNA biosynthesis pathway and vitamin B6 metabolism pathway. Our study discovered 14 genes as the potential candidate markers for sperm motility, including FBXO39. We observed a broad correlation between transcriptome of sperm cells and seminal plasma metabolome, such as three metabolites, namely, mesaconic acid, 2-coumaric acid, and 4-formylaminoantipyrine, might regulate FBXO39 expression through potential pathways. The genes related to seminal plasma metabolites expressed in sperm cells are not only located near the quantitative trait loci of reproductive traits, but also enriched in the genome-wide association study signal of sire conception rate. Collectively, this study was the first to investigate the interplays among transcriptome of sperm cells and seminal plasma metabolome from Holstein stud bulls with different sperm motility.

A Holstein stud bull can produce thousands of doses of frozen semen, which are used to distribute its selected genetics to dairy herds all over the world. The semen quality of stud bulls has an impact on the economics of the breeding centers. Our previous study found that monozygotic twin stud bulls showed different semen quality traits and different transcriptomic profiles in sperm cells. The number of motile sperm per ejaculate (NMSPE) is an integrated trait for assessing sperm motility in stud bulls, which is one of the most important semen quality traits. In the present study, we selected 7 stud bulls that had a high NMSPE (named as H group) and 7 stud bulls with low NMSPE (named as L group) from a Chinese Holstein bull population based on 9 yr of semen quality records. In this study, we investigated the sperm cells transcriptomic differences between the two groups and observed the influences of seminal plasma metabolites on the transcriptomic profiles of the sperm cells. The results showed that the expression level of the differentially expressed genes in the sperm cells is closely related to NMSPE. Our study discovered 14 genes as the potential candidate markers for sperm motility, including FBXO39. Our data provide new insights into the improvement of bovine semen quality traits.

Does digital finance enhance industrial green total factor productivity? Theoretical mechanism and empirical test.

The development and application of digital finance has brought profound changes to the real economy, and its impact on industrial green total factor productivity is worthy of attention and evaluation. The industrial green total factor productivity of each province in China is measured by using EBM-ML index with the provincial panel data collected from 2011 to 2020. The panel fixed effects model is used to estimate the impact of digital finance on industrial green total factor productivity. The intermediary effect model is constructed to analyze its conduction mechanisms. The heterogeneity of the impact of digital finance on industrial green total factor productivity is further explored. The results indicate that digital finance makes a significant contribution to the promotion of industrial green total factor productivity. Digital finance indirectly promotes the enhancement of industrial green total factor productivity by promoting technological innovation, driving industrial upgrading and stimulating entrepreneurial dynamism. The impact of digital finance on industrial green total factor productivity has obvious sub-dimension heterogeneity and regional heterogeneity. Based on the above conclusions, we also suggest policy recommendations such as unblocking the conduction channels of digital finance and implementing the differentiated digital finance development strategy. The highlight of this paper is that it takes digital finance as the entry point and shifts the research content to the real economy, broadening the research perspective of "digital finance".

Canalization of Phenotypes-When the Transcriptome is Constantly but Weakly Perturbed.

Recent studies have increasingly pointed to microRNAs (miRNAs) as the agent of gene regulatory network (GRN) stabilization as well as developmental canalization against constant but small environmental perturbations. To analyze mild perturbations, we construct a Dicer-1 knockdown line (dcr-1 KD) in Drosophila that modestly reduces all miRNAs by, on average, ∼20%. The defining characteristic of stabilizers is that, when their capacity is compromised, GRNs do not change their short-term behaviors. Indeed, even with such broad reductions across all miRNAs, the changes in the transcriptome are very modest during development in stable environment. By comparison, broad knockdowns of other regulatory genes (esp. transcription factors) by the same method should lead to drastic changes in the GRNs. The consequence of destabilization may thus be in long-term development as postulated by the theory of canalization. Flies with modest miRNA reductions may gradually deviate from the developmental norm, resulting in late-stage failures such as shortened longevity. In the optimal culture condition, the survival to adulthood is indeed normal in the dcr-1 KD line but, importantly, adult longevity is reduced by ∼90%. When flies are stressed by high temperature, dcr-1 KD induces lethality earlier in late pupation and, as the perturbations are shifted earlier, the affected stages are shifted correspondingly. Hence, in late stages of development with deviations piling up, GRN would be increasingly in need of stabilization. In conclusion, miRNAs appear to be a solution to weak but constant environmental perturbations.

Outcomes associated with different surgical approaches to radical hysterectomy: A systematic review and network meta-analysis.

OBJECTIVE: To evaluate the efficacy and safety of five different approaches to cervical cancer surgery. METHODS: We conducted a systematic search for comparative studies on different radical hysterectomy types for cervical cancer in PubMed, Embase, the Cochrane Library, and Web of Science databases. All included observational studies used survival analyses to compare clinical outcomes of patients undergoing different radical hysterectomy types. All studies were assessed by the Newcastle-Ottawa Scale with scores of at least seven points. We extracted the relevant data and conducted a network meta-analysis to compare clinical outcomes among five surgical approaches. RESULTS: Thirty studies (n = 11 353) were included. Robotic surgery had the lowest blood loss volume and hospitalization duration; open surgery had the shortest operative time. Vaginal assisted laparoscopic surgery was associated with the highest number of resected lymph nodes and lowest rate of perioperative complications. Survival outcomes and tumor recurrence outcomes were similar among the approaches. CONCLUSION: The current approaches to cervical cancer surgery have comparable efficacies.

Transcriptomic analysis of mid-secretory endometrium reveals essential immune factors associated with pregnancy after single euploid blastocyst transfer.

PURPOSE: Implantation is a limiting factor for treatment success in assisted reproduction. Both embryonic and endometrial factors contribute to implantation. Embryonic factors have often been ignored in previous studies about the role of endometrium in implantation. In this study, we sought to identify the endometrial genes associated with negative pregnancy outcomes following the transfer of a single euploid blastocyst. METHODS: Computational analyses of the transcriptomes of mid-secretory endometria from nine pregnant and seven non-pregnant patients in a cycle preceding the transfer of a single euploid blastocyst in a vitrified-warmed cycle were performed. RESULTS: Principal component analysis of two reported endometrial receptivity gene sets showed close clustering of the pregnant and non-pregnant samples. Differential gene expression analysis and co-expression module analysis identified 131 genes associated with the pregnancy status. The endometrial signatures identified highlight the importance of immune and metabolic regulation in pregnancy outcome. Network analysis identified 20 hub genes that could predict pregnancy outcomes with 88.9% sensitivity and 85.7% specificity. Single-cell gene expression analysis highlighted the regulation of endometrial natural killer (NK) cells, T cells, and macrophages during embryo implantation. Immune cell abundance analysis supported the dysregulation of cytotoxic immune cells in the endometria of non-pregnant women. CONCLUSIONS: We reported the first endometrial gene signature associated with pregnancy after elimination of embryo aneuploidy and highlighted the importance of the endometrial immune microenvironment and metabolic status in pregnancy outcomes.

How does digital economy affect green total factor productivity? Evidence from China.

To date, digital economy has become an emerging driving force of economic growth in various countries. To further explore the green value of digital economy, full array polygon graphic index method and Global Malmquist productivity index are used to evaluate China's digital economy development and green total factor productivity respectively. Based on a comprehensive explanation of the influence mechanism, spatial econometric model and intermediary effect model are constructed to test the spatial spillover effect and transmission mechanism between digital economy and green total factor productivity. The results show that digital economy has a positive direct impact and spatial spillover effect on green total factor productivity with the significant U-shaped characteristics, and these effects mainly come from the promotion of green technology progress by digital economy. Industrial structure upgrading and factor market distortion respectively account for 22 % and 5.875 % of the impact of digital economy on green total factor efficiency, which means that they are the two primary channels for digital economy to influence green total factor productivity. Results of heterogeneity analysis show that digital economy is the key factor for resource-based cities to break the "resource curse", but the unbalanced development of digital economy leads to the "digital gap" between the central and peripheral cities.