MKLN1-AS promotes pancreatic cancer progression as a crucial downstream mediator of HIF-1α through miR-185-5p/TEAD1 pathway.

In pancreatic ductal adenocarcinomas (PDAC), profound hypoxia plays key roles in regulating cancer cell behavior, including proliferation, migration, and resistance to therapies. The initial part of this research highlights the important role played by long noncoding RNA (lncRNA) MKLN1-AS, which is controlled by hypoxia-inducible factor-1 alpha (HIF-1α), in the progression of PDAC. Human samples of PDAC showed a notable increase in MKLN1-AS expression, which was linked to a worse outcome. Forced expression of MKLN1-AS greatly reduced the inhibitory impact on the growth and spread of PDAC cells caused by HIF-1α depletion. Experiments on mechanisms showed that HIF-1α influences the expression of MKLN1-AS by directly attaching to a hypoxia response element in the promoter region of MKLN1-AS.MKLN1-AS acts as a competitive endogenous RNA (ceRNA) by binding to miR-185-5p, resulting in the regulation of TEAD1 expression and promoting cell proliferation, migration, and tumor growth. TEAD1 subsequently enhances the development of PDAC. Our study results suggest that MKLN1-AS could serve as a promising target for treatment and a valuable indicator for predicting outcomes in PDAC. PDAC is associated with low oxygen levels, and the long non-coding RNA MKLN1-AS interacts with TEAD1 in this context.

Overexpression of Let-7a mitigates diploidization in mouse androgenetic haploid embryonic stem cells.

Mouse androgenetic haploid embryonic stem cells (mAG-haESCs) can be utilized to uncover gene functions, especially those of genes with recessive effects, and to produce semicloned mice when injected into mature oocytes. However, mouse haploid cells undergo rapid diploidization during long-term culture in vitro and subsequently lose the advantages of haploidy, and the factors that drive diploidization are poorly understood. In this study, we compared the small RNAs (sRNAs) of mAG-haESCs, normal embryonic stem cells (ESCs), and mouse round spermatids by high-throughput sequencing and identified distinct sRNA profiles. Several let-7 family members and miR-290-295 cluster microRNAs (miRNAs) were found significantly differentially transcribed. Knockdown and overexpression experiments showed that let-7a and let-7g suppress diploidization while miR-290a facilitates diploidization. Our study revealed the unique sRNA profile of mAG-haESCs and demonstrated that let-7a overexpression can mitigate diploidization in mAG-haESCs. These findings will help us to better understand mAG-haESCs and utilize them as tools in the future.

Chromatin landscape instructs precise transcription factor regulome during embryonic lineage specification.

Embryos, originating from fertilized eggs, undergo continuous cell division and differentiation, accompanied by dramatic changes in transcription, translation, and metabolism. Chromatin regulators, including transcription factors (TFs), play indispensable roles in regulating these processes. Recently, the trophoblast regulator TFAP2C was identified as crucial in initiating early cell fate decisions. However, Tfap2c transcripts persist in both the inner cell mass and trophectoderm of blastocysts, prompting inquiry into Tfap2c's function in post-lineage establishment. In this study, we delineate the dynamics of TFAP2C during the mouse peri-implantation stage and elucidate its collaboration with the key lineage regulators CDX2 and NANOG. Importantly, we propose that de novo formation of H3K9me3 in the extraembryonic ectoderm during implantation antagonizes TFAP2C binding to crucial developmental genes, thereby maintaining its lineage identity. Together, these results highlight the plasticity of the chromatin environment in designating the genomic binding of highly adaptable lineage-specific TFs and regulating embryonic cell fates.

The gonadal niche safeguards human fetal germline cell development following maternal SARS-CoV-2 infection.

During pregnancy, germline development is vital for maintaining the continuation of species. Recent studies have shown increased pregnancy risks in COVID-19 patients at the perinatal stage. However, the potential consequence of infection for reproductive quality in developing fetuses remains unclear. Here, we analyze the transcriptome and DNA methylome of the fetal germline following maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We find that infection at early gestational age, a critical period of human primordial germ cell specification and epigenetic reprogramming, trivially affects fetal germ cell (FGC) development. Additionally, FGC-niche communications are not compromised by maternal infection. Strikingly, both general and SARS-CoV-2-specific immune pathways are greatly activated in gonadal niche cells to protect FGCs from maternal infection. Notably, there occurs an "in advance" development tendency in FGCs after maternal infection. Our study provides insights into the impacts of maternal SARS-CoV-2 infection on fetal germline development and serves as potential clinical guidance for future pandemics.

Effects of cycloplegia on crystalline lens morphology and location in acute acquired concomitant esotropia.

PURPOSE: The study aims to compare morphology and location of crystalline lens between acute acquired concomitant esotropia (AACE) patients and control subjects, both before and after cycloplegia. METHODS: This is a prospective and observational clinical study. Morphological and locational parameters of the crystalline lens in 53 AACE patients and 32 control subjects were assessed before and after cycloplegia using CASIA2 system, which represents the latest swept-source anterior segment optical coherence tomography. Cycloplegic refraction was recorded by administering 1% atropine in patients younger than 12 years and 1% cyclopentolate in those > 12 years old. Morphological parameters included anterior radius of curvature (ARC), posterior radius of curvature (PRC), lens thickness (LTH), and equivalent diameter of lens (LED). Locational parameters comprised lens decentration (LD) and lens tilt (LT). Comparison of these parameters before and after cycloplegia were conducted between AACE and controls. Additionally, the study analyzed and compared the changes in these parameter post-cycloplegia. RESULTS: Our findings suggest no significant difference in morphological parameters including ARC, PRC, LTH and LED between AACE patients and controls before or after cycloplegia. However, 2D-modeling data in the 0° meridian revealed that variation post-cycloplegia of LD (lens shift) in right eyes was different in AACE patients, measuring - 0.03(0.08) [median(interquartile range)] which was significantly distinct from the control group, exhibiting a measurement of 0.01(0.06) (z = - 2.373, p = 0.018). In left eyes, a similar trend was observed with lens shift in the 0° meridian being 0.02(0.06) in AACE, significantly differing from control group's measurement of - 0.02(0.08) (z = - 2.809, p = 0.005). Further, correlation analysis revealed that larger temporal shift of lens was associated with greater changes in ARC (r = 0.294, p = 0.006) and LTH (r = - 0.230, p = 0.031). CONCLUSIONS: The morphological features of the crystalline lens were similar in AACE patients and controls; however, the change of lens location by cycloplegia was observed only in AACE patients, suggesting an association with excessive accommodation.

Spatial analysis toolkits for RNA in situ sequencing.

Spatial transcriptomics (ST) is featured by high-throughput gene expression profiling within their native cell and tissue context, offering a means to investigate gene regulatory networks in tissue microenvironment. In situ sequencing (ISS) is an imaging-based ST technology that simultaneously detects hundreds to thousands of genes at subcellular resolution. As a highly reproducible and robust technique, ISS has been widely adapted and undergone a series of technical iterations. As the interest in ISS-based spatial transcriptomic analysis grows, scalable and integrated data analysis workflows are needed to facilitate the applications of ISS in different research fields. This review presents the state-of-the-art bioinformatic toolkits for ISS data analysis, which covers the upstream and downstream analysis workflows, including image analysis, cell segmentation, clustering, functional enrichment, detection of spatially variable genes and cell clusters, spatial cell-cell interactions, and trajectory inference. To assist the community in choosing the right tools for their research, the application of each tool and its compatibility with ISS data are reviewed in detailed. Finally, future perspectives and challenges concerning how to integrate heterogeneous tools into a user-friendly analysis pipeline are discussed. This article is categorized under: RNA Methods > RNA Analyses In Vitro and In Silico.

Origin of functional de novo genes in humans from "hopeful monsters".

For a long time, it was believed that new genes arise only from modifications of preexisting genes, but the discovery of de novo protein-coding genes that originated from noncoding DNA regions demonstrates the existence of a "motherless" origination process for new genes. However, the features, distributions, expression profiles, and origin modes of these genes in humans seem to support the notion that their origin is not a purely "motherless" process; rather, these genes arise preferentially from genomic regions encoding preexisting precursors with gene-like features. In such a case, the gene loci are typically not brand new. In this short review, we will summarize the definition and features of human de novo genes and clarify their process of origination from ancestral non-coding genomic regions. In addition, we define the favored precursors, or "hopeful monsters," for the origin of de novo genes and present a discussion of the functional significance of these young genes in brain development and tumorigenesis in humans. This article is categorized under: RNA Evolution and Genomics > RNA and Ribonucleoprotein Evolution.

A new plant-esterase inhibition based electrochemical sensor with signal amplification by MoS2@N-CDs for chlorpyrifos detection.

Chlorpyrifos (CPF) is the most common pesticide entering the food chain and posing a threat to human health. This study presents a new electrochemical biosensor based on molybdenum disulfide nanosheets and nitrogen-doped carbon dot nanocomposite (MoS2@N-CDs) and kidney bean esterase (KdBE), and it is shown to achieve accurate detection of CPF. MoS2@N-CDs were prepared by a facile solvothermal method and characterized by electron microscopy, X-ray diffraction and X-ray photoelectron spectroscopy. Electrochemical characterization confirmed that MoS2@N-CDs facilitated electron transfer and increased the electroactive surface area of the electrode, thereby improved the sensing performance of the electrode. The oxidation peak current of 1-naphthol, which was produced by the hydrolysis of 1-naphthyl acetate catalyzed by KdBE, was adopted as the signal of the sensor. CPF can suppress KdBE activity and consequently cause a decrease in the sensing signal. The experimental results show that the variation of sensing signal is a reliable index to evaluate the CPF level. Under the optimized conditions, the developed enzyme sensor showed superior CPF assay performance with a linear detection range as wide as 0.01-500 µg L-1 and LOD as low as 3.5 × 10-3 µg L-1 (S/N = 3). The inter- and intra-batch RSDs for electrode testing were 4.02% and 2.69%, respectively. Moreover, the developed biosensor also showed good stability and anti-interference. The spiked recoveries of CPF in oilseed rape and cabbage ranged from 98.09% to 106.01% with low relative standard deviation (RSD) (<5.23%), suggesting that the sensor is a promising tool to enable simple, low-cost but highly sensitive large-scale screening of CPF residues in food.

RBM22 regulates RNA polymerase II 5' pausing, elongation rate, and termination by coordinating 7SK-P-TEFb complex and SPT5.

BACKGROUND: Splicing factors are vital for the regulation of RNA splicing, but some have also been implicated in regulating transcription. The underlying molecular mechanisms of their involvement in transcriptional processes remain poorly understood. RESULTS: Here, we describe a direct role of splicing factor RBM22 in coordinating multiple steps of RNA Polymerase II (RNAPII) transcription in human cells. The RBM22 protein widely occupies the RNAPII-transcribed gene locus in the nucleus. Loss of RBM22 promotes RNAPII pause release, reduces elongation velocity, and provokes transcriptional readthrough genome-wide, coupled with production of transcripts containing sequences from downstream of the gene. RBM22 preferentially binds to the hyperphosphorylated, transcriptionally engaged RNAPII and coordinates its dynamics by regulating the homeostasis of the 7SK-P-TEFb complex and the association between RNAPII and SPT5 at the chromatin level. CONCLUSIONS: Our results uncover the multifaceted role of RBM22 in orchestrating the transcriptional program of RNAPII and provide evidence implicating a splicing factor in both RNAPII elongation kinetics and termination control.

Defining a TFAP2C-centered transcription factor network during murine peri-implantation.

Transcription factors (TFs) play important roles in early embryonic development, but factors regulating TF action, relationships in signaling cascade, genome-wide localizations, and impacts on cell fate transitions during this process have not been clearly elucidated. In this study, we used uliCUT&RUN-seq to delineate a TFAP2C-centered regulatory network, showing that it involves promoter-enhancer interactions and regulates TEAD4 and KLF5 function to mediate cell polarization. Notably, we found that maternal retinoic acid metabolism regulates TFAP2C expression and function by inducing the active demethylation of SINEs, indicating that the RARG-TFAP2C-TEAD4/KLF5 axis connects the maternal-to-zygotic transition to polarization. Moreover, we found that both genomic imprinting and SNP-transferred genetic information can influence TF positioning to regulate parental gene expressions in a sophisticated manner. In summary, we propose a ternary model of TF regulation in murine embryonic development with TFAP2C as the core element and metabolic, epigenetic, and genetic information as nodes connecting the pathways.

Development and validation of a radiomics-based model for predicting osteoporosis in patients with lumbar compression fractures.

BACKGROUND: Osteoporosis, a metabolic bone disorder, markedly elevates fracture risks, with vertebral compression fractures being predominant. Antiosteoporotic treatments for patients with osteoporotic vertebral compression fractures (OVCF) lessen both the occurrence of subsequent fractures and associated pain. Thus, diagnosing osteoporosis in OVCF patients is vital. PURPOSE: The aim of this study was to develop a predictive radiographic model using T1 sequence MRI images to accurately determine whether patients with lumbar spine compression fractures also have osteoporosis. STUDY DESIGN: Retrospective cohort study. PATIENT SAMPLE: Patients over 45 years of age diagnosed with a fresh lumbar compression fracture. OUTCOME MEASURES: Diagnostic accuracy of the model (area under the ROC curve). METHODS: The study retrospectively collected clinical and imaging data (MRI and DEXA) from hospitalized lumbar compression fracture patients (L1-L4) aged 45 years or older between January 2021 and June 2023. Using the pyradiomics package in Python, features from the lumbar compression fracture vertebral region of interest (ROI) were extracted. Downscaling of the extracted features was performed using the Mann-Whitney U test and the least absolute shrinkage selection operator (LASSO) algorithm. Subsequently, six machine learning models (Naive Bayes, Support Vector Machine [SVM], Decision Tree, Random Forest, Extreme Gradient Boosting [XGBoost], and Light Gradient Boosting Machine [LightGBM]) were employed to train and validate these features in predicting osteoporosis comorbidity in OVCF patients. RESULTS: A total of 128 participants, 79 in the osteoporotic group and 49 in the non-osteoporotic group, met the study's inclusion and exclusion criteria. From the T1 sequence MRI images, 1906 imaging features were extracted in both groups. Utilizing the Mann-Whitney U test, 365 radiologic features were selected out of the initial 1,906. Ultimately, the lasso algorithm identified 14 significant radiological features. These features, incorporated into six conventional machine learning algorithms, demonstrated successful prediction of osteoporosis in the validation set. The NaiveBayes model yielded an area under the receiver operating characteristic curve (AUC) of 0.84, sensitivity of 0.87, specificity of 0.70, and accuracy of 0.81. CONCLUSIONS: A NaiveBayes machine learning algorithm can predict osteoporosis in OVCF patients using t1-sequence MRI images of lumbar compression fractures. This approach aims to obviate the necessity for further osteoporosis assessments, diminish patient exposure to radiation, and bolster the clinical care of patients with OVCF.

The combination of paeonol, diosmetin-7-O-ß-D-glucopyranoside, and 5-hydroxymethylfurfural from Trichosanthis pericarpium alleviates arachidonic acid-induced thrombosis in a zebrafish model.

Trichosanthis fruit (TF) is a classic medicinal material obtained from Shandong, China. The peel of this fruit (Trichosanthis pericarpium, TP) is known to exert anti-thrombotic effects. However, the anti-thrombotic active components and mechanisms of TP have yet to be fully elucidated. Combined with zebrafish models and high-performance liquid chromatography (HPLC), this study evaluated the endogenous anti-thrombotic effects with the combination of three compounds from TP. First, we used HPLC to investigate the components in the water extract of TP. Next, we used the zebrafish model to investigate the anti-thrombotic activity of the three compound combinations by evaluating a range of indicators. Finally, the expression of related genes was detected by real-time quantitative polymerase chain reaction (qPCR). HPLC detected a total of eight components in TP water extract, with high levels of paeonol (Pae), diosmetin-7-O-ß-D-glucopyranoside (diosmetin-7-O-glucoside), and 5-hydroxymethylfurfural (5-HMF). The most significant anti-thrombotic activity was detected when the Pae: diosmetin-7-O-glucoside:5-HMF ratio was 4:3:3. qPCR analysis revealed that the abnormal expression levels of f2, fga, fgb, vwf, ptgs1, and tbxas1 induced by arachidonic acid (AA) were improved. The combination of Pae, diosmetin-7-O-glucoside, and 5-HMF may alleviate AA-induced thrombosis by inhibiting the inflammatory reaction, coagulation cascade reaction, and arachidonic acid metabolism pathways.

Electric field induced the changes in structure and function of human transforming growth factor beta receptor type I: from molecular dynamics to docking.

The transforming growth factor beta (TGF-ß) signaling pathway is believed to play essential roles in several physiological activities, including cancer. TGF-ß receptor type I (TBR-I) is a key membrane receptor protein in the TGF-ß signaling pathway, which relates to many intracellular biological effects. In recent years, cold atmospheric plasma (CAP) has been found to have promising prospects in selective anticancer therapy and has confirmed its essential role in the TGF-ß signaling pathway. However, the ambiguous effect of CAP-induced electric field (EF) on TBR-I still limits the application of CAP in clinical therapy. Molecular dynamics is applied to assess the effect of EF on the structure of the extracellular domain of TBR-I using a series of indicators and methods, and then we discuss the ligand binding ability of TBR-I. Results show that moderate EF intensities' structural restraints may contribute to the structural stability and ligand-binding ability of TBR-I, but an EF higher than 0.1 V/nm will be harmful. What's more, EF induces a change in the docking interface of TBR-I, showing the conformation and position of special sequences of residues decide the ligand binding surface. The relevant results suggest that CAP-induced EF plays a crucial role in receptor-receptor interaction and provides significant guidelines for EF-related anticancer therapy.Communicated by Ramaswamy H. Sarma.

ADNP modulates SINE B2-derived CTCF-binding sites during blastocyst formation in mice.

CTCF is crucial for chromatin structure and transcription regulation in early embryonic development. However, the kinetics of CTCF chromatin occupation in preimplantation embryos have remained unclear. In this study, we used CUT&RUN technology to investigate CTCF occupancy in mouse preimplantation development. Our findings revealed that CTCF begins binding to the genome prior to zygotic genome activation (ZGA), with a preference for CTCF-anchored chromatin loops. Although the majority of CTCF occupancy is consistently maintained, we identified a specific set of binding sites enriched in the mouse-specific short interspersed element (SINE) family B2 that are restricted to the cleavage stages. Notably, we discovered that the neuroprotective protein ADNP counteracts the stable association of CTCF at SINE B2-derived CTCF-binding sites. Knockout of Adnp in the zygote led to impaired CTCF binding signal recovery, failed deposition of H3K9me3, and transcriptional derepression of SINE B2 during the morula-to-blastocyst transition, which further led to unfaithful cell differentiation in embryos around implantation. Our analysis highlights an ADNP-dependent restriction of CTCF binding during cell differentiation in preimplantation embryos. Furthermore, our findings shed light on the functional importance of transposable elements (TEs) in promoting genetic innovation and actively shaping the early embryo developmental process specific to mammals.

The impact of Lactococcus lactis KUST48 on the transcription profile of Aeromonas hydrophila-infected zebrafish spleen.

Aeromonas hydrophila, an aquatic pathogenic bacterium, has been found to infect many fish species and cause huge aquaculture losses. Antibiotics are the most common drugs used to treat these infections. However, antibiotic abuse can lead to the development of antibiotic resistance. Probiotics have the potential to replace antibiotics for preventing infections. Zebrafish (Danio rerio) is a model organism used to study the innate immune system and host-pathogen interactions. Currently, there is little information on how the fish immune system responds to A. hydrophila and probiotic treatment. To increase the understanding of the molecular mechanisms behind the zebrafish defense against A. hydrophila and provide evidence that antibiotics can be replaced by probiotics, a transcriptome analysis of the zebrafish spleen was conducted 48 hours after infection by A. hydrophila, as well as after treatment using Lactococcus lactis KUST48 4 hours after infection. A total of 36,499 genes were obtained. There were 3,337 genes found to have significant differential expression between treatment and control groups. According to further annotation and enrichment analysis, differentially expressed genes (DEGs) were involved in signal transduction, endocrine system cancer, and the immune system. Insulin resistance disappeared in the zebrafish after treatment. Quantitative real-time PCR was performed to confirm the significant regulation of immune defense DEGs, the results of which were consistent with the RNA-sequencing data. These results could serve as a basis for future studies on the immune response to A. hydrophila and provide suggestions for probiotic alternatives to antibiotics, which will be of great significance to aquaculture and environmental protection.IMPORTANCEIn recent years, the unreasonable use of antibiotics has led to the emergence of drug-resistant pathogenic bacteria, antibiotic residues, cross infection, toxic side effects, and so on, which has caused a serious threat to human food safety and life health. In recent years, many studies have demonstrated the potential of probiotics as a substitute for antibiotics, but there is still a lack of understanding of the molecular mechanisms underlying probiotic therapy. We conduct a research on the impact of Lactococcus lactis KUST48 on the transcription profile of Aeromonas hydrophila-infected zebrafish spleen. Mortality of zebrafish infected with A. hydrophila was significantly reduced after treatment with L. lactis KUST48. Our results can help to strengthen our understanding of the pathogenic mechanisms of zebrafish and provide a valuable reference for the molecular mechanisms of probiotic therapy.

A Retrospective Study of the Effect of Spinopelvic Parameters on Fatty Infiltration in Paraspinal Muscles in Patients With Lumbar Spondylolisthesis.

OBJECTIVE: The effect on fat infiltration (FI) of paraspinal muscles in degenerative lumbar spinal diseases has been demonstrated except for spinopelvic parameters. The present study is to identify the effect of spinopelvic parameters on FI of paraspinal muscle (PSM) and psoas major muscle (PMM) in patients with degenerative lumbar spondylolisthesis. METHODS: A single-center, retrospective cross-sectional study of 160 patients with degenerative lumbar spondylolisthesis (DLS) and lumbar stenosis (LSS) who had lateral full-spine x-ray and lumbar spine magnetic resonance imaging was conducted. PSM and PMM FIs were defined as the ratio of fat to its muscle cross-sectional area. The FIs were compared among patients with different pelvic tilt (PT) and pelvic incidence (PI), respectively. RESULTS: The PSM FI correlated significantly with pelvic parameters in DLS patients, but not in LSS patients. The PSM FI in pelvic retroversion (PT > 25°) was 0.54 ± 0.13, which was significantly higher in DLS patients than in normal pelvis (0.41 ± 0.14) and pelvic anteversion (PT < 5°) (0.34 ± 0.12). The PSM FI of DLS patients with large PI ( > 60°) was 0.50 ± 0.13, which was higher than those with small ( < 45°) and normal PI (0.37 ± 0.11 and 0.36 ± 0.13). However, the PSM FI of LSS patients didn't change significantly with PT or PI. Moreover, the PMM FI was about 0.10-0.15, which was significantly lower than the PSM FI, and changed with PT and PI in a similar way of PSM FI with much less in magnitude. CONCLUSION: FI of the PSMs increased with greater pelvic retroversion or larger pelvic incidence in DLS patients, but not in LSS patients.

Efficacy and safety of ketamine as an adjuvant to regional anesthesia: A systematic review and meta-analysis of randomized controlled trials.

STUDY OBJECTIVE: To identify whether adding ketamine to the local anesthetics (LA) in the regional anesthesia could prolong the duration of analgesia. DESIGN: A Systematic review and meta-analysis of randomized controlled trials. SETTING: The major dates were obtained in the operating room and the postoperative recovery ward. PATIENTS: A total of 1011 patients at ASA physical status I and II were included in the analysis. Procedure performed including cesarean section, orthopedic, radical mastectomy, urological or lower abdominal surgery and intracavitary brachytherapy implants insertion. INTERVENTIONS: After an extensive search of the electronic database, patients received regional anesthesia combined or not combined general anesthesia and with or without adding ketamine to LA were included in the analysis. The regional anesthesia includes spinal anesthesia, brachial plexus block, pectoral nerve block, transversus abdominis plane block and femoral and sciatic nerve block. MEASUREMENT: The primary outcome was the duration of analgesia. Secondary outcomes were the duration and onset time of motor and sensory block as well as the ketamine-related adverse effect. Data are expressed in mean differences in continuous data and odds ratios (OR) for dichotomous data with 95% confidence intervals. The risk of bias of the included studies was evaluated using the revised Cochrane risk of bias tool for randomized trials. The quality of evidence for each outcome was rated according to the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) Working Group system. MAIN RESULT: Twenty randomized controlled trials were included in the analysis. When ketamine was used as an adjuvant to LA, the duration of analgesia could be prolonged(172.21 min, 95% CI, 118.20 to 226.22; P<0.00001, I2 = 98%), especially in the peripheral nerve block(366.96 min, 95% CI, 154.19 to 579.74; P = 0.0007, I2 = 98%). Secondary outcomes showed ketamine could prolong the duration of sensory block(29.12 min, 95% CI, 10.22 to 48.01; P = 0.003, I2 = 96%) but no effect on the motor block(6.94 min, 95% CI,-2.65 to 16.53;P = 0.16, I2 = 84%), the onset time of motor and sensory block (motor onset time, -1.17 min, 95% CI, -2.67 to 0.34; P = 0.13, I2 = 100%; sensory onset time, -0.33 min, 95% CI,-0.87 to 0.20; P = 0.23, I2 = 96%) as well as the ketamine-related adverse effect(OR, 1.97, 95% CI,0.93 to 4.17;P = 0.08, I2 = 57%). CONCLUSION: This study indicates that ketamine could be an ideal adjuvant to local anesthetics regardless of the types of anesthesia. Overall, the quality of the evidence is low.

A multi-dimensional approach to unravel the intricacies of lactylation related signature for prognostic and therapeutic insight in colorectal cancer.

BACKGROUND: Lactylation, a novel contributor to post-translational protein modifications, exhibits dysregulation across various tumors. Nevertheless, its intricate involvement in colorectal carcinoma, particularly for non-histone lactylation and its intersection with metabolism and immune evasion, remains enigmatic. METHODS: Employing immunohistochemistry on tissue microarray with clinical information and immunofluorescence on colorectal cell lines, we investigated the presence of global lactylation and its association with development and progression in colorectal cancer as well as its functional location. Leveraging the AUCell algorithm alongside correlation analysis in single-cell RNA sequencing data, as well as cox-regression and lasso-regression analysis in TCGA dataset and confirmed in GEO dataset, we identified a 23-gene signature predicting colorectal cancer prognosis. Subsequently, we analyzed the associations between the lactylation related gene risk and clinical characteristics, mutation landscapes, biological functions, immune cell infiltration, immunotherapy responses, and drug sensitivity. Core genes were further explored for deep biological insights through bioinformatics and in vitro experiments. RESULTS: Our study innovatively reveals a significant elevation of global lactylation in colorectal cancer, particularly in malignant tumors, confirming it as an independent prognostic factor for CRC. Through a comprehensive analysis integrating tumor tissue arrays, TCGA dataset, GEO dataset, combining in silico investigations and in vitro experiments, we identified a 23-gene Lactylation-Related Gene risk model capable of predicting the prognosis of colorectal cancer patients. Noteworthy variations were observed in clinical characteristics, biological functions, immune cell infiltration, immune checkpoint expression, immunotherapy responses and drug sensitivity among distinct risk groups. CONCLUSIONS: The Lactylation-Related Gene risk model exhibits significant potential for improving the management of colorectal cancer patients and enhancing therapeutic outcomes, particularly at the intersection of metabolism and immune evasion. This finding underscores the clinical relevance of global lactylation in CRC and lays the groundwork for mechanism investigation and targeted therapeutic strategies given the high lactate concentration in CRC.

Efficacy of Transcutaneous Electrical Acupoint Stimulation on Chronic Postsurgical Pain After Video-Assisted Thoracoscopic Lobectomy: Study Protocol for a Prospective Randomized Controlled Trial.

INTRODUCTION: Patients undergoing video-assisted thoracoscopic lobectomy (VATL) often experience chronic postsurgical pain (CPSP). Postoperative pain can affect the recovery of postoperative lung function, prolong postoperative recovery time, and increase patient hospitalization expenses. Transcutaneous electrical acupoint stimulation (TEAS) is an alternative therapy based on acupuncture that has shown promise in postoperative recovery and pain management across various medical fields. However, research specifically focused on the improvement of CPSP after VATL is currently lacking. The purpose of this study is to evaluate whether TEAS can effectively reduce the severity and occurrence of chronic postsurgical pain in patients undergoing VATL. By investigating the potential benefits of TEAS in mitigating CPSP after VATL, this study aims to provide valuable clinical evidence to support the integration of TEAS into postoperative care protocols for patients undergoing VATL. METHODS: This study is a prospective, single-center, double-blinded, randomized controlled trial to be conducted at the 920th Hospital of Joint Logistics Support Force. Eighty patients undergoing VATL will be randomly divided into an experimental group (TEAS group) and a control group (sham group). The experimental group will receive TEAS at bilateral PC6, LI4, LR3, LU5, TE5, and LI11. The control group will not receive TEAS at the same acupoints. Both groups will receive TEAS or no TEAS before anesthesia induction and 1-7 days after surgery, with each session lasting 30 min. PLANNED OUTCOMES: The primary outcome will be the incidence of CPSP at 3 months after surgery. Secondary outcomes will include the incidence of CPSP at 6 months after surgery, the numerical rating scale (NRS) scores at 3 and 6 months after surgery, as well as the NRS scores at 24, 48, and 72 h after surgery, remifentanil consumption during general anesthesia, demand for rescue analgesics, number and duration of indwelling chest tubes, incidence of postoperative nausea and vomiting, and changes of norepinephrine (NE), cortisol (Cor), tumor necrosis factor (TNF- α), and interleukin 6 (IL-6) in serum. TRIAL REGISTRATION: ChiCTR2300069458. Registered on March 16, 2023.

Risk Factors and Patient-Reported Outcomes in Chinese Women with Postpartum Diastasis Recti Abdominis: An Observational Study.

Purpose: Diastasis recti abdominis (DRA) is a condition in which the linea alba is stretched and widened, and the abdominal muscles are separated from each other. DRA typically occurs in pregnant and postpartum women. We aimed to determine the risk factors and patient-reported outcomes (PROs) of DRA in Chinese postpartum women. Methods: This observational study was conducted in Hangzhou Hospital of Traditional Chinese Medicine, and involved 534 women who filled out the following risk-factor and PRO questionnaires: SF-MPQ-2, SF-ICIQ, LDQ, EPDS, MBIS, HerQles, and SF-36 (all Chinese versions). The inter-recti distance was measured by palpation. Statistical analyses were performed using SPSS v25.0 software and the Mann-Whitney U-test, chi-square test, binary logistic regression analysis (for risk factors of DRA), and the Kendall and Spearman tests (for correlation analysis). Results: After childbirth, 78.1% (417/534) of the enrolled women had DRA. Abdominal surgery (P = 0.002), number of pregnancies (P = 0.035), parity (P = 0.012), number of births (P = 0.02), fetal birth weight (P = 0.014), and waist-to-hip ratio in the supine position (P = 0.045) significantly differed between the DRA and non-DRA groups. Caesarean delivery was an independent risk factor for DRA. The PROs were significantly worse in the DRA group than in the non-DRA group. Conclusion: Caesarean delivery was an independent risk factor for DRA. Women with DRA are more likely to have limited physical activity or function after childbirth, lower self-confidence, and a decreased quality of life.