Characterization of a secondary hydroxy-acyltransferase for lipid A in Vibrio parahaemolyticus.

Lipid A plays a crucial role in Vibrio parahaemolyticus. Previously we have reported the diversity of secondary acylation of lipid A in V. parahaemolyticus and four V. parahaemolyticus genes VP_RS08405, VP_RS01045, VP_RS12170, and VP_RS00880 exhibiting homology to the secondary acyltransferases in Escherichia coli. In this study, the gene VP_RS12170 was identified as a specific lipid A secondary hydroxy-acyltransferase responsible for transferring a 3-hydroxymyristate to the 2'-position of lipid A. Four E. coli mutant strains WHL00, WHM00, WH300, and WH001 were constructed, and they would synthesize lipid A with different structures due to the absence of genes encoding lipid A secondary acyltransferases or Kdo transferase. Then V. parahaemolyticus VP_RS12170 was overexpressed in W3110, WHL00, WHM00, WH300, and WH001, and lipid A was isolated from these strains and analyzed by using thin-layer chromatography and high-performance liquid chromatography-tandem mass spectrometry. The detailed structural changes of lipid A in these mutant strains with and without VP_RS12170 overexpression were compared and conclude that VP_RS12170 can specifically transfer a 3-hydroxymyristate to the 2'-position of lipid A. This study also demonstrated that the function of VP_RS12170 is Kdo-dependent and its favorite substrate is Kdo-lipid IVA. These findings give us better understanding the biosynthetic pathway and the structural diversity of V. parahaemolyticus lipid A.

Integrated 16S rRNA sequencing and metagenomics insights into microbial dysbiosis and distinct virulence factors in inflammatory bowel disease.

Introduction: The escalation of urbanization correlates with rising rates of inflammatory bowel disease (IBD), necessitating research into new etiological factors. This study aims to elucidate the gut microbiota profiles in IBD patients and compare them with healthy controls in a western city of China. Methods: We conducted a multicenter case-control study from the end of 2020, using 16S rRNA gene sequencing (n = 36) and metagenomic sequencing (n = 12) to analyze the gut microbiota of newly diagnosed IBD patients, including those with Crohn's disease (CD) and ulcerative colitis (UC). Results: Our results demonstrated a significant enrichment of the phylum Proteobacteria, particularly the genus Escherichia-Shigella, in CD patients. Conversely, the genus Enterococcus was markedly increased in UC patients. The core gut microbiota, such as the Christensenellaceae R-7 group, Fusicatenibacter, and Holdemanella, were primarily identified in healthy subjects. Additionally, significant interactions between the microbiome and virulence factors were observed. Discussion: The findings suggest that oxidative stress may play a pivotal role in the pathology of IBD. This study contributes to the growing dialogue about the impact of gut microbiota on the development of IBD and its variations across different geographies, highlighting potential avenues for further research.

Timing of early water intake post-general anaesthesia: a systematic review and meta-analysis.

BACKGROUND: Early water intake has gained widespread attention considering enhanced recovery after surgery (ERAS). In the present systematic evaluation and meta-analysis, we assessed the effects of early water intake on the incidence of vomiting and aspiration in adult patients who received general anaesthesia on regaining consciousness during the resuscitation period. OBJECTIVE: To systematically analyse the results of randomised controlled trials on early postoperative water intake in patients who underwent different types of surgery under general anaesthesia, both at home and abroad, to further explore the safety and application of early water intake and provide an evidence-based foundation for clinical application. DESIGN: Systematic review and meta-analysis. METHODS: To perform the systematic evaluation and meta-analysis, we searched the Web of Science, CINAHL, Embase, PubMed, Cochrane Library, Sinomed, China National Knowledge Infrastructure (CNKI), Wanfang, and Vipshop databases to identify randomised controlled trial studies on early water intake in adult patients who received general anaesthesia. RESULTS: Herein, we included 10 publications with a total sample size of 5131 patients. Based on statistical analysis, there was no statistically significant difference in the incidence of vomiting (odds ratio [OR] = 0.81; 95% confidence interval [CI] [0.58-1.12]; p = 0.20; I-squared [I2] = 0%) and aspiration (OR = 0.78; 95%CI [0.45-1.37]; p = 0.40; I2 = 0%) between the two groups of patients on regaining consciousness post-general anaesthesia. CONCLUSION: Based on the available evidence, early water intake after regaining consciousness post-anaesthesia did not increase the incidence of adverse complications when compared with traditional postoperative water abstinence. Early water intake could effectively improve patient thirst and facilitate the recovery of gastrointestinal function.

Application, knowledge and training needs regarding comprehensive geriatric assessment among geriatric practitioners in healthcare institutions: a cross-sectional study.

BACKGROUND: This study aimed to investigate the actual application, knowledge, and training needs of comprehensive geriatric assessment (CGA) among geriatric practitioners in China. METHODS: A total of 225 geriatric practitioners attending the geriatric medicine or geriatric nursing training were recruited for this cross-sectional study. The questionnaire included demographics, healthcare institution characteristics, the actual application, knowledge, training needs, and barriers to CGA and geriatric syndromes (GS). RESULTS: Physicians and nurses were 57.3% and 42.7%, respectively. 71.1% were female, with a median age was 35 years. Almost two-thirds (140/225) of geriatric practitioners reported exposure to CGA in their clinical practice. The top five CGA evaluation items currently used were malnutrition risk (49.8%), fall risk (49.8%), activity of daily living (48.0%), pain (44.4%), and cognitive function (42.7%). Median knowledge scores for the management procedures of GS ranged from 2 to 6. Physicians identified medical insurance payment issues (29.5%) and a lack of systematic specialist knowledge and technology (21.7%) as the two biggest barriers to practicing geriatrics. Nurses cited a lack of systematic specialist knowledge and technology (52.1%) as the primary barrier. In addition, physicians and nurses exhibited significant differences in their knowledge of CGA-specific evaluation items and management procedures for GS (all P < 0.05). However, there were no significant differences in their training needs, except for polypharmacy. CONCLUSIONS: The rate of CGA application at the individual level, as well as the overall knowledge among geriatric practitioners, was not adequate. Geriatric education and continuous training should be tailored to address the specific roles of physicians and nurses, as well as the practical knowledge reserves, barriers, and training needs they face.

Human Breast Milk Exosomal miRNAs are Influenced by Premature Delivery and Affect Neurodevelopment.

SCOPE: This study investigates the exosomal microRNA (miRNA) profiles of term and preterm breast milk, including the most abundant and differentially expressed (DE) miRNAs, and their impact on neurodevelopment in infants. METHODS AND RESULTS: Mature milk is collected from the mothers of term and preterm infants. Using high-throughput sequencing and subsequent data analysis, exosomal miRNA profiles of term and preterm human breast milk (HBM) are acquired and it is found that the let-7 and miR-148 families are the most abundant miRNAs. Additionally, 23 upregulated and 15 downregulated miRNAs are identified. MiR-3168 is the most upregulated miRNA in preterm HBM exosome, exhibiting targeting activity toward multiple genes involved in the SMAD and MAPK signaling pathways and playing a crucial role in early neurodevelopment. Additionally, the effects of miR-3168 on neurodevelopment is confirmed and it is determined that it is an essential factor in the differentiation of neural stem cells (NSCs). CONCLUSION: This study demonstrates that miRNA expression in breast milk exosomes can be influenced by preterm delivery, thereby potentially impacting neurodevelopment in preterm infants.

A promising target for breast cancer: B7-H3.

Breast cancer (BC) is the second-leading factor of mortality for women globally and is brought on by a variety of genetic and environmental causes. The conventional treatments for this disease have limitations, making it difficult to improve the lifespan of breast cancer patients. As a result, extensive research has been conducted over the past decade to find innovative solutions to these challenges. Targeting of the antitumor immune response through the immunomodulatory checkpoint protein B7 family has revolutionized cancer treatment and led to intermittent patient responses. B7-H3 has recently received attention because of its significant demodulation and its immunomodulatory effects in many cancers. Uncontrolled B7-H3 expression and a bad outlook are strongly associated, according to a substantial body of cancer research. Numerous studies have shown that BC has significant B7-H3 expression, and B7-H3 induces an immune evasion phenotype, consequently enhancing the survival, proliferation, metastasis, and drug resistance of BC cells. Thus, an innovative target for immunotherapy against BC may be the B7-H3 checkpoint.In this review, we discuss the structure and regulation of B7-H3 and its double costimulatory/coinhibitory function within the framework of cancer and normal physiology. Then we expound the malignant behavior of B7-H3 in BC and its role in the tumor microenvironment (TME) and finally focus on targeted drugs against B7-H3 that have opened new therapeutic opportunities in BC.

Variability in Leaf Color Induced by Chlorophyll Deficiency: Transcriptional Changes in Bamboo Leaves.

The diversity of leaf characteristics, particularly leaf color, underscores a pivotal area of inquiry within plant science. The synthesis and functionality of chlorophyll, crucial for photosynthesis, largely dictate leaf coloration, with varying concentrations imparting different shades of green. Complex gene interactions regulate the synthesis and degradation of chlorophyll, and disruptions in these pathways can result in abnormal chlorophyll production, thereby affecting leaf pigmentation. This study focuses on Bambusa multiplex f. silverstripe, a natural variant distinguished by a spectrum of leaf colors, such as green, white, and green-white, attributed to genetic variations influencing gene expression. By examining the physiological and molecular mechanisms underlying chlorophyll anomalies and genetic factors in Silverstripe, this research sheds light on the intricate gene interactions and regulatory networks that contribute to leaf color diversity. The investigation includes the measurement of photosynthetic pigments and nutrient concentrations across different leaf color types, alongside transcriptomic analyses for identifying differentially expressed genes. The role of key genes in pathways such as ALA biosynthesis, chlorophyll synthesis, photosynthesis, and sugar metabolism is explored, offering critical insights for advancing research and plant breeding practices.

Associations between HIFs and tumor immune checkpoints: mechanism and therapy.

Hypoxia, which activates a variety of signaling pathways to enhance tumor cell growth and metabolism, is among the primary features of tumor cells. Hypoxia-inducible factors (HIFs) have a substantial impact on a variety of facets of tumor biology, such as epithelial-mesenchymal transition, metabolic reprogramming, angiogenesis, and improved radiation resistance. HIFs induce hypoxia-adaptive responses in tumor cells. Many academics have presented preclinical and clinical research targeting HIFs in tumor therapy, highlighting the potential applicability of targeted HIFs. In recent years, the discovery of numerous pharmacological drugs targeting the regulatory mechanisms of HIFs has garnered substantial attention. Additionally, HIF inhibitors have attained positive results when used in conjunction with traditional oncology radiation and/or chemotherapy, as well as with the very promising addition of tumor immunotherapy. Immune checkpoint inhibitors (CPIs), which are employed in a range of cancer treatments over the past decades, are essential in tumor immunotherapy. Nevertheless, the use of immunotherapy has been severely hampered by tumor resistance and treatment-related toxicity. According to research, HIF inhibitors paired with CPIs may be game changers for multiple malignancies, decreasing malignant cell plasticity and cancer therapy resistance, among other things, and opening up substantial new pathways for immunotherapy drug development. The structure, activation mechanisms, and pharmacological sites of action of the HIF family are briefly reviewed in this work. This review further explores the interactions between HIF inhibitors and other tumor immunotherapy components and covers the potential clinical use of HIF inhibitors in combination with CPIs.

High B7-H3 expression with low PD-L1 expression identifies armored-cold tumors in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is generally regarded as the most aggressive subtype among breast cancers, but exhibits higher chemotherapeutic and immunotherapeutic responses due to its unique immunogenicity. Thus, appropriate discrimination of subtypes is critical for guiding therapeutic options in clinical practice. In this research, using multiple in-house and public cohorts, we investigated the expression features and immuno-correlations of B7-H3 in breast cancer and checked the anti-tumor effect of the B7-H3 monoclonal antibody in a mouse model. We also developed a novel classifier combining B7-H3 and PD-L1 expression in TNBC. B7-H3 was revealed to be related to immuno-cold features and accumulated collagen in TNBC. In addition, targeting B7-H3 using the monoclonal antibody significantly suppressed mouse TNBC growth, reversed the armored-cold phenotype, and also boosted anti-PD-1 immunotherapy. In addition, patients with B7-H3 high and PD-L1 low expression showed the lowest anti-tumor immune infiltration, the highest collagen level, and the lowest therapeutic responses to multiple therapies, which mostly belong to armored-cold tumors. Overall, this research provides a novel subtyping strategy based on the combination of B7-H3/PD-L1 expression, which leads to a novel approach for the management of TNBC.

Strategic interaction among stakeholders on low-carbon buildings: A tripartite evolutionary game based on prospect theory.

Low-carbon buildings (LCBs) are still in the early stages of development in China. The promotion and implementation of associated policies are not yet fully matured. Meanwhile, their status as public goods exacerbates the uncertainty and complexity regarding anticipated gains and potential losses. Few studies have explored the impact of perception parameters on the decision-making processes of LCBs' stakeholders. Thus, combined with prospect theory, this paper establishes a tripartite game model composed of governments, developers, and consumers to explore their interactions and influences in different stages. Real-life scenarios are further utilized to validate the effectiveness of the model in predicting the behaviors under respective preferences. The results show that the increase in subsidy and penalty intensity instead diminishes the enthusiasm for LCBs. More specifically, the existing subsidy policies offer limited incentives to consumers. With the addition of the perception parameter, there exist differences in the sensitivity of consumers and developers towards risk levels and potential losses. The findings also highlight the importance of consumers in the LCBs market. Future policies should encourage developers and consumers to jointly promote the LCBs implementation.

Assessing the journey of calcium supplementation: A mendelian randomization study on the causal link between calcium levels and sleep disorders.

BACKGROUND & AIM: Sleep disorder is a growing concern, and calcium supplementation is often recommended as a potential intervention for sleep disorders. However, the causal relationship between calcium levels and the incidence of sleep disorders remains unclear. Mendelian randomization techniques utilizing genetic variants that affect calcium levels, can provide valuable insights into causality. This study aims to examine the association between calcium levels and sleep disorders in a diverse population that includes both adolescents and adults, and investigate the effects of calcium levels on sleep disorders. METHODS: Mendelian randomization analysis was conducted using data from UK Biobank and FinnGen datasets. The inverse-variance weighting (IVW) was selected as the primary method. In addition, traditional mediation analysis was performed on a subset of the NHANES data spanning from 2007 to 2018. RESULTS: Our findings provide evidence supporting a causal relationship between calcium intake and reduced risk of sleep disorders (beta = -0.079, SE = 0.0395, P = 0.0457). While not reaching statistical significance, other MR methods such as weighted median and Mr-Egger exhibited similar directional trends. Analysis of the NHANES cohort revealed a negative association between calcium levels and the prevalence of sleep disorders in male, black, and physically active populations. However, this association was not observed in other demographic groups. CONCLUSION: Our results suggested that there is no significant correlation between calcium levels and sleep disorder in non-exercise populations. This raises concerns about the long-term high-dose calcium supplementation in clinical practice, which requires further investigation.

Profiling the genome and proteome of metabolic dysfunction-associated steatotic liver disease identifies potential therapeutic targets.

BACKGROUND & AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) affects over 25% of the population and currently has no effective treatments. Plasma proteins with causal evidence may represent promising drug targets. We aimed to identify plasma proteins in the causal pathway of MASLD and explore their interaction with obesity. METHODS: We analysed 2,941 plasma proteins in 43,978 European participants from UK Biobank. We performed genome-wide association study (GWAS) for all MASLD-associated proteins and created the largest MASLD GWAS (109,885 cases/1,014,923 controls). We performed Mendelian Randomization (MR) and integrated proteins and their encoding genes in MASLD ranges to identify candidate causal proteins. We then validated them through independent replication, exome sequencing, liver imaging, bulk and single-cell gene expression, liver biopsies, pathway, and phenome-wide data. We explored the role of obesity by MR and multivariable MR across proteins, body mass index, and MASLD. RESULTS: We found 929 proteins associated with MASLD, reported five novel genetic loci associated with MASLD, and identified 17 candidate MASLD protein targets. We identified four novel targets for MASLD (CD33, GRHPR, HMOX2, and SCG3), provided protein evidence supporting roles of AHCY, FCGR2B, ORM1, and RBKS in MASLD, and validated nine previously known targets. We found that CD33, FCGR2B, ORM1, RBKS, and SCG3 mediated the association of obesity and MASLD, and HMOX2, ORM1, and RBKS had effect on MASLD independent of obesity. CONCLUSIONS: This study identified new protein targets in the causal pathway of MASLD, providing new insights into the multi-omics architecture and pathophysiology of MASLD. These findings advise further therapeutic interventions for MASLD.

Identification and characterization of the cupin_1 domain-containing proteins in ma bamboo (Dendrocalamus latiflorus) and their potential role in rhizome sprouting.

Cupin_1 domain-containing protein (CDP) family, which is a member of the cupin superfamily with the most diverse functions in plants, has been found to be involved in hormone pathways that are closely related to rhizome sprouting (RS), a vital form of asexual reproduction in plants. Ma bamboo is a typical clumping bamboo, which mainly reproduces by RS. In this study, we identified and characterized 53 Dendrocalamus latiflorus CDP genes and divided them into seven subfamilies. Comparing the genetic structures among subfamilies showed a relatively conserved gene structure within each subfamily, and the number of cupin_1 domains affected the conservation among D. latiflorus CDP genes. Gene collinearity results showed that segmental duplication and tandem duplication both contributed to the expansion of D. latiflorus CDP genes, and lineage-specific gene duplication was an important factor influencing the evolution of CDP genes. Expression patterns showed that CDP genes generally had higher expression levels in germinating underground buds, indicating that they might play important roles in promoting shoot sprouting. Transcription factor binding site prediction and co-expression network analysis indicated that D. latiflorus CDPs were regulated by a large number of transcription factors, and collectively participated in rhizome buds and shoot development. This study significantly provided new insights into the evolutionary patterns and molecular functions of CDP genes, and laid a foundation for further studying the regulatory mechanisms of plant rhizome sprouting.

Lower urinary albumin-to-creatinine ratio predicted all-cause and cardiovascular mortality in Chinese population with diabetes and prediabetes-The Shanghai Changfeng cohort study.

INTRODUCTION: Elevated urinary albumin-to-creatinine ratio (UACR) was associated with increased mortality in general population and diabetic patients. However, whether the association remains similar in the subjects with different status of glucose metabolism was unclear. The optimal level of UACR in predicting mortality also remained unknown. This study aims to investigate the relationship between UACR with all-cause and cardiovascular mortality in population with different status of glucose metabolism and explore the predictive cutoff point of UACR. METHODS: Six thousand three hundred and eighty-six community-dwelling individuals aged ≥45 years were enrolled and followed for an average of 5.3 years. Cox proportional hazards model was performed to analysis the association of baseline UACR and all-cause as well as cardiovascular mortality according to the status of glucose metabolism. Receiver operating characteristic curve was plotted to explore the optimal predictive cutoff point of UACR. RESULTS: With UACR increasing, both the prevalence of all-cause and cardiovascular death increased. Cox analyses showed baseline UACR independently predicted the risk of all-cause and cardiovascular mortality in the patients with prediabetes mellitus (pre-DM) and diabetes mellitus (DM) but not in subjects with normal glucose tolerance (NGT). When divided by quartiles of UACR, the cumulative survival rate decreased acrossing the quartiles. Compared to the subjects with lowest quartile of UACR, participants with UACR ≥7.40 mg/gCr had a higher risk of all-cause mortality, and participants with UACR ≥16.60 mg/gCr had an increased risk of cardiovascular mortality in all hyperglycemia subjects. The optimal predictive cutoff point of UACR was about 17 mg/gCr. CONCLUSION: UACR was an independent predictor of all-cause and cardiovascular mortality in population with pre-DM and DM but not in the subjects with NGT. The optimal predictive cutoff point of UACR is about 17 mg/gCr, which was far below the diagnostic cutoff point of microalbuminuria. Earlier interventions of albuminuria should be initiated from very early stage of hyperglycemia to reduce the burden of death in all patients whose glucose metabolism are impaired.

Secreted proteins in plasma and placenta as novel non-invasive biomarkers for intrahepatic cholestasis of pregnancy: A case-control study.

Background: Intrahepatic cholestasis of pregnancy (ICP) is likely to lead to unfavorable consequences. Total bile acid (TBA) is thought to be the sole ICP indicator available as of now, but it comes with some kind of restrictions in terms of sensitivity and specificity. We were endeavoring to find potential diagnostic biomarkers for ICP in this investigation. Methods: This case-control study with a prospective nature included 40 females in the stage of pregnancy who were diagnosed with ICP. It also included another 20 females who were also pregnant but with sound physical condition(control). Placental and plasma samples were collected from all females that were in the stage of pregnancy, except for 20 ICP patients, in which only plasma was collected. We used four-dimensional data-independent acquisition followed by enzyme-linked immunosorbent assay and immunohistochemistry to identify and validate plasma and placental profiles in ICP patients and controls. Bioinformatics was adopted in an effort to demonstrate the relevant biological processes and signalling pathways. Correlation analysis was used to analyse the consistency of tissue and plasma protein expression and the correlation between sequencing and experimental results. Results: The expression levels of nectin-1 (NECTIN1), Kunitz-type protease inhibitor 1 (SPINT1), and inter-alpha-trypsin inhibitor heavy chain H3 (ITIH3) were remarkably higher in ICP patients than in controls. However, heparin cofactor 2 (SERPIND1) expression levels in female participants in the stage of pregnancy who were diagnosed with ICP were remarkably lower than those pregnant females with good physical fitness. In addition to the negative correlation between SERPIND1 and TBA, NECTIN1, SPINT1, and ITIH3 expression positively correlated with TBA. Area under the receiver operating characteristic curve (AUC) values of 0.7925, 0.8313, 0.8163, and 0.9025, respectively, were used to assess the diagnostic accuracies of NECTIN1, SPINT1, ITIH3, and SERPIND1. AUC (0.9438) was considerably greater when NECTIN1, SPINT1, and SERPIND1 were integrated, according to binary logistic regression. The AUC of the ROC curve for various combinations of SERPIND1 and other indicators was higher than itself, thus providing a more reliable ICP diagnosis. Furthermore, according to the bioinformatics analysis, the NECTIN1, SPINT1, ITIH3, and SERPIND1 were identified as secreted proteins because they were localized in the extracellular region. Conclusions: This research discovered new non-invasive ICP indicators. On top of this, it sheds new light on the crucial diagnostic function of secreted proteins in ICP.

Identification and validation of diagnostic biomarkers for intrahepatic cholestasis of pregnancy based on untargeted and targeted metabolomics analyses of urine metabolite profiles.

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is a prevalent pregnancy-specific complication that presents with maternal itching and elevated serum bile acid levels. ICP is associated with unfavorable pregnancy outcomes, severely decreasing the pregnant woman's quality of life. Timely identification of ICP is crucial for effective management and improved outcomes. METHODS: We collected urine samples from 8 patients with ICP and 8 healthy individuals. We used Liquid Chromatography-Mass Spectrometry (LC-MS) to detect metabolite expression levels, then conducted a series of bioinformatic analyses to explore the potential biological meanings of differentially expressed metabolites, and preliminarily discovered several candidate biomarkers. To validate these candidate biomarkers, we performed Gas Chromatography-Mass Spectrometry (GC-MS) detection and analyzed their diagnostic values using receiver operating characteristic (ROC) curve. RESULTS: Untargeted metabolomics data showed that 6129 positive peaks and 6218 negative peaks were extracted from each specimen. OPLS-DA analysis and the heat map for cluster analysis showed satisfactory capability in discriminating ICP specimens from controls. Subsequent analysis extracted 64 significantly differentially expressed metabolites, which could be potential biomarkers for diagnosis of ICP. Based on the KEGG enrichment analyses, six candidate biomarkers were preliminarily identified. Two most promising biomarkers (3-hydroxypropionic acid and uracil) were validated by targeted metabolomics analyses with the area under the curve (AUC) of 0.920 and 0.850 respectively. CONCLUSION: Based on preliminary screening from untargeted metabolomics and subsequent validation through targeted metabolomics, 3-hydroxypropionic acid and uracil were identified as promising diagnostic biomarkers for ICP.

Associations of intrinsic capacity, fall risk and frailty in old inpatients.

Introduction: This study explored the associations of intrinsic capacity (IC), fall risk, and frailty in geriatric inpatients. Methods: A total of 703 hospitalized patients aged 75 years or older were recruited for this retrospective observational study from Zhejiang Hospital using a comprehensive geriatric assessment. The IC composite score was constructed from the scores of the Chinese version of the Mini-Mental State Examination, Short Physical Performance Battery, Short Form Mini Nutritional Assessment, 15-item Geriatric Depression Scale, and self-reported hearing and vision impairment. Adverse outcomes were recorded as the fall risk and frailty using the Morse Fall Scale and the Clinical Frailty Scale. Spearman's correlation coefficient analyses and multivariate logistic regression models were used to explore the associations between IC, high fall risk, and frailty. Results: Declined IC composite scores were associated with increased risks of falls [odds ratio (OR) = 0.64, 95% confidence interval (CI): 0.57-0.72] and frailty (OR = 0.45, 95%CI: 0.37-0.54) among older hospitalized patients after adjusting for the related potential confounders. In addition, decreased cognitive, vitality, locomotion, and psychological scores were associated with increased adverse health conditions, with ORs ranging from 0.26 to 0.70. Vision impairment was observed to increase the risk of frailty (OR = 0.42, 95%CI: 0.23-0.76) after adjusting for the related potential confounders. Discussion: This study indicated that declined IC was associated with fall risk and frailty in older inpatients. Further prospective studies are needed to explore the longitudinal associations between baseline IC and subsequent risk of falls and frailty.

Ultrasound-guided acupotomy for trigger finger: a systematic review and meta-analysis.

BACKGROUND: Trigger finger is a common condition in the hand, and ultrasound-guided acupotomy for trigger finger has been widely used in recent years. PURPOSE: This study aims to investigate the efficacy and safety of ultrasound-guided acupotomy for trigger finger. METHODS: We searched for relevant studies in the Cochrane Library, China National Knowledge Infrastructure (CNKI), Embase, PubMed, Chinese Biomedical Literature Database (CBM), Wanfang Data, and other resources from their inception to January 2023. Randomized controlled trials of ultrasound-guided acupotomy for trigger finger were included. The meta-analysis was carried out using Review Manager 5.4 and Stata 15.1. RESULTS: Overall, 15 studies with 988 patients were included. The experimental group was treated with ultrasound-guided acupotomy, and the Control group received traditional acupotomy, traditional operation or injection of medication. Meta-analysis showed that the overall clinical effectiveness (OR = 4.83; 95% CI 2.49-9.37; I2 = 73.1%; P < 0.001) in the experimental group was significantly better than that of the control group. And the Visual Analogue Scale (VAS) score (WMD = - 1; 95% CI - 1.24, - 0.76; I2 = 99%; P < 0.001), the QuinneII classification (WMD = - 0.84; 95% CI - 1.28, - 0.39; I2 = 99.1%, P < 0.001), the incidence of complications (RR = 0.26; 95% CI 0.11, 0.63; I2 = 0%, P = 0.003), and the recurrence rate (RR = 0.14; 95% CI 0.03, 0.74; I2 = 0%; P = 0.021) were significantly lower in the experimental group. CONCLUSION: Our systematic review and meta-analysis can prove the effectiveness and safety of ultrasound-guided acupotomy in the treatment of trigger finger, but this still needs to be verified by a clinical standard large sample test.

The heterogeneity of tumour immune microenvironment revealing the CRABP2/CD69 signature discriminates distinct clinical outcomes in breast cancer.

BACKGROUND: It has been acknowledged that the tumour immune microenvironment (TIME) plays a critical role in determining therapeutic responses and clinical outcomes in breast cancer (BrCa). Thus, the identification of the TIME features is essential for guiding therapy and prognostic assessment for BrCa. METHODS: The heterogeneous cellular composition of the TIME in BrCa by single-cell RNA sequencing (scRNA-seq). Two subtype-special genes upregulated in the tumour-rich subtype and the immune-infiltrating subtype were extracted, respectively. The CRABP2/CD69 signature was established based on CRABP2 and CD69 expression, and its predictive values for the clinical outcome and the neoadjuvant chemotherapy (NAT) responses were validated in multiple cohorts. Moreover, the oncogenic role of CRABP2 was explored in BrCa cells. RESULTS: Based on the heterogeneous cellular composition of the TIME in BrCa, the BrCa samples could be divided into the tumour-rich subtype and the immune-infiltrating subtype, which exhibited distinct prognosis and chemotherapeutic responses. Next, we extracted CRABP2 as the biomarker for the tumour-rich subtype and CD69 as the biomarker for the immune-infiltrating subtype. Based on the CRABP2/CD69 signature, BrCa samples were re-divided into three subtypes, and the CRABP2highCD69low subtype exhibited the worst prognosis and the lowest chemotherapeutic response, while the CRABP2lowCD69high subtype showed the opposite results. Furthermore, CARBP2 functioned as a novel oncogene in BrCa, which promoted tumour cell proliferation, migration, and invasion, and CRABP2 inhibition triggered the activation of cytotoxic T lymphocytes (CTLs). CONCLUSION: The CRABP2/CD69 signature is significantly associated with the TIME features and could effectively predict the clinical outcome. Also, CRABP2 is determined to be a novel oncogene, which could be a therapeutic target in BrCa.