Efficacy of Huoxue Qianyang Qutan Recipe on essential hypertension: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Hypertension, a prevalent disease, is a significant risk factor for coronary heart disease. Huoxue Qianyang Qutan Recipe (HQQR), a traditional Chinese herbal remedy, has been used for treating hypertension over several years. OBJECTIVE: This study assesses HQQR's efficacy for controlling blood pressure among patients with hypertension related to blood stasis, yang hyperactivity and phlegm. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A randomized controlled trial was conducted at the Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, China, from July 2020 to June 2022. Major components of HQQR were identified using thin-layer chromatography and high-performance liquid chromatography. Participants aged 18-80 years, exhibiting traditional Chinese medicine syndromes of blood stasis, yang hyperactivity or phlegm, along with grades 1 or 2 hypertension, were randomly categorized into two groups. The intervention group was given HQQR granules alongside conventional hypertension treatment, while the control group was given placebo granules in addition to conventional treatment for 12 weeks. MAIN OUTCOME MEASURES: The primary outcome was clinic blood pressure, whereas secondary outcomes included metabolic indices (e.g., homeostasis model assessment of insulin resistance [HOMA-IR], total cholesterol [TC], low-density lipoprotein cholesterol and triglyceride), target organ damage indices (left ventricular mass index and urinary albumin creatinine ratio [UACR]) and inflammation indices (interleukin-6 [IL-6] and high-sensitivity C-reactive protein [hs-CRP]). RESULTS: HQQR's primary components were identified as salvianolic acid B, emodin and ferulic acid. Of the 216 participants (108 in each group), compared to the control, the intervention group exhibited significant improvements (P < 0.001) in clinic systolic blood pressure ([136.24 ± 7.63] vs [130.06 ± 8.50] mmHg), clinic diastolic blood pressure ([84.34 ± 8.72] vs [80.46 ± 6.05] mmHg), home systolic blood pressure ([131.64 ± 8.74] vs [122.36 ± 8.45] mmHg) and home diastolic blood pressure ([78.47 ± 9.53] vs [71.79 ± 6.82] mmHg). HQQR demonstrated a reduction in ambulatory blood pressure (24-hour systolic blood pressure: [133.75 ± 10.49] vs [132.46 ± 8.84] mmHg and 24-hour diastolic blood pressure: [84.12 ± 8.01] vs [82.11 ± 7.45] mmHg) and an improvement in HOMA-IR ([4.09 ± 1.72] vs [3.98 ± 1.44]), TC ([4.66 ± 1.47] vs [3.75 ± 1.81] mmol/L) and UACR (75.94 [5.12, 401.12] vs 45.61 [4.26, 234.26]). Moreover, HQQR demonstrated a decrease in hs-CRP (1.46 [0.10, 10.53] vs 0.57 [0.12, 3.99] mg/L) and IL-6 (6.69 [2.00, 29.74] vs 5.27 [2.00, 9.73] pg/mL), with no reported side effects (P < 0.001). CONCLUSION: This study highlights the therapeutic potential of HQQR use in ameliorating blood pressure, glycolipid metabolism, and inflammation in patients with hypertension. TRIAL REGISTRATION: ChiCTR2000035092 (https://www.chictr.org.cn/). Please cite this article as: Xie J, Ma YL, Gui MT, Yao L, Li JH, Wang MZ, Zhou XJ, Wang YF, Zhao MY, Cao H, Lu B, Fu DY. Efficacy of Huoxue Qianyang Qutan Recipe on essential hypertension: A randomized, double-blind, placebo-controlled trial. J Integr Med. 2024; Epub ahead of print.

Value of Molecular Typing Combined with Integrated Positron Emission Tomography/Magnetic Resonance Imaging in Risk Stratification of Endometrial Cancer.

Objective: In this study, we investigated the value of molecular typing combined with integrated positron emission tomography (PET)/magnetic resonance imaging (MRI) semi-quantitative indices in endometrial cancer risk stratification. Methods: A retrospective study was conducted on 86 patients who were pathologically diagnosed with endometrial cancer and underwent surgical treatment after curettage at the Department of Obstetrics and Gynecology, Xuanwu Hospital, Capital Medical University between January 2017 and March 2023. Prior to surgery, each patient underwent integrated PET/MRI examination. The postoperative samples were subjected to pathological diagnosis, immunohistochemistry, and POLE gene sequencing. The differences in clinicopathological features between the four molecular subtypes and the differences in integrated PET/MRI semi-quantitative indexes (SUV max, ADC min) between the four molecular subtypes were analyzed. The cutoff value of molecular typing combined with integrated PET/MRI semi-quantitative indices for endometrial cancer risk stratification was determined. Results: There were statistically significant differences in pathological types and tumor grades among the four molecular subtypes of endometrial cancer. The values of the four integrated PET/MRI semi-quantitative indices (SUV max and ADC min) of the molecular subtypes were statistically different. The SUV max was greater in the p53abn mutation group than in the POLE mutation group (P < 0.05). The ADC minimum of the POLE mutation group and the MMR-d group was lower than the NSMP group (P < 0.05). Molecular typing combined with the integrated PET/MRI semi-quantitative SUV max index can predict the low/medium risk group of endometrial cancer and the medium-high/high risk group, and the cut-off value of SUV max for predicting the risk of early endometrial cancer was 14.72 (sensitivity 66.7%, specificity 68.7%). Conclusion: Molecular typing combined with integrated PET/MRI semi-quantitative indicators is useful to achieve risk stratification in patients diagnosed with endometrial cancer and guide individualized treatment.

Regulation of Protein Conformation Enables Cell-Selective Targeting of Virus-Mimicking Nanoparticles for siRNA Therapy of Glioblastoma.

Orthotopic glioblastoma (GBM) has an aggressive growth pattern and complex pathogenesis, becoming one of the most common and deadly tumors of the central nervous system (CNS). The emergence of RNA therapies offers promise for the treatment of GBM. However, the efficient and precise delivery of RNA drugs to specific tumor cells in the brain with high cellular heterogeneity remains ongoing. Here, a strategy is proposed to regulate protein conformation through lipid nanoenvironments to custom-design virus-mimicking nanoparticles (VMNs) with excellent selective cell targeting capabilities, leading to efficient and precise delivery of small interfering RNA for effective treatment of GBM. The optimized VMNs not only retain the ability to cross the blood-brain barrier and release the RNA by lysosomal escape like natural viruses but also ensure precise enrichment in the GBM area. This study lays the conceptual foundation for the custom design of VMNs with superior cell-selective targeting capabilities and opens up the possibility of RNA therapies for the efficient treatment of GBM and CNS tumors.

Codon usage bias analysis in the mitochondrial genomes of five Rhingia Scopoli (Diptera, Syrphidae, Eristalinae) species.

This study presents the sequencing and annotation of mitochondrial genomes from five Rhingia species of the family Syrphidae, focusing on codon bias. Each species possessed 22 tRNAs genes, 13 protein-coding genes, 2 rRNAs genes, and a control region, without any observed gene rearrangements. Nucleotide composition analysis revealed a higher AT content compared with GC content, indicating AT enrichment. Neutrality plot, Parity rule 2 bias, and effective number of codons plot analyses collectively indicated that natural selection primarily influences the codon usage bias in the five Rhingia species. Relative synonymous codon usage analysis identified the optimal codons for Rhingia binotata, R. fromosana, R. campestris, R. louguanensis, and R. xanthopoda as 10, 14, 10, 11, and 12, respectively, all ending with A/U and exhibiting AT preference. Phylogenetic analysis, based on maximum likelihood and Bayesian inference methods applied to three datasets, confirmed the monophyly of Rhingia. In conclusion, this research establishes a foundation for understanding the phylogenetic evolution and codon usage patterns in Rhingia, offering valuable for future studies.

E93 is indispensable for reproduction in ametabolous and hemimetabolous insects.

Ecdysone-induced protein 93 (E93), known as the 'adult-specifier' transcription factor in insects, triggers metamorphosis in both hemimetabolous and holometabolous insects. Although E93 is conserved in ametabolous insects, its spatiotemporal expression and physiological function remain poorly understood. In this study, we first discover that, in the ametabolous firebrat Thermobia domestica, the previtellogenic ovary exhibits cyclically high E93 expression, and E93 mRNA is broadly distributed in previtellogenic ovarioles. E93 homozygous mutant females of T. domestica exhibit severe fecundity deficiency due to impaired previtellogenic development of the ovarian follicles, likely because E93 induces the expression of genes involved in ECM (extracellular matrix)-receptor interactions during previtellogenesis. Moreover, we reveal that in the hemimetabolous cockroach Blattella germanica, E93 similarly promotes previtellogenic ovarian development. In addition, E93 is also essential for vitellogenesis that is necessary to guarantee ovarian maturation and promotes the vitellogenesis-previtellogenesis switch in the fat body of adult female cockroaches. Our findings deepen the understanding of the roles of E93 in controlling reproduction in insects, and of E93 expression and functional evolution, which are proposed to have made crucial contributions to the origin of insect metamorphosis.

Effects of temperature and initial pH on the growth of four dominant cyanobacteria species in biological soil crusts.

Biological soil crusts are of great significance for environment health and sustainable development in arid and semi-arid areas. Cyanobacteria, Microcoleus vaginatus, Scytonema sp., Nostoc sp., and Anabaena sp. are the dominant species in microbial community of biological soil crusts worldwide. Considering their broad application prospect, it is meaningful to cultivate them extensively. We examined the effects of temperature (10, 20, 25, 30, 35 ℃) and initial pH (4, 6, 8, 10, 12) on biomass and solution pH towards the four species of cyanobacteria with liquid culture in laboratory. The results showed that the biomass of the four cyanobacterial species grew slowly under 20 ℃, and that all species could grow in 25-35 ℃, with the highest growth rate at 25 and 30 ℃. The optimum culture temperature of different cyanobacterial species was slightly different. The optimum culture temperature was 25-30 ℃ for Scytonema sp. and Nostoc sp., and 30 ℃ for M. vaginatus and Anabaena sp. The four cyanobacterial species had a strong ability to adjust solution pH and proliferate in five different initial pH conditions. The highest maximum biomass and specific growth rate were recorded in the culture environment with initial pH of 4, while the lowest maximum biomass and specific growth rate were observed in initial pH of 12. Our results would provide scientific basis for the propagation of dominant cyanobacteria in biological soil crusts.

[Plant community differentiation of desertification region in northwest Liaoning Province, China]. / è¾½è¥¿åŒ—è’æ¼ åŒ–åŒºæ¤ç‰©ç¾¤è½åˆ†å¼‚.

Understanding plant communities in desertification area is the scientific basis of evaluating the local eco-environmental quality and carrying out desertification control. According to longitude, we divided the desertification area in northwest Liaoning Province into three regions: the eastern region (122°50'37″ -123°49'40″ E), the middle region (121°16'41″-122°35'00″ E), and the western region (119°20'03″ -120°02'41″ E), and investigated the plant communities in each region. The results showed that the proportion of forest and canopy density of tree layer increased from the west to the east. Ass. Pinus sylvestris var. mongolica and Ass. Populus sp. in the eastern, Ass. Pinus tabuliformis and Ass. Populus sp. in the middle, as well as Ass. P. tabuliformis and Ass. Prunus sibirica in the western were dominant communities, respectively. The proportion of brush community in the eastern, middle and western was 0, 22.2%, and 28.0%, respectively. Grasslands formed mainly by human disturbance in the eas-tern and middle regions. The total species numbers were 110 in the middle, 88 in the western and 75 in the eastern, respectively. Therophytes were dominant in the eastern and middle with proportions of 68.2% and 66.7%, respectively. Hemicryptophytes were the dominant type (36.3%) in the western region. The proportion of microphanerophyt, nanophanerophyte, chamaephyte, and geophyte increased from the eastern to the western. The species number, Shannon index, and Simpson diversity index of the middle were the highest among the three regions. Pielou evenness index increased gradually from the eastern to the western. Community similarity between the eastern and the western was the lowest, as shown by the ß-biodiversity, and the similarity between the middle and the western was the highest. The community type, species number, characteristics of species composition and species biodiversity of the middle region had the characteristics of ecological transition zone. In general, vegetation status in the desertification area of northwest Liaoning Province was in good condition. There were still some problems including the monotonous vertical structure of forest and tree species as well as the serious human interference.

L-Type Calcium Channel Modulates Low-Intensity Pulsed Ultrasound-Induced Excitation in Cultured Hippocampal Neurons.

As a noninvasive technique, ultrasound stimulation is known to modulate neuronal activity both in vitro and in vivo. The latest explanation of this phenomenon is that the acoustic wave can activate the ion channels and further impact the electrophysiological properties of targeted neurons. However, the underlying mechanism of low-intensity pulsed ultrasound (LIPUS)-induced neuro-modulation effects is still unclear. Here, we characterize the excitatory effects of LIPUS on spontaneous activity and the intracellular Ca2+ homeostasis in cultured hippocampal neurons. By whole-cell patch clamp recording, we found that 15 min of 1-MHz LIPUS boosts the frequency of both spontaneous action potentials and spontaneous excitatory synaptic currents (sEPSCs) and also increases the amplitude of sEPSCs in hippocampal neurons. This phenomenon lasts for > 10 min after LIPUS exposure. Together with Ca2+ imaging, we clarified that LIPUS increases the [Ca2+]cyto level by facilitating L-type Ca2+ channels (LTCCs). In addition, due to the [Ca2+]cyto elevation by LIPUS exposure, the Ca2+-dependent CaMKII-CREB pathway can be activated within 30 min to further regulate the gene transcription and protein expression. Our work suggests that LIPUS regulates neuronal activity in a Ca2+-dependent manner via LTCCs. This may also explain the multi-activation effects of LIPUS beyond neurons. LIPUS stimulation potentiates spontaneous neuronal activity by increasing Ca2+ influx.

Environmental exposure to per- and polyfluoroalkyl substances mixture and asthma in adolescents.

BACKGROUND: Previous epidemiological studies about the relationship between per- and polyfluoroalkyl substances (PFAS) concentrations and adolescent asthma have typically examined single PFAS, without considering the mixtures effects of PFAS. METHODS: Using data from the 2013-2018 National Health and Nutrition Examination Survey (NHANES), 886 adolescents aged 12-19 years were included in this study. We explored the association between PFAS mixture concentrations and adolescent asthma using weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) models, respectively. RESULTS: After adjusting for confounders, the results of the WQS regression and BKMR models were consistent, with mixed exposure to the five PFAS not significantly associated with asthma in all adolescents. The association remained nonsignificant in the subgroup analysis by sex. CONCLUSIONS: Our study demonstrated no significant association between mixed exposure to PFAS and adolescent asthma, and more large cohort studies are needed to confirm this in the future.

The role of KLF2 in regulating hepatic lipogenesis and blood cholesterol homeostasis via the SCAP/SREBP pathway.

Liver steatosis is a common metabolic disorder resulting from imbalanced lipid metabolism, which involves various processes such as de novo lipogenesis, fatty acid uptake, fatty acid oxidation, and VLDL secretion. In this study, we discovered that KLF2, a transcription factor, plays a crucial role in regulating lipid metabolism in the liver. Overexpression of KLF2 in the liver of db/db mice, C57BL/6J mice, and Cd36-/- mice fed on a normal diet resulted in increased lipid content in the liver. Additionally, transgenic mice (ALB-Klf2) that overexpressed Klf2 in the liver developed liver steatosis after being fed a normal diet. We found that KLF2 promotes lipogenesis by increasing the expression of SCAP, a chaperone that facilitates the activation of SREBP, the master transcription factor for lipogenic gene expression. Our mechanism studies revealed that KLF2 enhances lipogenesis in the liver by binding to the promoter of SCAP and increasing the expression of genes involved in fatty acid synthesis. Reduction of KLF2 expression led to a decrease in SCAP expression and a reduction in the expression of SREBP1 target genes involved in lipogenesis. Overexpression of KLF2 also increased the activation of SREBP2 and the mRNA levels of its downstream target SOAT1. In C57BL/6J mice fed a high-fat diet, overexpression of Klf2 increased blood VLDL secretion, while reducing its expression decreased blood cholesterol levels. Our study emphasizes the novelty that hepatic KLF2 plays a critical role in regulating lipid metabolism through the KLF2/SCAP/SREBPs pathway, which is essential for hepatic lipogenesis and maintaining blood cholesterol homeostasis.

Dynamic biomechanical changes of clear aligners during extraction space closure: Finite element analysis.

INTRODUCTION: Clear aligners (CAs) have recently become popular and widely used orthodontic appliances. Research on CA biomechanics has become a focal point in orthodontics to improve the efficiency of CA treatment and address challenging issues, such as extraction. The biomechanical characteristics of CAs in space closure have been reported. However, previous studies have mainly focused on static biomechanical analysis that cannot demonstrate the dynamic biomechanical changes in CAs during space-closing. Given that these biomechanical changes can be significant and have considerable clinical value, this study aimed to investigate these characteristics. METHODS: Sequential extraction space-closing models were derived from included patient data and refined using modeling and CA design software. A finite element analysis was performed to obtain biomechanical raw data. This study introduced a dual coordinate system and space geometry analysis to demonstrate the biomechanical properties accurately. RESULTS: As space closure progressed, the instantaneous tooth displacements increased, indicating an enhanced space closure force because of the increased strain in the CA extraction area. Meanwhile, the central axis of rotation of the anterior teeth continuously moved toward the labial-apical direction, showing a gradually enhanced vertical and torque control effect. CONCLUSIONS: During space closure, CAs undergo specific biomechanical changes, including increased contraction and control forces on both sides of the gap. These biomechanical effects are beneficial to alleviate the roller coaster effect gradually. Meanwhile, more reasonable staging design strategies can be proposed on the basis of this biomechanical mechanism.

Ultramorphology of the proboscis and sensilla of the Asian corn borer Ostrinia furnacalis (Lepidoptera: Crambidae).

The Asian corn borer, Ostrinia furnacalis (Guenée), is one of the most destructive lepidopteran pests affecting maize in Asia. Previous research on the feeding behavior of O. furnacalis has mostly focused on larvae, but the adult feeding preference has been unclear hitherto. In this study, we investigated the ultramorphology of the proboscis and sensilla of O. furnacalis using scanning electron microscopy and made morphological comparisons between the sexes, attempting to make predictions on the food preference and feeding behavior of the adults. The proboscis of O. furnacalis is divided into zones 1 and 2 with three types of sensilla, namely chaetica, basiconica, and styloconica. The entire proboscis and zone 2 of the females are significantly longer than those of the males. The main sexual difference in the sensilla is shown in the number of sensilla styloconica, which are eight in females but nine in males. The feeding preference of adult O. furnacalis is discussed based on the morphology of the proboscis and sensilla.

Correlation between serum vitamin D level and uterine volume in girls with idiopathic central precocious puberty.

OBJECTIVES: Investigate serum vitamin D (vit D) levels' relation to uterine volume in idiopathic central precocious puberty (ICPP) girls and compare findings with normal peers. METHODS: Analyzed 278 ICPP cases from January 2017 to September 2022 alongside 239 normally developing girls. Collected clinical data and lab markers and performed subgroup analysis based on vit D levels. Correlation and regression analyses were conducted. RESULTS: The ICPP group exhibited elevated uterine volume and lower serum vit D compared to controls (p<0.05). A weak negative correlation was noted between vit D and uterine volume in ICPP (r=-0.193, p=0.004), and no such correlation in controls (r=-0.073, p=0.319). The ICPP vit D deficiency subgroup displayed higher uterine volume than the insufficiency and sufficiency subgroups (p<0.05). Uterine volume in the insufficiency subgroup exceeded the sufficiency subgroup (p<0.05). After adjusting for confounders, lower vit D is linked to increased ICPP uterine volume (non-standardized regression coefficient ß=-25.55, 95 % CI= -46.23, -4.87, p=0.016). A Limited correlation between vit D and uterine volume was seen in girls with normal pubertal timing. CONCLUSIONS: We demonstrated a correlation between vit D and uterine volume in ICPP girls, absent in normal peers. ICPP girls often exhibit lower vit D levels and increased uterine volume. Further research is vital for understanding vit D's role in ICPP pathogenesis and guiding prevention and treatment strategies.

Suicidality and its associated factors among mood disorder patients in emergency department in China: a comparative study using propensity score matching approach.

Suicidality in mood disorder patients is common, especially in emergency department (ED), but the patterns and associated factors of suicidality are not clear. This study compared biomarkers and mental health symptoms (i.e., depression, anxiety, and psychiatric symptoms) between mood disorder patients with and without the whole range of suicidality comprising suicidal ideation (SI), suicide plan (SP), and suicide attempt (SA). This cross-sectional, comparative, convenient-sampling study was conducted between January 2021 and March 2022, in emergency department of Beijing Anding Hospital, China. Patients with mood disorders at a psychiatric emergency department were assessed, with measurements of suicidality, biomarkers, depressive, anxiety, and psychiatric symptoms were assessed using the 24 items-Hamilton Depression Rating Scale (HAMD-24), Hamilton Anxiety Rating Scale (HAMA), Young Manic Rating Scale (YMRS) and Brief Psychiatric Rating Scale (BPRS), respectively. The propensity score matching (PSM) method was used to identify patients in mood disorder with and without SI, SP, and SA. A generalized linear model (GLM) was used to assess the differences in biomarkers, depressive, anxiety, and psychiatric symptoms between patients in mood disorder with and without SI, SP, and SA. In total, 898 participated in this survey and completed the assessment. Illness duration was significantly negatively associated with SA (OR = 0.969, 95%CI = 0.939-0.999, P = 0.046). HAMD-24 total score was significantly positively associated with the SI (OR = 1.167, 95%CI = 1.134-1.201, p < 0.001), SP (OR = 1.159, 95%CI = 1.126-1.192, p < 0.001) and SA (OR = 1.189, 95%CI = 1.144-1.235, p < 0.001) of the matched samptched sample. However, YMRS total score was significantly negatively associated with the SI (OR = 0.928, 95%CI = 0.905-0.951, p < 0.001), SP (OR = 0.920, 95%CI = 0.897-0.944, p < 0.001) and SA (OR = 0.914, 95%CI = 0.890-0.938, p < 0.001) of the matched sample after adjusting for age, gender, marital status, and occupation. The duration of illness, severity of depressive symptoms and severity of manic symptoms appeared to be more likely to influence suicidality. Considering the significant risk of suicide in mood disorders on psychiatric emergency care, timely treatment and effective management of suicidality in this population group need to be developed.

The direct transfer approach for transcellular drug delivery.

A promising paradigm for drug administration that has garnered increasing attention in recent years is the direct transfer (DT) of nanoparticles for transcellular drug delivery. DT requires direct cell-cell contact and facilitates unidirectional and bidirectional matter exchange between neighboring cells. Consequently, DT enables fast and deep penetration of drugs into the targeted tissues. This comprehensive review discusses the direct transfer concept, which can be delineated into the following three distinct modalities: membrane contact-direct transfer, gap junction-mediated direct transfer (GJ-DT), and tunneling nanotubes-mediated direct transfer (TNTs-DT). Further, the intercellular structures for each modality of direct transfer and their respective merits and demerits are summarized. The review also discusses the recent progress on the drugs or drug delivery systems that could activate DT.

Multimode Quasinormal Spectrum from a Perturbed Black Hole.

When two black holes merge, the late stage of gravitational wave emission is a superposition of exponentially damped sinusoids. According to the black hole no-hair theorem, this ringdown spectrum depends only on the mass and angular momentum of the final black hole. An observation of more than one ringdown mode can test this fundamental prediction of general relativity. Here, we provide strong observational evidence for a multimode black hole ringdown spectrum using the gravitational wave event GW190521, with a maximum Bayes factor of 56±1 (1σ uncertainty) preferring two fundamental modes over one. The dominant mode is the ℓ=m=2 harmonic, and the subdominant mode corresponds to the ℓ=m=3 harmonic. The amplitude of this mode relative to the dominant harmonic is estimated to be A_{330}/A_{220}=0.2_{-0.1}^{+0.2}. We estimate the redshifted mass and dimensionless spin of the final black hole as 330_{-40}^{+30}M_{⊙} and 0.86_{-0.11}^{+0.06}, respectively. We find that the final black hole is consistent with the no-hair theorem and constrain the fractional deviation from general relativity of the subdominant mode's frequency to be -0.01_{-0.09}^{+0.08}.

Clinicopathological and prognostic significance of Ephrin A3 in bladder urothelial carcinoma.

Ephrin A3 (EFNA3) is a member of the Eph/ephrin tyrosine kinase family, which is associated with multiple signaling pathways involved in cell growth and tumor cell metastasis. Aberrant regulation of EFNA3 is associated with the occurrence and development of various types of cancer. However, despite the high incidence of EFNA3 upregulation in cancer, studies concerning EFNA3 in urothelial carcinoma have not, to the best of our knowledge, been conducted. In the present study, bioinformatics analyses using data from multiple online databases were performed to confirm the upregulation of EFNA3 in bladder cancer. The co-expression gene set of EFNA3 and enriched signaling pathways were also analyzed. In addition, immunohistochemistry was conducted to detect EFNA3 expression in 491 clinically confirmed bladder urothelial carcinoma samples and 80 non-cancerous bladder tissues. Kaplan-Meier survival analysis, binary logistic regression analysis, and Cox regression analysis were conducted to confirm the validity of EFNA3 in predicting patient prognosis and its significance in clinical pathology. Statistical analysis demonstrated a significant association between EFNA3 expression levels with tumor size, lymph node metastasis, distant metastasis, and pathological grade. In conclusion, high EFNA3 expression may be a potential biomarker that indicates bladder tumor occurrence and patient prognosis.

Validation of an ICD-Based Algorithm to Identify Sepsis: A Retrospective Study.

Background: Sepsis surveillance was important for resources allocation, prevention, and development of health policy. Objective: The aim of the study was to validate a modified International Classification of Diseases (ICD)-10 based algorithm for identifying hospitalized patients with sepsis. Methods: We retrospectively analyzed a prospective, single-center cohort of adult patients who were consecutively admitted to one medical ICU ward and ten non-ICU wards with suspected or confirmed infections during a 6-month period. A modified ICD-10 based algorithm was validated against a reference standard of Sequential Organ Failure Assessment (SOFA) score based on Sepsis-3. Sensitivity (SE), specificity (SP), positive predictive value (PPV), negative predictive value (NPV), and areas under the receiver operating characteristic curves (AUROCs) were calculated for modified ICD-10 criteria, eSOFA criteria, Martin's criteria, and Angus's criteria. Results: Of the 547 patients in the cohort, 332 (61%) patients met Sepsis-3 criteria and 274 (50%) met modified ICD-10 criteria. In the ICU setting, modified ICD-10 criteria had SE (84.47%), SP (88.57%), PPV (95.60), and NPV (65.96). In non-ICU settings, modified ICD-10 had SE (64.19%), SP (80.00%), PPV (80.33), and NPV (63.72). In the whole cohort, the AUROCs of modified ICD-10 criteria, eSOFA, Angus's criteria, and Martin's criteria were 0.76, 0.75, 0.62, and 0.62, respectively. Conclusion: This study demonstrated that modified ICD-10 criteria had higher validity compared with Angus's criteria and Martin's criteria. Validity of the modified ICD-10 criteria was similar to eSOFA criteria. Modified ICD-10 algorithm can be used to provide an accurate estimate of population-based sepsis burden of China.

Organoids transplantation attenuates intestinal ischemia/reperfusion injury in mice through L-Malic acid-mediated M2 macrophage polarization.

Intestinal organoid transplantation is a promising therapy for the treatment of mucosal injury. However, how the transplanted organoids regulate the immune microenvironment of recipient mice and their role in treating intestinal ischemia-reperfusion (I/R) injury remains unclear. Here, we establish a method for transplanting intestinal organoids into intestinal I/R mice. We find that transplantation improve mouse survival, promote self-renewal of intestinal stem cells and regulate the immune microenvironment after intestinal I/R, depending on the enhanced ability of macrophages polarized to an anti-inflammatory M2 phenotype. Specifically, we report that L-Malic acid (MA) is highly expressed and enriched in the organoids-derived conditioned medium and cecal contents of transplanted mice, demonstrating that organoids secrete MA during engraftment. Both in vivo and in vitro experiments demonstrate that MA induces M2 macrophage polarization and restores interleukin-10 levels in a SOCS2-dependent manner. This study provides a therapeutic strategy for intestinal I/R injury.