Decoding physical principles of cell migration under controlled environment using microfluidics.

Living cells can perform incredible tasks that man-made micro/nano-sized robots have not yet been able to accomplish. One example is that white blood cells can sense and move to the site of pathogen attack within minutes. The robustness and precision of cellular functions have been perfected through billions of years of evolution. In this context, we ask the question whether cells follow a set of physical principles to sense, adapt, and migrate. Microfluidics has emerged as an enabling technology for recreating well-defined cellular environment for cell migration studies, and its ability to follow single cell dynamics allows for the results to be amenable for theoretical modeling. In this review, we focus on the development of microfluidic platforms for recreating cellular biophysical (e.g., mechanical stress) and biochemical (e.g., nutrients and cytokines) environments for cell migration studies in 3D. We summarize the basic principles that cells (including bacteria, algal, and mammalian cells) use to respond to chemical gradients learned from microfluidic systems. We also discuss about novel biological insights gained from studies of cell migration under biophysical cues and the need for further quantitative studies of cell function under well-controlled biophysical environments in the future.

Inhibitory fear memory engram in the mouse central lateral amygdala.

Engrams, which are cellular substrates of memory traces, have been identified in various brain areas, including the amygdala. While most identified engrams are composed of excitatory, glutamatergic neurons, GABAergic inhibitory engrams have been relatively overlooked. Here, we report the identification of an inhibitory engram in the central lateral amygdala (CeL), a key area for auditory fear conditioning. This engram is primarily composed of GABAergic somatostatin-expressing (SST(+)) and, to a lesser extent, protein kinase C-δ-expressing (PKC-δ(+)) neurons. Fear memory is accompanied by a preferential enhancement of synaptic inhibition onto PKC-δ(+) neurons. Silencing this CeL GABAergic engram disinhibits the activity of targeted extra-amygdaloid areas, selectively increasing the expression of fear. Our findings define the behavioral function of an engram formed exclusively by GABAergic inhibitory neurons in the mammalian brain.

Predicaments and coping strategies in implementing cancer truth-telling: a qualitative content analysis.

PURPOSE: The patient-centered communication principles in Western countries are widely esteemed. In Eastern countries, a family-centered approach to medical decision-making is preferred. However, the predicaments faced by attending physicians and their coping strategies in the process of truth-telling about cancer are unknown. Therefore, this study aimed to understand attending physicians' predicaments and coping strategies in implementing truth-telling for cancer in Taiwan. METHODS: This study used a qualitative description approach to conduct in-depth interviews with attending physicians. Data were collected from two medical centers in Taiwan. Purposive sampling was also conducted. A total of 17 attending physicians participated in individual semi-structured interviews. All interviews were audio recorded and transcribed verbatim. Inductive content analysis was used to analyze and develop the subcategories, generic categories, and main categories. RESULTS: Four main categories emerged: (1) Causing harm to the patient: Family members' cooperation is needed. (2) Family members' request to conceal the truth: Physicians should judge based on the patient's disease condition. (3) Delayed treatment: Physicians should prioritize establishing confidence. (4) Delivering bad news about relapse: Physicians have different coping strategies. CONCLUSION: Physicians in Taiwan face challenges but prioritize family-centered care despite having coping strategies to protect patients. When faced with a scenario in which family members request concealment of truth, most physicians cooperate with them to determine the level and method of disclosing unfavorable news to patients. Physicians should prioritize patients' psychological needs when they experience relapse or metastasis or face strong negative emotions.

The mediating role of depression in the association between socioeconomic status and cardiovascular disease: A nationwide cross-sectional study from NHANES 2005-2018.

Disparities in socioeconomic status (SES) are associated with an increased risk of cardiovascular disease (CVD). Depression is a highly prevalent cardiovascular risk factor among individuals with low SES. The present study aimed to gain a better understanding of the association between SES and CVD by examining the mediating effects of depression. 30,127 participants, 50.77 % female, with a mean age of 47.37 years from the National Health and Nutrition Examination Survey (NHANES) 2005-2018, were included. Weighted multivariable logistic regression analyses estimated the association between SES and CVD. Mediation analyses tested the mediating effects of depression. The multivariable-adjusted odds ratio (OR) of high SES for CVD was 0.42 (95 % confidence interval (CI): 0.36, 0.50; P < 0.001). In parallel, depression was negatively associated with SES, in which the multivariable-adjusted ß was -1.42 (95 % CI: -1.62, -1.22; P < 0.001) in high SES compared to low SES. For the association between depression and CVD, the multivariable-adjusted OR per 1-point increase of PHQ-9 score for CVD was 1.08 (95 % CI: 1.07, 1.09; P < 0.001). The mediation models indicated that depression mediated 10.92 % of the total association between SES and CVD when fully adjusted. Identifying individuals with depression for appropriate treatment is promising for reducing the CVD burden among populations with low SES.

Massive acceleration of SN2 reaction using the oriented external electric field.

Nucleophilic substitution is one of the most fundamental chemical reactions, and the pursuit of high reaction rates of the reaction is one of the ultimate goals in catalytic and organic chemistry. The reaction barrier of the nucleophilic substitution originates from the highly polar nature of the transition state that can be stabilized under the electric field created by the solvent environment. However, the intensity of the induced solvent-electric field is relatively small due to the random orientation of solvent molecules, which hinders the catalytic effects and restricts the reaction rates. This work shows that oriented external electric fields applied within a confined nanogap between two nanoscopic tips could accelerate the Menshutkin reaction by more than four orders of magnitude (over 39 000 times). The theoretical calculations reveal that the electric field inside the nanogap reduces the energy barrier to increase the reaction rate. Our work suggests the great potential of electrostatic catalysis for green synthesis in the future.

Persistent inflammation and lymphopenia and weaning outcomes of patients with prolonged mechanical ventilation.

BACKGROUND: Weaning outcomes of patients receiving mechanical ventilation (MV) are affected by multiple factors. A clinical feature of critically ill patients is the presence of lymphopenia, however the clinical significance of lymphopenia in patients receiving prolonged MV remains unclear. METHODS: We enrolled patients who received at least 21 consecutive days of MV in a medical center in Taiwan between 2007 and 2016. Patients with and without lymphopenia (mean count <1000/µL) were compared after propensity score matching. RESULTS: Of the 3460 patients included in the analysis, 1625 (47.0%) were liberated from MV within 100 days. Lymphopenia and severe lymphopenia (mean count <500/µL) during the first 21 days of MV were common (52.9% and 14.5%, respectively), and restricted cubic spline analysis showed a significant reduction in weaning success when the lymphocyte count dropped below 1000/µL. After propensity score matching, the patients with lymphopenia during the third week had a lower rate of weaning success within 100 days (p = 0.005) and a higher in-hospital mortality rate (p = 0.001) than those without lymphopenia. The lymphopenia group also had significantly reduced platelet (p < 0.001) and albumin (p < 0.001) levels. CONCLUSIONS: Our findings suggest that lymphopenia during the first 3 weeks may be a marker of poor weaning outcomes in patients with prolonged MV.

Ginsenoside Rg1 ameliorates cerebral ischemia-reperfusion injury by regulating Pink1/ Parkin-mediated mitochondrial autophagy and inhibiting microglia NLRP3 activation.

OBJECTIVE: This study aimed to further elucidate the mechanism of ginsenoside Rg1 in the treatment of cerebral ischemia-reperfusion. METHODS: In this study, we observed the apoptosis of RM cells (microglia) after oxygen-glucose deprivation/reoxygenation (OGD/R) modeling before and after Rg1 administration, changes in mitochondrial membrane potential, changes in the content of Reactive oxygen species (ROS) and inflammatory vesicles NLR Family Pyrin Domain Containing 3 (NLRP3), and the expression levels of autophagy-related proteins, inflammatory factors, and apoptosis proteins. We further examined the pathomorphological changes in brain tissue, neuronal damage, changes in mitochondrial morphology and mitochondrial structure, and the autophagy-related proteins, inflammatory factors, and apoptosis proteins expression levels in CI/RI rats before and after administration of Rg1 in vivo experiments. RESULTS: In vitro experiments showed that Rg1 induced mitochondrial autophagy, decreased mitochondrial membrane potential, and reduced ROS content thereby inhibiting NLRP3 activation, decreasing secretion of inflammatory factors and RM cell apoptosis by regulating the PTEN induced putative kinase 1(Pink1) /Parkin signaling pathway. In vivo experiments showed that Rg1 induced mitochondrial autophagy, inhibited NLRP3 activation, improved inflammatory response, and reduced apoptosis by regulating the Pink1/Parkin signaling pathway, and Rg1 significantly reduced the area of cerebral infarcts, improved the pathological state of brain tissue, and attenuated the neuronal damage, thus improving cerebral ischemia/reperfusion injury in rats. CONCLUSION: Our results suggest that ginsenoside Rg1 can ameliorate cerebral ischemia-reperfusion injury by modulating Pink1/ Parkin-mediated mitochondrial autophagy in microglia and inhibiting microglial NLRP3 activation.

Knocking down macrophages Caspase-6 through HMGB1 coordinates macrophage trophoblast crosstalk to suppress ferroptosis and alleviate preeclampsia.

OBJECTIVE: Caspase-6 is an important regulatory factor in innate immunity, inflammasome activation, and host defense, but its role in preeclampsia (PE) is unknown. This study aims to investigate the mechanism of Caspase-6 in the interaction between PE rats and macrophage-trophoblast cells, in order to provide a new theoretical basis for the treatment of PE. METHODS: Co-cultures of THP-1 cells and HTR8/SVneo cells were employed to investigate the HMGB1 signaling in macrophages (transfection with si-Caspase-6) and HTR8/SVneo cells. The PE rat model was constructed by using the reduced uterine perfusion pressure (RUPP) surgery to explore the therapeutic effects of bone marrow-derived macrophages (BMDM) transfected with si-Caspase-6 in PE rats. ELISA, Western blot, immunofluorescence, etc., were employed to characterize the expression of ferroptosis-related markers. RESULTS: Caspase-6 expression was significantly increased in CD14+ macrophages in the placental tissue of PE rats. Overexpression of Caspase-6 in THP-1 cells induced ferroptosis of HTR8/SVneo cells, but this process was blocked by anti-HMGB1 neutralizing antibody. Knockdown of Caspase-6 in macrophages could alleviate ferroptosis of HTR8/SVneo cells and restore its basic characteristics. Knockdown of Caspase-6 in BMDM downregulated ferroptosis in placental tissue of PE rats through HMGB1, thereby improving the disease phenotype in rats. CONCLUSION: Knocking down Caspase-6 in BMDM regulated the crosstalk between macrophages and HTR8/SVneo cells through HMGB1, inhibiting HTR8/SVneo cell ferroptosis, thereby improving adverse pregnancy outcomes of PE.

Osteoporosis in Relation to a Bone-Related Aging Biomarker Derived from the Urinary Proteomic Profile: A Population Study.

Screening for and prevention of osteoporosis and osteoporotic fractures is imperative, given the high burden on individuals and society. This study constructed and validated an aging-related biomarker derived from the urinary proteomic profile (UPP) indicative of osteoporosis (UPPost-age). In a prospective population study done in northern Belgium (1985-2019), participants were invited for a follow-up examination in 2005-2010 and participants in the 2005-2010 examination again invited in 2009-2013. Participants in both the 2005-2010 and 2009-2013 examinations (n = 519) constituted the derivation (2005-2016 data) and time-shifted validation (2009-2013 data) datasets; 187 participants with only 2005-2010 data formed the synchronous validation dataset. The UPP was assessed by capillary electrophoresis coupled with mass spectrometry. Analyses focused on 2372 sequenced urinary peptides (101 proteins) with key roles in maintaining the integrity of bone tissue. In multivariable analyses with correction for multiple testing, chronological age was associated with 99 urinary peptides (16 proteins). Peptides derived from IGF2 and MGP were upregulated in women compared to men, whereas COL1A2, COL3A1, COL5A2, COL10A1 and COL18A1 were downregulated. Via application of a 1000-fold bootstrapped elastic regression procedure, finally, 29 peptides (10 proteins) constituted the UPPost-age biomarker, replicated across datasets. In cross-sectional analyses of 2009-2013 data (n = 706), the body-height-to-arm-span ratio, an osteoporosis marker, was negatively associated with UPPost-age (p&;lt0.0001). Over 4.89 years (median), the 10-year risk of osteoporosis associated with chronological age and UPPost-age (53 cases including 37 fractures in 706 individuals) increased by 21% and 36% (p ≤ 0.044). Among 357 women, the corresponding estimates were 55% and 60% for incident osteoporosis (37 cases; p ≤ 0.0003) and 42% and 44% for osteoporotic fractures (25 cases; p ≤ 0.017). In conclusion, an aging-related UPP signature with focus on peptide fragments derived from bone-related proteins is associated with osteoporosis risk and available for clinical and trial research.

Acceptance level of advance care planning and its associated factors among the public: A nationwide survey.

BACKGROUND: Advance care planning (ACP) can contribute to individuals making decisions about their healthcare preferences in advance of serious illness. Up to now, the acceptance level and associated factors of ACP among the public in China remain unclear. This study aims to investigate the acceptance level of ACP in China and identify factors associated with it based on the socioecological model. METHODS: A total of 19,738 participants were included in this survey. We employed a random forest regression analysis to select factors derived from the socioecological model. Multivariate generalized linear model analysis was then conducted to explore the factors that were associated with the acceptance level of ACP. RESULTS: On a scale ranging from 0 to 100, the median score for acceptance level of ACP was 64.00 (IQR: 48.00-83.00) points. The results of the multivariate generalized linear model analysis revealed that participants who scored higher on measures of openness and neuroticism personality traits, as well as those who had greater perceptions of social support, higher levels of health literacy, better neighborly relationships, family health, and family social status, were more likely to accept ACP. Conversely, participants who reported higher levels of subjective well-being and greater family communication levels demonstrated a lower likelihood of accepting ACP. CONCLUSIONS: This study identified multiple factors associated with the acceptance level of ACP. The findings offer valuable insights that can inform the design and implementation of targeted interventions aimed at facilitating a good death and may have significant implications for the formulation of end-of-life care policies and practices in other countries facing similar challenges.

Diagnostic and prognostic value of double-negative T cells in colorectal cancer.

Objective: To evaluate the T-lymphocyte subset distribution and the diagnostic and prognosis value of double-negative T (DNT) cells in colorectal cancer (CRC). Methods: This retrospective study compared the T-lymphocyte subsets and DNT of 114 patients with CRC with those of 107 healthy controls (HC). The diagnostic potential of DNT and T-lymphocyte subsets was assessed using the receiver operating characteristic (ROC) curve, and prognostic values were evaluated using the Kaplan-Meier curve and the Cox regression model. Results: The percentages of CD8+ T cells and DNT cells, and value of carcinoembryonic antigen (CEA), were remarkably higher in patients with CRC than in those with HC, but the ratio of CD4+/CD8+ was decreased. Using ROC curve analysis, DNT cell percentage, CEA, and CD4+/CD8+ ratio all had good diagnostic efficacy, with areas under the curve (AUCs) of 0.865, 0.786 and 0.624, respectively. The combination of DNT cell percentage and CEA had an AUC of 0.905, which was significantly higher than that of any single biomarker (p < 0.05). In univariate analysis, the Tumor Node Metastasis (TNM) clinical stage, CD4+/CD8+ ratio, and DNT cell percentage were significantly associated with overall survival (OS) (p < 0.05). In multivariate analysis, TNM clinical staging (HR = 2.37, 95 % CI: 1.15-4.90), a decreased CD4+/CD8+ ratio (HR = 0.33, 95 % CI: 0.15-0.74), and an increased DNT cell percentage (HR = 2.29, 95 % CI: 1.11-4.73) were independent prognostic factors for CRC. Conclusion: The percentage of DNT cells may be useful as an evaluation index for CRC diagnosis and prognosis, which was even better when combined with serum CEA.

Heart rate reactivity, recovery, and endurance of the incremental shuttle walk test in patients prone to heart failure.

AIMS: Few randomized trials assessed the changes over time in the chronotropic heart rate (HR) reactivity (CHR), HR recovery (HRR) and exercise endurance (EE) in response to the incremental shuttle walk test (ISWT). We addressed this issue by analysing the open HOMAGE (Heart OMics in Aging) trial. METHODS: In HOMAGE, 527 patients prone to heart failure were randomized to usual treatment with or without spironolactone (25-50 mg/day). The current sub-study included 113 controls and 114 patients assigned spironolactone (~70% on beta-blockers), who all completed the ISWT at baseline and at Months 1 and 9. Within-group changes over time (follow-up minus baseline) and between-group differences at each time point (spironolactone minus control) were analysed by repeated measures ANOVA, unadjusted or adjusted for sex, age and body mass index, and additionally for baseline for testing 1 and 9 month data. RESULTS: Irrespective of randomization, the resting HR and CHR did not change from baseline to follow-up, with the exception of a small decrease in the HR immediately post-exercise (-3.11 b.p.m.) in controls at Month 9. In within-group analyses, HR decline over the 5 min post-exercise followed a slightly lower course at the 1 month visit in controls and at the 9 month visits in both groups, but not at the 1 month visit in the spironolactone group. Compared with baseline, EE increased by two to three shuttles at Months 1 and 9 in the spironolactone group but remained unchanged in the control group. In the between-group analyses, irrespective of adjustment, there were no HR differences at any time point from rest up to 5 min post-exercise or in EE. Subgroup analyses by sex or categorized by the medians of age, left ventricular ejection fraction or glomerular filtration rate were confirmatory. Combining baseline and Months 1 and 9 data in both treatment groups, the resting HR, CHR and HRR at 1 and 5 min averaged 61.5, 20.0, 9.07 and 13.8 b.p.m. and EE 48.3 shuttles. CONCLUSIONS: Spironolactone on top of usual treatment compared with usual treatment alone did not change resting HR, CHR, HRR and EE in response to ISWT. Beta-blockade might have concealed the effects of spironolactone. The current findings demonstrate that the ISWT, already used in a wide variety of pathological conditions, is a practical instrument to measure symptom-limited exercise capacity in patients prone to developing heart failure because of coronary heart disease.

Discovery of pyrrolo[2,3-d]pyrimidin-4-one derivative YCH3124 as a potent USP7 inhibitor for cancer therapy.

USP7 is one of the most studied deubiquitinating enzymes, which is involved in the regulation of multiple cell signaling pathways and has been shown to be associated with the occurrence and progression of a variety of cancers. Inhibitors targeting USP7 have been studied by several teams, but most of them lack selectivity and have low activities. Herein, we reported a serious of pyrrole[2,3-d]pyrimidin-4-one derivatives through scaffold hopping of recently reported 4-hydroxypiperidine compounds. The representative compound Z33 (YCH3124) exhibited highly potent USP7 inhibition activity as well as anti-proliferative activity against four kinds of cancer cell lines. Further study revealed that YCH3124 effectively inhibited the downstream USP7 pathway and resulted in the accumulation of both p53 and p21 in a dose-dependent manner. Notably, YCH3124 disrupted cell cycle progression through restricting G1 phase and induced significant apoptosis in CHP-212 cells. In summary, our efforts provided a series of novel pyrrole[2,3-d]pyrimidin-4-one analogs as potent USP7 inhibitors with excellent anti-cancer activity.

Prevalence of infection and reinfection among healthcare workers in a hospital of Northern China between BA.5/BF. 7 and XBB.1.5 wave.

BACKGROUND: Healthcare workers (HCWs) play a crucial role as frontline responders during the COVID-19 pandemic. This study aimed to analyze the epidemiological characteristics of the first SARS-CoV-2 infection and reinfection associated with the emergence of Omicron variant in HCWs. METHODS: We enrolled 760 HCWs who received 2-4 vaccination doses of COVID-19 and followed by BA.5/BF.7 and/or XBB.1.5 breakthrough infections between December 2022 and July 2023. Serum sample from each individual were collected approximately 1,3 and 6 months after last exposure. IgM, IgG and Total antibodies against SARS-CoV-2 were measured by chemiluminescent immunoassay. Meanwhile, we created an Enterprise WeChat link for HCWs to self-report SARS-CoV-2 infections, symptoms and post COVID-19 conditions. RESULTS: Our study revealed that the reinfection rate among HCWs reached 26.1%. The main symptoms were fever (91.2% vs. 60.1%), cough (78.8% vs. 58.0%), and sore throat (75.4% vs. 59.6%) during infection and reinfection in Omicron BA.5/BF.7 and XBB.1.5 wave, and the interval for reinfection ranged from 91 to 210 days (median 152 days). Fatigue (23.6%), memory loss (18.8%) and coughing (18.6%) were the most prevalent long COVID symptoms in HCWs, with a higher prevalence among female HCWs. CONCLUSIONS: HCWs reinfection with SARS-CoV-2 causes milder symptoms, but high reinfection rate and short intervals. Enhancing prevention strategies, protection and training is crucial to mitigating HCW infection risk and improving health services.

Tourniquet Use and Local Tissue Concentrations of Cefazolin During Total Knee Arthroplasty: A Randomized Clinical Trial.

Importance: Prophylactic administration of antibiotics before skin incision is an important component in the prevention of periprosthetic joint infection in arthroplasty surgery. For antibiotics to be effective, the local tissue concentration (LTC) must exceed the minimum inhibitory concentration of typical infecting organisms; however, the LTC of cefazolin during arthroplasty is poorly understood. Objective: To compare the systemic concentration of cefazolin in serum with the LTC in fat, synovium, and bone during primary total knee arthroplasty (TKA) while assessing the effect of tourniquet inflation. Design, Setting, and Participants: This prospective randomized clinical trial was conducted from March 1, 2022, to June 30, 2023, in patients undergoing TKA at a single academic center. Intervention: Total knee arthroplasty with or without a limb tourniquet. Main Outcomes and Measures: Systemic blood and local tissues from the surgical site (fat, synovium, and bone) were harvested at regular intervals during the surgery. The primary outcome was the LTC of cefazolin, quantified using the liquid chromatography-tandem mass spectrometry technique. Results: A total of 59 patients were included in the study, with 29 in the tourniquet group (mean [SD] age, 69.3 [9.6] years; 23 [79.3%] female) and 30 in the no tourniquet group (mean [SD] age, 69.9 [9.7] years; 21 [70.0%] female). In patients undergoing TKA without a tourniquet, the mean concentration of cefazolin in serum was 71.9 µg/mL (95% CI, 66.4-77.5 µg/mL), whereas the mean LTCs were 13.9 µg/g (95% CI, 12.1-15.7 µg/g) in fat, 27.7 µg/g (95% CI, 24.3-31.0 µg/g) in synovium, and 17.7 µg/g (95% CI, 14.8-20.5 µg/g) in bone. For patients undergoing TKA with a tourniquet, the mean concentration of cefazolin in serum was 72.0 µg/mL (95% CI, 66.3-77.7 µg/mL), and the mean LTCs were 9.9 µg/g (95% CI, 8.7-11.1 µg/g) in fat, 21.8 µg/g (95% CI, 18.7-25.0 µg/g) in synovium, and 13.0 µg/g (95% CI, 10.8-15.2 µg/g) in bone. The use of a tourniquet resulted in significantly lower mean LTCs by 60 minutes after cefazolin infusion (10.8 µg/g [95% CI, 9.1-12.4 µg/g] vs 16.9 µg/g [95% CI, 14.1-19.6 µg/g], P = .001 in fat; 18.9 µg/g [95% CI, 14.1-23.6 µg/g] vs 25.8 µg/g [95% CI, 21.4-30.3 µg/g], P = .03 in synovium; and 11.8 µg/g [95% CI, 9.3-14.2 µg/g] vs 19.4 µg/g [95% CI, 14.5-24.4 µg/g], P = .007 in bone). Conclusions and Relevance: In this randomized clinical trial, the concentration of cefazolin was lower in local tissues (fat, synovium, and bone) than in systemic blood, and the use of a limb tourniquet further significantly reduced these concentrations. Although the current prophylactic dosing regimen for cefazolin provides sufficient serum concentrations, the levels in the periarticular tissue during TKA may be insufficient to prevent periprosthetic joint infection. Trial Registration: ClinicalTrials.gov Identifier: NCT05604157.

Changes in urinary renal injury markers in children with Mycoplasma pneumoniae pneumonia and a prediction model for related early renal injury.

BACKGROUND: This study aims to analyse changes in urinary kidney injury markers in children with Mycoplasma pneumoniae pneumonia (MPP), investigate the risk factors for MPP-related acute kidney injury (AKI) and establish a model to predict MPP-related AKI. METHODS: Ninety-five children were enrolled based on the study's inclusion and exclusion criteria. They were divided into a severe MPP (SMPP) group and a non-SMPP group and then into an AKI group and a non-AKI group according to the presence of AKI. A univariate logistic regression analysis was performed to explore the early risk factors for AKI. Based on a multivariate logistic regression analysis and a least absolute shrinkage and selection operator regression analysis, appropriate variables were selected to establish a prediction model, and R 4.2.2 software was used to draw nomograms and generate a dynamic nomogram website. RESULTS: Seven urinary kidney injury markers were abnormally elevated in the SMPP group and the non-SMPP group: urinary N-acetyl-ß-D-glucosaminidase (NAG), ß2-microglobulin, α1-microglobulin, retinol-binding protein, urinary immunoglobulin G, urinary transferrin and urinary microalbumin. Sixteen children were identified with AKI during hospitalisation. The AKI group had higher levels of urinary NAG, α1-microglobulin, ß2-microglobulin, urinary microalbumin, urinary transferrin and retinol-binding protein than the non-AKI group (P < 0.05). The MPP-related AKI prediction model consists of four indicators (serum immunoglobulin M [IgM], C-reactive protein [CRP], urine NAG and sputum plug presence) and a dynamic nomogram. CONCLUSION: Urinary kidney injury markers are often elevated in children with MPP; urinary NAG is the marker most likely to be elevated, and it is especially evident in severe cases. The nomogram of the prediction model, comprising serum IgM, CRP, urinary NAG and sputum plug presence, can predict the probability of AKI in children with MPP.

[Regional Difference and Spatial Convergence of Land Use Carbon Emissions in Three Urban Agglomerations of Yangtze River Economic Belt].

It is of great significance to explore the regional differences of land use carbon emission （LUCE） in the Yangtze River Economic Belt and the path of coordinated emission reduction for regional sustainable development. Based on the LUCE estimation method, this study scientifically calculated the LUCE of the three major urban agglomerations of the Yangtze River Economic Belt （Yangtze River Delta, middle reaches of the Yangtze River, and Chengdu-Chongqing urban agglomeration） from 2010 to 2020. Kernel density estimation and the spatial convergence model were used to study the dynamic evolution, regional differences, and convergence characteristics of LUCE. The results showed that： ① The carbon absorption of forest land, water areas, grassland, and unused land were relatively small in terms of carbon emissions from cultivated land and construction land. The carbon emission of construction land increased gradually, whereas the carbon absorption of four carbon sinks fluctuated little during the study period. ② The core density curves of different urban agglomerations showed different distribution patterns, extensibility, and polarization characteristics but generally tended to be balanced. ③ From 2010 to 2020, the LUCE of the Yangtze River Economic Belt as a whole showed the spatio-temporal characteristics of increasing first and then decreasing and high in the east and low in the west. The LUCE of the central cities of the three urban agglomerations were at the highest level steadily, and stable coupling mechanisms had not been established between the economic development level and the ecological environment. ④ The LUCE of the three urban agglomerations in the Yangtze River Economic Belt all had absolute ß convergence and also had conditional ß convergence under the model control variables such as economic development level, urbanization level, industrial structure, population density, and environmental regulation, etc., and the conditional convergence speed was greater than the absolute convergence speed in each region. The convergence speed of the Yangtze River Delta urban agglomeration was the slowest. The above conclusions provide support for the coordinated emission reduction path of the three urban agglomerations in the Yangtze River Economic Belt and are also conducive to actively and steadily promoting the realization of the goals of carbon peak and carbon neutralization.

Peripheral hemoglobin to albumin ratio predicts prognosis in patients with nasopharyngeal carcinoma underwent concurrent chemoradiotherapy.

BACKGROUND: Recently, the hemoglobin to albumin ratio (HAR) has been shown to be closely associated with the survival of certain malignancies. However, its prognostic value in nasopharyngeal carcinoma (NPC) remained to be elucidated. Herein, we aimed to explore the correlation between HAR and overall survival (OS) in NPC patients treated with concurrent chemoradiotherapy (CCRT). METHODS: This retrospective study included a total of 858 patients with NPC receiving CCRT between January 2010 and December 2014 in Sun Yat-sen University Cancer Center. We randomly divided them into the training cohort (N = 602) and the validation cohort (N = 206). We performed univariate and multivariate Cox regression analyses to identify variables associated with OS, based on which, a predictive nomogram was constructed and assessed. RESULTS: In both the training and validation cohorts, patients were classified into low- and high-HAR groups according to the cutoff value determined by the maximally selected rank statistics. This HAR cutoff value effectively divided patients into two distinct prognostic groups with significant differences. Multivariable Cox analysis revealed that higher T-stage, N-stage, and HAR values were significantly related to poorer prognosis in NPC patients and served as independent prognostic factors for NPC. Based on these, a predictive model was constructed and graphically presented as a nomogram, whose predictive performance is satisfactory with a C-index of 0.744 [95%CI: 0.679-0.809] and superior to traditional TNM staging system [C-index = 0.609, 95%CI: 0.448-0.770]. CONCLUSION: The HAR value was an independent predictor for NPC patients treated with CCRT, the predictive model based on HAR with superior predictive performance than traditional TNM staging system might improve individualized survival predictions.

Prediction and verification of benignancy and malignancy of pulmonary nodules based on inflammatory related biological markers.

Objective: Inflammation plays an important role in the transformation of pulmonary nodules (PNs) from benign to malignant. Prediction of benignancy and malignancy of PNs is still lacking efficacy methods. Although Mayo or Brock model have been widely applied in clinical practices, their application conditions are limited. This study aims to construct a diagnostic model of PNs by machine learning using inflammation-related biological markers (IRBMs). Methods: Inflammatory related genes (IRGs) were first extracted from GSE135304 chip data. Then, differentially expressed genes (DEGs) and infiltrating immune cells were screened between malignant pulmonary nodules (MN) and benign pulmonary nodule (BN). Correlation analysis was performed on DEGs and infiltrating immune cells. Molecular modules of IRGs were identified through Consistency cluster analysis. Subsequently, IRBMs in IRGs modules were filtered through Weighted gene co-expression network analysis (WGCNA). An optimal diagnostic model was established using machine learning methods. Finally, external dataset GSE108375 was used to verify this result. Results: 4 hub IRGs and 3 immune cells showed significantly difference between MN and BN, C1 and C2 module, namely PRTN3, ELANE, NFKB1 and CTLA4, T cells CD4 naïve, NK cells activated and Monocytes. IRBMs were screened from black module and yellowgreen module through WGCNA analysis. The Support vector machines (SVM) was identified as the optimal model with the Area Under Curve (AUC) was 0.753. A nomogram was established based on 5 hub IRBMs, namely HS.137078, KLC3, C13ORF15, STOM and KCTD13. Finally, external dataset GSE108375 verified this result, with the AUC was 0.718. Conclusion: SVM model established by 5 hub IRBMs was able to effectively identify MN or BN. Accumulating inflammation and immune dysfunction were important to the transformation from BN to MN.

Causal relationship between gut microbiota and pathological scars: a two-sample Mendelian randomization study.

Background: Pathological scars, including keloids and hypertrophic scars, represent a significant dermatological challenge, and emerging evidence suggests a potential role for the gut microbiota in this process. Methods: Utilizing a two-sample Mendelian randomization (MR) methodology, this study meticulously analyzed data from genome-wide association studies (GWASs) relevant to the gut microbiota, keloids, and hypertrophic scars. The integrity and reliability of the results were rigorously evaluated through sensitivity, heterogeneity, pleiotropy, and directionality analyses. Results: By employing inverse variance weighted (IVW) method, our findings revealed a causal influence of five bacterial taxa on keloid formation: class Melainabacteria, class Negativicutes, order Selenomonadales, family XIII, and genus Coprococcus2. Seven gut microbiota have been identified as having causal relationships with hypertrophic scars: class Alphaproteobacteria, family Clostridiaceae1, family Desulfovibrionaceae, genus Eubacterium coprostanoligenes group, genus Eubacterium fissicatena group, genus Erysipelotrichaceae UCG003 and genus Subdoligranulum. Additional sensitivity analyses further validated the robustness of the associations above. Conclusion: Overall, our MR analysis supports the hypothesis that gut microbiota is causally linked to pathological scar formation, providing pivotal insights for future mechanistic and clinical research in this domain.