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BACKGROUND: The potential of Tocilizumab (TCZ) in preventing the cytokine storm caused by COVID-19 infection has been observed, while the survival benefits were inconclusive in solid-organ transplant recipients. We aimed to explore whether the timing of TCZ administration holds significance in the clinical course of COVID-19 infection and identify predicative factors of TCZ efficacy. METHODS: We conducted a prospective cohort study between December 2022, and January 2023. Early TCZ use referred to administration within 6 days after symptoms onset, while late TCZ use indicated administration after 6 days. The primary endpoint was 30-day mortality. RESULTS: Twenty-seven kidney transplant recipients with severe COVID-19 infection were enrolled, with 10 in the early use group and 17 in the late use group. In the early use group, ferritin, lactate dehydrogenase (LDH), C-reactive protein (CRP) and brain natriuretic peptide(BNP) levels had shown significant inhibitions comparing to the late use group, and those inflammatory cytokines demonstrated a noticeable decreasing trend after TCZ administration, whereas only CRP levels decreased in the late use group. The Kaplan-Meier survival curve demonstrated that the early use group had a higher likelihood of survival (P = 0.0078). Receiver Operating Characteristic (ROC) analyses revealed that the time from symptoms to TCZ use (AUC: 0.645), LDH (AUC: 0.803), CRP (AUC: 0.787), and IL-6 (AUC: 0.725) were potential predictive factors of TCZ efficacy. TCZ use within 6 days from symptoms onset, with CRP < 73.5 mg/L, LDH < 435.5 IU/L, and IL-6 < 103.5 pg/mL, had higher survival rates (P = 0.008, P = 0.009, P < 0.001, P < 0.001). CONCLUSION: This study highlights the survival benefits of early TCZ use and the predicative role of cytokines levels in predicting TCZ efficacy in kidney transplant recipients with severe COVID-19 infection.

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OBJECTIVE: To explore the preventive and therapeutic effects of Dahuang Zhechong Pill (DZP) on pulmonary fibrosis and the underlying mechanisms. METHODS: The first key rate-limiting enzyme hexokinase 2 (HK2) of glycolysis was silenced and over-expressed through small interfering RNA and lentivirus using lung fibroblast MRC-5 cell line, respectively. The cell viability, migration, invasion and proliferation were detected by cell counting kit-8, wound healing assay, transwell assay, and flow cytometry. The mRNA and protein expression levels of HK2 were detected by RT-PCR and Western blotting, respectively. The contents of glucose, adenosine triphosphate (ATP) and lactate in MRC-5 cells were determined by enzyme-linked immunosorbnent assay (ELISA). Then, the relationship between miR-29b-2-5p and HK2 was explored by luciferase reporter gene assay. Pulmonary fibrosis cell model was induced by transforming growth factor-ß 1 (TGF-ß 1) in MRC-5 cells, and the medicated serum of DZP (DMS) was prepared in rats. MRC-5 cells were divided into control, TGF-ß 1, TGF-ß 1+10% DMS, TGF-ß 1+10% DMS+miR-29b-2-5p inhibitor, TGF-ß 1+10% DMS+inhibitor negative control, TGF-ß 1+10% DMS+miR-29b-2-5p mimic and TGF-ß 1+10% DMS+mimic negative control groups. After miR-29b-2-5p mimics and inhibitors were transfected into MRC-5 cells, all groups except control and model group were treated with DMS. The effect of DMS on MRC-5 cells were detected using aforementioned methods and immunofluorescence. Similarly, the contents of glucose, ATP and lactate in each group were measured by ELISA. RESULTS: The mRNA and protein expressions of HK2 in MRC-5 cells were successfully silenced and overexpressed through si-HK2-3 and lentiviral transfection, respectively. After silencing HK2, the mRNA and protein expressions of HK2 were significantly decreased (P<0.01), and the concentrations of glucose, ATP and lactate were also significantly decreased (P<0.05). The proliferation, migration and invasion of MRC-5 cells were significantly declined (P<0.05 or P<0.01), while the apoptosis of MRC-5 cells was significantly increased (P<0.01). After overexpressing HK2, the mRNA and protein expressions of HK2 were significantly increased (P<0.05), and the concentrations of glucose, ATP and lactate were also significantly increased (P<0.05 or P<0.01). The proliferation, migration and invasion of MRC-5 cells were significantly increased (P<0.05 or P<0.01), while the apoptosis of MRC-5 cells was significantly decreased (P<0.05). The relative luciferase activity of 3'UTR-WT+hsa-miR-29b-2-5p transfected with HK2 was significantly decreased (P<0.01). After miR-29b-2-5p mimic and inhibitor were transfected into the MRC-5 cells, DMS intervention could significantly reduce the concentration of glucose, ATP and lactate, and the mRNA and proteins expressions of HK2, phosphofructokinase and pyruvate kinase isoform M2 (P<0.05 or P<0.01). The proliferation, migration and invasion of MRC-5 cells were alleviated (P<0.05 or P<0.01), and the deposition of fibronectin, α-smooth muscle actin, and collagen I were significantly decreased (P<0.05 or P<0.01). CONCLUSIONS: Glycolysis is closely related to pulmonary fibrosis. DZP reduced glycolysis and inhibited fibroblasts' excessive differentiation and abnormal collagen deposition through the miR-29b-2-5p/HK2 pathway, which played a role in delaying the process of pulmonary fibrosis.

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Maternal age is one of the most important factors affecting the success of maternal pregnancy. Uterine aging is the leading cause of pregnancy failure in older women. However, how uterine aging affects uterine receptivity and decidualization is unclear. In this study, naturally aged one-year-old female mice were used to investigate effects of maternal age on embryo implantation during early pregnancy. In our study, we found abnormal uterine receptivity in aged mice. Aged mouse uterus indicates a decrease in nuclear LAMIN A, and an increase in PRELAMIN A and PROGERIN. In aged mouse uterus, double-stranded DNA (dsDNA) in cytoplasmic fraction is significantly increased. PROGERIN overexpression in mouse uterine epithelial cells and epithelial organoids leads to nuclear DNA leakage and impaired uterine receptivity. DNase I, DNase II, and TREX1 are obviously reduced in aged mouse uterus. Treatments with foreign DNA or STING agonist significantly downregulate uterine receptivity markers and activate cGAS-STING pathway. Uterine estrogen (E2) concentration is significantly increased in aged mice. After ovariectomized mice are treated with a high level of E2, there are significant increase of PROGERIN and cytoplasmic DNA, and activation of cGAS-STING pathway. CD14 is significantly increased in aged uterus. Intrauterine CD14 injection inhibits embryo implantation. In vitro CD14 treatment of cultured epithelial cells or epithelial organoids decreases uterine receptivity. Uterine abnormality in aged mouse can be partially rescued by STING inhibitor. In conclusion, uterine PROGERIN increase in aged mouse uterus results in cytoplasmic DNA accumulation and cGAS-STING pathway activation. CD14 secretion in aged uterus impairs uterine receptivity.

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OBJECTIVE: Accurate diagnoses and personalized treatments in medicine rely on identifying causality. However, existing causal discovery algorithms often yield inconsistent results due to distinct learning mechanisms. To address this challenge, we introduce MINDMerge, a multi-causal investigation and discovery framework designed to synthesize causal graphs from various algorithms. METHODS: MINDMerge integrates five causal models to reconcile inconsistencies arising from different algorithms. Employing credibility weighting and a novel cycle-breaking mechanism in causal networks, we initially developed and tested MINDMerge using three synthetic networks. Subsequently, we validated its effectiveness in discovering risk factors and predicting acute kidney injury (AKI) using two electronic medical records (EMR) datasets, eICU Collaborative Research Database and MIMIC-III Database. Causal reasoning was employed to analyze the relationships between risk factors and AKI. The identified causal risk factors of AKI were used in building a prediction model, and the prediction model was evaluated using the area under the receiver operating characteristics curve (AUC) and recall. RESULTS: Synthetic data experiments demonstrated that our model outperformed significantly in capturing ground-truth network structure compared to other causal models. Application of MINDMerge on real-world data revealed direct connections of pulmonary disease, hypertension, diabetes, x-ray assessment, and BUN with AKI. With the identified variables, AKI risk can be inferred at the individual level based on established BNs and prior information. Compared against existing benchmark models, MINDMerge maintained a higher AUC for AKI prediction in both internal (AUC: 0.832) and external network validations (AUC: 0.861). CONCLUSION: MINDMerge can identify causal risk factors of AKI, serving as a valuable diagnostic tool for clinical decision-making and facilitating effective intervention.

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P-selectin has been shown to enhance growth and metastasis of mouse tumors by promoting regulatory T cell (Treg) infiltration into the tumors. Theoretically, a P-selectin antagonist could suppress the process. Popylene glycol alginate sodium sulfate (PSS) is a heparin-like marine drug, which was originally approved to treat cardiovascular disease in China. Previously, we reported that PSS was an effective P-selectin antagonist in vitro. However, it is unknown whether PSS can regulate Treg infiltration and its effect on lung metastasis in vivo. Our results showed that PSS at 30 mg/kg significantly suppressed lung metastasis and improved overall survival, with potency comparable to the positive control LMWH. Mechanistic study indicated that PSS blocked tumor cells adhesion and activated platelets by directly binding with activated platelet's P-selectin. Compared to the model group, PSS decreased the percent of Tregs by 63 % in lungs after treating for 21 days while increasing CD8+ T cells (1.59-fold) and Granzyme B+ CD8 T cells (2.08-fold)' percentage for generating an adaptive response for systemic tumor suppression. The study indicated that the P-selectin antagonist, PSS, suppressed lung metastasis by inhibiting the infiltration of regulatory T cells (Treg) into the tumors.

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HTR1A C-1019G polymorphism (rs6295) and serotonin transporter promoter polymorphism (5-HTTLPR) have been linked with panic disorder (PD) in different ethnic backgrounds. Both these polymorphisms are in the promoter regions. However, results are inconsistent and contrasting evidence makes reliable conclusions even more challenging. A meta-analysis was conducted to test whether C-1019G polymorphism and 5-HTTLPR were involved in the etiology of PD. Articles researching the link between C-1019G, 5-HTTLPR polymorphisms, and PD were retrieved by database searching and systematically selected on the basis of selected inclusion parameters. 21 studies were included that examined the relationship of rs6295,5-HTTLPR polymorphisms with PD risk susceptibility (rs62957 polymorphism - 7 articles, and 5-HTTLPR polymorphism - 14 articles). A significant association was seen between the rs6295 polymorphism and PD pathogenesis, especially in Caucasian PD patients. No significant genetic linkage was found between the 5-HTTLPR polymorphism and PD. C-1019G polymorphism was involved in the etiology of PD in Caucasian patients. The 5-HTTLPR polymorphism was not a susceptibility factor of PD.

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Checkpoint blockades have emerged as a frontline approach in cancer management, designed to enhance the adaptive immune response against tumors. However, its clinical efficacy is limited to a narrow range of tumor types, which necessitates the exploration of novel strategies that target another main branch of the immune system. One such potential strategy is the therapeutic modulation of pattern recognition receptors (PRRs) pathways in innate immune cells, which have shown promise in tumor eradication. Previously, a ß-1,3/1,6-glucan with high purity from Durvillaea antarctica (BG136) was reported by our group to exhibit pan-antitumor effects. In the current study, we systemically studied the antitumor activity of BG136 in combination with anti-PD1 antibody in MC38 syngeneic tumor model in vivo. Integrated transcriptomic and metabolomic analyses suggested that BG136 enhanced the antitumor immunity of anti-PD1 antibody by reprogramming the tumor microenvironment to become more proinflammatory. In addition, an increase in innate and adaptive immune cell infiltration and activation, enhanced lipid metabolism, and a decrease in ascorbate and aldarate metabolism were also found. These findings provide mechanistic insights that support the potent antitumor efficacy of BG136 when combined with immune checkpoint inhibitor antibodies.

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Background: Observational studies have shown that heart rate (HR), heart rate variability (HRV), P-wave terminal force, P-wave duration, T-wave amplitude and PR interval are associated with risk factors for atrial fibrillation (AF) or bradycardia. Arrhythmias are associated with many causes of hospitalization. However, observational studies are susceptible to confounding factors that have not yet been identified. The objective of this study was to clarify the causal relationships by Mendelian randomization analysis. Methods: We conducted a two-sample and multivariate Mendelian randomization (MVMR) analysis using genome-wide association study (GWAS) data from a European population to assess the total and direct causal effects of HR, three HRV traits, P-wave terminal force, P-wave duration, T-wave top amplitude in five-lead modes, and the PR interval on the risk of AF (N=191,205), bradycardia (N=463,010), and supraventricular tachycardia (SVT) (N=463,010). Results: The results of the univariate MR analysis revealed the following significant causal effects: the higher the genetically predicted PR interval, the lower the risk of AF; the higher the HR and T-wave top amplitude (aVR leads and V3 + V4 + aVL leads), the lower the risk of bradycardia; and the higher HR and the lower PR interval, the higher the risk of SVT. The multivariate MR results indicated that the HRV_standard deviation of the normal-to-normal (SDNN) interval had an independent causal effect on the risk of AF [odds ratio (OR): 0.515; 95% confidence interval (CI): 0.278-0.954; P=0.03], and the T-wave top amplitude in the aVR leads (OR: 0.998; 95% CI: 0.996-0.999; P<0.001) and the HRV_SDNN (OR: 0.988; 95% CI: 0.976-1.000; P=0.045) had independent causal effects on the risk of bradycardia. Conclusions: The HRV_SDNN had an independent causal effect on AF, while the HRV_SDNN and T-wave top amplitude in the aVR leads had independent causal effects on bradycardia, which suggests that some of the electrocardiographic parameters have preventive effects on the incidence of AF and bradycardia.

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The differences between the serum albumin determined by bromocresol green (BCG) and immunonephelometry (IN) were inconsistent in past studies, and the samples were all adults. We sought to determine the differences in children and reveal the impacts of these differences on the clinical diagnosis and treatments of primary nephrotic syndrome (PNS). Repeated measurements from 576 PNS children showed that albumin measured by BCG and IN (ALB-B and ALB-I) were 19.95 (11.15) g/L and 15.30 (11.05) g/L, respectively, and the mean difference was 4.68 g/L (P < 0.001). The cut-offs we calculated for hypoalbuminemia and severe hypoalbuminemia based on the IN were 25 and 15 g/L, which were 5 g/L lower than the cut-offs recommended by KIDGO, respectively. A pair of historical control samples (206 vs. 216) with ALB-B or ALB-I showed that the proportion of severe hypoalbuminemia was 14.60% greater in IN group (75.20% vs. 60.60%, P < 0.001). The misdiagnosis rate of severe hypoalbuminemia by IN was 33.77% when 20 g/L rather than 15 g/L was used as the cut-off. Furthermore, the proportion of patients receiving albumin injections increased by 10.20%, and the average consumption increased by 97.06% (P = 0.01) along with the use of IN. So, our results suggested that the difference between ALB-B and ALB-I led to misdiagnosis and prescription abuse in PNS children.

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Natural organisms have evolved precise sensing systems relying on unique ion channels, which can efficiently perceive various physical/chemical stimuli based on ionic signal transmission in biological fluid environments. However, it is still a huge challenge to achieve extensive applications of the artificial counterparts as an efficient wet sensing platform due to the fluidity of the working medium. Herein, nanofluidic membranes with selective cation transport properties and solid-state organic electrochemical transistors (OECTs) with amplified signals are integrated together to mimic human gustatory sensation, achieving ionic gustatory reagent recognition and a portable configuration. Cu-HHTP nanofluidic membranes with selective cation transport through their uniform micropores are constructed first, followed by assembly with OECTs to form the designed nanofluidic membrane-assisted OECTs (nanofluidic OECTs). As a result, they can distinguish typically ionic gustatory reagents, and even ionic liquids (ILs), demonstrating enhanced gustatory perception performance under a wide concentration range (10-7-10-1 m) compared with those of conventional OECTs. The linear correlations between the response and the reagent concentration further indicate the promising potential for practical application as a next-generation sensing platform. It is suggested that nanofluidic membranes mediated intramembrane cation transport based on the steric hindrance effect, resulting in distinguishable and improved response to multiple ions.

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OBJECTIVE: To explore the optimal blood glucose-lowering strategies for patients with diabetic ketoacidosis (DKA) to enhance personalized treatment effects using machine learning techniques based on the United States Critical Care Medical Information Mart for Intensive Care- IV (MIMIC- IV). METHODS: Utilizing the MIMIC- IV database, the case data of 2 096 patients with DKA admitted to the intensive care unit (ICU) at Beth Israel Deaconess Medical Center from 2008 to 2019 were analyzed. Machine learning models were developed, and receiver operator characteristic curve (ROC curve) and precision-recall curve (PR curve) were plotted to evaluate the model's effectiveness in predicting four common adverse outcomes: hypoglycemia, hypokalemia, reductions in Glasgow coma scale (GCS), and extended hospital stays. The risk of adverse outcomes was analyzed in relation to the rate of blood glucose decrease. Univariate and multivariate Logistic regression analyses were conducted to examine the relationship between relevant factors and the risk of hypokalemia. Personalized risk interpretation methods and predictive technologies were applied to individualize the analysis of optimal glucose control ranges for patients. RESULTS: The machine learning models demonstrated excellent performance in predicting adverse outcomes in patients with DKA, with areas under the ROC curve (AUROC) and 95% confidence interval (95%CI) for predicting hypoglycemia, hypokalemia, GCS score reduction, and extended hospital stays being 0.826 (0.803-0.849), 0.850 (0.828-0.870), 0.925 (0.903-0.946), and 0.901 (0.883-0.920), respectively. Analysis of the relationship between the rate of blood glucose reduction and the risk of four adverse outcomes showed that a maximum glucose reduction rate > 6.26 mmol×L-1×h-1 significantly increased the risk of hypoglycemia (P < 0.001); a rate > 2.72 mmol×L-1×h-1 significantly elevated the risk of hypokalemia (P < 0.001); a rate > 5.53 mmol×L-1×h-1 significantly reduced the risk of GCS score reduction (P < 0.001); and a rate > 8.03 mmol×L-1×h-1 significantly shortened the length of hospital stay (P < 0.001). Multivariate Logistic regression analysis indicated significant correlations between maximum bicarbonate levels, blood urea nitrogen levels, and total insulin doses with the risk of hypokalemia (all P < 0.01). In terms of establishing personalized optimal treatment thresholds, assuming optimal glucose reduction thresholds for hypoglycemia, hypokalemia, GCS score reduction, and extended hospital stay were x1, x2, x3, x4, respectively, the recommended glucose reduction rates to minimize the risks of hypokalemia and hypoglycemia should be ≤min{x1, x2}, while those to reduce GCS score decline and extended hospital stay should be ≥ max{x3, x4}. When these ranges overlap, i.e., max{x3, x4} ≤ min{x1, x2}, this interval was the recommended optimal glucose reduction range. If there was no overlap between these ranges, i.e., max{x3, x4} > min{x1, x2}, the treatment strategy should be dynamically adjusted considering individual differences in the risk of various adverse outcomes. CONCLUSIONS: The machine learning models shows good performance in predicting adverse outcomes in patients with DKA, assisting in personalized blood glucose management and holding important clinical application prospects.

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BACKGROUND: Donors with small asymptomatic kidney stones have been increasingly accepted because of organ shortages and advances in endoscopic urology. This study aims to evaluate and compare long-term living-donor kidney transplant outcomes following ex vivo surgical removal versus conservative management of donors' gifted asymptomatic stones. METHODS: Between January 2007 and December 2021, 119 kidney transplant recipients received stone-bearing kidneys, divided into the removal group (N = 63) and observation group (N = 56). We evaluated posttransplant stone events, urinary infections, kidney function, delayed graft function, length of hospital stay, and survival outcomes. RESULTS: After a median follow-up of 75.5 mo, the removal group had a 10.9% lower absolute incidence of stone events (7/56 [12.5%] versus 1/63 [1.6%]; hazard ratio, 0.08; 95% confidence interval, 0.01-0.77) and a 14.3% lower absolute incidence of urinary infections (16/56 [28.6%] versus 9/63 [14.3%]; hazard ratio, 0.42; 95% confidence interval, 0.19-0.95) than the observation group. The removal group also showed superior kidney graft function. The 2 groups had comparable length of hospital stay (11.0 versus 12.0 d; P = 0.297) and exhibited similar delayed graft function incidence (1/56 [1.8%] versus 2/63 [3.2%]; P = 1.000) and urinary stricture incidence (1/56 [1.8%] versus 3/63 [4.8%]; P = 0.621). Graft survival (P = 0.350) and patient survival (P = 0.260) were comparable between 2 groups. Subgroup analyses in recipients who received kidneys with stones <4 mm also reported similar results. CONCLUSIONS: Ex vivo surgical removal might outperform conservative management for donors' gifted asymptomatic kidney stones, improving long-term transplant outcomes and reducing stone events without increasing perioperative complications, even for stones <4 mm.

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INTRODUCTION: Due to the high cost and complexity, the oral glucose tolerance test is not adopted as the screening method for identifying diabetes patients, which leads to the misdiagnosis of patients with isolated post-challenge hyperglycemia (IPH), that is., patients with normal fasting plasma glucose (<7.0 mmoL/L) and abnormal 2-h postprandial blood glucose (≥11.1 mmoL/L). We aimed to develop a model to differentiate individuals with IPH from the normal population. METHODS: Data from 54301 eligible participants were obtained from the Risk Evaluation of Cancers in Chinese Diabetic Individuals: a longitudinal (REACTION) study in China. Data from 37740 participants were used to develop the diagnostic system. External validation was performed among 16561 participants. Three machine learning algorithms were used to create the predictive models, which were further evaluated by various classification algorithms to establish the best predictive model. RESULTS: Ten features were selected to develop an IPH diagnosis system (IPHDS) based on an artificial neural network. In external validation, the AUC of the IPHDS was 0.823 (95% CI 0.811-0.836), which was significantly higher than the AUC of the Taiwan model [0.799 (0.786-0.813)] and that of the Chinese Diabetes Risk Score model [0.648 (0.635-0.662)]. The IPHDS model had a sensitivity of 75.6% and a specificity of 74.6%. This model outperformed the Taiwan and CDRS models in subgroup analyses. An online site with instant predictions was deployed at https://app-iphds-e1fc405c8a69.herokuapp.com/. CONCLUSIONS: The proposed IPHDS could be a convenient and user-friendly screening tool for diabetes during health examinations in a large general population.

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Although evidence-based interventions can reduce the incidence of central line-associated bloodstream infection (CLABSI), there is a large gap between evidence-based interventions and the actual practice of central venous catheter (CVC) care. Evidence-based interventions are needed to reduce the incidence of CLABSI in intensive care units (ICU) in China. Professional association, guidelines, and database websites were searched for data relevant to CLABSI in the adult ICUs from inception to February 2020. Checklists were developed for both CVC placement and maintenance. Based on the Integrated Promoting Action on Research Implementation in Health Services framework, a questionnaire collected the cognition and practice of ICU nursing and medical staff on the CLABSI evidence-based prevention guidelines. From January 2018 to December 2021, ICU CLABSI rates were collected monthly. Ten clinical guidelines were included after the screening and evaluation process and used to develop the best evidence-based protocols for CVC placement and maintenance. The CLABSI rates in 2018, 2019, and 2020 were 2.98‰ (9/3021), 1.83‰ (6/3276), and 1.69‰ (4/2364), respectively. Notably, the CLABSI rate in 2021 was 0.38‰ (1/2607). In other words, the ICU CLABSI rate decreased from 1.69‰ to 0.38‰ after implementation of the new protocols. Additionally, our data suggested that the use of ultrasound-guidance for catheter insertion, chlorhexidine body wash, and the use of a checklist for CVC placement and maintenance were important measures for reducing the CLABSI rate. The evidence-based processes developed for CVC placement and maintenance were effective at reducing the CLABSI rate in the ICU.

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The objective of this study was to investigate the role of IL-12 in enhancing the anti-tumor efficacy of the small molecule targeted drug osimertinib in resistant tumor models and reversing resistance mechanisms. We utilized paired non-small cell lung cancer H1975 tumor tissues, establishing mouse tumor models with diverse tumor immune microenvironments. Analytical methods including immunohistochemistry and immunofluorescence were employed to compare immune cell infiltration, cytokines, effector molecules, and protein changes in resistant signaling pathways in tumor tissues, shedding light on IL-12's mechanism of action in enhancing osimertinib efficacy and reversing resistance. Results showed that osimertinib monotherapy had limited tumor suppression, whereas IL-12 exhibited more significant anti-tumor effects. Combination therapy groups demonstrated even greater tumor suppression with increased immune cell infiltration, elevated immune-related factor secretion, reduced immunosuppressive MDSCs, and decreased resistance-related signaling pathway markers. In conclusion, IL-12 enhances anti-tumor efficacy and reverses osimertinib resistance through various mechanisms, including increased immune cell infiltration, reduced immunosuppressive MDSCs, enhanced immune cell granzyme and IFN-γ release, decreased PDL-1 expression, improved tumor microenvironment, restored immune surveillance, and heightened cancer cell sensitivity to osimertinib.

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The strong coupling between optical resonance microcavity and matter excitations provides a practical path for controlling light-matter interactions. However, conventional microcavity, whose functions are fixed at the fabrication stage, dramatically limits the modulation of light-matter interactions. Here, we investigate the active strong coupling of resonance mode and exciton in GSST-WSe2 hybrid nanostructures. It is demonstrated that significant spectral splitting is observed in single nanostructures, tetramers, and metasurfaces. We further confirm the strong coupling by calculating the enhanced fluorescence spectra. The coupling effect between the excited resonance and exciton is dramatically modulated during the change of GSST from amorphous to crystalline, thus realizing the strong coupling switching. This switching property has been fully demonstrated in several systems mentioned earlier. Our work is significant in guiding the study of actively tunable strong light-matter interactions at the nanoscale.

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To evaluate the risk of acquiring syphilis from a donated kidney, we evaluated kidney transplantation pairs from West China Hospital, Sichuan, China, during 2007-2022. Donor-derived syphilis was rare. Risk may be higher if donors have active syphilis and may be reduced if recipients receive ceftriaxone.

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Objective: The objective of this study was to evaluate the efficacy of the combined treatment of Ying-Huang Decoction and San-ao Decoction compared to conventional treatment alone in patients with sepsis-associated acute lung injury (S-ALI) and to assess its potential mechanisms for improving clinical symptoms, reducing inflammatory response, and promoting respiratory function recovery. Methods: We included 84 S-ALI patients admitted to our hospital between January 2021 and January 2023. The patients were divided into a control group and an observation group, with 42 patients in each group. The control group received conventional treatment, while the observation group received the combined treatment of Ying-Huang Decoction and San-ao Decoction in addition to conventional treatment. The study was conducted in accordance with the principles of the Helsinki Declaration and received ethical approval. The main outcome measures assessed included symptom scores, levels of inflammatory factors, lung injury scores (such as LIS scores), respiratory function parameters (such as PVPI and EVLWL levels), and the incidence of adverse reactions. Results: The observation group receiving the combined treatment of Ying-Huang Decoction and San-ao Decoction demonstrated favorable outcomes compared to the control group. Significant improvements were observed in the observation group's symptom scores compared to the control group (P < .05). Patients in the observation group experienced a notable alleviation of clinical symptoms associated with S-ALI. In terms of inflammatory response, the observation group showed significantly lower levels of inflammatory factors, including IL-6, CRP, and IL-17, compared to the control group (P < .01). This suggests that the combined decoction treatment effectively reduced the systemic inflammatory response in S-ALI patients. Lung injury scores, as assessed by the LIS, were significantly reduced in the observation group compared to the control group (P < .05). This indicates that the combined treatment contributed to the mitigation of lung tissue damage in S-ALI patients. Respiratory function parameters, such as PVPI and EVLWL levels, showed significant improvement in the observation group compared to the control group (P < .01), indicating enhanced respiratory function. Conclusion: The combined treatment of Ying-Huang Decoction and San-ao Decoction, in addition to conventional treatment, demonstrated beneficial effects in the management of S-ALI, leading to improved clinical symptoms, reduced inflammatory response, and enhanced respiratory function. These findings suggest the potential integration of traditional Chinese medicine approaches, such as Ying-Huang Decoction and San-ao Decoction, in the treatment of S-ALI, providing additional options for clinicians and potentially improving patient outcomes. It is important to acknowledge the limitations of this study, such as its retrospective design and the need for further research with larger sample sizes to validate the results and minimize potential biases.

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OBJECTIVE: To explore the effect and mechanism of Dahuang Zhechong Pill (DHZCP) on liver fibrosis. METHODS: Liver fibrosis cell model was induced by transforming growth factor-ß (TGF-ß) in hepatic stellate cells (HSC-T6). DHZCP medicated serum (DMS) was prepared in rats. HSC-T6 cells were divided into the control (15% normal blank serum culture), TGF-ß (15% normal blank serum + 5 ng/mL TGF-ß), DHZCP (15% DMS + 5 ng/mL TGF-ß), DHZCP+PDTC [15% DMS + 4 mmol/L ammonium pyrrolidine dithiocarbamate (PDTC)+ 5 ng/mL TGF-ß], and PDTC groups (4 mmol/L PDTC + 5 ng/mL TGF-ß). Cell activity was detected by cell counting kit 8 and levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the cell supernatant were determined by enzyme-linked immunosorbnent assay. Western blot was used to measure the expressions of p38 mitogen-activated protein kinase/nuclear factor kappa B/transforming growth factor-ß1 (p38 MAPK/NF-κ B/TGF-ß1) pathway related proteins, and the localization and expressions of these proteins were observed by immunofluorescence staining. RESULTS: DHZCP improves the viability of cells damaged by TGF-ß and reduces inflammatory cytokines and ALT and AST levels in the supernatant of HSC-T6 cells induced with TGF-ß (P<0.05 or P<0.01). Compared with the TGF-ß group, NF-κ B p65 levels in the DHZCP group were decreased (P<0.05). p38 MAPK and NF-κ B p65 levels in the DHZCP+PDTC were also reduced (P<0.01). Compared with the TGF-ß group, the protein expression of Smad2 showed a downward trend in the DHZCP, DHZCP+PDTC, and PDTC groups (all P<0.01), and the decreasing trend of Samd3 was statistically significant only in DHZCP+PDTC group (P<0.01), whereas Smad7 was increased (P<0.05 or P<0.01). CONCLUSION: DHZCP can inhibit the process of HSC-T6 cell fibrosis by down-regulating the expression of p38 MAPK/NF-κ B/TGF-ß1 pathway.