Triptolide promotes differentiation of human monocytes into immunosuppressive MDSCs.

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) negatively modulate immune activity. Prior investigations have shown much promise in using MDSCs-assisted immunotherapy for organ transplantation patients. Additionally, owing to its immunosuppressive activity, MDSCs can also be used to manage immune-associated disorders. METHODS: Granulocyte-macrophage colony-stimulating factor (GM-CSF) was employed to stimulate myeloid progenitor cell differentiation. Triptolide (PG490) was introduced toward the later phases of in vitro MDSCs induction. Lastly, real-time PCR (RT-PCR) and flow cytometry were used to assess transcript expression and cell phenotype, and a mouse skin transplantation model was established to evaluate the MDSCs-mediated immune suppression in vivo. RESULTS: Co-stimulation with PG490 and GM-CSF potently induced myeloid-derived monocytes to form MDSCs, with remarkable immune-suppressive activity. The underlying mechanism involved downregulation of T cell proliferation, activation, enhancement of inflammatory cytokine release, as well as T cell conversion to Treg cells. PG490 strongly enhanced iNOS expression in MDSCs, and iNOS inhibition successfully reversed the immune-suppression. The PG490- and GM-CSF-induced MDSCs substantially extended survival duration of murine skin grafts, thereby validating their strong immune-suppressive activity in vivo. CONCLUSIONS: Herein, we presented a new approach involving MDSCs-based immunosuppression in vitro. PG490 and GM-CSF co-treatment strongly induced immuno-suppressive activity in MDSCs both in vitro and in vivo. Our findings highlight the promise of applying MDSCs-based therapy in clinical organ transplantation treatment.

PC (16:0/14:0) ameliorates hyperoxia-induced bronchopulmonary dysplasia by upregulating claudin-1 and promoting alveolar type II cell repair.

Bronchopulmonary dysplasia (BPD) remains a significant challenge in neonatal care, the pathogenesis of which potentially involves altered lipid metabolism. Given the critical role of lipids in lung development and the injury response, we hypothesized that specific lipid species could serve as therapeutic agents in BPD. This study aimed to investigate the role of the lipid Phosphatidylcholine (PC) (16:0/14:0) in modulating BPD pathology and to elucidate its underlying mechanisms of action. Our approach integrated in vitro and in vivo methodologies to assess the effects of PC (16:0/14:0) on the histopathology, cellular proliferation, apoptosis, and molecular markers in lung tissue. In a hyperoxia-induced BPD rat model, we observed a reduction in alveolar number and an enlargement in alveolar size, which were ameliorated by PC (16:0/14:0) treatment. Correspondingly, in BPD cell models, PC (16:0/14:0) intervention led to increased cell viability, enhanced proliferation, reduced apoptosis, and elevated surfactant protein C (SPC) expression. RNA sequencing revealed significant gene expression differences between BPD and PC (16:0/14:0) treated groups, with a particular focus on Cldn1 (encoding claudin 1), which was significantly enriched in our analysis. Our findings suggest that PC (16:0/14:0) might protect against hyperoxia-induced alveolar type II cell damage by upregulating CLDN1 expression, potentially serving as a novel therapeutic target for BPD. This study not only advances our understanding of the role of lipids in BPD pathogenesis, but also highlights the significance of PC (16:0/14:0) in the prevention and treatment of BPD, offering new avenues for future research and therapeutic development.

[Preventive early intervention strategies for neurodevelopmental disorders of high-risk infants]. / é«˜å±å„¿ç¥žç»å‘è‚²éšœç¢é¢„é˜²æ€§æ—©æœŸå¹²é¢„ç ”ç©¶è¿›å±•.

Neurodevelopmental disorders in children have become a significant global public health concern, impacting child health worldwide. In China, the current intervention model for high-risk infants involves early diagnosis and early treatment. However, in recent years, overseas studies have explored novel preventive early intervention strategies for neurodevelopmental disorders in high-risk infants, achieving promising results. This article provides a comprehensive review of the optimal timing, methods, and intervention models of the preventive early intervention strategies for neurodevelopmental disorders in high-risk infants. The aim is to enhance the awareness and knowledge of healthcare professionals regarding preventive early intervention strategies for neurodevelopmental disorders in high-risk infants, facilitate clinical research and application of such interventions in China, and ultimately reduce the incidence of neurodevelopmental disorders in this high-risk population.

Deep reinforcement learning navigation via decision transformer in autonomous driving.

In real-world scenarios, making navigation decisions for autonomous driving involves a sequential set of steps. These judgments are made based on partial observations of the environment, while the underlying model of the environment remains unknown. A prevalent method for resolving such issues is reinforcement learning, in which the agent acquires knowledge through a succession of rewards in addition to fragmentary and noisy observations. This study introduces an algorithm named deep reinforcement learning navigation via decision transformer (DRLNDT) to address the challenge of enhancing the decision-making capabilities of autonomous vehicles operating in partially observable urban environments. The DRLNDT framework is built around the Soft Actor-Critic (SAC) algorithm. DRLNDT utilizes Transformer neural networks to effectively model the temporal dependencies in observations and actions. This approach aids in mitigating judgment errors that may arise due to sensor noise or occlusion within a given state. The process of extracting latent vectors from high-quality images involves the utilization of a variational autoencoder (VAE). This technique effectively reduces the dimensionality of the state space, resulting in enhanced training efficiency. The multimodal state space consists of vector states, including velocity and position, which the vehicle's intrinsic sensors can readily obtain. Additionally, latent vectors derived from high-quality images are incorporated to facilitate the Agent's assessment of the present trajectory. Experiments demonstrate that DRLNDT may achieve a superior optimal policy without prior knowledge of the environment, detailed maps, or routing assistance, surpassing the baseline technique and other policy methods that lack historical data.

The application value of metagenomic next-generation sequencing technology in the diagnosis and treatment of neonatal infectious meningitis - a single center retrospective case-control study.

OBJECTIVE: This retrospective study was conducted to investigate the application value of metagenomics next generation sequencing (mNGS) technology in the diagnosis and treatment of neonatal infectious meningitis. METHODS: From 1 January 2020 to 31 December 2022, 73 newborns suspected of infectious meningitis were hospitalized. After screening by inclusion and exclusion criteria, 69 newborns were subsequently included in the study, containing 27 cases with positive mNGS result and 42 cases with negative mNGS result. Furthermore, according to the diagnosis of meningitis, mNGS positive group and mNGS negative group were further divided into infectious meningitis with mNGS (+) group (n = 27) and infectious meningitis with mNGS (-) group (n = 26), respectively. RESULTS: (1) Compared with cerebrospinal fluid (CSF) culture, mNGS has better diagnostic value [positive predictive value (PPV) = 100.00% (27/27), negative predictive value (NPV) = 38.10% (16/42), agreement rate = 62.32% (43/69), area under the curve (AUC) = 0.750, 95% confidence interval (CI): 0.636-0.864]. (2) There were significant differences in the onset age, age at first CSF test, CSF leukocyte count, CSF glucose, positive rate of CSF culture, blood leukocyte count, procalcitonin (PCT), C-reaction protein (CRP), age at first mNGS test and adjusting anti-infective medication in the comparison between infectious meningitis with mNGS (+) group and infectious meningitis with mNGS (-) group (p < 0.05). (3) mNGS could help improve the cure rate [crude odds ratio (OR) = 3.393, 95%CI: 1.072-10.737; adjusted OR = 15.580, 95%CI: 2.114-114.798]. CONCLUSION: Compared with classic meningitis detection methods, mNGS has better PPV, NPV, agreement rate, and AUC. mNGS could help improve the cure rate.

Recombinant Human Heavy Chain Ferritin Nanoparticles Serve as ROS Scavengers for the Treatment of Ischemic Stroke.

Purpose: Ischemic stroke is a high-incidence disease that threatens human well-being. The potent neuroprotective effects render reactive oxygen species (ROS) scavengers potential agents for acute ischemic stroke therapy. Challenges such as inadequate permeability across the blood-brain barrier (BBB), limited half-life, and adverse effects hinder the widespread utilization of small molecule and inorganic ROS scavengers. Thus, there is an urgent demand for efficacious neuroprotective agents targeting ischemic stroke. Our study discovered the superoxide dismutase (SOD)-mimetic activity of recombinant human heavy chain ferritin (rHF) nanoparticles expressed from Escherichia coli (E. coli). Subsequent investigations delved into the ROS-scavenging proficiency of rHF within neural cells, its therapeutic efficacy against ischemic stroke, and the elucidation of its neuroprotective mechanisms. Methods: rHF protein nanoparticles were expressed in E. coli and purified via size-exclusion chromatography. The superoxide anion (•O2-) scavenging SOD-mimetic activity of rHF nanoparticles was measured using a SOD detection kit. The ROS scavenging ability and protection effects against oxidative damage of rHF nanoparticles were studied in H2O2-induced PC12 cells. Therapeutic effects and neuroprotective mechanisms of rHF against ischemic stroke were investigated with transient middle cerebral artery occlusion (MCAO) reperfusion mice model. Results: rHF nanoparticles can eliminate excessive ROS in nerve cells and alleviate oxidative damage. The results of animal experiments demonstrated that rHF nanoparticles passed across BBB, reduced infarct areas in brain tissue, and lowered the neurological deficit score of ischemia-reperfusion model mice. Additionally, rHF nanoparticles mitigated neuronal apoptosis and ferroptosis, suppressed microglial activation, maintained oxygen homeostasis, and exhibited negligible organ toxicity. Conclusion: rHF nanoparticle could be developed as a new ROS scavenger for nerve cells and has therapeutic potential as a drug for cerebral ischemia-reperfusion injury.

Robot-Assisted Ureteroplasty with Labial Mucosal Onlay Grafting for Long Left-Sided Proximal Ureteral Stenosis in Children and Adolescents: Technical Tips and Functional Outcomes.

Purpose: To evaluate functional outcomes of robot-assisted ureteroplasty with labial mucosa grafting for long proximal ureteral stenosis (LPUS) in children and adolescents. Methods: Included in this study were 15 patients who underwent robot-assisted ureteroplasty with labial mucosal grafting in our center between July 2017 and September 2021. The left affected stenotic ureter was repaired using labial mucosal grafting. If the ureter was simply strictured but not obliterated, the ureter was spatulated longitudinally along the ventral side and the labial mucosa graft was interposed and anastomosed in a continuous manner. Faced with the obliterated segment, it was excised and the spatulated portion re-anastomosed with a pelvic flap as the dorsal wall. The labial mucosa graft was placed as the ventral wall. The preoperative clinical data and follow-up outcomes were collected and evaluated. Results: Labial mucosa graft onlay ureteroplasty was well performed in all the 15 patients with no occurrence of intraoperative complications or surgical conversion. Five patients underwent an onlay ureteroplasty, and 10 patients underwent a dorsally augmented pelvic flap anastomotic ureteroplasty. The mean (range) stricture length was 7.1 (3-10) cm. The mean operative time was 371.2 (216-480) minutes, and the median blood loss was 40 mL. At the median follow-up of 35 months (range 12-58 months), the overall success rate was 93.3%. Conclusions: Labial mucosa grafting appears to be safe and feasible for repairing long ureteral strictures in pediatric and adolescent patients. Our experience may provide beneficial references and conveniences to solve complex problems in LPUS. This study was approved by the institutional review board, and written informed consent was obtained from each participant (ethics number: 2017-30).

Robotic-assisted laparoscopic surgery for the treatment of Wilms' tumor in children: single-center experience and medium-term outcomes.

To report our institutional experience and the medium-term outcomes of utilizing robotic-assisted laparoscopic surgery (RALS) in patients with Wilms' tumor (WT). The robotic surgical interventions include nephron-sparing surgery (RAL-NSS), radical nephrectomy (RAL-RN), and nephrectomy with inferior vena cava thrombectomy (RAL-N-IVCT). We retrospectively collected medical records of WT patients who underwent RALS in our center between August 2019 and February 2022. Patients' baseline demographics, preoperative parameters, and perioperative/postoperative data were recorded and analyzed. Follow-up results were collected to evaluate the oncological outcomes. A total of 12 patients (13 sides) with a median age of 30 (IQR: 19.5-45.5) months were included. All operations were successfully completed without conversion. Seven patients received preoperative chemotherapy. Distribution of surgical interventions was as follows: five patients underwent RAL-RN, five received RAL-NSS, one with bilateral WT underwent concurrent RAL-RN and RAL-NSS, and one received RAL-RN-IVCT post preoperative chemotherapy. Postoperative chemotherapy was conducted in ten patients. The estimated intraoperative blood loss was 27 ± 4.0 ml for the RAL-NSS group, 41.67 ± 12.13 ml for the RAL-RN group, and 350 ml for the RAL-RN-IVCT groups, respectively. The median perioperative serum creatinine levels were 32.5 (IQR: 30.75-39.5) µmol/l preoperatively and 35 (IQR: 31.75-38.5) µmol/l postoperatively, which showed no significant difference. No positive lymph nodes were detected. Postoperative chemotherapy was performed according to the tumor volume and pathological findings. The median follow-up time was 17.5 (15.8-22.3) months. During this interval, neither distant metastasis nor recurrence was identified. Based on our medium-term follow-up observations, RAL-NSS, RAL-RN, and RAL-RN-IVCT exhibit promising feasibility and safety profiles in the therapeutic landscape of WT.

Unraveling spatial metabolome of the aerial and underground parts of Scutellaria baicalensis by matrix-assisted laser desorption/ionization mass spectrometry imaging.

BACKGROUND: Scutellaria baicalensis Georgi, a traditional Chinese medicine, is clinically applied mainly as the dried root of Scutellaria baicalensis, and the aerial parts of Scutellaria baicalensis, its stems and leaves, are often consumed as "Scutellaria baicalensis tea" to clear heat, dry dampness, reduce fire and detoxify, while few comparative analyses of the spatial metabolome of the aerial and underground parts of Scutellaria baicalensis have been carried out in current research. METHODS: In this work, Matrix-assisted laser desorption ionization-mass spectrometry imaging (MALDI-MSI) was used to visualize the spatial imaging of the root, stem, and leaf of Scutellaria baicalensis at a high resolution of 10 µm, respectively, investigating the spatial distribution of the different secondary metabolites in the aerial and underground parts of Scutellaria baicalensis. RESULTS: In the present results, various metabolites, such as flavonoid glycosides, flavonoid metabolites, and phenolic acids, were systematically characterized in Scutellaria baicalensis root, stem, and leaf. Nine glycosides, 18 flavonoids, one organic acid, and four other metabolites in Scutellaria baicalensis root; nine glycosides, nine flavonoids, one organic acid in Scutellaria baicalensis stem; and seven flavonoids and seven glycosides in Scutellaria baicalensis leaf were visualized by MALDI-MSI. In the underground part of Scutellaria baicalensis, baicalein, wogonin, baicalin, wogonoside, and chrysin were widely distributed, while there was less spatial location in the aerial parts. Moreover, scutellarein, carthamidin/isocarthamidin, scutellarin, carthamidin/isocarthamidin-7-O-glucuronide had a high distribution in the aerial parts of Scutellaria baicalensis. In addition, the biosynthetic pathways involved in the biosynthesis of significant flavonoid metabolites in aerial and underground parts of Scutellaria baicalensis were successfully localized and visualized. CONCLUSIONS: MALDI-MSI offers a favorable approach for investigating the spatial distribution and effective utilization of metabolites of Scutellaria baicalensis. The detailed spatial chemical information can not only improve our understanding of the biosynthesis pathways of flavonoid metabolites, but more importantly, suggest that we need to fully exert the overall medicinal value of Scutellaria baicalensis, strengthening the reuse and development of the resources of Scutellaria baicalensis aboveground parts.

MCSNet+: Enhanced Convolutional Neural Network for Detection and Classification of Tribolium and Sitophilus Sibling Species in Actual Wheat Storage Environments.

Insect pests like Tribolium and Sitophilus siblings are major threats to grain storage and processing, causing quality and quantity losses that endanger food security. These closely related species, having very similar morphological and biological characteristics, often exhibit variations in biology and pesticide resistance, complicating control efforts. Accurate pest species identification is essential for effective control, but workplace safety in the grain bin associated with grain deterioration, clumping, fumigator hazards, and air quality create challenges. Therefore, there is a pressing need for an online automated detection system. In this work, we enriched the stored-grain pest sibling image dataset, which includes 25,032 annotated Tribolium samples of two species and five geographical strains from real warehouse and another 1774 from the lab. As previously demonstrated on the Sitophilus family, Convolutional Neural Networks demonstrate distinct advantages over other model architectures in detecting Tribolium. Our CNN model, MCSNet+, integrates Soft-NMS for better recall in dense object detection, a Position-Sensitive Prediction Model to handle translation issues, and anchor parameter fine-tuning for improved matching and speed. This approach significantly enhances mean Average Precision (mAP) for Sitophilus and Tribolium, reaching a minimum of 92.67 ± 1.74% and 94.27 ± 1.02%, respectively. Moreover, MCSNet+ exhibits significant improvements in prediction speed, advancing from 0.055 s/img to 0.133 s/img, and elevates the recognition rates of moving insect sibling species in real wheat storage and visible light, rising from 2.32% to 2.53%. The detection performance of the model on laboratory-captured images surpasses that of real storage facilities, with better results for Tribolium compared to Sitophilus. Although inter-strain variances are less pronounced, the model achieves acceptable detection results across different Tribolium geographical strains, with a minimum recognition rate of 82.64 ± 1.27%. In real-time monitoring videos of grain storage facilities with wheat backgrounds, the enhanced deep learning model based on Convolutional Neural Networks successfully detects and identifies closely related stored-grain pest images. This achievement provides a viable solution for establishing an online pest management system in real storage facilities.

The nonlinear effects of digital economy on the low-carbon green total factor productivity: Evidence from China.

The production process has undergone significant changes due to the exponential expansion of digital economy, leading to implications for carbon emissions. This study aims to establish the digital economy (DE) index and measures low-carbon green total factor productivity (CTFP) in 30 Chinese provinces between 2011 and 2020. Utilizing the panel fixed-effects model and the spatial model, it examines the nonlinear effects of DE on CTFP and investigates its underlying mechanism. The results reveal the following findings: (1) CTFP has experienced a decline over the past decade, while DE has exhibited significant growth. (2) the contribution of DE to CTFP follows a U-shaped pattern, indicating that CTFP experiences a significant increase once DE reaches a specific turning point. (3) DE affects CTFP by influencing technological innovation progress. (4) The impact of DE on CTFP exhibits regional heterogeneity, with the eastern region experiencing a spatial spillover effect. These rigorous empirical findings provide valuable insights for national policymakers, emphasizing the importance of prioritizing the digital economy and technological innovation when formulating policies to facilitate sustainable economic growth and reduce carbon emissions.

Effectiveness and safety of rectal dexibuprofen versus oral ibuprofen for closure of patent ductus arteriosus in preterm infants with gestational age<34 weeks: A pilot study.

This pilot study aimed to explore the effectiveness and safety of dexibuprofen suppository in the treatment of PDA in preterm infants. Preterm infants with gestational age <34 weeks and color Doppler echocardiographic evidence of hemodynamically significant PDA (hs PDA) with systemic hypoperfusion was intended to be included into this study since January 2020. As of January 1, 2021, this trial had recruited 87 preterm infants who met the inclusion criteria. Neonates were admitted into hospital within 1 hour after birth and were randomly assigned into two groups. Group one included 44 preterm newborns administered with oral ibuprofen. Group two included 43 preterm newborns administered with dexibuprofen suppository. This preliminary study showed that rectal dexibuprofen and oral ibuprofen were both effective for the closure of PDA, and the closure rate of dexibuprofen suppository was comparable to that of oral ibuprofen after the 1st and 2nd courses of treatment. In addition, rectal dexibuprofen did not increase the incidence of adverse outcomes, including bronchopulmonary dysplasia, intraventricular hemorrhage, sepsis, and necrotising enterocolitis. This pilot study showed dexibuprofen suppository is as effective and safe as oral ibuprofen; yet, better designed, muticenter controlled studies are still needed.

Comprehensive Proteomics Analysis Identifies CD38-Mediated NAD+ Decline Orchestrating Renal Fibrosis in Pediatric Patients With Obstructive Nephropathy.

Obstructive nephropathy is one of the leading causes of kidney injury and renal fibrosis in pediatric patients. Although considerable advances have been made in understanding the pathophysiology of obstructive nephropathy, most of them were based on animal experiments and a comprehensive understanding of obstructive nephropathy in pediatric patients at the molecular level remains limited. Here, we performed a comparative proteomics analysis of obstructed kidneys from pediatric patients with ureteropelvic junction obstruction and healthy kidney tissues. Intriguingly, the proteomics revealed extensive metabolic reprogramming in kidneys from individuals with ureteropelvic junction obstruction. Moreover, we uncovered the dysregulation of NAD+ metabolism and NAD+-related metabolic pathways, including mitochondrial dysfunction, the Krebs cycle, and tryptophan metabolism, which led to decreased NAD+ levels in obstructed kidneys. Importantly, the major NADase CD38 was strongly induced in human and experimental obstructive nephropathy. Genetic deletion or pharmacological inhibition of CD38 as well as NAD+ supplementation significantly recovered NAD+ levels in obstructed kidneys and reduced obstruction-induced renal fibrosis, partially through the mechanisms of blunting the recruitment of immune cells and NF-κB signaling. Thus, our work not only provides an enriched resource for future investigations of obstructive nephropathy but also establishes CD38-mediated NAD+ decline as a potential therapeutic target for obstruction-induced renal fibrosis.

RNA sequencing and bioinformatics analysis of circular RNAs in asphyxial newborns with acute kidney injury.

As one kind of novel noncoding RNA, circular RNAs (circRNAs) are involved in different biological processes. Although growing evidences have supported the important role of circRNAs in renal diseases, the mechanism remains unclear in neonatal acute kidney injury (AKI). High-throughput sequencing analysis was used to investigate the expression of circRNAs between hypoxia-induced AKI neonates and controls. Bioinformatics analysis was conducted to predict the function of differentially expressed circRNAs. Finally, the differentially expressed circRNAs were screened and determined by quantitative real-time PCR (qPCR). (1) A total of 296 differentially expressed circRNAs were identified (Fold change >2 and p < 0.05). Of them, 184 circRNAs were markedly upregulated, and 112 were significantly downregulated in the AKI group. (2) The pathway analysis showed that ubiquitin-mediated proteolysis, renal cell carcinoma, Jak-STAT, and HIF-1 signaling pathways participated in AKI. (3) Top five upregulated and five downregulated circRNAs with higher fold changes were selected for qPCR validation. Hsa_circ_0008898 (Fold Change = 5.48, p = 0.0376) and hsa_circ_0005519 (Fold Change = 4.65, p = 0.0071) were significantly upregulated, while hsa_circ_0132279 (Fold Change = -4.47, p = 0.0008), hsa_circ_0112327 (Fold Change = -4.26, p = 0.0048), and hsa_circ_0017647 (Fold Change = -4.15, p = 0.0313) were significantly downregulated in asphyxia-induced AKI group compared with the control group. This study could contribute to future research on neonatal AKI and facilitate the identification of novel therapeutic targets.

Hepatotoxicity Associated with Immune Checkpoint Inhibitors in Clinical Practice: A Study Leveraging Data from the US Food and Drug Administration's Adverse Event Reporting System.

PURPOSE: Immune checkpoint inhibitors (ICIs) are a promising option for the treatment of patients with various cancers. Emerging case reports have raised awareness on hepatotoxicity, a potentially fatal adverse event (AE) that may be associated with the use of ICIs. This study assessed the potential association between ICIs and hepatotoxicity through the mining of data from the US Food and Drug Administration's AE Reporting System (FAERS). METHODS: A total of 9,217,181 AEs reported in the period from quarter 1 of 2004 to quarter 3 of 2021 were assessed. Information components (ICs) and reporting odds ratios (RORs) were used to evaluate the association between the use of ICIs and hepatotoxicity. FINDINGS: A total of 52,463 AE reports listed ICIs, used alone or in combination, as a suspected drug. Of these, 1481 cases were related to both ICIs and hepatotoxicity. The use of ICIs was significantly associated with hepatotoxicity compared to all other drugs, making it a safety signal (IC = 1.43 [95% CI, 1.36-1.51]; ROR = 2.78 [95% CI, 2.64-2.93]). With monotherapy, all ICIs, except tremelimumab, were associated with liver damage. The most commonly prescribed combination therapy was nivolumab + ipilimumab (321 cases) with a significant signal detected. Notably, ICI use was significantly associated with hepatic failure (IC = 1.24 [95% CI, 1.06-1.42]; ROR = 2.40 [95% CI, 2.13-2.72]). The risk for ICI-associated hepatotoxicity (including hepatic failure) was greater with ICI combination therapy than with ICI monotherapy. All subgroups by sex and age also showed significant associations between ICI use and hepatotoxicity. IMPLICATIONS: A significant association was detected between ICI use and hepatotoxicity. The risk for hepatotoxicity (including hepatic failure) was greater with ICI combination therapy compared with ICI monotherapy.

[Oxygen reserve index: a new parameter for oxygen therapy]. / 氧储备指数：氧疗监测的新方法.

Oxygen reserve index (ORI) is a novel dimensionless index used for noninvasive, real-time, and continuous monitoring of oxygenation, and ORI value ranges from 0 to 1, which reflects the range of 100-200 mmHg for arterial partial pressure of oxygen. ORI combined with pulse oximetry may help to accurately adjust the concentration of inspired oxygen and prevent hyperoxemia and hypoxemia. ORI is suitable for various clinical situations, and the medical staff should master this novel parameter and use it properly to assess the oxygenation of patients. In addition, several limitations of ORI should be noticed during clinical application.

MALDI-TOF-MS for Rapid Screening and Typing of ß-Globin Variant and ß-Thalassemia through Direct Measurements of Intact Globin Chains.

BACKGROUND: Traditional phenotype-based screening for ß-globin variant and ß-thalassemia using hematological parameters is time-consuming with low-resolution detection. Development of a MALDI-TOF-MS assay using alternative markers is needed. METHODS: We constructed a MALDI-TOF-MS-based approach for identifying various ß-globin disorders and classifying thalassemia major (TM) and thalassemia intermedia (TI) patients using 901 training samples with known HBB/HBA genotypes. We then validated the accuracy of population screening and clinical classification in 2 separate cohorts consisting of 16 172 participants and 201 ß-thalassemia patients. Traditional methods were used as controls. Genetic tests were considered the gold standard for testing positive specimens. RESULTS: We established a prediction model for identifying different forms of ß-globin disorders in a single MALDI-TOF-MS test based on δ- to ß-globin, γ- to α-globin, γ- to ß-globin ratios, and/or the abnormal globin-chain patterns. Our validation study yielded comparable results of clinical specificity (99.89% vs 99.71%), and accuracy (99.78% vs 99.16%) between the new assay and traditional methods but higher clinical sensitivity for the new method (97.52% vs 88.01%). The new assay identified 22 additional abnormal hemoglobins in 69 individuals including 9 novel ones, and accurately screened for 9 carriers of deletional hereditary persistence of fetal hemoglobin or δß-thalassemia. TM and TI were well classified in 178 samples out of 201 ß-thalassemia patients. CONCLUSIONS: MALDI-TOF-MS is a highly accurate, predictive tool that could be suitable for large-scale screening and clinical classification of ß-globin disorders.

[The role and mechanism of autophagy in lipopolysaccharide-induced inflammatory response of A549 cells]. / 自噬在脂多糖诱导的A549ç»†èƒžç‚Žç—‡ååº”ä¸­çš„ä½œç”¨åŠæœºåˆ¶ç ”ç©¶.

OBJECTIVES: To study the role and mechanism of autophagy in lipopolysaccharide (LPS)-induced inflammatory response of human alveolar epithelial A549 cells. METHODS: A549 cells were stimulated with LPS to establish a cell model of inflammatory response, and were then grouped (n=3 each) by concentration (0, 1, 5, and 10 µg/mL) and time (0, 4, 8, 12, and 24 hours). The A549 cells were treated with autophagy inhibitor 3-methyladenine (3-MA) to be divided into four groups (n=3 each): control, LPS, 3-MA, and 3-MA+LPS. The A549 cells were treated with autophagy agonist rapamycin (RAPA) to be divided into four groups (n=3 each): control, LPS, RAPA, and RAPA+LPS. The A549 cells were transfected with the Toll-like receptor 4 (TLR4) overexpression plasmid to be divided into four groups (n=3 each): TLR4 overexpression control, TLR4 overexpression, TLR4 overexpression control+LPS, and TLR4 overexpression+LPS. The A549 cells were transfected with TLR4 siRNA to be divided into four groups (n=3 each): TLR4 silencing control,TLR4 silencing, TLR4 silencing control+LPS, and TLR4 silencing+LPS. CCK-8 assay was used to measure cell viability. Western blot was used to measure the protein expression levels of inflammatory indicators (NLRP3, Caspase-1, and ASC), autophagic indicators (LC3B, Beclin-1, and P62), and TLR4. RESULTS: After stimulation with 1 µg/mL LPS for 12 hours, the levels of inflammatory indicators (NLRP3, Caspase-1, and ASC), autophagic indicators (LC3B, Beclin-1, and P62), and TLR4 increased and reached the peak (P<0.05). Compared with the LPS group, the 3-MA+LPS group had reduced expression of autophagy-related proteins and increased expression of inflammation-related proteins and TLR4, while the RAPA+LPS group had increased expression of autophagy-related proteins and reduced inflammation-related proteins and TLR4 (P<0.05). The TLR4 overexpression+LPS group had reduced autophagy-related proteins and increased inflammation-related proteins compared with the TLR4 overexpression control+LPS group, and the TLR4 silencing+LPS group had increased autophagy-related proteins and reduced inflammation-related proteins compared with the TLR4 silencing control+LPS group (P<0.05). CONCLUSIONS: In the LPS-induced inflammatory response of human alveolar epithelial A549 cells, autophagic flux has a certain protective effect on A549 cells. TLR4-mediated autophagic flux negatively regulates the LPS-induced inflammatory response of A549 cells.

Modified robotic-assisted laparoscopic pyeloplasty in children for ureteropelvic junction obstruction with long proximal ureteral stricture: The "double-flap" technique.

Objective: The objective of this study is to introduce a novel technique of robotic-assisted laparoscopic pyeloplasty (RALP) for ureteropelvic junction obstruction (UPJO) with long proximal ureteral stricture in children. Materials and methods: Clinical information on patients who underwent a modified RALP between July 2018 and May 2019 in our center was collected retrospectively. Our surgical modifications mainly include "double-flap" tailoring of the renal pelvis and anastomosis of spatulate ureter with the double-flap. Demographic, perioperative, postoperative, and follow-up information was recorded in detail. Results: A total of 13 patients were included in the study. All the patients underwent a modified RALP without conversion to open surgery. They were followed up with a median time of 36 months. The anteroposterior diameter of the renal pelvis was 1.19 ± 0.21 at 6 months after the surgery, which was significantly lower than that on admission (3.93 ± 0.79). The split renal function of the children was also significantly improved from 0.37 ± 0.05) to 0.46 ± 0.02 at 6 months after surgery (p < 0.05). The diuretic renography revealed that all the patients have a T1/2 time less than 20 min postoperatively. The children were in good condition during the follow-up period. Conclusions: Modified RALP is an effective surgical treatment for children with UPJO with long proximal ureteral stricture. The success rate of this modification has been preliminarily confirmed.