Investigation of thia-Diels-Alder Reactions by Ultrafast Transient Absorption Spectroscopy and DFT Calculations.

The thia-Diels-Alder reaction represents a versatile synthetic method for the preparation of six-membered sulfur-containing compounds. However, the mechanism of the thia-Diels-Alder reactions remains unclear. In this work, time-resolved spectroscopic experiments and DFT calculations demonstrate that phenacyl sulfide undergoes Norrish II cleavage to produce thioaldehyde, and ortho-hydroxy benzhydryl alcohol occurs in a dehydration reaction to generate o-QMs using diphenylphosphate as the catalyst. Then, the thia-Diels-Alder reaction takes place between thioaldehyde and o-QMs by an asynchronous concerted mechanism. The illustration of the thia-Diels-Alder reaction mechanism not only provides important support for organic synthesis and drug design but also enhances fundamental insights into reaction pathways and catalytic processes in the field of chemical synthesis.

Adjudin protects blood-brain barrier integrity and attenuates neuroinflammation following intracerebral hemorrhage in mice.

Secondary brain injury exacerbates neurological dysfunction and neural cell death following intracerebral hemorrhage (ICH), targeting the pathophysiological mechanism of the secondary brain injury holds promise for improving ICH outcomes. Adjudin, a potential male contraceptive, exhibits neuroprotective effects in brain injury disease models, yet its impact in the ICH model remains unknown. In this study, we investigated the effects of adjudin on brain injury in a mouse ICH model and explored its underlying mechanisms. ICH was induced in male C57BL/6 mice by injecting collagenase into the right striatum. Mice received adjudin treatment (50 mg/kg/day) for 3 days before euthanization and the perihematomal tissues were collected for further analysis. Adjudin significantly reduced hematoma volume and improved neurological function compared with the vehicle group. Western blot showed that Adjudin markedly decreased the expression of MMP-9 and increased the expression of tight junctions (TJs) proteins, Occludin and ZO-1, and adherens junctions (AJs) protein VE-cadherin. Adjudin also decreased the blood-brain barrier (BBB) permeability, as indicated by the reduced albumin and Evans Blue leakage, along with a decrease in brain water content. Immunofluorescence staining revealed that adjudin noticeably reduced the infiltration of neutrophil, activation of microglia/macrophages, and reactive astrogliosis, accompanied by an increase in CD206 positive microglia/macrophages which exhibit phagocytic characteristics. Adjudin concurrently decreased the generation of proinflammatory cytokines, such as TNF-α and IL-1ß. Additionally, adjudin increased the expression of aquaporin 4 (AQP4). Furthermore, adjudin reduced brain cell apoptosis, as evidenced by increased expression of anti-apoptotic protein Bcl-2, and decreased expression of apoptosis related proteins Bax, cleaved caspase-3 and fewer TUNEL positive cells. Our data suggest that adjudin protects against ICH-induced secondary brain injury and may serve as a potential neuroprotective agent for ICH treatment.

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.

Flipped online teaching of histology and embryology with design thinking: design, practice and reflection.

BACKGROUND: Flexible hybrid teaching has become the new normal of basic medical education in the postepidemic era. Identifying ways to improve the quality of curriculum teaching and achieve high-level talent training is a complex problem that urgently needs to be solved. Over the course of the past several semesters, the research team has integrated design thinking (DT) into undergraduate teaching to identify, redesign and solve complex problems in achieving curriculum teaching and professional talent training objectives. METHODS: This study is an observational research. A total of 156 undergraduate stomatology students from Jining Medical University in 2021 were selected to participate in two rounds of online flipped teaching using the design thinking EDIPT (empathy, definition, idea, prototype, and test) method. This approach was applied specifically to the chapters on the respiratory system and female reproductive system. Data collection included student questionnaires, teacher-student interviews, and exam scores. GraphPad Prism software was used for data analysis, and the statistical method was conducted by multiple or unpaired t test. RESULTS: According to the questionnaire results, the flipped classroom teaching design developed using design thinking methods received strong support from the majority of students, with nearly 80% of students providing feedback that they developed multiple abilities during the study process. The interview results indicated that teachers generally believed that using design thinking methods to understand students' real needs, define teaching problems, and devise instructional design solutions, along with testing and promptly adjusting the effectiveness through teaching practices, played a highly positive role in improving teaching and student learning outcomes. A comparison of exam scores showed a significant improvement in the exam scores of the class of 2021 stomatology students in the flipped teaching chapters compared to the class of 2020 stomatology students, and this difference was statistically significant. However, due to the limitation of the experimental chapter scope, there was no significant difference in the overall course grades. CONCLUSION: The study explores the application of design thinking in histology and embryology teaching, revealing its positive impact on innovative teaching strategies and students' learning experience in medical education. Online flipped teaching, developed through design thinking, proves to be an effective and flexible method that enhances student engagement and fosters autonomous learning abilities.

Small extracellular vesicles from young plasma reverse age-related functional declines by improving mitochondrial energy metabolism.

Recent investigations into heterochronic parabiosis have unveiled robust rejuvenating effects of young blood on aged tissues. However, the specific rejuvenating mechanisms remain incompletely elucidated. Here we demonstrate that small extracellular vesicles (sEVs) from the plasma of young mice counteract pre-existing aging at molecular, mitochondrial, cellular and physiological levels. Intravenous injection of young sEVs into aged mice extends their lifespan, mitigates senescent phenotypes and ameliorates age-associated functional declines in multiple tissues. Quantitative proteomic analyses identified substantial alterations in the proteomes of aged tissues after young sEV treatment, and these changes are closely associated with metabolic processes. Mechanistic investigations reveal that young sEVs stimulate PGC-1α expression in vitro and in vivo through their miRNA cargoes, thereby improving mitochondrial functions and mitigating mitochondrial deficits in aged tissues. Overall, this study demonstrates that young sEVs reverse degenerative changes and age-related dysfunction, at least in part, by stimulating PGC-1α expression and enhancing mitochondrial energy metabolism.

A graphene-like hollow sphere anode for lithium-ion batteries.

We report a flash Joule heating method for the rapid preparation of graphene-like materials. The L-GHS exhibited a uniform diameter of 200 nm and an ideal specific surface area of 670 m2 g-1. Meanwhile, the specific capacity of L-GHS remained at 942 mA h g-1 after 600 cycles (1 A g-1), which shows excellent electrochemical performance.

Effect of acupuncture on quality of life in patients with chronic prostatitis/chronic pelvic pain syndrome: a randomized controlled trial. / é’ˆåˆºæ²»ç–—å¯¹æ ¢æ€§å‰åˆ—è ºç‚Ž/æ ¢æ€§ç›†è ”ç–¼ç—›ç»¼åˆå¾æ‚£è€ ç”Ÿæ´»è´¨é‡çš„å½±å“ï¼šéšæœºå¯¹ç §è¯•éªŒ.

OBJECTIVES: To observe the effect and safety of acupuncture on quality of life, pain, and prostate symptoms in patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). METHODS: Seventy patients with CP/CPPS were randomly divided into an acupuncture group (35 cases, 1 case was eliminated) and a sham acupuncture group (35 cases, 3 cases dropped out). The patients in the acupuncture group were treated with routine acupuncture at bilateral Zhongliao (BL 33), Huiyang (BL 35), Shenshu (BL 23) and Sanyinjiao (SP 6), while the patients in the sham acupuncture group were treated with shallow needling at non-meridian and non-acupoint points beside bilateral Zhongliao (BL 33), Huiyang (BL 35), Shenshu (BL 23) and Sanyinjiao (SP 6),without manipulation to induce arrival of qi (deqi). Both groups retained the needles for 30 min, with one session every other day, three times a week, for a total of 8 weeks (24 sessions). Before and after treatment, and at the follow-up of 24 weeks after treatment completion, the scores of MOS 36-item short-form health survey (SF-36, including 8 dimensions of physical function [PF], role physical function [RP], bodily pain [BP], general health status [GH], vitality [VT], social function [SF], role emotional [RE], and mental health [MH], which can be summarized as physical component summary [PCS] and mental component summary [MCS]), pelvic pain visual analogue scale (VAS), National Institutes of Health chronic prostatitis symptom index (NIH-CPSI), and international prostate symptom score (IPSS) were evaluated, and safety of both groups was assessed. RESULTS: After treatment and at the follow-up, the scores of each dimension and PCS, MCS scores of SF-36 in the acupuncture group were higher than those before treatment (P<0.05, P<0.01); compared before treatment, the RP, BP, and SF scores and PCS score in the sham acupuncture group were increased after treatment (P<0.05, P<0.01). After treatment, the acupuncture group had higher scores in RP, BP, GH, MH and PCS, MCS than those in the sham acupuncture group (P<0.05, P<0.01); at the follow-up, except for PF and RE dimensions, the scores in each dimension and PCS, MCS scores in the acupuncture group were higher than those in the sham acupuncture group (P<0.05, P<0.01). After treatment and at the follow-up, pelvic pain VAS, NIH-CPSI, IPSS scores in the acupuncture group were lower than those before treatment (P<0.01); in the sham acupuncture group, pelvic pain VAS, NIH-CPSI scores were lower after treatment, and NIH-CPSI score at the follow-up was lower compared with those before treatment (P<0.01). After treatment and at the follow-up, pelvic pain VAS, NIH-CPSI, IPSS scores in the acupuncture group were lower than those in the sham acupuncture group (P<0.01, P<0.05). No significant adverse reactions were observed in both groups, and the incidence rates of adverse reactions had no significant difference (P>0.05). CONCLUSIONS: Acupuncture could effectively improve the quality of life, reduce pain levels, alleviate prostate symptoms, and shows favorable long-term efficacy in patients with CP/CPPS.

The association between systemic inflammatory response index and contrast-associated acute kidney injury in patients undergoing elective percutaneous coronary intervention.

BACKGROUND: The systemic inflammatory response index (SIRI), served as a novel inflammatory biomarker, is the synthesis of neutrophils, monocytes and lymphocytes. AIMS: We hypothesized that SIRI has predictive value for contrast-associated acute kidney injury (CA-AKI) and long-term mortality in patients undergoing elective percutaneous coronary intervention (PCI). METHODS: We retrospectively observed 5685 patients undergoing elective PCI from January 2012 to December 2018. Venous blood samples were collected to obtain the experimental data on the day of admission or the morning of the next day. SIRI = neutrophil count × monocyte count/lymphocyte count. CA-AKI was defined as an increase of 50% or 0.3 mg/dl in SCr from baseline within 48 h after contrast exposure. RESULTS: The incidence of CA-AKI was 6.1% (n = 352). The best cutoff value of SIRI for predicting CA-AKI was 1.39, with a sensitivity of 52.3% and a specificity of 67.3%. [AUC: 0.620, 95% confidence interval (CI): 0.590-0.651, p < 0.001]. After adjusting for potential confounders, multivariate analysis showed that the high SIRI group (SIRI > 1.39) was a strong independent predictor of CA-AKI in patients undergoing elective PCI compared with the low SIRI group (SIRI ≤ 1.39) (odds ratio = 1.642, 95% CI: 1.274-2.116, p < 0.001). Additionally, COX regression analysis showed that SIRI > 1.39 was significantly associated with long-term mortality at a median follow-up of 2.8 years. [Hazard ratio (HR)=1.448, 95%CI: 1.188-1.765; p < 0.001]. Besides, Kaplan-Meier survival curve also indicated that the cumulative rate of mortality was considerably higher in the high SIRI group. CONCLUSIONS: High levels of SIRI are independent predictors of CA-AKI and long-term mortality in patients undergoing elective PCI.

Aspirin/amoxicillin loaded chitosan microparticles and polydopamine modified titanium implants to combat infections and promote osteogenesis.

It is known that titanium (Ti) implant surfaces exhibit poor antibacterial properties and osteogenesis. In this study, chitosan particles loaded with aspirin, amoxicillin or aspirin + amoxicillin were synthesized and coated onto implant surfaces. In addition to analysing the surface characteristics of the modified Ti surfaces, the effects of the modified Ti surfaces on the adhesion and viability of rat bone marrow-derived stem cells (rBMSCs) were evaluated. The metabolic activities of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) biofilms on the modified Ti surfaces were also measured in vitro. Moreover, S. aureus was tested for its antibacterial effect by coating it in vivo. Using water as the droplet medium, the contact angles of the modified Ti surfaces increased from 44.12 ± 1.75° to 58.37 ± 4.15°. In comparison to those of the other groups tested, significant increases in rBMSC adhesion and proliferation were observed in the presence of aspirin + amoxicillin-loaded microspheres, whereas a significant reduction in the metabolic level of biofilms was observed in the presence of aspirin + amoxicillin-loaded microspheres both in vitro and in vivo. Aspirin and amoxicillin could be used in combination to coat implant surfaces to mitigate bacterial activities and promote osteogenesis.

Emergence of ceftazidime-avibactam resistance in blaKPC-33-harboring ST11 Klebsiella pneumoniae in pediatric patient.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) poses immense threats to the health of infected patients worldwide, especially in children. This study reports the infection caused by CRKP in a pediatric intensive care unit (PICU) child and its drug-resistant mutation during the treatment. Twelve Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae strains were isolated from the child. Broth microdilution method, plasmid transformation assay, and whole genome sequencing (WGS) were performed to investigate the antimicrobial susceptibility, resistance mechanisms, and genetic structural features of CRKPs. The results showed that twelve strains were highly resistant to most available antimicrobial agents. Among them, K. pneumoniae FD11 and K. pneumoniae FD12 were resistant to ceftazidime-avibactam (CZA, MIC>64mg/L) and restored the carbapenem susceptibility (IMP, MIC=0.25mg/L; MEM, MIC=2mg/L). The patient improved after treatment with CZA in combination with aztreonam. Plasmid transformation assay demonstrated that the blaKPC-33-positive transformant increased MICs of CZA by at least 33-fold and 8-fold compared with the recipient E.coli DH5α and blaKPC-2-positive transformants. WGS analysis revealed that all strains belonged to the ST11-KL64 type and showed highly homologous (3 to 26 single nucleotide polymorphisms (SNPs)). A single base mutation (G532T) of blaKPC-2 resulted in a tyrosine to aspartic acid substitution at Ambler amino acid position 179 (D179Y), which conferred CZA resistance in K. pneumoniae. This is the first report of a drug-resistant mutation evolving into blaKPC-33 during the treatment of blaKPC-2-positive CRKP in pediatric infected patients. It advises clinicians that routine sequential antimicrobial susceptibility testing and KPC genotyping are critical during CZA therapy in children infected with CRKP.

A young woman with Mycobacterium chelonae complex infection caused by facial stem cell injection.

In outpatient settings, Mycobacterium chelonae complex infection brought on by cosmetic injections are rather uncommon. We came across a case of infection brought on by a commercial stem cell injection.

Genome-wide association studies identified OsTMF as a gene regulating rice seed germination under salt stress.

Introduction: Salt tolerance during seed germination is an important trait for direct seeding and low-cost rice production. Nevertheless, it is still not clear how seed germination under salt stress is regulated genetically. Methods: In this study, genome-wide association studies (GWAS) were performed to decipher the genetic basis of seed germination under salt stress using 541 rice varieties collected worldwide. Results and discussion: Three quantitative trait loci (QTLs) were identified including qGRG3-1 on chromosome 3, qGRG3-2 on chromosome 5, and qGRG4 on chromosome 4. Assessment of candidate genes in these loci for their responses to salt stress identified a TATA modulatory factor (OsTMF) in qGRG3-2. The expression of OsTMF was up-regulated in both roots and shoots after exposure to salt stress, and OsTMF knockout mutants exhibited delayed seed germination under salt stress. Haplotype analysis showed that rice varieties carrying OsTMF-Hap2 displayed elevated salt tolerance during seed germination. These results provide important knowledge and resources to improve rice seed germination under salt stress in the future.

Intramedullary nailing for irreducible spiral subtrochanteric fractures: A comparison of cerclage and non-cerclage wiring.

PURPOSE: Intramedullary nailing is the preferred internal fixation technique for the treatment of subtrochanteric fractures because of its biomechanical advantages. However, no definitive conclusion has been reached regarding whether combined cable cerclage is required during intramedullary nailing treatment. This study was performed to compare the clinical effects of intramedullary nailing with cerclage and non-cerclage wiring in the treatment of irreducible spiral subtrochanteric fractures. METHODS: Patients with subtrochanteric fractures admitted to our center from January 2013 to December 2021 were retrospectively analyzed. The patients were enrolled in the case-control study according to the inclusion and exclusion criteria and divided into the non-cerclage group and the cerclage group. The patients' clinical data, including the operative time, intraoperative blood loss, hospital stay, reoperation rate, fracture union time, and Harris hip score, were compared between these 2 groups. Categorical variables were compared using Chi-square or Fisher's exact test. Continuous variables with normal distribution were presented as mean ± standard deviation and analyzed with Student's t-test. Non-normally distributed variables were expressed as median (Q1, Q3) and assessed using the Mann-Whitney test. A p value < 0.05 was considered significant. RESULTS: In total, 69 patients were included in the study (35 patients in the non-cerclage group and 34 patients in the cerclage group). The baseline data of the 2 groups were comparable. There were no significant difference in the length of hospital stay (z = -0.391, p = 0.696), operative time (z = -1.289, p = 0.197), or intraoperative blood loss (z = -1.321, p = 0.186). However, compared with non-cerclage group, the fracture union time was shorter (z = -5.587, p < 0.001), the rate of nonunion was lower (χ2 = 6.030, p = 0.03), the anatomical reduction rate was higher (χ2 = 5.449, p = 0.03), and the Harris hip score was higher (z = -2.99, p = 0.003) in the cerclage group, all with statistically significant differences. CONCLUSIONS: Intramedullary nailing combined with cable cerclage wiring is a safe and reliable technique for the treatment of irreducible subtrochanteric fractures. This technique can improve the reduction effect, increase the stability of fracture fixation, shorten the fracture union time, reduce the occurrence of nonunion, and contribute to the recovery of hip joint function.

Right ventricular volume and function by three-dimensional echocardiography: results of the echocardiographic measurements in normal Chinese adults (EMINCA) II.

Three-dimensional (3D) echocardiography is an emerging technique for assessing right ventricular (RV) volume and function, but 3D-RV normal values from a large Chinese population are still lacking. The aim of the present study was to establish normal values of 3D-RV volume and function in healthy Chinese volunteers. A total of 1117 Han Chinese volunteers from 28 laboratories in 20 provinces of China were enrolled, and 3D-RV images of 747 volunteers with optimal image quality were ultimately analyzed by a core laboratory. Both vendor-dependent and vendor-independent software platforms were used to analyze the 3D-RV images. We found that men had larger RV volumes than women did in the whole population, even after indexing to body surface area, and older individuals had smaller RV volumes. The normal RV volume was significantly smaller than that recommended by the American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines in both sexes. There were significant differences in 3D-RV measurements between the two vendor ultrasound systems and the different software platforms. The echocardiographic measurements in normal Chinese adults II study revealed normal 3D-RV volume and function in a large Chinese population, and there were significant differences between the sexes, ages, races, and vendor groups. Thus, normal 3D-RV values should be stratified by sex, age, race, and vendor.

Analysis of Factors and T-Lymphocyte Subset Changes in Pediatric Recurrent Respiratory Infections Post-Pidotimod Treatment.

Objective: This study aims to analyze factors contributing to recurrent respiratory tract infections (RRTIs) in pediatric patients and evaluate the efficacy of pidotimod (PI) treatment. Methods: This study utilized a retrospective cohort design, enrolling a total of 85 children diagnosed with RRTIs between September 2020 and September 2022, alongside 54 healthy children. Logistic regression analysis was employed to identify factors contributing to RRTI occurrence. Among the participants, 40 children underwent conventional treatment (control group), while 45 received PI treatment (research group). Comparative analyses were conducted to assess clinical efficacy and adverse effects between the two treatment groups. Results: The history of family members' smoking and parental allergy emerged as independent risk factors for RRTIs (P < .05, OR>1), whereas parental education level, outdoor activity, and micronutrient intake were identified as independent protective factors for RRTIs (P < .05, OR<1). Symptoms such as cough, fever, rhonchi, moist rales, and tonsillar enlargement resolved significantly faster in the research group compared to the control group (P < .05). Additionally, the research group exhibited reduced infection duration and fewer recurrent infections (P < .05). Following treatment, the overall treatment efficacy was superior in the research group compared to the control group (P < .05), with no significant difference in the incidence of adverse effects (P > .05). Post-treatment, levels of CD3+, CD4+, and CD4+/CD8+ were elevated in the research group compared to the control group, while CD8+ levels were lower (P < .05). Conclusions: Daily outdoor activity among children, family members' history of smoking, parental allergy history, education level, and micronutrient intake emerged as independent factors influencing pediatric RRTIs. Furthermore, PI was identified as a significant treatment option for RRTIs.

FLNA overexpression promotes papillary thyroid cancer aggression via the FAK/AKT signaling pathway.

BACKGROUND: Filamin A (FLNA) is a member of filamin family and has been found to be critical for the progression of several cancers. However, its biological function in papillary thyroid cancer (PTC) remains largely unexplored. METHODS: Data from The Cancer Genome Atlas (TCGA) databases were utilized to analyze the FLNA expression level and its influence on the clinical implication of patients with PTC. Gene Expression Omnibus (GEO) and quantitative real-time reverse transcriptase PCR (qRT-PCR) was used to verify the expression levels of FLNA in PTC. Kaplan-Meier survival analysis was conducted to evaluate the prognostic value of FLNA in PTC. Transwell assays and wound healing were performed to examine the biological function of FLNA knockdown in PTC cells. Gene set enrichment analysis (GSEA) and Western blotting were conducted to investigate the potential mechanisms underlying the role of FLNA in PTC progression. In addition, the relationship between FLNA expression and tumor immune microenvironment (TME) in PTC was explored. RESULTS: FLNA was significantly upregulated in PTC tissues. High expression level of FLNA was correlated with advanced TNM stage, T stage and N stage, as well as poor disease-free interval (DFI) and progression-free interval (PFI) time in PTC patients. Moreover, we found that FLNA knockdown inhibited the migration and invasion of PTC cells. Mechanistically, FLNA knockdown inhibited epithelial-mesenchymal transition (EMT) in PTC and affected the activation of the FAK/AKT signaling pathway. In addition, FLNA expression was associated with TME in PTC. CONCLUSION: FLNA may be regarded as a new therapeutic target for PTC patients.

Excitatory amino acid transporter supports inflammatory macrophage responses.

Excitatory amino acid transporters (EAATs) are responsible for excitatory amino acid transportation and are associated with auto-immune diseases in the central nervous system and peripheral tissues. However, the subcellular location and function of EAAT2 in macrophages are still obscure. In this study, we demonstrated that LPS stimulation increases expression of EAAT2 (coded by Slc1a2) via NF-κB signaling. EAAT2 is necessary for inflammatory macrophage polarization through sustaining mTORC1 activation. Mechanistically, lysosomal EAAT2 mediates lysosomal glutamate and aspartate efflux to maintain V-ATPase activation, which sustains macropinocytosis and mTORC1. We also found that mice with myeloid depletion of Slc1a2 show alleviated inflammatory responses in LPS-induced systemic inflammation and high-fat diet induced obesity. Notably, patients with type II diabetes (T2D) have a higher level of expression of lysosomal EAAT2 and activation of mTORC1 in blood macrophages. Taken together, our study links the subcellular location of amino acid transporters with the fate decision of immune cells, which provides potential therapeutic targets for the treatment of inflammatory diseases.

Exosomal miR-151-3p in saliva: A potential non-invasive marker for gastric cancer diagnosis and prognosis modulated by Sijunzi decoction (SJZD) in mice.

Gastric cancer (GC) is one of the most prominent malignancies that originate in the epithelial cells of the gastric mucosa and is one of the main causes of cancer-related mortality worldwide. New circulating biomarkers of exosomal RNA might have great potential for non-invasive early prognosis of GC. Sijunzi Decoction (SJZD) is a typical representative formula of the method of benefiting Qi and strengthening the spleen in Traditional Chinese Medicine (TCM). However, the effects and mechanism of SJZD in treating GC remain unclear. This study looked for biomarkers of exosomal RNA for early prognosis of GC, and explored the mechanism of SJZD in treating GC. A gastric cancer model with spleen deficiency syndrome was established in nude mice, and the curative effects of SJZD were investigated. Differentially expressed miRNAs in plasma and saliva exosomes were sequenced and analyzed. Potential target genes of these miRNAs were predicted and applied for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment annotation. Overlapping miRNAs in saliva and plasma samples were analyzed, and qRT-PCR was performed for verification. miR-151a-3p was selected, and qRT-PCR further determined that miR-151a-3p was downregulated in saliva and plasma exosomes from the SJZD group. The intersected miR-151a-3p target genes were predicted and enriched in the extrinsic apoptotic signaling pathways. SJZD significantly ameliorates gastric cancer with spleen deficiency syndrome in mouse models, and exosomal miRNAs, particularly miR-151-3p, might be modulated by SJZD in plasma and saliva. The exosomal miR-151-3p in saliva may serve as a non-invasive potential marker for gastric cancer diagnosis and prognosis.

[Survival and Prognosis of Patients with Acute Myeloid Leukemia with Myelodysplasia-Related Changes Transformed from Myelodysplastic Syndrome].

OBJECTIVE: To explore the risk factors affecting the survival and efficacy of patients with acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) transformed from myelodysplastic syndrome (MDS). METHODS: The clinical data of 60 patients with AML-MRC transformed from MDS who hospitalized in The Third Affiliated Hospital of Soochow University from January 2010 to December 2021 were retrospectively analyzed. The demographic data and laboratory parameters, cytogenetic karyotypes, target genes of AML detected by next generation sequence, risk stratification, treatment regimen, therapeutic efficacy and survival outcome were documented. Rank sum test and Chi-square test or Fisher exact test were used to compare the survival and efficacy. The effects of clinical parameters, risk stratification and treatment regimens on the survival and efficacy of the AML-MRC patients were analyzed by univariate and multivariate analysis. RESULTS: The median overall survival (OS) of the AML-MRC patients was 4.5 months, the 1-year OS rate was 28.3%, and the complete remission (CR) rate after treatment was 33.3%. The univariate analysis showed that age≥60 years, leukocytosis, severe thrombocytopenia, poor-risk group and only accepted hypomethylating agents(HMAs) or supportive therapy were the risk factors affecting OS. COX multivariate analysis showed that thrombocytopenia ( HR=4.46), HMAs therapy (compared to transplantation, HR=10.47), supportive therapy (compared to transplantation, HR=25.80) and poor-risk group (compared to medium-risk group, HR=13.86) were independent hazard factors for median OS of patients with AML-MRC. The univariate analysis showed that the risk factors affecting 1-year OS in patients with AML-MRC were age≥60 years, thrombocytopenia, time of transformation from MDS to AML (TTA)≥3 months, fibrinogen-albumin ratio index (FARI)≥0.07, CONUT score≥5, poor-risk group and supportive therapy. Binary logistic regression analysis showed that the independent risk factors for 1-year OS in AML-MRC patients were age≥60 years ( HR=11.23), thrombocytopenia ( HR=8.71), FARI≥0.07 ( HR=5.19) and poor-risk group ( HR=14.00). The risk factors affecting CR of AML-MRC patients in univariate analysis were age≥60 years, thrombocytopenia, FARI≥0.1, CONUT score≥5, poor-risk group and supportive therapy, while binary logistic regression analysis showed that age≥60 years( HR=7.35), CONUT score≥5 ( HR=9.60), thrombocytopenia ( HR=12.05) and poor-risk group ( HR=32.5) were independent risk factors affecting CR of the patients. CONCLUSION: The OS of AML-MRC patients is poor, old age(≥60 years old), supportive therapy, HMA therapy, poor-risk, thrombocytopenia, FARI≥0.07 and CONUT score≥5 may be associated with poor prognosis.

Clinical Application and Research Progress of Remimazolam for Pediatric Patients.

Remimazolam is a novel ultrashort-acting benzodiazepine that allosterically modulates γ-aminobutyric acid type A (GABAA) receptors to exert sedative effects. Remimazolam has the properties of controllable sedation, rapid onset, and a short duration of action, along with minor depression of circulation and respiration. Remimazolam has been approved for clinical use since 2020 in Japan, and it has been applied for procedural sedation, general anesthesia induction and maintenance, and sedation in ICU patients, and has been proven to be safe and effective. Currently, no consensus has been reached on the clinical application of remimazolam in pediatric patients. This review introduces the clinical research progress and limitations of remimazolam in recent years, aiming to supply scientific guidance and a theoretical reference for the application of remimazolam in pediatric anaesthesia.