Effective annotation of in vivo drug metabolites using liquid chromatography-mass spectrometry (LC-MS) remains a formidable challenge. Herein, a metabolic reaction-based molecular networking (MRMN) strategy is introduced, which enables the "one-pot" discovery of prototype drugs and their metabolites. MRMN constructs networks by matching metabolic reactions and evaluating MS² spectral similarity, incorporating innovations and improvements in feature degradation of MS² spectra, exclusion of endogenous interference, and recognition of redundant nodes. A minimum 75% correlation between structural similarity and MS² similarity of neighboring metabolites was ensured, mitigating false negatives due to spectral feature degradation. At least 79% of nodes, 49% of edges, and 97% of subnetworks were reduced by an exclusion strategy of endogenous ions compared to the Global Natural Products Social Molecular Networking (GNPS) platform. Furthermore, an approach of redundant ions identification was refined, achieving a 10%-40% recognition rate across different samples. The effectiveness of MRMN was validated through a single compound, plant extract, and mixtures of multiple plant extracts. Notably, MRMN is freely accessible online at https://yaolab.network, broadening its applications.

Background: A simple superoposterior approach to thoracic transforaminal epidural injections (TFEIs) under ultrasonographic guidance was proposed to reduce zoster-associated pain (ZAP) involving multiple thoracic nerves and the likelihood of transitioning to postherpetic neuralgia (PHN). Methods: Patients were prospectively enrolled. Primary endpoints were the burden of illness (BOI) scores and epidural contrast spread. Secondary endpoints included number of needle insertion attempts, sensory blockade, hemodynamic changes, procedure time, radiation dose, adverse events, rescue analgesics, PHN incidence and EuroQoL 5-Dimension scores. Results: Thirty-five injections were performed in 27 patients. Median levels of cephalad-caudad epidural contrast spread were 3, 4, and 5 ml following injections of 2, 3, and 4 ml. Dorsal epidural spread was observed at levels 3, 4, and 5, whereas concurrent ventral spread was observed at levels 2, 3, and 4. BOI scores at 30–180 days significantly decreased (mean difference: −25.3, 95% CI [−57.4 to 6.6], P = 0.005), accounting for reduced rescue analgesic requirements and PHN occurrence and improved EuroQoL 5-Dimension scores. Median sensory blockade at 5 min post-procedure was at level 2, 3, and 4 after 2, 3, and 4 ml of therapeutic injectate. No significant hemodynamic changes were noted at 15 min post-injection. No serious adverse events were observed. Conclusions Spread of thoracic epidural contrast to all involved nerves was confirmed using this novel technique. Simplified needle placement reduced the technical difficulty and risk of complications. It might be a promising alternative approach for ZAP.

Background: A simple superoposterior approach to thoracic transforaminal epidural injections (TFEIs) under ultrasonographic guidance was proposed to reduce zoster-associated pain (ZAP) involving multiple thoracic nerves and the likelihood of transitioning to postherpetic neuralgia (PHN). Methods: Patients were prospectively enrolled. Primary endpoints were the burden of illness (BOI) scores and epidural contrast spread. Secondary endpoints included number of needle insertion attempts, sensory blockade, hemodynamic changes, procedure time, radiation dose, adverse events, rescue analgesics, PHN incidence and EuroQoL 5-Dimension scores. Results: Thirty-five injections were performed in 27 patients. Median levels of cephalad-caudad epidural contrast spread were 3, 4, and 5 ml following injections of 2, 3, and 4 ml. Dorsal epidural spread was observed at levels 3, 4, and 5, whereas concurrent ventral spread was observed at levels 2, 3, and 4. BOI scores at 30–180 days significantly decreased (mean difference: −25.3, 95% CI [−57.4 to 6.6], P = 0.005), accounting for reduced rescue analgesic requirements and PHN occurrence and improved EuroQoL 5-Dimension scores. Median sensory blockade at 5 min post-procedure was at level 2, 3, and 4 after 2, 3, and 4 ml of therapeutic injectate. No significant hemodynamic changes were noted at 15 min post-injection. No serious adverse events were observed. Conclusions Spread of thoracic epidural contrast to all involved nerves was confirmed using this novel technique. Simplified needle placement reduced the technical difficulty and risk of complications. It might be a promising alternative approach for ZAP.

Background: A simple superoposterior approach to thoracic transforaminal epidural injections (TFEIs) under ultrasonographic guidance was proposed to reduce zoster-associated pain (ZAP) involving multiple thoracic nerves and the likelihood of transitioning to postherpetic neuralgia (PHN). Methods: Patients were prospectively enrolled. Primary endpoints were the burden of illness (BOI) scores and epidural contrast spread. Secondary endpoints included number of needle insertion attempts, sensory blockade, hemodynamic changes, procedure time, radiation dose, adverse events, rescue analgesics, PHN incidence and EuroQoL 5-Dimension scores. Results: Thirty-five injections were performed in 27 patients. Median levels of cephalad-caudad epidural contrast spread were 3, 4, and 5 ml following injections of 2, 3, and 4 ml. Dorsal epidural spread was observed at levels 3, 4, and 5, whereas concurrent ventral spread was observed at levels 2, 3, and 4. BOI scores at 30–180 days significantly decreased (mean difference: −25.3, 95% CI [−57.4 to 6.6], P = 0.005), accounting for reduced rescue analgesic requirements and PHN occurrence and improved EuroQoL 5-Dimension scores. Median sensory blockade at 5 min post-procedure was at level 2, 3, and 4 after 2, 3, and 4 ml of therapeutic injectate. No significant hemodynamic changes were noted at 15 min post-injection. No serious adverse events were observed. Conclusions Spread of thoracic epidural contrast to all involved nerves was confirmed using this novel technique. Simplified needle placement reduced the technical difficulty and risk of complications. It might be a promising alternative approach for ZAP.

Background: A simple superoposterior approach to thoracic transforaminal epidural injections (TFEIs) under ultrasonographic guidance was proposed to reduce zoster-associated pain (ZAP) involving multiple thoracic nerves and the likelihood of transitioning to postherpetic neuralgia (PHN). Methods: Patients were prospectively enrolled. Primary endpoints were the burden of illness (BOI) scores and epidural contrast spread. Secondary endpoints included number of needle insertion attempts, sensory blockade, hemodynamic changes, procedure time, radiation dose, adverse events, rescue analgesics, PHN incidence and EuroQoL 5-Dimension scores. Results: Thirty-five injections were performed in 27 patients. Median levels of cephalad-caudad epidural contrast spread were 3, 4, and 5 ml following injections of 2, 3, and 4 ml. Dorsal epidural spread was observed at levels 3, 4, and 5, whereas concurrent ventral spread was observed at levels 2, 3, and 4. BOI scores at 30–180 days significantly decreased (mean difference: −25.3, 95% CI [−57.4 to 6.6], P = 0.005), accounting for reduced rescue analgesic requirements and PHN occurrence and improved EuroQoL 5-Dimension scores. Median sensory blockade at 5 min post-procedure was at level 2, 3, and 4 after 2, 3, and 4 ml of therapeutic injectate. No significant hemodynamic changes were noted at 15 min post-injection. No serious adverse events were observed. Conclusions Spread of thoracic epidural contrast to all involved nerves was confirmed using this novel technique. Simplified needle placement reduced the technical difficulty and risk of complications. It might be a promising alternative approach for ZAP.

Objective To observe the impact factors of vascular heat sink effect during in vitro microwave ablation(MWA)of porcine lung.Methods Simulation models were established using in vitro porcine lung tissue blocks based on isobaric inflation with an air pump and cyclic perfusion of duck blood with a glass tube and peristaltic pump,etc.MWA was performed under 8 different combining conditions(vessel diameter of 3 or 5 mm,blood perfusion of 30 or 50 cm/s,as well as distance between vessel and ablation antenna of 5 or 10 mm)each for 3 times.The highest temperature TV on vessel side and TC on control side during MWA,and ablation depth DV on vessel side and DC on control side after MWA were recorded.Multi-factor linear regression equations were constructed based on simulated vessel diameters,blood perfusion and distance between vessel and ablation antenna,and the impact factors of|TC-TV|and|DC-DV|were screened,respectively.Results Simulated vessel diameter showed linear positive correlation with both|TC-TV|and|DC-DV|(both P＜0.001).Simulated distance between vessel and ablation antenna showed linear negative correlation with both|TC-TV|and|DC-DV|(both P＜0.001),and the latter had more obvious impact on vascular heat sink effect than the former.Meanwhile,no significant linear relationship was found between simulated blood perfusion and|TC-TV|nor|DC-DV|(both P＞0.05).Conclusion Simulated vessel diameter and distance between vessel and ablation antenna were both impact factors of vascular heat sink effect during in vitro MWA of porcine lung,and the latter was more influential,whereas simulated blood perfusion showed no significant impact on it.

Objective To explore the differences in gut microbiota among different histopathologi-cal subtypes of lung cancer.Methods A total of 80 lung cancer patients admitted to the Department of Oncology and Hematology of Anqing First People's Hospital from February 2020 to February 2024 were selected as study subjects.Meanwhile,80 healthy volunteers who underwent physical examina-tions during the same period were selected as control group.According to pathological examination re-sults,the lung cancer patients were divided into three subgroups:lung squamous cell carcinoma group,lung adenocarcinoma group,and lung small-cell cancer group.The 16S ribosomal RNA(16S rRNA)sequencing technology was used to compare the differences in gut microbiota diversity and the characteristics of species relative abundance between lung cancer patients with different patho-logical grades and the control group.Results The proportion of patients with a family history of lung cancer was higher in different lung cancer subtypes than in the control group,and the difference was statistically significant(P＜0.05).The abundance-based coverage estimator(ACE)index,Simpson index,and Shannon index of patients with different lung cancer pathological subtypes were all lower than those in the control group,and the differences were statistically significant(P＜0.05).β-diver-sity analysis showed that there were significant differences in the variation of gut microbial community structure between the control group and lung cancer patients with different pathological types(P＜0.05).The results of LEfSe indicated that there were differences in gut characteristic microbiota among patients with different pathological subtypes.Specifically,Megamonas was enriched in the LUAD group,Butyrivibrio was enriched in the LSCC group,and Akkermansia was enriched in the SCLC group.Conclusion There are significant differences in the composition of gut microbiota between lung cancer patients and the normal population,and the gut microbiota of patients with different lung cancer pathological subtypes have distinct characteristics.These differences may provide new bio-markers and therapeutic strategies for the diagnosis and treatment of lung cancer.

Objective To observe the impact factors of vascular heat sink effect during in vitro microwave ablation(MWA)of porcine lung.Methods Simulation models were established using in vitro porcine lung tissue blocks based on isobaric inflation with an air pump and cyclic perfusion of duck blood with a glass tube and peristaltic pump,etc.MWA was performed under 8 different combining conditions(vessel diameter of 3 or 5 mm,blood perfusion of 30 or 50 cm/s,as well as distance between vessel and ablation antenna of 5 or 10 mm)each for 3 times.The highest temperature TV on vessel side and TC on control side during MWA,and ablation depth DV on vessel side and DC on control side after MWA were recorded.Multi-factor linear regression equations were constructed based on simulated vessel diameters,blood perfusion and distance between vessel and ablation antenna,and the impact factors of|TC-TV|and|DC-DV|were screened,respectively.Results Simulated vessel diameter showed linear positive correlation with both|TC-TV|and|DC-DV|(both P＜0.001).Simulated distance between vessel and ablation antenna showed linear negative correlation with both|TC-TV|and|DC-DV|(both P＜0.001),and the latter had more obvious impact on vascular heat sink effect than the former.Meanwhile,no significant linear relationship was found between simulated blood perfusion and|TC-TV|nor|DC-DV|(both P＞0.05).Conclusion Simulated vessel diameter and distance between vessel and ablation antenna were both impact factors of vascular heat sink effect during in vitro MWA of porcine lung,and the latter was more influential,whereas simulated blood perfusion showed no significant impact on it.

Objective:To explore the distribution characteristics and antibiotic resistance of pathogen in children with hematological disorders and cancers complicated with sepsis in pediatric intensive care unit (PICU).Methods:The clinical data of children with hematological disorders and cancers complicated with sepsis hospitalized at Shenzhen Children′s Hospital affiliated to China Medical University from January 2016 to August 2023 were retrospectively analyzed. Patients were divided into survival group and death group based on the outcome of sepsis on 28 days after diagnosis.Results:A total of 202 sepsis episodes occurred in 176 children were enrolled in this study. Among all, 144 (71.3%) cases of bloodstream infection, 59 (29.2%) cases of pulmonary infection, 21 (10.4%) cases of abdominal infection, 9 (4.5%) cases of soft tissue infection, 9 (4.5%) cases of nervous system infection, and 3 (1.5%) cases of urinary tract infection. A total of 244 pathogenic strains were identified, in which 74 (30.3%) cases were gram-positive bacteria. The top 3 pathogens isolated were Coagulase negative Staphylococcus (21 strains), Staphylococcus aureus (19 strains) and Streptococcus pneumoniae (13 strains). Gram-negative bacteria accounted for 122 (50.0%) strains, in which top 3 were Klebsiella pneumonia (33 strains), Escherichia coli (25 strains), and Pseudomonas aeruginosa (23 strains). Fungi comprised 48 (19.7%) strains:the top 3 were Candida tropicalis (14 strains), Candida albicans (10 strains), Aspergillus and Pneumocystis jirovecii (7 strains each). The incidence of Acinetobacter baumannii, Stenotrophomonas maltophilia, and Pseudomonas aeruginosa were significantly higher in death group compared to survival group[9.0%（6/67）vs. 2.3%（4/177）, χ2＝3.971 ，P＝0.046; 9.0%（6/67）vs. 1.1%（2/177）, χ2＝7.080 ，P＝0.008;16.4%（11/67）vs. 6.8%（12/177）, χ2＝5.288 ，P＝0.021]. The samples of 57 cases were simultaneously detected by both culture and metagenomic next-generation sequencing (mNGS). Pathogens were detected in 25 cases by both culture and mNGS. In 30 cases, pathogen detection were mNGS positive but culture negative. Two cases showed positive results only with culture. A total of 79 (46.8%) strains were multi-drug resistant bacteria, including 27 (34.2%) strains of gram-positive bacteria and 52 (65.8%) strains of gram-negative bacteria. A total of 174 (86.1%) children with sepsis received empirical anti-infective drugs within 24 hours of fever onset. A total of 124 (61.4%) cases were appropriately covered by the initial empirical antibiotics, while 40 (19.8%) cases were not adequately covered and 10 (5.0%) cases had incomplete coverage. Despite the inclusion of pathogenic in the coverage, resistance to initial antibiotics was observed in 22 (10.9%) cases. Fifty-one patients died. Conclusion:The predominant pathogens responsible for sepsis in PICU with hematological disorders and cancers is gram-negative bacteria, followed by gram-positive bacteria and fungi. In comparison to healthy children with sepsis, there is a higher incidence of fungal infections among hematological disorders and cancers. The proportion of multi-drug resistant bacteria infection is high. Early identification and combination of local etiological distribution and drug resistance, along with the empirical selection of appropriate anti-infection treatment strategies, can greatly enhance survival rate.

Pyran- and furanocoumarins are key representatives of tetrahydropyrans and tetrahydrofurans, respectively, exhibiting diverse physiological and medical bioactivities. However, the biosynthetic mechanisms for their core structures remain poorly understood. Here we combined multiomics analyses of biosynthetic enzymes in Peucedanum praeruptorum and in vitro functional verification and identified two types of key enzymes critical for pyran and furan ring biosynthesis in plants. These included three distinct P. praeruptorum prenyltransferases (PpPT1-3) responsible for the prenylation of the simple coumarin skeleton 7 into linear or angular precursors, and two novel CYP450 cyclases (PpDC and PpOC) crucial for the cyclization of the linear/angular precursors into either tetrahydropyran or tetrahydrofuran scaffolds. Biochemical analyses of cyclases indicated that acid/base-assisted epoxide ring opening contributed to the enzyme-catalyzed tetrahydropyran and tetrahydrofuran ring refactoring. The possible acid/base-assisted catalytic mechanisms of the identified cyclases were theoretically investigated and assessed using site-specific mutagenesis. We identified two possible acidic amino acids Glu303 in PpDC and Asp301 in PpOC as vital in the catalytic process. This study provides new enzymatic tools in the epoxide formation/epoxide-opening mediated cascade reaction and exemplifies how plants become chemically diverse in terms of enzyme function and catalytic process.