Pulmonary nodules(PNs),a critical imaging indicator for early lung cancer screening,require deeper mechanistic explo-ration of their malignant transformation.Current Western medicine strategies—primarily surveillance—suffer from delayed interven-tion,while traditional Chinese medicine(TCM)theories(e.g.,"phlegm-blood stasis binding")inadequately explain the dynamic pro-gression of malignancy.Integrating You Yi's theory of"where there is mass hardness,there must be latent yang"with modern research on PN malignant transformation,this study proposes a novel pathogenic mechanism of"latent yang as cause,mass hardness as effect":Depressed latent yang drives pro-tumorigenic microenvironments(e.g.,immunosuppression,hypoxic stress,chronic inflammation),leading to the coagulation of phlegm,stasis,fire,and toxins into cancer toxin.Based on this framework,a core therapeutic principle of"dispersing latent yang and intercepting malignant transition in stages"was established,providing a new paradigm for TCM-based early intervention against PN malignancy.

Objective:To compare the effect of high frequency oscillatory ventilation (HFOV) and conventional mechanical ventilation (CMV) in the treatment of pediatric acute respiratory distress syndrome (ARDS).Methods:A prospective randomized controlled study was conducted on ARDS children treated with mechanical ventilation in the Intensive Care Unit (ICU) of Children′s Hospital, Capital Institute of Pediatric from January 2017 to December 2018.They were randomly (computer digital method) divided into HFOV group and CMV group.The basic data and clinical indicators, such as pediatric critical illness scores, oxygenation index (OI), blood gas, mechanical ventilation time, ventilator parameters, ICU hospitalization time, complications, prognosis, dynamic changes of inflammatory factors, use of sedative muscle relaxants and vasoactive drugs, were recorded.SPSS 22.0 software was used to analyze the data.The Mann Whitney U test was used for inter-group comparison.The χ2 test was adopted for the comparison of counting data. Results:A total of 45 children were included in the analysis.There were 21 cases in the HFOV group and 24 cases in the CMV group.Moderate and severe ARDS was detected in 34 cases, including 16 cases in the HFOV group and 18 cases in the CMV group.Compared with those in the CMV group, the levels of OI-24 h and OI-48 h in the HFOV group were significantly lower [7.4 (5.9, 8.6) vs.9.0 (6.7, 13.6), P=0.018] and [5.9 (5.2, 8.5) vs.9.2 (7.4, 12.4), P=0.001].The levels of OI-6 h [8.2(6.5, 10.0) vs.10.5(8.2, 13.0), P=0.037], OI-12 h[7.8(6.5, 9.0) vs.9.8(8.0, 12.8), P=0.009], OI-24 h [7.7(6.4, 8.6) vs.10.1(8.7, 15.5), P<0.001], OI-48 h [6.0(5.3, 8.6) vs.10.7(8.8, 13.1), P<0.001] and OI-72 h [5.8(5.0, 8.6) vs. 8.0(6.6, 10.6), P=0.031] in children with moderate to severe ARDS of the HFOV group were significantly lower than those of the CMV group.There were no significant differences in ICU hospitalization time, invasive mechanical ventilation time, total mechanical ventilation time, 28-day prognosis, vasoactive drugs, muscle relaxants, blood purification, fluid balance, inflammatory factors, intracranial hemorrhage and pneumothorax between the 2 groups. Conclusions:This study confirms that HFOV can improve the oxygenation level in pediatric patients with ARDS more rapidly than CMV.HFOV does not increase the incidence of complications such as pneumothorax and intracranial hemorrhage, and the use of vasoactive drugs and muscle relaxants, showing safety in clinical application.

Pulmonary nodules(PNs),a critical imaging indicator for early lung cancer screening,require deeper mechanistic explo-ration of their malignant transformation.Current Western medicine strategies—primarily surveillance—suffer from delayed interven-tion,while traditional Chinese medicine(TCM)theories(e.g.,"phlegm-blood stasis binding")inadequately explain the dynamic pro-gression of malignancy.Integrating You Yi's theory of"where there is mass hardness,there must be latent yang"with modern research on PN malignant transformation,this study proposes a novel pathogenic mechanism of"latent yang as cause,mass hardness as effect":Depressed latent yang drives pro-tumorigenic microenvironments(e.g.,immunosuppression,hypoxic stress,chronic inflammation),leading to the coagulation of phlegm,stasis,fire,and toxins into cancer toxin.Based on this framework,a core therapeutic principle of"dispersing latent yang and intercepting malignant transition in stages"was established,providing a new paradigm for TCM-based early intervention against PN malignancy.

Objective:To compare the effect of high frequency oscillatory ventilation (HFOV) and conventional mechanical ventilation (CMV) in the treatment of pediatric acute respiratory distress syndrome (ARDS).Methods:A prospective randomized controlled study was conducted on ARDS children treated with mechanical ventilation in the Intensive Care Unit (ICU) of Children′s Hospital, Capital Institute of Pediatric from January 2017 to December 2018.They were randomly (computer digital method) divided into HFOV group and CMV group.The basic data and clinical indicators, such as pediatric critical illness scores, oxygenation index (OI), blood gas, mechanical ventilation time, ventilator parameters, ICU hospitalization time, complications, prognosis, dynamic changes of inflammatory factors, use of sedative muscle relaxants and vasoactive drugs, were recorded.SPSS 22.0 software was used to analyze the data.The Mann Whitney U test was used for inter-group comparison.The χ2 test was adopted for the comparison of counting data. Results:A total of 45 children were included in the analysis.There were 21 cases in the HFOV group and 24 cases in the CMV group.Moderate and severe ARDS was detected in 34 cases, including 16 cases in the HFOV group and 18 cases in the CMV group.Compared with those in the CMV group, the levels of OI-24 h and OI-48 h in the HFOV group were significantly lower [7.4 (5.9, 8.6) vs.9.0 (6.7, 13.6), P=0.018] and [5.9 (5.2, 8.5) vs.9.2 (7.4, 12.4), P=0.001].The levels of OI-6 h [8.2(6.5, 10.0) vs.10.5(8.2, 13.0), P=0.037], OI-12 h[7.8(6.5, 9.0) vs.9.8(8.0, 12.8), P=0.009], OI-24 h [7.7(6.4, 8.6) vs.10.1(8.7, 15.5), P<0.001], OI-48 h [6.0(5.3, 8.6) vs.10.7(8.8, 13.1), P<0.001] and OI-72 h [5.8(5.0, 8.6) vs. 8.0(6.6, 10.6), P=0.031] in children with moderate to severe ARDS of the HFOV group were significantly lower than those of the CMV group.There were no significant differences in ICU hospitalization time, invasive mechanical ventilation time, total mechanical ventilation time, 28-day prognosis, vasoactive drugs, muscle relaxants, blood purification, fluid balance, inflammatory factors, intracranial hemorrhage and pneumothorax between the 2 groups. Conclusions:This study confirms that HFOV can improve the oxygenation level in pediatric patients with ARDS more rapidly than CMV.HFOV does not increase the incidence of complications such as pneumothorax and intracranial hemorrhage, and the use of vasoactive drugs and muscle relaxants, showing safety in clinical application.

Objective:To investigate the protective effects of an anti-inflammatory mixture on acute lung injury (ALI) induced by sepsis in rats, as well as its possible mechanisms.Methods:A total of 40 Sprague-Dawley (SD) rats were randomly divided into the sham group, septic ALI model group (model group), 3-methyladenine (3-MA) control group, and anti-inflammatory mixture pretreatment group, with 10 rats in each group. Cecal ligation and perforation (CLP) was performed to reproduce a septic ALI model. The rats in the sham group only underwent opening and closing the abdomen without perforation and ligation. Both groups were given saline gavage and intraperitoneal injection for 3 consecutive days before surgery. The 3-MA control group was given intraperitoneal injection of saline and autophagy inhibitor 3-MA 15 mg/kg for 3 consecutive days before modeling. The anti-inflammatory mixture pretreatment group was given 8.8 mL/kg of anti-inflammatory mixture by gavage [the composition of anti-inflammatory mixture: rhubarb 15 g (after the next), coptis chinensis 15 g, baical skullcap root 12 g, magnoliae cortex 12 g, dahurian patrinia herb 30 g] and saline intraperitoneal injection for 3 consecutive days before modeling. The rats in each group were anesthetized 24 hours after surgery and died due to abdominal aortic blood collection. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of serum inflammatory cytokines interleukins (IL-1β and IL-6). Lung tissue was taken and then the bronchoalveolar lavage fluid (BALF) was collected, and the levels of IL-1β and IL-6 were detected by ELISA. Lung wet/dry weight (W/D) ratio was measured. After hematoxylin-eosin (HE) staining, the histopathological changes of the lungs were observed under light microscopy. Western blotting was used to detect the expression of autophagy markers microtubule-associated protein 1 light chain 3-Ⅱ/Ⅰ (LC3-Ⅱ/Ⅰ) and Beclin-1 protein in lung tissue. Autophagosomes in lung tissue were observed with transmission electron microscopy.Results:Compared with the sham group, the rats in the model group exhibited severe destruction of lung tissue structure, with significant infiltration of inflammatory cells, the lung W/D ratio and the levels of IL-1β and IL-6 in serum and BALF were significantly increased, the expressions of LC3-Ⅱ/Ⅰ and Beclin-1 protein were down-regulated, the autophagosomes were more. The rats in the 3-MA control group exhibited more severe lung tissue injury as compared with the model group, the lung W/D ratio and the levels of inflammatory cytokines in serum and BALF were further increased, the expressions of LC3-Ⅱ/Ⅰ and Beclin-1 protein still showed a decrease tendency as compared with the sham group, and the autophagosomes were less than that in the model group. Compared with the model group, the anti-inflammatory mixture pretreatment group showed milder lung tissue injury with a minimal amount of inflammatory cell infiltration, the lung W/D ratio was significantly reduced (7.07±1.02 vs. 11.33±1.85, P < 0.05), the levels of IL-1β and IL-6 in both serum and BALF were significantly decreased [IL-1β (ng/L): 26.04±3.86 vs. 40.83±5.46 in serum, 17.75±2.02 vs. 26.86±4.32 in BALF; IL-6 (ng/L): 91.28±10.15 vs. 129.44±13.05 in serum, 76.06±7.51 vs. 120.91±7.47 in BALF, all P < 0.05], and the ratio of LC3-Ⅱ/Ⅰ and Beclin-1 protein expression were significantly increased [LC3-Ⅱ/Ⅰ ratio: 1.23±0.02 vs. 0.60±0.02, Beclin-1 protein (Beclin-1/GAPDH): 2.37±0.33 vs. 0.62±0.05, both P < 0.05]. Furthermore, an increase in the number of autophagosomes was observed. Conclusion:The anti-inflammatory mixture improves lung injury in rats with sepsis induced by CLP and reduce inflammation levels, potentially through upregulation of Beclin-1-mediated autophagy.

This study compared the effects on bone metabolism and morphology of pathological obesity induced by excessive fat intake in a non-hibernator (mice) versus healthy obesity due to pre-hibernation fattening in a hibernator (ground squirrels). Kunming mice were fed a high-fat diet to provide a model of pathological obesity (OB group). Daurian ground squirrels fattened naturally in their pre-hibernation season (PRE group) were used as a healthy obesity model. Micro-computed tomography (micro-CT) and three-point bending tests were used to determine the microstructure and mechanical properties of bone. Western blots were used to analyze protein expression levels related to bone metabolism (Runt-related transcription factor 2 (RunX2), osteocalcin (OCN), alkaline phosphatase (ALP), osteoprotegerin (OPG), receptor activator of nuclear factor-‍κB ligand (RANKL), cathepsin K, matrix metallopeptidase 9 (MMP9), patched protein homolog 1 (Ptch1), phosphorylated β‍-‍catenin (P‍-‍β‍-‍catenin), and glycogen synthase kinase-3β (GSK-3β)). Compared with controls, there was no obvious bone loss in the OB mice, and the stiffness of the femur was increased significantly. Compared with summer active squirrels, bone formation was enhanced but the mechanical properties did not change in the PRE group squirrels. In OB mice, western blots showed significantly increased expression levels of all proteins except RunX2, OPG, and Ptch1. PRE ground squirrels showed significantly increased expression of most proteins except OCN and Ptch1, which decreased significantly, and P‍-‍β‍-‍catenin and OPG, which did not change. In conclusion, for non-hibernating mice, moderate obesity had a certain protective effect on bones, demonstrating two-way regulation, increasing both bone loss and bone formation. For pre-hibernating ground squirrels, the healthy obesity acquired before hibernation had a positive effect on the microstructure of bones, and also enhanced the expression levels of proteins related to bone formation, bone resorption, and Wnt signaling.
Mice ; Animals ; Hibernation ; Core Binding Factor Alpha 1 Subunit/metabolism* ; Glycogen Synthase Kinase 3 beta/metabolism* ; Diet, High-Fat ; X-Ray Microtomography ; Sciuridae/metabolism* ; Obesity

Objective:To investigate the clinical features and risk factors of left ventricular systolic dysfunction in children with septic shock.Methods:A retrospective analysis was performed on the clinical data of children diagnosed with septic shock in the Department of Critical Care Medicine of Children’s Hospital, Capital Institute of Pediatrics from February 2016 to June 2021. Inclusion criteria: (1) patients met the diagnostic criteria of septic shock; (2) Cardiac ultrasound was performed within 48 h after shock treatment and was dynamically monitored during shock treatment. Exclusion criteria: (1) Previous history of chronic cardiac insufficiency, cardiomyopathy, or organic heart disease; (2) patients with acute cerebral infarction, cerebral hemorrhage and necrotizing encephalopathy; (3) congenital genetic metabolic diseases; and (4) incomplete information. Left ventricular systolic dysfunction was defined as a left ventricular ejection fraction (LVEF) <50% and a ≥10% decrease in the patient’s initial LVEF assessed on admission. Patients with left ventricular systolic dysfunction and without left ventricular systolic dysfunction were compared. Comparisons between groups were performed with unpaired Student’s t test, or Mann-Whitney U test, or chi-square test. Multivariate logistic regression analysis was used to analyze the correlation factors of left ventricular systolic dysfunction. Results:The incidence of left ventricular systolic dysfunction in children with septic shock was 30.0% with the lowest LVEF of (42±8)%. Left ventricular systolic dysfunction occurred on (2.4±1.3) days after shock onset, and the LVEF returned to normal on (6.7±3.3) days. Hematogenous infection was more frequent (77.8% vs. 40.5%, P=0.018), ventilator application (83.3% vs. 50.0%, P=0.033) and inotropes and vasopressor drugs (100.0% vs. 64.3%, P=0.009) were used more frequently in patients with left ventricular systolic dysfunction(n =18), compared with patients without left ventricular systolic dysfunction(n =42). Patients with left ventricular systolic dysfunction had a lower LVEF [(42±8)% vs. (67±5)%, P<0.001], a lower pediatric critical illness score [(64±13) vs. (76±14), P=0.003], a lower resuscitation success rate at 6 h (38.9% vs. 73.8%, P=0.010), a higher lactate at admission [3.80 (3.15, 5.88) mmol/L vs. 2.70 (1.85, 3.80) mmol/L, P=0.001) and a higher 28-d mortality (38.9% vs. 12.8%, P=0.025) compared with patients without left ventricular systolic dysfunction. Hematogenic infection ( OR=7.358, 95% CI: 1.198~45.197, P=0.031) and lactate at admission ( OR=1.743, 95% CI: 1.041~2.917, P=0.034) were independent risk factors for left ventricular systolic dysfunction. Conclusions:The incidence of left ventricular systolic dysfunction in children with septic shock was 30.0%. Left ventricular systolic dysfunction usually occurred on (2.4±1.3) days after shock onset and resolved within 7 days, which was associated with 28-d mortality. Hematogenous infection and high lactate value were independent risk factors for left ventricular systolic dysfunction.

AIM: To investigate the effect of extracorporeal membrane oxygenation (ECMO) on the pharmacokinetics/pharmacodynamics (PK/PD) of daptomycin in critically ill patients. METHODS: Twenty four patients with severe infection in our hospital were randomly selected and divided into ECMO group and non ECMO group. They were intravenously injected with daptomycin 500 mg qd. After the drug reached the stability statement, venous blood was collected at different time points before and after the infusion. The plasma drug concentration was measured and the pharmacokinetic parameters were calculated. The probability target acquisition (PTA) and the cumulative fraction response (CFR) were calculated by Monte Carlo simulation. RESULTS: After dosing, the main pharmacokinetic parameters in ECMO and non-ECMO group were calculated and listed as follows: C

Objective:To investigate the value of synthetic MRI for evaluating lumbar intervertebral disc degeneration.Methods:A total of 414 lumbar intervertebral discs from 85 patients were included prospectively from September 2018 to February 2019 in First Affiliated Hospital of China Medical University. The T 1, T 2 and proton density (PD) mapping were generated from synthetic MRI. Two doctors measured the T 1, T 2 and PD values to evaluate intraobserver agreement by using ICC. For Pfirrmann grade comparisons, the variables with normal distribution were analyzed with the one-way analysis of variance, whereas those with skewed distribution were analyzed with the Kruskal-Wallis H test. Furthermore, the ROC curves were used on significant parameters to evaluate their diagnostic efficacy. The Z test was used to compare the differences of area under the ROC curves (AUC). Results:The color of the quantitative mapping changed along with the increase of the Pfirrmann grade of the intervertebral discs, which corresponded to the decrease of the T 2WI signal intensity. The ICC values of the quantitative values of nucleus pulposus indicated excellent agreement (ICC>0.900), followed by anterior annulus fibrosus (ICC>0.700) and then the posterior annulus fibrosus (ICC>0.600). The results of the adjacent Pfirrmann grade comparisons were as follows: between Pfirrmann grade Ⅰ and Ⅱ, the differences of T 2 and PD values of nucleus pulposus were statistically significant ( P=0.004 and P<0.001, respectively); between Pfirrmann grade Ⅱ and Ⅲ, the differences of T 1, T 2 and PD values of nucleus pulposus were statistically significant (all P<0.001); between Pfirrmann grade Ⅲ to Ⅳ, the T 1, T 2 and PD values of nucleus pulposus (all P<0.001) and the T 1 and PD values of posterior annulus fibrosus ( P=0.025, P<0.001, respectively) had statistically significant differences; between Pfirrmann grade Ⅳ to Ⅴ, the difference of T 2 values of nucleus pulposus were statistically significant ( P=0.031). The AUC of T 2 values of nucleus pulposus between Pfirrmann grade Ⅱ to Ⅲ and grade Ⅳ to V were higher than those of the PD values ( Z=2.443, 3.591 and P=0.015,<0.001). Conclusions:Synthetic MRI can quantitatively evaluate lumbar disc degeneration, in which the T 2 value of nucleus pulposus may be the most effective parameter with high repeatability.

Objective: To investigate the regulation of emodin on microRNA expressions in mouse model with sepsis by GeneChip microRNA array. Methods: Forty two c57 mice were randomly (random number) divided into 3 groups: sham operation group (sham group, n=14),sepsis group(n=14) and emodin group (n=14). The sepsis model of the mouse was subjected to cecal ligation and puncture (CLP). Mice in emodin group received intraperitoneal injection of emodin (40 mg/kg) half an hour before operation and every 12 hours after CLP. All mice were sacrificed 48 h after surgery and part of the ileum were removed for intestine tissue stained with hematoxylin eosin. The levels of tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6) and intestinal fatty acid binding protein (I-FABP) in peripheral blood were measured by enzyme-linked immunosorbent assay (ELISA). Total RNA of ileum tissues was extracted from the sepsis group and emodin group, and then subjected to miRNA microarray. The results of microarray were further verified by quantitative real-time PCR (qRT-PCR). Target genes of differentially expressed miRNAs were predicted and subjected to gene ontology (GO) and KEGG pathway enrichment analysis. Data of multi-groups were analyzed by one way variance (ANOVA) and inter-group comparisons were made by SNK-q tests. Mann-Whitney U test was used when homogeneity of variance were not met. The value of P<0.05 was considered statistically significant. Results: Compared to the sepsis group, the levels of serum TNF-α, IL-6 and I-FABP in the emodin group were decreased significantly. MiRNA microarray showed that 23 miRNAs were differentially expressed in the emodin group as compared to the sepsis group, among which 17 miRNAs were up-regulated and 6 miRNAs were down-regulated. qRT-PCR results were consistent with miRNA array data. Target genes of 10 selected miRNAs were predicted and subjected to bioinformatic analysis. A total of 3 410 target genes were significantly enriched in 2 072 GO biological process terms, 246 GO cellular component items and 277 GO molecular function terms. Moreover, KEGG pathway analysis showed that these differential miRNAs were involved in the regulation of PI3K-Akt signaling pathway, MAPK signaling pathway, and TNF signaling pathway. Conclusions Emodin can regulate the expression of multiple microRNAs, and play an important role in protecting the intestinal mucosal barrier via a variety of targets and pathways.