[A case of interstitial lung and liver disease caused by MARS1 gene mutation]. / MARS1åŸºå› å˜å¼‚æ‰€è‡´é—´è´¨æ€§è‚ºç— åŠè‚ç— 1例.

The patient is a female infant, 4 months and 9 days old, who was admitted to the hospital due to recurrent fever, cough, and hepatomegaly for over a month. The patient was a healthy full-term infant with a normal birth history. At 2 months and 22 days after birth, she developed recurrent fever, cough, and respiratory distress. Chest imaging revealed diffuse bilateral lung lesions, and fiberoptic bronchoscopy showed interstitial changes in both lungs. These suggested the presence of interstitial lung disease. The patient also presented with hepatomegaly, anemia, hyperlipidemia, hypothyroidism, and malnutrition. Genetic testing indicated compound heterozygous variations in the MARS1 gene. This mutation can cause interstitial lung and liver disease, which is a severe rare disorder that typically manifests in infancy or early childhood. It is inherited in an autosomal recessive manner and characterized by early-onset respiratory insufficiency and liver disease in infants or young children. Since its first reported case in 2013, as of June 2023, only 38 related cases have been reported worldwide. This article reports the multidisciplinary diagnosis and treatment of interstitial lung and liver disease in an infant caused by MARS1 gene mutation.

Autophagy impairment is involved in midazolam-induced lipid droplet accumulation and consequent phagocytosis decrease in BV2 cells.

An increasing number of experimental and clinical observation suggest that the use of anaesthetics is closely associated with postoperative central nervous system (CNS) complications, such as delirium and cognitive dysfunction. Brain energy rescue is an emerging therapeutic strategy for central nervous system disease (CNSDs). However, the effect of anaesthetics on nerve cell energy utilisation, especially microglia, and its potential effects on cell function still unclear. Elucidating the effects of anaesthetics on lipid droplets, which are specific lipid storage organs, and phagocytosis of microglia is crucial to discover a new therapeutic concept for postoperative CNS complications. Here, we studied the effects of the commonly used anaesthetic midazolam on lipid droplets and phagocytosis in immortalised microglial BV2 cells. Lipid droplets were assessed by flow cytometry and triglyceride quantification. The phagocytosis of BV2 cells was evaluated by detecting their phagocytosis by latex beads. Additionally, the autophagy of BV2 cells was evaluated by western blot and observation under microscopy. Our results showed that midazolam caused lipid droplet accumulation and reduced phagocytosis in BV2 cells, and inhibition of lipid droplet accumulation partially restored phagocytosis. Furthermore, midazolam blocks autophagic degradation by increasing phosphorylated TFEB in BV2 cells, inhibition of midazolam-increased phosphorylated TFEB might contribute to the improvement of autophagic flux by rapamycin. Moreover, promoting autophagy reverse the lipid droplet accumulation and phagocytosis decrease. This study suggests autophagy is a target for attenuating lipid droplet accumulation, normal degradation of lipid droplets is important for maintaining microglia phagocytosis and attenuating the side effects of midazolam on the CNS.

Submucosal Enhancing Stripe as a Contrast Material-enhanced MRI-based Imaging Feature for the Differentiation of Stage T0-T1 from Early T2 Rectal Cancers.

Background Accurate differentiation of stage T0-T1 rectal tumors from stage T2 rectal tumors facilitates the selection of appropriate surgical treatment. MRI is a recommended technique for local staging, but its ability to distinguish T1 from T2 tumors is poor. Purpose To explore the value of a submucosal enhancing stripe (SES), an uninterrupted enhancing band between the rectal tumor and the muscular layer on contrast material-enhanced T1-weighted images, as a potential imaging feature to differentiate T0-T1 from T2 rectal tumors. Materials and Methods This retrospective study included patients with pT0-T1 and pT2 rectal tumors who underwent pretreatment MRI and rectal tumor resection between January 2012 and November 2019. Two radiologists independently evaluated tumor characteristics (SES; status of muscularis propria [SMP]; and tumor shape, location, and size) at MRI. The associations of clinical and imaging characteristics with stage T0-T1 or T2 tumors were assessed, ß values were calculated, and predictive models were built. The diagnostic accuracies for the differentiation of T0-T1 tumors from T2 tumors with SES and SMP were compared. Results Data from 431 patients (mean age, 60 years ± 10 [standard deviation]; 261 men) were evaluated. SES (ß = 3.9; 95% CI: 3.1, 4.7; P < .001), SMP (ß = 1.3; 95% CI: 0.7, 1.9; P < .001), and carpetlike shape (ß = 1.6; 95% CI: 0.5, 2.8; P = .01) were independent factors distinguishing T0-T1 tumors from T2 tumors. The diagnostic accuracy was 87% (95% CI: 84, 90; 376 of 431) for SES and 67% (95% CI: 63, 72; 290 of 431) for SMP (P < .001). Conclusion Submucosal enhancing stripe (SES) at contrasted-enhanced MRI, status of muscularis propria (SMP) on T2-weighted images, and tumor shape can serve as independent imaging features to differentiate stage T0-T1 rectal tumors from stage T2 rectal tumors. Moreover, SES is a more accurate feature than is SMP. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Turkbey in this issue.

Antibacterial Effect and Mode of Action of Flavonoids From Licorice Against Methicillin-Resistant Staphylococcus aureus.

Staphylococcus aureus is a bacterial pathogen that causes food poisoning, various infections, and sepsis. Effective strategies and new drugs are needed to control S. aureus associated infections due to the emergence and rapid dissemination of antibiotic resistance. In the present study, the antibacterial activity, potential mode of action, and applications of flavonoids from licorice were investigated. Here, we showed that glabrol, licochalcone A, licochalcone C, and licochalcone E displayed high efficiency against methicillin-resistant Staphylococcus aureus (MRSA). Glabrol, licochalcone A, licochalcone C, and licochalcone E exhibited low cytotoxicity without hemolytic activity based on safety evaluation. Glabrol displayed rapid bactericidal activity with low levels of resistance development in vitro. Meanwhile, glabrol rapidly increased bacterial membrane permeability and dissipated the proton move force. Furthermore, we found that peptidoglycan, phosphatidylglycerol, and cardiolipin inhibited the antibacterial activity of glabrol. Molecular docking showed that glabrol binds to phosphatidylglycerol and cardiolipin through the formation of hydrogen bonds. Lastly, glabrol showed antibacterial activity against MRSA in both in vivo and in vitro models. Altogether, these results suggest that glabrol is a promising lead compound for the design of membrane-active antibacterial agents against MRSA and can be used as a disinfectant candidate as well.

EVALUATION OF THE ACUTE AND SUBCHRONIC TOXICITY OF Aster tataricus L. F.

BACKGROUND: Aster tataricus L. f. is used as a traditional Chinese drug to relieve cough and asthma symptoms and to eliminate phlegm. However, Aster tataricus L. f. possesses toxicity, and little systematic research has been conducted on its toxic effects in the laboratory. METHODS AND MATERIALS: The acute group was administered 75% alcohol extract of Aster tataricus L. f. in a single dose. A subchronic toxicity study was performed via daily oral administration of Aster tataricus L. f. at a dose of 0.34 g/kg body weight in SD rats. The rats were divided into six groups: a petroleum ether extract (PEA) group, an ethyl acetate extract (EEA) group, an n-butyl alcohol extract (NEA) group, a remaining lower aqueous phases (REA) group, a 75% alcohol extract (AEA) group and a control group. Quantitative measurements of cytokines were obtained by fluorescence with a laser scanner using a Cy3 equivalent dye. RESULTS: The LD50 of the 75% alcohol extract of Aster tataricus L. f. was 15.74 g/kg bw. In the subchronic toxicity study, no significant differences were observed among groups in relative organ weights, urine traits, liver antioxidase levels, or cytokine levels. However, significant sporadic differences were observed in body weight gains, haematology indices, biochemistry values, and histopathology features in PEA, EEA group. In addition, sporadic changes in other groups in measures such as WBC, MCHC, CK, ALP, AST, ALT, LDH, T-BIL, LDL-C, HDL-C, and TC were observed. CONCLUSION: The toxicity study showed that Aster tataricus L. f. can produce toxic effects, mainly on the liver; much less on the heart. The LD50 was 15.74 g/kg BW in mice, and the subchronic toxicity study, used a dosage of 0.34 g/kg/d.BW, showed that the toxic components of Aster tataricus L. f. were mainly concentrated in the petroleum ether fraction, followed by the ethyl acetate fraction, the n-butyl alcohol fraction, the lower aqueous phase and the 75% ethanol extracts. Abbreviations: PEA, petroleum ether extract of Aster tataricus L. f.; EEA, ethyl acetate extract of Aster tataricus L. f.; NEA: n-butyl alcohol extract of Aster tataricus L. f.; REA: lower aqueous phases of Aster tataricus L. f.; AEA, 75% alcohol extract of Aster tataricus L. f.; WBC, white blood cell; RBC, red blood cell, PLT, platelet; HCT, haematocrit; MCV, mean corpuscular volume; HGB, haemoglobin; MCH, mean corpuscular haemoglobin; MCHC, mean corpuscular haemoglobin concentration; CREA, creatinine; LDH, lactate dehydrogenase; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; T-BIL, total bilirubin; ALT, alanine aminotransferase; ALP, alkaline phosphatase; AST, aspartate aminotransferase; TP, total protein; ALB, albumin; Glu, glucose; TC, total cholesterol; TG, triglycerides; CK, creatine kinase; GSH, Glutathione; MDA, malondialdehyde; T-SOD, total superoxide dismutase; TNF, tumour necrosis factor; IFN, interferon; MCP, monocyte chemotactic protein C.

[Research on the features of DNA damage in nasopharyngeal carcinoma patients of normal constitution and abnormal constitution and in high-risk population of nasopharyngeal carcinoma].

OBJECTIVE: To explore the features of DNA damage in nasopharyngeal carcinoma (NPC) patients of normal constitution and abnormal constitution and in high-risk population of NPC. METHODS: Using single cell gel electrophoresis technique, the DNA damage of peripheral blood lymphocytes was detected in 28 healthy subjects, 27 in high-risk population of NPC, and 13 NPC patients at their first visits. The DNA damage was detected in the populations of normal constitution and of abnormal constitution. The tail length, the tail moment, and the tail DNA% were taken as the indices of DNA damage. RESULTS: The tail length was (35.77 +/- 4.22) microm, the tail moment was (8.10 +/- 1.63) microm, and the tail DNA% was 57.48% +/- 4.63% in NPC patients. They were (15.25 +/- 4.15) microm, (5.01 +/- 1.92) microm, and 31.99% +/- 4. 11% in high-risk population of NPC. They were (14.31 +/- 3.64) microm, (4. 37 +/- 1.80) microm, and 29. 89% +/- 3. 15% in healthy subjects. There was statistical difference in the three indices among the three populations (P <0.05). In all the three populations, more DNA damage existed in those of abnormal constitution than in those of normal constitution (P <0.05). CONCLUSIONS: Obvious instability of genetic materials exists in NPC patients, manifested as severe DNA damage of lymphocytes. In all the three populations, more DNA damage existed in those of abnormal constitution than in those of normal constitution.