The current treatment of glioma is facing drug resistance,which limits the efficacy of traditional chemotherapy drugs.This study aims to explore the potential mechanisms of the trifluoromethylquinazoline compound(KZL204)against glioma.Through the Cell Counting Kit-8(CCK-8)assay,we found that KZL204 significantly inhibits the growth of drug-resistant cancer cells,with a 48-hour half-maximal inhibitory concentration(IC50)of 3.63±0.38 μmol/L,which is significantly better than the positive control drug temozolomide(TMZ)(IC50 value of 81.67±5.49 μmol/L).Additionally,flow cytometry analysis showed that KZL204 treatment significantly increased the apoptosis rate of drug-resistant tumor cells and arrested the cell cycle at the G2/M phase.At the same time,the Transwell assay confirmed the inhibitory effect of KZL204 on the migration and invasion of drug-resistant cancer cells.Transcriptome analysis revealed 2 435 differentially expressed genes in drug-resistant cancer cells treated with KZL204,of which 1 320 were upregulated,and 1 115 were downregulated.KEGG and GO enrichment analysis showed that these differential genes were significantly enriched in apoptosis-related signaling pathways.Further bioinformatics prediction and Venn diagram analysis identified 35 potential core targets,with the PI3K-AKT signaling pathway being the most significant among the differentially expressed genes.Quantitative real-time PCR(RT-qPCR)experiments confirmed the downregulating effects of KZL204 on genes such as CREB3L1,CSF1,CXCL5,BCL3,and the upregulating effects on genes like FOS,LT A,PTGS2,MAP2K3.Immunoblotting experiments at the protein level also confirmed the impact of KZL204 on the expression of apoptotic proteins,including the upregulation of Bax,cleaved Caspase-3 protein,and the downregulation ofAKT,Bcl-2,Caspase-3,and Caspase-8 protein expression.In summary,KZL204 significantly inhibits the growth and metastasis of drug-resistant glioblastoma and induces apoptosis and cell cycle arrest by regulating the PI3K-AKT and apoptosis-related signaling pathways,demonstrating its potential as a candidate drug against drug-resistant glioma.

Objective:To explore the clinical correlation and prognostic value of the Albumin-Bilirubin(ALBI)score in children with secondary hemophagocytic syndrome(sHLH).Methods:A retrospective analysis was conducted on the data of children's sHLH cases clearly diagnosed in the Affiliated Hospital of Zunyi Medical University from January 2012 to March 2023.Survival analysis was conducted according to the ALBI classification.Spearman correlation analysis was conducted between the ALBI score and clinical indicators.The Receiver Operating Characteristic(ROC)curve was used to evaluate the ALBI score,select the best cutoff value,and evaluate the accuracy of prognostic prediction value.Kaplan-Meier method was used to draw the survival curve.Log-rank method was used to compare the differences of survival curve between groups.Cox regression was used for prognostic analysis and restricted cubic spline curves used to calculate the relationship between ALBI scores and the risk of death in children with sHLH.Results:A total of 128 children with sHLH were included in this study,with a median age of 38(13.25,84)months.There were 70 males(54.69％)and 58 females(45.31％).The survival analysis results of ALBI grading showed that the survival rate of HLH patients with ALBI grade 3 was significantly lower than those with ALBI grades 1 and 2.Spearman correlation analysis results showed that ALBI score was positively correlated with splenomegaly,respiratory failure,disseminated intravascular coagulation(DIC),pulmonary hemorrhage,gastrointestinal hemorrhage,central nervous system involvement,ALT,AST,TG,LDH,PT,APTT,and SF(the correlation coefficients are:r=0.181,0.362,0.332,0.221,0.351,0.347,0.391,0.563,0.180,0.448,0.483,0.37,0.356),and was negatively correlated with HB,PLT,and FIB(the correlation coefficients are:r=-0.321,-0.316,-0.423),but was not significantly correlated with EBV infection,fungal infection,hepatomegaly,and ANC(P＞0.05).Using the ROC curve,the cutoff value of ALBI was-1.76.Single factor Cox regression analysis results showed that HB＜90 g/L,ALT ≥ 80 U/L,AST≥200 U/L,LDH ≥1 000 U/L,PT ≥20 s,APTT≥40 s,FIB＜1.5 g/L,ALBI ≥-1.76,combined pulmonary hemorrhage,DIC,central nervous system involvement,gastrointestinal bleeding,and not using blood purification may be the prognostic risk factors for children with sHLH(P＜0.05).Multivariate Cox regression results showed that FIB＜1.5 g/L(HR=2.119,95％CI:1.028-4.368),ALBI≥-1.76(HR=2.452,95％CI:1.233-4.875),and central nervous system involvement(HR=4.674,95％CI:2.486-8.789)were independent risk factors affecting prognosis,while blood purification(HR=0.306,95％CI:0.153-0.612)was an independent protective factor for prognosis.The application of restricted cubic splines shows that the risk of death increases with the increase of ALBI score.The area under the ROC curve(AUC)of the ALBI score for predicting the risk of 1-week,2-week,4-week,and overall mortality were 0.825,0.807,0.700,and 0.693,respectively,indicating good predictive performance for early mortality risk.According to subgroup analysis results of clinical manifestations,compared with the ALBI＜-1.76 group,ALBI≥-1.76 was associated with age ≤2 years,EBV infection,HLH-1994/2004 treatment,concomitant respiratory failure,and ANC≤1.0 × 109/L,HB＜90 g/L,PLT＜100 × 109/L,TG≥3.0 mmol/L,LDH ≥ 1 000 U/L,APTT≥40 s,and FIB＜1.5 g/L(P＜0.05).Conclusion:The ALBI score is related to the clinical characteristics and laboratory indicators of sHLH,and can be used as a beneficial indicator for assessing the prognostic risk of sHLH in children.It has good accuracy and clinical application value in predicting the prognosis of sHLH in children.

Background: and Purpose This study aimed to investigate early changes in interstitial fluid (ISF) flow in patients with severe carotid stenosis after carotid angioplasty and stenting (CAS). Methods: We prospectively recruited participants with carotid stenosis ≥80% undergoing CAS at our institute between October 2019 and March 2023. Magnetic resonance imaging (MRI), including diffusion tensor imaging (DTI), and the Mini-Mental State Examination (MMSE) were performed 3 days before CAS. MRI with DTI and MMSE were conducted within 24 hours and 2 months after CAS, respectively. The diffusion tensor image analysis along the perivascular space (DTI-ALPS) index was calculated from the DTI data to determine the ISF status. Increments were defined as the ratio of the difference between post- and preprocedural values to preprocedural values. Results: In total, 102 participants (age: 67.1±8.9 years; stenosis: 89.5%±5.7%) with longitudinal data were evaluated. The DTI-ALPS index increased after CAS (0.85±0.15; 0.85 [0.22] vs. 0.86±0.14; 0.86 [0.21]; P=0.022), as did the MMSE score (25.9±3.7; 24.0 [4.0] vs. 26.9±3.4; 26.0 [3.0]; P<0.001). Positive correlations between increments in the DTI-ALPS index and MMSE score were found in all patients (rs=0.468; P<0.001). Conclusion An increased 24-hour post-CAS DTI-ALPS index suggests early improvement in ISF flow efficiency. The positive correlation between the 24-hour DTI-ALPS index and 2-month MMSE score increments suggests that early ISF flow improvement may contribute to long-term cognitive improvement after CAS.

Humans ; Diabetes Mellitus ; Ketosis ; Magnetic Resonance Imaging

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

Humans ; Mississippi/epidemiology* ; Influenza, Human/epidemiology* ; Meteorological Concepts ; Virus Diseases

Objective To compare the effectiveness of loop-mediated isothermal amplification (LAMP) assay and microscopic examinations for detection of Schistosoma japonicum infections in Oncomelania hupensis in transmission-interrupted regions, so as to provide insights into the optimization of snail surveillance tools in these regions. Methods Four hilly schistosomiasis-endemic villages where transmission interruption was achieved were selected in Heqing County of Yunnan Province as the study villages, including Xinzhuang and Gule villages in hilly regions and Lianyi and Yitou villages in dam regions. Snail survey was performed by means of systematic sampling combined with environmental sampling in July 2018. All captured snails were identified for S. japonicum infections using microscopy. In addition, 10 to 20 snails were randomly sampled from each snail habitat following microscopy, numbered according to environments and subjected to LAMP assay. The positive rate of settings with S. japonicum-infected snails was compared among villages. Results A total of 7 949 living snails were captured from 83 snail habitats in 4 villages, and no S. japonicum infection was detected in snails. There were 226 mixed samples containing 1 786 snails subjected to LAMP assay, and positive LAMP assay was found in 3 mixed samples from 3 snail habitats in 2 dam villages. The positive rates of settings with S. japonicum-infected snails were comparable between Lianyi Village (one setting) and Yitou Village (2 set tings) (5.89% vs. 14.29%, P = 0.344). However, the overall positive rate of settings with S. japonicum-infected snails was significantly higher in dam villages (9.67%, 3/31) than in hilly villages (0) (P = 0.048). Conclusions LAMP assay is more sensitive to detect S. japonicum infections in O. hupensis than conventional microcopy method, which may serve as a supplementary method for detection of S. japonicum infections in O. hupensis in high-risk snail habitats in hilly transmission-interrupted regions.

Arsenic is a potent toxic heavy metal found in the environment that can causes health problems, including liver disease in humans and animals. Chronic exposure to arsenic remains an environmental health problem worldwide, affecting hundreds of millions of people. Although the oxidative stress and apoptosis induced by arsenic have been confirmed, the underlying mechanism of apoptosis has not been fully elucidated. The purpose of this study is to investigate whether sodium arsenite (SA)induced liver toxicity is related to the regulation of DNA replication and repair pathways. The results of MTT and microscopy showed that SA has an inhibitory effect on the proliferation of human hepatocytes (L02), and this effect is time and concentration dependent. Flow cytometry detected the effects of different concentrations of SA on L02 cells. Compared with the control group, high concentrations of SA significantly affected the L02 cell cycle. In addition, RNA sequencing results showed that the differentially expressed genes in cells after SA treatment were concentrated in the DNA replication process and repair pathways. The effect of SA treatment on the expression of human RECQ DNA helicase and repair genes was further confirmed by Western blot and real-time quantitative PCR. In vitro study showed that SA treatment inhibited cell proliferation, and induced apoptosis as well as DNA damage and cell cycle arrest of human liver cell L02. Collectively, these results indicate that arsenic poisoning is related to the regulation of DNA replication and repair pathways, which provides insight for understanding the molecular mechanism of arsenic poisoning.

A method was established for content determination of two kinds of phenolic acids, including rosmarinic acid)(RA) and caffeic acid(CA), and six kinds of flavonoids including scutellarein-7-O-diglucuronide(SDG), luteolin-7-O-diglucuronide(LDG), apigenin-7-O-diglucuronide(ADG), scutellarin-7-O-glucuronide(SG), luteolin-7-O-glucuronide(LG), and apigenin-7-O-glucuronide(AG) in Perilla frutescens leaves. The content of eight chemical components was measured based on ten P. frutescens germplasms of different chemotypes of volatile oil, different cultivated years, and different harvesting periods. The results showed that there was a great difference between the two kinds of constituents of different germplasms. The total content of the two phenolic acids was 2.24-34.44 mg·g~(-1), and the total content of the six flavonoids was 11.55-34.71 mg·g~(-1). Then according to content from most to least, the order of each component was RA(2.13-33.97 mg·g~(-1)), LDG(1.31-14.80 mg·g~(-1)), SG(1.97-8.45 mg·g~(-1)), ADG(2.68-7.60 mg·g~(-1)), SDG(1.16-5.87 mg·g~(-1)), LG(0.78-1.91 mg·g~(-1)), AG(0.56-1.00 mg·g~(-1)), and CA(0.11-0.68 mg·g~(-1)). The chemical contents of the 5 PA-type germplasms in 2017 were mostly higher than those in 2018 showing a large variation with the cultivation years. These contents of two kinds of phenolic acids of 9 germplasms fluctuated with the harvesting time. The content decreased before early flower spike(the 3~(rd) to 18~(th) in August) at first and began to increase in flowering and fruiting period(the 18~(th) in August to 2~(nd) in September). However, these contents had slowly decreasing trend after 2~(nd) in September till 17~(th) in the same month. Interestingly, the content raised again in the maturity of fruits. The variation tendency of contents in six kinds of flavonoids components was inconsistent in different germplasms with the variation of harvesting time. The content of flavonoids in part of germplasms was negatively correlated with the fluctuation of phenolic acids. There was no correlation between phenolic acids and chemical type of the volatile oil. This paper may provide a reference for the high-quality germplasm of P. frutescens cultivation.
Flavonoids ; Oils, Volatile ; Perilla frutescens ; Phenols ; Plant Leaves

The Qinling-Daba Mountains area is the main producing areas of Gynostemma longipes for medicinal usage, and samples of wild whole plants in Pingli, Shaanxi Province and Qingchuan, Sichuan Province were collected. The ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UHPLC-Q-TOF-MS~E) was used to profile the chemical compositions and analyze the similarities and differences of G. longipes samples in these areas. Based on the accurate molecular weight and fragment information obtained from Q-TOF-MS~E, the structures of the main components were identified by combining with the mass spectra, chromatographic behaviors of reference standards and related literatures. The results showed that the components of wild G. longipes from different places among Qinling-Daba Mountains area were similar. Forty-five chemical components were identified in the whole plant of G. longipes from Pingli, Shaanxi Province, including 43 triterpenoid saponins and 2 flavonoids which contain all main peaks in its fingerprint. The main components are dammarane-type triterpenoid saponins, such asgypenoside ⅩLⅨ, gypenoside A and its malonylated product of glycosyl.
Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; Gynostemma ; Mass Spectrometry ; Saponins