Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage* ; Bile Acids and Salts/metabolism* ; Animals ; Male ; Liver/injuries* ; Chemical and Drug Induced Liver Injury/genetics* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Rats, Sprague-Dawley ; Mice ; Rats

Cardiac fibrosis(CF) is a cardiac pathological process characterized by excessive deposition of extracellular matrix(ECM). When the heart is damaged by adverse stimuli, cardiac fibroblasts are activated and secrete a large amount of ECM, leading to changes in cardiac fibrosis, myocardial stiffness, and cardiac function declines and accelerating the development of heart failure. There is a close relationship between heart yin deficiency and cardiac fibrosis, which have similar pathogenic mechanisms. Heart Yin deficiency, characterized by insufficient Yin fluids, causes the heart to lose its nourishing function, which acts as the initiating factor for myocardial dystrophy. The deficiency of body fluids leads to stagnation of blood flow, resulting in blood stasis and water retention. Blood stasis and water retention accumulate in the heart, which aligns with the pathological manifestation of excessive deposition of ECM, as a tangible pathogenic factor. This is an inevitable stage of the disease process. The lingering of blood stasis combined with water retention eventually leads to the generation of heat and toxins, triggering inflammatory responses similar to heat toxins, which continuously stimulate the heart and cause the ultimate outcome of CF. Considering the syndrome of heart Yin deficiency, traditional Chinese medicine capable of nourishing Yin, activating blood, and promoting urination can reduce myocardial cell apoptosis, inhibit fibroblast activation, and lower the inflammation level, showing significant advantages in combating CF.
Humans ; Fibrosis/drug therapy* ; Animals ; Yin Deficiency/metabolism* ; Myocardium/metabolism* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use*

OBJECTIVES: To identify potential plasma lipidomic biomarkers that distinguish non-metastatic medulloblastoma (nmMB) from metastatic medulloblastoma (mMB) in children. METHODS: In this prospective study, 17 children with mMB and 20 matched children with nmMB were enrolled. Plasma samples were analyzed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Lipid metabolites were evaluated for their associations and diagnostic performance. RESULTS: Orthogonal partial least squares discriminant analysis based on lipid profiles clearly separated nmMB from mMB, and 14 differential lipids were identified, including DG(18:2/20:4/0:0) and SM(d18:1/20:0). Receiver operating characteristic analysis showed nine metabolites with area under the curve greater than 0.7. Differential lipids were enriched in sphingolipid, glycerophospholipid, and arachidonic acid metabolism, suggesting an association with the metastatic phenotype. CONCLUSIONS Plasma lipidomics provides a new approach to identify mMB, and the identified lipid metabolites may support early diagnosis and treatment, prognostic assessment, and selection of therapeutic targets for metastatic medulloblastoma.
Humans ; Medulloblastoma/diagnosis* ; Lipidomics ; Child ; Male ; Female ; Child, Preschool ; Cerebellar Neoplasms/blood* ; Biomarkers, Tumor/blood* ; Neoplasm Metastasis ; Prospective Studies ; Adolescent ; Lipids/blood*

DNA polymerase theta (Polθ), also known as DNA polymerase θ, is the member of the DNA polymerase A family and plays a crucial role in the repair of DNA double-strand breaks (DSB). Polθ has 3 distinct structural domains: the N-terminal helicase-like domain with a conserved sequence, the C-terminal polymerase domain, and the central domain, which is a disordered sequence connecting these two regions. Notably, Polθ is the only known polymerase in eukaryotes that possesses helicase activity. However, it is also an error-prone polymerase. When DNA DSBs occur, a specialized network consisting of at least 4 pathways, including classical-non homologous end joining (C-NHEJ), homologous recombination (HR), single-strand annealing (SSA), and alternative-end joining (Alt-EJ), is responsible for repairing DNA damage caused by DSBs. In the absence of major DNA repair pathways like HR, cells rely on Alt-EJ pathway mediated by Polθ to repair damaged DNA and maintain genomic stability. Nevertheless, due to the low fidelity of Polθ, Alt-EJ repair often leads to errors. Depletion of Polθ has shown to increases DSB formation and compromise genomic stability. Conversely, overexpression of Polθ has been associated with increases DNA damage markers and impairs cell cycle progression. As a result, the impact of Polθ on genome stability remains controversial. Furthermore, overexpression of Polθ is frequently observed in cancer and is associated with a characteristic mutational signature and poor prognosis. Depleting Polθ in an HR-deficient background has been shown to impair cell viability, suggesting a synthetic lethal (SL) relationship between Polθ and HR factors. In recent years, targeted chemotherapy drugs that inhibit tumor growth have gained significant attention. However, off-target effects and drug resistance pose challenges for clinical application, particularly with poly-ADP-ribose polymerase inhibitor (PARPi). Blocking Polθ activity in HR-deficient tumor cells has been found to reverse PARPi resistance, making Polθ a very promising therapeutic target in cancer treatment. The availability of crystal structures for both helicase and polymerase domain has facilitated the design of potent inhibitors of Polθ. Currently, several highly specific and effective small molecule inhibitors targeting Polθ, such as Novobiocin, RP-6685, and ART558, have been reported to effectively block various cancers with HR deficiency. The initial success of these inhibitors points to new directions for treating BRCA1/2-mutated tumors. Additionally, reducing the Alt-EJ repair pathway mediated by Polθ can improve HR repair efficiency and increase the chance of exogenous gene target integration (TI), suggesting potential new applications for Polθ inhibitors. This article reviews the recent research progress on the molecular function of Polθ and its involvement in the Alt-EJ pathway modification mechanism, providing insights for a deeper understanding of this field.

Objective:To understand the whole genome and genetic evolution characteristics of the first epidemic influenza A (H3N2) viruses in Wuxi from 2022-2023.Methods:Real time fluorescence quantitative RT-PCR method was used to perform typing on respiratory samples of influenza cases. Virus isolation was performed on samples with positive nucleic acid of subtype A H3N2 influenza virus detected. After cell culture, nucleic acid was extracted from strains with red blood cell agglutination test (HA) ≥ 1∶8, whole genome sequence was amplified, library was constructed, and computer sequencing was performed using MiSeq sequencer. Using NC_007366.1 as reference strain, the data were analyzed using CLC Genomics Workbench (Version 23) software. The phylogenetic tree was constructed using MEGA 7.0 software, and the N-glycosylation sites were predicted by NetNGlyc 1.0 Server software.Results:The nucleotide homology and amino acid homology among 35 strains of influenza A H3N2 virus from 2022 to 2023 were 96.4%-100% and 95.2%-100%, respectively. The 16 epidemic strains in 2022 belong to the 3C.2a1b.2a.1a evolutionary branch, while the 19 epidemic strains in 2023 belong to the 3C.2a1b.2a.2a.3a.1 evolutionary branch. There are 7 differences in the nucleotide sequence of the HA gene between the 2022 epidemic strain and the corresponding vaccine strain, sharing 15 mutation sites; There are 28 differences in the nucleotide sequence of the HA gene between the 2023 epidemic strain and the corresponding vaccine strain, sharing 17 mutation sites. The HA genes of 35 epidemic strains all lack N-glycosylation site 61: NSS, while in 2023, the HA genes of 19 epidemic strains added N-glycosylation site 110: NSS.Conclusions:The HA and NA genes of influenza A H3N2 virus in 2022 and 2023 belong to two evolutionary branches, respectively, and both show specific amino acid site changes compared to the corresponding vaccine strains. The antigen matching between the 2022 epidemic strain and the vaccine strain is relatively good, while there is a risk of low antigen matching between the 2023 epidemic strain and the vaccine strain.

To clone and express the K26 gene of Leishmania isolated from three types of visceral leishmaniasis epidemic ar-eas in China and evaluate its effect on detecting specific antibodies against visceral leishmaniasis.The K26 fragments from Leishmania isolated KS-6,SC6 and JIASHI-1 was synthesized and cloned into pET32a vector.The recombinant plasmid pET32a-K26 was transformed into Escherichia coli BL21 strains and induced by isopropyl-β-D-thiogalactopyranoside(IPTG).The expressed recombinant protein was purified by the His-tagged affinity column(Ni-NTA).Serum samples of 110 visceral leishmaniasis patients were used for evaluating the sensitivity by ELISA.Serum samples from patients with malaria,schisto-somiasis japonica,cystechinococcosis,toxoplasmosis,paragon-imiasis,clonorchiosis and 40 healthy people were used for eval-uating the specificity.Detection results of ELISA were compared with that of rK39 strip of American InBios company.Comparation among three K26 antigens were given by x2 test.The sensitivity of the recombinant K26 protein of KS-6,SC6 and JIASHI-5 strains of Leishmania and rK39 strip test to detect the sera of patients with visceral leishmaniasis was 90.00％(99/110),92.73％(102/110),90.91％(100/110)and 93.64％(103/110),respectively.There was no cross reactivity with malaria(10),schistosomiasis japonica(10),cystechinococcosis(10),toxoplasmosis(5),paragonimiasis(5)and clonorchiosis(5),and 40 sera from healthy people were also negative.The specificity was 100.00％.There was no statistical difference in the sensitivity of the recombinant K26 protein of KS-6,SC6 and JIASHI-1 strains of Leishmania and rK39 strip test,x2 values are 0.97,0.07 and 0.57 respectively and the P values are 0.33,0.79 and 0.45,respectively.There was no statis-tical difference in the sensitivity of three K26 antigens(x2=0.53,P=0.97).Conclusion The recombinant K26 antigen has po-tential application value in the diagnosis of visceral leishmaniasis.

A new method was developed for simultaneous detection of total 19 kinds of organophosphate esters(OPEs)and their diester metabolites(di-OPEs)in human serum(1.0 mL)and urine(1.5 mL)with low volume of samples.The target compounds were determined using ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)after acetonitrile liquid-liquid extraction combined with purification using an ENVI-18 solid-phase extraction(SPE)column.OPEs and di-OPEs were separated using a Shim-pack GIST C18 column(100 mm×2.1 mm,2 μm)with a Shim-pack GIST-HP(G)C18 guard column.An electrospray ionization source(ESI)was employed in mass spectrometry analysis,with positive/negative ion mode using the multiple reaction monitoring(MRM).All target compounds were separated within 15 min,and exhibited good linear relationships in the concentration range of 2-100 ng/mL,with correlation coefficients(R2)above 0.994.The method detection limits(MDL)in serum ranged from 0.001 to 0.178 ng/mL and the MDL in urine ranged from 0.001 to 0.119 ng/mL.The recoveries of the analytes spiked in serum and urine matrices at two concentration levels were 30.5%-126.8%,with the relative standard deviations(RSDs)ranged from 1%to 23%.In addition,paired serum and urine samples from 11 patients were analyzed.For all samples tested,the internal standards of OPEs exhibited recoveries between 61%and 114%,whereas the internal standards for di-OPEs had recoveries ranging from 43%to 103%.OPEs and di-OPEs exhibited high detection frequencies in 22 serum and urine samples.Triethyl phosphate(TEP),tributyl phosphate(TBP),tris(2-ethylhexyl)phosphate(TEHP),tris(2-butoxyethyl)phosphate(TBEP),tris(1-chloro-2-propyl)phosphate(TCIPP),triphenyl phosphate(TPHP),tri-m-tolyl-phosphate(TMTP)and 2-ethylhexyl diphenyl phosphate(EHDPP)were universally detected in all serum samples.TCIPP was identified at the highest concentrations(median 0.548 ng/mL)in serum samples.In urine samples,the detection frequency for 12 kinds of target compounds reached 100%.Notably,TBP emerged as the predominant OPE in urine,demonstrating a median concentration of 0.506 ng/mL.Regarding di-OPEs,bis(2-chloroethyl)phosphate(BCEP)and bis(2-butoxyethyl)hydrogen phosphate(BBOEP)were the most abundant in urine,with median concentrations of 6.404 and 2.136 ng/mL,respectively.The total concentrations of OPEs and di-OPEs in serum and urine were 1.580-3.843 ng/mL and 5.149-17.537 ng/mL,respectively.These results not only confirmed the effectiveness of the method in detection of OPEs and di-OPEs in biological matrices,but also revealed the widespread presence of OPE compounds in human body and pointed to potential exposure risks.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective:There is a lack of scientifically validated tools to measure the knowledge attitude and practice(KAP)of informal caregivers for patients with pressure injury(PI).This study aims to develop a KAP Scale for Informal Caregivers of PI Patients and to evaluate its reliability and validity. Methods:Based on the KAP theory framework and relevant literature,an initial pool of items was created through expert brainstorming sessions.The initial scale was formed after a Delphi expert consultation and a preliminary survey.From April to October 2023,a convenient sample of informal caregivers for PI patients was recruited from an inpatient department of the Third Xiangya Hospital of Central South University,as well as its associated community and nursing homes.The first round included 186 participants,and the second round included 213 participants,who were used for item analysis and reliability and validity testing.After a 3-week interval,20 participants from the initial group were randomly selected for a retest to assess the test-retest reliability of the scale. Results:The KAP Scale for informal caregivers of PI patients consists of 3 dimensions with 19 items.The overall internal consistency(Cronbach's α)of the scale was 0.916.The item-level content validity index(I-CVI)ranged from 0.826 to 1.000,and the scale level-content validity index/average(S-CVI/Ave)was 0.94.Exploratory factor analysis extracted 3 common factors,accounting for 64.643％of the total variance.Confirmatory factor analysis showed that the model fit the data well,with x2/df=2.54,root mean square error of approximation(RMSEA)=0.085,comparative fit index(CFI)=0.920,and standardized root mean square residual(SRMR)=0.059. Conclusion:The KAP scale for informal caregivers of PI patients demonstrates good reliability and validity and can be used to assess the KAP levels of informal caregivers regarding PI.

Since the end of 2019,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has swept the world,bringing great harm to human society and significantly increasing the health burden.Due to stron-ger infectivity,faster transmission,and higher reinfection rate of the Omicron variant,it has now replaced the Delta variant as the main epidemic strain for both imported and local outbreaks in China.Chinese Diagnosis and treatment protocol for SARS-CoV-2 infection(10th trial version)emphasizes"strengthening the protection of key popula-tions,"which includes the increasing number of immunocompromised population.These people have a high inci-dence of severe diseases and a high fatality rate after infected with SARS-CoV-2,and belong to the high-risk popula-tions of severe or critical diseases.Moreover,due to underlying diseases,these people take immunosuppressants and other related drugs chronically.The interactions between anti-SARS-CoV-2 infection treatment drugs and origi-nal drugs are complicated,thus bring significant challenges to the treatment after the SARS-CoV-2 infection.Cur-rently,there is a lack of guidelines or consensus on the diagnosis and treatment of SARS-CoV-2 infection among im-munocompromised population.Therefore,the Guangzhou Institute of Respiratory Health and National Center for Respiratory Medicine organized experts from multiple disciplines(respiratory and critical care medicine,organ transplantation,rheumatology and immunology,hematology,infection,critical care medicine,etc.)in China.Af-ter multiple rounds of discussions,13 items of recommendations are made as the reference for peers based on evi-dence-based medical evidence,so as to provide a theoretical and practical reference for the diagnosis and treatment strategies of this population.