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*

OBJECTIVE: Poxviruses are zoonotic pathogens that infect humans, mammals, vertebrates, and arthropods. However, the specific role of ticks in transmission and evolution of these viruses remains unclear. METHODS: Transcriptomic and metatranscriptomic raw data from 329 sampling pools of seven tick species across five continents were mined to assess the diversity and abundance of poxviruses. Chordopoxviral sequences were assembled and subjected to phylogenetic analysis to trace the origins of the unblasted fragments within these sequences. RESULTS: Fifty-eight poxvirus species, representing two subfamilies and 20 genera, were identified, with 212 poxviral sequences assembled. A substantial proportion of AT-rich fragments were detected in the assembled poxviral genomes. These genomic sequences contained fragments originating from rodents, archaea, and arthropods. CONCLUSION Our findings indicate that ticks play a significant role in the transmission and evolution of poxviruses. These viruses demonstrate the capacity to modulate virulence and adaptability through horizontal gene transfer, gene recombination, and gene mutations, thereby promoting co-existence and co-evolution with their hosts. This study advances understanding of the ecological dynamics of poxvirus transmission and evolution and highlights the potential role of ticks as vectors and vessels in these processes.
Animals ; Poxviridae/physiology* ; Ticks/virology* ; Phylogeny ; Transcriptome ; Evolution, Molecular ; Poxviridae Infections/virology* ; Genome, Viral

OBJECTIVES: To characterize fine particulate matter (PM _2.5)-bound polycyclic aromatic hydrocarbons (PAHs) emitted from different cooking fumes and their exposure routes and assess their health-associated impact to provide a reference for health risk prevention from PAH exposure across different age and sex groups. METHODS: Sixteen PM _2.5-bound PAHs emitted from 11 cooking styles were analyzed using GC-MS/MS. The health hazards of these PAHs in the Handan City population (stratified by age and sex) were predicted using the incremental lifetime cancer risk ( ILCR) model. The respiratory deposition doses ( RDDs) of the PAHs in children and adults were calculated using the PM _2.5 deposition rates in the upper airway, tracheobronchial, and alveolar regions. RESULTS: The total concentrations of PM _2.5-bound PAHs ranged from 61.10 to 403.80 ng/m ³. Regardless of cooking styles, the ILCR _total values for adults (1.23 × 10 ^-6 to 3.70 × 10 ^-6) and older adults (1.28 × 10 ^-6 to 3.88 × 10 ^-6) exceeded the acceptable limit of 1.00 × 10 ^-6. With increasing age, the ILCR _total value first declined and then increased, varying substantially among the population groups. Cancer risk exhibited particularly high sensitivity to short exposure to barbecue-derived PAHs under equivalent body weights. Furthermore, barbecue, Sichuan and Hunan cuisine, Chinese cuisine, and Chinese fast food were associated with higher RDDs for both adults and children. CONCLUSION ILCR _total values exceeded the acceptable limit for both females and males of adults, with all cooking styles showing a potentially high cancer risk. Our findings serve as an important reference for refining regulatory strategies related to catering emissions and mitigating health risks associated with cooking styles.
Humans ; Polycyclic Aromatic Hydrocarbons/analysis* ; Cooking/methods* ; Male ; Female ; Particulate Matter/analysis* ; Adult ; Child ; Middle Aged ; Air Pollutants/analysis* ; Adolescent ; Air Pollution, Indoor/analysis* ; Young Adult ; Child, Preschool ; Aged ; China ; Inhalation Exposure ; Age Factors ; Sex Factors ; Cities ; Infant

Objective To evaluate the bioequivalence and safety of two pyrazinamide tablets in healthy Chinese subjects.Methods An open,randomized,single-dose,two-sequence,two-cycle,double-cross trial design was used.All 48 healthy subjects(24 in fasting and 24 in fed trial)were randomized to receive a single oral dose of a 0.5 g pyrazinamide tablet(test or reference)per cycle.The plasma concentration of the drug was determined by liquid chromatography coupled to tandem mass spectrometry method.The pharmacokinetic parameters were calculated by WinNonlin v8.2,and the bioequivalence was evaluated by SAS 9.4.Results In the fasting group,the Cmax of the test and reference preparation of pyrazinamide tablets were(13.28±2.82)and(12.88±4.49)μg·mL-1,the AUC0-t were(139.17±26.58)and(138.63±28.92)h·μg·mL-1,the AUC0-∞ were(148.96±33.65)and(148.71±36.97)h·μg·mL-1 respectively.In the fed group,the Cmax of the test and reference preparation of pyrazinamide tablets were(11.89±1.96)and(11.99±1.92)μg·mL-1,the AUC0-t were(138.22±37.21)and(141.68±25.80)h·μg·mL-1,the AUC0-∞ were(152.20±32.41)and(151.04±28.05)h·μg·mL-,respectively.The 90％confidence intervals of Cmax,AUC0-t and AUC0-∞ geometric mean ratios of the test and reference preparation were all within 80.00％to 125.00％.The incidence of adverse events was 16.70％for both the test and reference preparation in the fasting group and 8.30％for both the test and reference preparation in the fed group,all of which were mild in severity.Conclusion The test and reference preparation of pyrazinamide tablets were bioequivalent,safe and well tolerated in healthy Chinese subjects under fasting and fed conditions.

Objective:To explore inhibiting effect of miR-515-5p on proliferation,migration and invasion of esophageal cancer cells by targeting TPX2-IL-6 axis.Methods:Esophageal cancer cells EC9706 were treated with IL-6,and divided into Con group,IL-6 group,IL-6+miR-NC group,IL-6+miR-515-5p group,IL-6+miR-515-5p+pcDNA group,IL-6+miR-515-5p+TPX2 group.qRT-PCR was used to detect expressions of miR-515-5p and TPX2 mRNA;clone formation experiment and Transwell were used to de-tect cell proliferation,migration and invasion;Western blot was used to detect CyclinD1,MMP2,MMP9 and TPX2 protein expres-sions;dual luciferase report experiment was used to detect targeting relationship between miR-515-5p and TPX2.Results:Compared with Con group,expression of miR-515-5p in IL-6 group was decreased,expressions of TPX2 mRNA and protein were increased,numbers of cloned,migrating and invasion cells were increased,protein expressions of CyclinD1,MMP2 and MMP9 were increased.Compared with IL-6+miR-NC group,expression of miR-515-5p in IL-6+miR-515-5p group was increased,expressions of TPX2 mRNA and protein were decreased,numbers of cloned,migrating and invasion cells were reduced,CyclinD1,MMP2,MMP9 protein expressions were decreased.miR-515-5p targeting regulated expression of TPX2.Overexpression of TPX2 could reverse effect of up-regulation of miR-515-5p on IL-6-induced proliferation,migration and invasion of esophageal cancer cells.Conclusion:miR-515-5p can targeting inhibit TPX2 to inhibit IL-6-induced proliferation,migration and invasion of esophageal cancer cells.

Objective To explore the prediction of hospital indoor microbial concentration in air based on real-time indoor air environment monitoring data and machine learning algorithms.Methods Four locations in a hospital were selected as monitoring sampling points from May 23 to June 5,2022.The"internet of things"sensor was used to monitor a variety of real-time air environment data.Air microbial concentration data collected at each point were matched,and the gradient boosting decision tree(GBDT)was used to predict real-time indoor microbial concentra-tion in air.Five other common machine learning models were selected for comparison,including random forest(RF),decision tree(DT),k-nearest neighbor(KNN),linear regression(LR)and artificial neural network(ANN).The validity of the model was verified by the mean absolute error(MAE),root mean square error(RMSE)and mean absolute percentage error(MAPE).Results The MAPE value of GBDT model in the outpa-tient elevator room(point A),bronchoscopy room(point B),CT waiting area(point C),and nurses'station in the supply room(point D)were 22.49％,36.28％,29.34％,and 26.43％,respectively.The mean performance of the GBDT model was higher than that of other machine learning models at three sampling points and slightly lower than that of the ANN model at only one sampling point.The mean MAPE value of GBDT model at four sampling points was 28.64％,that is,the predicted value deviated from the actual value by 28.64％,indicating that GBDT model has good prediction results and the predicted value was within the available range.Conclusion The GBDT machine learning model based on real-time indoor air environment monitoring data can improve the prediction accuracy of in-door air microbial concentration in hospitals.

Objective To investigate the efficacy of endoscopic Delta large channel unilateral laminotomy for bilateral decompression(ULBD)in the treatment of lumbar spinal stenosis(LSS),and the postoperative complications was analyzed.Methods A total of 100 patients with LSS in our hospital from January 2021 to February 2023 were selected and divided into the control group and the observation group according to random number table method,with 50 cases in each group.Patient in the control group were treated with bilateral or unilateral decompression through the median incision adjacent to the lateral spinous process,and patients in the observation group were treated with endoscopic Delta large channel ULBD.The visual analogue scale(VAS)scores,Japanese Orthopaedic Association(JOA)scores,Oswestry disability index(ODI)scores before surgery and 1 month,3 months,6 months after surgery,as well as clinical efficacy and incidence of postoperative complications of patients between the two groups were compared.Results Compared with preoperative results,the VAS scores of leg pain and low back pain and ODI scores of patients 1 month,3 months and 6 months after surgery in both groups were significantly lower(P<0.05),and JOA scores were significantly higher(P<0.05).Moreover,compared with the control group,the VAS scores of leg pain and low back pain and ODI scores of patients 1 month,3 months and 6 months after surgery in the observation group were lower(P<0.05),the JOA scores were higher(P<0.05).The total effective rate in the observation group was 98.00%,which was higher than 72.00%in the control group(P<0.05).The incidence of postoperative complications in the observation group was 4.00%,which was lower than 24.00%in the control group(P<0.05).Conclusion Endoscopic Delta large channel ULBD in the treatment of LSS can effectively reduce postopera-tive leg pain and low back pain,improve lumbar function,improve clinical therapeutic effect,and reduce postoperative complications.

Background/Aims: Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. Methods: We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development. Results: Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. Conclusions Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.

Malaria, one of the major global public health events, is a leading cause of mortality and morbidity among children and adults in tropical and subtropical regions(mainly in sub-Saharan Africa), threatening human health. It is well known that malaria can cause various complications including anemia, blackwater fever, cerebral malaria, and kidney damage. Conventionally, cardiac involvement has not been listed as a common reason affecting morbidity and mortality of malaria, which may be related to ignored cases or insufficient diagnosis. However, the serious clinical consequences such as acute coronary syndrome, heart failure, and malignant arrhythmia caused by malaria have aroused great concern. At present, antimalarials are commonly used for treating malaria in clinical practice. However, inappropriate medication can increase the risk of cardiovascular diseases and cause severe consequences. This review summarized the research advances in the cardiovascular complications including acute myocardial infarction, arrhythmia, hypertension, heart failure, and myocarditis in malaria. The possible mechanisms of cardiovascular diseases caused by malaria were systematically expounded from the hypotheses of cell adhesion, inflammation and cytokines, myocardial apoptosis induced by plasmodium toxin, cardiac injury secondary to acute renal failure, and thrombosis. Furthermore, the effects of quinolines, nucleoprotein synthesis inhibitors, and artemisinin and its derivatives on cardiac structure and function were summarized. Compared with the cardiac toxicity of quinolines in antimalarial therapy, the adverse effects of artemisinin-derived drugs on heart have not been reported in clinical studies. More importantly, the artemisinin-derived drugs demonstrate favorable application prospects in the prevention and treatment of cardiovascular diseases, and are expected to play a role in the treatment of malaria patients with cardiovascular diseases. This review provides reference for the prevention and treatment of malaria-related cardiovascular complications as well as the safe application of antimalarials.
Child ; Adult ; Humans ; Antimalarials/pharmacology* ; Cardiovascular Diseases/drug therapy* ; Artemisinins/pharmacology* ; Quinolines ; Malaria, Cerebral/drug therapy* ; Heart Failure/drug therapy* ; Arrhythmias, Cardiac/drug therapy*

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death among urban and rural residents in China, and elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for ASCVD. Considering the increasing burden of ASCVD, lipid management is of the utmost importance. In recent years, research on blood lipids has made breakthroughs around the world, hence a revision of China guidelines for lipid management is imperative, especially since the target lipid levels in the general population vary in respect to the risk of ASCVD. The level of LDL-C, which can be regarded as appropriate in a population without frisk factors, can be considered abnormal in people at high risk of developing ASCVD. As a result, the "Guidelines for the prevention and treatment of dyslipidemia" were adapted into the "China Guidelines for Lipid Management" (henceforth referred to as the new guidelines) by an Experts' committee after careful deliberation. The new guidelines still recommend LDL-C as the primary target for lipid control, with CVD risk stratification to determine its target value. These guidelines recommend that moderate intensity statin therapy in adjunct with a heart-healthy lifestyle, be used as an initial line of treatment, followed by cholesterol absorption inhibitors or/and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, as necessary. The new guidelines provide guidance for lipid management across various age groups, from children to the elderly. The aim of these guidelines is to comprehensively improve the management of lipids and promote the prevention and treatment of ASCVD by guiding clinical practice.