ObjectiveIn the realm of forensic science, dust is a valuable type of trace evidence with immense potential for intricate investigations. With the development of DNA sequencing technologies, there is a heightened interest among researchers in unraveling the complex tapestry of microbial communities found within dust samples. Furthermore, striking disparities in the microbial community composition have been noted among dust samples from diverse geographical regions, heralding new possibilities for geographical inference based on microbial DNA analysis. The pivotal role of microbial community data from dust in geographical inference is significant, underscoring its critical importance within the field of forensic science. This study aims to delve deeply into the nuances of fungal community composition across the urban landscapes of Beijing, Fuzhou, Kunming, and Urumqi in China. It evaluates the accuracy of biogeographic inference facilitated by the internal transcribed spacer 2 (ITS2) fungal sequencing while concurrently laying a robust foundation for the operational integration of environmental DNA into geographical inference mechanisms. MethodsITS2 region of the fungal genomes was amplified using universal primers known as 5.8S-Fun/ITS4-Fun, and the resulting DNA fragments were sequenced on the Illumina MiSeq FGx platform. Non-metric multidimensional scaling analysis (NMDS) was employed to visually represent the differences between samples, while analysis of similarities (ANOSIM) and permutational multivariate analysis of variance (PERMANOVA) were utilized to statistically evaluate the dissimilarities in community composition across samples. Furthermore, using Linear Discriminant Analysis Effect Size (LEfSe) analysis to identify and filter out species that exhibit significant differences between various cities. In addition, we leveraged SourceTracker to predict the geographic origins of the dust samples. ResultsAmong the four cities of Beijing, Fuzhou, Kunming and Urumqi, Beijing has the highest species richness. The results of species annotation showed that there were significant differences in the species composition and relative abundance of fungal communities in the four cities. NMDS analysis revealed distinct clustering patterns of samples based on their biogeographic origins in multidimensional space. Samples from the same city exhibited clear clustering, while samples from different cities showed separation along the first axis. The results from ANOSIM and PERMANOVA confirmed the significant differences in fungal community composition between the four cities, with the most pronounced distinctions observed between Fuzhou and Urumqi. Notably, the biogeographic origins of all known dust samples were successfully predicted. ConclusionSignificant differences are observed in the fungal species composition and relative abundance among the cities of Beijing, Fuzhou, Kunming, and Urumqi. Employing fungal ITS2 sequencing on dust samples from these urban areas enables accurate inference of biogeographical locations. The high feasibility of utilizing fungal community data in dust for biogeographical inferences holds particular promise in the field of forensic science.

Eightly-four novel thioheterocyclic nucleoside derivatives were designed, synthesized, and evaluated for antitumor activity in vitro and in vivo. Most of the compounds inhibited the growth of HCT116 and HeLa cancer cells in vitro, among them 33a and 36b exhibited potent activity against HCT116 cells (IC₅₀ = 0.27 and 0.49 μmol/L, respectively). Both compounds 33a and 36b inhibited cell metastasis, arrested the cell cycle in the G₂/M phase, and induced apoptosis in vitro. Mechanistic studies revealed that 33a and 36b increased ROS levels, led to DNA damage, ER stress, and mitochondrial dysfunction, and inhibited autophagy in HCT116 cells. Biological information analysis, RNA-sequencing, Gene Set Enrichment Analysis (GSEA), drug affinity responsive target stability (DARTS) assay, cellular thermal shift assay (CETSA), and SPR experiments identified that compounds 33a and 36b showed antitumor activity by suppressing the c-MYC pathway. c-MYC silencing assays indicated that c-MYC proteins participated in 33a-mediated anticancer activities in HCT116 cells. More importantly, compound 33a presented favorable pharmacokinetic properties in mice (T _1/2 = 6.8 h) and showed significant antitumor efficacy in vivo without obvious toxicity, showing promising potential for further clinical development.

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 investigate the association between baseline hemoglobin level and early neurologic deterioration(END)after intravenous thrombolysis in patients with acute ischemic stroke(AIS).Methods:Data of AIS patients who received intravenous thrombolytic therapy at multiple hospitals across the country between January 2017 and July 2020 were collected from the online database Acute Stroke Patients for Stroke Management Quality Evaluation(CASE-Ⅱ,NCT04487340).Binary logistic regression analysis was used to study the factors affecting the occurrence of END after intravenous thrombolytic therapy,and the correlation between baseline hemoglobin level and END was investigated by limiting cubic spline curve analysis.Results:A total of 8162 patients were included.Patients with END had lower baseline hemoglobin levels(136 and 140 g/L,P<0.01)and higher rates of anemia(24.2%and 16.9%,P<0.01)compared with non-END patients.Binary logistic regression analysis showed that baseline hemoglobin level(OR=0.995,95%CI:0.991-0.999,P<0.05)and anemia(OR=1.238,95%CI:1.055-1.454,P<0.01)were independently correlated with the occurrence of END after intravenous thrombolysis in AIS patients.Restricted cubic spline regression showed that there was a U-shaped relationship between hemoglobin level and the risk of END after intravenous thrombolysis in AIS patients(P<0.01),although this relationship was only significant in male patients(P<0.05)and not in female patients(P>0.05).Conclusion:There is a correlation between baseline hemoglobin level and the risk of END in AIS patients after intravenous thrombolysis,especially in male patients,in whom both lower and higher hemoglobin level may increase the risk of END.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

This study was aimed at understanding the detection rate,drug resistance characteristics,virulence characteris-tics,multi-locus sequence typing,and other molecular epidemic and pathogenic characteristics of Campylobacter jejuni and Campylobacter coli in children in Guangdong Province from 2020 to 2022.Anal swabs or stool samples of suspected infection cases in children from 2020 to 2022 were collected from two hospitals in Guangzhou,Guangdong Province.Campylobacter was isolated and cultured through the filtration method,and identified with a microbial mass spectrometry system;antibiotic resist-ance was analyzed with the agar dilution method;bacterial genome nucleic acids were extracted,and whole-genome sequencing was conducted;and drug resistance genes,virulence genes,multi-locus sequence typing,and phylogenetic analysis based on whole-genome single nucleotide polymorphisms were analyzed from whole-genome sequencing results.First,53 strains of Campy-lobacter were detected through continuous routine monitoring in this study,with a positive detection rate of 2.94％.Among them,Campylobacter jejuni accounted for 81.13％(43/53)and Campylobacter coli accounted for 18.87％(10/53).In addition,16 strains of Campylobacter were screened through multi-pathogen surveillance,including 11 strains of Campylobacter jejuni and 5 strains of Campylobacter coli.Drug resistance ex-periments and whole genome sequencing were conducted on 46 Campylobacter isolates,including 33 isolates of Campylobacter jejuni and 13 isolates of Campylobacter coli.The resistance rate of Campylobacter to erythromycin,a widely used clinical treatment,was21.73％(10/46);that to tetracycline was 80.43％(37/46);those to the quinolone antibiotics nalidixic acid and ciprofloxacin were 76.08％(35/46)and 71.73％(33/46)respectively;and that to chloramphenicol was lowest,at 2.17％(1/46).The drug resistance rate was generally higher for Campylobacter coli than Campylobacter jejuni,and the differences in the indicators of erythromycin,gentamicin,streptomycin,telithromycin,and clindamycin were statistically significant.A total of 30 isolates of multidrug-resistant Campylobacter were detected,including nine multidrug-resistant phenotypes.Whole-ge-nome sequence analysis indicated that 46 Campylobacter isolates carried antibiotic resistance genes for antibiotics such as quino-lones,tetracyclines,β-lactams,and aminoglycosides,and carried 128 virulence factor genes in five categories.All 46 isolates of Campylobacter were identified as 35 ST type through MLST typing,and phylogenetic analysis indicated no obvious dominant ST type.Campylobacter coli had more SNPs than Campylobacter jejuni.In conclusion,the positive detection rate of Campy-lobacter in Guangzhou City,Guangdong Province stabilized from 2020 to 2022,and the detection rate of Campylobacter jejuni was higher than that of Campylobacter coli.Campylobacter isolates were resistant to tetracyclines and quinolone,and showed a wide spectrum of multi-drug resistance,which was relatively severe among Campylobacter coli.Resistance genes and drug-resistant phenotypes were correlated and had predictive significance.The virulence genes of Campylobacter jejuni were more a-bundant than those of Campylobacter coli,possibly because of the higher detection rate and pathogenicity of Campylobacter jejuni.The phylogenetic tree showed clear branches with high genetic diversity and no clearly dominant clonal group.

Objective:To evaluate the effect of low-dose recombinant interleukin-2(rIL-2)therapy on immunocyte subsets and its side effects in children with solid tumor.Methods:A total of 22 children(11 males and 11 females)with solid tumor in our department from December 2012 to November 2017 were selected,with a median age of 9(3-16)years old when starting IL-2 therapy.ALL surgeries and chemotherapy of children had been completed before low-dose rIL-2 therapy,and 17 cases achieved complete remission(CR)and 5 cases achieved partial remission(PR).A low-dose rIL-2 therapy was given 1 month after chemotherapy for 1 year:4 × 105 IU/(m2·d),s.c.for every other day,3 times per week.The immunocyte subsets were detected every 3 months until the end of treatment,meanwhile,disease condition and therapy-related side effects were followed up.Results:After low-dose rIL-2 therapy in 22 children,the absolute values of CD3+T cells,CD3-CD56+natural killer cells,CD3+CD4+helper T cells(Th)and CD3+CD8+cytotoxic T cells were up-regulated remarkably,as well as Th/suppressor T cells(all P＜0.05).While,there were no significant differences in absolute value and proportion of CD4+CD25+CD127-Treg cells during therapy.Among the 17 children who achieved CR before rIL-2 therapy,14 cases continued to maintain CR after therapy,while 3 cases relapsed,and with 2 died after treatment abandonment.The 5 children who achieved PR before low-dose rIL-2 therapy were evaluated CR by PET/CT scan after treatment.In the early stage of low-dose rIL-2 therapy,1 child developed skin rashes at the injection sites,and 2 children ran a slight to mild transient fever.Their symptoms disappeared without any organ damage after symptomatic treatment.Conclusion:Low-dose rIL-2 therapy has good drug tolerance,and changes the distribution of anti-tumor immune-cell subgroup in peripheral blood of children with solid tumor remarkably without up-regulation of absolute value and ratio of Treg cells.

Objective To explore the postmortem diffusion rule of Aconitum alkaloids and their metabo-lites in poisoned rabbits,and to provide a reference for identifying the antemortem poisoning or post-mortem poisoning of Aconitum alkaloids.Methods Twenty-four rabbits were sacrificed by tracheal clamps.After 1 hour,the rabbits were administered with aconitine LD50 in decocting aconite root powder by intragastric administration.Then,they were placed supine and stored at 25℃.The biological samples from 3 randomly selected rabbits were collected including heart blood,peripheral blood,urine,heart,liver,spleen,lung and kidney tissues at 0 h,4 h,8 h,12 h,24 h,48 h,72 h and 96 h after intragastric administration,respectively.Aconitum alkaloids and their metabolites in the biological samples were ana-lyzed by high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS).Results At 4 h after intragastric administration,Aconitum alkaloids and their metabolites could be detected in heart blood,peripheral blood and major organs,and the contents of them changed dynamically with the preservation time.The contents of Aconitum alkaloids and their metabolites were higher in the spleen,liver and lung,especially in the spleen which was closer to the stomach.The average mass fraction of benzoylmesaconine metabolized in rabbit spleen was the highest at 48 h after intragastric administration.In contrast,the contents of Aconitum alkaloids and their metabolites in kidney were all lower.Aconi-tum alkaloids and their metabolites were not detected in urine.Conclusion Aconitum alkaloids and their metabolites have postmortem diffusion in poisoned rabbits,diffusing from high-content organs(stomach)to other major organs and tissues as well as the heart blood.The main mechanism is the dispersion along the concentration gradient,while urine is not affected by postmortem diffusion,which can be used as the basis for the identification of antemortem and postmortem Aconitum alkaloids poisoning.