A noninvasive multianalytical approach establishment for risk assessment and gastric cancer screening.

Effective screening and early detection are critical to improve the prognosis of gastric cancer (GC). Our study aims to explore noninvasive multianalytical biomarkers and construct integrative models for preliminary risk assessment and GC detection. Whole genomewide methylation marker discovery was conducted with CpG tandems target amplification (CTTA) in cfDNA from large asymptomatic screening participants in a high-risk area of GC. The methylation and mutation candidates were validated simultaneously using one plasma from patients at various gastric lesion stages by multiplex profiling with Mutation Capsule Plus (MCP). Helicobacter pylori specific antibodies were detected with a recomLine assay. Integrated models were constructed and validated by the combination of multianalytical biomarkers. A total of 146 and 120 novel methylation markers were found in CpG islands and promoter regions across the genome with CTTA. The methylation markers together with the candidate mutations were validated with MCP and used to establish a 133-methylation-marker panel for risk assessment of suspicious precancerous lesions and GC cases and a 49-methylation-marker panel as well as a 144-amplicon-mutation panel for GC detection. An integrated model comprising both methylation and specific antibody panels performed better for risk assessment than a traditional model (AUC, 0.83 and 0.63, P < .001). A second model for GC detection integrating methylation and mutation panels also outperformed the traditional model (AUC, 0.82 and 0.68, P = .005). Our study established methylation, mutation and H. pylori-specific antibody panels and constructed two integrated models for risk assessment and GC screening. Our findings provide new insights for a more precise GC screening strategy in the future.

The predictive utility of cytokines, procalcitonin and C-reactive protein among febrile pediatric hematology and oncology patients with severe sepsis or septic shock.

Severe sepsis and septic shock are life-threatening for pediatric hematology and oncology patient receiving chemotherapy. Th1/Th2 cytokines, C-reactive protein (CRP), and procalcitonin (PCT) are all thought to be associated with disease severity. The aim of this study was to prospectively verify the utility of Th1/Th2 cytokines and compare them with PCT and CRP in the prediction of adverse outcomes. Data on patients were collected from January 1, 2011, to December 31, 2020. Blood samples were taken for Th1/Th2 cytokine, CRP, and PCT measurements at the initial onset of infection. Severe infection (SI) was defined as severe sepsis or septic shock. Th1/Th2 cytokine levels were determined by using flow cytometric bead array technology. In total, 7,735 febrile episodes were included in this study. For SI prediction, the AUCs of IL-6, IL-10 and TNF-α were 0.814, 0.805 and 0.624, respectively, while IL-6 and IL-10 had high sensitivity and specificity. IL-6 > 220.85 pg/ml and IL-10 > 29.95 pg/ml had high odds ratio (OR) values of approximately 3.5 in the logistic regression. Within the subgroup analysis, for bloodstream infection (BSI) prediction, the AUCs of IL-10 and TNF-α were 0.757 and 0.694, respectively. For multiorgan dysfunction syndrome (MODS) prediction, the AUC of CRP was 0.606. The AUC of PCT for mortality prediction was 0.620. In conclusion, IL-6 and IL-10 provide good predictive value for the diagnosis of SI. For children with SI, IL-10 and TNF-α are associated with BSI, while CRP and PCT are associated with MODS and death, respectively.

Clinical features and prognostic implications of ecotropic viral integration site 1 (EVI1) in childhood acute lymphoblastic leukemia.

In contrast to the extensive knowledge on EVI1 in myeloid malignancies, few data are available on the EVI1 transcript in pediatric ALL. The purpose of this study was to examine the clinical and biological significance of EVI1 and validate its prognostic significance in pediatric patients with ALL. Here, we examined the clinical and biological significance of EVI1 expression, as measured by real-time polymerase chain reaction (PCR) in 837 children with newly diagnosed ALL treated on the National Protocol of Childhood Leukemia in China (NPCLC)-ALL-2008 protocol, and aimed to explore their prognostic significance in pediatric ALL patients. The EVI1 expression was detected in 27 of 837 (3.2%) patients. No statistically significant differences in prednisone response, complete remission (CR) rates and relapse rates were found between EVI1 overexpression (EVI1+) group and EVI1- group. Moreover, we found no significant difference in event-free survival (EFS) and overall survival (OS) between these two groups, also multivariate analysis did not identify EVI1+ as an independent prognostic factor. In the subgroup analysis, there was no difference in clinical outcome between EVI1+ and EVI1- patients in standard­risk (SR), intermediate-risk (IR) and high-risk (HR) groups. In the minimal residual disease (MRD)<10-4 group, EVI1+ patients have significantly lower EFS and OS rates compared to EVI1- patients. Further large­scale and well­designed prospective studies are required to confirm the results in the future.

Beneficial effects of endoscopic screening on gastric cancer and optimal screening interval: a population-based study.

BACKGROUND : The effectiveness of endoscopic screening on gastric cancer has not been widely investigated in China and the screening interval of repeated screening has not been determined. METHODS : In a population-based prospective study, we included 375,800 individuals, 14,670 of whom underwent endoscopic screening (2012-2018). We assessed the associations between endoscopic screening and risk of incident gastric cancer and gastric cancer-specific mortality, and examined changes in overall survival and disease-specific survival following screening. The optimal screening interval for repeated endoscopy for early detection of gastric cancer was explored. RESULTS : Ever receiving endoscopic screening significantly decreased the risk of invasive gastric cancer (age- and sex-adjusted relative risk [RR] 0.69, 95 % confidence interval [CI] 0.52-0.92) and gastric cancer-specific mortality (RR 0.33, 95 %CI 0.20-0.56), particularly for noncardia gastric cancer. Repeated screening strengthened the beneficial effect on invasive gastric cancer-specific mortality of one-time screening. Among invasive gastric cancers, screening-detected individuals had significantly better overall survival (RR 0.18, 95 %CI 0.13-0.25) and disease-specific survival (RR 0.18, 95 %CI 0.13-0.25) than unscreened individuals, particularly for those receiving repeated endoscopy. For individuals with intestinal metaplasia or low grade intraepithelial neoplasia, repeated endoscopy at an interval of < 2 years, particularly within 1 year, significantly enhanced the detection of early gastric cancer, compared with repeated screening after 2 years (P-trend = 0.02). CONCLUSION : Endoscopic screening prevented gastric cancer occurrence and death, and improved its prognosis in a population-based study. Repeated endoscopy enhanced the effectiveness. Screening interval should be based on gastric lesion severity.

Suppression of Helicobacter pylori infection by daily cranberry intake: A double-blind, randomized, placebo-controlled trial.

BACKGROUND AND AIM: Dietary strategies that contribute to reducing incidence of Helicobacter pylori infection without negative side effects are highly desirable owing to worldwide bacterial prevalence and carcinogenesis potential. The aim of this study was to determine dosage effect of daily cranberry consumption on H. pylori suppression over time in infected adults to assess the potential of this complementary management strategy in a region with high gastric cancer risk and high prevalence of H. pylori infection. METHODS: This double-blind, randomized, placebo-controlled trial on 522 H. pylori-positive adults evaluated dose-response effects of proanthocyanidin-standardized cranberry juice, cranberry powder, or their placebos on suppression of H. pylori at 2 and 8 weeks by 13 C-urea breath testing and eradication at 45 days post-intervention. RESULTS: H. pylori-negative rates in placebo, low-proanthocyanidin, medium-proanthocyanidin, and high-proanthocyanidin cranberry juice groups at week 2 were 13.24%, 7.58%, 1.49%, and 13.85% and at week 8 were 7.35%, 7.58%, 4.48%, and 20.00%, respectively. Consumption of high-proanthocyanidin juice twice daily (44 mg proanthocyanidin/240-mL serving) for 8 weeks resulted in decreased H. pylori infection rate by 20% as compared with other dosages and placebo (P < 0.05). Percentage of H. pylori-negative participants increased from 2 to 8 weeks in subjects who consumed 44 mg proanthocyanidin/day juice once or twice daily, showing a statistically significant positive trend over time. Encapsulated cranberry powder doses were not significantly effective at either time point. Overall trial compliance was 94.25%. Cranberry juice and powder were well-tolerated. CONCLUSIONS: Twice-daily consumption of proanthocyanidin-standardized cranberry juice may help potentiate suppression of H. pylori infection. TRIAL REGISTRATION: ChiCTR1800017522, per WHO ICTRP.

Analysis of rice root bacterial microbiota of Nipponbare and IR24.

The root-associated bacterial microbiota is closely related to life activities of land plants, and its composition is affected by geographic locations and plant genotypes. However, the influence of plant genotypes on root microbiota in rice grown in northern China remains to be explained. In this study, we performed 16S rRNA gene amplicon sequencing to generate bacterial community profiles of two representative rice cultivars, Nipponbare and IR24. They are planted in Changping and Shangzhuang farms in Beijing and have reached the reproductive stage. We compared their root microbiota in details by Random Forest machine learning algorithm and network analysis. We found that the diversity of rice root microbiota was significantly affected by geographic locations and rice genotypes. Nipponbare and IR24 showed distinct taxonomic composition of the root microbiota and the interactions between different bacteria. Moreover, the root bacteria could be used as biomarkers to distinguish Nipponbare from IR24 across regions. Our study provides a theoretical basis for the in-depth understanding of rice root microbiota in Northern China and the improvement of rice breeding from the perspective of the interaction between root microorganisms and plants.

DOES IT WORK? -a randomized controlled trial to test the efficacy of HCV and HIV-related education on drug users in MMT, China.

BACKGROUND: HCV (Hepatitis C virus) is a prevalent chronic disease with potentially deadly consequences, especially for drug users. However, there are no special HCV or HIV (human immunodeficiency virus)-related intervention programs that are tailored for drug users in China; to fill this gap, the purpose of this study was to explore HCV and HIV-related knowledge among drug users in MMT (methadone maintenance treatment) sites of China and to investigate the effectiveness of HCV and HIV-related education for improving the knowledge of IDUs (injection drug users) and their awareness of infection. METHODS: The study was a randomized cluster controlled trial that compared a usual care group to a usual care plus HCV/HIV-REP (HCV/HIV-Reduction Education Program) group with a 24-week follow-up. The self-designed questionnaires, the HCV- and HIV-related knowledge questionnaire and the HIV/HCV infection awareness questionnaire, were used to collect the data. Four MMT clinics were selected for this project; two MMT clinics were randomly assigned to the research group, with subjects receiving their usual care plus HCV/HIV-REP, and the remaining two MMT clinics were the control group, with subjects receiving their usual care over 12 weeks. Sixty patients were recruited from each MMT clinic. A total of 240 patients were recruited. Follow-up studies were conducted at the end of the 12th week and the 24th week after the intervention. RESULTS: At baseline, the mean score (out of 20 possible correct answers) for HCV knowledge among the patients in the group receiving the intervention was 6.51 (SD = 3.5), and it was 20.57 (SD = 6.54) for HIV knowledge (out of 45 correct answers) and 8.35 (SD = 2.8) for HIV/HCV infection awareness (out of 20 correct answers). At the 12-week and 24-week follow-up assessments, the research group showed a greater increase in HCV-/HIV-related knowledge (group × time effect, F = 37.444/11.281, P < 0.05) but no difference in their HIV/HCV infection awareness (group × time effect, F = 2.056, P > 0.05). CONCLUSION: An MMT-based HCV/HIV intervention program could be used to improve patient knowledge of HCV and HIV prevention, but more effort should be devoted to HIV/HCV infection awareness. TRIAL REGISTRATION: Protocols for this study were approved by institution review board (IRB) of Shanghai Mental Health Center (IRB:2009036), and registered in U.S national institutes of health (http://www.clinicaltrials.gov, NCT01647191 ). Registered 23 July 2012.

Chronic exposure to dichloroacetamide induces biochemical and histopathological changes in the gills of zebrafish.

To evaluate the impact of DCAcAm on zebrafish gill, we measure the responses of antioxidant enzyme (superoxide dismutase, SOD), lipid peroxidation (malondialdehyde, MDA), ATPase (Na+ /K+ -ATPase and Ca2+ /Mg2+ -ATP) and histopathological changes of gill in adult zebrafish, after exposed to different concentrations of DCAcAm (0, 1, 10, 100, and 1000 µg L-1 ) for 30 days. Results indicated that DCAcAm first increased and then decreased SOD activity, and DCAcAm also lowered the activities of Na+ /K+ -ATPase and Ca2+ /Mg2+ -ATPase. These results indicated that high affinity of DCAcAm probably be a main factor, which can damage the structures of enzymes, thereby inhibiting the SOD and ATPase activities. Besides, histopathological investigation results also manifested that chronic exposure to DCAcAm can damage the gill tissues, disrupting the normal function of gills. We conclude that chronic exposure to DCAcAm was harmful to organisms, not only influence gill function, but also further cause damage on the gill tissues.

Hook1 inhibits malignancy and epithelial-mesenchymal transition in hepatocellular carcinoma.

Hook1 is a member of the hook family of coiled-coil proteins, which is recently found to be associated with malignant tumors. However, its biological function in hepatocellular carcinoma is yet unknown. Here, we evaluated the Hook1 levels in human hepatocellular carcinoma samples and matched peritumoral tissues by real-time polymerase chain reaction. Small interfering RNA knockdown and a transforming growth factor-ß-induced epithelial-mesenchymal transition model were employed to investigate the biological effects of Hook1 in hepatocellular carcinoma. Our results indicated that Hook1 levels were significantly lower in hepatocellular carcinoma tissues than in the peritumoral tissues. In addition, Hook1 expression was significantly associated with hepatocellular carcinoma malignancy. Hook1 was downregulated after transforming growth factor-ß-induced epithelial-mesenchymal transition. Moreover, Hook1 knockdown promoted epithelial-mesenchymal transition and attenuated the sensitivity of hepatocellular carcinoma cells to doxorubicin. In summary, our results indicate that downregulation of Hook1 plays a pivotal role in hepatocellular carcinoma progression via epithelial-mesenchymal transition. Hook1 may be used as a novel marker and therapeutic molecular target in hepatocellular carcinoma.

Gene identification of rare B(A) blood group.

OBJECTIVE: To study serologic and gene characteristics of the B(A) blood group of blood donation volunteers in Jilin Province, China. METHODS: ABO subgroups were identified by standard serologic techniques in ABO typing discrepancy samples from all donors at the Jilin Blood Center (410,354 non-repeat donors). DNA (deoxyribonucleic acid) was collected from each sample and PCR (polymerase chain reaction) was used to sequence exons 6 and 7 and intron 6, part 5 from the ABO subgroup samples. PCR products were sequenced to identify ABO subgroups and the B(A) allele. RESULTS: Four cases of B(A) blood type were found after sequencing, including two different alleles: B(A)02 and B(A)04. Three of the four alleles were B(A)04. CONCLUSION: Among blood donation volunteers in Jilin Province, China, B(A)04 is the most common B(A) blood group allele, followed by B(A)02. The B(A) blood group is associated with a complicated serologic phenotype and DNA detection is necessary for this atypical phenotype sample.

A new in-frame deletion in ribosomal protein S19 in a Chinese infant with Diamond-Blackfan anemia.

Diamond-Blackfan anemia (DBA) is a congenital erythroid aplasia that usually presents as macrocytic anemia during infancy. Ribosomal protein S19 (RPS19) is identified as the first gene associated with DBA. RPS19 is mutated in 25% of DBA patients, but its role in DBA pathogenesis remains to be elucidated. We have identified a novel heterozygous frameshift mutation in RPS19 gene in a DBA child presenting with profound anemia after birth. A single nucleotide heterozygous deletion (C.251delG) results in frameshift in RPS19 gene in exon 4 at codon 84 with possible premature stop codon (p.Arg84LysfsX21). The mutant allele was not detected in her parents, indicating de novo mutation. Both alleles were expressed at the same level. Using an immunofluorescence technique, the mutated-type RPS19 expressions were mostly localized to entire nuclei with little staining for nucleoli and its intracellular localization significantly differed from the wild-type RPS19, which was localized to both nuclei and nucleoli. This type of a mutation could be very helpful in further understanding the role of the RPS19 protein in DBA pathogenesis.

LB-100 sensitizes hepatocellular carcinoma cells to the effects of sorafenib during hypoxia by activation of Smad3 phosphorylation.

Hepatocellular carcinoma (HCC) is a common cancer with poor prognosis. The multikinase inhibitor sorafenib is the only clinically proved systematic treatment for HCC. However, few patients respond to sorafenib. Hypoxic microenvironments contribute to sorafenib resistance. LB-100, a serine/threonine protein phosphatase 2A (PP2A) inhibitor was previously found to be a chemosensitizer in HCC. Here, we tested whether LB-100 could sensitize HCC to the effects of sorafenib. Intriguingly, LB-100 enhanced the effects of sorafenib in HCC cells only during hypoxic environments. LB-100 dramatically increased intracellular p-Smad3 level, which was responsible for the effect of LB-100 as a sensitizer. LB-100 downregulated Bcl-2 expression and enhanced sorafenib-induced apoptosis in HCC cells. We further proved that PP2A mediated LB-100-induced p-Smad3 overexpression. In addition, p38 mitogen-activated protein kinase pathway was activated in hypoxic conditions, and enhanced p-Smad3-dependent Bcl-2 inhibition and consequent apoptosis. In conclusion, LB-100 sensitized HCC cells to sorafenib in hypoxic environments. This effect was mediated by inactivation of PP2A, resulting in enhanced level of p-Smad3. Increased p-Smad3 downregulated Bcl-2, causing increased apoptosis of HCC cells.

The effect of the plasma methotrexate concentration during high-dose methotrexate therapy in childhood acute lymphoblastic leukemia.

Two hundred and thirty-one acute lymphoblastic leukemia (ALL) children with 1376 high-dose methotrexate (HD-MTX) courses (3-5 g/m2) were enrolled to analyze the influence of the plasma MTX concentration (CMTX) in ALL. The 24-h target peak CMTX (C24h) was set at 33 µmol/l for low-risk (LR) and 65 µmol/l for intermediate/high-risk (IR/HR) groups. The median C24h was 42.0 µmol/l and 69.7 µmol/l for LR and IR/HR groups, respectively. MTX excretion delay was observed in 14.6% of courses, which was more frequent in IR/HR groups (56.9% vs. LR group 40.2%, p = .014) and T-ALL patients (82.6% vs. B-ALL 47.1%, p = .001). MTX-related toxicities were more common in courses with MTX excretion delay. However, survival between the patients who failed to reach the target C24h or not, with or without MTX excretion delay, was comparable. These findings suggest that, owing to the effectiveness of risk stratification chemotherapy, CMTX does not exert an independent influence on the prognosis of childhood ALL.

Helicobacter pylori Treatment and Gastric Cancer Risk Among Individuals With High Genetic Risk for Gastric Cancer.

Importance: Helicobacter pylori treatment and nutrition supplementation may protect against gastric cancer (GC), but whether the beneficial effects only apply to potential genetic subgroups and whether high genetic risk may be counteracted by these chemoprevention strategies remains unknown. Objective: To examine genetic variants associated with the progression of gastric lesions and GC risk and to assess the benefits of H pylori treatment and nutrition supplementation by levels of genetic risk. Design, Setting, and Participants: This cohort study used follow-up data of the Shandong Intervention Trial (SIT, 1989-2022) and China Kadoorie Biobank (CKB, 2004-2018) in China. Based on the SIT, a longitudinal genome-wide association study was conducted to identify genetic variants for gastric lesion progression. Significant variants were examined for incident GC in a randomly sampled set of CKB participants (set 1). Polygenic risk scores (PRSs) combining independent variants were assessed for GC risk in the remaining CKB participants (set 2) and in an independent case-control study in Linqu. Exposures: H pylori treatment and nutrition supplementation. Main Outcomes and Measures: Primary outcomes were the progression of gastric lesions (in SIT only) and the risk of GC. The associations of H pylori treatment and nutrition supplementation with GC were evaluated among SIT participants with different levels of genetic risk. Results: Our analyses included 2816 participants (mean [SD] age, 46.95 [9.12] years; 1429 [50.75%] women) in SIT and 100 228 participants (mean [SD] age, 53.69 [11.00] years; 57 357 [57.23%] women) in CKB, with 147 GC cases in SIT and 825 GC cases in CKB identified during follow-up. A PRS integrating 12 genomic loci associated with gastric lesion progression and incident GC risk was derived, which was associated with GC risk in CKB (highest vs lowest decile of PRS: hazard ratio [HR], 2.54; 95% CI, 1.80-3.57) and further validated in the analysis of 702 case participants and 692 control participants (mean [SD] age, 54.54 [7.66] years; 527 [37.80%] women; odds ratio, 1.83; 95% CI, 1.11-3.05). H pylori treatment was associated with reduced GC risk only for individuals with high genetic risk (top 25% of PRS: HR, 0.45; 95% CI, 0.25-0.82) but not for those with low genetic risk (HR, 0.81; 95% CI, 0.50-1.34; P for interaction = .03). Such effect modification was not found for vitamin (P for interaction = .93) or garlic (P for interaction = .41) supplementation. Conclusions and Relevance: The findings of this cohort study indicate that a high genetic risk of GC may be counteracted by H pylori treatment, suggesting primary prevention could be tailored to genetic risk for more effective prevention.

The incremental significance of heart rate recovery as a predictor during exercise-stress myocardial perfusion SPECT imaging in individuals with suspected coronary artery disease.

Background: Major adverse cardiac events (MACE) are more likely to occur when abnormal heart rate recovery (HRR). This study aimed to assess the incremental predictive significance of HRR over exercise stress myocardial perfusion single-photon emission computed tomography (MPS) results for MACE in individuals with suspected coronary artery disease (CAD). Methods: Between January 2014 and December 2017, we continually gathered data on 595 patients with suspected CAD who received cycling exercise stress MPS. HRR at 1, 2, 3, and 4 min were used as study variables to obtain the optimal cut-off values of HRR for MACE. The difference between the peak heart rate achieved during exercise and the heart rate at 1, 2, 3, and 4 min was used to calculate the HRR, as shown in HRR3. Heart rate variations between two locations in time, such as HRR2 min-1 min, were used to establish the slope of HRR. All patients were followed for a minimum of 4 years, with MACE as the follow-up goal. The associations between HRR and MACE were assessed using Cox proportional hazards analyses. Results: Patients with MACE were older (P = 0.001), and they also had higher rates of hypertension, dyslipidemia, diabetes, abnormal MPS findings (SSS ≥ 5%), medication history (all P < 0.001), and lower HRR values (all P < 0.01). Patients with and without MACE did not significantly vary in their HRR4 min-3 min. The optimal cut-off of HRR1, 2, and 3 combined with SSS can stratify the risk of MACE in people with suspected CAD (all P < 0.001). HRR 1, 2, and 3 and its slope were linked to MACE in multivariate analysis, where HRR3 was the most significant risk predictor. With a global X2 increase from 101 to 126 (P < 0.0001), HRR3 demonstrated the greatest improvement in the model's predictive capacity, incorporating clinical data and MPS outcomes. Conclusions: HRR at 3 min has a more excellent incremental prognostic value for predicting MACE in patients with suspected CAD following cycling exercise stress MPS. Therefore, incorporating HRR at 3 min into known predictive models may further improve the risk stratification of the patients.

A global study for acute myeloid leukemia with RARG rearrangement.

Acute myeloid leukemia (AML) with retinoic acid receptor γ (RARG) rearrangement has clinical, morphologic, and immunophenotypic features similar to classic acute promyelocytic leukemia. However, AML with RARG rearrangement is insensitive to alltrans retinoic acid (ATRA) and arsenic trioxide (ATO) and carries a poor prognosis. We initiated a global cooperative study to define the clinicopathological features, genomic and transcriptomic landscape, and outcomes of AML with RARG rearrangements collected from 29 study groups/institutions worldwide. Thirty-four patients with AML with RARG rearrangements were identified. Bleeding or ecchymosis was present in 18 (54.5%) patients. Morphology diagnosed as M3 and M3v accounted for 73.5% and 26.5% of the cases, respectively. Immunophenotyping showed the following characteristics: positive for CD33, CD13, and MPO but negative for CD38, CD11b, CD34, and HLA-DR. Cytogenetics showed normal karyotype in 38% and t(11;12) in 26% of patients. The partner genes of RARG were diverse and included CPSF6, NUP98, HNRNPc, HNRNPm, PML, and NPM1. WT1- and NRAS/KRAS-mutations were common comutations. None of the 34 patients responded to ATRA and/or ATO. Death within 45 days from diagnosis occurred in 10 patients (∼29%). At the last follow-up, 23 patients had died, and the estimated 2-year cumulative incidence of relapse, event-free survival, and overall survival were 68.7%, 26.7%, and 33.5%, respectively. Unsupervised hierarchical clustering using RNA sequencing data from 201 patients with AML showed that 81.8% of the RARG fusion samples clustered together, suggesting a new molecular subtype. RARG rearrangement is a novel entity of AML that confers a poor prognosis. This study is registered with the Chinese Clinical Trial Registry (ChiCTR2200055810).

Diagnosing temporomandibular joint disorders using second harmonic imaging of collagen fibers.

This proposed optical imaging method is a nondestructive, real-time and high-resolution approach to distinguish healthy and injured temporomandibular joint (TMJ) tissues. And the TMJ health index was invented. TMJ pathologies are commonly and reported frequently. It could be associated with the damage of collagen, cartilage and bone tissue. The second harmonic generation images could be obtained by a femtosecond laser pulses, so the aligned information of the collagen fibers in all directions for the TMJ disorders was collected. The disorder degree of collagen fibers was quantified and ranked using a fast Fourier transform (FFT) method. The TMJ health index can effectively present the TMJ healthy condition and the disorder degree of collagen fibers, a valuable objective tool for tissue characterization for TMJ healthy condition. Integrated with the staining methods, we can provide the scaling information at different injury degree.

Integration of Interleukin-6 Improves the Diagnostic Precision of Metagenomic Next-Generation Sequencing for Infection in Immunocompromised Children.

The performance of metagenomic next-generation sequencing (mNGS) in identifying pathogens in immunocompromised children was not very clear. The purpose of this study is to assess the performance of mNGS in this population and to investigate whether the integration of serum cytokines and mNGS assay could improve diagnostic accuracy. We retrospectively collected the clinical data of pediatric patients who suffered febrile diseases and underwent mNGS determination simultaneously in the department of hematology/oncology between January 2019 and March 2021. Specimens were sent for conventional microbiological test (CMT), mNGS, and serum cytokine measurement in parallel. A total of 258 episodes of febrile diseases were enrolled, mNGS was positive in 224 cases, while CMT was positive in 78 cases. mNGS and CMT were both positive in 70 (27.1%) cases and were both negative in 26 (10.1%) cases. There were 154 (59.7%) cases positive by mNGS only while 8 (3.1%) were positive by CMT only. It was common that two or more pathogens were simultaneously detected by mNGS in a single specimen, with only 61 tests identified a single organism. Whether the organisms reported by mNGS were the microbiological etiology of infection was evaluated. Of the 224 cases with positive mNGS results, 135 (58.4%), 30 (13.0%), and 59 (28.6%) were considered as "probable," "possible," and "unlikely," respectively. Patients with high IL-6 (≥ 390 pg/ml) were likely to be bacterial infection. Although mNGS reported mixed pathogens, 84.6% (33/39) and 83.3% (10/12) of patients presenting high IL-6 were confirmed as bacterial infection in the training and validation cohort, respectively. In conclusion, mNGS analysis demonstrates promising diagnostic potential in rapidly identifying clinically relevant pathogens. Given the detection of many clinically irrelevant organisms, the integration of IL-6 improves the precision of mNGS results interpretation.

Metagenomic next-generation sequencing for the diagnosis of fever of unknown origin in pediatric patients with hematological malignancy.

BACKGROUND AND AIMS: The aim of this study was to evaluate the performance of metagenomic next-generation sequencing (mNGS) in identifying microbiological etiologies in pediatric patients with hematological malignancies undergoing fever of unknown origin (FUO). METHODS: A total of 147 children with hematological malignancy suffering febrile diseases without definite microbiological etiologies under conventional tests were enrolled. The clinical record, serum inflammatory biomarkers and mNGS results were analyzed. RESULTS: At least one microorganism was identified by mNGS in 112 of 147 patients (76.2 %). Two or more types of organisms were detected simultaneously in 35.7 % (40/112) of samples. Of the 112 cases with positive mNGS results, the reported microorganisms were considered as etiologies of fever in 50 (44.6 %) cases. The initial antimicrobial regimens were adjusted according to the mNGS results in 48 cases, with 41 patients' febrile diseases resolved. Totally, 27.9 % (41/147) of patients benefit from mNGS. High IL-6 (>390 pg/mL) level was associated with bacterial infection and could help to interpret the results of mNGS. CONCLUSION: mNGS is a novel approach to determine the microbiological etiology of FUO in hematological malignancy patients, which benefits about a quarter of all patients tested. Integration of IL-6 can improve the diagnostic precision of bacterial infection.

Pediatric blastic plasmacytoid dendritic cell neoplasm: report of four cases and review of literature.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematological malignancy with poor outcome. Four children with BPDCN treated at our hospital were enrolled. All the four cases presented with cutaneous lesions. Bone marrow and central nervous system was involved in 50% and 25% of patients, respectively. The whole exome sequencing analysis revealed that KMT2 family genes were the most frequently mutated (4/4, 100%), followed by IKZF2 (2/4, 50%). The point mutation p.D348N was found in three patients and one patient had p.C394Y mutation in the KMT2C gene. Translocation of KMT2A-MLLT3 was found in Case 2. Case 1 had complex karyotype, who was induced by acute myeloid leukemia-like regimens. Although he received allogeneic hematopoietic stem cell transplantation twice as well as CD123 chimeric antigen receptor T cell therapy, the disease still progressed and he died 37 months after diagnosis. The other three patients were treated with Interfant-99 protocol. They tolerated the therapy well without significant toxicities and now in complete remission so far with a median follow up time of 9 months. More studies are needed to address the question whether the complex karyotype and KMT2 family genes are the causes of the relapse and refractory in BPDCN.