Objective: To establish a real-time quality control scheme based on the median (MD-IC) of internal control cycle threshold value in negative samples (NEG-IC-CT), so as to monitor anomalies such as progressive drift in nucleic acid testing system not covered by conventional internal quality control (IQC) in blood center nucleic acid laboratories, and to verify its feasibility. Methods: The internal control CT values of 54 426 negative samples were retrospectively collected. These samples were from four reagent batches of the two new and old equipment sets during the operation of the Wantai nucleic acid testing system in our blood center. The daily median of NEG-IC-CT values was used as the research indicator. Control limits were calculated using median absolute deviation (MAD) to construct the Median-MAD quality control chart. The monitoring performance of this scheme for the operation status of the testing system was simultaneously evaluated. Results: Statistical analysis showed significant differences in NEG-IC-CT value distribution between the new and old equipment sets, as well as between the two different reagent batches of the old equipment (P<0.000 1). The NEG-IC-CT value performance of the two different reagent batches of the new equipment was no significant difference in distribution (P>0.05). This scheme identified three typies of distinct anomalies. The out-of-control events observed with the old equipment in both the O1 and O2 reagent batches suggested potential performance decay due to equipment aging. The unreported change of reagent batch in time of Phase B with new equipment caused a stepwise drift on the quality control chart. In the later stage of Phase A with the new equipment, an alert was triggered, indicating potential quality risks associated with practices such as the mixed use of the remaining reagents and extremely long operator working hours. Conclusion: The realtime quality control scheme based on NEG-IC-CT value established in this study has been preliminarily validated for its monitoring effectiveness in nucleic acid testing in our blood center. This scheme performed well in detecting differences among testing systems and reagent batches, serving as an effective supplement to routine internal quality control. It can provide an intuitive and effective evaluation method for monitoring the performance of the nucleic acid testing process at blood center.

A 51-year-old male presented with nasal obstruction, followed by progressive hearing loss and blurred vision. Imaging identified space-occupying lesions in the paranasal sinuses, orbits, and paraspinal regions, while laboratory tests confirmed positive anti-proteinase 3 anti-neutrophil cytoplasmic antibody(PR3- ANCA) immunoglobulin G (IgG)and markedly elevated serum IgG4. Despite treatment with corticosteroids, immunosuppressants, and radiotherapy, the patient exhibited steroid dependency with relentless disease progression. Following multidisciplinary consultation, a diagnosis of inflammatory myofibroblastic tumor (IMT) coexisting with ANCA- associated vasculitis (AAV) was favored, though IgG4-related disease remained a critical differential. Ultimately, profound immunosuppression precipitated a severe herpesvirus infection, leading to disseminated intravascular coagulation and multiple organ dysfunction syndrome. This case underscores the rarity and diagnostic complexity of concurrent IMT and AAV, highlights the therapeutic dilemma of balancing primary disease control against fatal opportunistic infections, and emphasizes the critical role of multidisciplinary collaboration in the diagnosis and treatment of complex diseases.

ObjectiveThis paper aims to clarify the material basis of Gualou Niubangtang and establish a quantitative analysis method for its main constituents， providing a reference for the overall quality control of this preparation. MethodsThe constituents in the formula were systematically characterized based on ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry （UPLC-Q-TOF-MS/MS）. Identification was performed by matching with the UNIFI 9.6 software and utilizing database platforms such as PubChem， ChemicalBook， and ChemSpider， combined with relevant literature reports. A quantitative analysis method for the seven main constituents in Gualou Niubangtang was established by using high performance liquid chromatography （HPLC）. ResultsUPLC-Q-TOF-MS/MS analysis identified 155 constituents， including 69 flavonoids， 36 terpenoids， 23 phenylpropanoids， 8 phenylethanoid glycosides， and 19 other types of constituents. In the established quantitative analysis method， the seven main constituents showed good linearity within their respective linear ranges. The precision， repeatability， stability， and spike recovery all met the required standards. The results showed that the content ranges of geniposide， liquiritin， hesperidin， arctiin， baicalin， oroxylin A-7-O-β-D-glucuronide， and wogonoside in 15 batches of Gualou Niubangtang were 13.67-21.25， 1.20-7.64， 5.45-7.45， 22.97-33.51， 29.95-39.07， 2.58-4.80， and 6.56-9.31 mg·g^-1， respectively. ConclusionThis study successfully characterizes and attributes multi-category constituents in Gualou Niubangtang， clarifying that its material basis is primarily composed of flavonoids， terpenoids， phenylethanoid glycosides， and phenylpropanoids. Furthermore， it enables the quantification of seven constituents within the formula. This work lays a foundation for research on the quality control， action mechanism， and clinical application of this formula.

Objective: To analyze the epidemiological characteristics of infectious diseases among children and adolescents in Lanshan District, Linyi City, 2014-2023,so as to provide a scientific basis for prevention and control strategies in schools. Methods: The surveillance data were obtained from the China Information System for Disease Control and Prevention (CISDCP). Data on reported infectious disease cases and related demographic information among school children and kindergarteners in the study area from 2014 to 2023 were collected. Rate comparison was performed by using the χ 2 test. Trend analysis was conducted by using Joinpoint Regression Progrom, and the annual percent change (APC) and average annual percent change (AAPC) were calculated. Results: A total of 10 222 cases of infectious diseases among children and adolescents were reported from 2014 to 2023, with an average annual incidence rate of 273.32 per 100 000. The overall incidence trend remained stable from 2014 to 2023 (AAPC=12.33%, 95%CI=-2.63%-29.59%, P >0.05). Whereas a significant upward trend was observed from 2014 to 2019 (AAPC=37.08%, 95% CI =12.92%-66.41%, P <0.05), followed by a stable trend from 2019 to 2023 (AAPC=-0.31%, 95%CI=-39.70%-64.83%, P>0.05). Seasonal distribution exhibited dual peaks in summer and winter. The incidence rate in urban areas(707.29/100 000) was significantly higher than that in rural areas(257.50/100 000), and the incidence rate among kindergarteners (325.49/100 000) was higher than that among school children (257.07/100 000) (χ2=1 518.60, 116.36, both P<0.01). The reported infectious diseases among children and adolescents were predominantly respiratory and intestinal infectious diseases, with incidence rates of 156.13/100 000 and 108.51/100 000, respectively. Hand, foot, and mouth disease (HFMD) was the predominant infectious disease among kindergarteners, accounting for 47.51%. Influenza was the leading condition in the primary school group, accounting for 38.64%, and other infectious diarrheal diseases were most common in junior and senior high school group, accounting for 53.34%. The top six diseases by incidence rate were other infectious diarrheal diseases(65.22/100 000), influenza(63.24/100 000), varicella(46.34/100 000), HFMD(41.07/100 000), mumps(23.42/100 000), and scarlet fever(10.56/100 000). Among them, the incidence of other infectious diarrheal diseases rose significantly (AAPC=35.31%, 95% CI =14.32%-60.14%, P <0.01). The trend transitioned from a rapid escalation during 2014-2019 (APC=69.98%, 95% CI =17.58%-145.74%, P =0.01) to a stable phase during 2019-2023 (APC=1.74%, 95% CI =-15.61%- 22.66%, P >0.05). Conclusions In Lanshan, urban educational institutions should prioritize the prevention and control of infectious diseases, with particular emphasis on other infectious diarrheal diseases, influenza and varicella. Targeted interventions should be implemented in accordance with seasonal patterns and the specific characteristics of the school age populations.

Objective To use imaging features of pulmonary nodules to predict the risk of lymph node metastasis in patients with cT1-stage non-small cell lung cancer (NSCLC), providing a reference for clinical decision-making. Methods A retrospective analysis was conducted on the imaging features and postoperative pathological results of cT1 NSCLC patients who underwent surgical treatment at Linyi People’s Hospital from July 2019 to July 2022. Patients were grouped and analyzed according to lymph node metastasis status. Results A total of 1 123 patients were included, comprising 471 males and 652 females, with a median age of 59 (52, 66) years. Comparative analysis revealed that sex, age, nodule location, nodule size on imaging, solid component size, consolidation tumor ratio (CTR), average CT value, and tumor proximity to the pleura all influenced lymph node metastasis. A nomogram was constructed, indicating that the probability of lymph node metastasis in cT1 NSCLC was positively correlated with solid component size, CTR, and average CT value of the pulmonary nodule, and negatively correlated with patient age. The area under the receiver operating characteristic curve was 0.929. Conclusion For cT1 NSCLC patients, the probability of lymph node metastasis can be predicted by measuring the solid component size, CTR, and average CT value of the pulmonary nodule, in conjunction with patient age. However, relying solely on pulmonary nodule imaging characteristics is insufficient to determine a specific lymph node dissection strategy.

Objective:To evaluate the efficacy and safety of IBUCy(idarubicin,busulfan,and cyclophosphamide)and FABC(fludarabine,cyta-rabine,busulfan,and cyclophosphamide)conditioning regimens followed by allogeneic hematopoietic stem cell transplantation(allo-HSCT)for the treatment of medium-to-high risk acute myelocytic leukemia(AML).Methods:We retrospectively analyzed data of 49 patients with medium-to-high risk AML who received IBUCy(n=17)or FABC(n=32)conditioning regimens followed by allo-HSCT between January 2015 and December 2021 at The First Affiliated Hospital of Chongqing Medical University.Hematopoietic reconstruction time,adverse events,and survival outcomes were compared between the two groups to assess the efficacy and safety of the two regimens.Additionally,we analyzed factors that may be associated with prognosis.Results:Hematopoietic reconstruction was successful in all 49 patients.No significant differ-ences were observed between the two groups in terms of hematopoietic reconstruction time.Similarly,no significant differences were ob-served in the 5-year progression-free survival(PFS)and overall survival(OS)rates between the two groups.The incidence rates of oral mu-cositis,nausea and vomiting,diarrhea(≥grade 3 based on CTCAE v5.0),and chronic graft-versus-host disease(GVHD)were significantly high-er in the IBUCy group than that in the FABC group.However,the incidence rate of hemorrhagic cystitis in the FABC group was significantly higher than that in the IBUCy group.The time from diagnosis to allo-HSCT>6 months and being minimal residual disease(MRD)-positive be-fore transplantation were identified as the risk factors for PFS(P=0.019 and P=0.048,respectively).Patients who were MRD-negative before transplantation had significantly longer PFS when treated with the IBUCy conditioning regimen(P=0.039).Conclusions:Both IBUCy and FABC conditioning regimens prior to allo-HSCT are safe and effective for treating medium-to-high risk AML.Allo-HSCT should be performed as soon as possible when patients achieve their first complete remission.Patients with an MRD-negative status before transplantation tend to have longer PFS.Compared with the FABC regimen,the IBUCy regimen has some advantages;however,attention should be given to the prevention and management of gastrointestinal adverse events and chronic GVHD.

Objective:To generate a chronic lymphocytic leukemia (CLL) mouse model with intact immune competence and short latency by adoptively transferring (AT) splenocytes from immunoglobulin heavy-chain enhancer-driven T-cell leukemia/lymphoma 1 (Eμ-TCL1) transgenic donors into wild-type (WT) recipients.Methods:Specific pathogen-free C57BL/6J WT mice and H11-Eμ-VH-TCL1-β-globin-PolyA knock-in mice were utilized. The H11-Eμ-VH-TCL1-β-globin-PolyA knock-in mice were generated using CRISPR/Cas9 technology, and their genotypes were confirmed by PCR. Experimental animals were randomly divided into an adoptive transfer (AT) group and a WT control group ( n=10 per group). Mice in the AT group received an intraperitoneal injection of splenocytes from H11-Eμ-VH-TCL1-β-globin-PolyA knock-in mice. The weight and general condition of the mice were monitored. Mice were euthanized by cervical dislocation at 9 weeks post-transplantation. The CLL model was validated using key indicators, including pathological manifestations, changes in peripheral blood leukocyte counts, and immunophenotype. Results:AT group mice exhibited significantly increased spleen weight [ (0.92±0.16) g vs (0.06±0.01) g in WT group, P<0.05] and liver weight [ (2.11±0.56) g vs (1.42±0.13) g in WT group, P=0.006], indicative of marked splenomegaly and hepatomegaly. The peripheral blood leukocyte count was significantly higher in the AT group [ (124.33±8.74) ×10 9/L] compared to the WT group [ (5.55±1.67) ×10 9/L] ( P=0.002). Similarly, the percentage of peripheral blood B lymphocytes was markedly increased in the AT group versus the WT group [ (69.13±6.88) % vs (39.78±5.94) %, P<0.05]. Histopathological examination revealed CLL manifestations in the spleen, lymph nodes, and bone marrow of AT group mice, with significant lymphocytic infiltration observed in the liver, lung, and kidney tissues. Flow cytometry analysis showed that the percentages of CD19 +CD5 + B lymphocytes among total lymphocytes in peripheral blood, bone marrow, and spleen of the AT group were (61.37±9.92) %, (28.61± 7.08) %, and (86.03±5.78) %, respectively. These were significantly higher (all P<0.05) than in the WT group [ (4.51±1.32) %, (5.58±1.46) %, and (14.33±3.20) %]. Furthermore, these CLL-like cells in the AT group were positive for CD43 and CD200, but showed lower expression of CD20, CD22, and CD79b compared to WT B cells. Conclusion:Adoptive transfer of splenocytes from Eμ-TCL1 transgenic mice successfully established a CLL mouse model with a relatively short latency period. This model represents a valuable preclinical tool for investigating CLL and related pathologies.

Objective To explore the application value of different deep learning models in predicting the lung cancer spread through air spaces(STAS).Methods A total of 203 patients with stage Ⅰ—Ⅱ primary lung cancer were included,of which 74 were STAS-positive and 129 were STAS-negative.Patients were randomly divided into training set(142 cases)and test set(61 cases)at a 7∶3 ratio.Region of interest(ROI)was outlined using ITK-SNAP software,facilitating the extraction of tumor and peritumoral images.The Resnet18,Inception_v3,and Vision Transformer(Vit)were employed for model training and feature extraction.Feature selection was performed by the least absolute shrinkage and selection operator(LASSO)algorithm and Spearman correlation coefficient,followed by the establishment of a predictive model using the Naive Bayes machine learning algorithm.The receiver operating characteristic(ROC)curve was drawn to compare the prediction performance of each model.The assessment of calibration was performed using calibration curves,and the evaluation of clinical application value was conducted using decision curve analysis(DCA).Results The area under the curve(AUC)for the training and test sets were as follows:the training set Resnet18 0.849-0.930,Inception_v3 0.848-0.888,Vit 0.747-0.842;and the test set Resnet18 0.796-0.846,Inception_v3 0.783-0.804,Vit 0.690-0.796.In tumor-peritumoral images,Resnet18 had a higher calibration and better clinical net benefit,while Vit showed superior calibration and clinical net benefit when only tumor tissue was considered.Conclusion Deep learning models can effectively predict lung cancer STAS,providing more decision support for the preoperative diagnosis and treatment of stages Ⅰ—Ⅱ lung cancer.

OBJECTIVE: To explore the genetic etiology for a child presenting with motor retardation, language delay, intellectual disability, and dysmorphic features. METHODS: A child presented at Linyi People's Hospital in June 2022 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples were obtained from the child and her parents. Following extraction of genomic DNA, whole-exome sequencing (WES) was carried out. Candidate variant was validated by Sanger sequencing. Amniotic fluid samples were obtained from the mother's subsequent pregnancies for prenatal diagnosis. This study has been reviewed and approved by the Medical Ethics Committee of Linyi People's Hospital (Ethics No.: 2019-134). RESULTS: The proband was a 2-year-old girl showing developmental delays in motor, language, and intellectual domains, strabismus, hypertelorism, hearing impairment, obesity, and brachymesophalangy of the fifth finger. Magnetic resonance imaging revealed abnormalities of the white matter. Chromosomal microarray analysis (CMA) identified a 15q26.3 duplication (chr15:101562020_102060896 × 3) inherited from her mother. WES has uncovered a heterozygous c.1931A>G (p.Tyr644Cys) variant in the FBXO11 gene. Sanger sequencing confirmed the variant to be de novo in origin. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic. Prenatal diagnosis revealed that the fetuses from the mother's second and third pregnancies did not harbor the same variant. CONCLUSION The c.1931A>G (p.Tyr644Cys) variant of the FBXO11 gene probably underlay the abnormal phenotype in the child. Based on its genotype and phenotype, the proband was diagnosed with Intellectual developmental disorder with dysmorphic facies and behavioral abnormalities.
Humans ; Female ; Intellectual Disability/genetics* ; Child, Preschool ; F-Box Proteins/genetics* ; Protein-Arginine N-Methyltransferases/genetics* ; Exome Sequencing