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.

Yuejuwan is a classic formula widely used by doctors to relieve liver and depression， with precise clinical efficacy in traditional Chinese medicine （TCM）. The authors used bibliometric methods to collect and collate 495 ancient data related to Yuejuwan， and 105 valid data were screened out， involving 68 ancient Chinese medical books. After systematic verification of the origin of the formula of Yuejuwan， the main treatment symptoms， the principle of the formula， the composition of the drug， the dosage， the preparation method， the decoction method， and other information， the results showed that Yuejuwan originated from the Danxi Xinfa （《丹溪心法》） of the Yuan Dynasty by ZHU Zhenheng， and it is composed of five medicines， namely Atractylodis Rhizoma， Cyperi Rhizom， Chuanxiong Rhizoma， Massa Medicata Fermentata， and Gardeniae Fructus. In terms of drug base， Atractylodis Rhizoma， Cyperi Rhizom， Chuanxiong Rhizoma， and Gardeniae Fructus are in line with the records in the 2020 edition of Chinese Pharmacopoeia， and Massa Medicata Fermentata is used. The preparation method is as follows： Massa Medicata Fermentata and Gardeniae Fructus are fried， and Cyperi Rhizoma is roasted in vinegar. Chuanxiong Rhizoma is used in the raw form， and Atractylodis Rhizoma is prepared with rice swill. The formula can regulate Qi and relieve depression and broaden the middle and remove fullness. It is clinically used for the treatment of six types of depression syndromes， chest and diaphragm plumpness， abdominal distension and leg acid， acid swallowing and vomiting， eating and drinking disharmony， toothache， mouth and tongue sores， and other diseases. The most used dosage of the formula in the ancient records through the ages is converted into the modern dosage， namely 3.05 g Atractylodis Rhizoma， 3.05 g Cyperi Rhizoma， 3.05 g Chuanxiong Rhizoma， 3.05 g Massa Medicata Fermentata， and 3.05 g Gardeniae Fructus， and the daily dosage is 15.25 g. The converted dosage is similar to that recorded in the 2020 edition of the Chinese Pharmacopoeia. The formula is in pill form， and medicine should be taken with lukewarm boiled water after the meal. Through the excavation of the ancient literature related to Yuejuwan， the key information of the formula is identified， with a view to providing a more accurate reference for the clinical application of Yuejuwan and subsequent in-depth investigation.

Yuejuwan is a classic formula widely used by doctors to relieve liver and depression， with precise clinical efficacy in traditional Chinese medicine （TCM）. The authors used bibliometric methods to collect and collate 495 ancient data related to Yuejuwan， and 105 valid data were screened out， involving 68 ancient Chinese medical books. After systematic verification of the origin of the formula of Yuejuwan， the main treatment symptoms， the principle of the formula， the composition of the drug， the dosage， the preparation method， the decoction method， and other information， the results showed that Yuejuwan originated from the Danxi Xinfa （《丹溪心法》） of the Yuan Dynasty by ZHU Zhenheng， and it is composed of five medicines， namely Atractylodis Rhizoma， Cyperi Rhizom， Chuanxiong Rhizoma， Massa Medicata Fermentata， and Gardeniae Fructus. In terms of drug base， Atractylodis Rhizoma， Cyperi Rhizom， Chuanxiong Rhizoma， and Gardeniae Fructus are in line with the records in the 2020 edition of Chinese Pharmacopoeia， and Massa Medicata Fermentata is used. The preparation method is as follows： Massa Medicata Fermentata and Gardeniae Fructus are fried， and Cyperi Rhizoma is roasted in vinegar. Chuanxiong Rhizoma is used in the raw form， and Atractylodis Rhizoma is prepared with rice swill. The formula can regulate Qi and relieve depression and broaden the middle and remove fullness. It is clinically used for the treatment of six types of depression syndromes， chest and diaphragm plumpness， abdominal distension and leg acid， acid swallowing and vomiting， eating and drinking disharmony， toothache， mouth and tongue sores， and other diseases. The most used dosage of the formula in the ancient records through the ages is converted into the modern dosage， namely 3.05 g Atractylodis Rhizoma， 3.05 g Cyperi Rhizoma， 3.05 g Chuanxiong Rhizoma， 3.05 g Massa Medicata Fermentata， and 3.05 g Gardeniae Fructus， and the daily dosage is 15.25 g. The converted dosage is similar to that recorded in the 2020 edition of the Chinese Pharmacopoeia. The formula is in pill form， and medicine should be taken with lukewarm boiled water after the meal. Through the excavation of the ancient literature related to Yuejuwan， the key information of the formula is identified， with a view to providing a more accurate reference for the clinical application of Yuejuwan and subsequent in-depth investigation.

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

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 understand the functional requirements and suggestions of relevant stakeholders on the Internet platform for remote rehabilitation management of patients after arthroscopy, so as to provide a reference basis for building a home rehabilitation management scheme and developing a remote Internet platform.Methods:Based on the technology acceptance model, a descriptive qualitative study was conducted using purposive sampling and maximum difference method to select 11 arthroscopic postoperative patients, 4 patient caregivers, and 7 clinical professionals from the Sports Medicine Department of Wuxi Ninth People′s Hospital (Orthopaedic Hospital) from October to December 2022. A total of 22 stakeholders were interviewed in a semi-structured manner, and the Colaizzi was used to analyze the interview data.Results:Among 22 interviewers, 12 males, 10 females, aged 25-65 years. A total of four topics were summarized: the willingness to use the Internet platform for remote rehabilitation management, the demand for the content provided by the Internet platform for remote rehabilitation management, the demand for the module functions of the Internet platform for remote rehabilitation management, and the demand for the operability of the Internet platform for remote rehabilitation management.Conclusions:The general attitude of the stakeholder groups towards the use of the Internet platform for remote rehabilitation management of patients after arthroscopy is positive. It is hoped that the platform will have diversified functions and good usability, improve the compliance and enthusiasm of patients in home rehabilitation exercise, and thus promote the recovery of limb function.

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.