Chemotherapy-induced peripheral neurotoxicity (CIPN) is a severe dose-limiting adverse event of chemotherapy. Presently, the mechanism underlying the induction of CIPN remains unclear, and no effective treatment is available. In this study, through metabolomics analyses, we found that nab-paclitaxel therapy markedly increased serum serotonin [5-hydroxtryptamine (5-HT)] levels in both cancer patients and mice compared to the respective controls. Furthermore, nab-paclitaxel-treated enterochromaffin (EC) cells showed increased 5-HT synthesis, and serotonin-treated Schwann cells showed damage, as indicated by the activation of CREB3L3/MMP3/FAS signaling. Venlafaxine, an inhibitor of serotonin and norepinephrine reuptake, was found to protect against nerve injury by suppressing the activation of CREB3L3/MMP3/FAS signaling in Schwann cells. Remarkably, venlafaxine was found to significantly alleviate nab-paclitaxel-induced CIPN in patients without affecting the clinical efficacy of chemotherapy. In summary, our study reveals that EC cell-derived 5-HT plays a critical role in nab-paclitaxel-related neurotoxic lesions, and venlafaxine co-administration represents a novel approach to treating chronic cumulative neurotoxicity commonly reported in nab-paclitaxel-based chemotherapy.
Paclitaxel/toxicity* ; Animals ; Albumins/adverse effects* ; Serotonin/metabolism* ; Mice ; Humans ; Male ; Female ; Venlafaxine Hydrochloride/therapeutic use* ; Neurotoxicity Syndromes/metabolism* ; Middle Aged ; Schwann Cells/metabolism* ; Peripheral Nervous System Diseases/drug therapy* ; Antineoplastic Agents

Objectives:To investigate the physical growth status of pediatric patients with transfusion-dependent thalassemia (TDT) and analyze the effects of treatment-related and socioeconomic factors on physical growth.Methods:Based on the specialized thalassemia database from gene therapy clinical research at the Institute of Hematology & Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, we collected data on height and weight development, family economic status, and medical records of 338 pediatric patients with TDT from October 2023 to May 2024. The length/height-for-age and body mass index (BMI) -for-age were classified based on the Growth Standard for Children under 7 Years of Age, Standard for Height Level Classification among Children and Adolescents Aged 7-18 Years, and Dietary Guidelines for Chinese Residents. Logistic regression analysis was conducted to assess the effects of family economic status and disease-related treatment on length/height-for-age and BMI-for-age.Results:Among the 338 patients, 118 were children and 220 were adolescents (192 males and 146 females), with a median age of 12 years (range: 0.8-18) and a median diagnosis duration of 10.3 years (range: 0.5-17.9). Subtypes included α-thalassemia [21 cases (6.2%) ], β-thalassemia [288 cases (85.2%) ], and combined αβ-thalassemia[29 cases (8.6%) ]. The monthly household income of patients was concentrated in 3 000-5 000 yuan (39.9%) and 5 001-10 000 yuan (34.9%), whereas 67.2% of the families had monthly medical expenses of <3 000 yuan. Of the patients, 75.5% received their first transfusion before 1 year of age. The proportions of children and adolescents with pretransfusion hemoglobin (HGB) of ≤70 g/L were 4.2% and 6.4%, respectively. Adolescents demonstrated significantly higher rates of transfusion frequency of <4 weeks/session, monthly red blood cell infusion of >2 U, serum ferritin (SF) of ≥5 000 μg/L, iron chelation therapy, and splenectomy compared with children (all P<0.05). Of the 338 patients, 26.0%, 22.8%, and 8.9% demonstrated stunted growth, underweight, and concurrent stunted growth with underweight, respectively. No significant difference was observed in the stunted growth rates between children (22.9%) and adolescents (27.7%) ( P=0.402). However, the underweight rate in adolescents (26.8%) was significantly higher than that in children (15.3%) ( P=0.023). The multivariate analysis determined the following risk factors for stunted growth: monthly household income of <10 000 yuan (5 001-10 000 yuan: OR=5.49, 95% CI: 1.48-35.76; 3 000-5 000 yuan: OR=6.87, 95% CI: 1.88-44.60; <3 000 yuan: OR=9.29, 95% CI: 2.20-64.77), pretransfusion HGB of ≤70 g/L ( OR=3.25, 95% CI: 1.07-10.18), and SF of ≥5 000 μg/L ( OR = 3.04, 95% CI: 1.20-7.70). Longer diagnostic duration was associated with underweight ( OR=1.10, 95% CI: 1.01-1.20) . Conclusions:Children and adolescents with TDT with pretransfusion SF of ≥5 000 μg/L, HGB of ≤70 g/L, low monthly household income, or longer diagnosis duration were significantly more likely to experience delayed physical growth.

Objective:To evaluate the efficacy of cyclophosphamide in patients with T-cell large granular lymphocytic leukemia (T-LGLL) and the maintenance of treatment-free remission (TFR) following drug discontinuation.Methods:Clinical data were collected from 37 patients with T-LGLL who received oral cyclophosphamide at the Regenerative Medicine Clinic of the Institute of Hematology and Blood Diseases Hospital between June 2019 and March 2024. Patient clinical characteristics, treatment efficacy, and long-term TFR were analyzed.Results:The median age of the 37 patients was 60 years (range: 37-86), and 22 (59.5%) were male. Anemia was observed in 30 patients (81.1%), and 28 (75.7%) met the diagnostic criteria for secondary pure red cell aplasia. Neutropenia occurred in 15 patients (40.5%), lymphocytosis in 11 (29.7%), and thrombocytopenia in three (8.1%). Sixteen patients (43.2%) had not received prior immunosuppressive therapy (treatment-naive group), while 21 patients (56.8%) were refractory to or had relapsed after immunosuppressive treatment (refractory/relapsed group). All patients met the treatment criteria and received oral cyclophosphamide at doses of 50-100 mg/day. Among the 36 evaluable patients, hematologic remission was achieved in 25 (69.4%), with a median time of 2.0 months (range: 0.7-7.0). There was no statistically significant difference in remission rates between the treatment-naive and refractory/relapsed groups (68.5% vs. 66.7%, P=0.589). Among the 25 patients who achieved hematologic remission, 24 discontinued cyclophosphamide. With a median follow-up of 39.0 months (range: 8.0-56.0), the median TFR duration was not reached. The estimated TFR rates were (90.87± 6.16) % at 12 months and (75.72±11.04) % at 36 months. No significant difference in TFR was observed between the treatment-naive and refractory/relapsed groups ( P=0.451) . Conclusion:Oral cyclophosphamide is effective in the treatment of T-LGLL, and patients may maintain long-term TFR following drug discontinuation.

OBJECTIVE: This study reports the first imported case of Lassa fever (LF) in China. Laboratory detection and molecular epidemiological analysis of the Lassa virus (LASV) from this case offer valuable insights for the prevention and control of LF. METHODS: Samples of cerebrospinal fluid (CSF), blood, urine, saliva, and environmental materials were collected from the patient and their close contacts for LASV nucleotide detection. Whole-genome sequencing was performed on positive samples to analyze the genetic characteristics of the virus. RESULTS: LASV was detected in the patient's CSF, blood, and urine, while all samples from close contacts and the environment tested negative. The virus belongs to the lineage IV strain and shares the highest homology with strains from Sierra Leone. The variability in the glycoprotein complex (GPC) among different strains ranged from 3.9% to 15.1%, higher than previously reported for the seven known lineages. Amino acid mutation analysis revealed multiple mutations within the GPC immunogenic epitopes, increasing strain diversity and potentially impacting immune response. CONCLUSION The case was confirmed through nucleotide detection, with no evidence of secondary transmission or viral spread. The LASV strain identified belongs to lineage IV, with broader GPC variability than previously reported. Mutations in the immune-related sites of GPC may affect immune responses, necessitating heightened vigilance regarding the virus.
Humans ; China/epidemiology* ; Genome, Viral ; Lassa Fever/virology* ; Lassa virus/classification* ; Molecular Epidemiology ; Phylogeny

Objectives:To investigate the physical growth status of pediatric patients with transfusion-dependent thalassemia (TDT) and analyze the effects of treatment-related and socioeconomic factors on physical growth.Methods:Based on the specialized thalassemia database from gene therapy clinical research at the Institute of Hematology & Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, we collected data on height and weight development, family economic status, and medical records of 338 pediatric patients with TDT from October 2023 to May 2024. The length/height-for-age and body mass index (BMI) -for-age were classified based on the Growth Standard for Children under 7 Years of Age, Standard for Height Level Classification among Children and Adolescents Aged 7-18 Years, and Dietary Guidelines for Chinese Residents. Logistic regression analysis was conducted to assess the effects of family economic status and disease-related treatment on length/height-for-age and BMI-for-age.Results:Among the 338 patients, 118 were children and 220 were adolescents (192 males and 146 females), with a median age of 12 years (range: 0.8-18) and a median diagnosis duration of 10.3 years (range: 0.5-17.9). Subtypes included α-thalassemia [21 cases (6.2%) ], β-thalassemia [288 cases (85.2%) ], and combined αβ-thalassemia[29 cases (8.6%) ]. The monthly household income of patients was concentrated in 3 000-5 000 yuan (39.9%) and 5 001-10 000 yuan (34.9%), whereas 67.2% of the families had monthly medical expenses of <3 000 yuan. Of the patients, 75.5% received their first transfusion before 1 year of age. The proportions of children and adolescents with pretransfusion hemoglobin (HGB) of ≤70 g/L were 4.2% and 6.4%, respectively. Adolescents demonstrated significantly higher rates of transfusion frequency of <4 weeks/session, monthly red blood cell infusion of >2 U, serum ferritin (SF) of ≥5 000 μg/L, iron chelation therapy, and splenectomy compared with children (all P<0.05). Of the 338 patients, 26.0%, 22.8%, and 8.9% demonstrated stunted growth, underweight, and concurrent stunted growth with underweight, respectively. No significant difference was observed in the stunted growth rates between children (22.9%) and adolescents (27.7%) ( P=0.402). However, the underweight rate in adolescents (26.8%) was significantly higher than that in children (15.3%) ( P=0.023). The multivariate analysis determined the following risk factors for stunted growth: monthly household income of <10 000 yuan (5 001-10 000 yuan: OR=5.49, 95% CI: 1.48-35.76; 3 000-5 000 yuan: OR=6.87, 95% CI: 1.88-44.60; <3 000 yuan: OR=9.29, 95% CI: 2.20-64.77), pretransfusion HGB of ≤70 g/L ( OR=3.25, 95% CI: 1.07-10.18), and SF of ≥5 000 μg/L ( OR = 3.04, 95% CI: 1.20-7.70). Longer diagnostic duration was associated with underweight ( OR=1.10, 95% CI: 1.01-1.20) . Conclusions:Children and adolescents with TDT with pretransfusion SF of ≥5 000 μg/L, HGB of ≤70 g/L, low monthly household income, or longer diagnosis duration were significantly more likely to experience delayed physical growth.

Objective:To evaluate the efficacy of cyclophosphamide in patients with T-cell large granular lymphocytic leukemia (T-LGLL) and the maintenance of treatment-free remission (TFR) following drug discontinuation.Methods:Clinical data were collected from 37 patients with T-LGLL who received oral cyclophosphamide at the Regenerative Medicine Clinic of the Institute of Hematology and Blood Diseases Hospital between June 2019 and March 2024. Patient clinical characteristics, treatment efficacy, and long-term TFR were analyzed.Results:The median age of the 37 patients was 60 years (range: 37-86), and 22 (59.5%) were male. Anemia was observed in 30 patients (81.1%), and 28 (75.7%) met the diagnostic criteria for secondary pure red cell aplasia. Neutropenia occurred in 15 patients (40.5%), lymphocytosis in 11 (29.7%), and thrombocytopenia in three (8.1%). Sixteen patients (43.2%) had not received prior immunosuppressive therapy (treatment-naive group), while 21 patients (56.8%) were refractory to or had relapsed after immunosuppressive treatment (refractory/relapsed group). All patients met the treatment criteria and received oral cyclophosphamide at doses of 50-100 mg/day. Among the 36 evaluable patients, hematologic remission was achieved in 25 (69.4%), with a median time of 2.0 months (range: 0.7-7.0). There was no statistically significant difference in remission rates between the treatment-naive and refractory/relapsed groups (68.5% vs. 66.7%, P=0.589). Among the 25 patients who achieved hematologic remission, 24 discontinued cyclophosphamide. With a median follow-up of 39.0 months (range: 8.0-56.0), the median TFR duration was not reached. The estimated TFR rates were (90.87± 6.16) % at 12 months and (75.72±11.04) % at 36 months. No significant difference in TFR was observed between the treatment-naive and refractory/relapsed groups ( P=0.451) . Conclusion:Oral cyclophosphamide is effective in the treatment of T-LGLL, and patients may maintain long-term TFR following drug discontinuation.

OBJECTIVES: To evaluate the performance of different multi-modality fusion models for predicting radiation-induced oral mucositis (RIOM) following radiotherapy in patients with nasopharyngeal carcinoma (NPC). METHODS: We retrospectively collected the data from 198 patients with locally advanced NPC who experienced RIOM following radiotherapy at the Affiliated Tumor Hospital of Guangzhou Medical University from September, 2022 to February, 2023. Based on oral radiation dose-volume parameters and clinical features of NPC, basic classification models were developed using different combinations of feature selection algorithms and classifiers and integrated using a multi-criterion decision-making (MCDM)-based classifier fusion (MCF) strategy and its variant, the H-MCF model. The basic classification models, MCF model, the H-MCF model with a single modality or multiple modalities and other ensemble classifiers were compared for performances for predicting RIOM by assessing the area under the ROC curve (AUC), accuracy, sensitivity, and specificity. RESULTS: The H-MCF model, which integrated multi-modality features, achieved the highest accuracy for predicting severe RIOM with an AUC of 0.883, accuracy of 0.850, sensitivity of 0.933, and specificity of 0.800. CONCLUSIONS Compared with each of the individual classifiers, the multimodal multi-classifier fusion algorithm combining clinical and dosimetric modalities demonstrates superior performance in predicting the incidence of severe RIOM in NPC patients following radiotherapy.
Humans ; Nasopharyngeal Carcinoma/radiotherapy* ; Nasopharyngeal Neoplasms/radiotherapy* ; Retrospective Studies ; Stomatitis/diagnosis* ; Algorithms ; Radiation Injuries/diagnosis* ; Female ; Male ; ROC Curve

This study was aimed at predicting the biological function of Streptococcus suis serotype 2(S.suis 2)tyrosine kinase Cps2C through bioinformatics and analyzing its effects on S.suis 2 pathogenicity.Online bioinformatics tools were used to analyze and predict the localization,conserved domains,transmembrane domains,protein similarity,and protein three-di-mensional structure of Cps2C.A BALB/c mouse infection model was used to compare and analyze clinical characteristics,mor-tality rates,and blood bacterial loads in mice infected with the wild-type strain 05ZYH33 and the cps2C gene knockout strainΔcps2C.Additionally,heart,brain,and joint tissue sections from infected mice were stained with hematoxylin and eosin(HE)for comparative pathological analysis.The Cps2C protein-coding gene is located upstream of the capsule biosynthesis locus cps,lacks transmembrane domains,is a homologous protein to Streptococcus pneumoniae tyrosine kinase CpsD with a 64％amino acid sequence similarity,and is potentially involved in bacterial capsule synthesis regulation.Cps2C deficiency significantly de-creased the pathogenicity of S.suis 2 in mice(P＜0.05).Compared with the wild-type strain,the Δcps2C strain showed a sig-nificantly lower blood bacterial load(P＜0.000 1).Heart,brain,and joint tissues of mice infected intraperitoneally with strains 05ZYH33 and Δcps2C remained structurally intact without e-dema,hemorrhage,or inflammatory cell infiltration;moreo-ver,characteristic lesion features of endocarditis,meningitis,or arthritis were absent.Streptococcus suis serotype 2 tyrosine kinase Cps2C may be an important regulatory factor in capsule biosynthesis,and its deficiency decreases bacterial blood survival capability and pathogenicity in mice.

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.

Objective To explore the cut-off value of three dimensional(3D)vena contracta area(VCA)in diagnosing severe tricuspid regrugitation(TR)under different etiologies and its accuracy and practicality in clinical application.Methods From Mar 2019 to May 2021,ninety-two patients with confirmed TR underwent two dimensional(2D)and 3D transthoracic echocardiography.The correlation and consistency between 3D VCA 3D calculated based on the proximal isokinetic surface area(PISA)effective regurgitant orifice area(EROA)was calculated.Comprehensive 2D multi-parameter method was used as a reference method to calculate the cut-off value of the diagnosis of severe TR.Results A total of 85 patients were ultimately included.3D VCA and 3D PISA EROA had similar and acceptable correlations in both primary TR and secondary TR(primary TR:r=0.831,P<0.01;secondary TR:r=0.806,P<0.01).Bland-Altman analysis showed that 3D VCA overestimated TR compared with 3D PISA EROA(62%overestimated in the total patient population,51%overestimated in primary TR,and 74%overestimated in secondary TR).In secondary TR,the cut-off value of 3D VCA for diagnosing severe TR was 0.45 cm2(sensitivity 89%,specificity 82%);combining clinical symptoms,positive 2D PISA EROA results and 3D VCA results for severe TR,the chi-square value was higher than those only included clinical symptoms or incorporated clinical symptoms and positive 2D PISA EROA results(42.168 vs.26.059 and 16.759,P<0.01).Conclusion 3D VCA would overestimate TR,and had high and incremental diagnostic value for evaluating severe TR in secondary TR.