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.

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 investigate the status of application of the central venous access in the departments of hematology to develop targeted administrative strategies and provide evidence for management.Methods A self-de-signed questionnaire was applied and convenience sampling was adopted in 93 hematology departments from 48 hospitals in 19 provinces(autonomous regions,municipalities).Results A total of 91 valid questionnaires were col-lected,with a valid questionnaire response rate of 97.85％.Among the 91 hematology departments,91(100％),73(80.22％),and 68(74.73％)carried out PICC,central venous catheter,and totally implantable access port catheteriza-tion,respectively.In the evaluation of blood test indicators before central venous access,the items with a higher e-valuation proportion were platelet count(100％)and D-dimer concentration(87.91％),while the evaluation proportion of other items was＜85％.When PICC catheterization,97.80％of hematology departments prefer basilic vein;83.52％of hematology departments used zone insertion method;95.60％of hematology departments had a skin disinfection range of ≥20 cm;98.90％of hematology departments had catheterization under ultrasound guidance;67.03％and 96.70％of hematology departments used the intracardiac electrocardiogram method or ultrasound assisted localiza-tion,postoperative X-ray localization;12.09％and 53.85％of hematology departments carried out tunnel catheteriza-tion and blunt separation expansion techniques,respectively.In terms of maintenance of central venous access de-vices,82.42％of hematology departments used disposable specialized maintenance kits;61.54％of hematology de-partments used transparent patches to fix PICC;45.21％of hematology departments used suture to fix central venous catheters;24.18％of hematology departments used cotton swabs to disinfect infusion joints;60.44％of hematology departments did not use disposable infusion joint disinfection cap;74.73％of hematology departments used gauze compression to prevent puncture site bleeding;only 6.59％hematology departments used antibacterial dressings con-taining chlorhexidine to prevent puncture site infections.In terms of quality management of central venous access devices,94.51％and 86.81％of hematology departments regularly conducted quality inspections of central venous access,and collected,calculated and analyzed relevant data.50.55％of hematology departments conducted complica-tion risk assessments,and 10.99％of hematology departments had established information management systems for venous therapy.Conclusion The implementation rate of PICC catheterization in the hematology department was relatively high,and the insertion operation basically meets the standard requirements.The evaluation before central venous access catheterization was relatively completed,and the maintenance and management are relatively stan-dardized.However,the evaluation of blood test indicators before the placement of central venous access urgently needs to be standardized and unified.When PICC catheterization,attention should be paid to the application of new technologies,and the information management of venous therapy needs to be improved.

Single-cell or low-input multi-omics techniques have revolutionized the study of pre-implantation embryo development.However,the single-cell or low-input proteomic research in this field is rela-tively underdeveloped because of the higher threshold of the starting material for mammalian embryo samples and the lack of hypersensitive proteome technology.In this study,a comprehensive solution of ultrasensitive proteome technology(CS-UPT)was developed for single-cell or low-input mouse oocyte/embryo samples.The deep coverage and high-throughput routes significantly reduced the starting material and were selected by investigators based on their demands.Using the deep coverage route,we provided the first large-scale snapshot of the very early stage of mouse maternal-to-zygotic transition,including almost 5,500 protein groups from 20 mouse oocytes or zygotes for each sample.Moreover,significant protein regulatory networks centered on transcription factors and kinases between the MII oocyte and 1-cell embryo provided rich insights into minor zygotic genome activation.

Major challenges for cancer treatment are how to effectively eliminate primary tumor and sufficiently induce immunogenic cell death (ICD) to provoke a robust immune response for metastasis control. Here, a self-assembled cascade bioreactor was developed to improve cancer treatment with enhanced tumor penetration and synergistic therapy of starvation, chemodynamic (CDT) and photothermal therapy. Ultrasmall FeS-GOx nanodots were synthesized with glucose oxidase (GOx) as template and induced by paclitaxel (PTX) to form self-assembling FeS-GOx@PTX (FGP)

BACKGROUND/OBJECTIVES: Hyperuricemic nephropathy is a common cause of acute kidney injury. Resveratrol can ameliorate kidney injury, but the explicit mechanism remains unclear.We investigated the effects of resveratrol on the inflammatory response and renal injury in hyperuricemic rats.MATERIALS/METHODS: A rat model of hyperuricemic nephropathy was established by the oral administration of a mixture of adenine and potassium oxinate. Biochemical analysis and hematoxylin and eosin staining were performed to assess the rat kidney function. Enzymelinked immunosorbent assays were performed to evaluate the immune and oxidative responses. RESULTS: The expression levels of urine albumin and β2-microglobulin were significantly decreased after resveratrol treatment. In addition, the levels of serum creatinine and uric acid were significantly decreased in the resveratrol groups, compared with the control group.The levels of proinflammatory factors, such as interleukin-1β and tumor necrosis factor-α, in kidney tissue and serum were also increased in the hyperuricemic rats, and resveratrol treatment inhibited their expression. Moreover, the total antioxidant capacity in kidney tissue as well as the superoxide dismutase and xanthine oxidase levels in serum were all decreased by resveratrol treatment. CONCLUSIONS Resveratrol may protect against hyperuricemic nephropathy through regulating the inflammatory response.

Objective:To summarize the patient profiles and therapeutic efficacies of ABO-incompatible living-related kidney transplantations at 19 domestic transplant centers and provide rationales for clinical application of ABOi-KT.Methods:Clinical cases of ABO-incompatible/compatible kidney transplantation (ABOi-KT/ABOc-KT) from December 2006 to December 2009 were collected. Then, statistical analyses were conducted from the aspects of tissue matching, perioperative managements, complications and survival rates of renal allograft or recipients.Results:Clinical data of 342 ABOi-KT and 779 ABOc-KT indicated that (1) no inter-group differences existed in age, body mass index (BMI), donor-recipient relationship or waiting time of pre-operative dialysis; (2) ABO blood type: blood type O recipients had the longest waiting list and transplantations from blood type A to blood type O accounted for the largest proportion; (3) HLA matching: no statistical significance existed in mismatch rate or positive rate of PRA I/II between two types of surgery; (4) CD20 should be properly used on the basis of different phrases; (5) hemorrhage was a common complication during an early postoperative period and microthrombosis appeared later; (6) no difference existed in postoperative incidence of complications or survival rate of renal allograft and recipients at 1/3/5/10 years between ABOi-KT and ABOc-KT. The acute rejection rate and serum creatinine levels of ABOi-KT recipients were comparable to those of ABOc-KT recipients within 1 year.Conclusions:ABOi-KT is both safe and effective so that it may be applied at all transplant centers as needed.

Objective:This study aims to evaluate the prognostic effect of peripheral blood cells in multiple myeloma (MM) patients treated with bortezomib.Methods:The clinical data of 155 newly diagnosed MM patients in two blood disease treatment centers from January 2014 to December 2016 were retrospectively studied. All patients received bortezomib as the first-line treatment. The results of the peripheral blood cell counts, including absolute neutrophil count, absolute monocyte count (AMC) , hemoglobin level, mean corpuscular volume (MCV) , and platelet count, and other clinical features were analyzed.Results:AMC (>0.6×10 9/L) , MCV (>99.1 fl) , and platelet count (<150×10 9/L) significantly affected patients’ PFS and OS. The above three factors were assigned 1 point, respectively, to form the blood cell score. The analysis showed that 64 cases (41.3% ) had a score of 0, 57 cases (36.8% ) had 1, 32 cases (20.6% ) had 2, and 2 cases (1.3% ) had 3. The median PFS of the four groups were 42.8 m, 26.5 m, 15.8 m, and 6.4 m, respectively ( P<0.001) . The median OS were NR, 48.2 m, 31.1 m, and 31.4 m, respectively ( P=0.001) . Multivariate analysis suggested that the blood cell score (2-3 vs 0-1) and the proportion of marrow plasma cells (>30% ) were independent prognostic factors for PFS ( HR=1.95 and 1.76, respectively) , while age (>65y vs ≤65y) , R-ISS stage (3 vs 1-2) , and blood cell score (2-3 vs 0-1) were independent prognostic factors for OS ( HR=2.08, 2.13 and 2.12, respectively) . Conclusion:As an easy-to-access biomarker, the blood cell score can be used to evaluate the prognosis of newly diagnosed MM patients in the era of new drugs, but it is still necessary to expand the cases and make further confirmation in the prospective study.

Objective Analysis of hybrid cardiac and non-cardiac operations.Methods 11 patients received hybrid operations during 2000 ～2016 in our hospital were summarized, meanwhile another 11 patients undergoing only cardiac sur-gery served as controls.The level of CK-MB, TNI and visual analogue pain scores were recorded.The hospitalization expenses and postoperative hospital time were compared between the two groups .Results There was no death during hospitalization . There were no serious complications such as wound infection, delayed wound healing, postoperative bleeding requiring re-thora-cotomy and hemostasis, malignant arrhythmia, cerebral infarction and so on.Longer operation time[(358 ±79)min vs.(224 ±56)min, P<0.01], more allogeneic red blood cells transfusion[(3.2 ±1.6)U/case vs.(1.1 ±0.8)U/case, P<0.05] and more plasma transfusion[(515 ±234)ml/case vs.(284 ±92)ml/case, P<0.01]in hybrid operation group than those in the control group.There was no significant difference about CK-MB and TNI between two groups perioperatively(P>0.05). The wound pain was mild after cardiac surgery , and the wound pain was moderate after hybrid operation , which had little effect on rehabilitation exercises such as cough.4 days longer of postoperative hospital stay and 23 thousand yuan of hospitalization cost in hybrid operation group than those in the control group.One patient diagnosed of unstable angina pectoris and sigmoid colon cancer with intestinal obstruction was failed to resection of the tumor after received pericardial stripping and coronary ar-tery bypass surgery.The patient died three weeks after surgery due to intestinal obstruction and cachexia .The remaining 10 pa-tients were underwent successful surgery, cured and left hospital.No serious cardiovascular events, tumor recurrence and me-tastasis were found as followed up for 6-20 months.Conclusion Our practices show that hybrid cardiac and non-cardiac op-erations can be done safely and effectively.

Clinical success of the proteasome inhibitor established bortezomib as one of the most effective drugs in treatment of multiple myeloma (MM). While survival benefit of bortezomib generated new treatment strategies, the primary and secondary resistance of MM cells to bortezomib remains a clinical concern. This study aimed to highlight the role of p53-induced RING-H2 (Pirh2) in the acquisition of bortezomib resistance in MM and to clarify the function and mechanism of action of Pirh2 in MM cell growth and resistance, thereby providing the basis for new therapeutic targets for MM. The proteasome inhibitor bortezomib has been established as one of the most effective drugs for treating MM. We demonstrated that bortezomib resistance in MM cells resulted from a reduction in Pirh2 protein levels. Pirh2 overexpression overcame bortezomib resistance and restored the sensitivity of myeloma cells to bortezomib, while a reduction in Pirh2 levels was correlated with bortezomib resistance. The levels of nuclear factor-kappaB (NF-κB) p65, pp65, pIKBa, and IKKa were higher in bortezomib-resistant cells than those in parental cells. Pirh2 overexpression reduced the levels of pIKBa and IKKa, while the knockdown of Pirh2 via short hairpin RNAs increased the expression of NF-κB p65, pIKBa, and IKKa. Therefore, Pirh2 suppressed the canonical NF-κB signaling pathway by inhibiting the phosphorylation and subsequent degradation of IKBa to overcome acquired bortezomib resistance in MM cells.
Antineoplastic Agents ; pharmacology ; therapeutic use ; Apoptosis ; drug effects ; Bortezomib ; pharmacology ; therapeutic use ; Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Dose-Response Relationship, Drug ; Drug Resistance, Neoplasm ; drug effects ; Drug Screening Assays, Antitumor ; Humans ; Multiple Myeloma ; drug therapy ; metabolism ; pathology ; NF-kappa B ; metabolism ; Signal Transduction ; drug effects ; Structure-Activity Relationship ; Ubiquitin-Protein Ligases ; genetics ; metabolism