Effectiveness of Acupoint Application in Patients with Pharyngeal Pain: Evidence from CHUNBO, A Prospective Real-World Study / 中国结合医学杂志

OBJECTIVE@#To assess the outcomes after acupoint application in patients with pharyngeal pain in a real-world settings, and analyze the characteristics of effective population and prescription characteristics of acupoint application.@*METHODS@#Based on CHUNBO platform, patients with pharyngeal pain who were candidates for acupoint application on the basis of physician-evaluation, were enrolled in a nationwide, prospective, 69-week multicenter observational study from August 2020 to February 2022. Propensity score matching (PSM) was used to match the confounding factors and the association rules were used to analyze the characteristics of effective population and prescription characteristics of acupoint application. Outcome assessments included the disappearance rate of pharyngeal pain (within 3, 7, and 14 days), disappearance time of pharyngeal pain, as well as adverse events.@*RESULTS@#Of 7,699 enrolled participants, 6,693 (86.9%) received acupoint application and 1,450 (21.7%) with non-acupoint application. After PSM, there were 1,004 patients each in the application group (AG) and non-application group (NAG). The disappearance rate of pharyngeal pain in the AG at 3, 7, and 14 days were all higher than those in the NAG (P<0.05). The disappearance time of pharyngeal pain in the AG were shorter than that in the NAG (logrank P<0.001, hazard ratio=1.51, 95% confidence interval: 1.41-1.63). The median age of effective cases was 4 years, mainly 3-6 years old (40.21%). The disappearance rate of pharyngeal pain in the application group with tonsil diseases was 2.19 times higher than that in the NAG (P<0.05). The commonly used acupoints for the effective cases were Tiantu (RN 22), Shenque (RN 8) and Dazhui (DU 14). The commonly used herbs for the effective cases were Natrii sulfas, Radix et Rhizoma Rhei, and Herba Ephedrae. Among them, Natrii sulfas was applied to RN 8 most frequently (support 84.39%). A total of 1,324 (17.2%) patients experienced AEs, and mainly occurred in the AG, with significant difference in the incidence of AEs between goups (P<0.05). All AEs reported were the first grade, and the average regression days of AEs was 2.8 days.@*CONCLUSIONS@#Acupoint application in patients with pharyngeal pain resulted in improved effective rate and shortened duration, especially children aged 3-6 years old, and those with tonsil diseases. Acupoint of RN 22, RN 8 and DU 14, Natrii sulfas, Radix et Rhizoma Rhei, and Herba Ephedrae were the most commonly used herbs in the treatment of pharyngeal pain.

Mechanism of levosimendan in treating hypoxic pulmonary hypertension based on network pharmacology and molecular docking technology / 中国药理学通报

Aim To explore the efficacy of levosimendan on hypoxia pulmonary hypertension through animal experiments, and to further explore the potential mechanism of action using network pharmacological methods and molecular docking technique. Methods The rat model of hypoxia pulmonary hypertension was constructed to detect right heart systolic pressure and right heart remodeling index. HE , Masson, and VG staining were core targets were screened out. GO and KEGG pathway enrichment analysis were performed using the DAVID database. Molecular docking of the core targets was performed with the AutoDock software. Results The results of animal experiments showed that levosimendan had obvious therapeutic effect on hypoxia pulmonary hypertension. The network pharmacology results showed that SRC, HSP90AA1, MAPK1, PIK3R1, AKT1, HRAS, MAPK14, LCK, EGFR and ESR1 used to analyze the changes of rat lung histopathology. Search the Swiss Target Prediction, DrugBank Online, BatMan, Targetnet, SEA, and PharmMapper databases were used to screen for drug targets. Disease targets were retrieved from the GeneCards, OMIM databases. The "drug-target-disease" network was constructed after identification of the two intersection targets. The protein interaction network was constructed and the were the key targets to play a therapeutic role. Molecular docking showed good docking of levosimendan with all the top five core targets with degree values. Conclusions Levosimendan may exert a therapeutic effect on hypoxia-induced pulmonary hypertension through multiple targets.

Influences of aerobic exercise associated with the pharmacological treatment of copd / Influências do exercício aeróbico associado ao tratamento farmacológico da dpoc / Influencias del ejercicio aeróbico asociado al tratamiento farmacológico de la epoc

ABSTRACT Introduction: Chronic obstructive pulmonary disease (COPD) is a type of inflammatory respiratory system disease characterized by chronic airflow limitation. Aerobic exercise training is believed to influence the drug treatment of this disease positively. Objective: Study the impact of complementary aerobic exercise intervention on pharmacological treatment in patients with COPD. Methods: In a controlled experiment, 40 volunteers under pharmacological treatment for COPD were selected and equally divided into two groups. The experimental group was treated with aerobic exercise training and drug treatment, while the control group was treated with regular drug treatment only. The exercise protocol lasted 60 minutes daily for a total period of eight weeks. Borg scale, oxygen saturation, and six-minute walk test among other markers were checked before and after the intervention. Results: According to the data obtained from the experiment, the peak oxygen consumption of aerobic exercise combined with the drug group was from 1,205.42±293.74ml/min to 1,301.84±293.91ml/min, peak ventilation started at 37.85±11.67L/min to 48.81±13.11L/min. However, the variations in the control group were not significant. Conclusion: Aerobic exercise associated with pharmacological intervention positively influenced the treatment of patients with COPD. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: A doença pulmonar obstrutiva crônica (DPOC) é um tipo de doença inflamatória do sistema respiratório caracterizada pela limitação crônica do fluxo de ar. Acredita-se que o treinamento com exercícios aeróbicos possa influenciar positivamente no tratamento medicamentoso dessa enfermidade. Objetivo: Estudar os impactos da intervenção complementar com exercícios aeróbicos sobre o tratamento farmacológico em portadores de DPOC. Métodos: Através de um experimento controlado, 40 voluntários sob tratamento farmacológico para DPOC foram selecionados e igualmente divididos em dois grupos. O grupo experimental foi tratado com treinamento de exercício aeróbico combinado com o tratamento medicamentoso, enquanto o grupo controle foi tratado apenas com o tratamento medicamentoso regular. O protocolo de exercícios teve duração de 60 minutos diários, num período total de oito semanas. A escala de Borg, saturação de oxigênio, teste de caminhada de seis minutos entre outros marcadores foram verificados antes e após a intervenção. Resultados: De acordo com os dados obtidos do experimento, o pico de consumo de oxigênio do exercício aeróbico combinado com o grupo de fármacos foi de 1.205,42±293,74ml/min para 1.301,84±293,91ml/min, pico de ventilação iniciou em 37,85±11,67L/min para 48,81±13,11L/min. Porém as variações no grupo controle não foram significativas. Conclusão: O exercício aeróbico associado à intervenção farmacológica representou uma influência positiva no tratamento dos pacientes portadores de DPOC. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: La enfermedad pulmonar obstructiva crónica (EPOC) es un tipo de enfermedad inflamatoria del sistema respiratorio caracterizada por la limitación crónica del flujo aéreo. Se cree que el entrenamiento con ejercicios aeróbicos puede influir positivamente en el tratamiento farmacológico de esta enfermedad. Objetivo: Estudiar el impacto de la intervención complementaria con ejercicios aeróbicos sobre el tratamiento farmacológico en pacientes con EPOC. Métodos: Mediante un experimento controlado, se seleccionaron 40 voluntarios bajo tratamiento farmacológico para la EPOC y se dividieron equitativamente en dos grupos. El grupo experimental fue tratado con entrenamiento de ejercicio aeróbico combinado con tratamiento farmacológico, mientras que el grupo de control fue tratado únicamente con tratamiento farmacológico regular. El protocolo de ejercicio duró 60 minutos diarios durante un período total de ocho semanas. Se comprobaron la escala de Borg, la saturación de oxígeno y la prueba de la marcha de seis minutos, entre otros marcadores, antes y después de la intervención. Resultados: Según los datos obtenidos del experimento, el consumo máximo de oxígeno del grupo de ejercicio aeróbico combinado con fármaco fue de 1.205,42±293,74ml/min a 1.301,84±293,91ml/min, la ventilación máxima comenzó en 37,85±11,67L/min a 48,81±13,11L/min. Sin embargo, las variaciones en el grupo de control no fueron significativas. Conclusión: El ejercicio aeróbico asociado a la intervención farmacológica tuvo una influencia positiva en el tratamiento de los pacientes con EPOC. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Establishment and validation of a nomogram to predict progression free survival of patients with thymoma / 中华胸心血管外科杂志

Objective:To explore the prognostic risk factors of thymoma patients after resection, and establish a novel nomogram to predict progression free survival(PFS) of patients with thymoma.Methods:A retrospectively analysis was performed on clinicopathological datas of 267 cases of thymoma patients underwent thymoma resection in Beijing Tongren Hospital from January 2010 to December 2019. The univariate and multivariate Cox risk ratio models were used to analyze the related factors that might affect PFS, and the prediction nomogram of PFS after thymoma resection was established using the screened independent risk factors. Then the predictive ability of the model was evaluated. Results:The univariate analysis showed that age, type of surgery, completeness of resection, WHO histologic classification, TNM stage and postoperative adjuvant therapy were significantly correlated with PFS after thymoma resection( P<0.05). The multivariate analysis showed that only age and TNM stage were independent prognostic factors affecting PFS after thymoma resection( P<0.05). The concordance index( C- index) of the prediction model for the prognosis of thymoma patients established by this method was 0.866(95% CI: 0.809-0.923), which had remarkable predictive efficiency. Conclusion:The nomogram model is constructed and verified based on age and TNM stage, excluding the interference of other clinicopathological factors on prognosis assessment, and which is convenient for clinicians to quickly and individually evaluate the prognosis of patients after thymoma resection.

Protective effect and mechanism of AKAP1 on myocardial injury induced by highland hypobaric hypoxia / 中华劳动卫生职业病杂志

Objective: To investigate the protective effect and its possible mechanism of A-kinase anchored protein 1 (AKAP1) on the myocardial injury induced by highland hypobaric hypoxia. Methods: From January 2021 to May 2022, male C57BL/6 SPF grade mice were divided into wild type control (WT) group and highland hypobaric hypoxia (HH) group with 6 mice in each group. HH group simulated 6000 m altitude with low pressure oxygen chamber for 4 weeks to build the model. Primary myocardial cells of SD rats were divided into normoxia control group and hypoxia experimental group (n=3). Cell models were constructed in a three-gas hypoxia incubator with 1% oxygen concentration for 24 h. AKAP1 protein and mRNA expression in myocardial tissue and cells were detected by western blotting, immunohistochemistry and quantitative real-time polymerase chain reaction (qPCR). After myocardial point injection of the AKAP1 or the control adenovirus, the mice were divided into 3 groups (n=6) : WT group, highland hypobaric hypoxia overexpression control group (HH+Ad-Ctrl group) and highland hypobaric hypoxia overexpression experimental group (HH+Ad-AKAP1 group). The cardiac function of mice was detected by noninvasive M-type ultrasonic cardiomotive, myocardial fibrosis was detected by Masson and Sirius Red staining, and cardiomyocyte hypertrophy was detected by wheat germ agglutinin. After the expression of AKAP1 in primary cardiomyocytes was downregulated by siRNA and upregulated by adenovirus, the cells were divided into three groups (n=3) : normoxia control group, hypoxia interference control group (hypoxia+siCtrl group), hypoxia AKAP1 knockdown group (hypoxia+siAKAP1 group) ; normoxia control group, hypoxia overexpression control group (hypoxia+Ad-Ctrl group), hypoxia AKAP1 overexpression group (hypoxia+Ad-AKAP1 group). Apoptosis was detected by flow cytometry, AKAP1, apoptosis-related protein and mRNA expression levels were detected by western blotting and qPCR, mitochondrial membrane potential was detected by JC-1 staining, and mitochondrial reactive oxygen specie (ROS) level was detected by MitoSOX. Results: The expression of AKAP1 in cardiac muscle of HH group was lower than that in the WT group, and the expression of AKAP1 in hypoxia experimental group was lower than that in normoxia control group (P<0.01). Compared with WT group, the left ventricular ejection fraction and fraction shortening of left ventricle in HH+Ad-Ctrl group were decreased (P<0.01), myocardial fibrosis and hypertrophy were aggravated (P<0.01), and the expression of B-cell lymphoma-2 (BCL-2) was decreased, the expressions of BCL-2-associated X protein (BAX), Caspase 3 and Caspase 9 were increased (P<0.01). After AKAP1 overexpression, compared with HH+Ad-Ctrl group, the left ventricular ejection fraction and left ventricular fraction shortening were increased in HH+Ad-AKAP1 group (P<0.01), myocardial fibrosis and hypertrophy were reduced (P<0.01), and the expression of BCL-2 was increased, the expressions of BAX, Caspase 3 and Caspase 9 were decreased (P<0.01). Compared with normoxia control group, the expression of BCL-2 in hypoxia+siCtrl group was decreased, the expressions of BAX, Caspase 3, Caspase 9 were increased, the apoptosis level was increased (P<0.01), the mitochondrial membrane potential was decreased and the production of ROS was increased (P<0.01). After AKAP1 knockdown, compared with hypoxia+siCtrl group, the expression of BCL-2 in hypoxia+siAKAP1 group was decreased, the expressions of BAX, Caspase 3, Caspase 9 were increased, the apoptosis level was increased (P<0.01), mitochondrial membrane potential was decreased, and the production of ROS was increased (P<0.01). After AKAP1 overexpression, compared with hypoxia+Ad-Ctrl group, the expression of BCL-2 in hypoxia+Ad-AKAP1 group was increased, the expressions of BAX, Caspase 3 and Caspase 9 were decreased (P<0.05), the apoptosis level was decreased (P<0.01), and the mitochondrial membrane potential was enhanced, and the production of ROS was decreased (P<0.01) . Conclusion: The downregulation of AKAP1 in cardiomyocytes under highland hypobaric hypoxia may lead to the decrease of mitochondrial membrane potential and the increase of ROS generation, leading to the apoptosis of cardiomyocytes, and thus aggravating the myocardial injury at highland hypobaric hypoxia.

Clinical features of SF3B1 mutation in patients with myelodysplastic syndrome with excess blasts / 中华内科杂志

Objective: To exploring the clinical features of SF3B1-mutated myelodysplastic syndrome with excess blasts (MDS-EB) and analyzing the association between SF3B1 mutation, and efficacy and prognostic significance for patients with MDS-EB. Methods: This was a retrospective case series study. The clinical data of 266 patients with MDS-EB diagnosed in the First Affiliated Hospital of Zhengzhou University between April 2016 and November 2021 were analyzed. The observed indicators included blood routine counts, mutated genes, overall response rate (ORR), overall survival (OS), progression-free survival (PFS), and leukemia-free survival (LFS). The Kaplan-Meier method was used to depict the survival curves. The Log-rank test method was equally used to compare survival across groups and performed the Cox proportional hazard regression model for prognostic analysis. Results: In 266 patients with MDS-EB, 166 (62.4%) were men, and the median age was 57 (17-81) years. Moreover, there were included 26 and 240 patients in the SF3B1-mutated and SF3B1 wild-type groups. Patients in the SF3B1-mutated group were older [median age 65 (51, 69) years vs. 56 (46, 66) years, P=0.033], had higher white blood cell (WBC) counts [3.08 (2.35, 4.78) × 109/L vs. 2.13 (1.40, 3.77) × 109/L], platelet (PLT) counts [122.5 (50.5, 215.0) ×109/L vs. 49.0 (24.3, 100.8) × 109/L], absolute neutrophil counts (ANC) [1.83 (1.01, 2.88) × 109/L vs. 0.80 (0.41, 1.99) × 109/L]and occurrence of DNMT3A mutation [23.1% (6/26) vs. 6.7% (16/240)] (all P<0.05). The ORR were similar in both groups after 2 and 4 cycles of therapy (P=0.348, P=1.000). Moreover, the LFS (P=0.218), PFS (P=0.179) and OS (P=0.188) were similar across the groups. Univariate Cox analysis revealed that SF3B1 mutation did not affect the prognosis of patients with MDS-EB (OS: P=0.193; PFS: P=0.184). Conclusions: Patients with SF3B1 mutation were older, with greater WBC, PLT, and ANC, and SF3B1 mutation easily co-occurred with DNMT3A mutation. From this model, there were no significant differences in efficacy and survival of MDS-EB with or without SF3B1 mutation.

Minor triterpenoid acids from an aqueous extract of Uncaria rhynchophylla / 药学学报

Seventeen minor triterpenoid acids (1-17) were isolated from an aqueous decoction of Uncaria rhynchophylla by a combinatory application of column chromatography using multiple stationary phases, including macroporous adsorbent resin, MCI resin, Sephadex LH-20, Toyopearl HW-40C, silica gel, and C18 reversed phase silica gel, combined with separation techniques of flash chromatography (FC) and high performance liquid chromatography (HPLC). Their structures were determined by analysis of HR-ESI-MS, UV, CD, and IR as well as 1D and 2D NMR spectroscopic data, of which eight new compounds (1-8) are named successively uncarinic acids Q-X, while the structures of 2 and 7 were confirmed by single crystal X-ray diffraction. In the in vitro assays, 27-hydroxyolean-12-en-28-oic acid (17) inhibited TGF-β-induced HSC-T6 cell activation at the concentration of 5 μmol·L-1.

Prevention and treatment of hepatic artery dissection in donors and recipients during liver transplantation / 器官移植

Hepatic artery reconstruction is one of the key procedures in liver transplantation. Accidental dissection of the hepatic artery to be reconstructed caused by donor and recipient factors or surgical factors will disrupt the surgical plan, increase the difficulty of arterial reconstruction, significantly prolong the operation time, increase the risk of postoperative arterial stenosis and thrombosis and probably lead to acute allograft failure, which requires emergency surgical interventions or even secondary liver transplantation. Understanding of how to avoid dissection of the artery to be anastomosed during liver transplantation and corresponding treatment will contribute to preventing the incidence of artery-related complications during liver transplantation and improving clinical prognosis of liver transplant recipients. In this article, the causes, prevention and treatment of hepatic artery dissection and hepatic artery reconstruction in donors and recipients during liver transplantation were illustrated.

nNOS and Neurological, Neuropsychiatric Disorders: A 20-Year Story / 神经科学通报·英文版

In the central nervous system, nitric oxide (NO), a free gas with multitudinous bioactivities, is mainly produced from the oxidation of L-arginine by neuronal nitric oxide synthase (nNOS). In the past 20 years, the studies in our group and other laboratories have suggested a significant involvement of nNOS in a variety of neurological and neuropsychiatric disorders. In particular, the interactions between the PDZ domain of nNOS and its adaptor proteins, including post-synaptic density 95, the carboxy-terminal PDZ ligand of nNOS, and the serotonin transporter, significantly influence the subcellular localization and functions of nNOS in the brain. The nNOS-mediated protein-protein interactions provide new attractive targets and guide the discovery of therapeutic drugs for neurological and neuropsychiatric disorders. Here, we summarize the work on the roles of nNOS and its association with multiple adaptor proteins on neurological and neuropsychiatric disorders.

Isobaric tags for relative and absolute quantitation quantitative proteomics research of human lens epithelial cells after ultraviolet-B irradiation / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the changes of protein expressions in human lens epithelial cells(SRA01/04)undergoing oxidative damage, hoping to provide new protein target for the pathogenesis of age-related cataract(ARC).METHODS: SRA01/04 cells were divided into experimental group and control group. In the experimental group, cells were irradiated with ultraviolet-B(UVB)for 10min to establish the model of oxidative damage, whereas cells in the control group were untreated. Protein expression profile from the two groups was sequenced by isobaric tags for relative and absolute quantitation(iTRAQ). The filtering criteria that fold change &#x0026;#x003E;1.2 and p&#x0026;#x003C;0.05 was used to determine the differentially expressed proteins(DEPs). Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)database were utilized for functional enrichment analysis of the top 50 DEPs with either up-regulated or down-regulated significance. Furthermore, Pathway commons software was used to establish the protein-protein interaction(PPI)network.RESULTS: Overall, 552 DEPs were screened out. A total of 176 DEPs were up-regulated in the experimental group compared with the control group, including HMGB1 and USP1, while 376 DEPs were down-regulated, including POLR2A and POLR2B. GO and KEGG enrichment analysis indicated that the top 50 DEPs with up-regulated or down-regulated significance were involved in various crucial biological processes and signaling pathways. PPI network revealed that oxidative damage repair(ODR)-related proteins might play a key role in UVB-induced oxidative damage.CONCLUSIONS: The expressions of multiple proteins, especially ODR-related proteins, can be altered in SRA01/04 cells via UVB irradiation. These findings may provide cellular-related insights into the pathogenesis of ARC and into proteins or pathways associated with therapeutic targets.

Advances in the study of new BCR-ABL kinase inhibitors / 药学学报

The oncogenic product of BCR-ABL is an abnormal tyrosine kinase that causes chronic myeloid leukemia (CML). With further research into the pathogenesis of CML, the discovery of compounds that selectively inhibit abnormal BCR-ABL tyrosine kinases is a research focus worthy of attention. The first three generations of BCR-ABL inhibitors are orthosteric inhibitors, which competitively block the binding of ABL protein tyrosine kinase to ATP and prevent it from activating downstream signals. The fourth-generation BCR-ABL inhibitors allosterically inhibit ABL protein tyrosine kinase by binding to the myristoyl pocket, providing greater selectivity and maintaining activity against drug-resistant mutations proteins. Novel drug design strategies such as proteolytic targeting chimera (PROTAC), covalent inhibitors and dual targeting inhibitors also provide new directions for the development of BCR-ABL kinase inhibitors. This paper reviews recent research advances on BCR-ABL kinase inhibitors and discusses drug design strategies for various novel BCR-ABL inhibitors.

Anti-inflammatory Therapy Progress in Major Adverse Cardiac Events after PCI: Chinese and Western Medicine / 中国结合医学杂志

Acute coronary syndrome (ACS) is one of the leading causes of death in cardiovascular disease. Percutaneous coronary intervention (PCI) is an important method for the treatment of coronary heart disease (CHD), and it has greatly reduced the mortality of ACS patients since its application. However, a series of new problems may occur after PCI, such as in-stent restenosis, no-reflow phenomenon, in-stent neoatherosclerosis, late stent thrombosis, myocardial ischemia-reperfusion injury, and malignant ventricular arrhythmias, which result in the occurrence of major adverse cardiac events (MACE) that seriously reduce the postoperative benefit for patients. The inflammatory response is a key mechanism of MACE after PCI. Therefore, examining effective anti-inflammatory therapies after PCI in patients with ACS is a current research focus to reduce the incidence of MACE. The pharmacological mechanism and clinical efficacy of routine Western medicine treatment for the anti-inflammatory treatment of CHD have been verified. Many Chinese medicine (CM) preparations have been widely used in the treatment of CHD. Basic and clinical studies showed that effectiveness of the combination of CM and Western medicine treatments in reducing incidence of MACE after PCI was better than Western medicine treatment alone. The current paper reviewed the potential mechanism of the inflammatory response and occurrence of MACE after PCI in patients with ACS and the research progress of combined Chinese and Western medicine treatments in reducing incidence of MACE. The results provide a theoretical basis for further research and clinical treatment.

Establishment and Clinical Significance of Prognostic Nomogram Model for Diffuse Large B-Cell Lymphoma Based on Immunohistochemistry Markers and International Prognostic Index Scores / 中国实验血液学杂志

OBJECTIVE@#To retrospectively analyze clinical characteristics and survival time of patients with diffuse large B-cell lymphoma (DLBCL), detect prognosis-related markers, and establish a nomogram prognostic model of clinical factors combined with biomarkers.@*METHODS@#One hundred and thirty-seven patients with DLBCL were included in this study from January 2014 to March 2019 in the First Affiliated Hospital of Nanchang University. The expression of GCET1, LMO2, BCL-6, BCL-2 and MYC protein were detected by immunohistochemistry (IHC), then the influences of these proteins on the survival and prognosis of the patients were analyzed. Univariate and multivariate Cox regression analysis were used to gradually screen the prognostic factors in nomogram model. Finally, nomogram model was established according to the result of multivariate analysis.@*RESULTS@#The positive expression of GCET1 protein was more common in patients with Ann Arbor staging I/II (P =0.011). Compared with negative patients, patients with positive expression of LMO2 protein did not often show B symptoms (P =0.042), and could achieve better short-term curative effect (P =0.005). The overall survival (OS) time of patients with positive expression of LMO2 protein was significantly longer than those with negative expression of LMO2 protein (P =0.018), though the expression of LMO2 protein did not correlate with progression-free survival (PFS) (P >0.05). However, the expression of GCET1 protein had no significant correlation with OS and PFS. Multivariate Cox regression analysis showed that nomogram model consisted of 5 prognostic factors, including international prognostic index (IPI), LMO2 protein, BCL-2 protein, MYC protein and rituximab. The C-index applied to the nomogram model for predicting 4-year OS rate was 0.847. Moreover, the calibrated curve of 4-year OS showed that nomogram prediction had good agreement with actual prognosis.@*CONCLUSION@#The nomogram model incorporating clinical characteristics and IHC biomarkers has good discrimination and calibration, which provides a useful tool for the risk stratification of DLBCL.

Clinical characteristics of fetal cardiac disease in patients with anti-SSA antibody positive / 北京大学学报(医学版)

OBJECTIVE@#To investigate the clinical manifestations and laboratory indicators of anti-Sjögren's-syndrome-related antigen A (SSA) antibody associated fetal cardiac disease.@*METHODS@#Pregnant women hospitalized at Peking University People's Hospital from January 2013 to July 2023 were included. Eleven patients with anti-SSA antibody positive were eventually diagnosed with fetal cardiac di-sease. And patients with anti-SSA antibody positive without fetal cardiac disease were selected as controls. Clinical manifestations, laboratory indications and drug usage were compared between the two groups.@*RESULTS@#Among these 11 patients, congenital heart block was confirmed in seven, which was the most common manifestations of fetal cardiac malformation. The proportion of the patients diagnosed with autoimmune disease before pregnancy in fetal cardiac malformation group was significantly lower than that in the control group (P=0.032), while most of the patients in the fetal cardiac malformation group received immune-related examinations for the first time because of this time's fetal cardiac diagnosis. While most of the patients in the control group received routine examinations because of autoimmune diseases diagnosed before pregnancy. During pregnancy, the white blood cell level [(9.29±2.58)×109/L vs. (7.10±1.90×109/L, t=3.052, P=0.004], erythrocyte sedimentation rate [(49.50 (48.00, 51.00) mm/h vs. 23.00 (15.00, 30.25) mm/h, Z=-2.251, P=0.024], IgA level [3.46 (2.30, 5.06) g/L vs. 2.13 (1.77, 2.77) g/L, Z=-2.181, P=0.029], and antinuclear antibody (ANA) titers [1∶320 (1∶160, 1∶320) vs. 1∶80 (1∶40, 1∶160), Z=-3.022, P=0.003] were significantly higher in fetal cardiac malformation group than in the control group. The proportion of positive anti-SSB antibody during pregnancy did not show a statistically significant difference between the two groups (37.5% vs. 7.7%, P=0.053). There was no significant difference in hydroxychloroquine dosage and initiation time between the two groups. The dosage of prednisone in the second and third trimesters was significantly higher in the cardiac malformation group than that in the control group, but there was no significant difference in the first trimester.@*CONCLUSION@#Fetal cardiac disease is rare in pregnant women with anti-SSA antibody. White blood cell, erythrocyte sedimentation rate, IgA, the titer of ANA positivity were higher in the fetal heart disease group during pregnancy. Since congenital heart block is difficult to reverse, its prevention and monitoring are more important than remedial treatment.

Progress in Research and Application of CAR-T Cell Therapy in T-Lymphocyte Tumors --Review / 中国实验血液学杂志

T-lymphocyte tumors are a group of diseases containing various types of lymphatic system tumors, with strong heterogeneity and poor clinical outcomes. Chimeric antigen receptor T (CAR-T) cell therapy, as a new immune cell therapy, has made a breakthrough in the field of B-lymphocyte tumors. People are interested in the application prospect of this technique in the field of T-lymphocyte tumors. Some studies have shown that CAR-T cell therapy has made some progress in the treatment of T-lymphocyte tumors, and CAR-T for some targets has entered the stage of clinical trials. However, due to the characteristics of T cells, there are also many challenges. This article reviews the research and application of CAR-T cell therapy in T-lymphocyte tumors.

Investigation of Antigen and Gene Frequency of Kell(K) and Rh(D) Blood Groups in Xinjiang / 中国实验血液学杂志

OBJECTIVE@#To investigate the phenotypes and gene frequencies of Kell blood group system K antigen and Rh blood group system D antigen in Xinjiang, and summarize and understand the distribution of Kell(K) blood type and Rh(D) blood type in this area.@*METHODS@#A total of 12 840 patients who met the inclusion criteria during physical examination and treatment in our hospital and 18 medical institutions in our district from January 1, 2019 to December 31, 2019 were collected for identification of Kell blood group system K antigen and Rh blood group System D antigen, and the distribution of K and D blood groups in different regions, genders and nationalities were investigated and statistically analyzed.@*RESULTS@#The proportion of K positive in the samples was 1.39%, the highest was 1.91% in southern Xinjiang, and the lowest was 1.03% in northern Xinjiang(P<0.01). The proportion of Rh(D) negative samples was 2.75% and the gene frequency was 16.64%. The proportion of Rh(D) negative samples was 4.03% and the gene frequency was 20.10% in southern Xinjiang, followed by eastern Xinjiang and the lowest in northern Xinjiang (P<0.01). The frequency of K antigen in Uygur nationality was the highest, reaching 2.16%, Kirgiz 1.54%, and the distribution trend of D/d antigen was similar to that of K antigen. Among women, the K positive frequency of Kazak nationality was slightly higher than that of Mongolian nationality. The highest proportion of K positive in Uygur women was 2.38%, which was higher than that in Uygur men (1.86%). The frequency of d phenotype in Kazak women was 3.15%, which was higher than that in Kirgiz （2.89%） (P<0.01).@*CONCLUSION@#The distributions of Kell(K) and Rh(D) blood groups in northern and southern Xinjiang and eastern Xinjiang had its own unique characteristics and differences. There are significant differences in blood group distribution among different ethnic groups and gender groups. In the future, k antigen detection can be included to further improve the investigation on the distribution of Kell blood group system in this region.

Effect of Circulating Plasma Cells on the Prognosis of Patients with Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#to analyze the effect of circulating plasma cells(CPC) on the prognosis of patients with multiple myeloma(MM) in the era of new drugs, and to explore the new definition standard of primary plasma cell leukemia(pPCL).@*METHODS@#The clinical data of 321 patients with newly diagnosed MM and 21 patients with pPCL admitted to our hospital from January 2014 to May 2022 were retrospectively analyzed. According to the proportion of CPC in peripheral blood smears, all patients were divided into 4 groups: CPC 0% group(211 cases), CPC 1%-4% group(69 cases), CPC 5%-19% group(41 cases) and CPC≥20% group(21 cases). The clinical features of patients in each group were compared and the prognosis fators was analyzed.@*RESULTS@#The median OS of the four groups were 44.5,21.3,24.6 and 12.8 months, respectively. Among them, 295 patients(86.3%) were treated with new drugs, and the median OS of the four groups were not reached, 26.7, 24.6 and 14.9 months, respectively. As the survival curves of CPC 5%-19% group and CPC≥20% group were similar, the patients were divided into CPC<5% group and CPC≥5% group, the median OS of CPC<5% group was better than that in CPC≥5% (43.5 vs 22.3 months, P<0.001). In addition, the median OS of patients in the CPC 1%-4% group was also significantly lower than that in the CPC 0% group and similar to that in the CPC≥5% group. Multivariate analysis showed that 1%-4% CPC was an independent risk factor for the OS of patients with CPC<5%. The patients with CPC<5% were stratified by R-ISS staging, and the OS of R-ISS stage Ⅰ or stage Ⅱ with 1%-4% CPC was similar to that of R-ISS stage Ⅲ. The newly defined pPCL patients showed increased tumor load and obvious invasive characteristics. Multivariate analysis showed no independent prognostic factors for pPCL, and high-risk cytogenetic abnormalities(HRCA) had no significant effect on the prognosis.@*CONCLUSION@#The validity of IMWG's new pPCL definition standard was verified, and it was found that the survival of MM with 1%-4% CPC also is poor and the prognosis is very close to pPCL. In addition, the newly defined pPCL has unique clinical and biological characteristics.

Efficacy and Survival of Venetoclax Based Regimen in the Treatment of Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To explore the efficacy and survival of venetoclax based (VEN-based) regimen in the treatment of acute myeloid leukemia（AML）.@*METHODS@#A retrospective study was conducted in patients who received VEN-based regimen and completed at least 1 course of efficacy evaluation at the The First Affiliated Hospital of Nanchang University from July 2019 to July 2022. The incidence of complete remission （CR）/CR with incomplete hematologic recovery （CRi） rate, objective remission rate（ORR） and survival of patients with different risk strati- fication and gene subtypes were analyzed.@*RESULTS@#A total of 79 patients were enrolled, including 43 patients with newly diagnosed unfit AML （unfit AML） and 36 relapsed/refractory AML (R/R AML). The median age of the patients was 62(14-83) years old. 36 out of 79 patients achieved CR/CRi and the ORR of the whole cohort was 64.6%. The CR/CRi rate of unfit AML patients was significantly higher than that of R/R AML patients (60.5% vs 27.8%, P=0.004). In unfit AML cohort, the patients with NPM1 and IDH1/2 mutations were benefited, 8 out of 9 patients ahcieved CR/CRi, 7/8 and 5/8 patients achieved minimal residual disease (MRD) negativity, respectively. Six out of 9 patients with TET2 mutation achieved CR/CRi, 3/6 patients achieved MRD negativity. In R/R AML cohort, 2 out of 3 patients with RUNX1 mutation achieved CR/CRi, without MRD negative, while the CR/CRi rate of patients with other gene mutations was lower than 40%. The median follow-up time was 10.1(95%CI: 8.6-11.6) months. In whole cohort, the median overall survival (mOS) time was 9.1 months and the relapse free survival (RFS) time was not reached. The mOS and RFS of unfit AML patients were significantly longer than those of R/R AML patients (14.1 vs 6.8 months, P=0.013; not reached vs 3.3 months, P=0.000). In unfit AML cohort, the mOS of patients with NPM1 or IDH1/2 mutations was not reached, while that of patients without NPM1 or IDH1/2 mutations was 8.0 months (P=0.009; P=0.022). Furthermore, the mOS of patients with TP53 mutaion was significantly shorter than that of patients without TP53 mutation (5.2 vs 14.1 months， P=0.049). In R/R AML cohort, there was no significant difference in mOS between patients with mutation in each gene subtype and those without gene mutation (P>0.05). All patients had hematology adverse reactions, 91.1% patients had AE grade≥3. The most common non-hematology adverse reactions was infection, with an incidence of 91.1%. VEN-based regimen was tolerable for AML patients.@*CONCLUSION@#VEN-based regimen can achieve a high response rate, especially in unfit AML with acceptable safety, and some patients can achieve MRD negative. It is also effective in NPM1-, IDH1/2-positive patients with long survival time.

Research Progress and Application of Daratumumab in Non-Multiple Myeloma--Review / 中国实验血液学杂志

Daratumumab is the first CD38 monoclonal antibody drug approved for the treatment of patients with multiple myeloma. It can bind to CD38 expressed by tumor cells, inhibit tumor cell growth and induce myeloma cell apoptosis through a variety of immune-related mechanisms. Meanwhile, CD38 is also expressed in other cells, including regulatory T cells, regulatory B cells and myeloid-derived suppressor cells, which provides a theoretical basis for the treatment of hematological tumor diseases other than non-multiple myeloma diseases. This article reviews the research progress and application of this part.

Efficacy and Safety of Etoposide Combined with Cyclophosphamide for Autologous Peripheral Blood Stem Cell Mobilization in Patients with Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To evaluate the efficacy and safety of etoposide combined with cyclophosphamide (EC) regimen for mobilization of autologous peripheral blood stem cells (APBSCs) in patients with multiple myeloma (MM).@*METHODS@#The clinical data of 48 MM patients who received APBSC transplantation (APBSCT) in Department of Hematology of the First Affiliated Hospital of Nanchang University from January 2015 to October 2021 were retrospectively analyzed. The mobilization success rate and mobilization optimal rate of EC regimen were counted, and its effect on transplant efficacy, adverse reactions, hematopoietic reconstitution after transplantation, and survival time of MM patients were analyzed.@*RESULTS@#APBSCs were collected on day 14 (10-19) after EC administration. The median of collected CD34+ cells was 6.82 (1.27-22.57)×106/kg, and the median number of apheresis session was 2 (1-4). The mobilization success rate (collecting CD34+ cells≥2×106 cells/kg after completion of apheresis) was 98% (47/48), and mobilization optimal rate (collecting CD34+ cells≥5×106 cells/kg after completion of apheresis) was 71% (34/48). The depth of remission were improved after APBSCT, and the complete remission (CR) rate increased from 45.8% before transplantation to 87.5% after transplantation (P <0.01). There was no transplant-related death, no blood transfusion during mobilization, and no mucositis occurred in the patients. The most common complication was neutropenia, with an incidence of 75.0% (36/48). After transplantation, all the patients successfully achieved hematopoietic reconstitution. The median time to neutrophil engraftment was 10 (9-26) days, and median time to platelet engraftment was 10 (8-33) days. By the end of follow-up, both the median progression-free survival (PFS) and overall survival (OS) time were not reached. The 5-year estimated PFS rate and OS rate was 53.8% and 82.4%, respectively.@*CONCLUSION@#The EC regimen for mobilization of APBSC has a high acquisition success rate and controllable adverse reactions, which can be an effective and safe mobilization regimen in MM patients.