Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and highly aggressive hematological malignancy, there is no standard treatment and the prognosis is very poor. Affiliated Zhongshan Hospital of Dalian University report a case of 85-year-old BPDCN male patient treated with DVT regimen (decitabine combined with Venetoclax and thalidomide) and achieved complete remission. The patient with skin nodules and the pathology diagnosed BPDCN, the next generation sequencing of skin nodules showed mutations of IDH2 and ASXL1. DVT (decitabine combined with Venetoclax and thalidomide) has significant efficacy with rapid and deep remission for BPDCN, and the adverse effects is less, especially suitable for elderly patients who cannot tolerate intense chemotherapy.

Objective:To investigate the clinical features, efficacy and risk factors for the development of anemia in newly-diagnosed multiple myeloma (NDMM) patients with anemia.Methods:A retrospective case-control study was conducted. General data and laboratory findings of 165 NDMM patients hospitalized at the People's Hospital of Qiannan in Guizhou Province and Affiliated Zhongshan Hospital of Dalian University from January 2018 to December 2022 were retrospectively analyzed. The patients were treated with chemotherapy regimens based on at least 2 new drugs including proteasome inhibitors and immunomodulators, and the efficacy was assessed after 4 cycles of treatment. According to peripheral blood hemoglobin (Hb) concentration, patients were divided into anemia group (Hb < 100 g/L) and non-anemia group (Hb ≥ 100 g/L). The general data, hematological indexes, and treatment effects of the two groups were compared. Pearson correlation coefficient was used to analyze the correlation between Hb and hematological indexes; multivariate logistic regression was used to analyze the risk factors for the occurrence of anemia in patients with NDMM; anemia defined by Hb was used as the gold standard, and receiver operating characteristic (ROC) curve was used to analyze the effect of the above risk factors for anemia on judging the occurrence of anemia in MM patients.Results:There were 120 cases in the anemia group with a median age [ M ( Q1, Q3)] of 64 years old (59 years old,74 years old), including 61 (50.8%) males and 59 (49.2%) females, and 45 cases in the non-anemia group with a median age of 61 years old (54 years old, 68 years old), including 27 (60.0%) males and 18 (40.0%) females. The age of patients and the proportion of patients with Durie-Salmon (DS) stage Ⅲ, international staging system (ISS) stage Ⅲ, renal impairment, and hypercalcemia in the anemia group were higher than those in the non-anemia group (all P < 0.05); peripheral blood platelet counts and serum albumin concentrations in the anemia group were lower than those in the non-anemia group, and the differences were statistically significant (all P < 0.05); the concentrations of globulin, the erythrocyte sedimentation rate (ESR) and serum β 2-microglobulin (β 2-MG) concentration, creatinine concentration, uric acid concentration, serum corrected calcium concentration, and the proportion of abnormal plasma cells in bone marrow in the anemia group were higher than those in the non-anemic group, and the differences were statistically significant (all P < 0.05). The objective remission rate in the anemia group was lower than that in the non-anemia group [42.5% (51/120) vs. 71.1% (32/45), χ2 = 10.72, P = 0.001]. Pearson correlation coefficient showed that Hb concentration was positively correlated with serum albumin concentration and platelet count ( r values were 0.569 and 0.229, both P < 0.05), and it was negatively correlated with ESR, globulin, β 2-MG, creatinine, uric acid, serum corrected calcium concentration and the proportion of abnormal plasma cells in bone marrow ( r values were -0.318, -0.465, -0.373, -0.230, -0.303, -0.248, and -0.368, all P < 0.05). Multivariate logistic regression analysis showed that the increased serum albumin concentration was the independent protective factor for the occurrence of anemia in patients with NDMM ( OR = 0.891, 95% CI: 0.798-0.994, P = 0.039), and the increased proportion of abnormal plasma cells in bone marrow was the independent risk factor for the occurrence of anemia in patients with NDMM ( OR = 0.941, 95% CI: 0.908-0.974, P = 0.001). ROC curve analysis showed that the areas under the curve for the occurrence of anemia in NDMM patients based on serum albumin concentration and the proportion of abnormal plasma cells in bone marrow were 0.813 (95% CI: 0.743-0.882, P < 0.001) and 0.792 (95% CI: 0.715-0.870, P < 0.001). Conclusions:Compared with NDMM patients without anemia, NDMM patients with anemia have abnormalities in several tests and poor treatment outcomes, and these patients should be actively corrected for anemia and hypovitaminosis, and clear plasma cell load as early as possible in conjunction with antimyeloma therapy.

Objective:To investigate the clinical features and family gene mutation results of the adult onset Gaucher disease patient.Methods:The diagnosis and treatment of a patient with Gaucher disease who was admitted to the Affiliated Zhongshan Hospital of Dalian University in March 2020 were retrospectively analyzed, and the literature was reviewed.Results:The patient (the proband) was a 34-year-old female, the anemia, thrombocytopenia and splenomegalia were found in 2005. After regular physical examination, the decrease of leukocyte, red blood cell and platelet was gradually aggravated, and the progressive enlargement of the spleen was aggravated. She visited the clinic on March 19, 2020 due to worsening of fatigue. The physical examination revealed hepatomegaly, splenomegaly; blood routine examination showed pancytopenia, and bone marrow morphology showed a large number of Gaucher cells. Peripheral blood β- glucocerebrosidase (GBA) of the proband was 1.8 nmol·mg -1·h -1 (reference value 10-25 nmol·mg -1·h -1), and the GBA of her father, mother, brother, and daughter was normal. The second-generation sequencing results showed that the proband had a mutation in the BCL2 gene at locus c.127G>A p.A43T, with a mutation frequency of 49.53%. GBA gene testing showed that the proband had a heterozygous mutation at c.1448T>C (a pathogenic mutation), heterozygous mutations at c.1026A>G and c.1038C>T (homozygous mutations), and a heterozygous mutation at c.1075G>T (mutation of unknown clinical significance). The proband's father had c.1448T>C heterozygous mutation, and he was a carrier; the proband's mother had c.1075G>T heterozygous mutation; the proband's brother had no gene mutation; the proband's daughter had c.1448T>C heterozygous mutation, and she was a carrier. The diagnosis was type Ⅰ Gaucher disease (non-neuropathic). The patient was proposed to participate in the clinical trial of imiglucerase, and during the follow-up, the blood routine was relatively stable, and the spleen remained progressively enlarged. Conclusions:Gaucher disease is rare, which is easy to be misdiagnosed and underdiagnosed. It is necessary to be alert to the possibility of Gaucher disease when there are patients with unexplained hemocytopenia, liver and spleen enlargement and multiple organs involvement, and enzyme and genetic tests should be performed as soon as possible.

Objective:To assess the clinical significance of next-generation sequencing (NGS)-based IGH/ IGK gene rearrangement analysis versus flow cytometry (FCM) in diagnosing minimal residual disease (MRD) of children with acute B-cell lymphoblastic leukemia (B-ALL). Methods:Clinical data, NGS-MRD and FCM-MRD findings at the initial diagnosis and after induction chemotherapy of 85 children diagnosed as B-ALL in Children′s Hospital of Nanjing Medical University from July 2019 to July 2021, were retrospectively analyzed.The sensitivity of the two methods, and the positive rate were compared by χ2 test or Fisher′ s test.The correlation was identified by Spearman correlation analysis. Results:Dominant clone sequences were detected in all children at the initial diagnosis by NGS, while selection markers were identified by FCM in 75(88.2%) patients.Positive MRD rate detected by NGS-MRD was significantly higher than that of FCM-MRD at the same time point after induction chemotherapy[31.8%(27/85) vs.9.4%(8/85), P<0.001]. Compared with those of FCM-MRD, NGS-MRD had good sensitivity (100.0%), specificity (75.3%) and negative predictive value (100.0%), and the positive predictive value was 29.6%.MRD results detected by NGS were consistent with that of FCM ( r=0.569, P<0.001). By July 27, 2022, 2 patients with NGS-MRD (+ )FCM-MRD (-)relapsed during maintenance chemotherapy. Conclusions:NGS is highly consistent with FCM in the detection of MRD in children with B-ALL, which is more sensitive.The combination of NGS-MRD and FCM-MRD benefits more in monitoring MRD in children with B-ALL after induction chemotherapy.

Objective:To explore the detection and segmentation of ischemic core infarct volume of the acute stroke in diffusion weighted imaging (DWI) images using cascaded VB-Net.Methods:MRI data of 1 500 patients (2 456 lesions) with acute ischemic stroke in Henan Provincial People′s Hospital from December 2016 to December 2018 were retrospectively analyzed. Firstly, manual segmentation of ischemic core was performed on DWI images (b=1 000 s/mm 2), and then all data were divided into training set, validation set and independent test set by 8∶1∶1. Then, the cascaded VB-Net was constructed, and the core infarct was automatically detected and segmented in the test set. Interclass correlation coefficient (ICC) was used to evaluate the consistency of volume size measured by manual segmentation and cascaded VB-Net. The patients were divided into large ischemic core lesion group (ischemic core volume ≥10 ml) and small ischemic core lesion group (ischemic core volume<10 ml), and the Dice coefficient difference between the two groups was compared using Mann-Whitney U test. Results:In independent test set, cascaded model had the detection rate of 94.6% (243/257) with Dice coefficient of 0.76 (0.68, 0.84). The agreement of cacade VB-Net segmented [4.19(1.21,14.13)ml] and manual segmented ischemic core infarct volume [4.08(1.19,17.92)ml] was high (ICC=0.97, P<0.001). There was no significant difference in Dice coefficient between large and small lesion groups [0.76 (0.69, 0.85), 0.76 (0.67, 0.84), Z=-0.44, P=0.657]. Conclusions:The cascaded VB-Net model provided a tool to realize automatic detection, segmentation, and calculation of ischemic core infarct volume. It has good segmentation accuracy and high consistency with manual segmentation, which can provide an auxiliary decision-making tool for the selection of treatment plans.

Objective:To analyze the clinical and genetical characteristics of children with Gaucher disease and to explore the relationship between genotype and phenotype.Methods:In this retrospective study, the clinical data of 14 children with Gaucher disease diagnosed in Children′s Hospital of Nanjing Medical University from August 2016 to October 2021 were analyzed. Their general conditions, clinical manifestations, laboratory tests and gene variations were collected, followed by the analysis of the clinical phenotypes and genotypes.Results:Among 14 children diagnosed with Gaucher disease, 9 were males and 5 were females, with the age of diagnosis ranging from 0.7 to 15.8 years. There were 10 patients with type 1 Gaucher disease, 2 patients with type 2, and 2 patients with type 3. The most common clinical manifestations were splenomegaly, thrombocytopenia (14 cases), hepatomegaly (8 cases) and anemia (8 cases). There were 6 patients with growth retardation, and 5 patients lag in height compared with their peers. Bone abnormalities were revealed by magnetic resonance imaging in 7 type 1 Gaucher disease patients, but only 1 patient experienced bone pain. Patients with type 2 and type 3 Gaucher disease also presented with convulsions, nystagmus and hearing loss. Gaucher cells were found in bone marrow smears in 12 patients. The glucocerebrosidase gene variations identified in 13 patients were heterozygous and in 1 type 1 patient was homozygous of L483P. L483P variation accounted for 33%(10/30) of the variation alleles, followed by V414L, D448H and R159W. The variation alleles were L483P and L422R, F252I and L483P in 2 children with severe neurological manifestations of Gaucher disease. A novel variation c.22A>G was detected.Conclusions:Splenomegaly and thrombocytopenia are the main clinical presentations of Gaucher disease in children and bone lesions revealed by radiologic imaging appear prior to the occurrence of bone diseases, type 2 and type 3 Gaucher disease also present growth retardation and neurological manifestation. The most frequent variant allele is L483P, which are detected in all 3 subtypes of Gaucher disease. The L422R, F252I gene variants correlated with the neuronopathic phenotype.

Objective:To understand the degree of professional autonomy of nurses in Pediatric Nursing Alliance and the status of pediatric nursing practice environment, which providing guidance for the development of a series of specialized training in the alliance.Methods:Stratified random sampling method was used to conduct a questionnaire survey on nursing staff of different professional levels in Pediatric Nursing Alliance, which through the questionnaire star by using the questionnaire general information and training demand questionnaire, nurses practice professional autonomy scale, pediatric nursing staff structural empowerment questionnaire and nursing practice influencing factors questionnaire through the questionnaire star.Results:The total score for professional autonomy of nurses in the pediatric alliance was 192.66±18.63, the structural empowerment ( OR=1.137, 95% CI=1.084-1.194), lack of caring team ( OR=2.763, 95% CI=1.443-5.292) and performance evaluation ( OR=0.498, 95% CI= 0.274-0.908), specialized education and professional experience ( OR=0.548, 95% CI= 0.334-0.871) were affecting the clinical nursing practice. Conclusion:The degree of professional autonomy of nurses in the Pediatric Nursing Alliance is in the middle and high level. Key factors affecting nursing practice including insufficient structural empowerment, lack of opportunities to continue learning, lack of nursing teams, lack of effectiveness evaluation and the lack of specialized education and work experience, which guiding the pediatric nursing alliance to continuously deepen the connotation of pediatric nursing professional and innovative team collaboration new model, utilize the advantages of resources to actively cultivate specialized nursing research personnel, carry out multi-disciplinary and cross-disciplinary cooperation, improve the nursing quality evaluation index system, so as to enhance the professional nursing service capacity and value.

Objective: To explore the effects and molecular mechanism of the selective JAK1inhibitor SHR0302 and Ruxolitinib on myeloproliterative neoplasms (MPN) cell line SET2 and primary cells in vitro. Methods: Cell proliferation was detected by CCK8 kit. Colony forming experiment was conducted to evaluate erythroid burst colony formation unit (BFU-E) of primary cells from MPN patients. Multi-factor kits were used to detect six inflammatory cytokines. Phosphorylated proteins of Jak-Stat signaling pathway were tested by Western blot. Results: At different time points after treated with SHR0302 and Ruxolitinib, the inhibition of cell proliferation was dose dependent by both drugs (P<0.01) . The inhibitory rates of 2.5 μmol/L SHR0302 and 0.1 μmol/L Ruxolitinib on SET2 cells for 72 h were comparable, i.e. (59.94±0.60) % and (64.00±0.66) %, respectively, suggesting that the inhibitory effect of SHR0302 was weaker than that of Ruxolitinib. Similarly, both SHR0302 and Ruxolitinib inhibited BFU-E in primary marrow cells from MPN patients in a dose-dependent manner. SHR0302 1.0 μmol/L produced similar degree of inhibition compared to Ruxolitinib 0.2 μmol/L. Except IL-12, the expression of other 5 cytokines (IL-6, TNF-α, IL-1β, IL-2, IL-8) was significantly inhibited by 1.6 μmol/L SHR0302 in SET2 cells at 24 h (P<0.01) , while Ruxolitinib 1.0 μmol/L had the same effect. Several phosphorylated molecules of Jak-Stat signaling pathway were significantly inhibited by SHR0302 in SET2 cells only for 3 h. P-stat1 (Tyr701) , p-stat3 (Tyr705) were down-regulated when treated with SHR0302 1.0 μmol/L (P<0.05) , p-jak1 (tyr1022/1023) and p-stat5 (Tyr694) were inhibited at 5.0 μmol/L (P<0.05) . Ruxolitinib significantly inhibited the downstream STAT protein at 0.1 μmol/L. Again, the inhibitory effect of SHR0302 on protein expression was weaker than that of Ruxolitinib. Conclusion SHR0302 can effectively inhibit the proliferation of MPN cell line and patients' primary cells, as well as the expression of inflammatory factors. The molecular mechanism is possibly related to the down-regulation of phosphorylated proteins of Jak-Stat signaling pathway. Overall, the anti-proliferative and anti-inflammatory effects of SHR0302 are weaker than those of Ruxolitinib.

BACKGROUND/AIMS: Functional dyspepsia (FD) remains a great clinical challenge since the FD subtypes, defined by Rome III classification, still have heterogeneous pathogenesis. Previous studies have shown notable differences in visceral sensation processing in the CNS in FD compared to healthy subjects (HS). However, the role of CNS in the pathogenesis of each FD subtype has not been recognized. METHODS: Twenty-eight FD patients, including 10 epigastric pain syndrome (EPS), 9 postprandial distress syndrome (PDS), and 9 mixed-type, and 10 HS, were enrolled. All subjects underwent a proximal gastric perfusion water load test and the regional brain activities during resting state and water load test were investigated by functional magnetic resonance imaging. RESULTS: For regional brain activities during the resting state and water load test, each FD subtype was significantly different from HS (P < 0.05). Focusing on EPS and PDS, the regional brain activities of EPS were stronger than PDS in the left paracentral lobule, right inferior frontal gyrus pars opercularis, postcentral gyrus, precuneus, insula, parahippocampal gyrus, caudate nucleus, and bilateral cingulate cortices at the resting state (P < 0.05), and stronger than PDS in the left inferior temporal and fusiform gyri during the water load test (P < 0.05). CONCLUSIONS: Compared to HS, FD subtypes had different regional brain activities at rest and during water load test, whereby the differences displayed distinct manifestations for each subtype. Compared to PDS, EPS presented more significant differences from HS at rest, suggesting that the abnormality of central visceral pain processing could be one of the main pathogenesis mechanisms for EPS.
Brain ; Broca Area ; Caudate Nucleus ; Classification ; Dyspepsia ; Functional Neuroimaging ; Healthy Volunteers ; Humans ; Magnetic Resonance Imaging ; Parahippocampal Gyrus ; Parietal Lobe ; Perfusion ; Prefrontal Cortex ; Sensation ; Somatosensory Cortex ; Visceral Pain ; Water

Objective To investigate the clinical symptoms and mental state of patients with irritable bowel syndrome with diarrhea (IBS-D ) , and to analyze the characteristics of psychological disorders in patients with IBS-D and their impacts on intestinal symptoms .Methods From July 2009 to June 2012 ,patients met Rome Ⅲ criteria of IBS-D were consecutively enrolled at Peking Union Medical College Hospital .The symptoms of IBS were investigated by IBS symptoms questionnaire and mental state were evaluated by Hamilton anxiety scale (HAMA ) and Hamilton depression scale (HAMD ) . The differences in intestinal symptoms between patients with comorbid psychological disorders and without psychological disorders were compared .And the correlation between the scores of HAMA ,HAMD and intestinal symptoms were analyzed . Two independent sample t-tests ,chi square test and Fisher exact probability were performed for statistical analysis .Spearman rank correlation was used for correlation analysis .Results A total of 231 patients with IBS-D were enrolled .There were 133 males and 98 females with an age of (42 .8 ± 11 .1) years old and a disease course of (4 .5 years (8 .0 years)) .The HAMA and HAMD scores were 17 .00 ± 7 .12 and 14 .05 ± 6 .00 ,respectively ,and 72 .29％ (167/231) patients had comorbid psychological disorders ,32 .90％ (76/231 ) patients had moderate to severe anxiety and/or depression ,mainly had anxiety .The proportion of patients with ordinary abdominal pain or discomfort and the proportion of moderate to severe abdominal pain or discomfort in patients with psychological disorders were higher than those of patients without psychological disorders (53 .29％ , 89/167 vs . 34 .37％ , 22/64;49 .44％ ,44/89 vs .18 .18％ ,4/22) ,and the differences were statistically significant (χ2=6 .634 and 7 .002 , P=0 .010 and 0 .009) .In patients with comorbid psychological disorders ,more patients had frequent onset of abdominal pain or discomfort ,less achieved completely improvement after defecation , and often accompanied with defecation related symptoms .The HAMD score was positively correlated with the onset frequency of IBS (r=0 .172 ,P=0 .009) ,and the HAMA score was positively correlated with the degree of abdominal pain or discomfort before defecation (r=0 .134 , P= 0 .042) .The HAMA and HAMD scores were negatively correlated with the improvement degree of abdominal pain or discomfort after defecation (r= -0 .215 , P=0 .001 ;r= -0 .251 , P<0 .01) ,and were positively correlated with waiting time for symptoms improvement (r=0 .175 , P=0 .008;r=0 .219 , P= 0 .001) .Conclusion Most IBS-D patients have comorbid psychological disorders , anxiety and/or depression greatly impact the intestinal symptoms of patients with IBS .