Objective:To investigate the clinical efficacy and safety of ferric derisomaltose injection versus iron sucrose injection in the treatment of iron deficiency anemia (IDA) .Methods:A total of 120 patients with iron deficiency anemia admitted from June 2021 to March 2023 were given intravenous iron supplementation with ferric derisomaltose to assess the efficacy and safety of hemoglobin (HGB) elevation before and after treatment. Simultaneously, the clinical effects of iron supplementation with iron sucrose were compared to those of inpatient patients during the same period.Results:Baseline values were comparable in both groups. Within 12 weeks of treatment, the elevated HGB level in the ferric derisomaltose group was higher than that of the iron sucrose group, with a statistical difference at all time points, and the proportion of HGB increased over 20 g/L in the patients treated for 4 weeks was higher (98.7%, 75.9% ). During the treatment with ferric derisomaltose and iron sucrose, the proportion of mild adverse reactions in the ferric derisomaltose group was slightly lower than that of the iron sucrose group, and neither group experienced any serious adverse reactions. The patients responded well to the infusion treatment, with no reports of pain or pigmentation at the injection site.Conclusion:The treatment of IDA patients with ferric derisomaltose has a satisfactory curative effect, with the advantages of rapidity, accuracy, and safety. Therefore, it is worthy of widespread clinical use.

Objective:This study aimed at investigating the efficacy and safety of eltrombopag in the treatment of adult primary immune thrombocytopenia (ITP) and evaluated the factors influencing its efficacy and side effects.Methods:A total of 198 patients with adult ITP who were admitted to Tianjin Medical University General Hospital between January 2018 and March 2022 were retrospectively analyzed. The efficacy of each starting dose of eltrombopag was evaluated, and adverse events were analyzed. The factors influencing efficacy were investigated, including sex, age, adult ITP type, platelet antibodies, and combined drug treatments.Results:Of the 198 patients, 70 males and 128 females with a median age of 45 years (18-88 years) were included; 130 (65.7%) had newly diagnosed adult ITP, 25 (12.6%) had persistent adult ITP, and 43 (21.7%) had chronic adult ITP. The bleeding event scores at baseline were assessed; 84.3% had scores of<4 and 15.7% had scores of ≥4. The eltrombopag response rate (initial response) at 6 weeks was 78.8% (complete response [CR]: 49.0%; CR1: 14.6%; CR2: 15.2%). The median response time to eltrombopag was 7 (7, 14) days. The initial response rates to 25, 50, and 75 mg eltrombopag were 74.1%, 85.9%, and 60.0%, respectively ( P=0.031). The initial response rate to the 50 mg dose was significantly higher than that of the 25-mg and 75-mg doses. Two patients received 100 mg as the starting dose, and their initial response was 0. Regarding dose adjustment, 70.7% of the patients remained on the starting dose, 8.6% underwent dose adjustment to 50 mg, and 6.1% underwent dose adjustment to 75 mg. Another two patients underwent dose adjustment to 100 mg. After dose adjustment, the persistent response rates were 83.6%, 85.3%, and 85.7% for the 25-, 50-, and 75-mg doses, respectively, with no significant difference. After dose adjustment, the sustained efficacy rate for the 100-mg dose (4 patients) was 100.0%. After 6 weeks of treatment with eltrombopag, the overall bleeding score of patients with ITP decreased. The number of patients with a score of ≥4 decreased to 0, the number of patients with a score of<4 decreased, and there was no significant change in the number of patients with a score of 1-2. The most common adverse event associated with eltrombopag was impaired liver function (7.7%). No thrombosis events or other adverse events were observed. ITP type and number of megakaryocytes significantly affected the initial response to eltrombopag. The initial response rates to eltrombopag for newly diagnosed adult ITP, persistent adult ITP, and chronic adult ITP were 85.3%, 56.0%, and 76.2%, respectively ( P=0.003). For megakaryocytes, the initial response rates were 61.8%, 87.1%, and 84.3% ( P=0.009) for the decreased, normal, and increased megakaryocyte groups, respectively. Conclusion:Eltrombopag, as a second-line or higher treatment for adult ITP, has a rapid onset of action and good safety. The initial response rate is significantly higher with a dose of 50 mg than with a dose of 25 mg. Patients with newly diagnosed ITP and those with normal or increased megakaryocyte numbers have a higher initial response rate to eltrombopag.

Objective:To analyze the distribution and drug resistance of pathogens of bacterial bloodstream infection in patients with hematological diseases in the Department of Hematology of Tianjin Medical University General Hospital, and to provide etiological data for clinical empirical anti-infection treatment.Methods:A retrospective analysis was conducted on the general clinical information, pathogenic bacteria and drug susceptibility test results of patients with hematological diseases diagnosed with bacterial bloodstream infection by menstrual blood culture in our center from January 2016 to December 2022.Results:Patients included 498 inpatients, with a total of 639 bacterial strains. Among the patients, 86.9% patients had malignancies, and 76.7% had agranulocytosis. Symptoms of concurrent infections, including those of the respiratory tract, oral mucosa, skin and soft tissues, and abdominal sources were observed in 68.3% patients. Gram-negative bacteria (G -) accounted for 79.0% of the isolated bacteria, and gram-positive bacteria (G +) accounted for 21.0%. The top five isolated pathogens were Klebsiella pneumoniae (22.5%), Escherichia coli (20.8%), Pseudomonas aeruginosa (15.0%), Enterococcus faecium (5.5%), and Stenotrophomonas maltophilum (5.0%). Escherichia coli exhibited a decreasing trend of resistance to quinolones, cephalosporins, and carbapenems. Klebsiella pneumoniae exhibited increasing rates of resistance to quinolones and cephalosporins between 2016 and 2018, but the rated decreased after 2019. The resistance rate to carbapenems exhibited by Pseudomonas aeruginosa was approximately 20%. Carbapenem-resistant strains of Pseudomonas aeruginosa strains were first detected in 2017, with a peak resistance rate of 35.7%, detected in 2019. A 60.0% resistance rate to methicillin was observed in methicillin-resistant coagulase-negative staphylococci (MRCNS), and one case of linezolid-resistant MRCNS was detected. Conclusions:Pathogenic bacteria of bacterial bloodstream infections were widely distributed in our center, and precautions are warranted against carbapenem resistant P. aeruginosa and Klebsiella pneumoniae.

Objective:This study aimed to investigate the role and clinical significance of MUC4 gene mutations in thrombotic events in patients with classic paroxysmal nocturnal hemoglobinuria (PNH) patients.Methods:A retrospective analysis was conducted on the clinical data and gene sequencing results of 45 patients with classic PNH admitted to the Department of Hematology, Tianjin Medical University General Hospital, from June 2018 to February 2022. MUC4 gene mutations in patients with classic PNH were summarized, and the risk factors for thrombotic events in these patients were analyzed. Additionally, the effects of MUC4 gene mutations on the cumulative incidence and survival of thrombotic events in patients with classic PNH were determined.Results:The detection rate of MUC4 gene mutations in patients with classic PNH who experienced thrombotic events (thrombotic group) was 68.8% (11/16), which was significantly higher than that in the non-thrombotic group [10.3% (3/29) ] ( P<0.001). All mutations occurred in exon 2. MUC4 mutation ( OR=20.815, P=0.010) was identified as an independent risk factor for thrombotic events in patients with classic PNH. The cumulative incidence of thrombotic events was 78.6% (11/14) in the MUC4 gene mutation group (mutation group) and 16.1% (5/31) in the non-mutation group, showing a statistically significant difference between the two groups ( P<0.001). Survival analysis showed a lower overall survival (OS) rate in the thrombotic group compared with that in the non-thrombotic group [ (34.4±25.2) % vs. (62.7±19.3) % ] ( P=0.045). The OS rate of patients was (41.7±29.9) % in the mutation group and (59.1±18.3) % in the non-mutation group ( P=0.487) . Conclusion:MUC4 gene mutations are associated with an increased incidence of thrombotic events in classic PNH patients, highlighting their role as independent risk factors for thrombosis in this population. These mutations can be considered a novel predictive factor that aids in evaluating the risk of thrombosis in patients with classic PNH.

ObjectiveTo evaluate the effects of high intensity interval training (HIIT) on patients with type 2 diabetes mellitus (T2DM). MethodsFrom May to October, 2021, twelve patients with T2DM were recruited with internet. An HIIT exercise intervention based on WHO Guidelines on Physical Activity and Sedentary Behaviour and World Health Organization Family of International Classifications (WHO-FICs) was constructed. They received aerobic combined with resistance training in a multi-combination HIIT using whole-body exercise, 30 to 35 minutes a time, three times a week, for eight weeks. Before and after intervention, their blood glucose levels, lipid levels, pancreatic fat content and body composition were measured. ResultsOne cased was dropped. After intervention, the fasting glucose, 2-hour postprandial glucose, hemoglobin A1c, fasting serum insulin, insulin resistance index, serum total cholesterol, serum triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, pancreatic fat content, body weight, body mass index, and body fat percentage improved (t > 2.258, P < 0.05). ConclusionHIIT exercise intervention based on the Guidelines and WHO-FICs could improve the related functions of patients with T2DM, such as blood glucose levels, blood lipid levels, pancreatic fat content and body composition, and reduce the consumption of hypoglycemic drugs.

Objective:To investigate the clinical application value of peripheral blood metagenomic next-generation sequencing (mNGS) test for patients with hematological diseases accompanied by fever.Methods:The blood mNGS results and clinical data of inpatients with hematological diseases accompanied by fever treated in the Hematology Department of Tianjin Medical University General Hospital in March 2020 to June 2021were retrospectively analyzed. A total of 90 patients with 98 cases of specimens were included. The pathogen distribution characteristics and mNGS test performance were analyzed.Results:The positive rate of peripheral blood mNGS was significantly higher than that of traditional examination (68.37% vs 37.76%, P<0.001) and blood culture (68.37% vs 9.18%, P<0.001) . Viral, bacterial, and fungal infections accounted for 38.81%, 14.93%, and 2.99% in patients with single-pathogen infections, respectively. Polymicrobial infections accounted for 43.28%, in which viral and bacterial coinfections were the most common type (25.37%) . There were 55 virus-positive cases (82.09%) , 30 bacteria-positive cases (44.78%) , and 14 fungus-positive cases (20.90%) . The clinical approval rate of peripheral blood mNGS was 64.63% (63/98) . The sensitivity, specificity, positive predictive value, and negative predictive value (NPV) of peripheral blood mNGS were 75.68%, 36.07%, 41.79%, and 70.97%, respectively, and the overall consistency rate with traditional examination was 51.02%. Of the 22 pulmonary infection cases with no detectable pathogens by conventional tests, the pathogens were identified by peripheral blood mNGS in 14 cases, 10 of which were clinically approved. Conclusion:The positive rate of peripheral blood mNGS was significantly higher than that of blood culture and traditional laboratory examination. Peripheral blood mNGS had a high clinical recognition rate, sensitivity, and NPV in the detection of pathogens in patients with hematological diseases accompanied by fever.

OBJECTIVE: To assess the association of single nucleotide polymorphisms (SNPs) of dual specificity phosphatase 9 (DUSP9) gene rs5945326 locus with gestational diabetes mellitus (GDM). METHODS: Genotypes for the rs5945326 locus were determined for 206 pregnant women with GDM (GDM group) and 189 unaffected pregnant women (control group). Allelic and genotypic frequencies of the GDM and control groups were compared. For individuals with various genotypes, the level of blood glucose, serum lipids, and body mass index (BMI) were also compared. RESULTS: The frequencies of AA, AG and GG genotypes for the GDM group were 32.2%, 52.2% and 15.6%, respectively, and 41.2%, 43.9% and 15.0%, for the control group, respectively. No significant difference was detected in the distribution of above genotypes between the two groups (chi-square=3.601, P=0.165). The frequencies of alleles A and G were 58.3% and 41.7% in the GDM group, and 63.1% and 36.9% in the control group, respectively. No significant difference was detected between the two groups too (chi-square=1.894, P=0.188). The high density lipoprotein (HDL) levels of the GG genotype [(2.34×0.61) mmol/L] was significantly higher than that of the AG+AA genotype [(2.06×0.56) mmol/L] (t=2.993, P=0.003). No significant difference was detected in other clinical indexes between the two groups (P> 0.05). CONCLUSION The SNP rs5945326 in DUSP9 gene may be not associated with the risk of GDM. However, there are correlated with HDL levels.
Alleles ; Diabetes, Gestational ; genetics ; Dual-Specificity Phosphatases ; genetics ; Female ; Gene Frequency ; Genotype ; Humans ; Mitogen-Activated Protein Kinase Phosphatases ; genetics ; Polymorphism, Single Nucleotide ; Pregnancy

OBJECTIVETo explore the role of sphingomyedlin phosphodiesterase 1 (SMPD1) gene mutations in the pathogenesis of Parkinson's disease (PD).

METHODSFor 110 Chinese patients with PD, all exons of the SMPD1 gene were sequenced, and the results were compared with reference sequence from GenBank to identify possible mutations.

RESULTSA novel heterozygous mutation Ex2:c.677C>A/p.P226Q (likely pathogenic) was identified in a patient, which resulted in substitution of Glutamic acid by Proline at position 226. In addition, two known single nucleotide polymorphisms (SNPs) Ex1:c.107T>C/p.V36A (benign) and Ex6:c.1522G>A/p.G508R (benign), and three previously reported SMPD1 mutations Ex2:c.T371T>G/p.L124R (uncertain significance), Ex2:c.636T>C/P.(=)(benign) and Ex6:c.1598C>T/p.P533L (uncertain significance) were identified. The novel p.P226Q mutation and p.P533L mutation were predicted to have a possibly damaging effect on the structure and function of SMPD1 protein, which in turn may lead to PD.

CONCLUSIONThe mutation rate of the SMPD1 gene was 3.64% among Chinese PD patients. Genetic variants of SMPD1 may increase the risk of PD.

Objective: To investigate the change of autophagy level of bone marrow nucleated red blood cell (RBC) in patients with myelodysplastic syndromes (MDS) . Methods: Fifty-four MDS patients and thirty-three controls were enrolled in this study. The mitophagy were observed by transmission electron microscopy (TEM) . The level of autophagy-associated protein LC3B in GlycoA⁺ nucleated RBC was measured by flow cytometry. The expressions of ULK1 and mTOR mRNA in GlycoA⁺ nucleated RBC were measured by real-time PCR. The expression of the mitochondrial outer membrane protein TOM20 in GlycoA⁺ nucleated RBC was detected by Western blot. Results: Autophagosomes or autolysosomes were scarcely observed by TEM in MDS patients. The expression of LC3B in GlycoA⁺ nucleated RBC in high-risk MDS patients (0.22±0.12) was significantly lower than that in normal controls (0.43±0.22, P<0.001) , and lower than that in low-risk MDS patients (0.40±0.16, P=0.001) . The expression of AMPK [0.26 (0.60) ] in GlycoA⁺ nucleated RBC in high-risk MDS patients was significantly lower than that in controls [1.00 (2.07) , P<0.017) . The expression of ULK1 mRNA in GlycoA⁺ nucleated RBC in high-risk MDS patients [0.27 (3.31) ] was significantly lower than that in controls [1.07 (4.41) , P<0.017]. The level of mTOR mRNA in GlycoA⁺ nucleated RBC in high-risk MDS patients [1.82 (3.74) ] was significantly higher than that in controls [1.26 (1.38) , P<0.017]. The level of LC3B in GlycoA⁺ nucleated RBC was negatively correlated with the HGB (r=0.529, P=0.009) in high-risk MDS patients. The expression of mitochondrial outer membrane protein TOM20 in high-risk MDS patients was 9.42±4.42. Conclusion Autophagy is impaired in nucleated RBC of MDS patients.

Objective: To explore characteristic and function of peripheral blood mononuclear cells (PBMNC) -induced macrophages in patients with myelodysplastic syndrome (MDS) to couple with its progression. Methods: A total of 24 MDS patients (11 low-risk patients and 13 high-risk group patients) referred to Department of Hematology of Tianjin Medical University General Hospital and normal controls were enrolled from September 2014 to December 2015. PBMNC was stimulated with GM-CSF to transform to macrophages. The morphology of macrophages was observed by microscope. The quantity of macrophages, CD206 and SIRPα on surface of macrophages were detected by flow cytometry. The phagocytic function of macrophages was analyzed by fluorescence microscopy and flow cytometry. Results: The morphology of macrophages from MDS patients was abnormal. The percentage of transformed macrophages was (5.17±3.47) % in patients with MDS, which was lower than that in controls significantly[ (66.18±13.43) %, t=3.529, P=0.001]. The expression of CD206 on macrophages from MDS patients was significantly lower than that of controls[ (9.73±2.59) % vs (51.15±10.82) %, t=4.551, P<0.001]. The SIRPα level of macrophages from MDS patients was significantly lower than that of controls [ (0.51±0.09) % vs (0.77±0.06) %, t=2.102, P=0.043]. The phagocytic index and the percentage of phagocytic of macrophages from MDS patients were significantly lower than those of macrophages from normal controls[0.45±0.08 vs 0.92±0.07, t=-6.253, P=0.008; (23.69±3.22) % vs (42.75±2.13) %, t=-6.982, P=0.006 respectively]by flow cytometry. The phagocytic index of MDS patients was significantly lower than that of controls (0.24±0.04 vs 0.48±0.96, t=3.464, P=0.001) by fluorescence microscopy. Conclusion The quantity, recognization receptors and phagocytosis of PBMNC-induced macrophages decreased in MDS patients.