Objective To investigate whether aberrant DNA methylation of ubiquinol-cytochrome C reductase core protein 1(UQCRC1)is related to cognitive impairment caused by neonatal sevoflurane exposure.Methods A total of 94 SPF C57 mice of either sex,aged 6 d,and weighing 4～6 g,were randomly divided into 7 groups:control group(Con,n=6),sevoflurane-6 and-24 h exposure groups(Sev-6 and-24 h,n=6),control+DMSO group(Con+DMSO,n=19),control+5-aza-2'-deoxycytidine(5-AZA,methylation inhibitor)group(Con+5-AZA,n=19),sevoflurane+DMSO group(Sev+DMSO group,n=19),and sevoflurane+5-AZA group(Sev+5-AZA group,n=19).From 6 to 8 d after birth,the mice of the Sev-6 and-24 h exposure groups were exposed to 3％sevoflurane daily(with 97％oxygen,2 L/min,2 h per day),while those from the Con groups were given exposure of 100％oxygen(2 L/min,2 h per day).For the mice of the 5-AZA and DMSO groups,1 mg/kg of 5-AZA or an equal volume of DMSO was injected intraperitoneally 30 min before daily exposure.In 6 and 24 h after the last exposure to sevoflurane,6 mice from the Con,Sev-6 h,and Sev-24 h groups were euthanized for biochemical analysis,and in 24 h post-exposure,6 mice from the Con+DMSO,Con+5-AZA,Sev+DMSO,and Sev+5-AZA groups were randomly selected for biochemical analysis,while another 3 mice from above each group were also randomly selected for morphological analysis.The remaining 10 mice in these groups underwent behavioral testing(open field test,novel object test,and Y-maze test)at 30～33 d after birth to assess cognitive function,and were euthanized in 24 h after the final behavioral test.RT-qPCR and Western blotting were used to detect the hippocampal expression of UQCRC1,DNA methyltransferases(Dnmts),and methyl CpG binding protein 2(Mecp2)at mRNA and protein levels,respectively.Immunofluorescence assay was employed to observe the distribution and expression of UQCRC1 in the hippocampus.Bisulfite sequencing PCR(BSP)was applied to measure the methylation in the UQCRC1 promoter region.Results Compared with the Con group,the mRNA and protein levels of UQCRC1 were down-regulated(P<0.05),and the mRNA level of Dnmts was up-regulated(P<0.05)in both the Sev-6 h and Sev-24 h exposure groups,while the methylation level in the UQCRC1 promoter region was enhanced in the Sev-24 h exposure group(P<0.05).Additionally,the Sev+5-AZA group had obviously increased mRNA and protein levels of UQCRC1(P<0.05),and notable improvement in cognitive impairment(P<0.05)when compared with the Sev+DMSO group.Conclusion Hypermethylation of UQCRC1 promoter region and thus down-regulating its mRNA and protein expression might be the main mechanism by which repeated neonatal sevoflurane exposure induces cognitive impairment later in life.

Myelodysplastic syndrome (MDS), a myeloid tumor derived from the malignant clones of hematopoietic stem cells, has an annually increasing incidence. The contemporary research direction has shifted to analyzing the synergistic effect of immune surveillance collapse and abnormal bone marrow microenvironment in the pathological process of MDS. Against this backdrop, the immune checkpoint molecule TIM3 has emerged as a key target because of its persistently high expression on the surface of important immune cells such as T and NK cells. The abnormal activation of the TIM3 pathway is the mechanism by which solid tumors and hematological malignancies achieve immune escape and is a key hub in the formation of immune exhaustion phenotypes. This work integrates the original discoveries of our team with the latest international progress, systematically demonstrating the bidirectional regulatory network of TIM3 between the malignant clone proliferation of MDS and the immunosuppressive microenvironment. Integrating the evidence from emerging clinical trials allows us to consider the clinical significance of TIM3-targeted blocking for MDS, providing a transformative path to overcome the resistance of traditional treatments and marking a new chapter in the active immune reconstitution of MDS treatment.

Objective:To analyze mortality risk factors in patients with severe pneumonia and investigate their varying influences across different time periods.Methods:A total of 134 patients with severe pneumonia admitted to the Emergency Department of Xiang’an Hospital, Xiamen University, between June 2019 and February 2020 were enrolled. All patients were treated in the EICU and followed up for four years. Based on outcomes, they were categorized into a death group ( n=77) and a survival group ( n=57). COX regression analysis was employed to identify mortality risk factors at different time points, while logistic regression analysis was used to assess risk factors influencing mortality during hospitalization, ICU stay, 1-month, and 1-year follow-up periods. Results:Mortality rates were 11.9% ( n=16) during ICU admission, 20.8% ( n=28) during hospitalization, 16.4% ( n=22) within 1 month, and 31.3% ( n=42) within 1 year. By the end of the follow-up, 57.4% ( n=77) of patients had died. Ten mortality risk factors were identified, with the number increasing over time. During ICU admission and hospitalization, significant risk factors included total bilirubin levels, APACHE-II score, invasive ventilation, ARDS, and vasopressor use in the ICU. One-month mortality risk additionally involved bacterial infection. One-year mortality risk further incorporated advanced age and chronic heart failure. By the end of follow-up, acute kidney injury (AKI) during ICU admission also emerged as a contributing factor, while higher body weight was identified as a protective factor. Conclusions:The number of mortality risk factors in severe pneumonia patients increases progressively over time. Early-stage factors during hospitalization and ICU admission exert a stronger impact on short-term mortality, whereas bacterial infection, advanced age, and chronic heart failure become increasingly significant in later stages. These findings highlight the dynamic nature of risk factors and underscore the importance of tailored monitoring and intervention strategies at different disease phases.

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 level and clinical significance of IL-18 and IL-18-binding protein (BP) in the bone marrow of patients with myelodysplastic syndrome (MDS) .Methods:A total of 43 newly diagnosed patients with MDS who were admitted to the Department of Hematology, Tianjin Medical University General Hospital, from July 2020 to February 2021 were randomly selected. The control group consisted of 14 patients with acute myeloid leukemia (AML) and 25 patients with iron-deficiency anemia (IDA). The levels of IL-18 and IL-18 BP in the bone marrow supernatant were measured, and their correlations with MDS severity, as well as the functionality of CD8 + T cells and natural killer cells, was analyzed. Results:The levels of IL-18, IL-18 BP, and free IL-18 (fIL-18) in the bone marrow supernatant of patients with MDS were higher than in the IDA group. The level of fIL-18 was linearly and negatively correlated with the MDS-International Prognostic Scoring System (IPSS) score. IL-18 receptor (IL-18Rα) expression on CD8 + T cells in the MDS group was lower than in the IDA group, and the levels of fIL-18 and IL-18Rα were positively correlated with CD8 + T-cell function in the MDS group. Conclusion:IL-18 BP antagonizes IL-18, leading to a decrease in fIL-18 in the bone marrow microenvironment of patients with MDS, affecting CD8 + T-cell function, which is closely related to MDS severity; therefore, it may become a new target for MDS treatment.

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:To evalaute the role of hippocampal ubiquinol cytochrome C reductase core protein 1 (UQCRC1) in cognitive dysfunction after global cerebral ischemia (GCI) in mice.Methods:Forty SPF healthy male C57BL/6J mice, aged 12 weeks, weighing 22-26 g, were selected, and 20 of them were divided into 2 groups ( n=10 each) using a random number table method: sham operation group and GCI1 group. The other 20 mice were divided into 2 groups ( n=10 each) by the random number table method: GCI2 group and GCI+ UQCRC1 overexpression group (GCI+ UQCRC1 group). In Sham group, the skin was directly sutured after exposing both common carotid arteries. Global cerebral ischemia was induced by occlusion of bilateral common carotid arteries for 20 min in GCI1, GCI2 and GCI+ UQCRC1 group, and lentivirus VSVG-Lentivirus-hSyn-EGFP-P2A-UQCRC1-WPRE-pA 500 nl was injected into the bilateral hippocampus at 2 weeks before developing the model in GCI+ UQCRC1 group. The novel object recognition task was carried out on the 2nd day following completion of model development, and the percentage of time spent exploring the novel object was calculated. The fear conditioning test was carried out on days 3-4 after completion of model development, and the freezing time was recorded. Morris water maze test was performed on days 5-10 after completion of model development, and the escape latency and time spent in the target quadrant were recorded. After the Morris water maze test, the expression of UQCRC1 in the hippocampal CA1 region was detected by immunofluorescence and Western blot. Results:Compared with Sham group, the percentage of time spent exploring the novel object was significantly decreased, the percentage of freezing time in training and test stages was decreased, the escape latency on days 6-9 was prolonged, the percentage of time spent in the target quadrant was decreased, and the expression of UQCRC1 in the hippocampal CA1 was down-regulated in GCI1 group ( P<0.05). Compared with GCI2 group, the percentage of time spent exploring the novel object was significantly increased, the percentage of freezing time in training and test stages was increased, the escape latency on days 6-9 was shortened, the percentage of time spent in the target quadrant was increased, and the expression of UQCRC1 in the hippocampal CA1 region was up-regulated in GCI+ UQCRC1 group ( P<0.05). Conclusions:Hippocampal UQCRC1 is involved in the process of cognitive dysfunction following GCI in mice.

Objective:To evalaute the role of hippocampal ubiquinol cytochrome C reductase core protein 1 (UQCRC1) in cognitive dysfunction after global cerebral ischemia (GCI) in mice.Methods:Forty SPF healthy male C57BL/6J mice, aged 12 weeks, weighing 22-26 g, were selected, and 20 of them were divided into 2 groups ( n=10 each) using a random number table method: sham operation group and GCI1 group. The other 20 mice were divided into 2 groups ( n=10 each) by the random number table method: GCI2 group and GCI+ UQCRC1 overexpression group (GCI+ UQCRC1 group). In Sham group, the skin was directly sutured after exposing both common carotid arteries. Global cerebral ischemia was induced by occlusion of bilateral common carotid arteries for 20 min in GCI1, GCI2 and GCI+ UQCRC1 group, and lentivirus VSVG-Lentivirus-hSyn-EGFP-P2A-UQCRC1-WPRE-pA 500 nl was injected into the bilateral hippocampus at 2 weeks before developing the model in GCI+ UQCRC1 group. The novel object recognition task was carried out on the 2nd day following completion of model development, and the percentage of time spent exploring the novel object was calculated. The fear conditioning test was carried out on days 3-4 after completion of model development, and the freezing time was recorded. Morris water maze test was performed on days 5-10 after completion of model development, and the escape latency and time spent in the target quadrant were recorded. After the Morris water maze test, the expression of UQCRC1 in the hippocampal CA1 region was detected by immunofluorescence and Western blot. Results:Compared with Sham group, the percentage of time spent exploring the novel object was significantly decreased, the percentage of freezing time in training and test stages was decreased, the escape latency on days 6-9 was prolonged, the percentage of time spent in the target quadrant was decreased, and the expression of UQCRC1 in the hippocampal CA1 was down-regulated in GCI1 group ( P<0.05). Compared with GCI2 group, the percentage of time spent exploring the novel object was significantly increased, the percentage of freezing time in training and test stages was increased, the escape latency on days 6-9 was shortened, the percentage of time spent in the target quadrant was increased, and the expression of UQCRC1 in the hippocampal CA1 region was up-regulated in GCI+ UQCRC1 group ( P<0.05). Conclusions:Hippocampal UQCRC1 is involved in the process of cognitive dysfunction following GCI in mice.

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.