Inflammatory bowel disease (IBD) is a refractory disease characterized by chronic intestinal inflammation. Its typical pathological characteristics are the destruction of intestinal mucosal barrier and the imbalance of immune microenvironment. In severe cases, it can cause intestinal fibrosis and functional failure. Sulfation, a critical post-translational modification, plays an essential role in regulating intestinal homeostasis. Abnormal sulfation metabolism in the intestine of IBD patients can lead to the impairment of intestinal barrier function, immune system disorders and changes in the composition of microbiota. Consequently, targeting the sulfation pathway may be a novel therapeutic strategy for IBD. By supplementing exogenous sulfation substrates, regulating the activity of related key enzymes involved in sulfation or remodeling the microbiota, the level of intestinal sulfation can be effectively restored, thereby repairing the intestinal barrier function and inhibit the inflammatory response. This article systematically summarizes the pathogenic mechanisms of sulfation in IBD, providing a theoretical foundation for developing precision therapeutic strategies targeting the intestinal microenvironment.

Objective To analyze the clinical distribution,drug resistance characteristics,molecular prevalence,and impact of immunocompromised status on the infection rate of carbapenem-resistant Enterobacteriaceae(CRE)isolated from pediatric respiratory tract samples(sputum,bronchoalveolar lavage fluid).Methods A retrospective analysis was conducted on clinical data of hospitalized children from 2019 to 2023.A total of 1 235 non-repetitive strains of Enterobacteriaceae bacteria were obtained from pediactric respiratory tract samples.Drug susceptibility testing,multilocus sequencing typing(MLST),and resistance-related gene sequencing were performed on 100 isolated CRE strains,to study the clinical distribution,drug resistance characteristics,and molecular prevalence of CRE,and to further analyze the impact of immunocompromised status on the respiratory CRE infection rate in children.Results From 2019 to 2023,the detection rate of CRE in 1 235 strains of Enterobacteriaceae bacteria was 8.10%(100/1 235).Among them,51.0%(51/100)of CRE were isolated from the intensive care unit(ICU),of which 33.0%(33/100)were isolated from the Surgical ICU,18.0%(18/100)of CRE was isolated from the Medical ICU;32.0%(32/100)of CRE were isolated from Department of Neonatology,with the majority(74.0%)isolated from infants under 6 months of age.Of all pediatric patients,85.0%recovered and were discharged after treatment.Immunocompromised status was identified as an independent risk factor for CRE infection.Among 100 strains of CRE,Carbapenem-resistant Klebsiella pneumoniae(CRKP)was the most commonly detected strain,accounting for 88.0%(88/100),followed by Escherichia coli at 6.0%(6/100)and Enterobacter cloacae at 4.0%(4/100).CRE strains were highly resistant to carbapenems and cephalosporins,with prevalent resistance to amikacin,ciprofloxacin,and levofloxacin.However,their resistance rates were relatively low to tigecycline,colistin,minocycline,ceftazidime/avibactam,meropenem/vaborbactam,and imipenem/relebactam.The screening results of carbapenem resistance genes showed that blaKPC-2 was the most prevalent gene(74.0%),followed by blaNDM-1(14.0%)and blaNDM-5(11.0%).Molecular typing showed that ST11 type CRE was the dominant type,comprising 72.0%(72/100)and was the primary epidemic clone.Conclusions CRKP is the most prevalent CRE strain isolated from pediatric respiratory tract samples,primarily identified in the ICU,Department of Neonatology,and among infants under 6 months of age.Immunocompromised status is an independent risk factor for respiratory CRE infection in children.CRE generally has high resistance to antibacterial drugs,with blaKPC-2 being the dominant resistance genotype,and ST11 as the predominant multilocus sequence type.Clinical management should account for these characteristics to implement timely interventions and rational therapeutic strategies.

Inflammatory bowel disease (IBD) is a refractory disease characterized by chronic intestinal inflammation. Its typical pathological characteristics are the destruction of intestinal mucosal barrier and the imbalance of immune microenvironment. In severe cases, it can cause intestinal fibrosis and functional failure. Sulfation, a critical post-translational modification, plays an essential role in regulating intestinal homeostasis. Abnormal sulfation metabolism in the intestine of IBD patients can lead to the impairment of intestinal barrier function, immune system disorders and changes in the composition of microbiota. Consequently, targeting the sulfation pathway may be a novel therapeutic strategy for IBD. By supplementing exogenous sulfation substrates, regulating the activity of related key enzymes involved in sulfation or remodeling the microbiota, the level of intestinal sulfation can be effectively restored, thereby repairing the intestinal barrier function and inhibit the inflammatory response. This article systematically summarizes the pathogenic mechanisms of sulfation in IBD, providing a theoretical foundation for developing precision therapeutic strategies targeting the intestinal microenvironment.

Objective To analyze the clinical distribution,drug resistance characteristics,molecular prevalence,and impact of immunocompromised status on the infection rate of carbapenem-resistant Enterobacteriaceae(CRE)isolated from pediatric respiratory tract samples(sputum,bronchoalveolar lavage fluid).Methods A retrospective analysis was conducted on clinical data of hospitalized children from 2019 to 2023.A total of 1 235 non-repetitive strains of Enterobacteriaceae bacteria were obtained from pediactric respiratory tract samples.Drug susceptibility testing,multilocus sequencing typing(MLST),and resistance-related gene sequencing were performed on 100 isolated CRE strains,to study the clinical distribution,drug resistance characteristics,and molecular prevalence of CRE,and to further analyze the impact of immunocompromised status on the respiratory CRE infection rate in children.Results From 2019 to 2023,the detection rate of CRE in 1 235 strains of Enterobacteriaceae bacteria was 8.10%(100/1 235).Among them,51.0%(51/100)of CRE were isolated from the intensive care unit(ICU),of which 33.0%(33/100)were isolated from the Surgical ICU,18.0%(18/100)of CRE was isolated from the Medical ICU;32.0%(32/100)of CRE were isolated from Department of Neonatology,with the majority(74.0%)isolated from infants under 6 months of age.Of all pediatric patients,85.0%recovered and were discharged after treatment.Immunocompromised status was identified as an independent risk factor for CRE infection.Among 100 strains of CRE,Carbapenem-resistant Klebsiella pneumoniae(CRKP)was the most commonly detected strain,accounting for 88.0%(88/100),followed by Escherichia coli at 6.0%(6/100)and Enterobacter cloacae at 4.0%(4/100).CRE strains were highly resistant to carbapenems and cephalosporins,with prevalent resistance to amikacin,ciprofloxacin,and levofloxacin.However,their resistance rates were relatively low to tigecycline,colistin,minocycline,ceftazidime/avibactam,meropenem/vaborbactam,and imipenem/relebactam.The screening results of carbapenem resistance genes showed that blaKPC-2 was the most prevalent gene(74.0%),followed by blaNDM-1(14.0%)and blaNDM-5(11.0%).Molecular typing showed that ST11 type CRE was the dominant type,comprising 72.0%(72/100)and was the primary epidemic clone.Conclusions CRKP is the most prevalent CRE strain isolated from pediatric respiratory tract samples,primarily identified in the ICU,Department of Neonatology,and among infants under 6 months of age.Immunocompromised status is an independent risk factor for respiratory CRE infection in children.CRE generally has high resistance to antibacterial drugs,with blaKPC-2 being the dominant resistance genotype,and ST11 as the predominant multilocus sequence type.Clinical management should account for these characteristics to implement timely interventions and rational therapeutic strategies.

Objective:To explore the safety and efficacy of Obinutuzumab in the treatment of immune thrombotic thrombocytopenic purpura.Methods:Data from a case of immune thrombotic thrombocytopenic purpura (iTTP) admitted to the Department of haematology of the First Affiliated Hospital of Harbin Medical University were evaluated retrospectively and a literature review was performed.Results:A 66-year-old female patient was admitted to our hospital for thrombocytopenia. On admission, physical examination showed that yellow skin and sclera. The patient was fully conscious but had a decreasing ability to calculate. Laboratory examination revealed a platelet count of 7×10 9/L; liver function: alanine aminotransferase 55.2 U/L, azelaic aminotransferase 117.5 U/L; total bilirubin 142.7 μmol/L, direct bilirubin 64.6 μmol/L, indirect bilirubin 78.1 μmol/L; lactate dehydrogenase: 2362 U/L; creatinine: 260.7 μmol/L; peripheral blood smear showed 4% fragmented erythrocytes; ADAMTS13 activity 2.7% and positive inhibitor (1.12 BU). The patient is treated with plasma exchange and glucocorticoids, but the patient’s symptoms worsened. Rituximab was permanently discontinued for severe infusion reactions. Treatment with Obinutuzumab (1000 mg, qw×2 w) and she achieved a complete remission for 18 months. The treatment was well tolerated with no adverse events related to Obinutuzumab. Conclusion:For iTTP patients with rituximab intolerance, obinutuzumab is a safe and effective alternative treatment option.

Objective:To explore the safety and efficacy of Obinutuzumab in the treatment of immune thrombotic thrombocytopenic purpura.Methods:Data from a case of immune thrombotic thrombocytopenic purpura (iTTP) admitted to the Department of haematology of the First Affiliated Hospital of Harbin Medical University were evaluated retrospectively and a literature review was performed.Results:A 66-year-old female patient was admitted to our hospital for thrombocytopenia. On admission, physical examination showed that yellow skin and sclera. The patient was fully conscious but had a decreasing ability to calculate. Laboratory examination revealed a platelet count of 7×10 9/L; liver function: alanine aminotransferase 55.2 U/L, azelaic aminotransferase 117.5 U/L; total bilirubin 142.7 μmol/L, direct bilirubin 64.6 μmol/L, indirect bilirubin 78.1 μmol/L; lactate dehydrogenase: 2362 U/L; creatinine: 260.7 μmol/L; peripheral blood smear showed 4% fragmented erythrocytes; ADAMTS13 activity 2.7% and positive inhibitor (1.12 BU). The patient is treated with plasma exchange and glucocorticoids, but the patient’s symptoms worsened. Rituximab was permanently discontinued for severe infusion reactions. Treatment with Obinutuzumab (1000 mg, qw×2 w) and she achieved a complete remission for 18 months. The treatment was well tolerated with no adverse events related to Obinutuzumab. Conclusion:For iTTP patients with rituximab intolerance, obinutuzumab is a safe and effective alternative treatment option.

Objective:This study aims to explore the key points of the operation mode and construction of psychiatric research ward, provide possible reference for the construction of research ward.Methods:In this study, the construction of research ward in a psychiatric hospital was considered and explored through literature review, drawing on the operation mode of other research wards, combined with the characteristics of psychiatric clinical research.Results:This Study put forward the construction orientation and operation management mode of the psychiatric research ward, and analyzed the advantages of existing platform and key points for future development.Conclusions:The construction of psychiatric research ward should be based on clinical needs and hospital practice. Strategies including tailored fine management, optimize platform supporting, efficient organizing and management system, talent team and appropriate incentive mechanism should be implemented to strengthen the construction.

Objective:To evaluate the effect of VX-765 on cognitive function in acute rapid eye movement (REM) sleep-deprived juvenile rats.Methods:Thirty-six clean-grade healthy male Sprague-Dawley rats, aged 3-4 weeks, weighing 52-101 g, were divided into 3 groups ( n=12 each) using a random number table method: control group (group C), acute REM group (group AREM) and VX-765 group (group V). Sleep deprivation model was established by modified multi-platform water environment method.In group V, VX-765 solution 10 mg/kg was intravenously injected via the tail vein at 9: 00 a. m.every day for 4 consecutive days.The equal volume of normal saline was given instead in C and AREM groups.Morris water maze and novel object recognition tests were performed for 4 consecutive days during sleep deprivation.The rats were then sacrificed after the end of Morris water maze and novel object recognition tests on 5th day, and hippocampi were removed for determination of the expression of interleukin-1beta (IL-1β) and IL-18 by Western blot. Results:Compared with group C, the latency of novel object recognition was significantly prolonged, the percentage of novel object exploration was shortened, and the number of head exploration was decreased, the percentage of novel object exploration and discrimination index were decreased, the number of crossing the original platform in Morris water maze test was reduced, the time of staying at the target quadrant was shortened, and the expression of IL-1β and IL-18 was up-regulated in AREM and V groups ( P<0.05). Compared with group AREME, the latency of novel object recognition was significantly shortened, the percentage of novel object exploration was prolonged, and the number of head exploration was increased, the percentage of novel object exploration and discrimination index were increased, the number of crossing the original platform in Morris water maze test was increased, the time of staying at the target quadrant was prolonged, and the expression of IL-1β and IL-18 was down-regulated ( P<0.05). Conclusion:VX-765 can improve the cognitive function in acute REM sleep-deprived juvenile rats, which is related to inhibiting hippocampal inflammatory responses.

Objective: Symptomatic intracranial hemorrhage (sICH) is one of the severe complications of ischemic stroke thrombolysis. Several prognostic scales have been developed to predict the risk of sICH. The performance of seven scales was compared in a single center cohort. Methods: Data of patients with consecutive ischemic stroke who received 0.9 mg/kg intravenous recombinant tissue plasminogen activator (rt-PA) thrombolysis within 4.5 h time window from stroke onset were collected. Seven scales that can provide an estimate of risk of sICH were identified and evaluated: Hemorrhage After Thrombolysis (HAT), blood Sugar, Early infarct signs, (hyper) Dense cerebral artery sign, Age, National Institutes of Health (NIH) Stroke Scale (SEDAN), Stroke Prognostication using Age and NIH Stroke Scale (SPAN)-100, Safe Implementation of Thrombolysis in Stroke (SITS), Total Health Risks In Vascular Events (THRIVE), Glucose at presentation, Race (Asia), Age, Sex (male), systolic blood Pressure at presentation, and Severity of stroke at presentation (NIH Stroke Scale; GRASPS) and Multicenter Stroke Survey (MSS). The area under the receiver operating characteristic curve (AUROC) was calculated and Logistic regression and the Hosmer-Lemeshow test were also performed. Results: The current study included 293 patients, of whom 7.85% (23/293) had sICH by National Institute of Neurological Disorders and Stroke (SICH_NINDS), 5.46% (16/293) by Europe Cooperative Acute Stroke Study Ⅱ (SICH_ECASSⅡ) and 4.44% (13/293) by Safe Implementation of Thrombolysis in Stroke (SICH_SITS) criteria. SEDAN had the highest AUROC for predicting sICH: sICH_NINDS: AUROC=0.843, OR=3.167, 95%CI 2.106-4.762, P<0.01; sICH_ECASSⅡ: AUROC=0.797, OR=2.509, 95%CI 1.652-3.812, P<0.01; sICH_SITS: AUROC=0.784, OR=2.172, 95%CI 1.405-3.357, P<0.01. And SPAN-100 had the lowest AUROC among all the seven scales and was only associated with risk of SICH_NINDS in regression analysis. Furthermore, when sub-grouped the cohort into anterior circulation infarction and posterior circulation infarction, regression analysis suggested that all the seven scales were however not associated with sICH risk in patients with posterior circulation infarction. Conclusions SEDAN constantly had the highest predictive power, SPAN-100 had the worst. The seven scales studied could not predict sICH in posterior circulation infarction.

Objective To explore the role of CORM-3 in alleviating cognitive dysfunction and cortical neuronal pyroptosis of rats exposed to hemorrhage shock and resuscitation. Methods One hundred and sixty-eight male SD rats, weighting 350-400 g, in accordance with random number table, were divided into 4 groups (n=42):sham-operated group, hemorrhage shock and resuscitation (H group), hemorrhage shock and resuscitation plus CORM-3 (CO group), hemorrhage shock and resuscitation plus iCORM-3 (ICO group). The rat hemorrhagic shock resuscitation models were established in H, CO and ICO groups:bleeding from femoral vein was performed to achieve mean arterial pressure of 25-35 mmHg (1 mmHg=0.133 kPa) for 60 min;and then, the collected blood was returned to the body within 15 min to reach the initial blood pressure level as resuscitation, and normal saline was injected if necessary. The rats in CO group were injected CORM-3 (4 mg/kg) via femoral vein after resuscitation, the rats in ICO group were injected iCORM-3 (4 mg/kg), and rats in the sham-operate group and H group were only injected equal amount of normal saline containing DMSO. Rats were sacrificed for cortex 12 h after end of resuscitation;CO content was assessed by gas chromatograph assay; Western blotting was used to detect the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and BTB-CNC homology 1 (Bach1) in the nuclear, and heme oxygenase-1 (HO-1), interleukin (IL)-1β and IL-18 in cytosol; and neuronal pyroptosis rate was detected by cleaved caspase-1-Cy3/neuron-specific nucleoprotein (NeuN)-FITC/DAPI. Thirty d after resuscitation, open field test was used to assess the cognitive ability of the rats. Results At 12 h after resuscitation, as compared with sham-operated group, rats in the H, CO and ICO groups had significantly increased CO content, neuronal pyroptosis, ratio of Nrf2/Bach1, and expressions of HO-1, IL-1β and IL-18, statistically longer time spending in the central square, significantly smaller times crossing the grid and times standing on the back legs (P<0.05). As compared with H and ICO group, CO group had significantly increased CO content, ratio of Nrf2/Bach1, and HO-1 expression, times crossing the grid, times standing on the back legs, but significantly decreased neuronal pyroptosis, expressions of IL-1β and IL-18, and time spending in the central square (P<0.05). Conclusion CORM-3 can reduce the neuronal pyroptosis rate and alleviate cognitive dysfunction in rats with hemorrhagic shock and resuscitation, whose mechanism may be related to the increase of HO-1 expression after up-regulation of Nrf2/Bach1 ratio.