OBJECTIVES: To investigate the efficacy and safety of empagliflozin in patients with glycogen storage disease (GSD)-associated inflammatory bowel disease (IBD). METHODS: A cross-sectional study was conducted, enrolling 25 patients with GSD-associated IBD who received empagliflozin treatment. General data, details of empagliflozin use, and adverse events were collected. Clinical symptoms and biochemical parameters before and after empagliflozin therapy were compared. RESULTS: Twenty-five patients with GSD-associated IBD were included, with a median age at diagnosis of 0.7 years, and a mean age at initiation of empagliflozin therapy of (11 ± 6) years. The initial dose of empagliflozin was (0.30 ± 0.13) mg/(kg·d), with a maintenance dose of (0.40 ± 0.21) mg/(kg·d), and a treatment duration of (34 ± 6) months. Seventy-eight percent (18/23) of patients' parents reported that empagliflozin therapy reduced the frequency of infections and oral ulcers, and increased neutrophil counts. Clinically, the number of patients with anorexia decreased from 12 to 5 after treatment, and 30% showed improved appetite (P<0.05). The numbers of patients with diarrhea, mucus/bloody stools, perianal disease, and oral ulcers decreased from 19, 9, 11, and 21 before treatment to 7, 1, 0, and 10 after treatment, respectively (P<0.05). Laboratory findings showed that absolute neutrophil counts increased, while platelet counts, lactate, and uric acid levels decreased significantly after empagliflozin treatment (P<0.05). Adverse reactions occurred in 7 patients (28%) during empagliflozin treatment. Two cases occurred in the treatment initiation phase, presenting as hypotension or profuse sweating with dehydration, along with urinary tract infections (UTIs); empagliflozin was discontinued in both cases. During the maintenance phase, 3 cases of UTIs and 2 cases of hypoglycemia (one with profuse sweating) were reported. CONCLUSIONS Empagliflozin therapy can increase neutrophil counts, reduce the incidence of infections and oral ulcers, alleviate diarrhea and abdominal pain, improve appetite, and ameliorate platelet count, lactate, and uric acid levels in patients with GSD-associated IBD, demonstrating significant clinical benefit. UTIs, hypoglycemia, hypotension, profuse sweating, and dehydration may be potential adverse reactions associated with empagliflozin therapy.
Humans ; Benzhydryl Compounds/adverse effects* ; Male ; Female ; Glucosides/adverse effects* ; Inflammatory Bowel Diseases/etiology* ; Child ; Child, Preschool ; Cross-Sectional Studies ; Adolescent ; Glycogen Storage Disease/drug therapy* ; Infant

OBJECTIVE: To investigate the clinical characteristics, treatment and prognosis of adult AML patients with NUP98::HOXA9 fusion gene. METHODS: From May 2017 to October 2023， among 2 113 AML patients who visited the Hematology Department of our hospital, patients with NUP98 rearrangements were screened. The clinical characteristics, chromosome karyotypes, immunophenotypes, gene mutations, treatment efficacy and prognosis of the patients with NUP98::HOXA9 positive were analyzed. RESULTS: Among the 2 113 AML patients, there were 18 cases with NUP98 rearrangement, including 14 NUP98::HOXA9 positive cases, with a detection rate of 0.66% (14/2 113). The median age of the NUP98::HOXA9 positive patients was 42.5 (23-64) years old. The most common chromosome karyotype was t(7; 11)(p15; p15). The immunophenotypes of all patients expressed CD13, CD33, CD117 and CD38, and most patients expressed CD34 and cMPO, while only a few expressed HLA-DR. Second-generation sequencing (NGS) was performed to detect genetic mutations associated with leukemia in all 14 patients, and the genes exhibiting a high frequency of mutation were WT1 (10/14), TET2 (7/14), and FLT3-ITD (6/14). Additionally, mutations were also observed in KRAS/NRAS, IDH1, and KIT. Of the 13 patients who received treatment, 9 achieved complete remission (CR), and all 3 patients who received azacytidine(AZA)+ venetoclax (VEN) regimen achieved CR after the first course of treatment. Within this cohort, 6 patients were classified as relapsed/refractory (6/13). 4 patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), of which two achieved long-term survival. The median follow-up time was 12 (2.1-65.0) months, while the median overall survival (OS) and relapse-free survival (RFS) were recorded as 11.4 months and 9.6 months, respectively. CONCLUSION The most common type of NUP98 rearrangement in adults AML patients is NUP98::HOXA9 , which is often accompanied by somatic mutations in WT1, TET2, and FLT3-ITD. These patients are prone to relapse, have short survival time, and generally face poor prognoses. Hopefully, utilization of the AZA+VEN regimen is anticipated to enhance the rate of induced remission in the patients, and some patients may prolong their survival through allo-HSCT. However, more effective treatment methods are still needed to improve the overall prognosis of these patients.
Humans ; Adult ; Leukemia, Myeloid, Acute/genetics* ; Middle Aged ; Prognosis ; Nuclear Pore Complex Proteins/genetics* ; Oncogene Proteins, Fusion/genetics* ; Mutation ; Male ; Female ; Young Adult ; Homeodomain Proteins/genetics*

Acute pancreatitis (AP) is a life-threatening gastrointestinal disorder for which no effective pharmacological treatments are currently available. One of the pharmacological targets that merits further research is the neurokinin 1 receptor (NK1R), which is found on pancreatic acinar cells and responds to the neuropeptide substance P (SP) that participates in AP. Although a few studies have stated the involvement of SP/NK1R in neurogenic inflammation in AP development, the regulatory mechanism remains unclear. In this study, we found that following activation of NK1R by SP, β-arrestin1, a scaffold protein of NK1R, down-regulated transcription of Adss, Adsl, and Ampd in the purine nucleotide cycle, thereby inhibiting mitochondrial function through fumarate depletion. Interestingly, we identified magnolol as a new and natural NK1R inhibitor with a non-nitrogenous biphenyl core structure. It exhibited a beneficial effect on AP by restoring purine nucleotide cycle metabolic enzymes and fumarate levels. Our study not only provides new therapeutic strategies, leading compounds, and drug translation possibilities for AP, but also provides important clues for the study of downstream mechanisms driven by SP in other diseases.

Biosensors based on acetylcholinesterase (AChE) are crucial for early diagnosis, less invasive treatment, and drug evaluation of Alzheimer's disease (AD). However, existing technologies often suffer from enzyme conformational changes, leading to altered activity and loss and reduced sensor efficacy. To address this challenge, we developed a novel right-side-out-oriented red blood cell membrane-coated electrochemical biosensors (ROCMCBs) to evaluate AChE inhibitors from traditional Chinese medicines (TCMs) as potential anti-AD agents. The developed right-side-out-oriented coating based on immunoaffinity not only fully exposed the binding sites of AChE on the cell membrane but also ensured its conformation and stability as a peripheral membrane-anchoring protein, which was conducive to maintaining its biological activity and producing optimal interaction with drugs. At the same time, the biosensors exhibited a satisfactory sensitivity (limit of detection = 0.41 pmol/L). Ultimately, six potentially active compounds against AD (baicalin, geniposide, gastrodin, berberine, rhynchophylline, and senkyunolide A) were rapidly identified and evaluated from TCMs. This project provides a promising strategy for developing cell membrane-coated electrochemical biosensors. The application of cell membrane-coated electrochemical biosensors with well-defined cell membrane orientation further expands new perspectives and methods for AChE-targeted anti-AD research.

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

Here,5 important pathogens carried by ticks in Maanshan City,Anhui Province,China were identified.In to-tal,642 ticks were collected from 13 villages around Maanshan City and identified by morphological and mitochondrial COI genes.The 16S rRNA gene of Francisella tularensis,ssrA gene of Bartonella,16S rRNA,ompA and ompB genes of Rickett-sia,16S rRNA and gltA genes of Anaplasma,and groEL and rpoB genes of Coxiella were sequenced.Reference sequences were retrieved from a public database.Phylogenetic trees were constructed with MEG A1 1.0 software.In total,36 Rickettsiae isolates were detected in 640 Haemaphysalis longicornis ticks,which included 20 isolates of Rickettsia heilongjian-gensis,16 of Candidatus Rickettsia jingxinensis,2 of Ana-plasma bovis,and 186 of Coxiella-like endosymbiont.R.hei-longjiangensis HY2 detected in this study and Anhui B8 strain,Ca.R.jingxinensis QL3 and those from Shanxi Prov-ince and Jiangsu Province,A.bovis JX4 and those from Shanxi Province were clustered on the same branch.Overall,17 ticks had combined infections and none of the 5 bacteria were detected in two Amblyomma testudinarium ticks.This is the first report of Ca.R.jingxinensis detected in H.longicornis ticks from Anhui Province.It is recommended that the two types of Rickettsia that cause spotted fever and A.bovis should be reported to local health authorities to initiate appropriate prevention and control measures.

Objective To investigate the nutritional status of children with Crohn's Disease (CD) at diagnosis and its association with clinical characteristics. Methods A retrospective analysis was performed for the clinical data and nutritional status of 118 children with CD who were admitted to Beijing Children's Hospital,Capital Medical University,from January 2016 to January 2024. A multivariate logistic regression analysis was used to investigate the risk factors for malnutrition. Results A total of 118 children with CD were included,among whom there were 68 boys (57.6％) and 50 girls (42.4％),with a mean age of (11±4) years. Clinical symptoms mainly included recurrent abdominal pain (73.7％,87/118),diarrhea (37.3％,44/118),and hematochezia (32.2％,38/118),and 63.6％ (75/118) of the children had weight loss at diagnosis. The incidence rate of malnutrition was 63.6％ (75/118),and the children with moderate or severe malnutrition accounted for 67％ (50/75). There were 50 children (42.4％) with emaciation,8 (6.8％) with growth retardation,and 9 (7.6％) with overweight or obesity. Measurement of nutritional indices showed a reduction in serum albumin in 83 children (70.3％),anemia in 74 children (62.7％),and a reduction in 25 hydroxyvitamin D in 15 children (60％,15/25). The children with malnutrition had significantly higher disease activity,proportion of children with intestinal stenosis,and erythrocyte sedimentation rate and a significant reduction in serum albumin (P<0.05). The multivariate logistic regression analysis showed that intestinal stenosis was an independent risk factor for malnutrition in children with CD (OR=4.416,P<0.05). Conclusions There is a high incidence rate of malnutrition in children with CD at diagnosis,which is associated with disease activity and disease behavior. The nutritional status of children with CD should be closely monitored.

Objective:To explore the optimization of the standardized assessment tool for clinical diagnosis of Chinese developmental dyslexia (DD).Methods:A cross-sectional study was conducted from May to December 2023, in which 130 primary school children in grades 1 to 3 with clinical signs of literacy lag and positive screening results on the screening scales were recruited from the outpatient clinic of Child Health Care Medical Division, Shanghai Children′s Hospital, Shanghai Jiao Tong University School of Medicine. Chinese dyslexia screening behavior checklist for primary students (CDSBC) was used as the screening scales, and supplemented by dyslexia checklist for Chinese children. Referring to the standard procedure of the"expert advice on diagnosis and intervention of Chinese developmental dyslexia", the developmental dyslexia scale for standard mandarin (DDSSM) was used to evaluate the children′s literacy-related cognitive abilities and conduct the diagnostic assessment, and divided the children into learning backward group and the DD group. The t-test and χ2 test were used to compare the differences in the distribution of intelligence, literacy and attention deficit hyperactivity disorder between the two groups. Spearman′s correlation was used to analyze the correlation between the scores for each cognitive ability in the DDSSM and the CDSBC. Results:Of the 130 children, 90 were male, aged (8.3±1.0) years; 40 were female, aged (8.1±0.9) years. A final diagnosis of DD was made in 59 cases, of which 41 were males. There was no statistically significant difference in operational intelligence quotient (101±15 vs.100±15, t=0.53, P>0.05) and statistically significant difference in literacy of DDSSM (32±5 vs.21±4, t=11.56, P<0.001) between the learning backward group and the DD group. Eighteen cases (25.4%) of the learning backward group were children with attention deficit subtype attention deficit hyperactivity disorder (ADHD-I), and 16 cases (27.1%) in DD group, the difference in incidence between the two groups was not statistically significant ( χ2=0.05, P>0.05). There were correlations between the DDSSM (for oral vocabulary, morphological awareness and orthographic awareness) and the CDSBC total score ( r=-0.42, -0.32, -0.35, all P<0.01), but the correlations for visuospatial perception and rapid automatized naming with CDSBC total score were not statistically significant ( r=-0.09 and -0.20,both P>0.05). Conclusion:For literacy-related cognitive abilities, screening scales CDSBC are not sufficiently useful for assessment, so the introduction of standardized assessment tools DDSSM is an optimization of the clinical diagnosis of Chinese DD, which is crucial for achieving accurate diagnosis and intervention.

Objective:To explore the short-term clinical efficacy, safety and patients' prognostic influencing factors of CyberKnife for the treatment of brain metastases in non-small cell lung cancer (NSCLC).Methods:A retrospective case series study was conducted. The clinical data of 58 NSCLC patients who received CyberKnife treatment for brain metastases at Jilin Cancer Hospital from July 2020 to January 2022 were retrospectively analyzed. At 3 months after CyberKnife treatment for brain metastases, and the efficacy of radiotherapy was evaluated on the basis of changes of brain metastases detected by contrast-enhanced magnetic resonance imaging (MRI) of the head. Overall survival (OS) and local recurrence-free survival (LRRFS) were analyzed in 58 patients by using the Kaplan-Meier method; the efficacy of cumulative brain metastasis volume for determining the survival of CyberKnife-treated NSCLC patients with brain metastases was analyzed by using the receiver operating characteristic (ROC) curve with the survival status of patients during the follow-up period as the gold standard, and the optimal cut-off value of cumulative brain metastasis volume was obtained; the clinical factors affecting OS and LRRFS of CyberKnife-treated NSCLC patients with brain metastases were analyzed by univariate and multivariate Cox proportional hazards models, and the adverse reactions associated with CyberKnife treatment were evaluated.Results:Among the 58 patients, 26 (44.8%) were male and 32 (55.2%) were female, with a median age [ M ( Q1, Q3)] of 64 years old (56 years old, 70 years old); there were 1-7 brain metastatic lesions in each patient, and there were 98 brain metastatic lesions in the 58 patients. There were 2 deaths (3.4%) within 3 months after CyberKnife treatment. At 3 months after treatment, there were 3 cases (5.4%) in complete remission, 36 cases (64.3%) in partial remission, 13 cases (23.2%) in stable disease, and 4 cases (7.1%) in disease progression in the remaining 56 patients. ROC curve analysis showed that the area under the curve for determining the survival of CyberKnife-treated NSCLC patients with brain metastases based on the cumulative brain metastasis volume was 0.593 (95% CI: 0.423-0.763), and the optimal cut-off value of cumulative brain metastasis volume was 15 cm 3. Median follow-up time was 12.6 months (7.5 months, 17.9 months). The 6- and 12-month OS rates were 91.3% and 79.5%, respectively, and the 6- and 12-month LRRFS rates were 93.0% and 89.2%, respectively. Multivariate Cox regression analysis showed that the Karnofsky functional status score (>70 points vs. ≤70 points, HR= 0.103, 95% CI: 0.019-0.545, P = 0.007), control of extracranial tumor (controlled vs. uncontrolled, HR = 0.145, 95% CI: 0.049-0.429, P < 0.001), cumulative brain metastasis volume (≤15 cm 3vs. >15 cm 3, HR = 0.105, 95% CI: 0.028-0.399, P = 0.001) were independent influencing factors for poor OS, and the control of extracranial tumor (controlled vs. uncontrolled, HR = 0.062, 95% CI: 0.006-0.616, P = 0.018), cumulative brain metastasis volume (≤15 cm 3vs. >15 cm 3, HR = 0.440, 95% CI: 0.007-0.292, P = 0.001), and target area total bioequivalent dose (BED) (≤60 Gy vs. >60 Gy, HR = 5.299, 95% CI: 1.020-27.530, P = 0.047) were independent influencing factors for poor LRRFS. Only grade 1-2 headache [53.5% (31/58)], nausea and vomiting [36.2% (21/58)] and other adverse reactions occurred after treatment, and no ≥grade 3 adverse reactions occurred. Conclusions:CyberKnife treatment for NSCLC brain metastases has high local control rate and short-term survival rate with mild adverse effects. Karnofsky functional status score, control of extracranial tumor and cumulative brain metastasis volume may affect OS of CyberKnife-treated NSCLC patients with brain metastases, and the control of extracranial tumor, cumulative brain metastasis volume and total BED may affect local recurrence.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.