The ICR(Institute of Cancer Research)mouse infection model was constructed to study the pathogenicity of Sal-monella Telelkebir serotype,and the pathogenic identification of mouse isolates was carried out.Observe the bacterial excretion cycle,evaluate the pathogenicity of Salmonella serotype to mice,and calculate the LD50 by the changes in clinical characteris-tics,histopathology and tissue bacterial load of infected mice;by flight mass spectrometry,biochemical identification,serotype identification,molecular typing and other experiments,compared with human isolates;virulence gene analysis was carried out by PCR experiment and whole genome sequencing.The LD50 of Salmonella Telelkebir is 2.67 × 108 CFU/mL;curling and fluffing may occur 0.5 h after infection;autopsy of dead mice showed that the small intestine was severely congested,with more bubbles and fluid accumulation,cecal necrosis,liver apical degeneration and necrosis,necrotic foci on the surface of the kidney and spleen atrophy;the bacterial load of spleen,kidney,lung,liver and jejunum in mice reached its peak at 3 days after infection,while that of heart at 6 days;the bacterial excretion time of the high-dose group exceeded 100 days;The level of CD3 in tissues increased with increasing dose,with inflammatory cell infiltration,myocardial capillary dilation and hyperemia,large area of vacuoles,degeneration and necrosis of hepatocytes,obvious enlargement of splenic sinus,blurred zoning,thickening of glomerular basement membrane,partial exfoliation of ciliated epithelium,atrophy and exfoliation of jejunal villi;PCR and whole genome sequencing revealed Salmonella-related virulence genes such as cdtB,plt A and pltB.This study was the first to successfully establish the ICR mouse model of Salmonella Telelkebir,demonstrating that this serotype of Salmonella has some pathogenicity.

Objective·To explore the effect of a prehospital multimodal prehabilitation program on the preoperative functional status and postoperative recovery of patients with gastrointestinal malignant tumors.Methods·A total of 78 patients with gastrointestinal malignant tumors,hospitalized in Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine from June to December 2023,were enrolled.They were divided into the standard group(SD group,n=40)and the prehospital multimodal prehabilitation group(PMP group,n=38)by using random number table.From the time the operation was agreed upon by both the doctor and patient to the day before the operation,the SD group followed the routine preoperative guidance,while the PMP group received a home-based prehospital multimodal prehabilitation program.The general data of patients were collected,and the six-minute walk distance(6MWD)was compared between the two groups at baseline and on the day before operation.The length of postoperative hospitalization,time to first flatus,time to first ambulation,time to first oral intake,drainage removal time and postoperative complication rate were also compared between the two groups.Results·There was no difference in general data and duration of preoperative intervention of patients between the two groups.At baseline,there was no significant difference in 6MWD between the two groups.On the day before operation,the 6MWD in the PMP group was higher than that in the SD group(P=0.016).Changes in 6MWD in the PMP group were significantly higher compared to SD group during the preoperative period,with values of(23.42±13.59)m vs.(-3.75±12.08)m(P＜0.001).Time to first flatus,time to first ambulation and time to first oral intake in the PMP group were earlier than those in the SD group(P＜0.05).However,there was no significant difference in drainage removal time,postoperative hospitalization and postoperative complication rate between the two groups(P＞0.05).Conclusion·Prehospital multimodal prehabilitation can improve the preoperative function and accelerate the postoperative recovery in patients with gastrointestinal malignancies.

Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

This study assessed and explored the pharmacological effects and mechanisms of action of IMMH002 {2-amino-2-(2-(4ʹ-(2-ethyloxazol-4-yl)-[1,1ʹ-biphenyl]-4-yl)ethyl)propane-1,3-dio}, a selective sphingosine-1-phosphate receptor subtype 1 (S1P1) modulator, in a concanavalin A (ConA)-induced autoimmune hepatitis (AIH) mouse model. The experimental protocol strictly adhered to the guidelines of the Ethics Committee for Animal Research of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College (Approval No.: 00004046). Male ICR mice were pre-treated with the drug for four days, followed by induction of AIH through tail vein injection of ConA protein. Liver function, hepatic tissue pathology, peripheral blood parameters, as well as immunoglobulin G (IgG), inflammatory cytokines, T cell distribution, and inflammatory pathways were evaluated in mice. Results demonstrated that IMMH002 significantly reduced liver function indicators such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), alleviated hepatic tissue inflammation and necrotic damage, decreased serum IgG levels, and lowered the expression of inflammatory mediators including interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and interferon γ (IFN-γ). Additionally, it facilitated T lymphocyte homing, downregulated the phosphorylation of nuclear factor kappa-B (NF-κB), IκB kinase β (IKKβ) and nuclear factor inhibitor protein-α (IκBα) proteins in hepatic tissue and cellular inflammation models. Collectively, IMMH002 effectively ameliorated ConA-induced autoimmune hepatitis in mice, exhibiting extensive anti-inflammatory and anti-necrotic effects, thereby laying a theoretical foundation for AIH clinical treatment.

BACKGROUND: Tri-ponderal mass index (TMI) has been reported to be a more accurate estimate of body fat than body mass index (BMI). This study aims to compare the effectiveness of TMI and BMI in identifying hypertension, dyslipidemia, impaired fasting glucose (IFG), abdominal obesity, and clustered cardio-metabolic risk factors (CMRFs) in 3- to 17-year-old children. METHODS: A total of 1587 children aged 3 to 17 years were included. Logistic regression was used to evaluate correlations between BMI and TMI. Area under the curves (AUCs) were used to compare discriminative capability among indicators. BMI was converted to BMI- z scores, and accuracy was compared by false-positive rate, false-negative rate, and total misclassification rate. RESULTS: Among children aged 3 to 17 years, the mean TMI was 13.57 ± 2.50 kg/m 3 for boys and 13.3 ± 2.33 kg/m 3 for girls. Odds ratios (ORs) of TMI for hypertension, dyslipidemia, abdominal obesity, and clustered CMRFs ranged from 1.13 to 3.15, higher than BMI, whose ORs ranged from 1.08 to 2.98. AUCs showed similar ability of TMI (AUC: 0.83) and BMI (AUC: 0.85) in identifying clustered CMRFs. For abdominal obesity and hypertension, the AUC of TMI was 0.92 and 0.64, respectively, which was significantly better than that of BMI, 0.85 and 0.61. AUCs of TMI for dyslipidemia and IFG were 0.58 and 0.49. When 85th and 95th of TMI were set as thresholds, total misclassification rates of TMI for clustered CMRFs ranged from 6.5% to 16.4%, which was not significantly different from that of BMI- z scores standardized according to World Health Organization criteria. CONCLUSIONS TMI was found to have equal or even better effectiveness in comparison with BMI in identifying hypertension, abdominal obesity, and clustered CMRFs TMI was more stable than BMI in 3- to 17-year-old children, while it failed to identify dyslipidemia and IFG. It is worth considering the use of TMI for screening CMRFs in children and adolescents.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Body Mass Index ; Dyslipidemias ; East Asian People ; Hypertension ; Obesity, Abdominal ; Pediatric Obesity/diagnosis* ; Cardiometabolic Risk Factors

Objective: To analyze the factors associated with readmission within three months of surgery for gastric cancer and the impact of readmission on patients' long-term nutritional status and quality of life. Methods: This was a prospective cohort study comprising patients who underwent radical gastrectomy in the Department of Pancreatic and Gastric Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences from October 2018 to August 2019. Patients who failed to complete postoperative follow-up, whose body mass index (BMI) could not be accurately estimated, or who were unable to complete a quality-of-life questionnaire were excluded. The patients were followed up for 12 months. Time to, cause(s) of, and outcomes of readmission were followed up 1, 2 and 3 months postoperatively. BMI was followed up 1, 3, 6 and 12 months postoperatively. Results of blood tests were collected and patients' nutritional status and quality of life were assessed 12 months postoperatively. Nutritional status was evaluated by BMI, hemoglobin, albumin, and total lymphocyte count. Quality of life was evaluated using the European Organization for Research in the Treatment of Cancer (EORTC) Quality of Life scale. The higher the scores for global health and functional domains, the better the quality of life, whereas the higher the score in the symptom domain, the worse the quality of life. Results: The study cohort comprised 259 patients with gastric cancer, all of whom were followed up for 3 months and 236 of whom were followed up for 12 months. Forty-four (17.0%) patients were readmitted within 3 months. The commonest reasons for readmission were gastrointestinal dysfunction (16 cases, 36.3%), intestinal obstruction (8 cases, 18.2%), and anastomotic stenosis (8 cases, 18.2%). Logistic regression analysis showed that preoperative Patient-Generated Subjective Global Assessment score ≥ 4 points (OR=1.481, 95% CI: 1.028‒2.132), postoperative complications (OR=3.298, 95%CI:1.416‒7.684) and resection range (OR=1.582, 95% CI:1.057‒2.369) were risk factors for readmission within 3 months of surgery. Compared with patients who had not been readmitted 12 months after surgery, patients who were readmitted within 3 months of surgery tended to have greater decreases in their BMI [-2.36 (-5.13,-0.42) kg/m² vs. -1.73 (-3.33,-0.33) kg/m², Z=1.850, P=0.065), significantly lower hemoglobin and albumin concentrations [(122.1±16.6) g/L vs. (129.8±18.4) g/L, t=2.400, P=0.017]; [(40.9±5.0) g/L vs. (43.4±3.3) g/L, t=3.950, P<0.001], and significantly decreased global health scores in the quality of life assessment [83 (67, 100) vs. 100 (83, 100), Z=2.890,P=0.004]. Conclusion: Preoperative nutritional risk, total or proximal radical gastrectomy, and complications during hospitalization are risk factors for readmission within 3 months of surgery for gastric cancer. Perioperative management and postoperative follow-up should be more rigorous. Readmission within 3 months after surgery may be associated with a decline in long-term nutritional status and quality of life. Achieving improvement in long-term nutritional status and quality of life requires tracking of nutritional status, timely evaluation, and appropriate interventions in patients who need readmission.
Humans ; Nutritional Status ; Quality of Life ; Patient Readmission ; Stomach Neoplasms/complications* ; Prospective Studies ; Postoperative Complications/etiology* ; Gastrectomy/adverse effects* ; Retrospective Studies

Objective: To explore the prognostic factors of extracellular NK/T cell lymphoma (ENKTL) treated with pegaspargase/L-asparaginase. Methods: The clinical data of 656 ENKTL patients diagnosed at 11 medical centers in the Huaihai Lymphoma Working Group from March 2014 to April 2021 were retrospectively analyzed. The patients were randomly divided into two groups: a training set (460 cases) and a validation set (196 cases) at 7∶3, and the prognostic factors of the patients were analyzed. A prognostic scoring system was established, and the predictive performance of different models was compared. Results: Patients' median age was 46 (34, 57) years, with 456 males (69.5% ) and 561 nasal involvement (85.5% ). 203 patients (30.9% ) received a chemotherapy regimen based on L-asparaginase combined with anthracyclines, and the 5-year overall survival rate of patients treated with P-GEMOX regimen (pegaspargase+gemcitabine+oxaliplatin) was better than those treated with SMILE regimen (methotrexate+dexamethasone+cyclophosphamide+L-asparaginase+etoposide) (85.9% vs 63.8% ; P=0.004). The results of multivariate analysis showed that gender, CA stage, the Eastern Cooperative Oncology Group performance status (ECOG PS) score, HGB, and EB virus DNA were independent influencing factors for the prognosis of ENKTL patients (P<0.05). In this study, the predictive performance of the prognostic factors is superior to the international prognostic index, Korean prognostic index, and prognostic index of natural killer lymphoma. Conclusion: Gender, CA stage, ECOG PS score, HGB, and EB virus DNA are prognostic factors for ENKTL patients treated with pegaspargase/L-asparaginase.
Male ; Humans ; Middle Aged ; Asparaginase/therapeutic use* ; Prognosis ; Retrospective Studies ; Lymphoma, Extranodal NK-T-Cell/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Etoposide ; Cyclophosphamide ; Methotrexate/therapeutic use* ; DNA/therapeutic use* ; Treatment Outcome

As a recognized rare and highly fatal disease, hereditary angioedema (HAE) is difficult to diagnose and characterized by recurrent edema involving the head, limbs, genitals and larynx, etc. Diagnosis of HAE is not difficult. However, low incidence and lack of clinical characteristics lead to difficulty of doctors on timely diagnosis and correct intervention for HAE patients. Therefore, it is crucial to improve the awareness of this disease and prevent its recurrence. for HAE patients. In view of absent cognition of doctors and the general public on HAE, patients often suffer from sudden death or become disabled due to laryngeal edema which cannot be treated in time. Thus, based on the Internet mobile terminal platform, the team set up an all-day rapid emergency response system which is provided for HAE patients by setting up "one-click help". The aim is to offer optimization on overall management of HAE and designed the intelligent follow-up management to provide timely assistance and specialized suggestion for patients with acute attacks.
Humans ; Angioedemas, Hereditary/drug therapy*

Allergic diseases affect about 40% of the world's population. Environmental factors are important in the occurrence and development of allergic diseases. Dust mites are one of the most important allergens in the indoor environment. The World Health Organization proposes the "four-in-one, combination of prevention and treatment" treatment principle for allergic diseases, in which environmental control to avoid or reduce allergens is the first choice for treatment. Modern people spend much more time at home (including sleeping) than outdoors, and the control of the home environment is particularly critical. This practice introduces the hypoallergenic home visit program, which including home environment assessment, environmental and behavioral intervention guidance, and common household hypoallergenic supplies and service guidance for the patient's home environment. The real-time semi-quantitative testing of dust mite allergens, qualitative assessments of other indoor allergens, record of patients' household items and lifestyle, and precise, individualized patient prevention and control education will be conducted. The hypoallergenic home visit program improves the doctors' diagnosis and treatment data dimension, and becomes a patient management tool for doctors outside the hospital. It also helps patients continue to scientifically avoid allergens and irritants in the environment, effectively build a hypoallergenic home environment, reduce exposure to allergens in the home environment, and achieve the goal of combining the prevention and treatment of allergic diseases.
Humans ; Hospitals ; Life Style ; Sleep

As a recognized rare and highly fatal disease, hereditary angioedema (HAE) is difficult to diagnose and characterized by recurrent edema involving the head, limbs, genitals and larynx, etc. Diagnosis of HAE is not difficult. However, low incidence and lack of clinical characteristics lead to difficulty of doctors on timely diagnosis and correct intervention for HAE patients. Therefore, it is crucial to improve the awareness of this disease and prevent its recurrence. for HAE patients. In view of absent cognition of doctors and the general public on HAE, patients often suffer from sudden death or become disabled due to laryngeal edema which cannot be treated in time. Thus, based on the Internet mobile terminal platform, the team set up an all-day rapid emergency response system which is provided for HAE patients by setting up "one-click help". The aim is to offer optimization on overall management of HAE and designed the intelligent follow-up management to provide timely assistance and specialized suggestion for patients with acute attacks.
Humans ; Angioedemas, Hereditary/drug therapy*