Tumor metastasis is closely related to high mortality rate of cancer.It is well known that glutamine plays an important role in the malignant progression of cancer.Notably,as an important carbon and nitrogen donor,glutamine has been found to be closely related to tumor metastasis in recent years.Glutamine is not only involved in regulating the proliferation of tumor cells,but is also closely related to the migration and invasion of tumor cells.Furthermore,various enzymes along with transporters in the metabolism of glutamine are involved in the process of tumor metastasis through different signaling pathways.This review provided a summary of the role of glutamine in tumor metastasis in recent years and proposed therapeutic targets to provide new strategies for the clinical treatment of tumor metastases.

This article presents a case of acute ST-segment elevation myocardial infarction (STEMI) in a pregnant woman caused by coronary artery dissection. The 41-year-old patient had undergone cardiac valve surgery at the age of 1 and had no risk factors such as hypertension, diabetes, smoking, alcohol use, or a family history of coronary artery disease. At 31 +1 weeks of gestation, she experienced sudden chest pain for 4 hours and was emergently referred to Peking University First Hospital on June 1, 2021. Electrocardiogram revealed ST-segment elevation in leads I, aVL, and V 2 to V 6. Biochemical assays showed elevated levels of high-sensitivity cardiac troponin I and creatine kinase-MB. Echocardiography indicated segmental ventricular wall motion abnormalities (apical) and reduced left ventricular function, confirming the diagnosis of acute anterior wall STEMI. The patient promptly underwent emergency coronary angiography and percutaneous coronary intervention and confirmed coronary artery dissection. Postoperative care included antiplatelet, anticoagulation, and supportive treatment. At 34 +3 weeks of gestation, with the condition of acute anterior wall STEMI being relatively stable, a cesarean section was successfully performed. Regular cardiology follow-ups were scheduled postpartum, and cardiac function was normal in two years after discharge.

Objective:To analyze the clinical characteristics and prognosis of patients with infant acute lymphoblastic leukemia (IALL).Methods:A retrospective cohort study.Clinical data, treatment and prognosis of 28 cases of IALL who have been treated at Beijing Children′s Hospital, Capital Medical University and Baoding Children′s Hospital from October 2013 to May 2023 were analyzed retrospectively. Based on the results of fluorescence in situ hybridization (FISH), all patients were divided into KMT2A gene rearrangement (KMT2A-R) positive group and KMT2A-R negative group. The prognosis of two groups were compared. Kaplan-Meier method and Log-Rank test were used to analyze the survival of the patients.Results:Among 28 cases of IALL, there were 10 males and 18 females, with the onset age of 10.9 (9.4,11.8) months. In terms of immune classification, 25 cases were B-ALL (89%), while the remaining 3 cases were T-ALL (11%). Most infant B-ALL showed pro-B lymphocyte phenotype (16/25,64%). A total of 22 cases (79%) obtained chromosome karyotype results, of which 7 were normal karyotypes, no complex karyotypes and 15 were abnormal karyotypes were found. Among abnormal karyotypes, there were 4 cases of t (9; 11), 2 cases of t (4; 11), 2 cases of t (11; 19), 1 case of t (1; 11) and 6 cases of other abnormal karyotypes. A total of 19 cases (68%) were positive for KMT2A-R detected by FISH. The KMT2A fusion gene was detected by real-time PCR in 16 cases (57%). A total of 24 patients completed standardized induction chemotherapy and were able to undergo efficacy evaluation, 23 cases (96%) achieved complete remission through induction chemotherapy, 4 cases (17%) died of relapse. The 5-year event free survival rate (EFS) was (46±13)%, and the 5-year overall survival rate (OS) was (73±10)%.The survival time was 31.3 (3.3, 62.5) months. There was no significant statistical difference in 5-year EFS ((46±14)% vs. (61±18)%) and 5-year OS ((64±13)% vs. (86±13)%) between the KMT2A-R positive group (15 cases) and the KMT2A-R negative group (9 cases) ( χ2=1.88, 1.47, P=0.170, 0.224). Conclusions:Most IALL patients were accompanied by KMT2A-R. They had poor tolerance to traditional chemotherapy, the relapse rate during treatment was high and the prognosis was poor.

Objective:To investigate the current situation of fall fear in elderly patients after operation of intertrochanteric fracture, analyze the influencing factors and build a prediction model.Methods:A prospective cohort study and convenient sampling method were used to select 303 elderly patients with intertrochanteric fracture after surgery in the Department of Orthopedics, Affiliated Hospital of Jining Medical University from January 2021 to December 2022 as the modeling group. According to the scores of fall fear when getting out of bed for the first time, they were divided into 211 cases in the fall fear group and 92 cases in the non-fall fear group. Multivariate Logistic regression was used to analyze the influencing factors of fall fear after operation of femoral intertrochanteric fracture in elderly patients, and a risk prediction score model was established. ROC curve was used to evaluate the differentiation of the model, calibration chart was used to evaluate the calibration degree of the model, and Bootstrap method was used for internal verification. Data of 81 elderly patients with intertrochanteric fracture treated from January to May 2023 were collected as a validation set for external verification of the model.Results:A total of 6 influencing factors were included in the prediction of fall fear risk model for elderly patients after operation of intertrochanteric fracture: gender ( OR = 3.229, 95% CI 1.672 - 6.401), number of co-existing diseases ( OR = 9.578, 95% CI 4.532 - 20.245), pain ( OR = 1.684, 95% CI 1.074 - 2.463), depression ( OR = 1.719, 95% CI 1.371 - 2.155), social support ( OR = 0.859, 95% CI 0.784 - 0.942), and ability to perform activities of daily living ( OR = 0.960, 95% CI 0.932 - 0.989) (all P<0.05). The area under ROC curve of the prediction model was 0.853, the sensitivity was 0.896, and the specificity was 0.663. The area under the externally verified ROC curve was 0.766, the sensitivity was 0.800, and the specificity was 0.645. The calibration curve was close to the reference curve in the model prediction, indicating that the model hasd a good prediction effect. Conclusions:The prediction effect of this model is good, and it can quickly predict the risk of fall fear in elderly patients after operation of intertrochanteric fracture, and provide a basis for medical personnel to provide timely intervention measures.

Aim To explore the correlation between carotid atherosclerosis(CAS)and neutrophil/lymphocyte ratio(NLR)in patients with early morning hypertension,and to construct a line chart model to predict the risk of CAS in patients with hypertension in the morning.Methods 255 patients with early morning hypertension hospitalized in the Affiliated Hospital of Chengde Medical College from October 2019 to November 2022 were collected,and their basic data,blood routine and blood biochemical indexes were collected.All selected patients need to improve 24-hour ambulatory blood pressure monitoring and carotid artery color ultrasound detection.According to the presence or absence of CAS,all selected patients were divided into morning hypertension with CAS group(n=197)and morning hypertension without CAS group(n=58).Multivariate Logistic regression analysis was used to explore the risk factors of early morning hypertension with CAS,and to construct and verify an individual line chart model to predict the risk of early morning hypertension pa-tients with CAS.Results The age,NLR,neutrophils(NE),monocytes(MO),white blood cell(WBC),total cho-lesterol(TC),triglyceride(TG)and low density lipoprotein cholesterol(LDLC)increased in the early morning hyperten-sion with CAS group compared with those in the morning hypertension group without CAS,while the HDLC decreased(P＜0.05).The results of multivariate Logistic regression analysis showed that the age,NLR and TC were higher in the early morning hypertension with CAS group than those in the early morning hypertension without CAS group,while HDLC was lower;Age,NLR and TC were independent risk factors of early morning hypertension with CAS,while HDLC was inde-pendent protective factors of morning hypertension with CAS.Based on the results of multivariate Logistic regression anal-ysis,an individualized line chart model for predicting early morning hypertension with CAS was constructed.The area un-der the ROC curve of the line chart model was 0.853(95％CI:0.802-0.904,P＜0.01).The result of Hosmer Leme-show fit test was x2=1.665(P＞0.05).Conclusions There was a positive correlation between NLR and morning hy-pertension with CAS,and NLR was an independent risk factor for morning hypertension with CAS.The individualized line chart model based on age,NLR,TC and HDLC can effectively predict the risk of hypertension with CAS in the early morn-ing,which provides a theoretical basis for early detection and prevention of atherosclerosis.

Objective:To analyze the value of minute ventilation to carbon dioxide production slope (VE/VCO 2 slope) combined with peak systolic blood pressure (SBP) in predicting prognosis for patients with chronic heart failure (CHF). Methods:A total of 170 patients with CHF who visited the Cardiac Rehabilitation Center of Tongji Hospital Affiliated to Tongji University and completed cardiopulmonary exercise test from March 2007 to December 2018 were enrolled in the study. The clinical data, cardiopulmonary exercise testing results and follow-up information of patients were collected to explore the predictors of all-cause mortality in patients with CHF.Results:The median follow-up time was 647 (182-1 764) days. All-cause death occurred in 34 patients. Compared with surviving patients, the proportion of diabetes and angiotensin-converting enzyme inhibitor/angiotensin Ⅱ receptor blocker (ACEI/ARB) use in fatal patients was significantly higher ( P<0.01). The VE/VCO 2 slope and peak SBP*VE/VCO 2 in the fatal patients were significantly higher, and the peak oxygen consumption (peak VO 2) was lower than those in the surviving patients ( P<0.01). The areas under the receiver operating characteristic curve (AUC) of VE/VCO 2 slope and peak SBP*VE/VCO 2 in predicting all-cause mortality in patients with CHF were 0.648 ( P=0.008) and 0.681 ( P=0.001), respectively; the optimal thresholds were >40.95 ( P=0.008) and > 5 423.50 mmHg (1 mmHg=0.133 kPa, P=0.006), the sensitivity was 0.559 and 0.588, and the specificity was 0.728 and 0.735, respectively. Multivariate Cox regression analysis showed that after adjusting for age, gender, diabetes and ACEI/ARB use, VE/VCO 2 slope ( HR=2.12, P=0.036) and peak SBP*VE/VCO 2 ( HR=2.42, P=0.016) were independent risk factors for all-cause mortality in patients with CHF. Conclusion:Compared to the traditional index VE/VCO 2 slope, a novel index peak SBP* VE/VCO 2 provides a relatively better predictive value for all-cause death of CHF patients.

New threats posed by the emerging circulating variants of SARS-CoV-2 highlight the need to find conserved neutralizing epitopes for therapeutic antibodies and efficient vaccine design. Here, we identified a receptor-binding domain (RBD)-binding antibody, XG014, which potently neutralizes β-coronavirus lineage B (β-CoV-B), including SARS-CoV-2, its circulating variants, SARS-CoV and bat SARSr-CoV WIV1. Interestingly, antibody family members competing with XG014 binding show reduced levels of cross-reactivity and induce antibody-dependent SARS-CoV-2 spike (S) protein-mediated cell-cell fusion, suggesting a unique mode of recognition by XG014. Structural analyses reveal that XG014 recognizes a conserved epitope outside the ACE2 binding site and completely locks RBD in the non-functional "down" conformation, while its family member XG005 directly competes with ACE2 binding and position the RBD "up". Single administration of XG014 is effective in protection against and therapy of SARS-CoV-2 infection in vivo. Our findings suggest the potential to develop XG014 as pan-β-CoV-B therapeutics and the importance of the XG014 conserved antigenic epitope for designing broadly protective vaccines against β-CoV-B and newly emerging SARS-CoV-2 variants of concern.
Angiotensin-Converting Enzyme 2 ; Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 ; Epitopes ; Humans ; SARS-CoV-2/genetics* ; Spike Glycoprotein, Coronavirus/genetics*

Objective　To retrospectively analyze the relationship between the age of smoking initiation and young stroke.Methods　Patients with ischemic stroke who were ever smokers or current smokers were enrolled in Beijing Tiantan Hospital from January 2018 to December 2020.Young stroke was defined as ages between 18 and 45 years.A multivariate logistic regression model was used to analyze the relationship between the age of smoking initiation and young stroke after adjusting for other confounding factors.Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated.Results　Among 869 patients with ischemic stroke,85 (9.8%) patients were young stroke and 817 (94.5%) patients were males,the average age of smoking initiation was 27.4±10.5 years.In the young stroke group,the average age of smoking initiation was 21.6±5.9 years,significantly lower than that in the middle-aged and older stroke group (28.0±10.7 years,P<0.001).In multivariate logistic regression,compared with the age of smoking initiation ≤25 group,older age of smoking initiation was significantly associated with a higher risk of young stroke (OR 0.17,95% CI 0.08~0.37,P<0.001).As the age of smoking initiation increased,the risk of young stroke decreased (OR 0.41,95%CI 0.26~0.63 per 10 years increment,P<0.001).Conclusion　The age of smoking initiation is an independent predictor of young stroke.The age of smoking initiation was younger,and the risk of young stroke was higher.

Objective:To investigate the prognostic factors of differentiated thyroid cancer (DTC) patients with positive thyroglobulin antibody (TgAb) and varying ages after operation and 131I treatment. To explore the value of TgAb level and its change in the prognosis of DTC patients. Methods:Clinical data of 131 TgAb positive DTC patients were retrospectively analyzed. According to age, they were divided into young group(age<55 years, n=95) and elder group (age≥55 years, n=36). According to response, it was divided into excellent response group (110 cases) and non-excellent response group (21 cases). χ2 test and t test were used to compare the clinicopathological features between excellent response group and non-excellent response group. By logistic regression analysis, the independent risk factors affecting the prognosis of patients were analyzed. The receiver operating characteristic curve was used to determine the TgAb value of persistent or recurrent DTC, and the Kaplan-Meier regression curve was used to analyze the time of TgAb becoming negative. P<0.05 was statistically significant. Results:In young patients, the higher serum TgAb level before 131I treatment and the lateral lymph node metastasis were the independent influencing factors of poor prognosis [ OR=0.89(95% CI 0.83-0.95), OR=0.15(95% CI 0.05-0.52); both P<0.05]. In elder group, extraglandular invasion and higher serum TgAb before 131I treatment were associated with poorer prognosis [ OR=0.05(95% CI 0-0.83), OR=0.91(95% CI 0.76-1.13); P<0.05]. The serum TgAb thresholds for predicting DTC persistence/recurrence were 315.5 IU/mL(246.0 IU/mL in the young group and 516.5 IU/mL in the elder group). The mean time TgAb sera turned negative was (26.37±2.22) months [(23.28±2.37) months for young group and (32.64±4.07) months for elder group]. The TgAb decreased >50% in one year of the patients who had a lower probability of disease persistence/recurrence than the group without ( P<0.05). Conclusions:The high level of serum TgAb before 131I treatment and lateral lymph node metastasis were independent factors of poor prognosis in young patients, while in elder patients, extraglandular tumor invasion and the high level of serum TgAb before 131I treatment were independent factors of poor prognosis. The rate of TgAb change one year after treatment may be used as an early marker for predicting the disease status of TgAb positive patients.

To construct TeI3c/4c-based and temperature-inducible gene inactivation system (Thermotargetron) and to apply it to gene inactivation of mesophilic bacteria. The subunit of flagellum (fliC) and C4 dicarboxylate orotate:H⁺ symporter (dctA) genes were chosen as targets in the genome of Escherichia coli HMS174 (DE3) strain. According to recognition roles of TeI3c/4c intron, the fliC489a, fliC828s, fliC1038s and dctA2a sites were chosen as target sites. Gene-targeting plasmids were constructed based on pHK-TT1A by using overlap PCR method and transformed into HMS174 cells. An aliquot mid-log phase cultures of the transformants were shocked at 48 °C and plated on LB plate (containing chloramphenicol). Afterwards, gene mutants were screened by using colony PCR and DNA sequencing. After the mutants were obtained, the phenotypes of ΔfliC and ΔdctA gene mutants were characterized by using agar puncture and carbon metabolism experiments. Colony PCR and sequencing results show that TeI3c/4c intron was inserted in the designed sites of fliC and dctA genes. The gene-targeting efficiency of Thermotargetron system was 100%. Phenotype verification experiments of the mutants demonstrated that the cell motility of all ΔfliC mutants was damaged and the malate assimilation ability of ΔdctA mutant was deprived comparing to wild-type HMS174 strain. In our study, a temperature-inducible and high-efficiency gene inactivation system was established for mesophilic bacteria. This system could achieve high efficiency and precise gene inactivation by modulation of the incubation duration of the transformants at 48 °C.