Objective: To classify the ABO blood group phenotypes of 5 cases from a family, and to explore the molecular mechanism for reduced B antigen expression in ABO blood group system. Methods: Serological identification of the ABO blood group was performed using microcolumn gel assay and saline tube method. The soluble antigens in saliva were detected by the agglutination inhibition assay. The full-length sequences and upstream promoter regions of ABO gene were sequenced for genotyping using PacBio SMRT sequencing technology. Results: The results of serological tests indicated the expression of B antigen decreased in 3 out of 5 blood samples. A mixed-field agglutination was observed with anti-B antibody. B antigen was not detected in all 5 saliva samples. The ABO genotype for all samples were ABO B.01/ABO O.01.02, and a novel mutation c. 28+5875C>T within the DNA-binding region of RUNX1 in +5.8-kb site were found in the B allele for 3 samples with reduced expression of B antigen. Conclusion: Results of serological and genetic analyses classify the 3 cases with reduced B antigen expression as B phenotype. The novel mutation c. 28+5875C>T of RUNX1 could be the key reason for reduced B antigen expression in 3 cases with B phenotype.

Objective To investigate the fatigue and workload status among medical students,and to explore the latent profiles of fatigue and workload and their effects on sleep and emotion.Methods A cross-sectional study design with convenience sampling was employed to distribute a comprehensive survey via mixed online and offline modes,and medical college students were enrolled as the subjects for this investigation.The general demographic data,depression,anxiety and stress scale,Pittsburgh sleep quality index,Epworth sleepiness scale,insomnia severity index,National Aeronautics and Space Administration task load index(NASA-TLX)and fatigue scale-14(FS-14)were used to investigate the basic information of the medical students,their emotions(depression,anxiety and stress),sleep(sleep quality,sleepiness and insomnia),workload and fatigue status.Based on latent profile analysis,the types of workload-fatigue profiles and differences in sleep and emotion were analyzed.Results A total of 485 medical students were enrolled,with an average age of(22.07±2.42)years.The total score of the NASA-TLX was 64.44±12.50,and the total score of the FS-14 was 7.90±3.63.Latent profile analysis identified 3 distinct workload-fatigue profiles:low workload-medium fatigue group(12.8％),medium workload-low fatigue group(32.8％),and high workload-high fatigue group(54.4％).Among these,the medium workload-low fatigue group exhibited the highest performance level(all P＜0.05),while the low workload-medium fatigue group showed the lowest effort level and performance level(all P＜0.05).The high workload-high fatigue group showed the highest task-related demand and frustration level(all P＜0.05).Regarding sleep and emotional status,the medium workload-low fatigue group had significantly better outcomes compared to the high workload-high fatigue group and the low workload-medium fatigue group(all P＜0.05).Conclusion Medical students experience a heavy workload and subjective fatigue.It is essential to appropriately adjust their workload,prioritize sleep and emotional well-being,and alleviate fatigue levels,so as to sustain personal physical and mental health.

This study investigated the role of the nuclear factor of activated T cells c3 (NFATc3) in vascular smooth muscle cells (VSMCs) during aortic aneurysm and dissection (AAD) progression and the underlying molecular mechanisms. Cytoplasmic and nuclear NFATc3 levels were elevated in human and mouse AAD. VSMC-NFATc3 deletion reduced thoracic AAD (TAAD) and abdominal aortic aneurysm (AAA) progression in mice, contrary to VSMC-NFATc3 overexpression. VSMC-NFATc3 deletion reduced extracellular matrix (ECM) degradation and maintained the VSMC contractile phenotype. Nuclear NFATc3 targeted and transcriptionally upregulated matrix metalloproteinase 9 (MMP9) and MMP2, promoting ECM degradation and AAD development. NFATc3 promoted VSMC phenotypic switching by binding to eukaryotic elongation factor 2 (eEF2) and inhibiting its phosphorylation in the VSMC cytoplasm. Restoring eEF2 reversed the beneficial effects in VSMC-specific NFATc3-knockout mice. Cabamiquine-targets eEF2 and inhibits protein synthesis-inhibited AAD development and progression in VSMC-NFATc3-overexpressing mice. VSMC-NFATc3 promoted VSMC switch and ECM degradation while exacerbating AAD development, making it a novel potential therapeutic target for preventing and treating AAD.

Objective To evaluate the molluscicidal effect of spraying different formulations of niclosamide ethanolamine salt with drones against Oncomelania hupensis in ditches. Methods A semi-dry and semi-wet ditch with O. hupensis snails was selected in the second branch field of Jiangbei Farm, Jiangling County, Hubei Province in May 2023, and divided into 4 experimental areas, named groups A1, A2, B1 and B2. Environmental cleaning was performed in groups A1 and B2, and was not conducted in groups A2 or B2. Then, 50% wettable powder of niclosamide ethanolamine salt was sprayed with drones at an effective dose of 2 g/m² in groups A1 and A2, and 5% niclosamide ethanolamine salt granule was sprayed with drones at an effective dose of 2 g/m² in groups B1 and B2. O. hupensis snails were surveyed using the systematic sampling method 1, 3, 5, 7, 14 days after spraying, and the natural mortality and corrected mortality of O. hupensis snails were calculated. Results The occurrence of frames with living snails, mean density of living snails and natural mortality of snails were 97.50% (117/120), 6.30 snails/0.1 m² and 1.18% (9/765) in the test ditch before spraying, respectively. There were significant differences in the mortality of snails among four groups 1, 3, 5, 7 and 14 days after spraying niclosamide formulations with drones (χ² = 17.230, 51.707, 65.184, 204.050 and 34.435, all P values < 0.01). The overall mortality rates of snails were 94.51% (1 051/1 112), 79.44% (908/1 143), 96.54% (977/1 012) and 88.55% (1 021/1 153) in groups A1, A2, B1 and B2 (χ² = 207.773, P < 0.05), respectively. In addition, there was no significant difference in the overall snail mortality between groups A1 and B1 (P > 0.05), and the snail mortality in groups A1 and B1 were both statistically different from that in groups A2 and B2 (all P values < 0.05). Conclusion Both 50% wettlable powder of niclosamide ethanolamine salt and 5% niclosamide ethanolamine salt granule sprayed with drones are active against O. hupensis snails in ditches, and environmental cleaning may improve the molluscicidal effect.

Objective: To explore the association of milk tea consumption with comorbid of overweight/obesity and depressive symptoms among college students, so as to provide a reference for promoting the physical and mental health of college students. Methods: A questionnaire survey was conducted from August to October 2023 using convenience sampling among 13 920 students from nine universities in Shanghai, Jiangxi, and Hubei provinces (municipality directly under the central government). Information on college students demographic characteristics, milk tea consumption, overweight/obesity status, and depressive symptoms was collected. Chi square tests were used to compare the association between different demographic characteristics and milk tea consumption with comorbid overweight/obesity and depressive symptoms. Multivariate Logistic regression analysis was performed to infer the strength of the association. Results: The detection rate of comorbidity of overweight/obesity and depressive symptoms was 5.8% among college students. The univariate analysis revealed statistically significant differences in the detection rate of comorbidity of overweight/obesity and depressive symptoms among various groups, including gender, grade, parents education level, only child status, family economic status, meeting moderate to high levels of physical activity standards, sleep quality, and frequent fast food consumption ( χ 2= 82.10, 23.07, 8.91, 10.87 , 4.56, 47.60, 17.60, 386.74, 96.61, P <0.05). There were also statistically significant differences between groups based on milk tea consumption frequency and quantity ( χ 2=42.12, 38.76, P <0.01). Compared with the group of without consuming milk tea, Logistic regression analysis showed that college students who consumed milk tea 4-5 times and ≥6 times had higher risk of comorbid overweight/obesity and depressive symptoms ( OR =1.98, 2.46), and college students who consumed 1-1 500 mL and ≥3 000 mL of milk tea also had higher comorbidity risk ( OR =1.52, 1.22) ( P <0.05). Conclusions Frequent and excessive milk tea consumption among college students may increase the risk of comorbid of overweight/obesity and depressive symptoms. It is recommended to reduce the frequency and quantity of milk tea consumption to improve college students physical and mental health.

Objective To explore the automated identification and diameter measurement methods for inferior vena cava (IVC) based on clinical ultrasound images of IVC. Methods An automated identification and localization method based on topology and automatic tracking algorithm was proposed. Tracking algorithm was used for identifying and continuously locating to improve the efficiency and accuracy of measurement. Tests were conducted on 18 sets of ultrasound data collected from 18 patients in intensive care unit (ICU),with clinicians' measurements as the gold standard. Results The recognition accuracy of the automated method was 94.44％ (17/18),and the measurement error of IVC diameter was within the range of±1.96s (s was the standard deviation). The automated method could replace the manual method. Conclusion The proposed IVC automated identification and localization algorithm based on topology and automatic tracking algorithm has high recognition success rate and IVC diameter measurement accuracy. It can assist clinicians in identifying and locating IVC,so as to improve the accuracy of IVC measurement.

Dysregulated Epiregulin(EREG)can activate epidermal growth factor receptor(EGFR)and promote tumor progression in head and neck squamous cell carcinoma(HNSCC).However,the mechanisms underlying EREG dysregulation remain largely unknown.Here,we showed that dysregulated EREG was highly associated with enhanced PDL1 in HNSCC tissues.Treatment of HNSCC cells with EREG resulted in upregulated PDL1 via the c-myc pathway.Of note,we found that N-glycosylation of EREG was essential for its stability,membrane location,biological function,and upregulation of its downstream target PDL1 in HNSCC.EREG was glycosylated at N47 via STT3B glycosyltransferases,whereas mutations at N47 site abrogated N-glycosylation and destabilized EREG.Consistently,knockdown of STT3B suppressed glycosylated EREG and inhibited PDL1 in HNSCC cells.Moreover,treatment of HNSCC cells with NGI-1,an inhibitor of STT3B,blocked STT3B-mediated glycosylation of EREG,leading to its degradation and suppression of PDL1.Finally,combination of NGI-1 treatment with anti-PDLl therapy synergistically enhanced the efficacy of immunotherapy of HNSCC in vivo.Taken together,STT3B-mediated N-glycosylation is essential for stabilization of EREG,which mediates PDL1 upregulation and immune evasion in HNSCC.

Dysregulated Epiregulin(EREG)can activate epidermal growth factor receptor(EGFR)and promote tumor progression in head and neck squamous cell carcinoma(HNSCC).However,the mechanisms underlying EREG dysregulation remain largely unknown.Here,we showed that dysregulated EREG was highly associated with enhanced PDL1 in HNSCC tissues.Treatment of HNSCC cells with EREG resulted in upregulated PDL1 via the c-myc pathway.Of note,we found that N-glycosylation of EREG was essential for its stability,membrane location,biological function,and upregulation of its downstream target PDL1 in HNSCC.EREG was glycosylated at N47 via STT3B glycosyltransferases,whereas mutations at N47 site abrogated N-glycosylation and destabilized EREG.Consistently,knockdown of STT3B suppressed glycosylated EREG and inhibited PDL1 in HNSCC cells.Moreover,treatment of HNSCC cells with NGI-1,an inhibitor of STT3B,blocked STT3B-mediated glycosylation of EREG,leading to its degradation and suppression of PDL1.Finally,combination of NGI-1 treatment with anti-PDLl therapy synergistically enhanced the efficacy of immunotherapy of HNSCC in vivo.Taken together,STT3B-mediated N-glycosylation is essential for stabilization of EREG,which mediates PDL1 upregulation and immune evasion in HNSCC.

OBJECTIVE: To explore the prognostic value of early multiple detection indicators in combination with sequential organ failure assessment (SOFA) in sepsis patients. METHODS: A retrospective analysis was conducted. Patients with sepsis admitted to the department of critical care medicine of Huanggang Central Hospital of Yangtze University from May 2020 to May 2022 were selected as the research subjects. Coagulation indicators, inflammatory factors, blood routine, liver and kidney function, and blood gas analysis were collected at admission. Organ dysfunction was assessed based on the SOFA score within 24 hours after admission. Patients were divided into a survival group and a death group according to the outcome of 28 days in ICU. Differences in the above indicators between the two groups were compared. Multifactorial Logistic regression analysis was used to analyze prognostic factors of 28-day mortality in sepsis patients. Receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive performance of various indicators, the SOFA score, and the combine model for the 28-day outcome in patients with sepsis. RESULTS: A total of 101 patients with sepsis were enrolled, 56 patients survived and 45 patients died. Compared to the survival group, patients in the death group were older, the proportion of patients with septic shock was larger, the SOFA score, and the proportion of pulmonary infection were higher, the prothrombin time (PT) and activated partial thromboplastin time (APTT) were significantly prolonged, the prothrombin activity (PTA) was significantly shortened, and antithrombin (AT) was significantly decreased, the levels of hypersensitivity C-reactive protein (hs-CRP), blood urea nitrogen (BUN), total bilirubin (TBil), and lactic acid (Lac) were significantly increased, while the platelet count (PLT) was significantly decreased. Multifactorial Logistic regression analysis showed that pulmonary infection [odds ratio (OR) = 0.010, 95% confidence interval (95%CI) was 0.001-0.164, P = 0.001], AT (OR = 0.944, 95%CI was 0.910-0.978, P = 0.002), hs-CRP (OR = 1.008, 95%CI was 1.001-1.015, P = 0.017), Lac (OR = 1.619, 95%CI was 1.195-2.193, P = 0.002), and SOFA score (OR = 1.363, 95%CI was 1.076-1.727, P = 0.010) were independent prognostic factors for 28-day mortality in patients. A combined model was constructed using pulmonary infection, AT, hs-CRP, Lac, and SOFA score. ROC curve analysis showed that the area under the ROC curve (AUC) for the combine model in predicting sepsis prognosis was 0.936 (95%CI was 0.869-0.975, P < 0.001), which was higher in value compared to single indicators (AUC of AT, hs-CRP, Lac, and SOFA score were 0.775, 0.666, 0.802, 0.796, respectively, all P < 0.05). CONCLUSIONS The predictive ability of the SOFA score for sepsis patient outcomes is limited. The combine model combining infection site, AT, hs-CRP, and Lac shows better predictive ability.
Humans ; Organ Dysfunction Scores ; Retrospective Studies ; C-Reactive Protein ; ROC Curve ; Sepsis/metabolism* ; Prognosis ; Anticoagulants ; Antithrombin III ; Intensive Care Units

Objective To evaluate the long-term prognostic value of coronary CT angiography-derived fractional flow reserve(CT-FFR)in elderly patients with coronary heart disease(CHD).Methods A retrospective analysis was performed on 1133 patients with clinically suspected CHD from a prospective observational study based on coronary CTA and CT-FFR at the General Hos-pital of Eastern Theater from April 2018 to March 2019,and 330 elderly CHD patients were even-tually included.According to major adverse cardiovascular events(MACE)occurred or not,295 patients were assigned into non-MACE group and 35 patients into the MACE group.Based on cor-onary CTA data,plaque features were analyzed and CT-FFR values were measured in all lesioned vessels.The relationship of plaque features and CT-FFR with MACE was evaluated by using Cox proportional risk regression model,Kaplan-Meier survival curve,and ROC curve analyses.Results The patients with coronary stenosis(≥50％)or CT-FFR value ≤0.8 had a higher risk of MACE(P＜0.01).Univariate Cox analysis showed that coronary stenosis ≥50％and CT-FFR value 0.8 were risk factors of MACE(P＜0.01).After adjusting confounding factors,multivariate Cox analysis indicated that CT-FFR ≤0.8(HR=17.037,95％CI:5.060-57.358,P=0.000)was only independent predictor for MACE.The risk prediction model based on CT-FFR presented better performance than the model based on coronary CTA stenosis(C-index:0.820 vs 0.696,P=0.000).Conclusion CT-FFR≤0.8 is an important independent predictor for long-term MACE in elderly CHD patients.Clinical risk stratification based on CT-FFR may optimize prognostic man-agement strategies in these patients.