OBJECTIVE: To identify early potential risk factors for hospital-acquired pneumonia (HAP) in patients with mild traumatic brain injury (mTBI), construct a risk prediction model, and evaluate its predictive efficacy. METHODS: A case-control study was conducted using clinical data from mTBI patients admitted to the neurosurgery department of Changzhou Second People's Hospital from September 2021 to September 2023. The patients were divided into two groups based on whether they developed HAP. Clinical data within 48 hours of admission were statistically analyzed to identify factors influencing HAP occurrence through univariate analysis. Least absolute shrinkage and selection operator (LASSO) regression analysis was employed for feature selection to identify the most influential variables. The dataset was divided into training and validation sets in a 7:3 ratio. A multivariate Logistic regression analysis was then performed using the training set to construct the prediction model, exploring the risk factors for HAP in mTBI patients and conducting internal validation in the validation set. Receiver operator characteristic curve (ROC curve), decision curve analysis (DCA), and calibration curve were utilized to assess the sensitivity, specificity, decision value, and predictive accuracy of the prediction model. RESULTS: A total of 677 mTBI patients were included, with 257 in the HAP group and 420 in the non-HAP group. The significant differences were found between the two groups in terms of age, maximum body temperature (MaxT), maximum heart rate (MaxHR), maximum systolic blood pressure (MaxSBP), minimum systolic blood pressure (MinSBP), maximum respiratory rate (MaxRR), cause of injury, and laboratory indicators [C-reactive protein (CRP), procalcitonin (PCT), neutrophil count (NEUT), erythrocyte sedimentation rate (ESR), fibrinogen (FBG), fibrinogen equivalent units (FEU), prothrombin time (PT), activated partial thromboplastin time (APTT), total cholesterol (TC), lactate dehydrogenase (LDH), prealbumin (PAB), albumin (Alb), blood urea nitrogen (BUN), serum creatinine (SCr), hematocrit (HCT), hemoglobin (Hb), platelet count (PLT), glucose (Glu), K⁺, Na⁺], suggesting they could be potential risk factors for HAP in mTBI patients. After LASSO regression analysis, the key risk factors were enrolled in the multivariate Logistic regression analysis. The results revealed that the cause of injury being a traffic accident [odds ratio (OR) = 2.199, 95% confidence interval (95%CI) was 1.124-4.398, P = 0.023], NEUT (OR = 1.330, 95%CI was 1.214-1.469, P < 0.001), ESR (OR = 1.053, 95%CI was 1.019-1.090, P = 0.003), FBG (OR = 0.272, 95%CI was 0.158-0.445, P < 0.001), PT (OR = 0.253, 95%CI was 0.144-0.422, P < 0.001), APTT (OR = 0.689, 95%CI was 0.578-0.811, P < 0.001), Alb (OR = 0.734, 95%CI was 0.654-0.815, P < 0.001), BUN (OR = 0.720, 95%CI was 0.547-0.934, P = 0.016), and Na⁺ (OR = 0.756, 95%CI was 0.670-0.843, P < 0.001) could serve as main risk factors for constructing the prediction model. Calibration curves demonstrated good calibration of the prediction model in both training and validation sets with no evident over fitting. ROC curve analysis showed that the area under the ROC curve (AUC) of the prediction model in the training set was 0.943 (95%CI was 0.921-0.965, P < 0.001), with a sensitivity of 83.6% and a specificity of 91.5%. In the validation set, the AUC was 0.917 (95%CI was 0.878-0.957, P < 0.001), with a sensitivity of 90.1% and a specificity of 85.0%. DCA indicated that the prediction model had a high net benefit, suggesting practical clinical applicability. CONCLUSIONS The cause of injury being a traffic accident, NEUT, ESR, FBG, PT, APTT, Alb, BUN, and Na⁺ are identified as major risk factors influencing the occurrence of HAP in mTBI patients. The prediction model constructed using these parameters effectively assesses the likelihood of HAP in mTBI patients.
Humans ; Risk Factors ; Case-Control Studies ; Logistic Models ; Healthcare-Associated Pneumonia/epidemiology* ; Brain Injuries, Traumatic/complications* ; Male ; Female ; ROC Curve ; Pneumonia/etiology* ; Middle Aged ; Adult

Synthetic promoters are novel promoters artificially designed and do not exist in nature. They can initiate the expression of target genes with specific regulatory modes, offering advantages such as high expression efficiency, precise regulation, and modularity. These features endow synthetic promoters with significant application potential in fields such as industrial production, environmental monitoring, and disease diagnosis and treatment. This paper reviews the basic structures, functions, and classification of promoters, discusses various regulatory elements that influence promoter functions, including enhancers, signal response elements, and transcription factors. Additionally, the conventional and deep learning-based strategies for designing synthetic promoters are summarized. Finally, the theoretical significance of synthetic promoters is emphasized, which is followed by an overview of their current applications, along with a rational discussion on the challenges and future development directions of synthetic promoters. Given the critical role of promoters in gene regulation, this article provides a review and outlook on the research progress of synthetic promoters, which holds reference value for the design of cellular gene circuits.
Promoter Regions, Genetic/genetics* ; Transcription Factors/genetics* ; Synthetic Biology/methods* ; Gene Expression Regulation ; Humans ; Deep Learning

Background Chronic excessive exposure to fluoride can cause damage to the central nervous system and a certain degree of learning and memory impairment. However, the associated mechanism is not yet clear and further exploration is needed. Objective Using 4D unlabelled quantitative proteomics techniques to explore differentially expressed proteins and their potential mechanisms of action in chronic excessive fluoride exposure induced brain injury. Methods Twenty-four SPF-grade adult SD rats, half male and half male, were selected and divided into a control group and a fluoride group by random number table method, with 12 rats in each group. Among them, the control group drank tap water (fluorine content<1 mg·L⁻¹), the fluoride group drank sodium fluoride solution (fluorine content 10 mg·L⁻¹), and both groups were fed with ordinary mouse feed (fluoride content<0.6 mg·kg⁻¹). After 180 d of feeding, the SD rats were weighed, and then part of the brain tissue was sampled for pathological examination by hematoxylin-eosin (HE) staining and Nissl staining. The rest of the brain tissue was frozen and stored at −80 ℃. Three brain tissue samples from each group were randomly selected for proteomics detection. Differentially expressed proteins were screened and subcellular localization analysis was performed, followed by Gene Ontology (GO) function analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, cluster analysis, and protein-protein interaction analysis. Finally, Western blotting was used to detect the expression levels of key proteins extracted from the brain tissue samples. Results After 180 d of feeding, the average weight of the rats in the fluoride group was significantly lower than that in the control group (P<0.05). The brain tissue stained with HE showed no significant morphological changes in the cerebral cortex of the fluoride treated rats, and neuron loss, irregular arrangement of neurons, eosinophilic changes, and cell body pyknosis were observed in the hippocampus. The Nissl staining results showed that the staining of neurons in the cerebral cortex and hippocampus of rats exposed to fluoride decreased (Nissl bodies decreased). The proteomics results showed that a total of 6927 proteins were identified. After screening, 206 differentially expressed proteins were obtained between the control group and the fluoride group, including 96 up-regulated proteins and 110 down-regulated proteins. The differential proteins were mainly located in cytoplasm (30.6%), nucleus (27.2%), mitochondria (13.6%), plasma membrane (13.6%), and extracellular domain (11.7%). The GO analysis results showed that differentially expressed proteins mainly participated in biological processes such as iron ion transport, regulation of dopamine neuron differentiation, and negative regulation of respiratory burst in inflammatory response, exercised molecular functions such as ferrous binding, iron oxidase activity, and cytokine activity, and were located in the smooth endoplasmic reticulum membrane, fixed components of the membrane, chloride channel complexes, and other cellular components. The KEGG significantly enriched pathways included biosynthesis of secondary metabolites, carbon metabolism, and microbial metabolism in diverse environments. The results of differential protein-protein interaction analysis showed that the highest connectivity was found in glucose-6-phosphate isomerase (Gpi). The expression level of Gpi in the brain tissue of the rats in the fluoride group was lower than that in the control group by Western blotting (P<0.05). Conclusion Multiple differentially expressed proteins are present in the brain tissue of rats with chronic fluorosis, and their functions are related to biosynthesis of secondary metabolites, carbon metabolism, and microbial metabolism in diverse environments; Gpi may be involved in cerebral neurological damage caused by chronic overdose fluoride exposure.

Objective:To investigate the risk factors that affected pathological diagnosis upgrading after resection of colorectal adenoma.Methods:From January 2017 to December 2022, a total of 1 059 patients who underwent adenoma resection after pathologically diagnosed as adenoma by endoscopic forceps biopsy(EFB)were included in General Hospital of Ningxia Medical University. The patients were divided into the pathologically no difference group (1 003 cases) and the pathologically upgraded group (56 cases) based on the comparison of pathological diagnosis of EFB specimens and the specimens after adenoma resection. Clinical information and endoscopic characteristics of the adenoma were compared between the 2 groups. The clinical information included smoking history, family history of colorectal cancer, and the endoscopic characteristics included maximum diameter, morphological characteristics, surface depression, erosion or ulceration, and surface color of adenoma. Chi-square test and Fisher′s exact test were used for statistical analysis. Multivariate logistic regression model was used to analyze the risk factors for pathological diagnosis upgrading after adenoma resection.Results:The proportions of patients with smoking history, family history of colorectal cancer, concomitant hypertension, and coronary heart disease in the pathologically upgraded group were higher than those in the pathologically no difference group (46.43%, 26/56 vs.26.12%, 262/1 003; 8.93%, 5/56 vs.0.70%, 7/1 003; 46.43%, 26/56 vs.30.11%, 302/1 003; 21.43%, 12/56 vs.9.27%, 93/1 003), and the differences were statistically significant( χ2=11.05, Fisher′s exact test, χ2=6.61 and 8.78; all P<0.05). There were statistically significant differences between the pathologically no difference group and pathologically upgraded group in the maximum diameter (929 cases (92.62%) and 23 cases (41.07%) of < 20 mm, and 74 cases (7.38%) and 33 cases (58.93%) of ≥20 mm, respectively), morphological characteristics (220 cases (21.93%) and 28 cases (50.00%) with pedicle, and 783 cases (78.07%) and 28 cases (50.00%) without pedicle, respectively), surface color (347 cases (34.60%) and 3 cases (5.36%) of near normal mucosa, 613 cases (61.12%) and 50 cases (89.29%) of red surface color, and 43 cases (4.29%) and 3 cases (5.36%) of white surface color, respectively), erosion or ulceration (78 cases (7.78%) and 36 cases (64.29%) had erosion or ulceration, and 925 cases (92.22%) and 20 cases (35.71%) had no erosion or ulceration, respectively), and surface depression (6 cases (0.60%) and 8 cases (14.29%) of depression, and 997 cases (99.40%) and 48 cases (85.71%) of non depression, respectively) ( χ2=155.18, 23.30, 20.58 and 176.31, Fisher′s exact test; all P<0.001). The result of multivariate logistic regression analysis showed that surface depression ( OR=25.198, 95% confidence interval (95% CI) 5.812 to 109.246, P<0.001), erosion or ulceration( OR=9.913, 95% CI 4.652 to 21.124, P<0.001), red surface color ( OR=4.276, 95% CI 1.053 to 17.363, P=0.042), white surface color ( OR=8.803, 95% CI 1.398 to 55.435, P=0.021), maximum diameter≥20 mm ( OR=4.689, 95% CI 2.265 to 9.706, P<0.001), family history of colorectal cancer ( OR=8.764, 95% CI 1.418 to 54.162, P=0.019) and smoking history ( OR=2.713, 95% CI 1.376 to 5.349, P=0.004) were independent risk factors for pathological diagnosis upgrading after adenoma resection. Conclusion:Surface depression, maximum diameter ≥20 mm, erosion or ulceration, white or red surface color, family history of colorectal cancer and smoking history may enhance the heterogeneity of adenomas, interfere with the accuracy of EFB pathology, and lead to an upgrade of pathological diagnosis after adenoma resection.

Objective:To investigate factors associated with acute kidney injury(AKI) in postoperative colorectal cancer patients.Methods:The clinical data of 376 colorectal carcinoma (CRC) patients at Department of General Surgery, Affiliated Cancer Hospital of Zhengzhou University from Jan 2018 to Jun 2021 were retrospectively analyzed. Patients were divided into acute kidney injury (AKI) ( n=29) and non-AKI groups ( n=347). The demographic information, perioperative status, laboratory results and other relevant data of the two groups were compared . Binary logistic regression was used to analyze the independent risk factors for postoperative AKI. Results:Twenty-nine CRC patients (7.7%) had postoperative AKI. Binary Logistic regression analysis showed that preoperative hypertension ( OR=3.487, 95% CI: 1.081-11.251, P=0.037), anemia ( OR=3.158, 95% CI: 1.114-8.953, P=0.031), inadequate intraoperative crystalloid infusion ( OR=0.998, 95% CI: 0.997-0.999, P=0.007), low intraoperative mean arterial pressure ( OR=0.915, 95% CI: 0.863-0.970, P=0.003) and moderate to severe postoperative decline in hemoglobin levels ( OR=4.105, 95% CI: 1.487-11.335, P=0.006) were independent risk factors. Conclusion:Preoperative hypertension, anemia, inadequate intraoperative crystalloid infusion, low intraoperative mean arterial pressure, and moderate to severe postoperative decline in hemoglobin levels were independent risk factors for AKI development in colorectal cancer patients.

Objective: To explore the predictor of lower airway inflammation among the index of nasal inflammation by investigating the expression and association of eosinophils (EOS) in the upper-lower airways and blood of patients with chronic rhinitis. Methods: A total of 162 patients with allergic rhinitis (AR), 117 patients with non-allergic rhinitis (NAR) and 104 controls were enrolled from June 2010 to December 2013 from General Hospital of Eastern Theater Command, People′s Liberation Army. All subjects were required detailed medical history collection and nasal resistance measurement. Skin prick test (SPT), blood total immunoglobin E (tIgE) and blood EOS, nasal lavage and induced sputum EOS, nasal provocation and bronchial provocation test (NPT, BPT), nasal and forced exhaled nitric oxide (NNO, FeNO) were performed in all patients. One-way analysis of variance was used for comparison between groups. LSD t test or Mann-Whitney U test was used for comparison between the two groups. Pearson or Spearman related parameter test was used for correlation analysis. Results: The nasal lavage EOS, NNO, induced sputum EOS, FeNO, blood EOS and tIgE were higher in the AR group than that in the NAR group (3.70[1.20, 14.23]/200 HP vs 1.40[0.20, 3.40]/200 HP, 673.50[466.80, 936.00] ppb vs 455.80[248.10, 705.60] ppb, 2.97[0.00, 10.63]% vs 1.00[0.23, 2.00]%, (49.28±26.37)ppb vs (34.07±19.11)ppb, 4.00[2.00, 7.00]% vs 2.00[1.00, 5.00]%, 208.01[61.70, 387.50] IU/ml vs 43.30[19.00, 122.00] IU/ml, F or χ² value was 11.442, 19.440, 70.727, 69.449, 47.453, 46.525, respectively, all P<0.05). But there was no significant difference in nasal resistance, NPT and BPT between the two groups. Nasal lavage EOS in AR group and NAR group was correlated with induced sputum EOS, FeNO, tIgE and blood EOS (r value of AR group was 0.448, 0.202, 0.159, 0.321, r value of NAR group was 0.442, 0.268, 0.268, 0.334, respectively, all P<0.05), but not with BPT. After adjustment for gender, age, height and weight, nasal EOS was positively correlated with sputum EOS. Multiple linear regression analysis showed that nasal EOS, blood EOS and SPT were factors affecting sputum EOS levels. The optimal threshold for nasal EOS to determine induced sputum EOS was 3.30/200 HP by (receiver operating characteristic,ROC) analysis. Conclusion The nasal EOS is correlated with multiple lower airway and systemic inflammatory markers, and is a risk factor for the induced sputum EOS, which can be used as an inflammation biomarker to predict the lower air inflammation.

Objective     To analyze the effect of myocardial protection between modified Del Nido cardioplegia and St. Thomas Hospital Cardioplegia in adult patients with aortic valve and mitral valve replacement. Methods     From January 2014 to June 2016, 140 patients underwent aortic valve and mitral valve replacement in our hospital. According to different cardioplegia, the patients were divided into two groups including a modified Del Nido cardioplegia group (70 patients, 37 males, 33 females at mean age of 53.13±9.52 years) and a St. Thomas cardioplegia group (70 patients, 32 males, 38 females, at age of 50.71±9.29 years). We collected clinical data of the patients before operation (T1), 2 h after aortic unclamping (T2), 24 h after operation (T3) and 48 h after operation (T4). Indexes of muscle enzymes including blood center creatine kinase (CK), creatine kinase isoenzyme (CK-MB) concentration and liver function indexes including urea nitrogen (BUN), creatinine (Cr), alanine aminotransferase (ALT), aspartate aminotransferase (AST) concentrations, and compared the postoperative and follow-up clinical data. Results     There was no statistical difference in age, weight, gender, ejection fraction baseline data between the two groups (P>0.05). All patients were successfully completed  combined valve replacement under cardiopulmonary bypass. The cardiopulmonary time was no statistical difference between the two groups (P>0.05). However, compared with St. Thomas cardioplegia group, modified Del Nido group was less in perfusion (1.19±0.39 vs. 2.99±0.75, P<0.001), shorter in aortic clamping time (P=0.003). No statistical difference was found in defibrillation rate after resuscitation between the two groups (P=0.779). Biochemical indicators were not statistically different at different time points between the two groups (P>0.05). Conclusion     Modified Del Nido cardioplegia has the same effect on myocardial protection with St. Thomas cardioplegia in adult patients. It reduces the frequency of reperfusion, and shortens the clamping time. There is no additional injury in the important organs such as liver, kidney. Modified Del Nido cardioplegia myocardial protection ability in adult heart valve surgery is feasible.

Objective: To study the mechanism of vocal mucosal barrier damage mediated by NF-κB and NF-κB-regulated signaling pathway via probing the expression of inflammatory factors and essential proteins for node of NF-κB signaling pathway. Methods: The patients suffering from vocal leukoplakia accompanied with larygopharyngeal reflux(LPR) were treated with oral administration of proton pump inhibitor(PPI). Mucosal specimens of vocal cord were collected from all patients before PPI treatment. And the mucosal specimens of vocal cord were collected from the patients with suspected recurrence at 8 weeks after PPI treatment. HE staining was used to observe the histopathological changes of the mucosa. ELISA was utilized to detect the levels of inflammatory factors including tumor necrosis factor(TNF)-α, interleukin(IL)-1 and IL-6. Western blot was used to detect the expression of p-p65, p-IKK and p-IκB. Immunofluorescence method was adopted to detect the entrance of p65 to cell nucleus.Data was analyzed by SPSS 23.0 software. Results: In PPI untreated group, the expressions of IL-1β, TNF-α and IL-6 in the specimens of 8 weeks after operation were not different significantly from those obtained during operation.But in the PPI-treated group, the expressions were down-regulated.The expression of p-p65 in the middle and high grade heterogenous hyperplasia group was higher than that of low level heterogenous hyperplasia group.The difference of p65 and p-p65 expression between 8 weeks after surgery and surgery in PPI-untreated group was statistically insignificant (P>0.05). The difference of p65 expression between PPI-treated group and PPI pre-treatment group was statistically insignificant (P>0.05). The expression of p-p65 in the PPI-treated group was lower than that of the PPI pre-treatment group (P<0.05). The expressions of IL-1β, TNF-α and IL-6 were positively related with that of NF-κB-p65. Immun of luorescence method revealed the entrance of p65 to cell nucleus in PPI pre-treatment group, which meant that NF-κB was activated. In the PPI-treated group, few activated p65 could be observed in the cell nucleu. Conclusion The possible mechanism of vocal mucosal barrier damage in vocal leukoplakia accompanied with LPR maybe the vocal mucosal inflammation mediated by NF-κB and NF-κB-regulated signaling pathway activated with refluxed materials.

[Abstract ] Objective Clinically, the necessity of acid suppression treatment in vocal leukoplakia is still controversial .This paper aims to investigate the roles of LPR in the pathogenesis and pathological process of vocal leukoplakia , and to clear the signifi-cance of acid suppression in the treatment of this disease through observing the influence of laryngopharyngeal reflux ( LPR) on the symptoms of postoperative vocal leukoplakia . Methods We collected 97 cases underwent vocal leukoplakia surgery from June 2013 to December 2015 in the Department of Otorhinolarygology Head and Neck Surgery , Nanjing General Hospital of Nanjing Military Re-gion.According to the results of ambulatory 24-hour double probe ( simultaneous esophageal and pharyngeal ) pH monitoring ( pH-me-try), the patients with vocal leukoplakia were divided into LPR group (n=26, laryngopharyngeal reflux) and non-LPR group(n=71, non-laryngopharyngeal reflux).Meanwhile, the patients in LPR group were then randomly divided into acid-suppressing group(n=13, oral esomeprazole ) and non-acid-suppressing ( n=13, oral placebo ) . All patients received evaluation and compared by electrolaryngendo-scope, voice handicap index-10 ( VHI-10), reflux symptom index ( RSI) and reflux finding score ( RFS) before operation and 8 weeks after operation, and observe the effect of laryngopharyngeal reflux and acid suppression on the symptoms of postoperative vocal leukoplakia . Results RSI and RFS after operation were significantly lower than before operation in LPR group[(13.6±5.8) vs (18.2±6.2), (9.2±2.4) vs (10.6±2.8), P<0.05].The difference of RSI and RFS between before and after operation in LPR group was higher than the non-LPR group[(5.8±1.4) vs (2.3±0.8), (1.2±0.6) vs (0.5±0.2), P<0.05].The difference of RSI and RFS between before and after operation in acid-suppressing group was higher than the non-acid-suppressing group[(6.6±1.2) vs (0.8±0.6), (2.6±0.6) vs (0.5±0.3), P<0.05].VHI-10 after operation was significantly lower than before operation in acid-suppressing group[(12.6±3.6) vs (15.2±4.2), P<0.05] Conclusion Standard PPI administration to patients suffering from vocal leukoplakia accompanied with LPR can alleviate the symptoms of LPR and improve hoarseness .

Objective Allergic rhinitis (AR) is studied extensively while nonallergic rhinitis (NAR) insufficiently in the recent years .The aim of this study is to describe the inflammation characteristics of different types of NAR . Methods Using the skin prick test , we investigated the characteristics , nasal cytokine levels , serum cytokine levels , and the proportion of peripheral blood Treg cells in 12 cases of AR, 10 cases of NAR with eosinophilia (EOS) syndrome (NARES), 12 cases of NAR without ES (NAR), and 11 control adults . Results The NARES patients had a signifi-cantly higher level of IFN-γ(28.89 [10.97-127.07] pg/mL) than the control (8.98 [7.88-14.90] pg/mL) and the NAR patients (7.92 [7.67-45.85] pg/mL) ( P<0.05) but a lower level of nasal IL-10 than the control ([3.97±0.68] vs [4.80±1.32] pg/mL, P<0.05) .The contents of nasal IL-4, serum IL-4, nasal IL-17 and ser-um IL-17 were all markedly higher in the AR and NARES groups than in the control (P<0.05).The proportion of CD4+CD25+FOXP3+Treg cells in the CD4+T cells in the peripheral blood was (4.5±1.3)%in the AR group and (4.0±1.8) %in the NARES group, both significantly lower than (6.5±1.0) %in the control group (P<0.05) and (6.5±1.0) %in the NAR group (P<0.05). Conclusion NAR was classified according to the EOS level into NARES and NAR without EOS, which had different mechanisms and manifestations of inflammation and similar inflammatory manifestations of Th 2 and Th17.The classification of rhinitis by the level of EOS has more practical significance .