Objective To analyse the distribution characteristics and drug resistance of multidrug-resistant bacteria infections in patients with diabetic foot ulcers, and to investigate the relevant risk factors affecting the infection of multidrug-resistant bacteria in patients with diabetic foot ulcers. Methods We selected 352 patients with diabetic foot ulcers admitted to our hospital from January 2021 to December 2023, and retrospectively collated and analysed the clinical data of all patients, collected the ulcer wound specimens of all patients, analysed the infection of multidrug-resistant bacteria and bacterial resistance, compared the differences in the relevant data of patients with different infections, and analysed the risk factors affecting the patients with diabetic foot ulcers by using multivariate logistic regression model. Multiple logistic regression model was used to analyse the risk factors affecting patients with diabetic foot ulcers infected with multi-drug resistant bacteria. Results A total of 352 patients with diabetic foot ulcers, 20.45% developed multidrug-resistant bacterial infections, and a total of 91 strains of bacteria were detected, with the predominant strains being Staphylococcus aureus (41.76%), Pseudomonas aeruginosa (24.18%) and Enterobacteriaceae (21.98%).Compared with uninfected patients, patients with MDRI had a longer duration of diabetes, longer duration of ulcers, a higher proportion of Wagner grade 3-5, ischaemic ulcers, multiple hospitalisations, combined osteomyelitis, larger ulcers, and a longer duration of antibiotic use (P < 0.05).Multifactorial analysis showed that long duration of diabetes mellitus, high Wagner grading, long duration of ulcer, large ulcer size, multiple hospitalisations, prolonged antibiotic use, and comorbid osteomyelitis were all risk factors for MDRI (P < 0.05). Conclusion Patients with diabetic foot ulcers are at risk of multi-resistant bacterial infections, and longer duration of diabetes mellitus, Wagner grade 3-5, longer duration of ulcers prior to hospitalisation, larger ulcer size, hospitalisation for the same wound >2 times/year, prolonged use of antibiotics prior to hospitalisation, and comorbidity with osteomyelitis can increase the risk of multi-resistant bacterial infections in patients with diabetic foot ulcers, therefore, controlling and reducing multi-resistant bacterial infections is the key to improving the prognosis of patients with diabetic foot ulcers.

Metastasis serves as an indicator of malignancy and is a biological characteristic of carcinomas. Epithelial-mesenchymal transition (EMT) plays a key role in the promotion of tumor invasion and metastasis and in the enhancement of tumor cell aggressiveness. Prostaglandin E synthase 3 (p23) is a cochaperone for heat shock protein 90 (HSP90). Our previous study showed that p23 is an HSP90-independent transcription factor in cancer-associated inflammation. The effect and mechanism of action of p23 on lung cancer metastasis are tested in this study. By utilizing cell models in vitro and mouse tail vein metastasis models in vivo, the results provide solid evidence that p23 is critical for promoting lung cancer metastases by regulating downstream CXCL1 expression. Rather than acting independently, p23 forms a complex with RNA-binding motif protein 14 (RBM14) to facilitate EMT progression in lung cancer. Therefore, our study provides evidence for the potential role of the RBM14-p23-CXCL1-EMT axis in the metastasis of lung cancer.

Elemene is widely recognized as an effective anti-cancer compound and is routinely administered in Chinese clinical settings for the management of several solid tumors, including non-small cell lung cancer (NSCLC). However, its detailed molecular mechanism has not been adequately demonstrated. In this research, it was demonstrated that elemene effectively curtailed NSCLC growth in the patient-derived xenograft (PDX) model. Mechanistically, employing high-throughput screening techniques and subsequent biochemical validations such as microscale thermophoresis (MST), microRNA-145-5p (miR-145-5p) was pinpointed as a critical target through which elemene exerts its anti-tumor effects. Interestingly, elemene serves as a binding stabilizer for miR-145-5p, demonstrating a strong binding affinity (dissociation constant (K _D) = 0.39 ± 0.17 μg/mL) and preventing its degradation both in vitro and in vivo, while not interfering with the synthesis of the primary microRNA transcripts (pri-miRNAs) and precursor miRNAs (pre-miRNAs). The stabilization of miR-145-5p by elemene resulted in an increased level of this miRNA, subsequently suppressing NSCLC progression through the miR-145-5p/mitogen-activated protein kinase kinase kinase 3 (MAP3K3)/nuclear factor kappaB (NF-κB) pathway. Our findings provide a new perspective on revealing the interaction patterns between clinical anti-tumor drugs and miRNAs.

OBJECTIVES: This study aimed to investigate the potential mediating role of plasma phosphorylated tau217 (p-tau217) in the association between periodontitis and mild cognitive impairment (MCI). METHODS: In this case-control study, patients diagnosed with MCI in the Neurology Department of the First Affiliated Hospital of Shandong Second Medical University from November 2023 to May 2024 were selected as the case group (MCI group). Cognitively normal (CN) volunteers, matched for age and education level and recruited from the physical examination center during the same period, served as the control group (CN group). The general demographic data of the study participants were collected. The Beijing versions of the Montreal Cognitive Assessment (MoCA), clinical dementia rating (CDR), and activities of daily living scale (ADL) were used to assess neuropsychological functions. Clinical periodontal examinations were conducted, the periodontal inflamed surface area (PISA) was calculated, and the periodontitis stage was determined in accordance with the 2018 classification. Fasting elbow venous blood samples were collected in the morning, and blood biochemical indicators were measured. Plasma p-tau217 levels were detected using enzyme-linked immunosorbent assay (ELISA). Statistical analyses were performed using t-test, Mann-Whitney U test, chi-square test, partial correlation analysis, multivariate Logistic regression analysis, multiple linear regression analysis, restricted cubic spline (RCS) regression analysis, and mediation effect analysis. RESULTS: Among the 192 participants, 96 belong to the MCI group and 96 to the CN group. The prevalence of periodontitis was 63.5% in the MCI group and 43.8% in the CN group, with a statistically significant difference (χ²=7.561, P=0.006). The plasma p-tau217 levels in the MCI group were significantly higher than those in the CN group [7.00 (4.27-9.65) ng/mL versus 2.02 (0.80-3.81) ng/mL, Z=-8.108, P<0.001]. Partial correlation analysis revealed that plasma p-tau217 levels were positively correlated with all the clinical periodontal indices (all P<0.001). After adjustments for baseline covariates, multivariate Logistic regression indicated that periodontitis was an independent risk factor for MCI. Patients with periodontitis had a 1.977-fold higher MCI risk than those without periodontitis (OR=1.977, 95%CI: 1.088-3.594, P=0.025). Moreover, the MCI risk for stage Ⅰ/Ⅱ periodontitis and stage Ⅲ/Ⅳ periodontitis was 1.878 times (OR=1.878, 95%CI: 1.029-3.425, P=0.040) and 2.625 times (OR=2.625, 95%CI: 1.073-6.246, P=0.035) higher than that for patients without periodontitis, respectively. Trend test showed that the MCI risk increased with periodontitis severity (P_trend=0.016). After adjustments for baseline covariates, multiple linear regression analysis showed that periodontitis was an independent risk factor for increased plasma p-tau217 levels (β=3.309, 95%CI: 2.363-4.254, P<0.001). Compared with patients without periodontitis, those with stage Ⅰ/Ⅱ periodontitis (β=1.838, 95%CI: 0.869-2.806, P<0.001) and stage Ⅲ/Ⅳ periodontitis (β=5.539, 95%CI: 4.442-6.636, P<0.001) had significantly higher plasma p-tau217 levels. In addition, trend test indicated that plasma p-tau217 levels increased with periodontitis severity (P_trend<0.001). After adjustments for baseline covariates, RCS regression analysis further revealed that PISA had a positive linear dose-response relationship with MCI risk (P_overall=0.002, P_nonlinear=0.344) and plasma p-tau217 levels (P_overall<0.001, P_nonlinear=0.140). After adjustments for baseline covariates, mediation analysis showed that plasma p-tau217 mediated the association between periodontitis and MCI, with a mediation proportion of 13.99% (95% Bootstrap CI: 0.38%-49.39%, P=0.038). CONCLUSIONS Periodontitis was independently positively associated with MCI risk, and plasma p-tau217 plays a mediating role in this association.
Humans ; Cognitive Dysfunction/complications* ; tau Proteins/blood* ; Periodontitis/complications* ; Case-Control Studies ; Male ; Female ; Phosphorylation ; Aged ; Middle Aged ; Activities of Daily Living

Objective To investigate the effects and mechanism of Zhachong Shisanwei Pills on rats with cerebral ischemia.Methods Totally 75 rats were randomly divided into sham-operation group,model group,positive drug group(Ginaton,21.6 mg/kg),and Zhachong Shisanwei Pills low-,medium-,and high-dosage groups(81,162,324 mg/kg).Each treatment group was given the corresponding drug by gavage for 5 days.On the 6th day,a cerebral ischemia rat model was prepared by suture method.After 24 hours of modeling,the drugs were given in the same manner for 2 days.Neurological function scoring,horizontal beam walking scoring,and grip strength testing were performed on rats.TTC staining was used to detect the cerebral infarction rate,HE staining and Nissl staining were used to observe the morphology of brain tissue.TUNEL staining was used to detect the apoptosis rate of brain tissue cells.Differential genes in the treatment of cerebral ischemia using Zhachong Shisanwei Pills were screened by transcriptomics,and RT-qPCR,immunohistochemistry and Western blot were used to detect differential gene mRNA and protein expression.Results Compared with the sham-operation group,the model group rats showed a decrease in neurological function scores,horizontal beam walking scores,grip strength,an increase in cerebral infarction rate,neuronal nucleus condensation,vacuolar changes,widened intercellular spaces,the number of Nissl bodies reduced,and the apoptosis rate increased(P<0.01,P<0.001);compared with the model group,the Zhachong Shisanwei Pills medium-dosage group showed an increase in neurological function score,horizontal beam walking score,and grip strength in rats,a decrease in cerebral infarction rate,a lower degree of neuronal damage,an increase in the number of Nissl bodies,and a decrease in cell apoptosis rate(P<0.05,P<0.01).Transcriptome and bioinformatics analysis screened the Hippo signaling pathway related to the anti-cerebral ischemia effect of Zhachong Shisanwei Pills.The key genes of this pathway,mammalian sterile line 20 like kinase(MST1)1,Yes related protein(YAP)1,large tumor suppressor kinase(LATS)1,and TEA domain family member(TEAD)1 were detected.The results showed that the expression of MST1 mRNA and protein in brain tissue of model rats significantly increased,while the expressions of YAP1,LATS1,TEAD1 mRNA and protein significantly decreased;Zhachong Shisanwei Pills could down-regulate the expression of MST1 in brain tissue of model rats,and up-regulate the expressions of YAP1,LATS1 and TEAD1.Conclusion Zhachong Shisanwei Pills may exert anti-cerebral ischemia effects through the Hippo signaling pathway.

As one of the most attention-attracting immunotherapy, immune checkpoint inhibitors (ICIs) have been approved as the first-line drugs for the therapy of various types of cancers.Nevertheless, the single application of ICIs exhibited limited efficacy, and it is easy to develop drug resistance.Therefore, the development of combination therapies become a hot topic in this field to improve the efficacy of ICIs therapy.This article describes some new ICIs targets, reveals the mechanisms of resistance, and introduces the current status of combination other therapies with ICIs therapy systematically including chemotherapy, radiotherapy, hyperthermia, antiangiogenic therapy, tumor vaccines, cytokine therapy and adoptive cellular therapy.Furthermore, the synergistic mechanism of combination therapy to enhance antitumor effect.Thus, this article provides solid references for personalized combination therapy according to the pathological characteristics of patients.

Objective:The aim of this study was to explore the perception and cognition of patients with laryngeal cancer post total laryngectomy accepted expressive writing intervention, analyze the intervention effect from the perspective of patients, and provide a basis for psychological intervention of these patients.Methods:From July to August 2021, the descriptive research method was applied to 13 patients with laryngeal cancer post total laryngectomy who had participated in the expressive writing intervention hosted in the General Hospital of Ningxia Medical University, in order to understand the patients′ perception and cognition of the intervention, and the data were analyzed by using content analysis method.Results:A total of 2 themes and 9 sub themes were extracted. Theme 1: the positive feedback of expressive writing intervention: relieve related physical symptoms and improve sleep; reduce anxiety and regulate emotions effectively; reduce psychological stress and promote positive coping; reduce stigma and improve social withdrawal; make up for lost pronunciation and clear mind. Theme 2: Difficulties and challenges in the application of expressive writing intervention: physical discomfort affects the compliance of patients, poor economic status affects the enthusiasm of patients to participate, poor social and family support affects the willingness of patients to participate, and literacy and writing habits affect the completion of participation.Conclusions:The application of expressive writing intervention promotes the psychological and social functional rehabilitation of patients with laryngeal cancer post total laryngectomy and has satisfactory effects and certain feasibility. The researchers should fully consider the influencing factors of intervention and optimize the plan in the future.

Objective To investigate the HIV-1 genotype and distribution of newly diagnosed HIV-1 cases in Fujian Province in 2020, so as to provide insights into formulation of the precise AIDS control strategy in the province. Methods Newly diagnosed HIV-1 cases without antiretroviral therapy (excluding AIDS patients) were randomly sampled from each city of Fujian Province in 2020 at a proportion of 50% of the mean number of HIV-infected cases reported across 9 cities of Fujian Province during the past three years. Subjects’ demographic and epidemiological data were collected and blood samples were collected. The HIV-1 pol gene was amplified using nested reverse-transcription PCR assay, and the gene sequences were used for HIV-1 genotyping and phylogenetic analysis. The gene sequences were uploaded to the HIV Drug Resistance Database (http://hivdb.stanford.edu) for genotypic drug resistance assays, and the scores and level of HIV drug resistance were estimated using the HIVDB Algorithm version 9.5. Results A total of 1 043 newly diagnosed HIV-1 cases were reported in Fujian Province in 2020, and 936 gene sequences were successfully obtained following sequencing of blood samples. There were 9 HIV-1 genotypes characterized in blood samples from 936 newly diagnosed HIV-1 cases, with CRF07_BC (52.1%) and CRF01_AE (30.4%) as predominant subtypes, followed by CRF08_BC (4.9%), CRF55_01B (3.0%), subtype C (2.5%), subtype B (2.1%), CRF85_BC (1.7%), CRF59_01B (0.3%) and CRF65_CPX (0.1%), and unidentified subtypes were found in 26 blood samples. HIV-1 drug resistance was detected in 43 out of the 936 newly diagnosed HIV-1 cases, with 4.6% prevalence of HIV-1 drug resistance prior to therapy, and the highest drug resistance was found in the HIV CRF59_01B subtype, followed by in CRF08_BC, B, C, CRF01_AE, CRF07_BC and other subtypes, with a significant difference in the genotype-specific prevalence of HIV-1 drug resistance (χ² = 45.002, P < 0.05). Conclusions There was a HIV-1 genotype diversity in Fujian Province in 2020, and emerging recombinant and drug-resistant HIV-1 strains were detected and spread across patients and regions. Monitoring of HIV-1 genotypes is recommended to be reinforced for timely understanding of the transmission and spread of novel recombinant and drug-resistant HIV-1 strains.

Objective:To construct an evaluation index system for the core competence of hospital specialist service operation assistants and provide reference for the evaluation of such competence.Methods:From January to March 2022, literature analysis and behavioral event interviews were used to initially establish a core competence evaluation index system of hospital specialist service operation assistants, based on the Donabedian model. Subsequently, the Delphi expert consultation method was applied to conduct correspondence consultation, inviting experts to evaluate the contents and importance of the index system, using analytic hierarchy process to determine the weights of the indexes at all levels.Results:Two rounds of expert consultation were carried out, and the valid recovery rate of the questionnaire was 100%. The familiarity coefficient of the second round of correspondence was 0.87, the basis of judgment coefficient was 0.90, and the authority coefficient was 0.89. The final evaluation index system for core competence of hospital specialist service operation assistant consisted of 3 first-level indexes, 13 second-level indexes and 81 third-level indexes. The weight of the first-level index structure index was 0.266, and the highest weight among the second-level indexes was the operational development ability (0.083), while the highest weight among the third-level indexes of operational development ability was the comprehensive coordination ability (0.193); The weight of the first-level index process index was 0.405, and the corresponding second-level and third-level indexes with the highest weight were department operation practice work (0.157) and reasonable resource allocation (0.303), respectively; The weight of the first-level index result index was 0.329, and the corresponding second-level and third-level indexes with the highest weight were the weight of medical quality and safety (0.103) and drug adverse reaction reporting rate (0.237), respectively.Conclusions:The evaluation index system constructed in this study proves scientific and reasonable in weight assignment, proving a reference for the management of the specialist service operation assistants.

OBJECTIVE: To explore the risk factors of acute respiratory distress syndrome (ARDS) in patients with sepsis and to construct a risk nomogram model. METHODS: The clinical data of 234 sepsis patients admitted to the intensive care unit (ICU) of Tianjin Hospital from January 2019 to May 2022 were retrospectively analyzed. The patients were divided into non-ARDS group (156 cases) and ARDS group (78 cases) according to the presence or absence of ARDS. The gender, age, hypertension, diabetes, coronary heart disease, smoking history, history of alcoholism, temperature, respiratory rate (RR), mean arterial pressure (MAP), pulmonary infection, white blood cell count (WBC), hemoglobin (Hb), platelet count (PLT), prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), D-dimer, oxygenation index (PaO₂/FiO₂), lactic acid (Lac), procalcitonin (PCT), brain natriuretic peptide (BNP), albumin (ALB), blood urea nitrogen (BUN), serum creatinine (SCr), acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA) were compared between the two groups. Univariate and multivariate Logistic regression were used to analyze the risk factors of sepsis related ARDS. Based on the screened independent risk factors, a nomogram prediction model was constructed, and Bootstrap method was used for internal verification. The receiver operator characteristic curve (ROC curve) was drawn, and the area under the ROC curve (AUC) was calculated to verify the prediction and accuracy of the model. RESULTS: There were no significant differences in gender, age, hypertension, diabetes, coronary heart disease, smoking history, alcoholism history, temperature, WBC, Hb, PLT, PT, APTT, FIB, PCT, BNP and SCr between the two groups. There were significant differences in RR, MAP, pulmonary infection, D-dimer, PaO₂/FiO₂, Lac, ALB, BUN, APACHE II score and SOFA score (all P < 0.05). Multivariate Logistic regression analysis showed that increased RR, low MAP, pulmonary infection, high Lac and high APACHE II score were independent risk factors for sepsis related ARDS [RR: odds ratio (OR) = 1.167, 95% confidence interval (95%CI) was 1.019-1.336; MAP: OR = 0.962, 95%CI was 0.932-0.994; pulmonary infection: OR = 0.428, 95%CI was 0.189-0.966; Lac: OR = 1.684, 95%CI was 1.036-2.735; APACHE II score: OR = 1.577, 95%CI was 1.202-2.067; all P < 0.05]. Based on the above independent risk factors, a risk nomograph model was established to predict sepsis related ARDS (accuracy was 81.62%, sensitivity was 66.67%, specificity was 89.10%). The predicted values were basically consistent with the measured values, and the AUC was 0.866 (95%CI was 0.819-0.914). CONCLUSIONS Increased RR, low MAP, pulmonary infection, high Lac and high APACHE II score are independent risk factors for sepsis related ARDS. Establishment of a risk nomograph model based on these factors may guide to predict the risk of ARDS in sepsis patients.
Humans ; Retrospective Studies ; Alcoholism ; Prognosis ; Respiratory Distress Syndrome ; Pneumonia ; Sepsis ; Intensive Care Units ; Procalcitonin ; Fibrinogen ; ROC Curve