PURPOSE: Septic shock is associated with high mortality and poor outcomes among sepsis patients with coagulopathy. Although traditional statistical methods or machine learning (ML) algorithms have been proposed to predict septic shock, these potential approaches have never been systematically compared. The present work aimed to develop and compare models to predict septic shock among patients with sepsis. METHODS: It is a retrospective cohort study based on 484 patients with sepsis who were admitted to our intensive care units between May 2018 and November 2022. Patients from the 908th Hospital of Chinese PLA Logistical Support Force and Nanchang Hongdu Hospital of Traditional Chinese Medicine were respectively allocated to training (n=311) and validation (n=173) sets. All clinical and laboratory data of sepsis patients characterized by comprehensive coagulation indexes were collected. We developed 5 models based on ML algorithms and 1 model based on a traditional statistical method to predict septic shock in the training cohort. The performance of all models was assessed using the area under the receiver operating characteristic curve and calibration plots. Decision curve analysis was used to evaluate the net benefit of the models. The validation set was applied to verify the predictive accuracy of the models. This study also used Shapley additive explanations method to assess variable importance and explain the prediction made by a ML algorithm. RESULTS: Among all patients, 37.2% experienced septic shock. The characteristic curves of the 6 models ranged from 0.833 to 0.962 and 0.630 to 0.744 in the training and validation sets, respectively. The model with the best prediction performance was based on the support vector machine (SVM) algorithm, which was constructed by age, tissue plasminogen activator-inhibitor complex, prothrombin time, international normalized ratio, white blood cells, and platelet counts. The SVM model showed good calibration and discrimination and a greater net benefit in decision curve analysis. CONCLUSION The SVM algorithm may be superior to other ML and traditional statistical algorithms for predicting septic shock. Physicians can better understand the reliability of the predictive model by Shapley additive explanations value analysis.
Humans ; Shock, Septic/blood* ; Machine Learning ; Male ; Female ; Retrospective Studies ; Middle Aged ; Aged ; Sepsis/complications* ; ROC Curve ; Cohort Studies ; Adult ; Intensive Care Units ; Algorithms ; Blood Coagulation ; Critical Illness

Objective:To discuss the mechanism of salidroside in the treatment of triple negative breast cancer(TNBC)by using the bioinformatics and network pharmacology methods,and to clarify the main targets and signaling pathways involved in the therapeutic effect.Methods:The dataset GSE45827 was obtained from the Gene Expression Omnibus(GEO)database;the gene set enrichment analysis(GSEA)was performed by using the R software package GSEABase;the differentially expressed genes(DEGs)between the adjacent normal tissue and TNBC tissue were identified by limma R software package;the Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis were performed on the DEGs,and the DEGs were integrated with the drug targets to import into gene/protein interaction retrieval tool String database,and the protein-protein interaction(PPI)networks were constructed;the functional module screening of the PPI network was conducted by MCODE plugin,and the top 2 modules ranked by SCORE value were further subjected to GO functional enrichment analysis and KEGG signaling pathway analysis.The pathways obtained from the two rounds of KEGG enrichment analysis were intersected with the results of GSEA enrichment analysis to identify the pathways involved in the therapeutic effect of salidroside on TNBC.The top 10 key node genes in the highest scoring module determined by the maximum clique centrality(MCC)score caculated by CytoHubba plugi were considered as the core genes;the molecular docking was performed by AutoDock Vina1.1.2 and PyMOL2.3.0 Software.Results:The intersection of KEGG and GSEA enrichment analysis results showed 13 singaling pathways,including the cell cycle,cellular senescence,and p53 signaling pathways,and so on.The biological processes involved in the GO functional analysis,such as mitosis,nuclear division,and sister chromatid separation,were closely related to the cell cycle and consistented with the results of the KEGG signaling pathway enrichment analysis.The top ranked module based on the SCORE value contained 5 drug target genes of Rhodiola glycoside,such as cyclin A2(CCNA2),checkpoint kinase 1(CHEK1),kinesin family member 11(KIF11),DNA topoisomerase 2-alpha(TOP2A),and thymidylate synthase(TYMS).The molecular docking results demonstrated strong binding affinities between the above proteins and Rhodiola glycoside(binding energy<-7.0 kcal·mol-1).Conclusion:The tightly binding target of salidroside is located in the key functional modules of DEGs of TNBC,which can directly regulate by binding with CCNA2 and protein,and indirectly regulate the key differentially genes of TNBC by binding with KIF11,TOPA2,CHEK1 and TYMS proteins.Therefore,salidroside may be a potential clinical therapeutic drug for TNBC.

Purpose::In patients with heatstroke, disseminated intravascular coagulation (DIC) is associated with greater risk of in-hospital mortality. However, time-consuming assays or a complex diagnostic system may delay immediate treatment. Therefore, the present study proposes a new heatstroke-induced coagulopathy (HIC) score in patients with heat illness as an early warning indicator for DIC.Methods::This retrospective study enrolled patients with heat illness in 24 Chinese hospitals from March 2021 to May 2022. Patients under 18 years old, with a congenital clotting disorder or liver disease, or using anticoagulants were excluded. Data were collected on demographic characteristics, routine blood tests, conventional coagulation assays and biochemical indexes. The risk factors related to coagulation function in heatstroke were identified by regression analysis, and used to construct a scoring system for HIC. The data of patients who met the diagnostic criteria for HIC and International Society on Thrombosis and Haemostasis defined-DIC were analyzed. All statistical analyses were performed using SPSS 26.0.Results::The final analysis included 302 patients with heat illness, of whom 131 (43.4%) suffered from heatstroke, including 7 death (5.3%). Core temperature ( OR = 1.681, 95% CI 1.291 - 2.189, p < 0.001), prothrombin time ( OR = 1.427, 95% CI 1.175 - 1.733, p < 0.001) and D-dimer ( OR = 1.242, 95% CI 1.049 - 1.471, p = 0.012) were independent risk factors for heatstroke, and therefore used to construct an HIC scoring system because of their close relation with abnormal coagulation. A total score ≥ 3 indicated HIC, and HIC scores correlated with the score for International Society of Thrombosis and Hemostasis-DIC ( r = 0.8848, p < 0.001). The incidence of HIC (27.5%) was higher than that of DIC (11.2%) in all of 131 heatstroke patients. Meanwhile, the mortality rate of HIC (19.4%) was lower than that of DIC (46.7%). When HIC developed into DIC, parameters of coagulation dysfunction changed significantly: platelet count decreased, D-dimer level rose, and prothrombin time and activated partial thromboplastin time prolonged ( p < 0.05). Conclusions::The newly proposed HIC score may provide a valuable tool for early detection of HIC and prompt initiation of treatment.

Background: Genetic defects in the human thyroid-stimulating hormone (TSH) receptor (TSHR) gene can cause congenital hypothyroidism (CH). However, the biological functions and comprehensive genotype–phenotype relationships for most TSHR variants associated with CH remain unexplored. We aimed to identify TSHR variants in Chinese patients with CH, analyze the functions of the variants, and explore the relationships between TSHR genotypes and clinical phenotypes. Methods: In total, 367 patients with CH were recruited for TSHR variant screening using whole-exome sequencing. The effects of the variants were evaluated by in-silico programs such as SIFT and polyphen2. Furthermore, these variants were transfected into 293T cells to detect their Gs/cyclic AMP and Gq/11 signaling activity. Results: Among the 367 patients with CH, 17 TSHR variants, including three novel variants, were identified in 45 patients, and 18 patients carried biallelic TSHR variants. In vitro experiments showed that 10 variants were associated with Gs/cyclic AMP and Gq/11 signaling pathway impairment to varying degrees. Patients with TSHR biallelic variants had lower serum TSH levels and higher free triiodothyronine and thyroxine levels at diagnosis than those with DUOX2 biallelic variants. Conclusions We found a high frequency of TSHR variants in Chinese patients with CH (12.3%), and 4.9% of cases were caused by TSHR biallelic variants. Ten variants were identified as loss-of-function variants. The data suggest that the clinical phenotype of CH patients caused by TSHR biallelic variants is relatively mild. Our study expands the TSHR variant spectrum and provides further evidence for the elucidation of the genetic etiology of CH.

Objective To observe the clinical and symptomatic improvement three months after uterine artery embolization(UAE),and to analyze the value of apparent diffusion coefficient(ADC)in MR diffusion weighted imaging(DWI)in assessing the response of fibroids volume after UAE.Methods A total of 40 patients with uterine fibroids were included.The volume changes of fibroids,clinical and symptomatic improvement before and after treatment were recorded,and the efficacy of UAE was comprehensively analyzed.All patients underwent MR DWI before UAE and were evaluated at three months postoperatively by outpatient MR follow-up,with fibroids vol-ume and ADC quantitative measurements were performed to compare the changes in ADC values of fibroids preoperatively and post-operatively at each b value.Pearson correlation analysis was performed to analyze the correlation between baseline ADC values and postoperative fibroids volume reduction.Regression analysis was performed to assess the relationship between ADC and fibroids volume reduction after UAE.And the receiver operating characteristic(ROC)curve were plotted to analyze the predictive value of ADC values for evaluating fibroids volume reduction of more than 30％after UAE.Results The patients'clinical symptoms was improved in the three months after surgery,the volume of fibroids was significantly reduced,and the life quality was improved,the difference was sta-tistically significant(P＜0.05).There was no significant effect on ovarian function,hormone levels did not change significantly com-pared to before surgery,with no statistical significance(P＞0.05).When b=50,1 000 s/mm2,the changes in ADC values before and after uterine fibroids treatment were not significant,with no statistical significance(P＞0.05).However,the changes in ADC values before and after uterine fibroids treatment were significant when b=800 s/mm2 and the difference was statistically significant(P＜0.05).Under the condition of b=800 s/mm2,Pearson correlation analysis showed ADC value had a positive correlation with postoperative uterine fibroids volume reduction rate(r=0.45,P＜0.05),and the area under the curve(AUC)for ADC value to predict the reduction rate of uterine fibroids volume by more than 30％after UAE was 0.787.The cut-off value was 1.143 × 10-3 mm2/s,with sensitivity and specificity of 0.793 and 0.818,respectively.Conclusion UAE is more effective in treating uterine fibroids.The baseline ADC value of uterine fibroids correlated significantly with the volume reduction after UAE.The ADC value can be used to assess the volume response after UAE.

Objective:To explore the effects of body mass index (BMI) on the incidence of nocturnal hypertension in patients with hypertension.Methods:Totally 341 hospitalized hypertensive patients treated at the Affiliated Hospital of Jining Medical University from February to May 2023 were selected by convenience sampling. Patients' general information, clinical data, and 24-hour ambulatory blood pressure results were collected. A binomial Logistic regression analysis was conducted to investigate the factors affecting the occurrence of nocturnal hypertension in these patients. The relationship between BMI and the incidence of nocturnal hypertension was examined using threshold effect tests and smooth curve fitting.Results:The binomial Logistic regression analysis indicated that blood phosphate level was a factor influencing the occurrence of nocturnal hypertension in hypertensive patients ( P<0.05). Smooth curve fitting and threshold effect test results showed that the relationship between BMI and the incidence of nocturnal hypertension was curve-correlated, with a turning point at 24.61 kg/m 2. To the left of the turning point, there was no correlation ( P=0.130) ; to the right, there was a correlation ( P=0.016) . Conclusions:When the BMI of hypertensive patients exceeds 24.61 kg/m 2, the likelihood of nocturnal hypertension increases with rising BMI, providing a precise intervention target for weight management-based patient care in hypertension.

AIM:To observe the toxic effects of zinc oxide nanoparticles(ZnO NPs)on cornea by constructing intoxicated model in vivo and in vitro.METHODS:Human corneal epithelial cells(HCEpiC)were cultured in vitro and exposed to different concentrations(0.5, 5, 12.5, 25, 50, 100, 250 μg/mL)of ZnO NPs for 24h. The cell culture medium without nano-solution was used as the blank control group. The viability of the cells was assessed by MTT assay. Three different concentrations(25, 50 and 100 μg/mL)of ZnONPs dispersions were exposed to the conjunctival sac of anesthetized mice three times a day for 7d consecutively. The phosphate buffered saline(PBS)eye group was the PBS control group. Corneal morphology was observed on 1, 3, 5 and 7d, and the eyes were removed on 8d for various laboratory examinations, including corneal pathological changes and expression levels of inflammatory factors(TNF-α, IL-6).RESULTS:After treatment of HCEpiC cells with different concentrations of ZnO NPs for 24h, the MTT results showed that Zno NPs cause damage to cells at 0.5 μg/mL, and the cell survival rate was about 80%(P<0.05). Half of the cells were killed at a dose of 5 μg/mL, the damaging effect on cells in the concentration range of 5～250 μg/mL was concentration-dependent(P<0.0001). After 7d of conjunctival capsule spotting in mice, dot-like staining of fluorescein was seen in the 25 μg/mL ZnO NPs and 50 μg/mL ZnO NPs groups. Localized circular fluorescein stained areas were seen in the corneas of the 100 μg/mL ZnO NPs group. HE staining showed that the corneal epithelial layer, stromal layer thickness and stromal layer immune cell number did not change significantly in the 25 μg/mL and 50 μg/mL ZnO NPs groups(all P>0.05), while the corneal epithelial layer thinned, the corneal stromal layer thickened and the stromal layer immune cells increased significantly in the 100 μg/mL ZnO NPs group(all P<0.05). Immunohistochemical staining showed that the number of corneal stromal immune cells producing TNF-α and IL-6 and the mean integral optical density(IOD)values of TNF-α and IL-6 were significantly higher in the 100 μg/mL ZnO NPs group than in the PBS control group(P<0.05), and the degree of inflammation response was concentration-dependent. Compared with the PBS control group, no significant increase in immune cell count and IOD values in the 25 μg/mL ZnO NPs and 50 μg/mL ZnO NPs groups(P>0.05).CONCLUSION:The toxic damaging effect of ZnO NPs on the cornea was confirmed from both in vitro and in vivo, which provided a theoretical basis for the ocular safety evaluation of ZnO NPs.

To enhance the clinical applicability of guidelines and provide more effective guidance for clinical practice, a clinical value assessment was conducted during the development of the World Federation of Acupuncture-Moxibustion Societies (WFAS) Clinical Practice Guideline of Acupuncture and Moxibustion for Migraine, which involved the evaluation of 59 acupuncture and moxibustion treatment protocols from randomized controlled trials (RCTs). This article introduced the methodology, content and results of the clinical value assessment of RCT-based acupuncture and moxibustion treatment protocols, which involved the integration of historical and contemporary medical evidence and expert consensus. It served as a methodological reference for the future development of acupuncture and moxibustion clinical practice guidelines.
Humans ; Moxibustion ; Acupuncture Therapy/methods* ; Acupuncture ; Clinical Protocols ; Migraine Disorders/therapy*

Background: and Purpose Intravenous tenecteplase (TNK) efficacy has not been well demonstrated in acute ischemic stroke (AIS) beyond 4.5 hours after onset. This study aimed to determine the effect of intravenous TNK for AIS within 4.5 to 24 hours of onset. Methods: In this pilot trial, eligible AIS patients with diffusion-weighted imaging (DWI)-fluid attenuated inversion recovery (FLAIR) mismatch were randomly allocated to intravenous TNK (0.25 mg/kg) or standard care within 4.5–24 hours of onset. The primary endpoint was excellent functional outcome at 90 days (modified Rankin Scale [mRS] score of 0–1). The primary safety endpoint was symptomatic intracranial hemorrhage (sICH). Results: Of the randomly assigned 80 patients, the primary endpoint occurred in 52.5% (21/40) of TNK group and 50.0% (20/40) of control group, with no significant difference (unadjusted odds ratio, 1.11; 95% confidence interval 0.46–2.66; P=0.82). More early neurological improvement occurred in TNK group than in control group (11 vs. 3, P=0.03), but no significant differences were found in other secondary endpoints, such as mRS 0–2 at 90 days, shift analysis of mRS at 90 days, and change in National Institutes of Health Stroke Scale score at 24 hours and 7 days. There were no cases of sICH in this trial; however, asymptomatic intracranial hemorrhage occurred in 3 of the 40 patients (7.5%) in the TNK group. Conclusion This phase 2, randomized, multicenter study suggests that intravenous TNK within 4.5–24 hours of onset may be safe and feasible in AIS patients with a DWI-FLAIR mismatch.