Objective To screen the targets related to the metabolic enzymes involved in the cholesterol synthesis pathway that inhibits the polarization of macrophages towards M1 phenotype,and verify the intervention effects and underlying mechanisms in colorectal cancer cells.Methods Mouse colorectal cancer MC38 cells were divided into control group(si-NC)and experimental groups(the expression of enzymes in cholesterol synthesis pathway was interfered with siRNA for corresponding targets).RT-qPCR was used to detect the mRNA levels of corresponding targets in MC38 cells after transfection.After peritoneal macrophages were extracted from male C57BL/6 mice(6 weeks old,weighing 13～18 g),the macrophages were then treated with the conditioned media of MC38 cells transfected with different siRNAs for 48 h.RT-qPCR was employed to detect the mRNA levels of IL-1β,IL-6 and TNF-α in the macrophages so as to evaluate the effect of the culture media on the M1 polarization.MC38 cells were divided into control groups(OE-NC and sh-NC),farnesyl-diphosphate farnesyltransferase 1(FDFT1)overexpression group(OE-FDFT1)and FDFT1 knockdown group(sh-FDFT1).RT-qPCR was applied to detect the mRNA expression of FDFT1,and Western blotting was conducted to measure the protein level of FDFT1.C57BL/6 mice were subjected randomly to construct a subcutaneous tumor-bearing model and a model of intraperitoneal metastatic tumor(n=5)respectively.The growth of tumor mass was then measured.Flow cytometry was used to observe the proliferation and apoptosis of MC38 cells,and Trans well assay to detect migration ability of MC38 cells.Five C57BL/6 macrophage-depleted mice(established with injection of clodronate liposome suspension through tail vein)received intraperitoneal implantation to construct a metastasis model,and then the obtained tumor masses were then weighted.Results Compared with MC38 cells after si-NC transfection,the mRNA levels of corresponding targets in MC38 cells in the experimental groups were significantly reduced(P＜0.05).Significant increases were found in the mRNA levels of IL-1β,IL-6 and TNF-α of the macrophages with FDFT1 interference than the control cells(P＜0.05).There were no statistical differences in the proliferation,apoptosis and migration of MC38 cells in the control group(OE-NC and sh-NC)and the cells of the FDFT1 overexpression group and FDFT1 knockdown group(P＞0.05).In both the subcutaneous tumor-bearing model and the model of intraperitoneal metastatic tumor,the mass weight was significantly heavier in the OE-FDFT1 group than the OE-NC group(P＜0.01),and was notably smaller in the sh-FDFT1 group than the sh-NC group(P＜0.01).For the macrophage-depleted mouse tumor model,no remarkable change was observed in the tumor weight between the OE-FDFT1 group and the OE-NC group as well as the sh-FDFT1 group and the sh-NC group.Conclusion FDFT1,the metabolic enzyme in the cholesterol synthesis pathway of colorectal cancer tumor cells,is a potential target for tumor immunotherapy targeting macrophages,which promotes tumor progression by regulating macrophages.

BACKGROUND: Recent studies have provided compelling evidence that exposure to brominated flame retardants (BFRs) can adversely affect human health. We aim to explore the potential impact of BFRs on adiposity and central obesity. METHODS: Data from the National Health and Nutrition Examination Surveys (NHANES) cycles conducted between 2009 and 2014 was used to study the connections between variables. After filtering, we analyzed a sample of 4,110 adults aged 20 years and above. Our goal was to examine the potential association between BFRs and consequences and investigate the part played by oxidative stress and inflammatory markers as intermediaries. To achieve this, we used advanced statistical methods such as weighted quantile sum (WQS) regression, quantile-based g-computation (QGC), and the Bayesian kernel machine regression (BKMR). RESULTS: The findings showed that among the examined chemicals, exposure to PBDE85 (weight: 41%), PBDE100 (24%), and PBB153 (23%) may be the dominant contributors to general obesity risk. Upon controlling for all variables that could impact the results, it was found that the QGC outcomes indicated a positive correlation between exposure to mixtures of brominated flame retardants and the occurrence of abdominal obesity (OR = 1.187, 95% CI: 1.056-1.334, p = 0.004). Significant contributions were made by PBDE85 (52%), PBB153 (27%), and PBDE100 (21%). Mediation analysis shows that lymphatic cells (LC) and albumin (ALB) partially mediate the link between brominated flame retardants and obesity. The results of BKMR are generally consistent with those of WQS and QGC. CONCLUSION At a population level, our research has revealed a noteworthy correlation between BFRs and obesity. However, further investigation is required through prospective cohort studies and in-depth mechanistic exploratory studies.
Humans ; Flame Retardants/adverse effects* ; Oxidative Stress/drug effects* ; Adult ; Male ; Female ; Middle Aged ; Inflammation/epidemiology* ; Obesity/chemically induced* ; Biomarkers/blood* ; Nutrition Surveys ; Mediation Analysis ; Young Adult ; United States/epidemiology* ; Environmental Exposure/adverse effects* ; Aged ; Environmental Pollutants/adverse effects* ; Halogenated Diphenyl Ethers/adverse effects*

Objective:To construct a nomogram model for predicting frailty in elderly hypertensive patients, and to evaluate the discrimination and consistency of the model.Methods:A total of 317 patients with essential hypertension who were admitted to Hebei Eighth People′s Hospital from February 2021 to June 2022 were taken, they were divided into modeling group (190 cases) and verification group (127 cases) according to the proportion of 6∶4, the patients in the modeling group were divided into the asthenic group (45 cases) and the non asthenic group (145 cases) according to whether the patients in the modeling group had asthenia. The nomograph model was constructed based on the results of Logistic analysis.Results:The age, obesity or overweight ratio, diabetes ratio and systolic blood pressure in the frail group were significantly higher than those in the non-frail group: (76.25 ± 3.64)years vs.(70.44 ± 3.82) years, 51.11%(23/45) vs. 24.83%(36/145), 46.67%(21/45) vs. 17.24%(25/145), (156.46 ± 18.64) mmHg (1 mmHg = 0.133 kPa) vs. (143.25 ± 12.38) mmHg, and the mini-nutrition assessment summary form (MNA-SF) score was significantly lower than that in the non-frail group: (11.45 ± 2.06) scores vs. (13.12 ± 1.22) scores, there were statistical differences ( P<0.05). Logistic results showed that age, body mass index, diabetes, and systolic blood pressure were the risk factors for frailty ( P<0.05). The receiver operating characteristic (ROC) curve evaluation showed that the area under the curve (AUC) in the modeling group was 0.998, and AUC in the validation group was 0.954. The Hosmer-Lemeshow goodness of fit test showed: modeling group χ2 = 6.18, P = 0.627; validation group χ2 = 6.58, P = 0.582. Conclusions:The nomogram prediction model of frailty risk in elderly hypertensive patients has good consistency and differentiation

Objective:To explore the relationship between the hypertensive snowbirds′ length of migratory stay and their blood pressure control and blood pressure levels.Methods:This study was a cross-sectional study. A population of snowbirds with hypertension was recruited between October and November 2022, and a structured questionnaire was used to collect their self-measured blood pressure and length of stay in Hainan Province. The blood pressure control status is determined based on self-measured blood pressure. According to the self-measured blood pressure to determine whether the blood pressure was well controlled. The associations between snowbirds′ length of stay and their blood pressure control as well as their self-measured blood pressure were analyzed using restricted cubic splines.Results:A total of 362 research subjects were included, 169(46.7%) of whom were male, and their age was (69.7±7.0) years old. The participants′ self-measured systolic blood pressure and diastolic blood pressure were (129.1±16.2) mmHg (1 mmHg=0.133 kPa) and (78.9±10.1) mmHg, respectively. Overall, 174 (48.1%) participants attained adequate blood pressure control. The median length of stay in Wuzhishan City was 7(6, 7) months. There was an inverted U-shaped association between snowbirds′ length of stay and blood pressure control (overall: P=0.023; nonlinearity: P=0.014), where participants with a length of stay of 7 months had the highest rate of blood pressure control. There is a U-shaped curve relationship between length of stay and systolic blood pressure (overall: P=0.001; nonlinearity: P=0.033), and a linear negative correlation with diastolic blood pressure ( β=-1.19, P=0.003). Conclusions:Compared with hypertensive snowbirds with too long or too short lengths of stay, snowbirds who stayed in Wuzhishan City for seven months have better blood pressure control, and systolic blood pressure is also lower.

Objective This study is focused on ultrasound multimodality examination,which refers to the combined use of three ultrasound examination modalities,ultrasound(US),acoustic radiation force impulse(ARFI)imaging,and contrast-enhanced ultrasound(CEUS).The purpose of this study is to analyze the value of applying ultrasound multimodality examination in the differential diagnosis of benign and malignant breast non-mass-like lesions(NMLs).Methods Cases of breast NMLs were analyzed retrospectively,and the nature of all the lesions was verified by pathological examination.Based on the gray-scale ultrasound image characteristics,the cases were classified into types Ⅰto Ⅴ,and type Ⅰ and type Ⅱ were further classified into 4 subtypes,Ⅰa,Ⅰ b,Ⅱ a,and Ⅱ b,according to whether there was also calcification,and the proportion of malignant cases in each subtype was statistically analyzed.Logistic regression models of US,US+ARFI,US+CEUS,and US+ARFI+CEUS for the diagnosis of malignant cases were established,ROC curves were drawn,the area under the curve(AUC)was calculated,and comparisons were made accordingly.The detection rate of malignant NMLs without calcification(atypical malignant NMLs)by the combination examination of US,ARFI,and CEUS was analyzed.Results A total of 407 cases were included in the study.All subjects were female,aged 22 to 81 years,with the average age being(47.0±1 1.0)years.There were 220 benign cases and 187 malignant cases.Ranked from the highest to the lowest,the malignancy proportion of the different types wasⅠb＞Ⅱb＞Ⅲ＞V＞Ⅰa＞Ⅱa＞Ⅳ.The malignant proportion of the low echo area with calcification was significantly higher than that of the lesions without calcification.The AUC(95％confidence interval[CI])for diagnosing malignant cases with the logistic regression models of US,US+ARFI,US+CEUS,and US+ARFI+CEUS were 0.895(0.862-0.927),0.908(0.878-0.937),0.921(0.893-0.948),and 0.927(0.902-0.952),respectively.Comparison of the AUC of the 4 regression models showed significant differences(P＜0.001).The detection rate of US for NMLs without calcification was 80.7％.When US was used in combination with ARFI and CEUS,86.4％of the malignant NMLs lesions without calcification could be detected if the lesion CEUS score was 4 or 5 points or if shear-wave velocity(SWV)≥4.28 m/s.Conclusion Breast NMLs with calcification show high risks of malignancy,and a pathological examination is always recommended for a conclusive diagnosis.Ultrasound multimodality examination can improve the diagnostic accuracy of breast NML without calcification.

BACKGROUND: Preliminary studies have indicated that Shexiang Baoxin Pill (MUSKARDIA) has a coronary artery dilation effect and increases the coronary blood flow, relieving the symptoms of angina. This study aimed to evaluate the benefit of MUSKARDIA on patients with stable coronary artery disease (CAD) and diabetes mellitus (DM). METHODS: This was a subgroup analysis of a multicenter, randomized, placebo-controlled phase IV trial. CAD patients with a medical history of DM or baseline fasting blood glucose (FBG) ≥7.0 mmol/L were grouped according to the treatment (standard therapy plus MUSKARDIA or placebo). The primary outcome was major adverse cardiovascular events (MACEs), which was the composite outcome of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. The secondary outcome was the composite outcome of all-cause death, non-fatal myocardial infarction, non-fatal stroke, hospitalization for unstable angina or heart failure, and coronary angioplasty. RESULTS: MACEs occurred in 2.6% (9/340) and 4.8% (18/376) of patients in the MUSKARDIA and placebo groups, respectively ( P  = 0.192). Secondary composite outcome was significantly less frequent with MUSKARDIA than with placebo (15.3% [52/340] vs . 22.6% [85/376], P  = 0.017). Risk of MACEs (hazard ratio [HR] = 0.69, 95% confidence interval [CI]: 0.31-1.57) was comparable between two groups. In patients with uncontrolled DM (≥4 measurements of FBG ≥7 mmol/L in five times of follow-up), the risk of secondary outcome was significantly lower with MUSKARDIA (5/83, 6.0%) than with placebo (15/91, 16.5%) (HR = 0.35, 95%CI: 0.13-0.95). CONCLUSION: As an add-on to standard therapy, MUSKARDIA shows a trend of reduced MACEs in patients with stable CAD and DM. Furthermore, MUSKARDIA may reduce the frequency of all-cause death, hospitalization, and coronary angioplasty in this population, especially in those with uncontrolled DM. TRIAL REGISTRATION ChiCTR.org.cn, ChiCTR-TRC-12003513.
Humans ; Coronary Artery Disease/complications* ; Diabetes Mellitus, Type 2/drug therapy* ; Myocardial Infarction/complications* ; Stroke/epidemiology*

Objective To investigate the effects of Osteoking on hyperglycemia and regulating gut microbiota in db/db mice.Methods Wildtype mice were used as the control group,and db/db mice were randomly divided into model and Osteoking groups.After intragastric administration for 12 weeks,fasting blood glucose and serum glycosylated hemoglobin and insulin levels were measured,changes in intestinal microflora were determined,and functional pathways related to intestinal microflora in mice were predicted by 16S rDNA sequencing.Results Compared with the model group,Osteoking decreased fasting blood glucose(P<0.01),serum glycosylated hemoglobin(P<0.01),and the insulin resistance index(P<0.01),and increased insulin content(P<0.01)in db/db mice.Osteoking increased the abundance of beneficial intestinal microflora and decreased the abundance of harmful bacteria.Moreover,the abundance of Marvinbryantia was increased.Osteoking alleviated the decrease in metabolism of D-arginine and D-ornithine,sphingolipid,and galactose metabolism(P<0.05)and inhibited lysine degradation,the sulfur relay system,and propanoate metabolism(P<0.05).Conclusions Osteoking has hypoglycemic properties and improves the intestinal microflora imbalance in db/db mice.

Objective:To explore the current situation of nursing human caring in hospital wards and analyze its influencing factors, so as to facilitate the development of nursing human caring practice.Methods:From July to November 2022, a total of 107 hospitals were surveyed through stratified convenience sampling method, and 4 072 ward nursing managers were recruited to finish the general information questionnaire and the ward nursing human caring status questionnaire. The general information included the region, class and type of the hospital, etc. The ward nursing human caring status questionnaire included 38 items in 5 dimensions of nursing human caring system and process, humanistic quality and training of nursing staff, humanistic environment and facilities, human caring procedures and measures, and human caring quality evaluation and improvement, with a full score of 190 points. Descriptive statistics were used to analyze the general data, independent samples t-test, ANOVA and correlation analysis were used to analyze the factors influencing the current status of nursing human caring in the ward, while multiple linear regression analysis was used to conduct a multivariate analysis. Results:The score of nursing human caring in hospital wards was 156.91±27.78. Whether the hospital had carried out nursing human caring pilot(demonstration) wards, whether the ward had previously been a hospital nursing human caring pilot(demonstration) nursing unit, the type of ward, and whether nursing managers had participated in human caring training were the influencing factors of the implication of nursing humanistic caring in wards( P<0.05). Conclusions:The practice of nursing human caring in hospital wards is at a good level, but needs to be further strengthened. Nursing managers should take systematically strategies to promote the development of nursing human caring practice.

Objective:To investigate the effects of sustained low-efficiency hemodialysis combined with hemoperfusion on routine blood indicators and inflammatory factors in patients with sepsis-induced acute kidney injury.Methods:Eighty-six patients with sepsis-induced acute kidney injury who received treatment in Yantai Laiyang Central Hospital from April 2018 to April 2021 were included in this study. They were randomly divided into an observation group and a control group, with 43 cases in each group. All patients received conventional supportive treatment. The control group received continuous renal replacement therapy and the observation group received sustained low-efficiency dialysis combined with hemoperfusion. Before and after treatment, routine blood indicators [hemoglobin (Hb), white blood cell (WBC) count, platelet (PLT) count, albumin (Alb)], inflammatory factors [interleukin-6 (IL-6), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), procalcitonin PCT)], renal function indicators [serum creatinine (Scr), blood urea nitrogen (BUN)], The Acute Physiology and Chronic Health Evaluation (APACHE) II score, length of hospital stay, and 28-day mortality rate were compared between the two groups.Results:Before treatment, there were no significant differences in Hb, WBC count, PLT count, Alb, IL-6, CRP, TNF-α, PCT, Scr, BUN, and APACHE II score between the two groups ( t = 0.04, 0.95, 0.23, 0.67, 1.54, 0.75, 0.98, 0.23, 1.04, 0.44, 0.07, all P > 0.05). After treatment, serum levels of Hb and Alb in each group were significantly increased compared with those before treatment. After treatment, serum levels of Hb and Alb in the observation group were (105.29 ± 15.80) g/L, (39.25 ± 7.87) g/L, respectively, which were significantly higher than (98.55 ± 12.93) g/L and (33.38 ± 7.29) g/L in the control group ( t = 2.16, 3.58, both P < 0.05). After treatment, WBC count, PLT count, IL-6, CRP, TNF-α, PCT, Scr, and BUN levels, and APACHE II score in each group were significantly decreased compared with those before treatment. After treatment, WBC count, PLT count, IL-6, CRP, TNF-α, PCT, Scr, and BUN levels, and APACHE II score in the observation group were (10.28 ± 1.87) × 10 9/L, (129.32 ± 14.79) × 10 9/L, (59.00 ± 12.77) μg/L, (22.41 ± 5.01) mg/L, (28.41 ± 4.77) μg/L, (18.41 ± 2.78) μg/L, (162.01 ± 21.04) μmol/L, (7.38 ± 1.17) mmol/L, (11.28 ± 3.60) points, respectively, which were significantly lower than (12.32 ± 2.27) × 10 9/L, (137.39 ± 18.30) × 10 9/L, (79.35 ± 14.36) μg/L, (29.31 ± 6.37) mg/L, (34.33 ± 5.38) μg/L, (22.32 ± 3.35) μg/L, (184.06 ± 24.03) μmol/L, (9.87 ± 1.66) mmol/L, (14.65 ± 3.38) points in the control group ( t = 4.54, 2.24, 6.94, 5.58, 5.39, 5.89, 4.52, 8.03, 4.47, all P < 0.05). The length of intensive care unit stay in the observation group was significantly shorter than that in the control group [(11.63 ± 2.18) days vs. (14.07 ± 2.71) days, t = 4.60, P < 0.05]. There was no significant difference in 28-day mortality rate between the two groups ( χ2 = 1.36, P > 0.05). Conclusion:Sustained low-efficiency dialysis combined with hemoperfusion is effective on sepsis-induced acute kidney injury. The combined therapy can improve routine blood indicators, inhibit inflammatory reactions, promote renal function recovery, and decrease the mortality rate to a certain degree.