Objective:This study investigates the influence of the apolipoprotein E ε4(APOE ε4)genotype on the relationship between glucose-lipid metabolism disorders and diabetes-related cognitive impairment(DCI).Methods:A case-control study was conducted involving 891 patients with type 2 diabetes mellitus(T2DM)with a mean age of(62.1±13.8)years, all of whom underwent elective surgery at the First Hospital of Shanxi Medical University between January 2017 and December 2022.Among these participants, 229 were diagnosed with DCI(case group), while 662 were cognitively normal(control group).Routine clinical information was collected, and peripheral venous blood samples were analyzed for glycated hemoglobin(HbA1c)and blood lipid levels.The single nucleotide polymorphisms rs429358 and rs7412 were analyzed to determine the presence of the APOE ε4 genotype.Stepwise Logistic regression was employed to identify independent risk factors for DCI, and subgroup analyses were performed to evaluate the effect of the APOE ε4 genotype on the relationship between HbA1c and blood lipid levels in relation to DCI risk. Results:Among all patients, female gender( OR=1.915, 95% CI: 1.393-2.631, P<0.001), longer duration of T2DM( OR=1.169, 95% CI: 1.087-1.257, P<0.001), elevated triglycerides( OR=1.161, 95% CI: 1.041-1.294, P=0.007), and being an APOE ε4 carrier( OR=1.638, 95% CI: 1.115-2.405, P=0.012)were identified as independent risk factors for developing DCI.High levels of low-density lipoprotein(LDL)were found to be independently associated with an increased risk of DCI specifically in APOE ε4 carriers( OR=1.408, 95% CI: 1.060-1.870, P=0.018), but not in non-APOE ε4 carriers( P>0.05).In contrast, elevated HbA1c was independently associated with a higher risk of DCI in non-APOE ε4 carriers( OR=1.220, 95% CI: 1.040-1.430, P=0.014), but not in APOE ε4 carriers( P>0.05).Additionally, elevated triglycerides were independently linked to an increased risk of DCI across the entire sample and within each APOE ε4 genotype subgroup. Conclusions:The APOE genotype plays a significant role in modulating the relationship between dyslipidemia and the risk of developing DCI.This highlights the critical importance of lipid metabolism disorders and APOE risk genes in both the development and progression of DCI.These findings offer valuable insights for future clinical and mechanistic studies focused on DCI.

BACKGROUND: Periodontitis is a severe chronic inflammatory disease, whose traditional systemic antimicrobial therapy faces great limitations. In-situ gels provide an effective solution as an emerging local drug delivery system. METHODS: In this study, the novel thermosensitive poloxamer/carbopol in-situ gels loaded with 20 lmol/L quercetin for the treatment of periodontitis were prepared by cold method. Thirteen batches of in-situ gels based on two independent factors (X1 : poloxamer 407 and X2 : carbopol 934P) were designed and optimized by the statistical method of central composite design (CCD). The transparency, pH, injectability, viscosity, gelation temperature, gelation time, elasticity modulus, degradation rate and in-vitro drug release studies of the batches were evaluated, and the percentage of drug release in the first hour, the time required for 90% drug release, gelation temperature, and gelation time were selected as dependent variables. RESULTS: These two independent factors significantly affected the four dependent variables (p < 0.05). The optimization result displayed that the optimized concentration of poloxamer 407 was 20.84% (w/v), and carbopol 934P was 0.5% (w/v). The optimized formulation showed a clear appearance (++), acceptable injectability (Pass), viscosity(151,798 mPa s), gelation temperature (36 °C), gelation time (213 s), preferable cell viability and cell proliferation, conformed to first-order release kinetics, and had a significant antibacterial effect. CONCLUSIONS The article demonstrates the great potential of the quercetin in-situ gel as an effective treatment for periodontitis.

BACKGROUND: Periodontitis is a severe chronic inflammatory disease, whose traditional systemic antimicrobial therapy faces great limitations. In-situ gels provide an effective solution as an emerging local drug delivery system. METHODS: In this study, the novel thermosensitive poloxamer/carbopol in-situ gels loaded with 20 lmol/L quercetin for the treatment of periodontitis were prepared by cold method. Thirteen batches of in-situ gels based on two independent factors (X1 : poloxamer 407 and X2 : carbopol 934P) were designed and optimized by the statistical method of central composite design (CCD). The transparency, pH, injectability, viscosity, gelation temperature, gelation time, elasticity modulus, degradation rate and in-vitro drug release studies of the batches were evaluated, and the percentage of drug release in the first hour, the time required for 90% drug release, gelation temperature, and gelation time were selected as dependent variables. RESULTS: These two independent factors significantly affected the four dependent variables (p < 0.05). The optimization result displayed that the optimized concentration of poloxamer 407 was 20.84% (w/v), and carbopol 934P was 0.5% (w/v). The optimized formulation showed a clear appearance (++), acceptable injectability (Pass), viscosity(151,798 mPa s), gelation temperature (36 °C), gelation time (213 s), preferable cell viability and cell proliferation, conformed to first-order release kinetics, and had a significant antibacterial effect. CONCLUSIONS The article demonstrates the great potential of the quercetin in-situ gel as an effective treatment for periodontitis.

BACKGROUND: Periodontitis is a severe chronic inflammatory disease, whose traditional systemic antimicrobial therapy faces great limitations. In-situ gels provide an effective solution as an emerging local drug delivery system. METHODS: In this study, the novel thermosensitive poloxamer/carbopol in-situ gels loaded with 20 lmol/L quercetin for the treatment of periodontitis were prepared by cold method. Thirteen batches of in-situ gels based on two independent factors (X1 : poloxamer 407 and X2 : carbopol 934P) were designed and optimized by the statistical method of central composite design (CCD). The transparency, pH, injectability, viscosity, gelation temperature, gelation time, elasticity modulus, degradation rate and in-vitro drug release studies of the batches were evaluated, and the percentage of drug release in the first hour, the time required for 90% drug release, gelation temperature, and gelation time were selected as dependent variables. RESULTS: These two independent factors significantly affected the four dependent variables (p < 0.05). The optimization result displayed that the optimized concentration of poloxamer 407 was 20.84% (w/v), and carbopol 934P was 0.5% (w/v). The optimized formulation showed a clear appearance (++), acceptable injectability (Pass), viscosity(151,798 mPa s), gelation temperature (36 °C), gelation time (213 s), preferable cell viability and cell proliferation, conformed to first-order release kinetics, and had a significant antibacterial effect. CONCLUSIONS The article demonstrates the great potential of the quercetin in-situ gel as an effective treatment for periodontitis.

BACKGROUND: Periodontitis is a severe chronic inflammatory disease, whose traditional systemic antimicrobial therapy faces great limitations. In-situ gels provide an effective solution as an emerging local drug delivery system. METHODS: In this study, the novel thermosensitive poloxamer/carbopol in-situ gels loaded with 20 lmol/L quercetin for the treatment of periodontitis were prepared by cold method. Thirteen batches of in-situ gels based on two independent factors (X1 : poloxamer 407 and X2 : carbopol 934P) were designed and optimized by the statistical method of central composite design (CCD). The transparency, pH, injectability, viscosity, gelation temperature, gelation time, elasticity modulus, degradation rate and in-vitro drug release studies of the batches were evaluated, and the percentage of drug release in the first hour, the time required for 90% drug release, gelation temperature, and gelation time were selected as dependent variables. RESULTS: These two independent factors significantly affected the four dependent variables (p < 0.05). The optimization result displayed that the optimized concentration of poloxamer 407 was 20.84% (w/v), and carbopol 934P was 0.5% (w/v). The optimized formulation showed a clear appearance (++), acceptable injectability (Pass), viscosity(151,798 mPa s), gelation temperature (36 °C), gelation time (213 s), preferable cell viability and cell proliferation, conformed to first-order release kinetics, and had a significant antibacterial effect. CONCLUSIONS The article demonstrates the great potential of the quercetin in-situ gel as an effective treatment for periodontitis.

BACKGROUND: Periodontitis is a severe chronic inflammatory disease, whose traditional systemic antimicrobial therapy faces great limitations. In-situ gels provide an effective solution as an emerging local drug delivery system. METHODS: In this study, the novel thermosensitive poloxamer/carbopol in-situ gels loaded with 20 lmol/L quercetin for the treatment of periodontitis were prepared by cold method. Thirteen batches of in-situ gels based on two independent factors (X1 : poloxamer 407 and X2 : carbopol 934P) were designed and optimized by the statistical method of central composite design (CCD). The transparency, pH, injectability, viscosity, gelation temperature, gelation time, elasticity modulus, degradation rate and in-vitro drug release studies of the batches were evaluated, and the percentage of drug release in the first hour, the time required for 90% drug release, gelation temperature, and gelation time were selected as dependent variables. RESULTS: These two independent factors significantly affected the four dependent variables (p < 0.05). The optimization result displayed that the optimized concentration of poloxamer 407 was 20.84% (w/v), and carbopol 934P was 0.5% (w/v). The optimized formulation showed a clear appearance (++), acceptable injectability (Pass), viscosity(151,798 mPa s), gelation temperature (36 °C), gelation time (213 s), preferable cell viability and cell proliferation, conformed to first-order release kinetics, and had a significant antibacterial effect. CONCLUSIONS The article demonstrates the great potential of the quercetin in-situ gel as an effective treatment for periodontitis.

BACKGROUND: Red-cell transfusion is critical for surgery during the peri-operative period; however, the transfusion threshold remains controversial mainly owing to the diversity among patients. The patient's medical status should be evaluated before making a transfusion decision. Herein, we developed an individualized transfusion strategy using the West-China-Liu's Score based on the physiology of oxygen delivery/consumption balance and designed an open-label, multicenter, randomized clinical trial to verify whether it reduced red cell requirement as compared with that associated with restrictive and liberal strategies safely and effectively, providing valid evidence for peri-operative transfusion. METHODS: Patients aged >14 years undergoing elective non-cardiac surgery with estimated blood loss > 1000 mL or 20% blood volume and hemoglobin concentration <10 g/dL were randomly assigned to an individualized strategy, a restrictive strategy following China's guideline or a liberal strategy with a transfusion threshold of hemoglobin concentration <9.5 g/dL. We evaluated two primary outcomes: the proportion of patients who received red blood cells (superiority test) and a composite of in-hospital complications and all-cause mortality by day 30 (non-inferiority test). RESULTS: We enrolled 1182 patients: 379, 419, and 384 received individualized, restrictive, and liberal strategies, respectively. Approximately 30.6% (116/379) of patients in the individualized strategy received a red-cell transfusion, less than 62.5% (262/419) in the restrictive strategy (absolute risk difference, 31.92%; 97.5% confidence interval [CI]: 24.42-39.42%; odds ratio, 3.78%; 97.5% CI: 2.70-5.30%; P <0.001), and 89.8% (345/384) in the liberal strategy (absolute risk difference, 59.24%; 97.5% CI: 52.91-65.57%; odds ratio, 20.06; 97.5% CI: 12.74-31.57; P <0.001). No statistically significant differences were found in the composite of in-hospital complications and mortality by day 30 among the three strategies. CONCLUSION: The individualized red-cell transfusion strategy using the West-China-Liu's Score reduced red-cell transfusion without increasing in-hospital complications and mortality by day 30 when compared with restrictive and liberal strategies in elective non-cardiac surgeries. TRIAL REGISTRATION ClinicalTrials.gov, NCT01597232.
Humans ; Adult ; Postoperative Complications ; Erythrocyte Transfusion/adverse effects* ; Blood Transfusion ; Hospitals ; Hemoglobins/analysis*

Purpose: In non-metastatic prostate cancer (nmPCa) setting, it is important to early identify the patients at risk of biochemical recurrence (BCR) for immediate postoperative intervention. Our study aimed to evaluate the potential clinical utility of circulating tumor DNA (ctDNA) for predicting disease recurrence. Materials and Methods: This real-world observational study evaluated 161 cases of nmPCa undergoing next-generation sequencing at our institution. A total of 139 ctDNA samples and 31 biopsied tumor tissue underwent genomic profiling. The study endpoint was BCR after radical prostatectomy. Relationships between the ctDNA status and the biochemical progression-free survival (bPFS) were analyzed by log-rank test and multivariate Cox regression. Results: Of 161 enrolled patients, 19 (11.8%) harbored deleterious alterations in NCOR2, followed by BRCA2 (3.7%), ATR (2.5%), and CDK12 (2.5%). Of available pre-operative blood samples (n=139), ctDNA was detectable in 91 (65.5%). Until last follow-up, 56 of 68 patients (85.3%) with detectable ctDNA had achieved BCR, whereas only eight of 39 patients (20.5%) with undetectable ctDNA had achieved BCR. Patients who had undetectable ctDNA experienced significantly longer bPFS compared with those who had detectable ctDNA (not available vs. 8.2 months; hazard ratio, 0.14; p < 0.01). Pre-operative ctDNA status was a significant prognostic factor of disease recurrence. Conclusion Pre-operative ctDNA detection could identify patients at high risk of recurrence and has the potential to inform immediate postoperative interventions, but these approaches remain to be validated in prospective studies. ctDNA studies can provide insights into accurate monitoring and precise treatment rather than simply following routine clinical care.

Objective To investigate effects of human postures on flow characteristics of iliac vein compression syndrome. Methods The numerical model of iliac vein was reconstructed from CT images of a typical patient with pelvic-type iliac vein compression syndrome with collateral veins. Based on the computational fluid dynamics method, the non-Newtonian model and the porous media model were adopted to describe effects of abnormal structures on blood flow and acquire the wall shear stress and pressure of iliac vein. The discrete phase model was used to study the residence conditions of erythrocytes under three human postures. Results The pressure gradient at two ends of the compressive region was lowest under lying state, while the iliac vein showed a high pressure under sitting and walking states. The local maximum wall shear stresses under three postures were found at narrow segment of the collateral vein and convergence region of two flows of right iliac vein. The maximum shear stress was largest under lying state and smallest under sitting state. The blood residence time of 52.2 s in the left iliac vein was the longest under sitting state. The residence time of 14.8 s was shortest under lying state. The blood residence time was 23.8 s under walking state. Conclusions Porous media model used to simulate the effect of abnormal structures was highly consistent with the angiography data. The venous hypertension under sitting and walking states was consistent with the clinical results, and the lying state could relieve the hypertensive condition. In terms of wall shear stress and blood residence time in iliac vein, the continual change between three human postures would cause endothelial damage and blood flow stasis alternately, thus increase the risk of thrombosis.

Objective To apply the concept of evidence-based nursing to the practice of non-invasive ventilation,and to introduce the method of using self-made pressure-resistant cap cotton cover and its application effect.Methods Fifty patients on non-invasive ventilation admitted to intensive care unit (ICU) of Harrison International Peace Hospital Affiliated to Hebei Medical University from September 2017 to April 2018 were enrolled as observation group.By retrieved the relevant literature at home and abroad to look for clinical evidence,the concept of evidence-based nursing care program was formulated and implemented,and self-made pressure-resistant cap cotton cover was used to prevent facial pressure sores in patients on non-invasive ventilation.Forty non-invasive ventilation patients admitted from January to August in 2017 were enrolled as the historical control group,and conventional nursing was conducted by using traditional hydrocolloid dressings to prevent pressure ulcers.The incidence of facial pressure ulcers,ocular complications,dressing replacement time and cost were compared between the two groups.Results All patients were enrolled in the final analysis.The incidence of pressure ulcers in the observation group was significantly lower than that in the control group [4.0％ (2/50) vs.22.5％ (9/40),P ＜ 0.05],and the incidences of ocular complications such as eyelid swelling [2.0％ (1/50) vs.5.0％ (2/40)],conjunctival congestion [2.0％ (1/50) vs.5.0％ (2/40)] and irritant keratitis [0％ (0/50) vs.7.5％ (3/40)] were also significantly lower than those in the control group (P ＜ 0.05).Because the pressure-resistant cap cotton cover made by ourselves was easy to be replaced at any time,the interval time of dressing change in the observation group was significantly shorter than that in the control group (minutes:1.5 ± 0.5 vs.2.0 ± 0.5,P ＜ 0.05).In addition it could be cleaned,used alternately,and the cost was low,so the dressing cost in the observation group was significantly lower than that in the control group (Yuan:30±10 vs.123±20,P ＜ 0.01).Conclusion The application of self-made pressure-resistant cap cotton cover could obviously reduce the occurrence of complications such as facial pressure sores in patients on non-invasive ventilation.