Objective:To develop a comprehensive training curriculum to enhance the effective implementation of the national initiative promoting dementia care and prevention.Methods:The Delphi method was utilized in an expert consultation that included 44 participants.The initial draft of the training curriculum was developed based on the current state of dementia care and prevention.This draft was subsequently evaluated for its importance, feasibility, and ease of dissemination.Experts offered targeted modifications and additional recommendations.Results:The recovery rate of the expert consultation questionnaire was 95.5%, with a recovery validity rate of 90.9%.The expert authority coefficient was 0.91, and the Kendall's coordination coefficient( W)for expert scoring was 0.316, with a significance level of P<0.001.Four course modules were ultimately identified: the foundation of memory clinic work, the complete management practice skills, group counseling techniques for caregivers, and practical skills for caregivers.The importance of these modules was rated with a mean of 4.92 to 4.95, and the coefficient of variation ranged from 0.044 to 0.063.Each module had a mean value of 4.92 to 4.95, with a coefficient of variation of 0.044 to 0.063; the mean value for practicality was between 4.78 and 4.92, with a coefficient of variation of 0.055 to 0.098; and the mean value for ease of generalization ranged from 4.28 to 4.65, with a coefficient of variation from 0.140 to 0.203.The four modules comprised a total of 55 specific course content items, with the mean value for each item ranging from 4.76 to 5.00 and a coefficient of variation from 0.000 to 0.121.The mean value of usefulness assigned to each entry ranged from 4.55 to 4.98, with a coefficient of variation from 0.031 to 0.150.Additionally, the mean value for ease of propagation assigned to each entry ranged from 4.00 to 4.83, with a coefficient of variation from 0.091 to 0.245. Conclusions:The developed training curriculum, which comprises four course modules and 55 items, demonstrated consistently high levels of importance, practicality, and ease of dissemination.These findings indicate that the curriculum is well-aligned with national initiatives aimed at enhancing dementia care and prevention.

Five new flavan-4-ol glycosides jixueqiosides A-E (1-5) and two new flavan glycosides jixueqiosides F and G (6 and 7), along with twelve known flavan-4-ol glycosides (8-19), were isolated from the roots of Pronephrium penangianum. Comprehensive spectral analyses, X-ray single-crystal diffraction, and theoretical electronic circular dichroism (ECD) calculations established structures and absolute configurations. A single crystal structure of flavan-4-ol glycoside (14) was reported for the first time, while the characteristic ECD and NMR data for all isolated flavan-4-ol glycosides (1-5 , 8-19) were analyzed, establishing a set of empirical rules. Activity screening of these isolates showed that 8 and 9 could inhibit the proliferation of MDA-MB-231 and MCF-7 cells with IC₅₀ values of 7.93 ? 2.85 ?mol?L^-1 and 5.87 ? 1.58 ?mol?L^-1 (MDA-MB-231), and 2.21 ? 1.38 ?mol?L^-1 and 3.52 ? 1.55 ?mol?L^-1 (MCF-7), respectively. Western blotting and flow cytometry analyses demonstrated that 8 and 9 dose-dependently induced apoptosis in MDA-MB-231 cells by up-regulating BAX, activating caspase-3 and down-regulating BCL-2. Additionally, compound 8 affected autophagy-related proteins, increasing the ratio of LC3-II/LC3-I and Beclin-1 levels to inhibit MDA-MB-231 cell proliferation. Moreover, anti-inflammatory studies indicated that 2, 3, 7, 13, 14, and 18 moderately inhibited tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), and nitric oxide (NO) release.
Humans ; Plant Roots/chemistry* ; Glycosides/isolation & purification* ; Anti-Inflammatory Agents/isolation & purification* ; Flavonoids/isolation & purification* ; Cell Proliferation/drug effects* ; Antineoplastic Agents, Phytogenic/isolation & purification* ; Molecular Structure ; Apoptosis/drug effects* ; Cell Line, Tumor ; Tumor Necrosis Factor-alpha/immunology* ; Drugs, Chinese Herbal/pharmacology* ; Interleukin-6/immunology* ; Animals ; Mice

OBJECTIVES: To study the molecular mechanisms of LDH-loaded si-NEAT1 for regulating paclitaxel resistance and tumor-associated macrophage (TAM) polarization in breast cancer. METHODS: qRT-PCR and Western blotting were used to detect the expression of lncRNA NEAT1, miR-133b, and PD-L1 in breast cancer SKBR3 cells and paclitaxel-resistant SKBR3 cells (SKBR3-PR). The effects of transfection with si-NEAT1 and miR-133b mimics on MRP, MCRP and PD-L1 expressions and cell proliferation, migration and apoptosis were investigated using qRT-PCR, Western blotting, scratch and Transwell assays, and flow cytometry. Rescue experiments were conducted using si-NEAT1 and miR-133b inhibitor. Human THP-1 macrophages were cultured in the presence of conditioned media (CM) derived from SKBR3 and SKBR3-PR cells with or with si-NEAT1 transfection for comparison of IL-4-induced macrophage polarization by detecting the surface markers. LDH@si-NEAT1 nanocarriers were constructed, and their effects on MRP, MCRP and PD-L1 expressions and cell behaviors of the tumor cells were examined. THP-1 cells were treated with the CM from LDH@si-NEAT1-treated tumor cells, and the changes in their polarization were assessed. RESULTS: SKBR3-PR cells showered significantly upregulated NEAT1 and PD-L1 expressions and lowered miR-133b expression as compared with their parental cells. Transfection with si-NEAT1 and miR-133b mimics inhibited viability, promoted apoptosis and enhanced MRP and BCRP expressions in SKBR3-PR cells. NEAT1 knockdown obvious upregulated miR-133b and downregulated PD-L1, MRP and BCRP expressions. The CM from SKBR3-PR cells obviously promoted M2 polarization of THP-1 macrophages, which was significantly inhibited by CM from si-NEAT1-transfected cells. Treatment with LDH@si-NEAT1 effectively inhibited migration and invasion, promoted apoptosis, and reduced MRP, BCRP and PD-L1 expressions in the tumor cells. The CM from LDH@si-NEAT1-treated SKBR3-PR cells significantly downregulated Arg-1, CD163, IL-10, and PD-L1 and upregulated miR-133b expression in THP-1 macrophages. CONCLUSIONS LDH@si-NEAT1 reduces paclitaxel resistance of breast cancer cells and inhibits TAM polarization by targeting the miR-133b/PD-L1 axis.
Humans ; MicroRNAs/genetics* ; RNA, Long Noncoding/genetics* ; Paclitaxel/pharmacology* ; Breast Neoplasms/metabolism* ; Drug Resistance, Neoplasm ; B7-H1 Antigen/metabolism* ; Cell Line, Tumor ; Female ; Tumor-Associated Macrophages ; Apoptosis ; Cell Proliferation ; Macrophages ; Cell Movement

Objective To investigate the impact of recent rhythmic interventions on the depth of sedation during anesthesia induction in patients undergoing general anesthesia with remazolam toluene sulfonate.Methods Patients aged 18～65 years who underwent elective surgery under general anesthesia were selected and divided into a day group(7:00～19:00)and a night group(19:00～7:00 the following day)based on the start time of anesthesia induction.Each group comprised 70 patients,further subdivided into five equal dose groups of remazolam toluene sulfonate at 0.11,0.13,0.16,0.18,and 0.22 mg/kg,with 14 patients in each subgroup.The Modified Observer's Assessment of Alertness/Sedation(MOAA/S)score and Bispectral Index(BIS)value were recorded 3 minutes post-administration,and the correlation coefficient between these two parameters was calculated.The induction dose and unit body weight dose of remazolam toluene sulfonate were documented when the MOAA/S score was≤1.Addition-ally,the induction dose of remazolam for both day and night groups as well as for patients of different genders was recorded.The half effective dose(ED50),95％effective dose(ED95),and 95％confidence interval(CI)for both the day and night groups were also calculated.Results When MOAA/S≤1,the induced dose of remazolam in the night group(12.34±3.51)mg was significantly lower than that in the day group(13.98±4.21)mg.Additionally,the dose per unit body weight of remazolam in the night group(0.20±0.049)mg/kg was also significantly lower than that in the day group(0.22±0.056)mg/kg.Statistically significant differences were observed in the ED50 and ED95 values of remazolam between the day and night groups(P<0.05).The correlation coefficient between BIS and MOAA/S was 0.902(95％CI:0.876～0.925)in the day group and 0.905(95％CI:0.879～0.929)in the night group,indicating a strong correlation between MOAA/S and BIS in both groups.However,there was no significant difference in the correlation coefficients between the two groups(P>0.05).The correlation coefficients between BIS and MOAA/S were 0.763(95％CI:0.726～0.799)in the daytime group and 0.777(95％CI:0.739～0.808)in the nighttime group.In a separate analysis,the correlation coefficients were 0.768(95％CI:0.723～0.804)for the day-time group and 0.771(95％CI:0.723～0.811)for the nighttime group.A strong correlation was observed between MOAA/S and BIS in both male and female patients during both day and night,with no significant difference in corre-lation coefficients between groups(P>0.05).However,BIS values were significantly lower in the nighttime group compared to the daytime group(P<0.05).Additionally,male patients required a higher total induced dose of rem-azolam than female patients during both day and night,with this difference being statistically significant(P<0.05).Furthermore,female patients exhibited a significant decrease in BIS values at night(P<0.05).Conclusions Recent studies have shown that circadian rhythm significantly influences anesthesia-induced sedation in patients undergoing general anesthesia with remazolam toluenesulfonate.Specifically,the sedation effect is more pronounced in nighttime procedures,and there is a notable gender difference,with female patients exhibiting better sedation outcomes during nighttime surgeries.

Objective To investigate the impact of recent rhythmic interventions on the depth of sedation during anesthesia induction in patients undergoing general anesthesia with remazolam toluene sulfonate.Methods Patients aged 18～65 years who underwent elective surgery under general anesthesia were selected and divided into a day group(7:00～19:00)and a night group(19:00～7:00 the following day)based on the start time of anesthesia induction.Each group comprised 70 patients,further subdivided into five equal dose groups of remazolam toluene sulfonate at 0.11,0.13,0.16,0.18,and 0.22 mg/kg,with 14 patients in each subgroup.The Modified Observer's Assessment of Alertness/Sedation(MOAA/S)score and Bispectral Index(BIS)value were recorded 3 minutes post-administration,and the correlation coefficient between these two parameters was calculated.The induction dose and unit body weight dose of remazolam toluene sulfonate were documented when the MOAA/S score was≤1.Addition-ally,the induction dose of remazolam for both day and night groups as well as for patients of different genders was recorded.The half effective dose(ED50),95％effective dose(ED95),and 95％confidence interval(CI)for both the day and night groups were also calculated.Results When MOAA/S≤1,the induced dose of remazolam in the night group(12.34±3.51)mg was significantly lower than that in the day group(13.98±4.21)mg.Additionally,the dose per unit body weight of remazolam in the night group(0.20±0.049)mg/kg was also significantly lower than that in the day group(0.22±0.056)mg/kg.Statistically significant differences were observed in the ED50 and ED95 values of remazolam between the day and night groups(P<0.05).The correlation coefficient between BIS and MOAA/S was 0.902(95％CI:0.876～0.925)in the day group and 0.905(95％CI:0.879～0.929)in the night group,indicating a strong correlation between MOAA/S and BIS in both groups.However,there was no significant difference in the correlation coefficients between the two groups(P>0.05).The correlation coefficients between BIS and MOAA/S were 0.763(95％CI:0.726～0.799)in the daytime group and 0.777(95％CI:0.739～0.808)in the nighttime group.In a separate analysis,the correlation coefficients were 0.768(95％CI:0.723～0.804)for the day-time group and 0.771(95％CI:0.723～0.811)for the nighttime group.A strong correlation was observed between MOAA/S and BIS in both male and female patients during both day and night,with no significant difference in corre-lation coefficients between groups(P>0.05).However,BIS values were significantly lower in the nighttime group compared to the daytime group(P<0.05).Additionally,male patients required a higher total induced dose of rem-azolam than female patients during both day and night,with this difference being statistically significant(P<0.05).Furthermore,female patients exhibited a significant decrease in BIS values at night(P<0.05).Conclusions Recent studies have shown that circadian rhythm significantly influences anesthesia-induced sedation in patients undergoing general anesthesia with remazolam toluenesulfonate.Specifically,the sedation effect is more pronounced in nighttime procedures,and there is a notable gender difference,with female patients exhibiting better sedation outcomes during nighttime surgeries.

Objective:To develop a comprehensive training curriculum to enhance the effective implementation of the national initiative promoting dementia care and prevention.Methods:The Delphi method was utilized in an expert consultation that included 44 participants.The initial draft of the training curriculum was developed based on the current state of dementia care and prevention.This draft was subsequently evaluated for its importance, feasibility, and ease of dissemination.Experts offered targeted modifications and additional recommendations.Results:The recovery rate of the expert consultation questionnaire was 95.5%, with a recovery validity rate of 90.9%.The expert authority coefficient was 0.91, and the Kendall's coordination coefficient( W)for expert scoring was 0.316, with a significance level of P<0.001.Four course modules were ultimately identified: the foundation of memory clinic work, the complete management practice skills, group counseling techniques for caregivers, and practical skills for caregivers.The importance of these modules was rated with a mean of 4.92 to 4.95, and the coefficient of variation ranged from 0.044 to 0.063.Each module had a mean value of 4.92 to 4.95, with a coefficient of variation of 0.044 to 0.063; the mean value for practicality was between 4.78 and 4.92, with a coefficient of variation of 0.055 to 0.098; and the mean value for ease of generalization ranged from 4.28 to 4.65, with a coefficient of variation from 0.140 to 0.203.The four modules comprised a total of 55 specific course content items, with the mean value for each item ranging from 4.76 to 5.00 and a coefficient of variation from 0.000 to 0.121.The mean value of usefulness assigned to each entry ranged from 4.55 to 4.98, with a coefficient of variation from 0.031 to 0.150.Additionally, the mean value for ease of propagation assigned to each entry ranged from 4.00 to 4.83, with a coefficient of variation from 0.091 to 0.245. Conclusions:The developed training curriculum, which comprises four course modules and 55 items, demonstrated consistently high levels of importance, practicality, and ease of dissemination.These findings indicate that the curriculum is well-aligned with national initiatives aimed at enhancing dementia care and prevention.

OBJECTIVE To investigate the effect of polymorphisms of solute carrier organic anion transporter family, member 1B3(SLCO1B3) gene on the pharmacodynamics of mycophenolate mofetil(MMF) in patients with lupus nephritis. METHODS Patients with lupus nephritis who were treated in Jieyang People’s Hospital from September 2019 to April 2021 were selected. All subjects were treated with MMF for at least 12 months, or discontinued due to poor efficacy. The efficacy of MMF was evaluated. The SLCO1B3 334T>G/699G>A(rs4149117/rs7311358) genotype was detected using Agena MassARRAY®, and the correlation between gene polymorphisms and MMF pharmacodynamics was analyzed using SPSS 25.0 software. RESULTS The genotype frequencies of SLCO1B3 334T>G/699G>A were in Hardy-Weinberg equilibrium. The probability of poor MMF treatment effect of 334GG/699AA carriers was significantly higher than that of 334TT/699AA and 334TG/699GA carriers(P<0.001); Logistic regression showed that both 334GG/699AA and urine protein>2.5 g·(24 h)−1 were the risk factors for poor MMF treatment[OR=4.038(1.731, 9.420), P<0.001; OR=4.157(1.705, 10.137), P=0.002]. Combined analysis showed that patients with both 334GG/699AA genotype and urine protein>2.5 g·(24 h)−1 were at higher risk for poor efficacy[OR=8.563(3.301, 22.216), P<0.001]. CONCLUSION SLCO1B3 334T>G/699G>A is related to the efficacy of MMF treating lupus nephritis, and 334GG/699AA carriers are more likely to result in poor efficacy.

Humans ; Asthma/drug therapy* ; Biological Therapy

Objective:To analyze the therapeutic effect of adding interleukin (IL)-4Rα monoclonal antibody (duplizumab) to patients with multiple types of inflammatory diseases.Methods:Six patients with multiple types of inflammatory diseases who started to use duplizumab from August 2020 were enrolled. The changes of airway inflammation, lung function, sinuses computed tomography (CT), Asthma Control Questionnaire-5 (ACQ-5), Sino-Nasal Outcome Test-22 (SNOT-22), Pennsylvania Smell Identification Test (UPSIT) and Numerical Rating Scale (NRS) score before and after duplizumab treatment were retrospectively analyzed. All patients were treated with doprilumab for more than 5 months.Results:4 of the 6 patients had both severe asthma and chronic sinusitis, and 2 patients had both severe asthma, chronic sinusitis and atopic dermatitis. After treatment, the pulmonary function of 6 patients was improved, the levels of sputum eosinophils, exhaled nitric oxide and total IgE were decreased (all P<0.05), and the scores of paranasal sinus CT, ACQ-5, SNOT-22 and UPSIT were significantly improved (all P<0.05). However, 3 patients had increased peripheral blood eosinophils during the treatment. Conclusions:Duplizumab is effective for a variety of type 2 inflammatory diseases without obvious adverse reactions, and the peripheral eosinophils may increase during the treatment.

Objective:To explore the application effect of quantitative exercise nursing intervention based on WeChat platform in the recovery of patients with lower extremity arteriosclerosis obliterans.Methods:A total of 128 patients with lower extremity arteriosclerosis obliterans who were treated in Department of Vascular Surgery of the First Affiliated Hospital of Zhengzhou University were selected from June 2019 to February 2021. They were randomly divided into the control group and the observation group, with 64 cases in each group. The control group used routine nursing, while the observation group used the quantitative exercise nursing intervention based on the WeChat platform. Ankle-brachial index (ABI) and walking ability [Walking Impairment Questionnaire (WIQ) ] were compared between the two groups. The quality of life and nursing satisfaction of patients in two groups were investigated by World Health Organization Quality of Life Assessment Brief Scale (WHOQOL-BREF) and Newcastle Satisfaction with Nursing Scale (NSNS) .Results:After the intervention, scores of ABI, WIQ, WHOQOL-BREF and nursing satisfaction of the observation group were higher than those of the control group, and the differences were statistically significant ( P<0.05) . Conclusions:Quantitative exercise nursing intervention based on the WeChat platform can promote the functional rehabilitation of patients with lower extremity arteriosclerosis obliterans and improve quality of life and satisfaction of patients, which is worthy of clinical application.