Working memory is an executive memory process that includes encoding, maintenance, and retrieval. These processes can be modulated by transcranial alternating current stimulation (tACS) with sinusoidal waves. However, little is known about the impact of the rate of current change on working memory. In this study, we aimed to investigate the effects of two types of tACS with different rates of current change on working memory performance and brain activity. We applied a randomized, single-blind design and divided 81 young participants who received triangular wave tACS, sinusoidal wave tACS, or sham stimulation into three groups. Participants performed n-back tasks, and electroencephalograms were recorded before, during, and after active or sham stimulation. Compared to the baseline, working memory performance (accuracy and response time) improved after stimulation under all stimulation conditions. According to drift-diffusion model analysis, triangular wave tACS significantly increased the efficiency of non-target information processing. In addition, compared with sham conditions, triangular wave tACS reduced alpha power oscillations in the occipital lobe throughout the encoding period, while sinusoidal wave tACS increased theta power in the central frontal region only during the later encoding period. The brain network connectivity results showed that triangular wave tACS improved the clustering coefficient, local efficiency, and node degree intensity in the early encoding stage, and these parameters were positively correlated with the non-target drift rate and decision starting point. Our findings on how tACS modulates working memory indicate that triangular wave tACS significantly enhances brain network connectivity during the early encoding stage, demonstrating an improvement in the efficiency of working memory processing. In contrast, sinusoidal wave tACS increased the theta power during the later encoding stage, suggesting its potential critical role in late-stage information processing. These findings provide valuable insights into the potential mechanisms by which tACS modulates working memory.
Humans ; Memory, Short-Term/physiology* ; Male ; Female ; Young Adult ; Transcranial Direct Current Stimulation/methods* ; Brain/physiology* ; Adult ; Electroencephalography ; Single-Blind Method

Objective:To compare the value of different quantification methods for intraoperative hypotension in predicting postoperative acute kidney injury (AKI) in patients undergoing off-pump coronary artery bypass grafting (OPCABG).Methods:The medical records of American Society of Anesthesiologists Physical Status classification Ⅲ-Ⅳ patients of either sex, aged 18-80 yr, with a body mass index of 18-30 kg/m 2, scheduled for elective OPCABG, were retrospectively collected at Tianjin Chest Hospital from September 2021 to October 2023. Intraoperative hypotension was quantified using the methods such as the number of occurrence, average decrease in magnitude, duration, and the area under the threshold (mean arterial pressure <65 mmHg, 1 mmHg = 0.133 kPa). Patients were divided into AKI group and non-AKI group based on the occurrence of AKI within 7 days postoperatively. The extended logistic regression model was used to adjust for confounding factors, and the receiver operating characteristic curves were plotted to compare the accuracy of different methods for intraoperative hypotension in predicting postoperative AKI. Results:The results of multivariate logistic regression analysis showed that the frequency of hypotension ( OR=1.03, 95% confidence interval [ CI] 1.01-1.05, P=0.010), duration of hypotension ( OR=1.04, 95% CI 1.01-1.08, P=0.007), and area under the threshold ( OR=1.03, 95% CI 1.01-1.06, P=0.023) were risk factors for postoperative AKI. The areas under the curve for the quantification methods predicting the occurrence of postoperative AKI within 7 days, including the duration of hypotension, area under the threshold, frequency of hypotension, and mean decrease in blood pressure, were 0.751, 0.652, 0.647 and 0.513, respectively. Conclusions:The duration of hypotension, area under the threshold and frequency of hypotension are independent risk factors for postoperative AKI in patients undergoing OPCABG. The duration of hypotension has a higher accuracy in predicting the occurrence of postoperative AKI.

Objective We aimed to evaluate the efficacy and safety of Shengxuebao Mixture in the treatment of cancer-related anemia(CRA)presenting with syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood.Methods A randomized,double-blind,placebo-controlled,multicenter clinical trial was conducted.Eligible patients with malignant tumors meeting the inclusion and exclusion criteria were enrolled from 26 hospitals,including Dongzhimen Hospital,Beijing University of Chinese Medicine,Xiaogan Central Hospital,and Yangzhou Hospital of Traditional Chinese Medicine,from June 1,2022,to September 30,2024.Patients were allocated 1:1 to either the experimental group receiving Shengxuebao Mixture or the control group receiving its simulator(placebo)using a block randomization method under double-blind conditions.Both groups received 15 mL orally three times daily for 28 consecutive days.The primary efficacy indicators included the hemoglobin(Hb)improvement rate(RHb)and the traditional Chinese medicine(TCM)syndrome improvement rate(RTCM)at week 4 of treatment.The secondary efficacy indicators encompassed Hb and red blood cell(RBC)count,Karnofsky Performance Status(KPS)score,TCM syndrome score,individual TCM symptom scores,and changes in each of these indicators compared to the baseline period at weeks 2,4,and 6 of treatment.Safety evaluations were conducted at week 4 of treatment.Results A total of 239 patients were enrolled,with 225 cases included in the Full Analysis Set(FAS)(109 in the experimental group vs.116 control group),163 in the Per Protocol Set(PPS)(77 vs.86),and 225 in the Safety Set(SS)(109 vs.116).Baseline characteristics between groups showed no significant differences.Significant differences were observed between the experimental and control groups in RHb at week 4(FAS:49.51%vs.35.24%,P<0.05;PPS:53.25%vs.36.05%,P<0.05)and RTCM at week 4(FAS:61.54%vs.39.62%,P<0.01;PPS:64.94%vs.40.70%,P<0.01).At weeks 2,4,and 6,the experimental group showed greater improvements in Hb and RBC counts than the control group.Additionally,the TCM syndrome scores were lower in the experimental group than in the control group at these time points.Except for week 2 in PPS,the KPS improvement was better in the experimental group than in the control group(P<0.05).The experimental group also demonstrated a greater reduction in scores for individual TCM symptoms such as spiritlessness and weakness,poor appetite and reduced food intake at weeks 4 and 6 compared to the control group(P<0.05,P<0.01).Furthermore,the reduction in vertigo score was more pronounced in the experimental group at week 6(P<0.01).For the score of pale and lusterless complexion,only in the PPS was the reduction from baseline more significant in the experimental group than in the control group at weeks 4 and 6(P<0.05).No significant differences were observed between the experimental and control groups in the incidence of all adverse events or drug-related adverse reactions.Conclusion Shengxuebao Mixture demonstrates significant efficacy in patients with CRA presenting syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood,effectively increasing Hb levels,ameliorating TCM syndromes,alleviating clinical symptoms,and enhancing functional status,with no significant difference in adverse drug reactions compared to the placebo.

Objective:To compare the value of different quantification methods for intraoperative hypotension in predicting postoperative acute kidney injury (AKI) in patients undergoing off-pump coronary artery bypass grafting (OPCABG).Methods:The medical records of American Society of Anesthesiologists Physical Status classification Ⅲ-Ⅳ patients of either sex, aged 18-80 yr, with a body mass index of 18-30 kg/m 2, scheduled for elective OPCABG, were retrospectively collected at Tianjin Chest Hospital from September 2021 to October 2023. Intraoperative hypotension was quantified using the methods such as the number of occurrence, average decrease in magnitude, duration, and the area under the threshold (mean arterial pressure <65 mmHg, 1 mmHg = 0.133 kPa). Patients were divided into AKI group and non-AKI group based on the occurrence of AKI within 7 days postoperatively. The extended logistic regression model was used to adjust for confounding factors, and the receiver operating characteristic curves were plotted to compare the accuracy of different methods for intraoperative hypotension in predicting postoperative AKI. Results:The results of multivariate logistic regression analysis showed that the frequency of hypotension ( OR=1.03, 95% confidence interval [ CI] 1.01-1.05, P=0.010), duration of hypotension ( OR=1.04, 95% CI 1.01-1.08, P=0.007), and area under the threshold ( OR=1.03, 95% CI 1.01-1.06, P=0.023) were risk factors for postoperative AKI. The areas under the curve for the quantification methods predicting the occurrence of postoperative AKI within 7 days, including the duration of hypotension, area under the threshold, frequency of hypotension, and mean decrease in blood pressure, were 0.751, 0.652, 0.647 and 0.513, respectively. Conclusions:The duration of hypotension, area under the threshold and frequency of hypotension are independent risk factors for postoperative AKI in patients undergoing OPCABG. The duration of hypotension has a higher accuracy in predicting the occurrence of postoperative AKI.

Objective We aimed to evaluate the efficacy and safety of Shengxuebao Mixture in the treatment of cancer-related anemia(CRA)presenting with syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood.Methods A randomized,double-blind,placebo-controlled,multicenter clinical trial was conducted.Eligible patients with malignant tumors meeting the inclusion and exclusion criteria were enrolled from 26 hospitals,including Dongzhimen Hospital,Beijing University of Chinese Medicine,Xiaogan Central Hospital,and Yangzhou Hospital of Traditional Chinese Medicine,from June 1,2022,to September 30,2024.Patients were allocated 1:1 to either the experimental group receiving Shengxuebao Mixture or the control group receiving its simulator(placebo)using a block randomization method under double-blind conditions.Both groups received 15 mL orally three times daily for 28 consecutive days.The primary efficacy indicators included the hemoglobin(Hb)improvement rate(RHb)and the traditional Chinese medicine(TCM)syndrome improvement rate(RTCM)at week 4 of treatment.The secondary efficacy indicators encompassed Hb and red blood cell(RBC)count,Karnofsky Performance Status(KPS)score,TCM syndrome score,individual TCM symptom scores,and changes in each of these indicators compared to the baseline period at weeks 2,4,and 6 of treatment.Safety evaluations were conducted at week 4 of treatment.Results A total of 239 patients were enrolled,with 225 cases included in the Full Analysis Set(FAS)(109 in the experimental group vs.116 control group),163 in the Per Protocol Set(PPS)(77 vs.86),and 225 in the Safety Set(SS)(109 vs.116).Baseline characteristics between groups showed no significant differences.Significant differences were observed between the experimental and control groups in RHb at week 4(FAS:49.51%vs.35.24%,P<0.05;PPS:53.25%vs.36.05%,P<0.05)and RTCM at week 4(FAS:61.54%vs.39.62%,P<0.01;PPS:64.94%vs.40.70%,P<0.01).At weeks 2,4,and 6,the experimental group showed greater improvements in Hb and RBC counts than the control group.Additionally,the TCM syndrome scores were lower in the experimental group than in the control group at these time points.Except for week 2 in PPS,the KPS improvement was better in the experimental group than in the control group(P<0.05).The experimental group also demonstrated a greater reduction in scores for individual TCM symptoms such as spiritlessness and weakness,poor appetite and reduced food intake at weeks 4 and 6 compared to the control group(P<0.05,P<0.01).Furthermore,the reduction in vertigo score was more pronounced in the experimental group at week 6(P<0.01).For the score of pale and lusterless complexion,only in the PPS was the reduction from baseline more significant in the experimental group than in the control group at weeks 4 and 6(P<0.05).No significant differences were observed between the experimental and control groups in the incidence of all adverse events or drug-related adverse reactions.Conclusion Shengxuebao Mixture demonstrates significant efficacy in patients with CRA presenting syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood,effectively increasing Hb levels,ameliorating TCM syndromes,alleviating clinical symptoms,and enhancing functional status,with no significant difference in adverse drug reactions compared to the placebo.

This study aims to prepare altrenogest extended-release tablets,evaluate their quality and establish a content determination method.The hydrophilic gel skeleton type,dosage and core thick-ness of altrenogest extended-release tablets were used as the investigating factors,and the release degree of the tablets was used as the investigating index,the prescription process of altrenogest ex-tended-release tablets was optimized by one-factor screening and central combinatorial design re-sponse surface method,and quality evaluation was carried out,the in vitro release model was es-tablished,and a high-performance liquid chromatography(HPLC)assay method was set up for the determination of altrenogest extended-release tablets.The results showed that the optimal pre-scription of altrenogest extended-release tablets was 2％as the main drug,70％as the solubilizer,0.5％as the lubricant,19.1％as the filler,8.4％as the hydrophilic gel skeleton material,and the thickness of the tablets was 3.8 mm.The in vitro drug release conformed to the Higuchi model,and the altrenogest showed a good linear relationship with the R2=0.999 98 in the range of 10-80 mg/L.The optimized process for the extended-release tablets was stable and had a good quality.The extended-release tablets were stable and had significant slow-release effect.The HPLC method is accurate and reliable and can be used for the determination of altrenogest in extended-release tablets.

Albendazole sulfoxide and ivermectin compound pouring agent were prepared with dime-thyl sulfoxide and 1,2-propanediol as solvents.The central composite design response surface method was used to optimize the formula of pouring agent.Franz diffusion cell method was used to investigate the transdermal performance of pouring agent in vitro.The permeation amounts of the two drugs were determined by HPLC.The best formula of pouring agent was ivermectin 0.5％,al-bendazole sulfoxide 5％,dimethyl sulfoxide 52％,propylene glycol 39％,and the rest was 100％anhydrous ethanol.The cumulative permeation amounts of ivermectin and albendazole sulfoxide were up to 20.78 μg/cm2 and 249.02 μg/cm2,respectively.The in vitro release model of the two drugs accords with the first-order kinetic equation.There is a good linear relationship between al-bendazole sulfoxide and ivermectin in the range of 1-100 mg/L and the peak area.The precision and stability RSD of the two methods are less than 2％.The preparation process of albendazole sul-foxide compound pouring agent is simple,stable and easy to pour.The established HPLC method is simple and accurate,and can be used for the determination of albendazole sulfoxide and ivermectin in pouring agent.

Periodontitis is a chronic inflammatory disease marked by a dysregulated immune microenvironment, posing formidable challenges for effective treatment. The disease is characterized by an altered glucose metabolism in macrophages, specifically an increase in aerobic glycolysis, which is linked to heightened inflammatory responses. This suggests that targeting macrophage metabolism could offer a new therapeutic avenue. In this study, we developed an immunometabolic intervention using quercetin (Q) encapsulated in bioadhesive mesoporous polydopamine (Q@MPDA) to treat periodontitis. Our results demonstrated that Q@MPDA could reprogram inflammatory macrophages to an anti-inflammatory phenotype (i.e., from-M1-to-M2 repolarization). In a murine periodontitis model, locally administered Q@MPDA reduced the presence of inflammatory macrophages, and decreased the levels of inflammatory cytokines (IL-1β and TNF-α) and reactive oxygen species (ROS) in the periodontium. Consequently, it alleviated periodontitis symptoms, reduced alveolar bone loss, and promoted tissue repair. Furthermore, our study revealed that Q@MPDA could inhibit the glycolysis of inflammatory macrophages while enhancing oxidative phosphorylation (OXPHOS), facilitating the shift from M1 to M2 macrophage subtype. Our findings suggest that Q@MPDA is a promising treatment for periodontitis via immunometabolic rewiring.

Objective:To evaluate the effect of ulinastatin on the postoperative pulmonary complications (PPCs) in the patients undergoing off-pump coronary artery bypass grafting (OPCABG).Methods:Medical records from patients scheduled for elective OPCABG from September 2021 to August 2023 were retrospectively collected. The patients were divided into ulinastatin and control groups based on the intraoperative use of ulinastatin. Confounding factors were adjusted using propensity score matching and an extended Cox proportional hazards model. The primary outcome was the development of PPCs within 30 days after surgery, and secondary outcomes included length of stay in intensive care unit, length of hospital stay and occurrence of other adverse events.Results:A total of 1 532 patients were included in this cohort study, and 585 cases (38.2%) experienced PPCs. Compared with control group, the incidence of PPCs was significantly decreased (before matching: 42.7% vs. 35.2%, P=0.004; after matching: 42.2% vs. 35.6%, P=0.033), the incidence of acute kidney injury was decreased and no significant differences were found in the length of stay in intensive care unit, length of hospital stay and incidence of other adverse events in ulinastatin group ( P>0.05). In the extended Cox proportional hazard model before and after adjustment for confounding factors, the risk of PPCs was significantly reduced after the use of ulinastatin ( HR value before adjustment was 0.81, 95% confidence interval [ CI] 0.67-0.99, P=0.004; the HR value after adjustment was 0.79, 95% CI 0.65-0.96, P=0.022). The risk of PPCs was significantly decreased in patients aged >65 yr and at high risk of PPCs after using ulinastatin ( HR=0.667, 95% CI 0.542-0.821, P<0.001; hR value was 0.641, 95% CI 0.516-0.812, P<0.001). Conclusions:The intraoperative use of ulinastatin is helpful in decreasing the risk of PPCs in patients undergoing OPCABG.

Objective:To analyse the core genes and mechanisms of brain injury induced by isoflurane using the bioinformatics analysis.Methods:The GSE358 and GSE359 isoflurane anesthesia data set were downloaded from the GEO database. Debatch processing, screening of differentially expressed genes (DEGs), construction and analysis of protein-protein interaction network, and functional enrichment analysis were performed. The gene expression heat map was plotted, and the diseases most related to the core genes were found by Comparative Toxicogenomics Database analysis.Results:A total of 500 DEGs were identified. According to the results of Gene Ontology analysis, they were mainly enriched in the response to foreign stimuli, the response to hypoxia, the apoptotic process, and the inflammatory response in the Biological Process analysis. In Cellular Component analysis, they were mainly enriched in the cytoplasm, extracellular space, and neuronal projections. In Molecular Function analysis, they focused on protein binding and sequence specific DNA binding in transcriptional regulatory regions. In Kyoto Encyclopedia of Genes and Genomes analysis, they were mainly enriched in phosphatidylinositol 3-kinase/protein kinase B signaling pathway, neuroactive ligand-receptor interaction, Toll-like receptor (TLR) signaling pathway, apoptosis and cAMP signaling pathway. Six core genes (interferon gamma [IFN-γ], TLR4, nuclear factor kappa B inhibitor alpha [NFKBIA], interleukins-1α [IL-1α], proto-oncogene fos[Fos]), CCAAT enhancer binding protein β [CEBPB]) were obtained by protein-protein interaction network. Comparative Toxicogenomics Database analysis revealed that core genes (IFN-γ, IL-1α, Fos) were associated with neurological disorders, brain injury, hyperalgesia, drug-related side effects and adverse reactions, neurodegeneration, etc. The inference score could reflect the degree of association between the gene and the disease, among which IFN-γ, IL-1α and Fos had higher inference scores in brain damage.Conclusions:IFN-γ, IL-1α, Fos, TLR4, NFKBIA and CEBPB are six core genes associated with isoflurane-induced brain injury, and these genes may play important roles in immune and inflammatory responses.