This study aims to explore the effects and action mechanisms of the active ingredients in Buyang Huanwu Decoction(BYHWD), namely tetramethylpyrazine(TMP) and hydroxy-safflor yellow A(HSYA), on oxygen-glucose deprivation/reglucose-reoxygenation(OGD/R)-induced inflammation and oxidative stress of microglia(MG). Network pharmacology was used to screen the effective monomer ingredients of BYHWD and determine the safe concentration range for each component. Inflammation and oxidative stress models were established to further screen the best ingredient combination and optimal concentration ratio with the most effective anti-inflammatory and antioxidant effects. OGD/R BV2 cell models were constructed, and BV2 cells in the logarithmic growth phase were divided into a normal group, a model group, an HSYA group, a TMP group, and an HSYA + TMP group. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of inflammatory cytokines such as interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6). Oxidative stress markers, including superoxide dismutase(SOD), nitric oxide(NO), and malondialdehyde(MDA), were also measured. Western blot was used to analyze the protein expression of both inflammation-related pathway [Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)] and oxidative stress-related pathway [nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)]. Immunofluorescence was used to assess the expression of proteins such as inducible nitric oxide synthase(iNOS) and arginase-1(Arg-1). The most effective ingredients for anti-inflammatory and antioxidant effects in BYHWD were TMP and HSYA. Compared to the normal group, the model group showed significantly increased levels of IL-1β, TNF-α, IL-6, NO, and MDA, along with significantly higher protein expression of NF-κB, TLR4, Nrf2, and HO-1 and significantly lower SOD levels. The differences between the two groups were statistically significant. Compared to the model group, both the HSYA group and the TMP group showed significantly reduced levels of IL-1β, TNF-α, IL-6, NO, and MDA, lower expression of NF-κB and TLR4 proteins, higher levels of SOD, and significantly increased protein expression of Nrf2 and HO-1. Additionally, the expression of the M1-type MG marker iNOS was significantly reduced, while the expression of the M2-type MG marker Arg-1 was significantly increased. The results of the HSYA group and the TMP group had statistically significant differences from those of the model group. Compared to the HSYA group and the TMP group, the HSYA + TMP group showed further significant reductions in IL-1β, TNF-α, IL-6, NO, and MDA levels, along with significant reductions in NF-κB and TLR4 protein expression, an increase in SOD levels, and elevated Nrf2 and HO-1 protein expression. Additionally, the expression of the M1-type MG marker iNOS was reduced, while the M2-type MG marker Arg-1 expression increased significantly in the HSYA + TMP group compared to the TMP or HSYA group. The differences in the results were statistically significant between the HSYA + TMP group and the TMP or HSYA group. The findings indicated that the combined use of HSYA and TMP, the active ingredients of BYHWD, can effectively inhibit OGD/R-induced inflammation and oxidative stress of MG, showing superior effects compared to the individual use of either component.
Oxidative Stress/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Animals ; Mice ; Glucose/metabolism* ; Cell Line ; Inflammation/genetics* ; Oxygen/metabolism* ; Pyrazines/pharmacology* ; Microglia/metabolism* ; NF-E2-Related Factor 2/immunology* ; NF-kappa B/immunology* ; Toll-Like Receptor 4/immunology* ; Anti-Inflammatory Agents/pharmacology* ; Humans

This study compared the differences in intestinal absorption characteristics of eleven active components in Rubus multibracteatus(RM) extract(protocatechuic acid, tiliroside, scutellarin, luteoloside, astragalin, epicatechin, catechin, xanthotoxin, p-coumaric acid, caffeic acid, and apigenin-7-O-glucuronide) between normal rats and inflammatory pain model rats using the in-vitro everted intestinal sac model. The RM extract was administered at absorption concentrations of 25.0, 50.0, and 100.0 mg·mL~(-1). The contents of the eleven components in intestinal absorption solution samples were quantified by ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS), and their cumulative absorption(Q) and absorption rate constant(K_a) were calculated to evaluate the absorption characteristics of these components in normal rats and inflammatory pain model rats. The results show that except for catechin, epicatechin, and caffeic acid, the cumulative absorption-time curves of the other eight components(protocatechuic acid, tiliroside, scutellarin, luteoloside, astragalin, xanthotoxin, p-coumaric acid, and apigenin-7-O-glucuronide) exhibit an upward trend without saturation, with correlation coefficients(R~2) all > 0.9, indicating linear absorption. However, the overall absorption of all components is not dose-dependent with increasing concentration, suggesting that their absorption mechanisms are not solely passive diffusion. In both normal and model rats, the jejunum shows the highest absorption for all components except xanthotoxin. The overall absorption of seven components(excluding protocatechuic acid, caffeic acid, apigenin-7-O-glucuronide, and luteoloside) in normal rats is better than that in model rats across all intestinal segments. These findings indicate that the pathological state of inflammatory pain alters the intestinal absorption of RM extract, and its mechanism needs further investigation.
Animals ; Rats ; Intestinal Absorption/drug effects* ; Male ; Rats, Sprague-Dawley ; Drugs, Chinese Herbal/metabolism* ; Disease Models, Animal ; Pain/metabolism* ; Intestines/drug effects* ; Intestinal Mucosa/metabolism*

Objective To investigate the population characteristics,distribution of traditional Chinese medicine(TCM)syndromes and influencing factors of long-term prognosis of diarrhea-predominant irritable bowel syndrome(IBS-D),and to provide evidence for the formulation of intervention program for IBS-D patients.Methods A total of 124 patients with IBS-D admitted to the medical institutions of the project team members from July 2020 to August 2022 were selected.According to the scoring results of IBS Quality of Life Measure(IBS-QOL),the patients were divided into the good prognosis group(81 cases)and the poor prognosis group(43 cases).The distribution of TCM syndromes in patients with IBS-D was explored,and the difference of IBS-QOL scores of the patients between good prognosis group and poor prognosis group was compared.Univariate logistic regression analysis and multivariate logistic regression analysis were used to determine the main risk factors for poor prognosis in patients with IBS-D.Results(1)The analysis of population characteristics showed that there was no significant difference in the proportion of male and female patients with IBS-D.The patients with IBS-D were usually middle-aged,and had a large interval span of the course of disease.The severity of their symptoms was mostly moderate.All of the patients with IBS-D had various degrees of anxiety and depression,and had nutritional imbalance.(2)The distribution of TCM syndromes in the patients with IBS-D were shown as the following:78 cases were identified as liver depression and spleen deficiency type,accounting for 62.90％;26 cases were identified as spleen-qi deficiency type,accounting for 20.97％;20 cases were identified as spleen and kidney yang deficiency type,accounting for 16.13％.(3)Analysis of IBS-QOL score showed that compared with the good prognosis group,the items scores of negative emotion,physical function,behavioral disorder,health status,being fastidious about food,social function,sexual behavior and interpersonal relationship of IBS-QOL in the poor prognosis group were significantly lowered(P＜0.01).(4)The univariate analysis showed that the risk of poor prognosis in patients with IBS-D would be increased by the factors of age,education level,course of disease,severity of symptoms,anxiety state,depression state,TCM syndrome types,Acute Physiology and Chronic Health Evaluation scoring system Ⅱ(APACHE 11)score,complication of neurological diseases,hemoglobin level,albumin level and total protein level(P＜0.01).(5)The multivariate Logistic regression analysis showed that the risk factors for poor prognosis of IBS-D patients involved age,education level below junior high school,the severity of symptoms being severe,Self-Rating Anxiety Scale(SAS)score,Self-Rating Depression Scale(SDS)score,TCM syndrome being liver depression and spleen deficiency type,hemoglobin level,albumin level and total protein level(P＜0.01).Conclusion Most of IBS-D patients exert long-term poor prognosis,and their long-term prognosis is affected by the factors of age,education level,severity of symptoms,anxiety and depression state,nutritional imbalance and TCM syndrome being liver depression and spleen deficiency type.The identification of the risk factors of poor prognosis will provide evidence for the formulation and adjustment of clinical intervention programs.

Objective:To investigate the clinical efficacy of single-incision plus one-port three dimensional (3D) laparoscopic pancreaticoduodenectomy (SILPD+1).Methods:The retrospective cohort study was conducted. The clinicopathological data of 40 patients who underwent 3D laparos-copic pancreaticoduodenectomy in Affiliated Hospital of North Sichuan Medical College from January to October 2023 were collected. There were 24 males and 16 females, aged (63±10)years. Of the 40 patients, 18 cases undergoing SILPD+1 were divided into the SILPD+1 group, and 22 cases under-going conventional five-trocar 3D laparoscopic pancreaticoduodenectomy (CLPD) were divided into the CLPD group. Observation indicators: (1) surgical situations; (2) postoperative situations and complications. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the Mann-Whitney rank sum test. Results:(1) Surgical situa-tions. Seventeen patients of the SILPD+1 group completed surgery successfully, and the rest of one patient with an inflammatory mass of the pancreatic head was converted to open surgery due to unclear boundary with mesenteric blood vessels and severe adhesion of surrounding tissues. All patients of the CLPD group completed surgery successfully, without conversion to open surgery. There was no significant difference in conversion to open surgery between the two groups ( P>0.05), and there was no significant difference in the volume of intraoperative blood loss, intraoperative blood transfusion or operation time ( P>0.05). (2) Postoperative situations and complications. There was no significant difference in tumor diameter, the number of lymph node dissected, the number of positive lymph node, R 0 resection, tumor type, time to postoperative first flatus, time to postopera-tive first intake liquid food, tome to first out-of-bed activity, time to postoperative drainage tube removal, duration of postoperative hospital stay, postoperative bleeding, pancreatic fistula, chylous leakage, delayed gastric emptying, abdominal fluid collection, incision infection, classification of com-plications between the two groups ( P>0.05). Postoperative pain score of the SILPD+1 group and the CLPD group was 5.0(4.5,6.0) and 6.5(6.0,7.0), respectively, showing a significant difference ( Z=-3.61, P<0.05). Both groups of patients had no occurrence of biliary fistula or abdominal infection after surgery, and there was no readmission within 30 days after surgery or no death within 90 days after surgery. Conclusions:Compared with CLPD, SILPD+1 is safe and feasible, with less postoperative pain. While ensuring oncological outcomes, SILPD+1 does not increase surgical time, postoperative hospital stay, or incidence of postoperative complications.

Carnosic acid (CA) is the main phenolic diterpenoid active ingredient in plants such as rosemary and sage, and has antiviral, antioxidant, anti-inflammatory effects and so on, however, its antiviral activity against influenza virus infections was not reported. In this study, antiviral activities against influenza A virus infections of three main bioactive ingredients from rosemary, including rosmarinic acid, CA and ursolic acid, were evaluated using virus titer titration assay, and CA showed remarkable inhibition on influenza H5N1 replication in A549 cells. The antiviral activity of CA was further confirmed and its mechanism of action was investigated using the indirect immunofluorescence assay (IFA), Western blot and real-time fluorescence quantification polymerase chain reaction (qRT-PCR). The results showed that the 50% effective concentration (EC₅₀) of CA against influenza H5N1 in A549 cells and MDCK cells were 4.30 and 3.64 μmol·L^-1, respectively. Meanwhile, CA also showed inhibition on influenza virus 2009panH1N1 (EC₅₀: 10.1 μmol·L^-1) and H3N2 (EC₅₀: 12.8 μmol·L^-1) replications in A549 cells. Mechanistic studies showed that antiviral activity of CA is related to its induction of heme oxygenase-1 (HO-1) in A549 cells and suppression on production of reactive oxygen in H5N1-infected cells.

Humans ; Diabetes Mellitus ; Ketosis ; Magnetic Resonance Imaging

Cardiovascular diseases(CVD) with high morbidity and mortality pose severe threats to human life. Allicin, a main active ingredient of garlic, possesses multiple pharmaceutical activities. It not only exerts cardioprotective effects but also prevents the risk factors for CVD. Allicin exerts cardioprotective effects via a variety of mechanisms, including inhibiting oxidative stress, apoptosis, autophagy, and inflammatory responses, regulating lipid metabolism and gut microbiota, inducing hydrogen sulfide production, and dilating vessels. Despite the valuable cardioprotective effects, the instability of allicin has hindered the basic research and clinical application. This paper reviews the progress in the cardioprotective effects and mechanisms of allicin in the last decade and summarizes the methods to improve the stability of allicin. In addition, this review provides a reference for further research and development of allicin in cardiovascular protection.

Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34⁺⁰ weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.
Infant ; Infant, Newborn ; Humans ; Birth Weight ; Intensive Care Units, Neonatal ; Retrospective Studies ; Tertiary Care Centers ; Infant, Extremely Low Birth Weight ; Gestational Age ; Infant, Extremely Premature ; Sepsis/epidemiology* ; Retinopathy of Prematurity/epidemiology* ; Bronchopulmonary Dysplasia/epidemiology*

This study aimed to explore the potential mechanism of Berberis atrocarpa Schneid. anthocyanin against Alzheimer's disease(AD) based on network pharmacology, molecular docking technology, and in vitro experiments. Databases were used to screen out the potential targets of the active components of B. atrocarpa and the targets related to AD. STRING database and Cytoscape 3.9.0 were adopted to construct a protein-protein interaction(PPI) network and carry out topological analysis of the common targets. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were performed on the target using the DAVID 6.8 database. Molecular docking was conducted to the active components and targets related to the nuclear factor kappa B(NF-κB)/Toll-like receptor 4(TLR4) pathway. Finally, lipopolysaccharide(LPS) was used to induce BV2 cells to establish the model of AD neuroinflammation for in vitro experimental validation. In this study, 426 potential targets of active components of B. atrocarpa and 329 drug-disease common targets were obtained, and 14 key targets were screened out by PPI network. A total of 623 items and 112 items were obtained by GO functional enrichment analysis and KEGG pathway enrichment analysis, respectively. Molecular docking results showed that NF-κB, NF-κB inhibitor(IκB), TLR4, and myeloid differentiation primary response 88(MyD88) had good binding abilities to the active components, and malvidin-3-O-glucoside had the strongest binding ability. Compared with the model group, the concentration of nitric oxide(NO) decreased at different doses of malvidin-3-O-glucoside without affecting the cell survival rate. Meanwhile, malvidin-3-O-glucoside down-regulated the protein expressions of NF-κB, IκB, TLR4, and MyD88. This study uses network pharmacology and experimental verification to preliminarily reveal that B. atrocarpa anthocyanin can inhibit LPS-induced neuroinflammation by regulating the NF-κB/TLR4 signaling pathway, thereby achieving the effect against AD, which provides a theoretical basis for the study of its pharmacodynamic material basis and mechanism.
NF-kappa B ; Alzheimer Disease ; Network Pharmacology ; Anthocyanins ; Berberis ; Lipopolysaccharides ; Molecular Docking Simulation ; Myeloid Differentiation Factor 88 ; Neuroinflammatory Diseases ; Toll-Like Receptor 4 ; I-kappa B Proteins

【Objective】 To analyze the hepatitis B virus (HBV) infection data of blood donors from 18 domestic blood stations, so as to investigate the HBV infection situation of blood donors. 【Methods】 The positive rate of HBV and its distribution characteristics of regions, the percentage of HBsAg+ ELISA in first-time vs repeated blood donors, and the percentage of HBsAg-/HBV DNA+ blood donors of 18 domestic blood stations during 2017 to 2020 were collected from the Working Platform for Practice Comparison of Blood Centers, and the HBV infection among blood donors were statistically analyzed. 【Results】 From 2017 to 2020, the positive rate of HBV in blood donors among 18 domestic blood stations was 13.48/10 000-144.02/10 000, with the average HBV positive rate in eastern, central and western region at 26.14/10 000, 51.98/10 000 and 41.00/10 000, respectively. The HBsAg+ rate by ELISA among first-time and repeated blood donors was 14.55/10 000-305.39/10 000 vs 1.04/10 000-87.43/10 000 The HBsAg-/HBV DNA+ yield was 1.80/10 000-35.31/10 000. 【Conclusion】 The distribution of HBV infection in blood donors has regional characteristics, and HBV prevalence was low in repeated blood donors. HBsAg ELISA combined with HBV DNA detection can better ensure blood safety.