BACKGROUND: Huaier granule is an important medicinal fungus extract widely used in cancer treatment. Previous retrospective studies have reported its effectiveness in breast cancer patients, but the imbalanced baseline characteristics of participants could have biased the results. Therefore, this retrospective study aimed to examine the efficacy of Huaier granule on the prognosis of breast cancer patients. METHODS: In this single-center cohort study, breast cancer patients diagnosed and treated at the Guangdong Provincial Hospital of Chinese Medicine between 2009 and 2017 were selected. The data were retrospectively analyzed and divided into two groups according to whether the patients received Huaier granules. The propensity score matching (PSM) method was used to eliminate selection bias. The disease-free survival (DFS) and overall survival (OS) for these groups were compared using the Kaplan-Meier method and the Cox regression. RESULTS: This study included 214 early invasive breast cancer patients, 107 in the Huaier group and 107 in the control group. In the Kaplan-Meier analysis, the 2-year and 5-year DFS rates were significantly different in the Huaier group and control group (hazard ratio [HR], 0.495; 95% confidence interval [CI], 0.257-0.953; P = 0.023). The 2-year and 5-year OS rates were also significantly different (HR, 0.308; 95% CI, 0.148-0.644; P = 0.001). On multivariable Cox regression, Huaier granule was associated with improved DFS (HR, 0.440; 95% CI, 0.223-0.868; P = 0.018) and OS (HR, 0.236; 95% CI, 0.103-0.540; P = 0.001). CONCLUSION In this retrospective study, Huaier granules improved the DFS and OS of early invasive breast cancer patients, providing real-world evidence for further prospective studies on treating breast cancer with Huaier granules.
Humans ; Breast Neoplasms/mortality* ; Retrospective Studies ; Female ; Propensity Score ; Middle Aged ; Adult ; Prognosis ; Disease-Free Survival ; Kaplan-Meier Estimate ; Aged ; Proportional Hazards Models ; Complex Mixtures/therapeutic use* ; Drugs, Chinese Herbal/therapeutic use* ; Trametes

Objective:To analyze the molecular mechanism of Huangqin Decoction in the treatment of acute lung injury (ALI) with network pharmacology; To conduct experimental validation.Methods:Active compounds and corresponding targets of Huangqin Decoction were retrieved from the TCMIP database. ALI-related targets were obtained from GeneCards, DisGeNet, TTD, and OMIM, and the intersection targets were obtained. The intersection targets were imported into the string database to build the PPI network, and the core targets were obtained through topology analysis by Cytoscape 3.10.1 software. GO and KEGG pathway enrichment analyses were conducted using clusterProfiler software. 16 SD rats were divided into two groups ( n = 8 per group) with random number table method: control and Huangqin Decoction. Rats in the Huangqin Decoction group received Huangqin Decoction by gavage at a dosage of 40 mg/kg, while the control group was administered an equal volume of distilled water. After seven consecutive treatments, drug-containing serum was collected. A549 cells were divided into four groups: control, model, Huangqin Decoction, and received relevant drugs as intervention for 24 h. Levels of SOD, MDA, GSH-Px, IL-1β, TNF-α, and IL-6 in the culture supernatant were measured by ELISA. Apoptosis was analyzed by flow cytometry. The expressions of PI3K, p-PI3K, Akt, p-Akt, mTOR, p-mTOR, LC3Ⅱ/Ⅰ, and Beclin-1 proteins were determined by Western blot. Results:A total of 137 active compounds and 178 common targets were identified in Huangqin Decoction, with TP53, AKT1, STAT3, TNF, IL6, and ESR1 as core nodes. GO enrichment indicated involvement in oxidative stress and responses to lipopolysaccharides, bacterial molecules, and hypoxia. KEGG analysis revealed enrichment in lipid and atherosclerosis, PI3K-Akt signaling pathway, hepatitis, MAPK signaling pathway, prostate cancer, small-cell lung cancer, and mTOR signaling pathway. In cell experiments, compared with the model group, Huangqin Decoction and inhibitor groups showed increased A549xibo ( P<0.05); levels of IL-1β, TNF-α, IL-6, and MDA in the supernatant were reduced ( P<0.05 or P<0.01), while SOD and GSH-Px levels were elevated ( P<0.05 or P<0.01); the apoptosis rate decreased ( P<0.05 or P<0.01); the expressions of LC3-Ⅱ/Ⅰ and Beclin-1 proteins decreased ( P<0.05 or P<0.01), whereas the expressions of p-mTOR/mTOR, p-Akt/Akt, and p-PI3K/PI3K increased ( P<0.05 or P<0.01). Conclusion:Huangqin Decoction exerts protective effects against ALI mainly by reducing cellular autophagy, and its mechanism may be related to the activation of the mTOR/Akt/PI3K signaling pathway.

OBJECTIVE To study the interventional effect and mechanism of 1，8-cineole on pancreatic β cell ferroptosis induced by type 2 diabetes. METHODS In vitro ferroptosis model was established in pancreatic β cells of mice by using high glucose. The effects of low-dose and high-dose 1，8-cineole （0.25， 0.5 μmol/L） on the level of Fe2+ in pancreatic β cells were investigated. The effects of 1，8-cineole （0.5 μmol/L） combined with ferroptosis inducer Erastin （20 μmol/L） and ferroptosis inhibitor Ferrostatin-1 （20 μmol/L） on the protein expressions of glutathione peroxidase-4 （GPX4） and cyclooxygenase-2 （COX2） were also detected. The type 2 diabetes model mice were established by feeding high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin. The effects of low-dose and high-dose 1，8-cineole （50， 200 mg/kg） on the pathological morphology of pancreatic tissue， the content of iron as well as the protein expressions of GPX4 and COX2 were investigated. RESULTS The results of the cell experiment showed that compared with the model group， pretreatment with 1，8-cineole significantly reduced intracellular Fe2+ levels and upregulated GPX4 protein expression， while downregulated COX2 protein expression in pancreatic β cells （P＜0.05）. After combining with Ferrostatin-1， the expression trends of the above two proteins were the same， while there was no statistically significant difference after combining with Erastin. The results of animal experiments showed that compared with the model group， after intervention with 1，8-cineole， the structure of the pancreatic islets in mice recovered intact and their morphology improved； the iron content of pancreatic tissue and protein expression of COX2 were decreased significantly （P＜0.05）， while protein expression of GPX4 was increased significantly （P＜0.05）. CONCLUSIONS 1，8-cineole could ameliorate pancreatic β cell injury induced by diabetes， the mechanism of which may be related to reducing intracellular iron deposition and regulating ferroptosis-related proteins.

AIM:To investigate the effect of conditioned medium from hypoxia/reoxygenation(H/R)-treated rat cardiac fibroblasts(CFs)on gap junction between cardiomyocytes and determine whether its mechanism is related to matrix metalloproteinase 2(MMP2)activity.METHODS:(1)H9c2 cells were randomly divided into five groups:con-trol group,normal group,ARP-100 group,H/R group,and H/R+ARP-100 group.Scrape loading/dye transfer assay was used to assess the gap junction function.Western blot was used to detect the expression and phosphorylation levels of Cx43.Gelatin zymography assay was performed to measure MMP2 activity.(2)SD rats were randomly divided into control group,ARP-100 group,ischemia-reperfusion(I/R)group,and I/R+ARP-100 group,with 8 rats in each group.Micro-electrode array technology was used to record the type and duration of arrhythmia.Immunohistochemistry experiment was performed to assess expression levels and distribution of Cx43 in myocardial tissues.RESULTS:Compared with the con-trol group,the H/R group showed decreased protein expression of Cx43(P＜0.01),narrowed distance of lucifer yellow dif-fusion(P＜0.01),and increased MMP2 activity(P＜0.01).ARP-100 attenuated H/R-induced gap junction dysfunction(P＜0.05).The arrhythmia score was also reduced after perfusion with ARP-100(P＜0.01).CONCLUSION:H/R-treated rat CFs can inhibit gap junction between cardiomyocytes,and its mechanism may involve increased MMP2 activity.

Objective To explore the effect of γ-aminobutyric acid(GABA)on the growth and related physiological metabolism of plantlets of Tetrastigma hemsleyanum Diels et Gilg from Huaiyu Mountain under low temperature stress,which provides a basis for its application of anti-freezing and cold resistance in the wild-imitation cultivation of T.hemsleyanum Diels et Gilg from Huaiyu mountain.Methods Plantlets of T.hemsleyanum Diels et Gilg from Huaiyu Mountain,which were treated with GABA under low temperature stress,were selected as research objects.The growth indicators,physiological indexes,the relative expression levels of chalcone synthase and flavonol synthase genes were measured using plant tissue culture,physiological and biochemical methods and qRT-PCR,respectively.Results Compared with the control group without GABA,the proliferation coefficient,plant height,fresh weight,dry weight,and tissue water content of the two cultivated plantlets of T.hemsleyanum Diels et Gilg from Huaiyu Mountain("Huaiyu 1"and"Huaiyu 2")reach their maximum value when 0.5 g·L-1 GABA was added to the culture medium.Moreover,content of soluble protein(SP),soluble sugar(SS),proline(Pro),reduced glutathione(GSH),ascorbic acid(AsA),indole acetic acid(IAA),zeatin nucleoside(ZR),gibberellin(GA3),jasmonic acid(JA),the activity of superoxide dismutase(SOD),peroxidase(POD),ascorbic acid peroxidase(APX)and glutathione reductase(GR),and the relative expression level(RQ value)of chalcone synthase(CHS)gene were significantly increased.Moreover,relative conductivity,content of abscisic acid(ABA),hydrogen peroxide(H2O2),malondialdehyde(MDA),rate of O2·-production,and relative expression levels(RQ value)of flavonol synthase(FLS)gene were obviously decreased.The growth of plantlets of T.hemsleyanum Diels et Gilg from Huaiyu Mountain,which were treated with GABA under low temperature stress,was positively correlated with the contents of IAA,ZR,GA3,JA,SS,AsA,GSH,and the expression of CHS genes.Conclusion Appropriate concentration of GABA can regulate the contents of endogenous plant hormones and osmoregulation substances,antioxidant substances,and the expression of key genes in secondary metabolites,so as to promote the growth of plantlets of T.hemsleyanum Diels et Gilg from Huaiyu Mountain under low temperature stress.

Objective:To investigate the regulative effects of Streptococcus mutans (Sm) antisense vicK RNA (ASvicK) on the multi-species biofilm formed by three common oral streptococci (Sm, Streptococcus sanguinis, and Streptococcus gordonii) (Sm+Ss+Sg). Methods:ASvicK over-expression strain was constructed by using a recombinant plasmid, and three-species biofilm UA159+Ss+Sg and ASvicK+Ss+Sg were cultured. The phenotypes of biofilms were detected by scanning electron microscopy (SEM). Crystal violet (CV) assay was used to detect biofilm biomass. Lactate kit and anthrone-sulfuric acid colorimetric assay were used to determine the abilities of lactic acid and exopolysaccharides production, respectively. The proportions of three-species and expression levels of the cariogenic-related genes in biofilms were detected by TaqMan fluorescence quantitative PCR and real-time fluorescence quantitative PCR. A biofilm demineralization model of human enamel slabs was further constructed, and the hardness of enamel surface was detected.Results:Compared to UA159+Ss+Sg, over-expression of ASvicK could inhibit biofilm formation and lactic acid production in ASvicK+Ss+Sg biofilm significantly decreased by 78.93% ( P<0.001) and 62.23% ( P<0.001), respectively. With ASvicK over-expression, the amounts of water-insoluble and-soluble glucoses in ASvicK+Ss+Sg biofilm were reduced respectively by 39.13% ( P<0.001) and 68.00% ( P<0.001). Compared to the UA159+Ss+Sg Group, the proportion of Sm, the cariogenic bacteria, showed 33.00% reduction ( P<0.01) in Sm+Ss+Sg biofilm, and the gene expressions of cariogenic-relative genes vicK/X, gtfB/C/D, and ftf significantly decreased ( P<0.05). The micro-hardness value of enamel slabs after demineralization by ASvicK+Ss+Sg biofilm was significantly increased to 183.84% ( P<0.001). Conclusions:ASvicK over-expression could reduce the Sm proportion and weaken the cariogenicity of oral Streptococcus biofilm, thereby possibly slowing down the progression of caries.

Objective To analyze the incidence of and risk factors for white matter hyperintensity(WMH)in pilots.Methods A retrospective case-control study was performed.The subjects were 1,415 pilots ages 19 to 58 who had undergone cranial MRI examination in a hospital between September 2020 and August 2023.They were divided into two groups:the WMH group and the control group(without WMH).Univariate and multivariate logistic regression analysis were used to identify the risk factors for WMH.Results There were 219 cases in the WMH group and 1,196 cases in the control group.The total incidence of WMH was approximately 15.48％,with mild,moderate and severe cases of WMH accounting for 70.78％,24.20％,and 0.47％,respectively.Regression analysis results showed that age(OR=1.625,95％CI:1.099-2.404)and flight time(OR=1.282,95％CI:1.033-1.592)were risk factors for WMH in pilots.Conclusion The incidence of WMH in pilots was approximately 15.48％.Most of WMH were mild according to Fazekas grading.Age increase and long flight time are risk factors for WMH in pilots.

Objective To investigate the antibacterial performance and biocompatibility of silver nanoparticles-coated root canal nickel titanium instruments(AgNPs-NiTi).Methods AgNPs-NiTi was prepared using pulse electrochemical deposition.The morphol-ogy of AgNPs-NiTi was observed using field emission scanning electron microscopy(FE-SEM),and the elemental composition and con-tent were analyzed using X-ray diffraction(XRD)and energy dispersive spectroscopy(EDS).The mechanical properties of AgNPs-NiTi were tested.After Co-culturing AgNPs-NiTi with E.faecalis,the antibacterial effect was detected by colony-forming units method.By constructing an in vitro model of E.faecalis biofilm in the root canal of teeth,the antibacterial effect of AgNPs-NiTi was observed using FE-SEM and live/dead bacterial staining.In addition,AgNPs-NiTi was co-cultured with Raw 264.7 cells,and its cytotoxicity was de-tected by CCK-8.Results The pulse electrochemical deposition was used to construct a silver nanoparticle(AgNPs)coating on NiTi instruments with no significant change in the mechanical properties.AgNPs-NiTi significantly inhibited the proliferation of E.faecalis and damaged E.faecalis biofilm in the root canal.AgNPs-NiTi had no significant influence on the proliferation of Raw264.7 cells and had no cytotoxicity.Conclusion The mechanical properties of AgNPs-NiTi are similar to those of nickel titanium instruments.AgNPs-NiTi inhibits E.faecalis proliferation with good biocompatibility.

Objective·To investigate the predictive value of the Clinical Frailty Scale(CFS)in the long term outcomes in acute myocardial infarction(AMI)patients who completed in-hospital cardiac rehabilitation(CR).Methods·A total of 501 AMI patients treated in the Cardiology Center of Shanghai Sixth People's Hospital,Shanghai Jiao Tong University of Medicine from May 2020 to May 2022 were prospectively enrolled,with their baseline clinical data collected.The patients completed graded in-hospital CR and were assessed by CFS based on their completion of CR before discharge.Patients were then categorized into three groups(norm group,vulnerable group and frail group)according to their CFS level.The difference in 1-year major cardiovascular event(all-cause death and re-hospitalization for heart failure)rates among the three groups was investigated.Logistic regression analysis was performed to explore the effective risk factors relevant to the outcomes,and receiver operator characteristic(ROC)curves were generated to analyze the prognostic value.Finally,an optimal prediction model was developed.Results·The CFS level in AMI patients who completed CR was positively correlated with age and peak pro-B-type natriuretic peptide(peak proBNP),and inversely correlated with gender difference(P<0.05).Accompanied with the elevated CFS level,the incidence of both outcomes increased,and there were significant differences in all-cause death(2.6%,5.6%and 15.2%,P=0.002),and while no significant differences in re-hospitalization for heart failure among the three groups(19.6%,22.2%and 24.2%).All-cause death of the frail group was significantly higher than that of the norm group(P=0.004),while there was no significant difference between the vulnerable group and the norm group.CFS could sensitively predict the 1-year all-cause death in AMI patients(β=1.89,OR=6.61,P=0.001),and the risk model combined with CFS had the best predictive effect(AUC=0.845,P=0.000).Conclusion·Assessment by CFS in AMI patients who completed in-hospital CR contributes to identifying AMI patients with high risk of all-cause death in 1 year.

Objective:To investigate the trajectories of intrinsic capacity in older adults and explore the impact of leisure activities on the decline of intrinsic capacity.Methods:This study is a prospective cohort study conducted in a community in Beijing, China.A convenience sampling method was used to select 284 cases of older adults from November to December 2020.The purpose of the study was to gather information on the general conditions, intrinsic abilities(including cognitive, vitality, motor, psychological, and sensory dimensions), and participation in leisure activities of older adults.A 2.5-year follow-up of the respondents was conducted.Results:A total of 243(85.6%, 243/284)respondents completed the 2.5-year follow-up.The follow-up intrinsic capacity score decreased from a baseline level of 4(3, 4)to 3(3, 4)( Z=-4.667, P<0.001).Among the respondents, 113(46.5%, 113/243)older adults showed a decrease in intrinsic capacity, with more significant decreases observed in the locomotor and psychometric dimensions( χ2=16.953, 23.510, both P<0.001).The number of declines in intrinsic ability was higher in the low group of leisure activities compared to the high group[62.2%(56/90) vs.37.3%(57/153), χ2=14.199, P<0.001].There was a positive correlation between leisure activity scores and the follow-up intrinsic capacity score( r=0.200, P=0.002), as well as with the value of change in the score of intrinsic capacity( r=0.146, P=0.023).The results of Logistic regression analysis indicated that leisure activities( OR=0.644, 95% CI: 0.507 to 0.818, P<0.001), physical leisure activities( OR=0.565, 95% CI: 0.395 to 0.809, P=0.002), and intellectual leisure activities( OR=0.742, 95% CI: 0.555 to 0.992, P=0.044)independently influenced the decline of intrinsic ability in the elderly, even after accounting for demographic information, number of diseases, and type of medicine taken. Conclusions:The decline in intrinsic abilities is a common occurrence among the elderly population.Engaging in leisure activities has been found to be effective in reducing this decline.It is important to emphasize the impact of leisure activities on the overall health of older individuals.