This study aims to explore the mechanism of Yanghe Decoction(YHD) against subcutaneous tumor in pulmonary metastasis from breast cancer, which is expected to lay a basis for the treatment of breast carcinoma with YHD. The chemical components of medicinals in YHD, and the targets of the components were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and SwissTargetPrediction. The disease-related targets were searched from GeneCards and Online Mendelian Inheritance in Man(OMIM). Excel was employed to screen the common targets and plot the Venn diagram. The protein-protein interaction network was constructed. R language was used for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment. A total of 53 female SPF Bablc/6 mice were randomized into normal group(same volume of normal saline, ig), model group(same volume of normal saline, ig), and low-dose and high-dose YHD groups(YHD, ig, 30 days), with 8 mice in normal group and 15 mice in each of the other groups. Body weight and tumor size was measured every day. Curves for body weight variation and growth of tumor in situ were plotted. In the end, the subcutaneous tumor sample was collected and observed based on hematoxylin and eosin(HE) staining. The mRNA and protein levels of hypoxia inducible factor-1α(HIF-1α), pyruvate kinase M2(PKM2), lactate dehydrogenase A(LDHA), and glucose transporter type 1(GLUT1) were detected by PCR and Western blot. A total of 213 active components of YHD and 185 targets against the disease were screened out. The hypothesis that YHD may regulate glycolysis through HIF-1α signaling pathway to intervene in breast cancer was proposed. Animal experiment confirmed that the mRNA and protein levels of HIF-1α, PKM2, LDHA, and GLUT1 in the high-and low-dose YHD groups were lower than those in the model group. YHD has certain inhibitory effect on subcutaneous tumor in pulmonary metastasis from breast cancer in the early stage, which may intervene pulmonary metastasis from breast cancer by regulating glycolysis through HIF-1α signaling pathway.
Female ; Mice ; Animals ; Glucose Transporter Type 1/genetics* ; Network Pharmacology ; Animal Experimentation ; Saline Solution ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Signal Transduction ; Glycolysis ; RNA, Messenger ; Neoplasms/drug therapy* ; Molecular Docking Simulation

Objective To investigate the Gram-positive coccus resistance in nationwide's tertiary hospitals and understand the trend of antimicrobial resistance.Methods All the clinical isolates were collected from 19 hospitals and the minimal inhibitory concentrations(MICs)were tested using agar/broth dilution method recommended.Results A total of 1 974 pathogenic Gram-positive coccus from 19 tertiary hospitals in 19 cities nationwide over the period from July 2021 to June 2022 were studied.Based on the MIC results,the prevalence of methicillin resistant Stapylococcus aureus(MRSA)and methicillin resistant Stapylococcus epidermidis(MRSE)were 36.4％and 79.9％respectively.No vancomycin insensitivity Staphylococcus was detected.Staphylococcus aureus were 100％susceptibility to linezolid and teicoplanin.Antibiotic resistance rate of Enterococcus faecalis and Enterococcus faecium to ampicillin were 3.1％and 92.9％.The detectation rate of vancomycin resistant Enterococcus(VRE)was 1.6％.Nonsusceptibility rate of Enterococcus faecalis to linezolid was 32.2％,two consecutive monitoring rises and nonsusceptibility rate of Enterococcus faecium(12.5％)was also significantly increased.The prevalence of penicillin non-susceptible Streptococcus pneumoniae(PNSSP)was 0.8％based on non-meningitis and parenteral administration criterion,decrease of nearly 30 percentage points from the previous surveillance.While for cases of oral penicillin,the rate was 71.8％,showing similar to last time.The results indicated that the number of strains with higher MIC value of penicillin(MIC ≥4 mg·L-1)decreased significantly.There were no significant differences of resistance rates of Stapylococcus aureus,Stapylococcus epidermidis,Enterococcus faecalis,Enterococcus faecium and Streptococcus pneumoniae among various groups such as different department,age,or specimen source.Conclusion VRE detection ratio stablized at a relatively low level.The number of Streptococcus pneumoniae with higher MIC value of penicillin decreased significantly compared with the previous monitoring.The increase of linezolidin-insensitive Enterococcus was noteworthy.

Objective To investigate the Gram-negative bacteria resistance in nationwide's tertiary hospitals and understand the trend of antimicrobial resistance.Method All the clinical isolates were collected from 19 hospitals and the minimal inhibitory concentrations(MICs)were tested using agar/broth dilution method recommended.Results A total of 4 066 pathogenic isolates from 19 tertiary hospitals in 19 cities nationwide over the period from July 2021 to June 2022 were studied.Based on the MIC results,Escherichia coli and Klebsiella pneumoniae showed extended spectrum β-lactamase(ESBLs)phenotype rates of 55.0％and 21.0％,respectively,ESBLs phenotype rate of Klebsiella pneumoniae keep going down.The ratios of carbapenems resistance Klebsiella pneumoniae increased by 5 percentage points compared with the previous monitoring.Carbapenems,moxalactam,sitafloxacin,β-lactam combination agents,fosfomycin trometamol,and amikacin displayed desirable antibacterial activity against Enterbacterales,susceptibal rates were above 75％.In addition,tigacycline,omacycline,colistin and fluoxefin maintained good antibacterial activity against their respective effective bacteria/species,and the bacterial sensitivity rates by more than 80％.Resistance rates of Pseudomonas aeruginosa and Acinetobacter baumannnii to imipenem were 26.3％and 72.1％and multidrug-resistant(MDR)detection rates were 41.1％and 77.3％,extensively drug-resistant(XDR)were 12.0％and 71.8％,respectively.Comparison of drug resistance rates from different wards,ages and specimen sources indicated that the proportion of resistance in Klebsiella pneumoniae and Acinetobacter baumannii isolated from intensive care unit(ICU)were significantly higher than non-ICU.Carbapenem resistance rates of Klebsiella pneumoniae isolated from ICU were more than 35％.Resistance rates of Haemophilus influenzae isolated in children to β-lactam,macrolide,clindamycin and ESBLs detection rate in Klebsiella pneumoniae isolated from children were more than those from adults and the old people,so bacterial resistance in children is an important problem in China.Conclusion ESBLs detection rate of Escherichia coli increased slightly after years of continuous decline.The proportion of carbapenem resistant Pseudomonas aeruginosa was stable,but the resistance rate of Klebsiella pneumoniae and Acinetobacter baumannii to carbapenems was still increased,which should be paid more attention.

OBJECTIVE: To examine whether the combination of Naoxintong Capsule with standard care could further reduce the recurrence of ischemic stroke without increasing the risk of severe bleeding. METHODS: A total of 23 Chinese medical centers participated in this trial. Adult patients with a history of ischemic stroke were randomly assigned in a 1:1 ratio using a block design to receive either Naoxintong Capsule (1.2 g orally, twice a day) or placebo in addition to standard care. The primary endpoint was recurrence of ischemic stroke within 2 years. Secondary outcomes included myocardial infarction, death due to recurrent ischemic stroke, and all-cause mortality. The safety of drugs was monitored. Results were analyzed using the intention-to-treat principle. RESULTS: A total of 2,200 patients were enrolled from March 2015 to March 2016, of whom 143 and 158 in the Naoxintong and placebo groups were lost to follow-up, respectively. Compared with the placebo group, the recurrence rate of ischemic stroke within 2 years was significantly lower in the Naoxintong group [6.5% vs. 9.5%, hazard ratio (HR): 0.665, 95% confidence interval (CI): 0.492-0.899, P=0.008]. The two groups showed no significant differences in the secondary outcomes and safety, including rates of severe hemorrhage, cerebral hemorrhage and subarachnoid hemorrhage (P>0.05). CONCLUSION The combination of Naoxintong Capsule with standard care reduced the 2-year stroke recurrence rate in patients with ischemic stroke without increasing the risk of severe hemorrhage in high-risk patients. (Trial registration No. NCT02334969).
Adult ; Humans ; Secondary Prevention/methods* ; Ischemic Stroke ; Stroke/prevention & control* ; Cerebral Hemorrhage/complications* ; Double-Blind Method ; Platelet Aggregation Inhibitors

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

Female ; Humans ; Methotrexate ; Pregnancy ; Pregnancy, Ectopic

OBJECTIVE: To investigate the related factors influencing plasma transfusion efficacy so as to improve the plasma transfusion efficiency. METHODS: According to the clinical symptoms and the laboratorial results, the patients were divided into transfusion efficient and inefficient groups. A total of13090.8 units of plasma were transfused to 4423 patients. The clinical symptoms and the hemorrhage related index per- and pro-transfusion, plasma components sorts, storage time, and the dose of plasma (kg/ml) transfusion were analyzed. RESULTS: The largest transfusion volume of plasma were in intensive care unit (ICU) accounted for 30.36%, the largest blood plasma per patient transfusion was in cardiac surgery (3.96 U). The analysis of transfusion efficiency showed that in terms of patient age, there were difference in transfusion efficiency among the patients with different ages (P＜0.001). The effective transfusion rate in the group of age ＜18 was 53%, which was higher than that in group of age 18-60(41%) and group of age ＞60 (30%); in terms of sex, the effective transfusion rate in female group was higher than that in male group (42% vs 37%) (P＜0.001); in terms of transfusion plasma volume/body weight, there were differences in transfusion efficiency (P＞0.05). The multi-factor logistic regression analysis showed that there was no significant correlation among the plasma sorts, storage time of the plasma pre-transfusion and transfusion efficiency(P＞0.05). The analysis of the non-hemolytic fever reaction caused by plasma transfusion revealed that there was no statistical difference between the plasma and the leukocyte-depleted plasma groups (P＞0.05). CONCLUSION The plasma transfusion effectiveness relates with age and sex, but not relates with the transfusion plasma voume/body weight, plasma sorts, and the duration of storage.

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

The present work is to establish an HPLC characteristic chromatograms of Asarum heterotropoides var. mandshuricum(AH) and A. sieboldii(AS), combined with cluster analysis for the identification of the two species, and predict their potential anti-inflammatory related targets by network pharmacological method. Eighty-nine samples(12 batches of AS and 77 batches of AH) were analyzed, and 11 characteristic peaks were identified by reference substances, UV spectrum and LC-MS. Cluster analysis showed that AS and AH were divided into two groups, and the ratio of characteristic peak areas can be used to distinguish them. When the ratio of characteristic peak sarisan to kakuol was greater than 5, it was AS, and when the ratio was less than 2, it was AH. The network pharmacological analysis of 119 constituents of Asari Radix et Rhizoma suggested that the anti-inflammatory effect of Asari Radix et Rhizoma might be related to COX-2, COX-1, iNOS, MAPK14, NR3 C1, PPARG and TNF. Among them, COX-2 is a relatively key target, which interacted with the characteristic constituents, asarinin, sesamin, safrole, methyleugenol and sarisan. The characteristic constituents asarinin and sesamin also interacted with the iNOS and MAPK14. Safrole and sarisan can also interact with iNOS, COX-1 and LAT4 H. Methyleugenol also showed interaction with COX-1 and LAT4 H. Since asarinin and sesamin interacted with three targets, COX-2, iNOS and MAPK14, it implied that they were the main active constituents for the anti-inflammatory activity of Asari Radix et Rhizoma. The COX-2 inhibitory activities of asarinin and sesamin were further studied by molecular docking and bioassay. The HPLC method established was simple, feasible and reliable, with predicted anti-inflammatory targets and anti-inflammatory constituents, which could provide a reference for improving the quality evaluation system of Asari Radix et Rhizoma.
Anti-Inflammatory Agents/isolation & purification* ; Asarum/chemistry* ; Chromatography, High Pressure Liquid ; Molecular Docking Simulation ; Phytochemicals/isolation & purification* ; Rhizome/chemistry*

Objective: To investigate the effect of Rhei Radix et Rhizoma on gastrointestinal function of normal rats and explore its therapeutic mechanism,and compare the difference of this herb before and after simmering. Method: Healthy SD rats were randomly divided into 7 groups,including the blank group,the high,medium and low dose groups of raw Rhei Radix et Rhizoma(1.5,3.0,6.0 g·kg^-1·d^-1) and the high,medium and low dose groups of simmered Rhei Radix et Rhizoma(1.5,3.0,6.0 g·kg^-1·d^-1),eight rats in each group were continuous intragastric administration for 10 days,the effect of Rhei Radix et Rhizoma on gastrointestinal function of rats were evaluated by body weight,food intake,gastric remnant rate,small intestine propelling rate,stomach weight coefficient and gastrointestinal tissue morphology;enzyme-linked immunosorbent assay(ELISA) was used to detect contents of motilin(MTL) in rat plasma and gastrin(GAS),tumor necrosis factor-α(TNF-α),interleukin-10(IL-10) in rat serum,the mechanism of effect of Rhei Radix et Rhizoma on gastrointestinal function was explored and the effect of Rhei Radix et Rhizoma on gastrointestinal function of normal rats before and after simmering was compared. Result: In each administration group,weight growth of rats was slowed down,gastric emptying and intestinal propulsion were inhibited,inflammatory reaction was triggered,and gastric mucosal injury was increased.Compared with the blank group, except for the low-dose and medium-dose groups of simmered Rhei Radix et Rhizoma,stomach weight coefficient,gastric remnant rate and content of TNF-α of rats were significantly increased(P<0.05,P<0.01), and the content of IL-10 was significantly reduced, in addition to the low-dose group of simmered Rhei Radix et Rhizoma,the weight,small intestine propelling rate,contents of GAS and MTL of rats were significantly decreased(P<0.05,P<0.01).Compared with the isodose raw Rhei Radix et Rhizoma group,the weight,small intestine propelling rate,contents of GAS,IL-10 and MTL were all increased with different degrees, the gastric weight coefficient,gastric remnant rate and content of TNF-α of rats were all decreased to different degrees. Conclusion: Gastrointestinal dysfunction caused by Rhei Radix et Rhizoma is related to inhibiting the expression of gastrointestinal hormones and promoting the expression of inflammatory cytokines, in addition,the effect of "stomach injured by bitterness and cold property" of Rhei Radix et Rhizoma is weakened after simmering,which provides scientific basis for clinical rational use of Rhei Radix et Rhizoma.