Objective:To detect the hypoglycemic drugs illegally added in Haokangshu capsules .Methods: High performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used with an ACQUITY BEH C18 column(50 mm ×2.1 mm, 1.7 μm)and methanol-0.01 mol· L-1 ammonium acetate as the mobile phase with gradient elution .Through the molecular ion peak, the second order mass fragment ion information and MRM mode chromatographic peak retention time and the other information , the cap-sules containing metformin hydrochloride and 11 kinds of chemical hypoglycemic drugs were determined .Results:Through the analysis of 11 chemical hypoglycemic drugs , two chemical hypoglycemic agents , phenformin and glyburide , were detected out in the capsules . Conclusion:Phenformin and glibenclamide are illegally added in Haokangshu capsules .

Object To develop a method for the identification of Fritillaria walujewii Regel by UV spectrum. Methods UV spectrum of the absolute alcoholic extract of F. walujewii was determined and compared with that of four other similarly treated Fritillaria species. Results The UV spectrum of F. walujewii was consistently different with that of the other four species. Conclusion UV spectrum can be used to differentiate F. walujewii from other species of Fritillaria.

Objective To study risk factors associated with predisposition to Lm -ABM in adult patients and to evaluate the clinical features,management and out in this cohort of patients because Listeria monocytogenes (Lm) is the third most common cause of acute community acquired bacterial meningitis (Ac-ABM),after Streptococcus pneumoniae and Neisseria meningitides aetiologies.Methods A descriptive,prospective study carried out in a tertiary grade medical center emergency department in Beijing over a 10 -year period.During the study period,15 patients of Lm- ABM were included.Comparison of episodes of Lm - ABM versus other aetiologies was made.Results Fifteen episodes of Lm - ABM were identified in327 adult Ac - ABM patients.Three cohorts of individuals were vulnerable to Lm - ABM:the elderly ( RR=3.14; 95％ CI 1.84-5.35),the immunocompromised (RR =3.34; 95％ CI2.08-5.38),and pregnant women ( RR 12.48 ; 95％ CI 3.29 ～ 47.39 ).The classic triad of fever,neck stiffness,and altered mental status was present in 40％ (6 of 15) Lm - ABM patients.Similarly,40％ patients had at least one of cerebrospinal fluid (CSF) samples with features met the criteria of typical bacterial meningitis.The coverage of empirical antimicrobial therapy was microbiologically inadequate for 13 ( 86.7％ ) patients.The mortality rate was 33.3％ (5 of 15),and 7 (46.7％ ) of 15 patients led to an unfavorable outcome ( GOS ＜ 4),both of which were significantly higher than those in other aetiologies of Ac - ABM ( P =0.015P =0.009 respectively). Conclusions Our study showed the elderly,the immunocompromised patients,and pregnant women predisposed to Ac - ABM most likely to be Listeria monocytogenes aetiology.In contrast with similar previous reports, the current study showed that patients with meningitis due to Listeria monocytogenes did not present with atypical clinical features.A high proportion of patients received empirical antimicrobial therapy that did not cover Listeria monocytogenes.Lm - ABM is still a serious disease that leads to high morbidity and mortality rates.With these important caveats in mind,our findings have implications for clinical practice and food safety policy makers.

ObjectiveTo evaluate the value of modified early warning score (MEWS) in predicting mortality of critically ill patients admitted to emergency department.Methods A prospective cohort study was conducted. Clinical data of emergency patients admitted to resuscitation room of Peking Union Medical College Hospital from Feburary 13rd, 2014 to April 20th, 2014 were collected, and their MEWS were calculated based on medical records and their clinical outcomes was followed. Incidence of primary outcome (3-day mortality) and secondary outcome [all deaths and composite outcome of intensive care unit (ICU) transfer, cardio-pulmonary resuscitation, and death] were compared between MEWS positive (MEWS≥5) or negative (MEWS 0-4) patients, and multi-regression logistic analysis was done to look for the impact factors of primary outcome in these patients.Results 176 patients, among them 98 (55.68%) were male, were enrolled in the study. Their mean age was (56.86±21.46) years old. Mean MEWS was 4.30±2.74. There was 74 cases in MEWS positive group, and 102 in negative group. Primary endpoint occurred in 41 patients, and the 3-days mortality in MEWS positive group was significantly higher than that in MEWS negative group [37.84 (28/74) vs. 12.74% (13/102), odds ratio (OR) = 4.167, 95% confidence interval (95%CI) = 1.973-8.804,P< 0.001]. At the meantime, incidence of all death [54.05% (40/74) vs. 17.65% (18/102),OR = 5.490, 95%CI = 2.770-10.883,P< 0.001] and the incidence of ICU transfer, cardio-pulmonary resuscitation and death [64.86% (48/74) vs. 25.49% (26/102),OR = 5.396, 95%CI = 2.809-10.366,P< 0.001] were also significantly higher in MEWS positive group as compared with negative group. Multi-regression logistic showed abnormal mental status (OR = 3.606, 95%CI = 1.541-8.436,P = 0.003) but not MEWS≥5 (OR = 1.672, 95%CI = 0.622-4.494,P = 0.308)was the predictor of 3-day mortality in emergency admitted critically ill patients.Conclusions Although the incidence of severe adverse events is significantly increased in patients with MEWS≥5 compared with those with MEWS 0-4, MEWS≥5 cannot be an efficient predictor for 3-day mortality. Abnormal mental status shows some predictive value for early mortality in critically ill patients seen in emergency department.

The purpose of this study was to determine whether the Ca2+ signaling pathway is involved in the ability of osteoprotegerin (OPG) to inhibit osteoclast differentiation and maturation. RAW264.7 cells were incubated with macrophage colony-stimulating factor (M-CSF) + receptor activator of nuclear factor-kappaB ligand (RANKL) to stimulate osteoclastogenesis and then treated with different concentrations of OPG, an inhibitor of osteoclast differentiation. The intracellular Ca2+ concentration [Ca2+]i and phosphorylation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) in the different treatment groups were measured by flow cytometry and Western blotting, respectively. The results confirmed that M-CSF + RANKL significantly increased [Ca2+]i and CaMKII phosphorylation in osteoclasts (p < 0.01), and that these effects were subsequently decreased by OPG treatment. Exposure to specific inhibitors of the Ca2+ signaling pathway revealed that these changes varied between the different OPG treatment groups. Findings from the present study indicated that the Ca2+ signaling pathway is involved in both the regulation of osteoclastogenesis as well as inhibition of osteoclast differentiation and activation by OPG.
Animals ; Calcium/*metabolism ; *Calcium Signaling ; *Cell Differentiation/drug effects ; Cell Line ; Cell Survival/drug effects ; Gene Expression Regulation/drug effects ; Macrophage Colony-Stimulating Factor/metabolism ; Mice ; Osteoclasts/*cytology/*drug effects/*metabolism ; Osteoprotegerin/*pharmacology ; RANK Ligand/metabolism

Gap junctions mediate direct communication between cells; however, toxicological cascade triggered by nonessential metals can abrogate cellular signaling mediated by gap junctions. Although cadmium (Cd) is known to induce apoptosis in organs and tissues, the mechanisms that underlie gap junction activity in Cd-induced apoptosis in BRL 3A rat liver cells has yet to be established. In this study, we showed that Cd treatment decreased the cell index (a measure of cellular electrical impedance) in BRL 3A cells. Mechanistically, we found that Cd exposure decreased expression of connexin 43 (Cx43), increased expression of p-Cx43 and elevated intracellular free Ca2+ concentration, corresponding to a decrease in gap junctional intercellular communication. Gap junction blockage pretreatment with 18β-glycyrrhizic acid (GA) promoted Cd-induced apoptosis, involving changes in expression of Bax, Bcl-2, caspase-3 and the mitochondrial transmembrane electrical potential (Δψm). Additionally, GA was found to enhance ERK and p38 activation during Cd-induced activation of mitogen-activated protein kinases, but had no significant effect on JNK activation. Our results indicated the apoptosis-related proteins and the ERK and p38 signaling pathways may participate in gap junction blockage promoting Cd-induced apoptosis in BRL 3A cells.
Animals ; Apoptosis/*drug effects ; Cadmium/*toxicity ; Calcium/metabolism ; Cell Communication/drug effects ; Connexin 43/genetics ; Enzyme Activation/drug effects ; Gap Junctions/*drug effects ; Gene Expression Regulation/drug effects ; Hepatocytes/cytology/*drug effects ; Rats ; Signal Transduction/drug effects

Exposure to cadmium (Cd) induces apoptosis in osteoblasts (OBs); however, little information is available regarding the specific mechanisms of Cd-induced primary rat OB apoptosis. In this study, Cd reduced cell viability, damaged cell membranes and induced apoptosis in OBs. We observed decreased mitochondrial transmembrane potentials, ultrastructure collapse, enhanced caspase-3 activity, and increased concentrations of cleaved PARP, cleaved caspase-9 and cleaved caspase-3 following Cd treatment. Cd also increased the phosphorylation of p38-mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinases (ERK)1/2 and c-jun N-terminal kinase (JNK) in OBs. Pretreatment with the caspase inhibitor, N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone, ERK1/2 inhibitor (U0126), p38 inhibitor (SB203580) and JNK inhibitor (SP600125) abrogated Cd-induced cell apoptosis. Furthermore, Cd-treated OBs exhibited signs of oxidative stress protection, including increased antioxidant enzymes superoxide dismutase and glutathione reductase levels and decreased formation of reactive oxygen species. Taken together, the results of our study clarified that Cd has direct cytotoxic effects on OBs, which are mediated by caspase- and MAPK pathways in Cd-induced apoptosis of OBs.
Animals ; Apoptosis/*drug effects ; Cadmium/*toxicity ; Caspases/metabolism ; Environmental Pollutants/*toxicity ; Osteoblasts/*drug effects/metabolism ; Oxidative Stress/drug effects ; Rats ; Rats, Sprague-Dawley ; p38 Mitogen-Activated Protein Kinases/metabolism

Objective:To explore the therapeutic characteristics of population with gout achieving treat-to-target (T2T) indicators through real-world research and evaluate their safety.Methods:A total of 3 287 patients diagnosed with gout by rheumatologists in 21 first-class tertiary hospitals in 10 provinces, municipalities, and autonomous regions in China from January 2015 to December 2021 were included in this polycentric cross-sectional study. The database included patients′ general information, disease characteristics, and clinical application of traditional Chinese and Western medicine treatment measures. SPSS and Excel software were used for data analysis. Frequency analysis, cluster analysis, and factor analysis were used to summarize the characteristics and rules of treatment measures for patients with gout who achieved the target after treatment. The occurrence of adverse events (AE) was recorded during treatment.Results:After treatment, 691 visits (7%) achieved the serum urate (SUA) target, and the most frequent use of urate-lowering therapy (ULT) was febuxostat, followed by benzbromarone. The most common treatment options were following: GroupⅠ: traditional Chinese medicine (TCM) decoction-TCM external treatment-physical exercise-proprietary Chinese medicine; GroupⅡ: ferulic acid-nonsteroidal anti-inflammatory drugs (NSAIDs); Group Ⅲ: allopurinol-sodium bicarbonate-benzbromarone; Group Ⅳ: glucocorticoid-colchicine; Group Ⅴ: febuxostat. A total of 5 898 visits (60%) chieved manifestations of joint pain VAS scores target, and the most frequently used drug to control joint symptoms was NSAIDs. The frequency of use of drugs to control joint symptoms were 2 118 times (usage rate reached 35.9%), while the frequency of ULT were 2 504 times (usage rate reached 42.5%), which was higher than the joint symptom control drug. The most common treatment options were following: Group Ⅰ: proprietary Chinese medicine-TCM decoction-TCM external treatment-physical exercise; Group Ⅱ: NSAIDs-colchicine hormones; Group Ⅲ: allopurinol, Group Ⅳ: benzbromarone; Group Ⅴ: febuxostat. A total of 59 adverse events occurred during treatment.Conclusion:The proportions of gout patients who reach target serum urate level & good control of joint symptoms are both very low, and ULT and anti-inflammatory prescription patterns are very different from international guidelines, so it is necessary to strengthen the standardized management of gout patients. At the same time, life intervention measures account for a certain proportion of the treatment plans for the T2T population, and further exploration is needed.