Objective To compare and analyze the occupational exposure limit（OEL）of hexavalent chromium compounds in China and foreign countries. Methods The OEL and background information of hexavalent chromium compounds released by nine official and unofficial organizations in seven countries/regions were collected and sorted. The classification，limit levels， formulation principles and compound characteristics labeling of OEL were compared. Results The OEL values published by nine organizations ranged from 0.000 02 to 0.050 00 mg/m3 . Among them，the limits of seven organizations（including China） did not clearly distinguish the soluble types of hexavalent chromium compounds；the limits of eight organizations（including China）were calculated in terms of chromium；seven organizations（including China）have only developed OEL for long-term exposure. The OEL of hexavalent chromium in China was 0.050 00 mg/m3 which is relatively loose. Its carcinogenicity label was consistent with international standards，its sensitization label was consistent with some countries，and its percutaneous absorption label had not been included in the characteristic labeling of limit values. Conclusion It is suggested that the OEL of hexavalent chromium in China should be revised timely，and the systemic adverse effects caused by percutaneous absorption of hexavalent chromium compounds should be focused on. At the same time，it is recommended to systematically adjust the management concepts and principles of all carcinogens.

Objective To explore the role and their relationship of Ki-67, VEGF and p27 expressed in adult patients with acute leukemia. Methods The expression of Ki-67, VEGF and p27 in bone marrow mononuclear cells (BMMNC) were analyzed by immunocytochemical staining, and their correlations of Ki-67, VEGF and p27 were statistically analyzed. Results The expression of Ki-67(42.48±25.78)% or VEGF (44.89±24.01)% on BMMNC from acute leukemia cells was significantly higher than that in the control (11.40±9.94)% or (16.90±12.54)% (P<0.01). But the expression of p27 (23.65±13.30)% was significantly lower than that in the control (50.23±22.68)% (P<0.01). The expressions of Ki-67 were positively correlated with and VEGF in patients with acute leukemia were positively correlated(r=-0.666, P<0.01), and the expressions of Ki-67 and p27 were negatively correlated with p27 in patients with acute leukemia (r=-0.316, P<0.05).Conclusion The evaluation of expression of Ki-67, VEGF and p27 on acute leukemic cells provides new insights to the pathogenesis is helpful in mechanism and is helpful in the diagnosis of acute leukemia.

This study was aimed to optimize the purification technology for Sambucus williamsii Hance. With the morroniside as a marker, the purification technology for Sambucus williamsii Hance was optimized by different types of macroporous resin. The results showed that the optimum purification technology was that, the extract of less than 1:250 (morroniside:resin) was adsorbed and the AB-8 resin was washed with distilled water, and then the morroni-side was eluted from the macroporous resin with 10% ethanol. And the content of the morroniside was more than 50%. It was concluded that the purification technology was simple, reliable, repeatable and suitable for industrial production.

Objective To explore the clinical nursing of Methotrexate combined with Mifepristone in patients with ectopic gestation .Methods Totals of 128 patients with ectopic gestation were treated by Methotrexate combined with Mifepristone , and blood β-HCG level and lump diameter size were measured .The patients were given comprehensive nursing including psychology , diet and daily activities , disease observation , drug adverse reaction and discharge guidance .Results The rate of successful treatment was 94.5%(121/128).The level of blood β-HCG and diameter of lump after 1 week were significantly smaller than those before the treatment (t=33.2,8.9, respectively;P<0.05).The level of blood β-HCG after 2,3,4 weeks were significantly lower than those after 1 week (t=64.2,78.3,105.9, respectively;P<0.05).And the diameter of lump after 2,3,4 weeks were significantly smaller than those after 1 week (t=6.4,7.5,8.3, respectively;P<0.05).Five patients (3.9%) had gastrointestinal reaction, three patients (2.3%) had slightly elevation of transaminase and leucopenia , two patients ( 1.6%) had oral ulcer and bone marrow suppression .Those symptoms were disappeared after treatment .Conclusions During the treatment of ectopic pregnancy , patients should be given positive psychological care , close clinical nursing and disease observation to promote the rehabilitation of patients .

Objective: To analyze the clinical characteristics of streptococcal toxic shock syndrome (STSS) caused by Streptococcus pyogenes (S. pyogenes) in the third trimester to improve clinical awareness of this disease. Methods: A retrospective study was conducted to analyze the clinical data of two patients with STSS caused by S. pyogenes in Jinan Maternal and Child Health Care Hospital and nine reported cases of healthy pregnant women infected with S. pyogenes at 28-42 gestational weeks with detailed data retrieved from Chinese National Knowledge Infrastructure and PubMed database from January 1997 to December 2018. Results: The two cases admitted to our hospital were both multiparas, with onset in winter and no specific symptoms in early stage. Disseminated intravascular coagulation (DIC) was developed in both cases on admission. In one case, the fetal heart rate was reduced and disappeared soon after admission. The other patient was diagnosed as stillbirth on admission. Both patients died and blood culture revealed infection of group A streptococcus. Nine previous cases were reported in one Chinese and five English articles. No high-risk pregnancy or premature rupture of membranes was reported in these 11 cases. Among the 11 cases, ten were positive for S. pyogenes indicated by blood or tissue culture and one was positive for streptococcal toxin. Ten cases had high fever and three presented with respiratory symptoms in early stage. Abdominal pain and watery diarrhea were common symptoms and all patients developed multiple organ dysfunction and DIC. Cases occurred in winter or spring were more common. Nine women died within 36 h after the onset of fulminant symptoms. Only two survived and hospitalized for 90 d and 25 d, respectively, after emergent cesarean section indicated by reduced fetal heart rate. Unfortunately, both neonates died after birth. For the babies, there were seven intrauterine fetal deaths, one stillbirth and three live births, but only one survived (whose mother developed respiratory cardiac arrest 90 min after delivery). Conclusions STSS caused by S. pyogenes in pregnant women exacerbates rapidly with a high mortality. Early identification of clinical manifestations and rapid progress of the disease are crucial for early diagnosis and treatment, which may help improve maternal and fetal outcomes.

To investigate the role of mitochondria in neuronal apoptosis, ischemia-reperfusion mediated neuronal cell injury model was established by depriving of glucose, serum and oxygen in media. DNA fragmentation, cell viability, cytochrome C releasing, caspase3 activity and mitochondrial transmembrane potential were observed after N2a cells suffered the insults. The results showed that N2a cells in ischemic territory exhibited survival damage, classical cell apoptosis change, DNA ladder and activation of caspase3. Apoptosis-related alterations in mitochondrial functions, including release of cytochrome C and depression of mitochondrial transmembrane potential (deltapsim) were testified in N2a cells after mimic ischemia-reperfusion. Moreover, activation of caspase3 occurred following the release of cytochrome C. However, the inhibitor of caspase3, Ac-DEVD-CHO, couldn't completely rescue N2a cells from apoptosis. Administration of cyclosporine A, an inhibitor of mitochondria permeability transition pore only partly inhibited caspase3 activity and reduced DNA damage. Interestingly, treatment of Z-IETD-FMK, an inhibitor of caspase8 could completely reverse DNA fragmentation, but can't completely inhibit caspase3 activity. It was concluded that there were caspase3 dependent and independent cellular apoptosis pathways in N2a cells suffering ischemia-reperfusion insults. Mitochondria dysfunction may early trigger apoptosis and amplify apoptosis signal.
Animals ; Apoptosis ; physiology ; Caspase 3 ; Caspases ; biosynthesis ; Cytochromes c ; biosynthesis ; Mice ; Mitochondria ; physiology ; Neuroblastoma ; pathology ; Neurons ; pathology ; Reperfusion Injury ; metabolism ; pathology ; Tumor Cells, Cultured

OBJECTIVE To explore the lipid-regulating mechanism of the classic prescription Zexie Decoction on hyperlipidemia model mice.METHODS ELISA method was used to detect the four blood lipid indexes,liver function indicators and cholesterol acyltransferase levels in serum.HE and Oil Red O staining were used to determine the pathology of liver tissue.Network pharmacology was used to predict the lipid-lowering related targets of Zexie Decoction,and the GO function and KEGG pathway enrichment analyses of the intersection targets were realized.PCR chip technology was used to detect the target genes for network pharmacology screening,and qPCR and Western blot were used to detect gene and protein expression levels.RESULTS Zexie Decoction significantly regula-ted the four blood lipid indexes in hyperlipidemia model mice,improved the increase in liver damage indicators caused by high lipids,and had a reverse regulatory effect on the key enzymes HMGR and CYP7A1 of lipid metabolism and the lipid transporters ABCA1 and Apo-A1 in liver tissue.HE and Oil Red O staining showed that Zexie Decoction improved the pathological morphology of liver tissue,reduced lipid deposition in liver tissue,and significantly decreased the positive area ratio(P<0.01).The PCR chip obtained 44 re-verse-regulated genes,GO functional enrichment analysis obtained 266 entries,and KEGG pathway enrichment analysis screened 99 signaling pathways.The results of qPCR and Western blot showed that Zexie Decoction significantly downregulated the expression of PIK3CG,AKT1,and IL-6 genes(P<0.05,P<0.01),upregulated the expression of ABCG1 gene(P<0.05),downregulated PI3Kinase p110β,p-AKT(Ser473)and SREBP-1c protein expression levels(P<0.01),and reversely regulated miR21-5p(P<0.01).CONCLUSION Zexie Decoction has a significant regulatory effect on lipid metabolism in hyperlipidemia model mice and can improve liver damage caused by hyperlipidemia.Its lipid-regulating effect may be related to regulating cholesterol metabolism and transport in the body,and is closely linked to the miR21/PI3K-Akt/SREBP pathway.The lipid-regulating effect of the whole formula of Zexie Decoction is better than that of a single herb.

OBJECTIVE To investigate the effect and mechanism of action of KRT8 small interfering RNA(si-KRT8)in exosomes derived from patient serum with hypopharyngeal carcinoma on chemosensitivity to 5-fluorouracil(5-FU)in human pharyngeal squamous cell carcinoma FaDu cell line.METHODS The cancerous tissues of hypopharyngeal cancer patients and The serum,cancerous tissues and paracancerous tissues of drug-resistant patients after treatment were collected.A 5-FU-resistant cell line of FaDu(FaDu/R)was constructed for subsequent experiments.Exosomes were isolated from patient serum by ultrafast gradient centrifugation,identified using transmission electron microscopy and Western blot(WB)techniques.si-KRT8 was encapsulated into exosomes(Exosome@si-KRT8)using electroporation technology and subsequently used to treat cells.Real-time fluorescence quantitative PCR(RT-qPCR)and WB were used to detect the expression levels of KRT8 in different tissues,exosomes after electroporation of si-KRT8,and FaDu cells,respectively.Cell counting kit-8(CCK-8),terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay,migration invasion technique and WB were used to detect the effects of Exosome@si-KRT8 on viability,apoptosis,and epithelial-mesenchymal transition of FaDu/R cells.RESULTS The expression level of KRT8 in drug-resistant tissues of hypopharyngeal carcinoma and FaDu/R cells was elevated compared with that in paraneoplastic tissues,cancer tissues and normal FaDu cells(t=15.79,P＜0.01).Isolated patient serum exosomes showed a double membrane structure and expressed both CD63 and TSG101 proteins,and KRT8 expression in exosomes was decreased after electro-transfection with si-KRT8(t=6.70,P＜0.01).Exosome@si-KRT8 inhibited KRT8 protein expression levels in FaDu/R cells(t=123.50,P＜0.01).Compared with the 5-FU group and the 5-FU+Exosome group,Exosome@si-KRT8 was able to inhibit the viability of FaDu/R cells(t=17.07,P＜0.01),promote the level of apoptosis in FaDu/R cells,and inhibit the expression of drug-resistance-associated proteins in FaDu/R cells(P-gp:t=103.20,MDR1:t=238.60,P＜0.01),and Exosome@si-KRT8 was able to suppress the expression of metastasis of FaDu/R cells(t=42.30,t=122.00,P＜0.01)and promoted the expression of E-cadherin while inhibiting the expression level of N-cadherin(t=130.80,t=83.90,P＜0.01).CONCLUSION Serum-derived exosome encapsulation of si-KRT8 enhances chemosensitivity of hypopharyngeal carcinoma cells and its mechanism of action may be related to inhibition of epithelial-mesenchymal transition.

ObjectiveTo investigate the effects of Yiqi Wenyang Huoxue Lishui components on the cardiac function and mitochondrial energy metabolism in the rat model of chronic heart failure （CHF） and explore the underlying mechanism. MethodsThe rat model of CHF was prepared by transverse aortic constriction （TAC）. Eight of the 50 SD rats were randomly selected as the sham group， and the remaining 42 underwent TAC surgery. The 24 SD rats successfully modeled were randomized into model， trimetazidine （6.3 mg·kg^-1）， and Yiqi Wenyang Huoxue Lishui components （60 mg·kg^-1 total saponins of Astragali Radix， 10 mg·kg^-1 total phenolic acids of Salviae Miltiorrhizae Radix et Rhizoma， 190 mg·kg^-1 aqueous extract of Lepidii Semen， and 100 mg·kg^-1 cinnamaldehyde） groups. The rats were administrated with corresponding agents by gavage， and those in the sham and model groups were administrated with the same amount of normal saline at a dose of 10 mL·kg^-1 for 8 weeks. Echocardiography was used to examine the cardiac function in rats. Enzyme-linked immunosorbent assay was employed to determine the serum levels of N-terminal pro-B-type natriuretic peptide （NT-ProBNP）， hypersensitive troponin（cTnI）， creatine kinase （CK）， lactate dehydrogenase （LD）， free fatty acids （FFA）， superoxide dismutase （SOD）， and malondialdehyde （MDA）. The colorimetric assay was employed to measure the levels of adenosine triphosphate （ATP）， adenosine diphosphate （ADP）， and adenosine monophosphate （AMP） in the myocardial tissue. The pathological changes in the myocardial tissue were observed by hematoxylin-eosin staining and Masson staining. The Na⁺-K⁺-ATPase and Ca²⁺-Mg²⁺-ATPase activities in the myocardial tissue were determined by the colorimetric assay. The ultrastructural changes of myocardial mitochondria were observed by transmission electron microscopy. Western blot was employed to determine the protein levels of ATP synthase subunit delta （ATP5D）， glucose transporter 4 （GLUT4）， and carnitine palmitoyltransferase-1 （CPT-1）. The mitochondrial complex assay kits were used to determine the activities of mitochondrial complexes Ⅰ， Ⅱ， Ⅲ， and Ⅳ. ResultsCompared with the sham group， the model group showed a loosening arrangement of cardiac fibers， fracture and necrosis of partial cardiac fibers， inflammatory cells in necrotic areas， massive blue fibrotic tissue in the myocardial interstitium， increased collagen fiber area and myocardial fibrosis， destroyed mitochondria， myofibril disarrangement， sparse myofilaments， and fractured and reduced cristae. In addition， the rats in the model group showed declined ejection fraction （EF） and fractional shortening （FS）， risen left ventricular end-diastolic diameter （LVIDd）， left ventricular end-systolic diameter （LVIDs）， left ventricular end-diastolic posterior wall thickness （LVPWd）， left ventricular end-systolic posterior wall thickness （LVPWs）， left ventricular end-diastolic volume （LVVOLd）， and left ventricular end-systolic volume （LVVOLs）， elevated levels of NT-ProBNP， cTnI， CK， MDA， FFA， and LD， lowered level of SOD， down-regulated protein levels of GLUT4 and CPT-1， decreased activities of Na⁺-K⁺-ATPase， Ca²⁺-Mg²⁺-ATPase， and respiratory complexes Ⅰ-Ⅳ， and declined levels of ATP5D， ATP， ADP， and AMP （P<0.05， P<0.01）. Compared with the model group， the Yiqi Wenyang Huoxue Lishui components and trimetazidine groups showed alleviated pathological damage of the mitochondria and mycardial tissue， risen EF and FS， declined LVIDd， LVIDs， LVPWd， LVPWs， LVVOLd， and LVVOLs， lowered levels of NT-ProBNP， cTnI， CK， MDA， FFA， and LD， elevated level of SOD， up-regulated protein levels of GLUT4 and CPT-1， increased activities of Na⁺-K⁺-ATPase， Ca²⁺-Mg²⁺-ATPase， and respiratory complexes Ⅰ-Ⅳ， and elevated levels of ATP5D， ATP， ADP， and AMP （P<0.05， P<0.01）. ConclusionYiqi Wenyang Huoxue Lishui components can improve the cardiac function， reduce myocardial injury， regulate glucose and lipid metabolism， optimize the utilization of substrates， and alleviate the damage of mitochondrial structure and function， thus improving the energy metabolism of the myocardium in the rat model of CHF.

Objective: To investigate the correlation between age-related hearing loss and cognitive impairment. Methods: 201 elderly patients, who were admitted to the Department of Otorhinolaryngology of Peking University People′s Hospital from March 1, 2017 to March 31, 2017, were evaluated with hearing screening and the Montreal Cognitive Assessment Scale. Among them, 101 were female and 100 were male, aged 60-90 years old. Taking the cognitive level as the dependent variable, and taking the age, sex, education, occupation, marital status, residence, and average hearing loss (average hearing threshold of 500, 1 000, 2 000, and 4 000 Hz), as well as the length of conscious hearing loss as the independent variables, the single factor analysis and multivariate linear regression analysis were used to screen the main factors affecting the cognitive level of the elderly. Results: Of the 201 elderly patients, 39 had normal hearing, 65 had mild hearing loss, 80 had moderate hearing loss, 16 had severe hearing loss, and 1 had profound hearing loss. The average degree of hearing loss was the influencing factor of cognitive impairment, and it mainly affected the directional force and abstract ability in the cognitive domains (P<0.05); The age, self-reported hearing loss, years of education, marital status, past ear diseases, and hypertension were relatively independent factors that affected the cognitive level(P<0.05). Conclusions Age-related hearing loss is the risk factor for the cognitive impairment, especially for abstraction and orientation, in the elderly. The self-reported hearing loss is an independent risk factor for cognitive impairment.