[Mechanism and clinical treatment strategy of heparin resistance].

Heparin resistance is becoming a hot issue of clinical concern. In critically ill patients, heparin resistance can lead to failure of anticoagulation therapy or increase the risk of major bleeding. Prompt recognition of heparin resistance can help to precisely adjust heparin dosage and avoid deterioration and adverse events. Heparin resistance can be mechanistically classified into the antithrombin-mediated and the non-antithrombin-mediated. Common etiologies include heparin-induced thrombocytopenia, severe infections such as severe COVID-19, treatment with extracorporeal circulation or extracorporeal membrane oxygenation (ECMO), and use of factor Xa reversal agents; heparin resistance is now often identified by the concordance of activated partial thromboplastin time (APTT) ratio with anti-FXa. Common clinical management strategies include antithrombin supplementation and replacement of anticoagulant drugs (e.g., direct thrombin inhibitors), but their safety and efficacy still need to be further validated.

[An occupational acute poisoning incident of diethylene glycol monobutyl ether].

Objective: To analyze the causes and clinical characteristics of 9 cases of occupational acute poisoning with diethylene glycol monobutyl ether, and provide a basis for clinical diagnosis, treatment, prognosis, and prevention. Methods: The leakage accident of diethylene glycol monobutyl ether occurred in an electronic company in Janvary 2021, in Weihai City was analyzed. The clinical manifestations, laboratory examinations, diagnosis, treatment and prognosis of 9 cases of diethylene glycol monobutyl ether poisoning were summarized. Results: All 9 patients had moderate chemical eye burns and chemical conjunctivitis, and were immediately given symptomatic treatment. They fully recovered after 14 days. Conclusion: Patients who inhale diethylene glycol monobutyl ether for a short time have obvious eye burns, but early detection and timely treatment can achieve better prognosis.

Association of placenta-derived extracellular vesicles with pre-eclampsia and associated hypercoagulability: a clinical observational study.

OBJECTIVE: Pre-eclampsia (PE) is a pregnancy-associated condition initiated by placental factors. We have demonstrated that placental extracellular vesicles (pcEVs) cause hypertension and proteinuria in pregnant and non-pregnant mice. STUDY DESIGN: An observational study with both case-control and longitudinal designs. SETTING: A single centre at the Department of Obstetrics and Gynaecology, Tianjin Medical University. POPULATION: We collected blood samples and clinical information from 54 PE patients, 33 normally pregnant women at 30-36 gestational weeks and on postpartum days 1 and 4 for the cross-sectional study, and at 22-31, 32-35 and 36-40 weeks for the longitudinal study. Non-pregnant women were also recruited. METHODS: Blood samples were analysed using flow cytometry, coagulation tests and ELISA. MAIN OUTCOME MEASURES: The primary outcome was plasma pcEV and other extracellular vesicles (EVs), and their expressions of anionic phospholipids and von Willebrand factor (VWF). Secondary variables included coagulation, ADAMTS-13 and the anionic phospholipid-binding proteins. RESULTS: Plasma pcEVs progressively increased from pregnant women during non-menstrual period (NW) to PE patients (interquartile range [IQR] for NW: 206/microlitre [116-255], normal pregnancy [NP]: 1108/microlitre [789-1969] and PE: 8487/microlitre [4991-16 752]) and predicted PE. EVs from endothelial cells, platelets and erythrocytes accounted for <10% of pcEVs. VWF became hyper-adhesive in PE patients and contributed to the pregnancy-associated hypercoagulability. CONCLUSION: Placental, platelet- and endothelial cell-derived EVs were significantly elevated in PE patients, but only pcEVs predicted PE. These EVs played a causal role in the pregnancy-induced hypercoagulability. TWEETABLE ABSTRACT: Placenta-derived extracellular vesicles predict pre-eclampsia and the associated hypercoagulability.

[Effect of hemocoagulase agkistrodon on coagulation status in patients with traumatic brain injury in vitro].

Objective: To analyze the effects of hemocoagulase agkistrodon (HCA) on the coagulation status of healthy people and traumatic brain injury (TBI) patients in vitro. Methods: A total of 10 TBI patients were enrolled from December 2018 to June 2019,and 24 age and sex matched healthy controls were also enrolled. Clinical and pathological data, blood samples of all subjects were collected. Different gradient concentrations of HCA were added to the blood samples which were detected by thromboelastography, and the R value, K value, α angle and MA value of thromboelastography parameters between the two groups were analyzed to explore the effect of HCA on the coagulation status of patients with TBI. Results: With the increase of HCA concentration in blood samples, the R and K values gradually increased, and the α angles and MA values gradually decreased in both TBI patients group which included 7 males and 3 females, with an median age of 33 (28-39) years old and healthy control group which included 11 males and 13 females, with an median age of 33 (23-49) years old. The differences in the R values, K values, α angles, and MA values of different concentration gradients were statistically significant in both healthy control group and TBI patients group (χ2 were 109.80, 131.28, 185.47, 165.97 and 54.92, 75.60, 80.12, 59.25, respectively, all P<0.001). The differences between R values after adding HCA of 0-0.105 U/ml in the healthy group were statistically significant (P=0.025), but K values, α angles and MA values were not statistically significant (P values were 0.275, 0.206 and 0.330, respectively); the R values of the TBI patients group were not statistically significant after adding HCA of 0 to 0.105 U/ml (P=0.976), and the K values, α angles, and MA values were statistically significant (P values were 0.047, 0.041, and 0.034, respectively).The R values of the healthy control group, the TBI patients group, and the overall data were significantly positively correlated with the HCA dose (r values were 0.552、0.700、0.420, respectively, P<0.001), the K values were significantly positively correlated with the HCA dose (r values were 0.726、0.861、0.750, respectively, P<0.001), the α angles were significantly negatively correlated with the HCA dose (r values were -0.815、-0.876、-0.807, respectively, P<0.001) and the MA values were significantly negatively correlated with the HCA dose (r values were -0.757、-0.710、-0.729, respectively, P<0.001). Conclusions: HCA does not aggravate the procoagulant state of blood in healthy people and TBI patients, and with the increase of HCA concentration in blood, the blood samples of both groups show a tendency to decrease the coagulation ability.

[Investigation on occupational hazards in 20 automobile manufacturing enterprises in Shandong Province].

Objective: To investigate the current situation of occupational hazards in automobile manufacturing enterprises in Shandong Province. Methods: From February to May 2019, the convenience sampling method was adopted to conduct on-site occupational health surveys with 20 automobile manufacturing enterprises in Shandong Province as the survey subjects, to detect the occupational hazard factors in the workplaces and individual exposure levels, and to analyze the occupational health check results of operators. Results: There were 13 small-sized, 4 medium-sized and 3 large-sized enterprises among the 20 automobile manufacturing enterprises. The detection results of benzene and toluene in the workplaces met the occupational exposure limits, and the detection results of welding fumes, manganese and its compounds, and xylene exceed the occupational exposure limits. The maximum short-term exposure concentration (C(STE)) of welding fume in the air of workplaces was 24.23 mg/m(3), and the over-standard rate was 11.0% (16/146) . The maximum time-weighted average concentration (C(TWA)) of welding fume of operators is 10.60 mg/m(3), and the over-standard rate was 11.0% (8/73) . The maximum C(STE) of manganese and its compounds in the air of workplaces was 0.879 mg/m(3), and the of manganese and its compounds of operators was 0.175 mg/m(3), and the over-standard rate was 5.7% (4/70) . The maximum xylene C(STE) in the air of workplaces was 230.00 mg/m(3), and the over-standard rate was 3.9% (2/51) . The maximum xylene C(TWA) of operators was 70.40 mg/m(3), the over-standard rate was 3.6% (1/28) . Among the 4775 workers exposed to occupational hazards, 38 (0.80%) were suspected of electric welder's pneumoconiosis, 27 (0.57%) were suspected of manganese poisoning and 31 (0.65%) were suspected of chronic low-concentration benzene and benzene series poisoning. The detection rates of suspected occupational diseases among workers in small and medium-sized enterprises were relatively high, 2.86% (30/1048) and 4.51% (51/1132) respectively. There was a statistically significant difference in the detection rates of suspected occupational diseases among the operators of different scale automobile manufacturers (P<0.05) . Conclusion: The exposure levels of electric welding fumes, manganese and its compounds in welding jobs and xylene exposure levels in spray painting jobsin Shandong Province's automobile manufacturing enterprises are more serious. The supervision and management of occupational hygiene should be strengthened, the working environment should be improved, and the health of welding and painting workers should be protected.

Discourse macrolinguistic impairment as a marker of linguistic and extralinguistic functions decline in early Alzheimer's disease.

BACKGROUND: Alzheimer's disease is characterized by macrolinguistic changes. This decline is often analyzed with quantitative scales. AIMS: To analyze discourse production in early Alzheimer's disease (AD) and to identify qualitative markers of macrolinguistic decline. METHODS & PROCEDURES: We analyzed macrolinguistic features of a clinical narrative task along with patients' cognitive changes. To do so, 17 early AD participants and 17 healthy controls were recruited and given a full neuropsychological and language assessment. Narrative discourses produced during the language assessment were transcribed and macrolinguistic features were qualitatively analyzed (i.e., local and global coherence marks and discourse informativeness). Inter-group comparison was complemented by intra-group correlation. As some inter-group comparisons revealed the existence of subgroups of patients, permutation tests were used to investigate how these subgroups differed vis-à-vis cognitive measures. OUTCOMES & RESULTS: Overall, the results indicate that AD participants presented declines in informativeness and global coherence, correlated with declines in memory and executive functions. Permutation tests showed that participants with AD producing referential errors or misinterpretations had a deeper lexical-executive decline and a lower Mini-Mental State Evaluation (MMSE). CONCLUSIONS & IMPLICATIONS: This study shows that two clinically relevant, qualitative signs differ in discourse production between typical ageing and early AD, namely information units and modalizing discourse. It also shows that macrolinguistic assessment is a useful tool for revealing impaired communication and cognition in early AD. Although lexical processing decline probably contributes to patients' macrolinguistic impairment, implications of extralinguistic functioning should be further investigated.

[An investigation of occupational exposure to welding fume, manganese, and manganese compounds in a large container manufacturing enterprise].

Objective: To investigate the current status of the occupational hazards of welding fume, manganese, and manganese compounds in the welding environment of a large container manufacturing enterprise, as well as the status of occupational health examination of workers, and to provide a basis for improving the welding environment of this enterprise. Methods: In August 2016, July 2017, and August 2018, convenience sampling was used to perform an on-site occupational hygiene survey of the welding workshop for three consecutive years, and welding fume, manganese and, manganese compounds (counted as manganese dioxide) were measured for their workplace exposure concentrations and exposure levels in workers. A comprehensive analysis was performed for the results of occupational health examination. Results: Welding fume, manganese, and manganese compounds in the welding environment gradually increased from 2016 to 2018 (χ(2)(trend)=5.14 and 5.54, P<0.05). The maximum over-standard rate of concentration-short term exposure limit was 43.3% (13/30) for welding fume and 40.0% (12/30) for manganese and its compounds, and the maximum over-standard rate of time-weighted average concentration was 26.7% (8/30) for welding fume and 23.3% (7/30) for manganese and its compounds. Abnormalities were observed in the occupational health examination of welding workers in 2016-2018, among which respiratory system abnormalities (cough, expectoration, and wheezing), nervous system abnormalities (dizziness, fatigue, sleep disorders, amnesia, hyperhidrosis, and palpitations), and electrocardiogram abnormalities (bundle conduction block) had an incidence rate of above 10.0%, and the incidence rate of abnormalities on posterior-anterior X-ray high-kV chest radiograph was close to 8.9% (30/336) . Conclusion: There is severe exposure to welding fume, manganese, and manganese compounds among workers in this enterprise, which cause great hazards to the health of workers. It is necessary to strengthen occupational health management, take measures to improve the welding environment, and enhance occupational disease prevention.

[Effect of long-term crotonaldehyde exposure on heart damage in male rats].

Objective: To observe the effect of long term crotonaldehyde exposure on heart damage in male rats, and to explore the possible mechanism of toxic action. Methods: 24 specific pathogen free healthy male wistar rats were randomly divided into 4 groups with 6 rats in each group. Rats were treated with with 8.5, 4.5, 2.5 and 0.0 mg/kg body weight crotonaldehyde by gavage, once a day for consecutive 150 days. After the last treatment, they were anesthetized and collected blood samples by cardiac puncture. The heart was rapidly separated after cervical dislocation. The cardiac organ coefficient was calculated and the histopathology changes in heart were observed by HE staining. At the same time, the activities of creatine kinase (CK) , lactate dehydrogenase-L (LDH-L) in serum were determined by automatic biochemical analyzer. Moreover, the levels of cardiac troponin (cTnT) , Angiotensin Ⅱ (Ang Ⅱ) , Brain natriuretic peptide (BNP) , Aldosterone (ALD) and interleukin (IL) -6, 8, 1ß, interferon (IFN) -γ and tumor necrosis factor (TNF) -α in heart were determined by enzyme linked immunosorbent assay. Results: At the 90d, 120 d, and 150 d exposure, compared with the control group, the body weight gain in 4.5 and 8.5 mg/kg groups were decreased. Moreover, the heart weight in 4.5 and 8.5 mg/kg groups, and heart coefficient in 8.5 mg/kg group were decreased (P<0.05) . With the increasing dosage of crotonaldehyde, the degree of pathological changes in the heart of exposed rats were aggravated. The major pathological changes of heart in 4.5 and 8.5 mg/kg groups could be summarized as lymphocyte infiltration, abnormal cardiac muscle fiber arrangements, necrosis and fibrous connective tissue hyperplasia. Compared with the control group, the serum CK activity in 4.5 mg/kg group, CK and LDH-L activitivies in 8.5 mg/kg group were increased (P<0.05) ; Compared with the control group, the levels of ALD and ANGII in the heart of 4.5 and 8.5 mg/kg groups were increased, BNP level were decreased, and cTNT level in 8.5 mg/kg group were increased (P<0.05) . Compared with the control group, the levels of IL-1ß、IL-6、IL-8 in 4.5 mg/kg group and IL-1ß、IL-6、IL-8、TNF-α、IFN-γ in 8.5 mg/kg group were increased (P<0.05) . Conclusion: Crotonaldehyde could up-regulate cardiac inflammatory cytokines and alter the balance ofangiotensin-aldosterone-brain natriuretic peptide causing heart damage.

[Study on occupational exposure limits of tributyl phosphate in the workplace air].

Objective: To put forward the suggestion of the occupational contact limit of tributyl phosphate in the air of the workplace. Methods: Data of production and usage, workers' basic information, occupational history, and physical examinations were collected, and the environmental and individual levels of exposure were monitored using fixed-point and individual sampling. The results of the questionnaire and health examination were statistically analyzed using exact probability method of Fisher in the workers exposed to tributyl phosphate and the control group. Results: The results showed that tributyl phosphate was widely distributed in the workplace of production and using enterprises, and the concentration of tributyl phosphate in packaging area was highest at 2.47 mg/m(3), and in feeder nose was highest at 2.13 mg/m(3). The discomfort symptoms were classified and results showed that tributyl phosphate exposure group of 136 people, all symptoms of 128 people, accounting for 94.44% of the total, the remaining 5.56% of the staff report had psychiatric symptoms or lethargy and irritability skin itching, the control group had no symptoms. There is or not discomfort symptoms in the tributyl phosphate exposure group and the control group was compared with the exact probability of Fisher, and the difference was statistically significant (P<0.05) . The results of healthy physical examination of workers exposed to tributyl phosphate and control group were statistically analyzed by the exact probability method of Fisher. The results showed that there was no significant difference in the results of routine internal medical examination, nervous system examination, skin examination, five senses examination, blood routine, urine routine, lung ventilation, and X ray chest fluoroscopy between the tributyl phosphate exposure group and the control group (P<0.05) . Conclusion: The workplace permissible time-weighted tributyl phosphate and short-term exposure limit concentrations in China were set at 2.5 mg/m(3) and 5 mg/m(3), respectively.

What happens when nothing happens? An investigation of pauses as a compensatory mechanism in early Alzheimer's disease.

Lexical-semantic impairment is one of the earliest symptoms of Alzheimer's disease (AD) and is usually examined by single word processing tasks. During speech production, pauses are often investigated as a hallmark of a patient's lexical-semantic decline. In the current study, we put forward the hypothesis that pauses reflect different processes according to the type of discourse. We believe that lexical and semantic impairment would predict a patient's pause frequency in a picture-based narrative (PBN) while anterograde memory would predict a patient's pause frequency in a memory-based narrative (MBN). To demonstrate this, we recruited 17 early AD patients and 17 matched controls. They underwent a full neuropsychological and language assessment and two narrative production assessments. We compared pause duration and frequency in the AD participants' and healthy controls' PBN and MBN. A multiple regression model was used in each narrative and in each group individually to assess the relationship between cognitive processes and pause frequency. Our results show that participants with AD produced more pauses in the PBN only. The frequency was predicted by semantic fluency performance with which it was positively correlated, contrary to what was expected. In the MBN, pause frequency in the AD participants was positively correlated with and predicted by their memory performance. We then examined the neuroanatomical correlates of pause frequency in the AD participants. Considering the PBN, pause frequency was also positively correlated with the grey matter density of the anterior temporal lobe. These findings suggest that patients use pauses as compensatory mechanisms in the earliest stages of AD. Pauses therefore may reflect the time required for the compensation and the realisation of a weak process depending on the narrative task and should be considered as a positive sign.

[Effect of zinc on the activities of ATPase of erythrocyte membrane].

The effects of zinc on the activities of Na+, K(+)-ATPase and Ca2+, Mg(2+)-ATPase of erythrocyte membrane were studied both in vivo and in vitro. Male adult rats were divided into three groups and fed on diets with different concentration of zinc (2.2, 28 and 128 mg/kg diet). Eight rats of each group were sacrificed after 25 days and the activities of the two ATPase were measured. The rest rats were changed diet for an other seven days to detect the sensitivities of the ATPases. The activities of these ATPase were also determined in fresh human erythrocyte membrane treated with different concentration of zinc (0, 5, 10, 50, 100, 500 mumol/L). The results showed that the activities of both Na+, K(+)-ATPase and Ca2+, Mg(2+)-ATPase were in close relationship with zinc concentration, too low or too high zinc could decrease them. Compared with Na+, K(+)-ATPase, Ca2+, Mg(2+)-ATPase was more sensitive to zinc deficiency and in a slower reaction to zinc supplement, but it could stand higher zinc concentration. It was concluded that zinc played an important role on maintaining the normal activities of Na+, K(+)-ATPase and Ca2+, Mg(2+)-ATPase.

[Three lethal cases of Angiostrongylus cantonensis infected children].

OBJECTIVE: To offer approaches to diagnosis and treatment of Angiostrongylus cantonensis infection on the basis of analyzing three lethal cases of the disease. METHODS: Clinical manifestations, pathological changes and species identification were pursued. RESULTS: Angiostrongyliasis is usually neglected in medical departments. The three cases here reported were all misdiagnosed and had not receiced anthelmintic treatment hence fatality ensued. CONCLUSION: Early examination of CSF, bronchial lavage fluid and feces is urged so as to secure accurate diagnosis and conduct efficacious anthelmintic therapy to cure the patients.