OBJECTIVE: To explore the effect of bear bile powder (BBP) on acute lung injury (ALI) and the underlying mechanism. METHODS: The chemical constituents of BBP were analyzed by ultra-high-pressure liquid chromatography-mass spectrometry (UPLC-MS). After 7 days of adaptive feeding, 50 mice were randomly divided into 5 groups by a random number table (n=10): normal control (NC), lipopolysaccharide (LPS), dexamethasone (Dex), low-, and high-dose BBP groups. The dosing cycle was 9 days. On the 12th and 14th days, 20 µL of Staphylococcus aureus solution (bacterial concentration of 1 × 10^-7 CFU/mL) was given by nasal drip after 1 h of intragastric administration, and the mice in the NC group was given the same dose of phosphated buffered saline (PBS) solution. On the 16th day, after 1 h intragastric administration, 100 µL of LPS solution (1 mg/mL) was given by tracheal intubation, and the same dose of PBS solution was given to the NC group. Lung tissue was obtained to measure the myeloperoxidase (MPO) activity, the lung wet/dry weight ratio and expressions of CD14 and other related proteins. The lower lobe of the right lung was obtained for pathological examination. The concentrations of inflammatory cytokines including interleukin (IL)-6, tumour necrosis factor α (TNF-α ) and IL-1β in the bronchoalveolar lavage fluid (BALF) were detected by enzyme linked immunosorbent assay, and the number of neutrophils was counted. The colonic contents of the mice were analyzed by 16 sRNA technique and the contents of short-chain fatty acids (SCFAs) were measured by gas chromatograph-mass spectrometer (GC-MS). RESULTS: UPLC-MS revealed that the chemical components of BBP samples were mainly tauroursodeoxycholic acid and taurochenodeoxycholic acid sodium salt. BBP reduced the activity of MPO, concentrations of inflammatory cytokines, and inhibited the expression of CD14 protein, thus suppressing the activation of NF-κB pathway (P<0.05). The lung histopathological results indicated that BBP significantly reduced the degree of neutrophil infiltration, cell shedding, necrosis, and alveolar cavity depression. Moreover, BBP effectively regulated the composition of the intestinal microflora and increased the production of SCFAs, which contributed to its treatment effect (P<0.05). CONCLUSIONS BBP alleviates lung injury in ALI mouse through inhibiting activation of NF-κB pathway and decreasing expression of CD14 protein. BBP may promote recovery of ALI by improving the structure of intestinal flora and enhancing metabolic function of intestinal flora.
Animals ; Acute Lung Injury/pathology* ; Lipopolysaccharides ; Ursidae ; Gastrointestinal Microbiome/drug effects* ; Bile/chemistry* ; Lipopolysaccharide Receptors/metabolism* ; Powders ; Male ; Lung/drug effects* ; Mice ; Peroxidase/metabolism* ; Signal Transduction/drug effects* ; Cytokines/metabolism*

【Objective】 To determine the best collection time period of plasma which can be used for human COVID-19 immunoglobulin for intravenous injection through SARS-CoV-2-IgG change and neutralizing antibody distribution against different virus strain in representative mixed plasma before and after Omicron strain infection by ELISA and pseudovirus neutralization test. 【Methods】 An ELISA method for quantitative detection of SARS-CoV-2-IgG was established and its linear range,accuracy and precision was verified. SARS-CoV-2-IgG potency was detected in 25 convalescent plasma which were collected 20-40 days after confirmed Omicron infection, two groups of mixed plasma samples WP1 and WP2 were prepared according to the SARS-CoV-2-IgG results, and pseudovirus neutralization experiments with different virus strain (prototype strain, BA. 1,BA.2, BA.4/5, BF.7, BQ.1.1) were carried out to determine the distribution of neutralizing antibodies against different virus strain. SARS-CoV-2-IgG potency of representative mixed plasma collected from 14 plasma stations subordinate to the company before and after Omicron strain infection was detected, including Omicron convalescent plasma (OP) collected from different plasma stations from December 2022 to May 2023 and normal pool plasma (VN) feed in March 2023 which collected from March 2022 to December 2022. According to the results, the difference and the change rule with time of SARS-CoV-2-IgG before and after Omicron strain infection were analyzed. 【Results】 The linearity of SARS-CoV-2-IgG ranged from 6.25 to 200 EIU/mL, the accuracy in-batch ranged from 81.793% to 106.985%, the precision in-batch ranged from 1. 100% to 13.000%, and the total error in-batch ranged from 2.988% to 22.679%. The accuracy between batches ranged from 90.788%to 96.893%, the precision between batches ranged from 4.870% to 6.272%, and the total error between batches ranged from 9.192% to 15.399%. The results of pseudovirus neutralizing antibody showed that the potency of different virus strain neutralizing antibodies were in the order of prototype strain>BA.2>BA.4/5>BF.7≈ BQ.1.1>BA.1 and the correlation between WP1 and WP2 was high (Pearson r=0. 931 1, P=0.002 3) which indicated that the potency distribution of neutralizing antibodies of different virus strain in Omicron convalescent plasma was basically stable. Compared with the mixed convalescent plasma sample G128 collected in June 2022, the potency of Omicron neutralizing antibodies of WP series were significantly higher, the ratio of BA.2 antibody to prototype antibody increased from 26.9% (before infection) to 82.6%-87.5% (after infection). The results of VN series before Omicron infection were < 100 EIU/mL, and the results of OP series after Omicron infection showed that the plasma collected from the beginning of December 2022 was the peak of antibody in the same month,and then dropped sharply, entering a short plateau in February-March 2023 (potency was about 40% of the peak value),and then dropped sharply again in April (potency was about 20% of the peak value). 【Conclusion】 The potency and proportion of neutralizing antibody against Omicron subtype in convalescent plasma after COVID-19 Omicron strain infection increased significantly. IgG antibody of plasma donors in different regions reached its peak in the month of infection, then continued to dropped sharply. The best collection period of plasma that can be used for human COVID-19 immunoglobulin for intravenous injection was 1 to 2 months after infection.

The incidence and mortality of HCC in China account for approximately 50% of all cases worldwide. Low early diagnosis rate and high postoperative recurrence rate are two major causes for poor 5-year survival rate of HCC patients in China. At present, multiple problems such as low performance and compliance of screening technology and lack of effective markers for predicting postoperative recurrence, remain to be resolved. Due to the simplicity and accuracy, new molecular markers, such as liquid biopsy, are expected to serve as supplementary tools to traditional screening and early warning approaches, thereby realizing early detection and accurate treatment of HCC. In this article, research progress upon the clinical application of liquid biopsy in early screening and prediction of postoperative recurrence of HCC was reviewed, and prospects the future research.
Biomarkers ; Carcinoma, Hepatocellular/pathology* ; Humans ; Liquid Biopsy ; Liver Neoplasms/pathology* ; Mass Screening ; Neoplasm Recurrence, Local

Objective: To observe the effects of Fufang Lishao Pills (FFLSP) on the proinflammatory factors, pain-relatedproteins and JAK2/STAT3 signaling pathways in nitroglycerin-induced chronic migraine model, and exploring thepharmacological target and mechanism of FFLSP on chronic migraine rats. Methods: Male Sprague-Dawley rats wererandomly divided into 6 groups: Control, Migraine, FFLSP-L (420 mg·kg-1), FFLSP-M (840 mg·kg-1), FFLSP-H (1680mg·kg-1) and Flunarizine Hydrochloride group (FH, 1 mg·kg-1) . Chronic migraine model was made by subcutaneousinjection of nitroglycerin (10 mg·kg-1) once every 3 days for 5 times. The rats were treated with FFLSP by intragastricadministration once a day for 30 days. Western blot was used to detect the protein expression of iNOS, COX-2, CGRPand c-Fos and the phosphorylation levels of JAK2 and STAT3 in cortex of rats. The production of IL-1β and TNF-αwere detected by enzyme linked immunosorbent assay (ELISA) . Results: Compared with Control rats, and the level ofiNOS, COX-2, CGRP, c-Fos expression (P ＜ 0.01) and IL-1β, TNF-α production remarkably up-regulated (P ＜ 0.05), and the phosphorylation of JAK2 and STAT3 also significantly increased in cotex of Migrainerats (P ＜ 0.01) . However, compared with Migrainerats, the levels of iNOS, COX-2, CGRP, c-Fos expression and IL-1β, TNF-α productionobviously declined (P ＜ 0.05; P ＜ 0.01), and the phosphorylation level of JAK2 and STAT3 showed a significantlydecrease in the cortex of Migraine rats with FFLSP treatment (P ＜ 0.01) . Conclusion: This study demonstrates that thepharmacological mechanism of FFLSP in improving chronic migraine may be achieved by inhibiting neuroinflammationthrough the blockage of JAK2/STAT3 pathwayin the cortex of rat with nitroglycerin induction.

Objective: To explore the clinical features, the serotype distribution and drug resistance of the isolates in patient with invasive pneumococcal disease (IPD). Methods: By retrieving the laboratory information system in 18 children′s hospitals from 2012 to 2017, the children with IPD were enrolled. Streptococcus pneumoniae (Spn) must be isolated from the sterile sites (blood, cerebrospinal fluid, hydrothorax and joint effusion etc.). The clinical characteristics, serotype, drug resistance, treatment and prognosis were reviewed and analyzed. According to the telephone follow up results, the patients were divided into death group and recovered group. The index as an independent risk factor of mortality was demonstrated by multivariate logistic regression analysis. Results: There were 1 138 children with IPD, including 684 male and 454 female. The proportion of male to female was 1.5∶1. The age ranged from one day to 16 years. The median age was 1 year 3 month. The majority was under 5 years of age (89.3%, n= 1 016), especially under 2 years of age (61.9%, n=704). In all cases, 88.2% (n=1 004) were community acquired infection. The infections included meningitis (n=446, 39.2%), pneumonia with bacteremia (n=339, 29.8%), and bacteremia without focus (n=232, 20.4%). Underlying diseases were found in 242 cases (21.3%). Co-infections were determined in 62 cases (5.4%) with mycoplasma, 27 cases (2.4%) with adenovirus and 34 cases with influenza virus (3.0%). The penicillin insensitivity (PNSP) rates in meningitis and non-meningitis isolates were 69.5% (276/397) and 35.9% (221/615), respectively. There were 81 strains serotyped, in which 93.8% (76/81) were covered by 13-valent protein-polysaccharide conjugate vaccine (PCV13). In the 965 patients who were followed up by phone call, 156 cases (16.2%) were confirmed dead. The independent risk factors for the death were under 2 years of age (OR=2.143, 95%CI 1.284-3.577, P=0.004), meningitis (OR=3.066, 95%CI 1.852-5.074, P<0.01), underlying disease (OR=4.801, 95%CI 2.953-7.804, P<0.01), septic shock(OR=3.542, 95%CI 1.829-6.859, P<0.01), disseminated intravascular coagulation (DIC) (OR=4.150, 95%CI 1.468-11.733, P=0.007), multiple organ failure (OR=12.693, 95%CI 6.623-24.325, P<0.01) and complications of central nervous system (OR=1.975, 95%CI 1.144-3.410, P=0.015). Conclusions Most children with IPD were under 5 years of age, having underlying diseases and acquired the infection in community. The independent risk factors for death were under two years old, meningitis, underlying diseases and multiple organ failure. The problem of drug resistance was severe. The universal immunization of PCV13 would be effective to prevent IPD in Chinese children.

Three-dimensional speckle tracking echocardiography was employed to evaluate the changes of left ventricular systolic strain in 23 heart transplant recipients at 1st, 3rd, 6th and 12th month after heart transplantation, and 23 healthy subjects served as controls. The three-dimensional full-volume echocardiographic images of left ventricle were recorded and then were analyzed using EchoPAC software. The strain curves and peak systolic strain values for each segment and overall left ventricular wall were obtained. Left ventricular global peak longitudinal strain (GPSL), global peak radial strain (GPSR), global peak circumferential strain (GPSC) and global peak area strain (GPSA) were measured and then statistically analyzed. There were no significant differences in left ventricular ejection fraction (LVEF) and cardiac output (CO) between heart transplant recipients and controls. The GPSL in heart transplant recipients at 1st month after surgery was significantly lower than that in controls, but close to the normal value at 3rd month after surgery and later. The GPSC, GPSA and GPSR were significantly lower in heart transplant recipients at 1st, 3rd, 6th and 12th month after surgery than those in controls. It is suggested that three-dimensional speckle tracking echocardiography can be used for monitoring changes of left ventricular systolic strains and evaluating left ventricular systolic function in cardiac allograft.
Adolescent ; Adult ; Allografts ; Echocardiography, Three-Dimensional ; methods ; Female ; Heart Function Tests ; methods ; Heart Transplantation ; methods ; Humans ; Male ; Middle Aged ; Reproducibility of Results ; Sensitivity and Specificity ; Systole ; Time Factors ; Ventricular Dysfunction, Left ; diagnosis ; diagnostic imaging ; Ventricular Function, Left ; Young Adult

OBJECTIVETo explore the characteristics of particulate matter pollution in coke oven plant, so as to provide scientific data for establishing occupational exposure limits for coke oven emissions.

METHODSConcentrations of CO, SO₂, BSM, BTEX (concentrations of benzene, toluene and xylene were determined in this study), PM₁₀, PM₂.₅, 16 selected PAHs in PM₁₀ and PM₂.₅ were determined in the work environment of a coke oven plant in Wuhan. The work environment was divided into the adjunct area, the bottom of, the side of and the top of coke oven.

RESULTSThe concentrations of CO, SO₂, BSM, BETX, PM₁₀, PM₂.₅, PAHs in PM₁₀ and PM₂.₅ were significantly related to working environmental categories, respectively, and were increasing as the adjunct area < bottom < side < top (P (trend) < 0.05). PM₁₀ was statistically significantly correlated with CO, SO₂, benzene, BTEX and BSM (0.705, 0.823, 0.664, 0.624 and 0.734, respectively). PM₂.₅ was statistically significantly correlated with CO, SO₂, benzene, BTEX and BSM (0.635, 0.916, 0. 680, 0.553 and 0.726, respectively). BSM was statistically significantly correlated with benzene (0.689). The ratios of PM₂.₅ to PM₁₀ between different work environments were not significantly different in one-way ANOVA (P > 0.05). The distribution of aromatic rings and the concentrations of total benzo[a] pyrene equivalents in PM₁₀ and PM₂.₅ were not statistically different between work environments.

CONCLUSIONThe concentrations of particulate matter was related with other contents of coke oven emissions in coke work environment, and the contents and types of PAHs in PM₁₀ and PM₂.₅ were similar.

Air Pollutants, Occupational ; analysis ; Benzene ; analysis ; Benzo(a)pyrene ; analysis ; Coke ; Occupational Exposure ; analysis ; Particulate Matter ; analysis ; Polycyclic Aromatic Hydrocarbons ; analysis ; Toluene ; analysis ; Workplace ; Xylenes ; analysis

OBJECTIVETo explore the effects of smoking on urinary 10 metabolites of polycyclic aromatic hydrocarbons (PAHs) in the coke oven workers.

METHODSOccupational health examination was performed on 1401 coke oven workers in one coking plant, their urine were collected respectively. The concentrations of the ten monohydroxy polycyclic aromatic hydrocarbons in urine were detected by gas chromatography/mass spectrometry. The 1401 workers were divided into four groups, namely control, adjunct workplaces, bottom and side, top group according to their workplaces and the different concentrations of PAHs in the environment. The concentrations of the ten monohydroxy polycyclic aromatic hydrocarbons between smokers and nonsmokers in each workplace group were compared using analysis of covariance, respectively.

RESULTSThe levels of concentrations of the sixteen polycyclic aromatic hydrocarbons we detected at control were significantly higher than those at other areas (P < 0.05). Comparing the ten monohydroxy polycyclic aromatic hydrocarbons levels between smokers and nonsmokers, the levels of 1-hydroxynaphthalene and 2-hydroxynaphthalene among smokers were higher than nonsmokers with statistically significance in control, adjunct workplaces, bottom and side and top groups (P < 0.05). However, the levels of 1-hydroxypyrene had no statistically significant differences between the four areas.

CONCLUSIONUrinary 1-hydroxynaphthalene and 2-hydroxynaphthalene may be used as biomarkers for the impact of smoking on monohydroxy polycyclic aromatic hydrocarbons in the coke oven workers.

Air Pollutants, Occupational ; urine ; Biomarkers ; urine ; Coke ; Humans ; Male ; Naphthols ; urine ; Occupational Exposure ; analysis ; Polycyclic Aromatic Hydrocarbons ; urine ; Pyrenes ; urine ; Smoking ; urine

OBJECTIVETo study the protective effects of Ginkgo biloba extract (EGb) on the lung injury of dogs undergoing hypothermic cardiopulmonary bypass (CPB).

METHODSFourteen healthy hybrid dogs were randomly divided into the control group and the EGb group, 7 in each group. EGb (8 mg/kg) was intravenously dripped to dogs in the EGb group before thoracotomy after anesthesia, while equal volume of normal saline was intravenously dripped to those in the control group. The lung tissue was collected after 60-min CPB and 120-min recovery of heart beat. The lung tissues were collected to detect the wet weight-dry weight ratio and the permeability. The contents of malondialdehyde (MDA), the activities of myeloperoxidase (MPO) and total superoxide dismutase (T-SOD) in the lung tissues were detected by biochemical assay. The levels of IL-1beta, IL-8, tumor necrosis factor alpha (TNF-alpha), platelet activating factor (PAF) in the lung tissue were detected by enzyme linked immunosorbent assay (ELISA).

RESULTSCompared with the control group, the wet weight-dry weight ratio was reduced and the permeability of the lung tissue decreased (P < 0.05), the MDA content was reduced, the activity of MPO decreased, and the activity of T-SOD increased (P < 0.05), and the levels of IL-1beta, IL-8, and PAF obviously decreased (P < 0.05).

CONCLUSIONSEGb showed better protective effects on the lung injury of dogs undergoing hypothermic CPB. Its possible mechanisms might be associated with alleviating ischemia-reperfusion injury of in vitro circulation and systemic inflammatory response.

Animals ; Cardiopulmonary Bypass ; adverse effects ; methods ; Dogs ; Ginkgo biloba ; Lung Injury ; etiology ; prevention & control ; Plant Extracts ; pharmacology

OBJECTIVETo investigate the erythrocyte protective effects of Ginaton, a ginkgo biloba extract, in patients undergoing hypothermic cardiopulmonary bypass (CPB).

METHODSSixty patients, who suffered from rheumatic heart disease of ASA grade II-III and scheduled for mitral valve replacement with intravenous anesthesia, were randomly assigned to two groups equally, the Ginaton group and the control group. They were administered with Ginaton 1 mg/kg and saline respectively via intravenous dripping before open heart surgery before beginning CPB. Blood samples were taken from radial artery at different time points, i.e., before CPB (T1), nasopharyngeal temperature (30-31 degrees C) stabilized stage (T2), nasopharyngeal temperature restoration (36 degrees C) stage (T3), 30 min after CPB (T4) and 3 h after CPB (T5), for determination of malondialdehyde (MDA) and superoxide dismutase (SOD) levels in plasma and erythrocyte (P-MDA, E-MDA, P-SOD and E-SOD), as well as the Na+ -K+ -ATPase and Ca+ -Mg2+ -ATPase activities in erythrocytes.

RESULTSAs compared with those at T1, in the control group, P-MDA, E-MDA, and E-SOD at T2-T5 and E-SOD at T2 were higher, but E-SOD at T3-T5 were lower (P < 0.01); while in the Ginaton group P-MDA, E-MDA, and E-SOD at T3-T4 were higher (P < 0.05 or P < 0.01). As compared with those in the control group, the levels of P-MDA and E-MDA at T2-T5 were significantly lower, and E-SOD at T3-T5 were higher (P < 0.05 or P < 0.01). Activities of Na+ -K+ -ATPase and Ca+ -Mg2+ -ATPase significantly increased at T2 and gradually decreased after then in both groups (P < 0.05 or P < 0.01), but those at T2-T5 were significantly higher in Ginaton group than in control group (P < 0.05 or P < 0.01).

CONCLUSIONGinaton displays an erythrocyte protecting effect by way of alleviating the lipid peroxidation in erythrocytes' membrane.

Adult ; Cardiopulmonary Bypass ; methods ; Drugs, Chinese Herbal ; pharmacology ; Erythrocytes ; drug effects ; metabolism ; Female ; Ginkgo biloba ; Humans ; Hypothermia, Induced ; Lipid Peroxidation ; drug effects ; Male ; Middle Aged