Clinical values of morphology of hemophagocytes in infection associated hemophagocytic lymphohistiocytosis / 中华检验医学杂志

Objective:To study the morphology of hemophagocytosis (HPC) in bone marrow smears of patients with infection-associated hemophagocytic lymphohistiocytosis (IAHLH), and further analyse if there were differences in the clinical and laboratory features, the cytokines level and prognosisMethods:24 patients newly diagnosed with IAHLH from 2016-Dec-1 to 2021-Dec-31 in Beijing Friendship Hospital were included as study group, and 20 patients with infectious disease as non-HLH control group. In IAHLH group, mean age was 34±13 years, including 17(71%) males and7(29%) females. In Non-HLH group, mean agewas 43±16 years, including 14 (70%) males and6 (30%) females. Depending on re-checking phagocytic cell type on the initial bone marrow smear, the HPCs were divided into HPC-1, phagocytizing non-nucleated cells (mature erythrocyte or platelets), and HPC-2, phagocytizing nucleated cells. The differences in clinical presentations covered in HLH-2004 criteria, cytokines value(IL-6, IL-10, IL-18, IFN-γ) recommended in HLH-2022-China guideline, and the mortality within 1 year of diagnosis, were compared between IAHLH and non-HLH groups, between patients with or without HPC, and between patients with HPC-2 or only with HPC-1. For categorical variables, two groups were compared with the use of either the chi-square test or Fisher′s exact test. For non-normal distribution continuous variables, the difference between two groups variation was performed by using Mann-Whitney U test, and for normal distribution continuous variables, the difference was by the Independent Samples t-test.Results:The positive rates of fever, hepatomegaly and splenomegalyand the motrtality in IAHLH were 100% (24/24), 63% (15/24), 92% (22/24) and 46% (11/24), respectivelyin non-HLH were 55%(11/20),0(0/20),25% (5/20),0(0/20),and the differences between two groups were all statistically significant( P<0.01), but thedifferences between groups with and without HPC and between IAHLH patients with HPC-2 or only with HPC-1 were no statistically significanlly, ( P>0.05).In IAHLH group, IFN-γ in patients with HPC-2 was 400(246, 532)ng/L, significantly higher than 146(38, 180)ng/L in patients only with HPC-1 [ P=0.02, 95% CI was 233(75.8 to 397)], andthe other test parameters and cytokines level showed no obvious differences ( P>0.05).

Comparison of calculation results of five population pharmacokinetic analysis tools / 中国临床药理学与治疗学

AIM: To compare the results calculated by population pharmacokinetic analysis tools Phoenix NLME, Monolix, R nlmixr package and CPhaMAS cloud platform with the gold standard sofeware NONMEM. METHODS: Fifty sparse sampling data sets based on a one-compartment model and fifty dense sampling data sets based on a two-compartment model were simulated, and the above five analysis tools were used to calculate the population typical value, individual variability and individual pharmacokinetic parameters. RESULTS: The population typical value and individual variability calculated by CPhaMAS and Phoenix NLME had the highest matching degree with NONMEM, followed by nlmixr. Monolix had the lowest matching degree, but Monolix and nlmixr might be more robust. The correspondence between clearance and distribution volume was better than the absorption rate constant. Except the absorption rate constant calculated by Monolix and intercompartmental clearance calculated by nlmixr, the correlation coefficients of individual pharmacokinetic parameters calculated by all analytical tools were greater than 0.99. CONCLUSION: The results calculated by the above four population pharmacokinetic analysis tools are highly correlated with that of NONMEM.

The role of frontal plane cardiac axis shift in the diagnosis of wide QRS tachycardia / 实用医学杂志

Objective To explore the value of axis shift between the baseline normal sinus rhythm (NSR) and WCT in diagnosis of wide QRS-complex tachycardia (WCT). Methods 390 surface ECGs of 186 patients with WCT were obtained from April 2012 to April 2018 at Ningbo Medical Center Lihuili Hospital at which the arrhythmia diagnosis was proven by intracardiac electrophysiological study. The axis shift between the baseline NSR and WCT was calculated by table lookup method. Then we analyzed the role of axis shift in diagnosis of WCT. Results Among the 186 patients with WCT, 147 (79.03％) were ventricular tachycardia (VT) , and 39 (20.97％) were supraventricual tachycardia (SVT) with conduction abnormalities. In the 95％ confidence interval, the axis shift showed an outstanding discrimination performance. The area under the ROC curve is 0.708 (0.579-0.817, P =0.007). Compared with left axis deviation, right axis deviation, the right axis deviation of LBBB morphology, the axis shift> 68 degree is more sensitive (53.06％) , and the specificity (91.43％) is also more desirable. Moreover, if the axis shift set> 130 degree, the specificity can reach 100％, and the sensitivity (12.24％) is equivalent to northwestern axis. Conclusion A significant axis shift between the baseline NRS and WCT can distinguish WCT accurately. Given the ease of grasping, it can probably be feasible to popularize as a routine diagnosis method for WCT in primary hospitals.

Clinical characteristics and prognosis of invasive pulmonary aspergillosis in the respiratory intensive care unit / 中国医师进修杂志

Objective To demonstrate the clinical characteristics and prognosis of invasive pulmonary aspergillosis (IPA) in respiratory intensive care unit (ICU), for early diagnosis and treatment. Methods The clinical features, treatment and outcome of 17 patients diagnosed as IPA in RICU from May 2015 to April 2018 were analyzed retrospectively. Results The basic diseases of 17 patients were mostly chronic respiratory diseases (14 cases, while 11 cases were chronic obstructive pulmonary disease). One case was proven by IPA criteria, 13 cases were probable and 3 cases were possible. All patients were treated with broad-spectrum antibiotics during hospitalization, and 6 patients were treated with glucocorticoids (oral/intravenous) within 3 weeks of admission and during hospitalization. The main clinical symptoms included cough sputum, dyspnea and fever, among which 4 cases had hemoptysis. Infiltrates were seen in 8 cases, multiple nodules with cavitary lesions in 4 cases, multiple small nodules along the bronchi in 2 cases, and left upper lobe consolidation in the proven case. Sixteen patients were treated with voriconazole alone or in combination with caspofungin. Fourteen patients were tested for voriconazole serum concentration, while 4 were in normal range, 10 were elevated (2 cases were significantly elevated, ＞10 μg/L). Serum concentration of bilirubin did not increase significantly in all paitents after treatment. Serum concentrations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were elevated in 4 cases with elevated serum concentration of voriconazole and 2 cases with normal serum concentration of voriconazole. Patients with elevated voriconazole concentration did not show significant difference in prognosis compared with those with normal concentration. Eight cases were improved and discharged and 9 gave up and died due to the worsening of the disease. Eight patients received mechanical ventilation (6 cases were invasive and 2 cases were non-invasive), 7 of them eventually gave up treatment and died. Conclusions The clinical features of chronic respiratory diseases with IPA are atypical, however, the patient is critically ill with high mortality. Elevated serum concentration of voriconazole might be more common in severe patients. For those who have a history of systemic application of glucocorticoids, clinical symptoms with hemoptysis, short of breath, radiology with infiltrates, nodular and/or with cavity, and with no response to antibiotics, clinicians should actively seeking evidence of IPA, for early diagnosis, standardized treatment, and improve the prognosis of patients with chronic respiratory diseases complicated with IPA.

Comparative study on common diagnostic methods for covert hepatic encephalopathy / 中华消化杂志

Objective To evaluate clinical application value of critical flicker frequency (CFF),psychometric hepatic encephalopathy score (PHES) and Stroop test in the diagnosis of covert hepatic encephalopathy (CHE).Methods A total of 110 patients with decompensated liver cirrhosis and 54 individuals without liver diseases were enrolled as control group.According to PHES＜-4 points as reference threshold for CHE,the threshold of CFF and time of Stroop test for CHE diagnosis was caculated.Positive results of at least two of PHES,CFF and Stroop tests was considered as the gold standard for CHE diagnosis,and then the value of these three methods in CHE diagnosis was evaluated.Student's t test and receiver operating characteristic curve (ROC) were used for statistical analysis.Results Among the 110 patients with liver cirrhosis,40 patients had no hepatic encephalopathy (HE0),52 patients had CHE,and 18 patients had grade 2 hepatic encephalopathy (HE2).The CFF value and total time of Stroop test of control group were (43.70±1.92) Hz and (201.17±20.65) s,respectively.The CFF value of HE0 group was (41.40 ± 1.85) Hz,which was higher than that of CHE group ((38.33 ± 2.32) Hz),and the difference was statistically significant (t=-7.116,P＜0.01).The total time of Stroop test of HE0 group was (197.91±26.68) s,which was shorter than that of CHE group ((253.24± 33.33) s),and the difference was statistically significant (t=8.936,P＜0.01).When PHES＜-4 points was considered as a reference threshold of CHE,the threshold of CFF for CHE diagnosis was 39 Hz,the sensitivity was 94.9％ and the specificity was 73.1％,the area under the curve (AUC) was 0.879.The threshold of the total time of Stroop test for CHE diagnosis was 233.80 s,the sensitivity was 83.3 ％ and the specificity was 71.1％,the AUC was 0.803.The completion time of the number connection test (NCT)-A,NCT-B and digit symbol test (DST),which were there of five subtests of PHES,of CHE group were (80.27±36.05) s,(124.18±55.96) s and (25.03±8.23) s,respectively,compared with those of HE0 patients ((56.68±18.82) s,(80.00±25.58) s and (34.68±8.75) s,respectively),the differences were statistically significant (t =3.691,4.108 and-4.780;all P＜0.01).Compared with the results of combined PHES and Stroop test in the diagnosis of HE0,CHE and HE2,the consistency rates of CFF＜39 Hz as threshold for diagnosis were 95.0％,61.5％ and 100.0％,respectively.Conclusions NCT-A,NCT-B and DST three subtests of PHES have higher efficiency in CHE diagnosis.CFF and Stroop test are also reliable screening methods for CHE,with advantage of objectivity and high specificity.

Aspergillus fumigatus conidia inhibit early apoptosis of alveolar epithelial cells / 中华传染病杂志

Objective To observe the impact of Aspergillus fumigatus conidia on the early apoptosis of alveolar epithelial cells.Methods A549 cells was first stimulated with tumor necrosis factor-α(TNF-α)or staurosporine (STS)to induce cell apoptosis,and then co-cultured with Aspergillus fumigatus conidia of three different concentrations (5 × 10 5 ,5 × 10 6 ,5 × 10 7 )simultaneously.The changes of the apoptosis rate of A549 cells were detected by flow cytometry.Results The early apoptosis of A549 cells was increased markedly after stimulated with TNF-α ([14.94 ± 0.82 ]% vs [3.26 ± 0.74]%,χ2 =9.18,P <0.05)and STS ([18.10±1 .00]% vs [3.26±0.74]%,χ2 =12.32,P <0.05). When Aspergillus fumigatus conidia of different concentrations were added,the apoptosis rate was decreased (χ2 =31 .23,P <0.05 ).The early apoptosis of A549 cells was negatively correlated with the concentration of Aspergillus fumigatus conidia (rTNF = - 0.92,r STS = - 0.94,both P < 0.05 ). Conclusion Aspergillus fumigatus conidia inhibits the early apoptosis of A549 cells induced by TNF-αor STS and the inhibit effect increases with the concentration of Aspergillus fumigatus conidia.

A preliminary study on the mutation of TLR4 gene in patients with invasive aspergillosis / 医学研究生学报

Objective Toll-like receptor ( TLR) gene family is the most important pathogen recognition receptor and animal experiment have found TLR4 mice is inclined to infect aspergillosis ( IA) .The study was to investigate the variation of TLR4 gene in Chinese Han nationality and its relation with the susceptibility of IA. Methods 25 patients diagnosed with proven IA from June 2011 to December 2012 in our hospital were enrolled, among which 17 were males.Their average age was 52.4 ±12.3, and 12 pa-tients had underlying diseases, the others had no underlying diseases.The control group consisted of 103 normal persons, among which 70 were males.Their average age was 56.0 ±17.2.All of the subjects were Chinese Han population.DNA was extracted from periph-eral blood.Polymerase chain reaction ( PCR) was applied to amplify the coding sequence of TLR4 gene followed by sequencing.The sequencing result was compared with TLR4 coding sequence in NCBI GenBank along with the analysis on amino acid change caused by genetic mutation and its effect on protein function.Comparison analysis was made on genetic mutation rate between IA group and con-trol group. Results Two missense mutations,TLR4 219 C>G and 1420 C>T, were identified in TLR4.The prediction result of protein structure showed 219 C>G resulted in the change of functional area for TLR4 to recognize pathogen and 1420 C>T caused no change in domains.The variation rate of TLR4 in IA group was 8%( 2/25 ) and both the patients had no underlying diseases. No mutation has been founded in control group and the difference between two groups was of statistical significance (P=0.037). Conclusion Two missense mutations (219 C>G and 1420 C>T) have been detec-ted in encoding area of TLR4 gene of IA patients.Variation in the cod-ing region of TLR4 gene may increase the susceptibility to IA.

Diagnostic values of noninvasive parameters in liver cirrhosis with severe esophageal varices / 中华消化杂志

Objective To analyze the correlation between Doppler ultrasound parameters, blood biochemical indexes and the severity of esophageal varices (EV), and to explore the values of them in the diagnosis of severe EV.Methods A total of 102 hospitalized patients with liver cirrhosis was consecutively collected.All patients underwent endoscopic examination to determine the presence and severity of EV, then they were divided into moderate/severe EV group (n=78) and non/mild EV group (n=24).Congestion index of the portal vein (PV-CI), damping index of hepatic vein(HV-DI), hepatic vein arrival time(HVAT) and intrahepatic circulatory time (IHCT) were measured by Doppler ultrasound and contrast-enhanced ultrasound.And at same time, the level of yon Willebrand factor antigen (vWF-Ag) and soluble CD163 (sCD163) in peripheral blood were detected by enzyme linked immunosorbent assay (ELISA) method.The differences of these parameters between two groups were compared by independent samples t-test or Mann-Whitney rank sum test.The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy (DA) of related parameters in the prediction of EV were calculated according to receiver operating characteristic(ROC) curve.Results Ultrasound parameters PV-CI, HV-DI and peripheral blood vWF-Ag, sCD163 levels of moderate/severe EV group were all significantly higher than those of none/mild EV group 0.11 (0.05) cm · s vs 0.07(0.03) cm· s;0.72±0.11 vs0.52±0.12;1 824.00(558.00) U/Lvs 1 533.80(311.50) U/L;(72.57±10.94) μg/L vs (57.91±10.40) μg/L;Z=-4.949, t=-7.759, Z=-5.420, t=-5.804, all P＜0.05).However HVAT and IHCT were significantly shorter than those of non/mild EV group (17.00(4.25) s vs 27.78(6.75) s;(6.62±1.85) s vs (9.33±2.26) s, Z=-3.822, t=5.820, both P＜0.05).ROC curve analysis showed that the areas under the ROC curve of HVDI, vWF-Ag and sCD163 predicting moderate/severe EV were all more than 0.8, the appropriate cutoff value of HV-DI, vWF-Ag and sCD163 was 0.64, 1 693.8 U/L and 63.98 μg/L, respectively.The sensitivity were all more than 75％,PPV were all greater than 90％ and DA were all more than 80％.Conclusion HV-DI, peripheral blood vWF-Ag and sCD163 levels can be taken as noninvasive parameters, which can effectively predict the presence of severe EV, facilitate early detection of these high-risk bleeding patients and prevent bleeding.

The change of serum IL-17 and Dectin-1 in non-neutropenic patients with invasive pulmonary aspergillosis / 中国感染与化疗杂志

Objective To explore the changing levels of serumIL-17 and Dectin-1 and their implication in non-neutropenic pa-tients with invasive pulmonary aspergillosis (IPA).Methods The clinical data were reviewed for 23 non-neutropenic patients with clinical diagnosis of IPA (IPA group),31 patients with clinical diagnosis of pneumonia (pneumonia group)and 51 healthy subjects(control group).The peripheral serum was collected to analyze IL-17 level by ELISA.Serum Dectin-1 level was also determined at the same time.Serum G test,GM test,WBC and CRP level were also assayed for the patients in IPA group.Pa-tient outcome was followed up and analyzed in terms of serum IL-17.Results The serum IL-17 level of the patients in IPA group was significantly higher than that in the control group (P 0.05).The serum Dectin-1 level in IPA group was significantly higher than that in the control group (P 0.05 ). Conclusions Dectin-1 may be produced and Th17 cell immunity activated in response to Aspergillus fumigatus in-fection in non-neutropenic patients.And,serum Dectin-1 level is correlated with Th17 response.

Serum Dectin-1 in non-agranulocytic patients with pulmonary aspergillosis / 中国感染与化疗杂志

Objective To explore the clinical implication of serum Dectin-1 level in the non-agranulocytic patients with pulmonary aspergillosis. Methods Serum specimen were collected from the non-agranulocytic patients with pulmonary aspergillosis to determine the serum level of Dectin-1 with ELISA.The relationship between serum Dectin-1 level,the results of G test and galactomannan (GM)test of Aspergillus,and white blood cell count was analyzed.Results The serum Dectin-1 level was (427.2 ± 42.6)pg/mL in the patients with Aspergillus infection,and (280.8 ± 39.4)pg/mL in the control patients (P<0.05 ).Dectin-1 level was not correlated to white blood cell count,or the result of G test,or GM test. Conclusions Serum Dectin-1 level increases significantly in the non-agranulocytic patients with pulmonary aspergillosis, suggesting that Dectin-1 is an important anti-Aspergillus immune molecule.

Resistance and infection case analysis for multidrug-resistant Acinetobacter baumannii / 中华检验医学杂志

Objective To investigate the resistance and infection case for the Multidrug-Resistant Acinetobacter baumanii (MDRAb) strains.Methods Retrospective study.Thirty-eight MDRAb strains were collected in Beijing Friendship Hospital from February to August 2008.VITEK2-compact system was used to detect the MDRAb.PCR was carried out to detect their resistance related genes and look up the medical records those who were infected by MDRAb.Results The resistance rate of the MDRAb is the highest in ICU.PCR confirmed that OXA-23 and OXA-51 were 100％ related with the MDRAb.Combination drug therapy such as sulbactam combined with β-lactam antibiotics was more effective than β-lactam antibiotics only to treat the infection with MDRAb.Cases analysis showed that a number of patients infected by MDRAb were the aged with basic diseases,low immunity,received a variety of antibiotic therapy even traumatic operation,and they had a poor prognosis finally.Conclusions The resistance rate of the MDRAb is the highest in ICU,OXA-23 is closely related to multidrug-resistance.Combination drug therapy is necessary and sulbactam can play a great role in curing the inpatients infected with MDRAb.

Resistance and Homology Analysis of Acinetobacter baumannii / 中华医院感染学杂志

OBJECTIVE To investigate the resistance and the homology of the Acinetobacter baumannii(ABA) strains isolated from inpatients to offer basis for clinical treatment and preservation.METHODS VITEK2-compact system was used to identify 110 ABA strains,and detect their susceptibility to antibiotics.REP-PCR was carried out to detect their homology.RESULTS The 110 isolated strains were multidrug resistant.Rate of sensitivity to amikacin was 91.3%,Rates of resistance to ceftazadime,ciprofloxacin and imipenem were 100.00%,97.83% and 91.30%,respectively.REP-PCR was confirmed part of them was from the same clone.CONCLUSIONS Most of the isolated strains are multidrug-resistant.The same clone of MDR-ABA probably leads to transmission among patients.

Mechanisms underlying the antibiotic resistance of Pseudomonas aeruginosa / 医学研究生学报

Pseudomonas aeruginosa,a ubiquitous organism,shows a remarkable resistance to antibiotics because of its low permeability of the outer-membrane,over-expression of efflux pumps,inactivation of antibotics,or mutations in targets.These mechanisms are often present simultaneously,and increase the burden on clinical therapy.

The study of bone marrow micrometastases in small cell lung cancer / 医学研究生学报

Small cell lung cancer, most malignant and highly aggressive has a high relapse rate due to drug resistance. Potential strategies as high dose chemotherapy with autologous bone marrow transplantation and analysis on genes of metastases are focused on. In spite of great improvement, methods and clinic significances of bone marrow micrometastases are still to be determinated. Bone micrometastases may be a resort to clarify the mechanism of metastases.

Resistance Analysis and Detection of Resistant Genes in Acinetobacter baumannii / 中华医院感染学杂志

OBJECTIVE To investigate the resistance and the resistant mechanism of the imipenem-resistant Acinetobacter baumannii(IRAb) strains isolated from inpatients to guide for the clinical treatment and prevention.METHODS VITEK2-compact system was used to identify 77 IRAb strains,and to detect their susceptibility to antibiotics.K-B susceptibility testing was used to detect their susceptibility to amikacin and minocycline.PCR was carried out to detect their related genes.RESULTS The 77 isolated strains were multidrug-resistant.The rate of resistance to cephalosporins and quinolones was respectively higher than to amikacin whose sensitivity came to 90%;PCR confirmed OXA-23 was 100% related with IRAbs,OXA-51 was the same.CONCLUSIONS Most of IRAb were MDRAb.The mechanism of A.baumannii(ABA) to imipenem is closely related with OXA-23,K-B susceptibility test is more accurate and minocycline could be used for IRAbs.