Objective To elaborate the changes of the soluble B cell-activating factor of the tumor necrosis factor family (BAFF) in the peripheral blood of chronic human immunodeficiency virus (HIV)-infected patients ,and to study the correlation between the soluble BAFF in HIV-infected patients and the progressions of acquired immune deficiency syndrome (AIDS).Methods Fifty untreated HIV outpatients and 30 healthy controls were recruited .According to the counts of CD4+T lymphocytes ,HIV-infected patients were divided into three groups ,＜ 200 cells／μL group , (200 － 350 ) cells／μL group and ＞350 cells／μL group .B cell counts and the BAFF levels were compared among the three groups and the healthy controls .The correlation analysis was conducted for the levels of BAFF ,the counts of CD4+T lymphocytes and B cells ,and viral load in HIV-infected patients .The value of BAFF in staging of HIV disease was identified by receiver operating characteristic (ROC) curve.Results The B cell counts were (90.3 ± 43.1)cells／μL in ＜200 cells／μL group ,(114 .4 ± 28 .8) cells／μL in (200 －350) cells／μL group ,and (162 .1 ± 29 .5) cells／μL in ＞350 cells／μL group and (307.1 ± 97 .0) cells／μL in healthy controls ,which was significantly different among the four groups (F＝47.92 ,P＜0.05).The concentrations of BAFF in the four groups were (1 737.5 ± 719.7) ,(962.8 ± 341.1) ,(859.8 ± 270.4) ,and (456.9 ± 163.7) ng／L ,with significant difference among the groups (F＝36.72 ,P＜0.05).The level of BAFF was negatively correlated with both B cell counts and CD4+T lymphocyte counts (r＝ －0.722 and －0.568 ,respectively ;both P＜0.05) ,and positively correlated with viral load (r＝0.607 ,P＜0 .05).The area under the ROC curve was 0 .881.If the level of BAFF was 1 281.5 ng／L ,the sensitivity and specificity to predict the period of AIDS were 74 .1% and 87.0%,respectively .Conclusion The levels of soluble BAFF in HIV-infected patients are significantly increased and related with the reduction of B cell counts and disease progression.

Objective:To investigate the prognostic factors of severe patients with bloodstream infection (BSI) caused by Enterobacteriaceae bacteria. Methods:Patients suffered from BSI caused by Enterobacteriaceae bacteria admitted to department of critical care medicine of Binzhou Medical University Hospital from October 2016 to October 2019 were enrolled. The information of gender, age, combined shock, acute physiology and chronic health evaluationⅡ(APACHEⅡ), sequential organ failure assessment (SOFA), sensitivity of initial antibiotics, as well as the baseline of procalcitonin (PCT), white blood cell count (WBC), platelet (PLT), albumin (ALB) were collected. The 72-hour PCT clearance rate (72 h PCTc) was calculated after 72 hours' treatment. According to the clinical outcome after 28 days, the patients were divided into recovery group and death group. The differences of clinical indicators between the two groups were compared, and then the statistical significant variables were further performed by Logistic regression to analyze the factors affecting the prognosis of patients. The receiver operating characteristic (ROC) curve was drawn to evaluate the predictive efficacy of the factors in severe BSI. Results:A total of 86 patients were enrolled, among whom 54 cases recovered while 32 cases died, and the 28-day mortality was 37.2%. There was no significant difference in gender, age, sensitivity of initial antibiotics, baseline levels of PCT and WBC between two groups. In the death group, the shock incidence, APACHEⅡscore, SOFA score were significantly higher than those in recovery group [shock incidence: 84.4% (27/32) vs. 46.3% (25/54), APACHEⅡ: 24.94±7.65 vs. 17.02±6.57, SOFA: 11.00±3.27 vs. 6.30±2.65, all P < 0.01]; the PLT and ALB baseline levels, 72 h PCTc were significantly lower than those in recovery group [PLT (×10 9/L): 73.38±49.15 vs. 138.69±101.80, ALB (g/L): 25.47±5.91 vs. 28.59±4.53, 72 h PCTc: -44 (-170, 27)% vs. 63 (40, 77)%, all P < 0.01]. The above 6 variables were included in Logistic regression. The results showed that SOFA score was a risk factor for death in these patients [odds ratio ( OR) = 1.930, P = 0.037], while 72 h PCTc and ALB were protective factors ( OR values were 0.043, 0.783, P values were 0.008, 0.047). The SOFA, 72 h PCTc and ALB can be used to predict the prognosis of severe BSI, and the diagnostic value of the combination of three factors was the largest [area under the ROC curve (AUC) = 0.953, 95% confidence interval (95% CI) was 0.909-0.997], the sensitivity was 100%, and the specificity was 79.6%. Conclusions:Severe patients with BSI caused by Enterobacteriaceae bacteria had a high mortality. Higher SOFA score, and lower ALB and 72 h PCTc predicted the adverse outcome. The combination of the three factors has the greatest prognostic efficacy.

Objective:To explore the value of high mobility group box 1 (HMGB1), von Willebrand factor (vWF) and other cytokines in predicting the severity and prognosis of sepsis patients.Methods:Patients with sepsis and septic shock who ≥18 years old and met the Sepsis-3 diagnostic criteria admitted to the department of critical care medicine of Binzhou Medical University Hospital from January to June 2019 were taken as the research objects. The healthy individuals for regular health examination in the same period were taken as the control. The basic information, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) and sequential organ failure assessment (SOFA) scores were recorded. The venous blood was taken within 24 hours after the patients were diagnosed. The levels of HMGB1, vWF, tumour necrosis factor-α (TNF-α), interleukin-10 (IL-10), soluble thrombomodulin (sTM), vascular endothelial growth factor receptor 2 (VEGFR-2), angiopoetin-2 (Ang-2) and other cytokines in serum were determined by enzyme linked immunosorbent assay (ELISA). Differences among patients with sepsis, septic shock, healthy physical examinees, and patients who died in 28-day and those who survived, were compared. Spearman rank correlation method was used to analyze the correlation among each cytokine and APACHEⅡ, SOFA scores. The receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of cytokines on the prognosis of patients with sepsis/septic shock. Logistic regression was used to analyze the risk factors of 28-day death.Results:Eleven patients with sepsis, 25 patients with septic shock and 30 healthy individuals were enrolled. Among the patients with sepsis/septic shock, 15 died in 28-day and 21 survived. The serum levels of TNF-α, IL-10, HMGB1, vWF, sTM and VEGFR-2 in patients with sepsis were significantly higher than those in the healthy control group. The levels of TNF-α, IL-10, HMGB1, vWF, sTM in septic shock group were higher than those in the sepsis group, while the Ang-2 level decreased significantly. The serum levels of TNF-α, IL-10, HMGB1, vWF and sTM in the death group were higher than those in the survival group, while Ang-2 was lower than the survival group. Spearman correlation analysis showed that HMGB1, TNF-α, sTM, IL-10, vWF were positively correlated with APACHEⅡ score when patients with sepsis/septic shock were enrolled ( r values were 0.652, 0.666, 0.445, 0.430 and 0.355, respectively, all P < 0.05), and HMGB1, TNF-α also positively correlated with SOFA score ( r values were 0.433, 0.479, both P < 0.05). Ang-2 was negatively correlated with APACHEⅡ and SOFA scores ( r values were -0.519, -0.440, both P < 0.05). ROC curve analysis showed that the predictive value of HMGB1, vWF, IL-10, sTM for 28-day death in patients with sepsis/septic shock were higher than the APACHEⅡ score [the area under ROC curve (AUC) and 95% confidence interval (95% CI): 0.946 (0.870-1.000), 0.902 (0.790-1.000), 0.877 (0.745-1.000), 0.868 (0.734-1.000) vs. 0.846 (0.700-0.991)]. Logistic regression analysis showed that APACHEⅡ score, vWF, sTM, and IL-10 were independent risk factors for 28-day death in patients with sepsis/septic shock (β values were 4.731, 0.407, -7.058, -0.887, all P < 0.05). Conclusion:HMGB1, vWF, IL-10, sTM and other cytokines all can be used to evaluate the severity and prognosis of sepsis patients.

Objective To study the correlation between CD169 expression of monocytes and disease progression in human immunodeficiency virus (HIV )-infected patients .Methods Sixty HIV-infected patients and 30 healthy controls were recruited .According to the CD4 + T lymphocyte counts ,HIV-infected patients were divided into three groups including < 200 cells/μL ,200 — 350 cells/μL and > 350 cells/μL groups . The differences in monocytes counts ,the proportions of CD16 + and CD169 + monocytes were analyzed among the three groups and healthy controls .The correlations between proportion of CD169 + monocytes and CD4 + T lymphocyte counts ,viral load ,and proportion of CD16 + monocytes were analyzed .Results The monocyte counts in CD4 + T lymphocytes < 200 cells/μL group , (200 — 350 ) cells/μL group , >350 cells/μL group and healthy control group were (342 ± 99) ,(396 ± 145) ,(365 ± 80) ,and (404 ± 106)/μL ,respectively ,which were not significantly different (F= 2 .55 , P > 0 .05) .The proportions of CD16 + monocytes in the four groups were (19 .8 ± 8 .8)％ ,(14 .3 ± 2 .8)％ ,(9 .7 ± 2 .0)％ and (4 .0 ± 0 .8)％ ,respectively ,which were significantly different ( F = 30 .90 , P < 0 .05 ) . The proportions of CD169 + monocytes in the four groups were (72 .6 ± 11 .4)％ ,(59 .4 ± 14 .7)％ ,(33 .3 ± 14 .5)％ and (2 .6 ± 0 .8)％ ,respectively ,which were significantly different (F = 152 .40 , P< 0 .05) .The proportion of CD169 + monocytes was negatively correlated with CD4 + T lymphocyte counts (r = 0 .792 , P< 0 .05) , while positively correlated with both viral load (r= 0 .485 ,P< 0 .05) and proportion of CD16 + monocytes (r= 0 .395 , P< 0 .05) .Conclusions The CD169 expressions of monocytes in HIV-infected patients are significantly increased and correlated with both monocyte activation and disease progression .

Objective:To explore the effect of continuous blood purification (CBP) on the immunity and endothelial cell function of patients with sepsis.Methods:A prospective study was conducted. The patients aged ≥18 years old and meeting the diagnostic criteria of sepsis admitted to the department of critical care medicine of Binzhou Medical University Hospital from March 2019 to October 2020 were selected as the research subjects, and the patients were divided into standard treatment group and CBP treatment group according to random number table method. Both groups were given standard treatment including initial fluid resuscitation, infection source control and antibiotics according to the 2016 international guidelines for the management of sepsis and septic shock. CBP treatment group was additionally given continuous veno-venous hemofiltration (CVVH) at a dose of 25-30 mL·kg -1·h -1 and blood flow rate of 150-200 mL/min for more than 20 hours a day for 3 days. The clinical data of patients including blood lactic acid (Lac), procalcitonin (PCT), lymphocyte count (LYM), acute physiology and chronic health evaluationⅡ(APACHEⅡ) score, sequential organ failure assessment (SOFA) score were recorded before treatment and 1 day and 3 days after treatment. At the same time, the venous blood was collected, and the immune function related indexes [interleukins (IL-4, IL-7), programmed death receptor-1 (PD-1), programmed death ligand-1 (PD-L1), interferon-γ (IFN-γ)] and endothelial cell injury related markers [soluble thrombomodulin (sTM), angiopoietin-2 (Ang-2), von Willebrand factor (vWF), heparan sulfate (HS), syndecan-1 (SDC-1)] levels in serum were determined by enzyme-linked immunosorbent assay (ELISA). The length of intensive care unit (ICU) stay of patients in the two groups was recorded, and the outcomes of patients in the two groups were followed up for 28 days. Results:Finally, 20 patients were enrolled in the standard treatment group, and 19 patients were enrolled in the CBP treatment group. There were no significant differences in gender, age and infection site between the two groups. The length of ICU stay in the standard treatment group was (10±5) days, and 5 patients died and 15 patients survived after 28 days. The length of ICU stay in the CBP treatment group was (9±4) days, and 8 patients died and 11 patients survived after 28 days. There were no significant differences in the length of ICU stay and number of patients who died within 28 days between the two groups (both P > 0.05). There were no significant differences in the Lac, PCT, LYM, APACHEⅡ score, SOFA score and immune function and endothelial cell injury related indexes before treatment and 1 day after treatment between the two groups. After 3 days of treatment, the Lac, PCT, APACHEⅡ score and SOFA score of the CBP treatment group were significantly lower than those before treatment, and pro-inflammatory and anti-inflammatory cytokines such as IFN-γ and IL-4, apoptosis-related indicators such as PD-1 and IL-7, and endothelial injury related factors such as sTM, SDC-1 and HS were significantly improved compared with the pre-treatment, the improvement degree of the above indicators was more obvious than that of the standard treatment group, and LYM was significantly higher than that of the standard treatment group (×10 9/L: 1.3±0.3 vs. 0.9±0.4, P < 0.05), IL-4, IFN-γ, IFN-γ/IL-4 ratio, IL-7, PD-1, sTM, SDC-1, HS, and Ang-2 were significantly lower than those of the standard treatment group [IL-4 (ng/L): 2.8 (1.5, 3.2) vs. 3.3 (2.7, 5.2), IFN-γ (ng/L): 6.3 (5.4, 106.5) vs. 217.9 (71.4, 517.1), IFN-γ/IL-4 ratio: 3.7 (1.8, 70.3) vs. 59.1 (18.3, 124.9), IL-7 (ng/L): 4.6 (3.2, 5.1) vs. 6.3 (5.2, 8.0), PD-1 (μg/L): 0.04 (0.03, 0.06) vs. 0.08 (0.05, 0.12), sTM (μg/L): 4.9 (4.3, 7.4) vs. 8.7 (6.0, 10.8), SDC-1 (μg/L): 0.6 (0.3, 1.1) vs. 0.9 (0.8, 2.5), HS (ng/L): 434.8 (256.2, 805.0) vs. 887.9 (620.1, 957.3), Ang-2 (ng/L): 934.0 (673.3, 1 502.1) vs. 2 233.9 (1 472.5, 3 808.4)], the differences were statistically significant (all P < 0.05). Conclusion:CBP treatment can eliminate the patient's immunosuppressive state, reduce a variety of endothelial injury markers and the degradation of glycocalyx, but cannot decrease the 28-day death risk or shorten the length of ICU stay.

Objective:To investigate the prognostic value of proprotein convertase subtilisin/kexin type 9 (PCSK9) and blood lipid indexes in patients with sepsis.Methods:Patients with sepsis or septic shock who were ≥ 18 years old and met the Sepsis-3.0 diagnostic criteria admitted to the department of critical care medicine of Binzhou Medical University Hospital from January to October 2021 were enrolled. Healthy adults at the same period were selected as healthy control group. Baseline characteristics, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) and sequential organ failure assessment (SOFA) score were recorded. Venous blood samples were collected within 24 hours after diagnosis, and serum PCSK9 was determined by enzyme-linked immunosorbent assay (ELISA) at 1, 3 days and 5 days. Meanwhile, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG) and lipoprotein A were detected. The differences of each index between sepsis group (28-day death group and survival group) and healthy control group were compared. Meanwhile, the indexes of patients with different severity and 28-day prognosis in sepsis group were compared. Receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of PCSK9 and blood lipid for the prognosis of sepsis. Multivariate Logistic regression was used to analyze the influencing factors for the prognosis of sepsis, and the Kaplan-Meier survival curve at 28th day was drawn.Results:There were 50 patients in sepsis group (including 19 patients with sepsis, 31 patients with septic shock) and 27 patients in healthy control group. In the sepsis group, 19 patients died and 31 patients survived within 28 days. The serum PCSK9 in the sepsis group was significantly higher than that in the healthy control group [μg/L: 223.09 (198.47, 250.82) vs. 188.00 (165.27, 214.90), P < 0.01], and HDL-C, LDL-C, TC and lipoprotein A were significantly lower than those in the healthy control group [HDL-C (mmol/L): 0.82±0.35 vs. 1.45±0.24, LDL-C (mmol/L): 1.53 (1.14, 2.47) vs. 2.89 (2.55, 3.19), TC (mmol/L): 2.03 (1.39, 2.84) vs. 4.24 (3.90, 4.71), lipoprotein A (g/L): 8.80 (5.66, 17.56) vs. 27.03 (14.79, 27.03), all P < 0.01]. PCSK9 in the sepsis death group was higher than that in the survival group [μg/L: 249.58 (214.90, 315.77) vs. 207.01 (181.50, 244.95), P < 0.01], and the HDL-C, LDL-C and TC were lower than those in the survival group [HDL-C (mmol/L): 0.64±0.35 vs. 0.93±0.30, LDL-C (mmol/L): 1.32±0.64 vs. 2.08±0.94, TC (mmol/L): 1.39 (1.01, 2.23) vs. 2.69 (1.72, 3.81), all P < 0.01]. With the progression of the disease, the PCSK9 in the sepsis death group and the survival group was significantly lower than that within 1 day of diagnosis (all P < 0.05). ROC curve analysis showed that PCSK9 had higher predictive value of 28-day death than HDL-C, LDL-C, TC [area under ROC curve (AUC) and 95% confidence interval (95% CI): 0.748 (0.611-0.885) vs. 0.710 (0.552-0.868), 0.721 (0.575-0.867), 0.702 (0.550-0.854)]. Multivariate Logistic regression analysis showed that PCSK9 was an independent risk factor affecting the 28-day prognosis of sepsis (β value was 1.014, P = 0.020). Kaplan-Meier survival curve analysis showed that when PCSK9 ≥ 208.97 μg/L, with the increase of PCSK9, the 28-day survival rate of sepsis patients decreased significantly. Conclusions:PCSK9, HDL-C, LDL-C and TC can all predict the 28-day prognosis of patients with sepsis. The prognostic value of PCSK9 is the highest. PCSK9 is an independent risk factor affecting the prognosis of sepsis. In the early stage of the disease, PCSK9 may have a good predictive value for the prognosis of sepsis. When PCSK9 ≥ 208.97 μg/L, the 28-day survival rate decreased significantly.