Rehabilitation strategy for the improvement of long-term outcomes of patients after sepsis / 中华烧伤杂志

Survivors of sepsis still face high risks of secondary infection and mortality after hospital discharge. Meanwhile, the persistent cognitive, psychological, and physical disorders affect their long-term outcomes and life qualities. In the current review, we analyze the factors for the poor outcomes and discuss the beneficial rehabilitation strategies to improve the long-term outcomes of patients after sepsis, including psychological intervention, early mobility, nutrition support, and immune modulation, etc.

Early predictive value of high density lipoprotein cholesterol for secondary acute kidney injury in sepsis patients / 中华烧伤杂志

Objective: To investigate the changes of high density lipoprotein cholesterol (HDL-C) in sepsis patients and its early predictive value for secondary acute kidney injury (AKI) in such patients. Methods: A retrospective case series study was conducted. From June 2019 to June 2021, 232 sepsis patients who met the inclusion criteria were admitted to the Second Hospital of Hebei Medical University, including 126 males and 106 females, aged 24 to 71 years. According to whether complicating secondary AKI, the patients were divided into non-AKI group (n=158) and AKI group (n=74). Data of patients between the two groups were compared and statistically analyzed with independent sample t test or chi-square test, including the sex, age, body mass index (BMI), body temperature, heart rate, primary infection site, combined underlying diseases, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score and sepsis-related organ failure assessment (SOFA) score at admission, and the serum levels of C-reactive protein (CRP), procalcitonin, creatinine, cystatin C, and HDL-C measured at diagnosis of sepsis. The multivariate logistic regression analysis was performed on the indicators with statistically significant differences between the two groups to screen the independent risk factors for developing secondary AKI in 232 sepsis patients, and the joint prediction model was established based on the independent risk factors. The receiver operating characteristic (ROC) curve of the independent risk factors and the joint prediction model predicting secondary AKI in 232 sepsis patients were drawn, and the area under the curve (AUC), the optimal threshold, and the sensitivity and specificity under the optimal threshold were calculated. The quality of the above-mentioned AUC was compared by Delong test, and the sensitivity and specificity under the optimal threshold were compared using chi-square test. Results: The sex, age, BMI, body temperature, heart rate, primary infection site, combined underlying diseases, and CRP level of patients between the two groups were similar (P>0.05). The procalcitonin, creatinine, cystatin C, and scores of APACHE Ⅱ and SOFA of patients in AKI group were all significantly higher than those in non-AKI group (with t values of -3.21, -16.14, -12.75, -11.13, and -12.88 respectively, P<0.01), while the HDL-C level of patients in AKI group was significantly lower than that in non-AKI group (t=6.33, P<0.01). Multivariate logistic regression analysis showed that creatinine, cystatin C, and HDL-C were the independent risk factors for secondary AKI in 232 sepsis patients (with odds ratios of 2.45, 1.68, and 2.12, respectively, 95% confidence intervals of 1.38-15.35, 1.06-3.86, and 0.86-2.56, respectively, P<0.01). The AUCs of ROC curves of creatinine, cystatin C, HDL-C, and the joint prediction model for predicting secondary AKI in 232 sepsis patients were 0.69, 0.79, 0.89, and 0.93, respectively (with 95% confidence intervals of 0.61-0.76, 0.72-0.85, 0.84-0.92, and 0.89-0.96, respectively, P values all below 0.01); the optimal threshold were 389.53 μmol/L, 1.56 mg/L, 0.63 mmol/L, and 0.48, respectively; the sensitivity under the optimal threshold were 76.6%, 81.4%, 89.7%, and 95.5%, respectively; the specificity under the optimal threshold values were 78.6%, 86.7%, 88.6%, and 96.6%, respectively. The AUC quality of cystatin C was significantly better than that of creatinine (z=2.34, P<0.05), the AUC quality and sensitivity and specificity under the optimal threshold of HDL-C were all significantly better than those of cystatin C (z=3.33, with χ2 values of 6.43 and 7.87, respectively, P<0.01) and creatinine (z=5.34, with χ2 values of 6.32 and 6.41, respectively, P<0.01); the AUC quality and sensitivity and specificity under the optimal threshold of the joint prediction model were all significantly better than those of creatinine, cystatin C, and HDL-C (with z values of 6.18, 4.50, and 2.06, respectively, χ2 values of 5.31, 7.23, 3.99, 6.56, 7.34, and 4.00, respectively, P<0.05 or P<0.01). Conclusions: HDL-C level in sepsis patients with secondary AKI is significantly lower than that in patients without secondary AKI. This is an independent risk factor for secondary AKI in sepsis patients with a diagnostic value being superior to that of creatinine and cystatin C. The combination of the aforementioned three indicators would have higher predicative valuable for secondary AKI in sepsis patients.

Research progress of receptor protein FUNDC1 in mitophagy / 医学研究生学报

Mitochondria, which play an important role in cell metabolism, stress response and cell death, are the key organelles that regulate the energy balance of cells. Under the influence of internal and external environment, damaged or senescent mitochondria pose a serious threat to cell survival. Mitophagy refers to the selective elimination of dysfunctional mitochondria to maintain the homeostasis of the intracellular environment. FUN14 domain containing 1 (FUNDC1) is a newly discovered mitophagy receptor protein, which plays an important regulatory role in mediating mitophagy. This paper mainly reviews the recent research progress of FUNDC1 regulation mechanism and its pathophysiological significance in mitophagy.

Mechanism of immune regulatory dysfunction in surgical sepsis / 医学研究生学报

Surgical sepsis induced by major trauma, burns and hemorrhage remains a main cause of death of the patients in intensive care units, and may result in both the widespread activation and dysfunction of the innate and adaptive responses in the host immune system. A large amount of information concerning the subsets of innate and adaptive immune cells in sepsis has implicated that these cells, including neutrophils, macrophages, dendritic cells, T lymphocytes, regulatory T cells, and natural killer cells, have significant effects on immunoreactivity during acute insults or sepsis through modulating multiple receptor expressions or cytokine release, in turn contributing to the development and outcome of sepsis. Therefore, a deeper insight into the mechanism of immune regulatory dysfunction in surgical sepsis is of great significance in helping assess the prognosis of sepsis and guide the treatment of its complications.

Analysis of late diagnosis and its influencing factors of newly reported HIV/AIDS in Guizhou Province from 2014 to 2018 / 中华疾病控制杂志

Objective To find late diagnosis and its influencing factors of newly reported HIV/AIDS in Guizhou Province from 2014 to 2018. Methods Through the Chinese National Comprehensive HIV/AIDS Prevention and Care Information System,all newly reported HIV/AIDS cases from 2014 to 2018 in Guizhou Province were analyzed and related factors of late diagnosis were analyzed using binary Logistic regression model. Results From 2014 to 2018, there were 33 611 newly reported HIV/AIDS cases in Guizhou Province, and the late diagnosis rates of newly reported cases were 35.46%, 34.49%, 38.35%, 39.74% and 38.80% respectively. The analysis showed that the proportion of late diagnosis cases from medical institutions increased year by year ( 2=64.603,P<0.001). By analyzing the late diagnosis rate of cases from different sample sources, medical institutions was significantly higher than that reported by voluntary counseling and testing, positive spouses or sexual partners( 2=276.033,P<0.001). Multivariate analysis showed that gender, marital status, route of transmission, occupation, ethnicity and source of samples were associated with the late diagnosis of newly reported cases (all P<0.05). Conclusions It shows a slow upward trend of late diagnosis rate among HIV/AIDS reported in Guizhou Province from 2014 to 2018.On the one hand, it is of great significance to continue to strengthen the publicity and education of the whole population in Guizhou , in order to improve the awareness of HIV active detection. On the other hand, we should continue to expand HIV testing in Guizhou Province to improve the early detection level of HIV/AIDS.

Mortality analysis among HIV/AIDS cases in Guizhou Province from 1995 to 2017 / 中华疾病控制杂志

Objective To investigate the distribution of death among human immunodeficiency virus/acquired immuno deficiency syndrome(HIV/AIDS) cases in Guizhou Province from 1995 to 2017. Methods The HIV/AIDS death cases from 1995 to 2017 were downloaded from “Chinese National Comprehensive HIV/AIDS Prevention and care Information system” in Guizhou Province and were analyzed. Results From 1995 to 2017, Guizhou Province reported a total of 43 794 HIV/AIDS cases and 11 527 deaths according to current address. After excluding missing persons, the HIV/AIDS mortality rate of the province was 29.8%. The proportion of reported HIV/AIDS cases died in the same year ( 21995-2012=139.5, P<0.001; 22012-2015=28.2, P<0.001) and the proportion of HIV/AIDS cases ( 21995-2012=109.1, P<0.001; 22012-2014=57.2, P<0.001) who survived at the beginning but died later in the year all showed a trend being low-high-low. In the analysis of the detection history of death cases, the detection proportion of cluster of differentiation 4(CD4) T-cell and the proportion of antiviral treatment had been increasing year by year. The analysis of the cause of death found that the proportion of death caused by AIDS increased firstly and then declined, and the proportion of death due to excessive drug abuse showed a trend of declining year by year. Conclusions The mortality rate of HIV/AIDS in Guizhou Province was still high, and decreased rather slow. Expanding the coverage of HIV monitoring and screening is one of the key tasks of AIDS prevention and control. CD4+T-cell testing and free antiviral treatment should be strengthened to reduce the mortality rate of HIV/AIDS in Guizhou Province in the future.

Protective effect of Sestrin2 on apoptosis of dendritic cells induced by high mobility group box-1 protein / 解放军医学杂志

Objective To investigate the potential role of Sestrin2 (SESN2) in regulating the apoptosis of dendritic cells (DCs) induced by high mobility group box-1 protein (HMGB1).Methods DCs (the murine DC cell line DC2.4) were cultured with or without HMGB1 stimulation (cultured with 10ng/ml HMGB1 for 8,24 and 48 hours,or cultured with HMGB1 for 48 hours at different concentrations of 1,10 and 100ng/ml,respectively,n=4).The protein level of SESN2,cleaved-caspase-3 and Bcl-2 were analyzed with Western blotting.Localization of SESN2 in cells was observed under confocal laser microscope (LSCM).Cell apoptosis was analyzed with flow cytometry.In addition,DC2.4 cells were transfected with lentivirus containing SESN2 LV-RNA,SESN2 siRNA sequence expressing plasmids or blank vector (NC,NS,n=4).These cells were then stimulated with HMGB1 (100ng/ml)for 48 hours,and the apoptosis was accessed as mentioned above.Results Compared with the control group,the expression of SESN2 was obviously up-regulated after HMGB1 (10ng/ml) stimulation for 24 and 48 hours (P＜0.05).In a dose-dependent response,the expression of SESN2 was markedly enhanced in treatment with 1,10,100ng/ml HMGB1 for 48 hours (P＜0.05).Compared with the control group (7.35％ ± 1.33％),the percentage of apoptosis was significantly increased with 10,100ng/ml HMGB1 for 48 hours [(17.02％ ± 4.85％,17.48％ ± 4.04％,respectively,P＜0.05 or P＜0.01].After transfection,compared with blank vector group,the apoptosis of SESN2 siRNA group obviously elevated [(65.96％ ± 2.50％) vs.(50.01％ ± 2.07％),P＜0.05],and cleaved-caspase-3 expression significantly increased while Bcl-2 expression obviously decreased.In SESN2 LV-RNA group,the apoptosis significantly decreased [(35.57％ ± 1.69％) vs.(49.04％ ± 4.87％),P＜0.05],and cleaved-caspase-3 expression decreased and Bcl-2 expression obviously increased compared with blank vector group (P＜0.05).Conclusion SESN2 has a protective effect against HMGB 1 induced apoptosis of D C2.4 cells.

Role of the Ca-Calcineurin-Nuclear Factor of Activated T cell Pathway in Mitofusin-2-Mediated Immune Function of Jurkat Cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Mitofusin-2 (MFN2), a well-known mitochondrial fusion protein, has been shown to participate in innate immunity, but its role in mediating adaptive immunity remains poorly characterized. In this study, we explored the potential role of MFN2 in mediating the immune function of T lymphocytes.</p><p><b>METHODS</b>We manipulated MFN2 gene expression in Jurkat cells via lentiviral transduction of MFN2 small interfering RNA (siRNA) or full-length MFN2. After transduction, the immune response and its underlying mechanism were determined in Jurkat cells. One-way analysis of variance and Student's t-test were performed to determine the statistical significance between the groups.</p><p><b>RESULTS</b>Overexpression of MFN2 enhanced the immune response of T lymphocytes by upregulating Ca2+ (359.280 ± 10.130 vs. 266.940 ± 10.170, P = 0.000), calcineurin (0.513 ± 0.014 vs. 0.403 ± 0.020 nmol/L, P = 0.024), and nuclear factor of activated T cells (NFATs) activation (1.040 ± 0.086 vs. 0.700 ± 0.115, P = 0.005), whereas depletion of MFN2 impaired the immune function of T lymphocytes by downregulating Ca2+ (141.140 ± 14.670 vs. 267.060 ± 9.230, P = 0.000), calcineurin (0.054 ± 0.030 nmol/L vs. 0.404 ± 0.063 nmol/L, P = 0.000), and NFAT activation (0.500 ± 0.025 vs. 0.720 ± 0.061, P = 0.012). Furthermore, upregulated calcineurin partially reversed the negative effects of MFN2 siRNA on T cell-mediated immunity evidenced by elevations in T cell proliferation (1.120 ± 0.048 vs. 0.580 ± 0.078, P = 0.040), interleukin-2 (IL-2) production (473.300 ± 24.100 vs. 175.330 ± 12.900 pg/ml, P = 0.000), and the interferon-γ/IL-4 ratio (3.080 ± 0.156 vs. 0.953 ± 0.093, P = 0.000). Meanwhile, calcineurin activity inhibitor depleted the positive effects of overexpressed MFN2 on T cells function.</p><p><b>CONCLUSIONS</b>Our findings suggest that MFN2 may regulate T cell immune functions primarily through the Ca2+-calcineurin-NFAT pathway. MFN2 may represent a potential therapeutic target for T cell immune dysfunction-related diseases.</p>

Tumor necrosis factor-α-induced protein 8 like-2 promotes apoptosis of CD4T lymphocytes in mice with severe burn injury / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of tumor necrosis factor-α-induced protein 8 like-2 (TIPE2) on apoptosis of CD4T lymphocytes in a murine model of severe burn injury.</p><p><b>METHODS</b>A total of 140 male mice were randomly allocated into 6 groups. Small RNA interference technique was used to construct a siTIPE2-overexpressing lentivirus, and severe burn injury models were established in the mice. CD4T cells were purified from spleen of the mice, and the expressions of TIPE2, Smad2/Smad3, P-Smad2/P-Smad3 and Bcl-2/Bimprotein in CD4Tregs were detected. The changes in mitochondrial membrane potential and cytochrome C in CD4T cells were detected, and the activities of caspase-3, caspase-8, and caspase-9 were analyzed.</p><p><b>RESULTS</b>Down-regulation of TIPE2 promoted the apoptosis of CD4T lymphocytes in siTIPE2-burn group, in which the protein expressions of P-smad2/P-Smad3 decreased, Bcl-2 expression increased and Bim expression decreased significantly as compared with the other groups (P<0.01 or 0.05). The mitochondrial membrane potential and cytochrome C expression in CD4T cells were down-regulated in siTIPE2-burn group (P<0.05) with a lowered caspase-3 activity compared with TIPE2-burn group (P<0.01) and decreased caspase-8 and caspase-9 compared with the other groups (P<0.05). The apoptosis rate was the highest in TIPE2-burn group, whose Smad2/Smad3 was higher than that in the sham group (P<0.05) and the expression of P-smad2/P-Smad3 significantly increased compared with the other groups (P<0.05). In TIPE2-burn group, the mitochondrial membrane potential in CD4T cells was decreased (P<0.01), the expression of cytochrome C increased markedly (P<0.01), and the activities of caspase-3, caspase-8, and caspase-9 were all obviously higher than those in the other groups (P<0.05).</p><p><b>CONCLUSION</b>As an important immunoregulatory molecule, TIPE2 can promote the apoptosis of CD4T lymphocyte in mice with sever burn injury.</p>

Identification and Treatment of the Early Form of Neurogenic Pulmonary Edema in Emergency Room / 中国医学科学院学报

<p><b>OBJECTIVE</b>To improve the management of the early neurogenic pulmonary edema(NPE)in patients with non-traumatic cerebral hemorrhage.</p><p><b>METHODS</b>Totally 140 eligible patients with non-traumatic cerebral hemorrhage who were treated in the emergency department of our hospital from October 2008 to October 2014 were divided into two groups:NPE group(n=25)and non-NPE group(n=115). The clinical data were analyzed and compared.</p><p><b>RESULTS</b>Although the mean arterial pressure was similar between these two groups,the median pH and the bicarbonate ion(HCO(3)(-))were significantly lower in the NPE group than in the non-NPE group(pH:7.32 vs.7.39,P=0.002;HCO(3)(-),20.6 mmol/L vs.22.7 mmol/L,P=0.01). Multivariate regression analysis indicated that younger age and higher glucose level were significantly correlated with the early onset of NPE in the NPE group than in the non-NPE group(age:50.1 years vs.65.1 years,P=0.0008;glucose,15.4 mmol/L vs.10.78 mmol/L,P=0.001).There were only 3 patients in all with non-traumatic cerebral hemorrhage happened the fulminant NPE in 1 hour. Within 24 hours after patients visited the emergency room,the condition was improved in 20 of 25 patients in the NPE group. However,5 patients died,among whom 3 patients with fulminant NPE(onset within 1 hour)died due to acute respiratory distress syndrome and complicated with multiple organ failure,and 2 died of cerebral hernia.</p><p><b>CONCLUSIONS</b>NPE is a rare and severe complication in patients with non traumatic cerebral hemorrhage. The possibility of NPE should be considered in relatively young patients with higher glucose and lower blood pH value. Timely prevention and treatment can improve the outcomes.</p>

Effect of inflammatory factors on cell proliferation and apoptosis in insulin-like grown factor 1-slienced human coronary artery smooth muscle cells / 中国医学科学院学报

<p><b>OBJECTIVE</b>To study the effect of inflammatory factors on cell proliferation and apoptosis in insulin-like grown factor 1 (IGF1)-slienced human coronary artery smooth muscle cells (hCASMCs).</p><p><b>METHODS</b>We silenced the expression of IGF1 in hCASMCs using the lentivirus-mediated RNA interference technology. Blank control group and negative control group were set using the hCASMCs without the infection of a virus vector and the hCASMCs with the infection of a negative control virus vector, respectively. After the treatment of these cells with both tumor necrosis factor-α 50 ng/ml and interleukin-1β 40 ng/ml, the concentration of IGF1 in cell-culture medium was detected by enzyme-linked immunosorbent assay, and the proliferation and apoptosis were evaluated by MTT assay and flow cytometry.</p><p><b>RESULTS</b>After the simulation with inflammatory factors, the concentration of IGF1 in the supernatant fluid of cultured IGF1-slienced hCASMCs was significantly lower than those in the blank control group and negative control group [(426.35±120.96) vs. (1 030.69±54.69) and (992.82±26.90)pg/ml, P=0.000). The proliferation of IGF1-slienced hCASMCs was substantially much less than the two control groups (0.302±0.011 vs. 0.401±0.028 and 0.302±0.011, F=37.628, P=0.000), and the apoptosis rate of IGF1-slienced hCASMCs was significant increased compared with the other two groups [(10.57±0.99)% vs. (0.19±0.13)% and (1.31±0.30)%, P=0.001].</p><p><b>CONCLUSION</b>Inflammatory factors can inhibit the cell proliferation and promote apoptosis after the knock-down of IGF1 in hCASMCs.</p>

Influence of intensive insulin therapy on vascular endothelial growth factor in patients with severe trauma / 华中科技大学学报（医学）（英德文版）

The influence of early-stage intensive insulin therapy on the plasma levels of vascular endothelial growth factor (VEGF) and the related parameters in patients with severe trauma and the clinical implication were investigated. Sixty-four cases of severe trauma (injury severity score ≥20) with stress hyperglycemia (blood glucose >9 mmol/L) were randomly divided into intensive insulin therapy group and conventional therapy group. ELISA method, radioimmunoassay and density gradient gradation one-step process were used to determine plasma VEGF, endothelin-1 (ET-1), and the number of circulating endothelial cells (CECs) at the day of 0, 2, 3, 5 and 7 after admission. Simultaneously, the changes of CRP concentration in plasma were monitored to evaluate inflammatory response. The results showed that plasma levels of observational indexes in patients receiving early-stage intensive insulin therapy were all significantly lower than those in conventional therapy groups 2, 3, 5 and 7 days after admission [for VEGF (ng/L), 122.2±23.8 vs. 135.9±26.5, 109.6±27.3 vs. 129.0±18.4, 88.7±18.2 vs. 102.6±27.3, 54.2±26.4 vs. 85.7±35.2, P<0.05, 0.01, 0.05, 0.05 respectively; for ET-1 (ng/L), 162.8±23.5 vs. 173.7±13.2, 128.6±17.5 vs. 148.8±22.4, 96.5±14.8 vs. 125.7±14.8, 90.7±16.9 vs. 104.9±22.5, P<0.05, 0.01, 0.01, 0.01 respectively; for CRP (mg/L), 23.2±13.8 vs. 31.9±16.5, 13.6±17.3 vs. 23.5±18.4, 8.7±10.2 vs. 15.6±13.3, 5.2±9.4 vs. 10.7±11.2, all P<0.05; for CECs (/0.9 μL), 10.9±5.6 vs. 13.9±6.2, 8.5±4.9 vs. 11.3±5.3, 6.3±6.4 vs. 9.4±5.7, 4.8±7.1 vs. 7.8±4.8, all P<0.05]. It was concluded that intensive insulin therapy could antagonize the endothelium injury after trauma and reduce inflammation response quickly, which was one of important mechanisms by which intensive insulin therapy improves the prognosis of trauma patients.

Influence of intensive insulin therapy on vascular endothelial growth factor in patients with severe trauma / 华中科技大学学报（医学）（英德文版）

The influence of early-stage intensive insulin therapy on the plasma levels of vascular endothelial growth factor (VEGF) and the related parameters in patients with severe trauma and the clinical implication were investigated. Sixty-four cases of severe trauma (injury severity score ≥20) with stress hyperglycemia (blood glucose >9 mmol/L) were randomly divided into intensive insulin therapy group and conventional therapy group. ELISA method, radioimmunoassay and density gradient gradation one-step process were used to determine plasma VEGF, endothelin-1 (ET-1), and the number of circulating endothelial cells (CECs) at the day of 0, 2, 3, 5 and 7 after admission. Simultaneously, the changes of CRP concentration in plasma were monitored to evaluate inflammatory response. The results showed that plasma levels of observational indexes in patients receiving early-stage intensive insulin therapy were all significantly lower than those in conventional therapy groups 2, 3, 5 and 7 days after admission [for VEGF (ng/L), 122.2±23.8 vs. 135.9±26.5, 109.6±27.3 vs. 129.0±18.4, 88.7±18.2 vs. 102.6±27.3, 54.2±26.4 vs. 85.7±35.2, P<0.05, 0.01, 0.05, 0.05 respectively; for ET-1 (ng/L), 162.8±23.5 vs. 173.7±13.2, 128.6±17.5 vs. 148.8±22.4, 96.5±14.8 vs. 125.7±14.8, 90.7±16.9 vs. 104.9±22.5, P<0.05, 0.01, 0.01, 0.01 respectively; for CRP (mg/L), 23.2±13.8 vs. 31.9±16.5, 13.6±17.3 vs. 23.5±18.4, 8.7±10.2 vs. 15.6±13.3, 5.2±9.4 vs. 10.7±11.2, all P<0.05; for CECs (/0.9 μL), 10.9±5.6 vs. 13.9±6.2, 8.5±4.9 vs. 11.3±5.3, 6.3±6.4 vs. 9.4±5.7, 4.8±7.1 vs. 7.8±4.8, all P<0.05]. It was concluded that intensive insulin therapy could antagonize the endothelium injury after trauma and reduce inflammation response quickly, which was one of important mechanisms by which intensive insulin therapy improves the prognosis of trauma patients.

Effect of Xuebijing injection on systemic lupus erythematosus in mice / 中国结合医学杂志

<p><b>OBJECTIVE</b>To observe the effects of Xuebijing injection on dendritic cells (DCs) and T lymphocytes, and the potential mechanisms of its therapeutic effect on systemic lupus erythematosus (SLE).</p><p><b>METHODS</b>A widely used mouse model, SLE-prone BLLF1 mice aged 8-10 weeks, was employed. Mice were randomly divided into 4 groups: a normal group, a model group and two treatment groups treated with Xuebijing Injection with a dose of 6.4 mL/kg via intraperitoneal administration for SLE-prone BLLF1 mice aged 8 weeks (treatment A group) and 10 weeks (treatment B group). Renal tissue sections were stained with Masson's trichrome and periodic acid-silver methenamine. Histopathological changes in the kidney were evaluated by a light microscopy. The capacity of the DCs isolated from the spleen to stimulate the T cell proliferation in response to concanavalin A (Con A) was determined.</p><p><b>RESULTS</b>Compared with the model group, levels of anti-dsDNA antibodies in the two treatment groups decreased remarkablly (P<0.01, P<0.05), and levels of serum creatinine and blood urea nitrogen increased (P<0.01, P<0.05). Pathological changes were found in the kidney in the model group. Histopathological abnormalities were alleviated in the two treatment groups. Treatment with Xuebijing injection also significantly upregulated the expression of CD80, CD86 and major histocompatibility class II by DCs compared with the model group (P<0.05). When splenic T lymphocytes from BLLF1 mice were co-cultured with DCs at ratios of 1:100, 1:150 and 1:200 for 3 and 5 days, the proliferation of T lymphocytes was suppressed compared with the normal group (P<0.05), but this was restored by Xuebijing Injection under the same conditions. In the model group, levels of tumor necrosis factor (TNF)-α in supernatants were significantly elevated compared with the normal group (P<0.01), interleukin-2 levels decreased (P<0.05), while these changes were significantly alleviated in the Xuebijing treatment groups.</p><p><b>CONCLUSIONS</b>Xuebijing Injection alleviated renal injury in SLE-prone BLLF-1 mice. The mechanism might be through influencing T cell polarization mediated by DCs, and Xuebijing Injection might be a potential drug that suppresses immune dysfunction in patients with SLE.</p>

Plasma gelsolin level and its relationship with the prognosis of patients with severe burns / 中华烧伤杂志

<p><b>OBJECTIVE</b>To observe the changes in plasma gelsolin (pGSN) level of patients with severe burn and to explore its relationship with sepsis and death of patients.</p><p><b>METHODS</b>One hundred and two patients with total burn area equal to or larger than 30% TBSA hospitalized from May 2010 to May 2012 were included as burn group. Twenty-five healthy volunteers were recruited as healthy control group. Peripheral venous blood of patients was harvested on post burn day (PBD) 1, 3, 7, 14, and 21 to determine the pGSN level with double antibody sandwich ELISA kits, and the same maneuver was carried out in healthy volunteers. (1) Patients in burn group were divided into three groups by burn size: small burn area group (30% - 49% TBSA, n = 39), medium burn area group (larger than 49% and smaller than or equal to 69% TBSA, n = 33), and large burn area group (larger than 69% and smaller than or equal to 99% TBSA, n = 30). (2) According to diagnostic criteria of burn sepsis, patients in burn group were divided into sepsis group (n = 43) and non-sepsis group (n = 59). (3) According to the prognosis of patients with sepsis, patients in sepsis group were further divided into non-survival sepsis group (n = 14) and survival sepsis group (n = 29). The levels of pGSN in above groups were compared, and their relationship with sepsis and death of patients was analyzed. Data were analyzed with analysis of variance, LSD test and one-way Logistic regressions.</p><p><b>RESULTS</b>(1) Levels of pGSN in burn group were obviously lower than those of healthy control group on PBD 1, 3, 7, 14, and 21 (with F values respectively 140.01, 369.52, 702.15, 360.14, 84.16, P values all below 0.01). (2) The mean levels of pGSN in large, medium, and small burn area groups at five time points were (43 ± 11), (85 ± 23), (124 ± 38) mg/L, showing statistically significant differences among them (F = 367.76, P < 0.01), and they were all lower than that of healthy control group [(326 ± 51) mg/L, P values all below 0.01]. (3) The mean levels of pGSN in sepsis group and non-sepsis group at the five time points were (77 ± 12), (122 ± 38) mg/L. Levels of pGSN in sepsis group were lower than those in non-sepsis group on PBD 3, 7, 14, and 21 (with F values respectively 30.35, 111.59, 209.36, 422.76, P values all below 0.01). (4) The mean levels of pGSN in non-survival sepsis group and survival sepsis group at the five time points were (53 ± 8) and (103 ± 25) mg/L. Levels of pGSN in non-survival sepsis group were lower than those in survival sepsis group on PBD 1, 3, 7, 14, and 21 (with F values respectively 9.05, 18.48, 41.34, 107.11, 180.48, P values all below 0.01). (5) Logistic regression analysis showed that the level of pGSN is the independent risk factor related to the complication of sepsis (odds ratio: 5.44, 95% confidence interval: 2.35 - 12.74, P < 0.01) and death (odds ratio: 5.52, 95% confidence interval: 2.34 - 12.19, P < 0.01) in burn patients.</p><p><b>CONCLUSIONS</b>Severe burn injury could down-regulate the pGSN level of patients, and it decreases along with the increase in the area and severity of burn trauma. pGSN level appears to be an early prognostic marker for patients suffering from severe burns.</p>

Advancement in the research of mechanism of immune dysfunction in sepsis and the regulatory effects of Xuebijing injection / 中华烧伤杂志

Sepsis is a systemic inflammatory response syndrome resulting from a host response to infection. The early stage of sepsis is characterized by excessive inflammatory response, accompanied by immune dysfunction characterized by aggravating cellular immunosuppression. The vast majority of patients with sepsis survive the initial excessive inflammatory response, but die of hospital-acquired infection, opportunistic pathogenic bacteria infection, latent virus reactivation, and multiple organ dysfunction syndrome. These facts indicate that immunosuppression may be a significant cause of exacerbation of the illness even death of the septic patients. The primary cellular mechanisms in inducing immune dysfunction include immune dysfunction of T lymphocytes, negative regulation of regulatory T lymphocytes and dendritic cells, and damage of intestinal mucosa associated lymphoid tissue. Xuebijing injection is a complex Chinese patent medicine, which is widely used in the treatment of sepsis. It has a potential immunoregulation ability, as well as effects on bacteriostasis, anti-endotoxin and anti-inflammation. Its target and mechanism of action need to be explored further.

Novel insights for high mobility group box 1 protein-mediated cellular immune response in sepsis:A systemic review / 世界急诊医学杂志（英文）

@#BACKGROUND: High mobility group box 1 protein (HMGB1) is a highly conserved, ubiquitous protein in the nuclei and cytoplasm of nearly all cell types. HMGB1 is secreted into the extracellular milieu and acts as a proinflammatory cytokine. In this article we reviewed briefly the cellular immune response mediated by HMGB1 in inflammation and sepsis. METHODS: This systemic review is mainly based on our own work and other related reports. RESULTS: HMGB1 can actively affect the immune functions of many types of cells including T lymphocytes, regulatory T cells (Tregs), dendritic cells (DCs), macrophages, and natural killer cells (NK cells). Various cellular responses can be mediated by HMGB1 which binds to cell-surface receptors [e.g., the receptor for advanced glycation end products (RAGE), Toll-like receptor (TLR)2, and TLR4]. Anti-HMGB1 treatment, such as anti-HMGB1 polyclonal or monoclonal antibodies, inhibitors (e.g., ethyl pyruvate) and antagonists (e.g., A box), can protect against sepsis lethality and give a wider window for the treatment opportunity. CONCLUSION: HMGB1 is an attractive target for the development of new therapeutic strategies in the treatment of patients with septic complications.

Effect of high mobility group box-1 protein on immune cells and its regulatory mechanism / 中国应用生理学杂志

High mobility group box-1 protein (HMGB1), which is a nuclear protein, participates in chromatin architecture and transcriptional regulation. When released from cells, HMGB1 also plays a well-established role as a pro-inflammatory mediator during innate immune responses to injury. In the initial stage of injury, there is a release of large quantities of early pro-inflammatory mediators to initiate or perpetuate immune responses against pathogens, but this pro-inflammatory period is transient, and it is followed by a prolonged period of immune suppression. At present, several lines of evidences have suggested that HMGB1 is a late cytokine provoking delayed endotoxin morbidity, which may enhance the production of early proinflammatory mediators, and it can contribute potently to the activation of different immune cells and play a role in the development of host cell-mediated immunity. The biology of HMGB1 has been extensively studied as a pro-inflammatory cytokine of systemic inflammation, however, this review will attempt to provide a summary of the effects of HMGB1 on different immune cells and its regulatory mechanism in acute insults.

Change of serum TGF-beta1 and TNF-alpha in silicosis patients / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To observe serum TGF-beta1 and TNF-alpha in silicosis patients and workers exposed to silica dust to study the role of TGF-beta1 and TNF-alpha in the development of silicosis.</p><p><b>METHODS</b>One hundred non-exposed workers were selected as control group, 200 workers exposed to silica dust for more than 1 year as exposed group, 32 suspected silicosis patients (originally diagnosed as 0+) as observing group, 130 silicosis patients were as silicosis group. Serum TGF-beta1 and TNF-alpha in each group were determined with ELISA.</p><p><b>RESULTS</b>Serum TNF-alpha in exposed group [(47.86 +/- 16.52) pg/ml], observing group [(109.11 +/- 31.08) pg/ml], silicosis group [(216.35 +/- 51.03) pg/ml] were significantly higher than that in control group [(6.90 +/- 2.24) pg/ml] (P < 0.01); Silicosis group and observing group were also higher than exposed group (P < 0.01, P < 0.05). Compared with control group [(23.28 +/- 12.24) pg/ml] and exposed group [(29.31 +/- 14.52) pg/ml], serum TGF-beta1 in silicosis group was much higher (P < 0.01).</p><p><b>CONCLUSION</b>TGF-beta1, and TNF-alpha were essential in the development of silicosis, so the detection of TGF-beta1 and TNF-alpha in peripheral blood was very useful for occupational health surveillance and early diagnosis of silicosis.</p>

The potential role of regulatory T cells in postburn sepsis / 中华烧伤杂志

It has been demonstrated that severe burn per se may contribute to activation and proliferation of regulatory T cells (Treg). This characteristic phenomenon might allow Treg to function for a prolonged period of time to regulate immune response, and to induce suppression of T lymphocyte immune function. Different degrees of elevated levels of cytokines produced by Treg and activation markers on Treg surface could also be involved in the development of sepsis and fatal outcome in patients with severe burn. Thus, the regulation of Treg as a cellular therapeutic strategy might be important to the Th1/Th2 cytokine balance in burn patients complicated with sepsis.