IL-1β and IL-17 in cutaneous lupus erythematous skin biopsies: could immunohistochemicals indicate a tendency towards systemic involvement?

Abstract Background: Only a fraction of patients with cutaneous lupus erythematosus (CLE) will eventually progress toward systemic disease (SLE). Objective: To find inflammatory biomarkers which could predict the progression of cutaneous lupus erythematosus (CLE) into systemic lupus erythematosus (SLE) using immunohistochemical (IHC) assays. Methods: Immunohistochemical markers for cytotoxic, inflammatory, and anti-inflammatory responses and morphometric methods were applied to routine paraffin sections of skin biopsies, taken from lesions of 59 patients with discoid lupus, subacute lupus, and lupus tumidus. For the diagnosis of SLE, patients were classified by both the American College of Rheumatology (ACR-82) and the Systemic Lupus International Collaborating Clinics (SLICC-12) systems. Results: Skin samples from CLE/SLE +patients presented higher expression of IL-1β (ARC-82: p = 0.024; SLICC-12: p = 0.0143) and a significantly higher number of cells marked with granzyme B and perforin (ARC: p = 0.0097; SLICC-12: p = 0.0148). Biopsies from CLE/SLE- individuals had higher expression of IL-17 (ARC-82: p = 0.0003; SLICC-12: p = 0.0351) and presented a positive correlation between the density of granzyme A+and FoxP3+ cells (ARC-82: p = 0.0257; SLICC-12: p = 0.0285) and CD8+ cells (ARC-82: p = 0.0075; SLICC-12: p = 0.0102), as well as between granulysin-positive and CD8+ cells (ARC-82: p = 0.0024; SLICC-12: p = 0.0116). Study limitations: Patients were evaluated at a specific point in their evolution and according to the presence or not of systemic disease. The authors cannot predict how many more, from each group, would have evolved towards SLE in the following years. Conclusions: In this cohort, immunohistochemical findings suggested that patients with a tendency to systemic disease will show strong reactivity for IL-1β, while those with purely cutaneous involvement will tend to express IL-17 more intensely.

Oral lichen planus in a young patient: a case report with nine-year follow-up / Líquen plano oral em paciente jovem: um relato de caso com acompanhamento de nove anos

INTRODUCTION: Oral lichen planus is an inflammatory condition that affects the stratified squamous epithelium of the oral mucosa. It occurs more frequently in female patients and it is rarely observed in children, adolescents, or young adults. This study aims to report a case of oral lichen planus in a young patient with a nine-year followup. CASE REPORT: A 19-year-old man reported to the Dentistry Department with a complaint of an asymptomatic white lesion on the dorsum and left lateral border of his tongue, which had appeared a few weeks before. Two weeks later, a second lesion, very similar to the previous one, appeared on the central region of his tongue. An incisional biopsy was performed. The histological slides were stained with hematoxylin-eosin and the expression of interleukin-1beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α) was assessed by immunohistochemistry. No pharmacological treatment was prescribed. The clinical and histopathological findings were suggestive of oral lichen planus. The IL-1ß/TNF-α expression was low. There was a spontaneous regression of the lesions after approximately one year. The nine-year follow-up showed no signs of recurrence. CONCLUSION: This case presents atypical features such as the age of the patient and the spontaneous remission of the lesions.

INTRODUÇÃO: O líquen plano oral é uma condição inflamatória que acomete o epitélio escamoso estratificado da mucosa oral. Ocorre mais frequentemente em pacientes do gênero feminino e é raramente encontrado em pacientes pediátricos ou juvenis. O objetivo do presente estudo é relatar um caso de líquen plano oral em um paciente jovem com acompanhamento de nove anos. RELATO DE CASO: Um rapaz de 19 anos procurou atendimento no Departamento de Odontologia com a queixa de uma lesão branca assintomática em região de dorso e borda lateral esquerda de sua língua, com tempo de evolução de algumas semanas. Duas semanas depois, uma segunda lesão, muito similar à primeira, apareceu na região central de sua língua. Uma biópsia incisional foi realizada. As lâminas histológicas foram coradas com hematoxilina-eosina e a expressão de interleucina-1beta (IL-1ß) e de fator de necrose tumoral alfa (TNF-α) foram avaliadas por imunohistoquímica. Nenhum tratamento farmacológico foi prescrito. Os achados clínicos e histopatológicos foram sugestivos de líquen plano oral. A expressão de IL-1ß/TNF-α foi baixa. Houve uma regressão espontânea das lesões após aproximadamente um ano. O acompanhamento de nove anos não detectou sinais de recorrência. CONCLUSÃO: Esse caso apresenta características atípicas, como a idade do paciente e a remissão espontânea das lesões.

Effects of different time point rolling massager on inflammation in rabbits with skeletal muscle injury / 国际中医中药杂志

Objective:To observe the effects of rolling method massager on local tissue morphology, tissue and serum TNF-α and IL-1β in rabbits with skeletal muscle injury at different time points; To investigate the mechanism of temporal effect of rolling method action on skeletal muscle injury.Methods:Totally 72 New Zealand rabbits were divided into blank group, model group and rolling method treatment group according to random number table method, with 24 rabbits in each group. Rabbits in each group were divided into 1 d, 3 d, 5 d, 7 d, 9 d and 11 d subgroups according to the time point of injury, with 4 rabbits in each group. Blunt contusion was used to model the model group and the rolling method treatment group. Each subgroup of the rolling method treatment group was subjected to rolling method intervention for 3 d, using a homemade rolling method massager, 2 times/d, 3 min/time. At 24 h after the completion of the intervention, the histomorphological changes were observed by HE staining, and the TNF-α and IL-1β contents in serum and damaged skeletal muscle tissues were detected by ELISA.Results:Compared with the blank group, the inflammatory cell infiltration in the model group was obvious, edema was severe, and myofibers were broken; the inflammatory cell infiltration in the 1 d rolling method treatment group was intensified, myocytes were apoptotic, and myofibers were broken and necrosed more seriously; the inflammation in the 7 d rolling method treatment group was obviously improved with the best effect, and the difference with normal healthy muscle tissue was smaller. After modeling, TNF-α and IL-1β levels in skeletal muscle tissues and serum TNF-α levels were higher in the 3 d model group than in the 1 d model group ( P<0.05). Compared with the blank group, TNF-α and IL-1β levels in skeletal muscle tissues and serum increased in each subgroup of the model group and each subgroup of the rolling method treatment group ( P<0.01); Compared with the 1 d model group, TNF-α and IL-1β levels in skeletal muscle tissues and serum TNF-α levels increased in the 1 d rolling method treatment group. The levels of TNF-α and IL-1β in the 3 d, 5 d, 7 d, 9 d and 11 d rolling method treatment group were lower than those in the model group subgroup ( P<0.05). TNF-α and IL-1β levels in skeletal muscle tissues and serum TNF-α levels were higher in the 1 d, 3 d and 5 d rolling method treatment group than in the 7 d rolling method treatment group ( P<0.05). TNF-α levels in skeletal muscle tissues were higher in the 1 d and 3 d rolling method treatment group than in the 7 d rolling method treatment group ( P<0.05). Conclusion:The inflammatory factors in the rolling treated group were significantly higher at 1 d after skeletal muscle injury, indicating that treatment with the rolling method was inappropriate at this time; seven days after injury, the application of rolling method can reduce the inflammatory effect, accelerate the repair of skeletal muscle, and improve the quality of functional recovery.

Expression and clinical significance of lnc-LFAR1 in patients with chronic hepatitis B cirrhosis / 中国热带医学

@#Abstract: Objective　To investigate the expression level and clinical significance of serum liver fibrosis-associated lncRNA1 (lnc-LFAR1) in patients with chronic hepatitis B cirrhosis, aiming to analyze its correlation with interleukin-6 (IL-6), interleukin-1β (IL-1β), and liver function. Methods　Patients with chronic hepatitis B (CHB) cirrhosis and CHB diagnosed and treated in Dongguan City People's Hospital from March 2016 to December 2019 were selected and divided into the liver cirrhosis group (n=80) and the CHB group (n=80), and 80 healthy people with physical examination during the same period were selected as healthy group. The serum levels of lnc-LFAR1, interleukin-6 (IL-6), albumin (ALB), interleukin-1β (IL-1β) and liver function indicators, including albumin (ALB) and alanine aminotransferase (ALT) were measured and analyzed. The correlation between serum lnc-LFAR1 expression level and IL-6, IL-1β was assessed, and the levels of lnc-LFAR1, IL-6, IL-1β, ALB and ALT were compared among patients with CHB cirrhosis of different Child-Pugh grades. Results The serum levels of lnc-LFAR1, IL-6, IL-1β and ALT in the patients with liver cirrhosis [(1.85± 0.62), (41.76±13.92) ng/mL, (7.78±1.95) pg/mL, (148.37±29.67) U/L] were higher than those in the CHB group [(1.42±0.47), (23.56± 7.85) ng/mL, (5.42±1.41) pg/mL, (87.59±17.52) U/L] and the healthy group [(1.01±0.34), (6.70±2.23) ng/mL, (3.13± 0.78) pg/mL, (15.44±3.10) U/L] (P<0.05), while the ALB levels (30.54±3.82) g/L were lower than those in the CHB group (37.27±4.34) g/L and the healthy group (45.26±5.66) g/L (P<0.05). Serum lnc-LFAR1, IL-6, IL-1β and ALT levels in the CHB group were higher than those in the healthy group (P<0.05), and ALB levels were lower than those in the healthy group (P<0.05); the serum levels of lnc-LFAR1, IL-6, IL-1β in patients with CHB cirrhosis were negatively correlated with ALB (P<0.05), and positively correlated with ALT (P<0.05); the serum expression level of lnc-LFAR1 in patients with CHB cirrhosis was positively correlated with IL-6 and IL-1β (r=0.598, 0.571, P<0.05); with the increase of Child-Pugh grade, the serum levels of lnc-LFAR1, IL-6, IL-1β, and ALT in patients with CHB cirrhosis gradually increased (P<0.05), and the level of ALB gradually decreased (P<0.05). Conclusions Serum lnc-LFAR1 expression level is higher in patients with CHB cirrhosis, which is obviously related to IL-6, IL-1β, ALB and ALT. Therefore, the evaluation of serum lnc-LFAR1 expression level is helpful in the clinical assessment of the condition of CHB cirrhosis patients.

Effect of aloperine on chondrocyte injury induced by interleukin-1β and its mechanism / 中国生物制品学杂志

@#Objective To investigate the effect of aloperine(ALO)on interleukin-1β(IL-1β)-induced chondrocyte injury and its mechanism. Methods Chondrocytes were randomly divided into control(Con)group,IL-1 β group,IL-1β + ALO-L(25 mg/L)group,IL-1β + ALO-M(50 mg/L)group and IL-1 β + ALO-H(100 mg/L)group;Con group,IL-1βgroup,IL-1β + miR-NC group and IL-1β + miR-16-5p group;Con group,IL-1β group,IL-1β + si-NC group and IL-1β + siSOX5 group. Cells in IL-1β group were treated with 10 ng/mL IL-1β,while no treatment was given in Con group. The transcription levels of miR-16-5p and SOX5 mRNA in chondrocytes were detected by qRT-PCR;The contents of IL-6,TNF-αand IL-1β were detected by ELISA;The expression levels of Bcl-2,Bax and SOX5 protein were detected by Western blot and the apoptosis was detected by flow cytometry. Results Compared with IL-1 β group,the contents of IL-6,TNF-α and IL-1βin IL-1β + ALO-L group,IL-1β + ALO-M group and IL-1β + ALO-H group decreased significantly(t = 5. 002～20. 653,each P < 0. 001),the apoptosis rate decreased significantly(t = 5. 473～17. 371,each P < 0. 001),the expression level of Bcl-2 protein increased significantly(t = 7. 800～16. 100,each P < 0. 001),and the expression level of Bax protein decreased significantly(t = 4. 993～14. 311,each P < 0. 001);The mRNA transcription level of miR-16-5p gene increased significantly(t = 6. 688～16. 545,each P < 0. 001),while the mRNA transcription level and protein expression level of SOX5 gene decreased significantly(t = 4. 609～15. 393,each P < 0. 001). Compared with the IL-1β + miR-NC group,the mRNA transcription level of miR-16-5p in the IL-1β + miR-16-5p group increased significantly(t = 17. 106,P < 0. 001),the contents of IL-6,TNF-α and IL-1 β decreased significantly(t = 15. 030～20. 013,each P < 0. 001),the apoptosis rate decreased significantly(t = 12. 273,P < 0. 001),the expression level of Bcl-2 protein increased significantly(t = 15. 652,P < 0. 001),and the expression level of Bax protein decreased significantly(t = 12. 999,P < 0. 001). Compared with IL-1β +si-NC group,the expression level of SOX5(t = 13. 444,P < 0. 001),IL-6,TNF-α and IL-1β in IL-1β + si-SOX5 group decreased significantly(t = 14. 087～17. 103,each P < 0. 001),the apoptosis rate decreased significantly(t = 11. 991,P < 0. 001),the expression level of Bcl-2 protein increased significantly(t = 13. 864,P < 0. 001),and the expression level of Bax protein decreased significantly(t = 11. 818,P < 0. 001). Conclusion Alo inhibited the apoptosis of chondrocytes induced by IL-1β,thus reducing the injury of chondrocytes,of which the mechanism might be regulating the expression of miR-16-5p and SOX5 and the secretion of inflammatory factors in chondrocytes.

A preliminary study on Candida albicans-induced pyroptosis of murine bone marrow-derived macrophages / 中华皮肤科杂志

Objective:To investigate the effect of Candida albicans ( C. albicans) on pyroptosis of murine bone marrow-derived macrophages (BMDMs) . Methods:Live-cell imaging was used to observe morphologic changes of in vitro C. albicans-infected BMDMs (multiplicity of infection [MOI] = 50) so as to evaluate whether pyroptosis occurred. Cultured BMDMs were divided into a control group and a C. albicans group, which were treated with phosphate-buffered saline and C. albicans suspensions respectively for 6 hours; then, real-time fluorescence-based quantitative PCR was performed to determine the mRNA expression of NOD-like receptor pyrin domain containing 3 (NLRP3), interleukin (IL) -1β and IL-18, and Western blot analysis to determine the protein expression and cleavage levels of NLRP3, caspase-1 and gasdermin D (GSDMD). BMDMs were cultured with C. albicans suspensions for different durations (0, 10, 15, 20, and 25 hours), and enzyme-linked immunosorbent assay was conducted to detect secretion levels of IL-1β and IL-18. Cultured wild-type BMDMs and GSDMD-knockout BMDMs were treated with C. albicans suspensions for 15 minutes, and then rates of phagocytosis of C. albicans by wild-type BMDMs and GSDMD-knockout BMDMs were estimated by flow cytometry; after 6-hour treatment with C. albicans, flow cytometry and lactate dehydrogenase (LDH) release assay were performed to assess mortality rates of wild-type BMDMs and GSDMD-knockout BMDMs. In addition, some wild-type BMDMs and GSDMD-knockout BMDMs were separately divided into blank control group, control group, maximum enzyme activity-sample control group, IL-1β alone group, C. albicans alone group, and IL-1β + C. albicans group, and cell mortality rates were detected by the LDH release assay after treatment with IL-1β and/or C. albicans. Statistical analysis was carried out by using unpaired t test, Kruskal-Wallis test, analysis of variance, and other statistical methods. Results:After in vitro treatment with C. albicans, swelling and ballooning with large bubbles blowing from the plasma membrane occurred in BMDMs, suggesting the occurrence of cell pyroptosis; compared with the control group, the C. albicans group showed significantly increased mRNA expression levels of NLRP3 and IL-1β after 6-hour treatment with C. albicans ( t = 13.02, 17.51, respectively, P = or < 0.001), but no significant change in the IL-18 mRNA expression level ( P = 0.486), and Western blot analysis showed that C. albicans could increase the expression of NLRP3 inflammasomes, as well as cleaved caspase-1 and GSDMD. After the treatment with C. albicans for different durations (0, 10, 15, 20, and 25 hours), the secretion level of IL-1β by BMDMs gradually increased over time ( H = 12.90, P = 0.012), while the secretion level of IL-18 did not significantly change ( F = 0.48, P = 0.753), and the secretion level of IL-1β was significantly lower in the GSDMD-knockout BMDM group than in the wild-type BMDM group ( F = 24.22, P = 0.008). After 15-minute in vitro treatment with C. albicans, the phagocytosis rate of C. albicans was significantly lower in the GSDMD-knockout BMDM group (50.3% ± 1.10%) than in the wild-type BMDM group (58.53% ± 1.19%, t = 5.09, P = 0.007) ; after 6-hour treatment with C. albicans, the cell mortality rate was significantly higher in the GSDMD-knockout BMDM group than in the wild-type BMDM group (flow cytometry: 38.40% ± 0.50% vs. 34.37% ± 0.52%, t = 4.72, P = 0.009; LDH release assay: 22.52% ± 0.18% vs. 12.48% ± 0.15%, t = 42.36, P < 0.001) ; the cell mortality rates of wild-type BMDMs and GSDMD-knockout BMDMs both significantly decreased in the IL-1β + C. albicans groups compared with the C. albicans groups (both P < 0.001) . Conclusion:Pyroptosis could be induced in murine BMDMs after C. albicans infection, which promotes the release of IL-1β and may reduce the mortality rate of macrophages by improving their immune activity.

Effects of intravenous thrombolysis combined with Xingnaojing injection on intracranial arterial hemodynamic indexes and neurological function in patients with cerebral infarction / 中国基层医药

Objective:To investigate the effects of intravenous thrombolysis combined with Xingnaojing injection on hemodynamic indexes and neurological function in patients with cerebral infarction. Methods:A total of 142 patients with cerebral infarction who were treated in Xing An Meng Hospital from April 2020 to May 2021 were included in this study. They were randomly divided into a control group ( n = 71, intravenous thrombolysis) and a Xingnaojing injection group ( n = 71, intravenous thrombolysis + Xingnaojing injection). Intracranial arterial hemodynamic indexes, National Institutes of Health Stroke Scale score, Fugl-Meyer Assessment Scale score, serum inflammatory factors, oxidative stress indexes, brain injury markers, and the incidence of adverse reactions were compared between the two groups. Results:After treatment, serum levels of interleukin-1β, interleukin-6, and tumor necrosis factor-α were significantly lower in the Xingnaojing injection group than the control group [interleukin-1β: (4.05 ± 0.83) ng/L vs. (6.85 ± 1.02) ng/L, interleukin-6: (43.61 ± 5.14) ng/L vs. (60.31 ± 7.04) ng/L, tumor necrosis factor-α: (35.93 ± 4.25) ng/L vs. (20.93 ± 3.11) ng/L, t = 17.94, 16.14, 15.37, all P < 0.001]. After treatment, the mean blood flow velocities of the anterior cerebral artery, middle cerebral artery, and posterior cerebral artery in the Xingnaojing injection group were significantly higher than those in the control group [anterior cerebral artery: (49.36 ± 5.28) cm/s vs. (41.15 ± 5.12) cm/s, middle cerebral artery: (61.27 ± 7.02) cm/s vs. (50.19 ± 6.08) cm/s, posterior cerebral artery: (44.92 ± 5.63) cm/s vs. (37.26 ± 4.93) cm/s, t = 9.40, 10.05, 8.62, all P < 0.001]. After treatment, the National Institutes of Health Stroke Scale score and Fugl-Meyer Assessment Scale score in the Xingnaojing injection group were superior to those in the control group [National Institutes of Health Stroke Scale score: (10.36 ± 1.52) points vs. (14.62 ± 2.05) points, Fugl-Meyer Assessment Scale score: (76.19 ± 8.08) points vs. (65.28 ± 7.14) points, t = 14.06, 8.52, both P < 0.05]. After treatment, the serum level of malondialdehyde in the Xingnaojing injection group was significantly higher than that in the control group [(6.35 ± 1.02) μmol/L vs. (10.05 ± 1.63) μmol/L), t = 16.21, P < 0.001]. The serum level of superoxide dismutase in the Xingnaojing injection group was significantly lower than that in the control group [(114.31 ± 13.69) U/L vs. (92.25 ± 10.16) U/L), t = 10.90, P < 0.001]. Serum levels of neuron-specific enolase and S100β in the Xingnaojing injection group were significantly lower than those in the control group [neuron-specific enolase: (24.01 ± 3.24) IU/L vs. (30.31 ± 4.02) IU/L, S100β: (0.73 ± 0.17) ng/L vs. (1.13 ± 0.22) ng/L, t = 10.28, 12.12, both P < 0.001). There was a significant difference in the incidence of adverse reactions between the two groups ( P > 0.05). Conclusion:Intravenous thrombolysis combined with Xingnaojing injection for the treatment of cerebral infarction can improve intracranial hemodynamics, reduce the inflammatory response and oxidative stress, and alleviate brain tissue injury. The combined therapy is beneficial to protect the neurological function of patients with cerebral infarction and is highly safe.

IL-1β inhibitor sensitizes to olaparib in homologous recombination deficiency proficient ovarian cancer cells / 中华妇产科杂志

Objective:To investigate the inhibitory effect of combined strategy of poly adenosine diphosphate ribose polymerase (PARP) inhibitor and interleukin-1β (IL-1β) inhibitor on homologous recombination deficiency (HRD)-proficient ovarian cancer cells.Methods:(1) HRD-proficient ovarian cancer cell lines OVCAR3 and CAOV3 were treated with PARP inhibitor olaparib. Screening by RNA sequencing analysis, the expression level of IL-1β was validated by enzyme-linked immunosorbent assay (ELISA) and western blot. (2) The dose-response curves of IL-1β inhibitor diacerein were evaluated by cell counting kit-8 (CCK-8) assays in OVCAR3 and CAOV3 cells. CCK-8 assays were further applied to determine the viabilities of OVCAR3 and CAOV3 cells. (3) To evaluate the synergistic effects of olaparib and IL-1β inhibitor in vivo, the transplanted ovarian cancer model was constructed. BALB/c-nude mice ( n=16) were injected intraperitoneally with 1×10 7 OVACR3 cells labelled with luciferase (OVCAR3-Luc). Immunohistochemistry (IHC) assay was performed to determine nuclear antigen associated with cell proliferation (Ki-67) expression. (4) Blood routine tests, kidney and liver function tests were performed to analyze the toxic reaction of different drug treatments. The potential drug-induced injuries of vital organs including heart, liver, spleen, lungs and kidneys of nude mice were determined by hematoxylin-eosin (HE) staining. Results:(1) The RNA sequencing results showed that the mRNA level of IL-1β was the most significantly increased among the 25 differentially expressed genes in OVCAR3 cells treated with olaparib, compared to the negative control group. Olaparib treatment significantly promoted the secretion and expression of IL-1β protein in both OVACR3 and CAOV3 cells by ELISA [(36.2±3.5) and (49.5±3.5) pg/ml, respectively; all P<0.001] and western bolt (2.87±0.37 and 2.05±0.08, respectively; all P<0.01). (2) The half maximal inhibitory concentration (IC 50) value of IL-1β inhibitor was determined as follows: 75 μmol/L for OVACR3 cells and 100 μmol/L for CAOV3 cells. The treatments were divided into four groups including control group, olaparib monotherapy group, IL-1β inhibitor monotherapy group and the combination therapy group. The cell viabilities of each group in OVCAR3 and CAOV3 were determined by CCK-8 assay. The data in each group were showed as follows for OVCAR3 and CAOV3 cells: (100.0±0.4)% and (100.0±3.5)% in control group; (63.1±6.2)% and (63.3±3.8)% in olaparib monotherapy group; (61.6±4.7)% and (63.8±3.5)% in IL-1β inhibitor monotherapy group; and (32.9±5.2)% and (30.0±1.3)% in the combination therapy group. The viability assay showed that the combined strategy exhibited a significant inhibition effect on OVACR3 and CAOV3 cells, compared to the monotherapy group and the control group (all P<0.01). (3) All mice with transplanted tumors of HRD-proficient ovarian cancer cells were randomly divided into four groups, and treated with four different treatments as mentioned above, respectively. After 4 weeks (on day 29), the vivo fluorescence imaging were determined. The results showed that the amount of fluorescence of transplanted tumors was mostly decreased in the combination therapy group [(0.5±0.4)×10 10 p/s], compared to the control group [(4.2±1.0)×10 10 p/s] or the groups treated with any single drug [(3.1±0.9)×10 10, (2.2±0.9)×10 10 p/s; all P<0.05]. Mice were then sacrificed under anesthesia, and all transplanted tumors detached and weighed for further investigation. The weight of transplanted tumors was significantly decreased in the combination therapy group [(0.09±0.03) g], compared to that in control group [(0.25±0.05) g] or groups treated with any single drug [(0.17±0.03), (0.19±0.04) g; all P<0.05]. The measurement of the expression of Ki-67 showed that it was significantly decreased in the combination therapy group (0.33±0.10), compared to that in the control group (1.00±0.20) or monotherapy groups (0.76±0.07, 0.77±0.12; all P<0.05). (4) There were no significant differences of body weights, blood routine test, renal and liver function tests among mice with different treatments (all P>0.05). Moreover, no significant injuries were observed in the vital organs among the four groups. Conclusions:The combination of olaparib and IL-1β inhibitor synergistically exhibits significant cytotoxicity in HRD-proficient ovarian cancer cells. Moreover, the blood routine and blood biochemistry results confirmed the biosafety of the combination of olaparib and IL-1β inhibitor.

Polimorfismo IL1B -511 e associação com suscetibilidade e prognóstico em pacientes com carcinoma papilífero de tireoide / IL1B -511 polymorphism and association with susceptibility and prognosis in patients with papillary thyroid carcinoma / IL1B -511 polimorfismo y asociación con susceptibilidad y pronóstico en pacientes con carcinoma papilar de tiroides

Objetivo: Associar a presença do SNP IL1B -511 (rs16944) à susceptibilidade ao CPT, bem como comparar níveis séricos da citocina antes e sete dias após a Iodoterapia, juntamente com outras características clínicas dos pacientes. Método: Trata-se de um estudo caso-controle, no qual foram obtidas amostras de sangue de 52 indivíduos (26 em cada grupo). A genotipagem foi realizada por meio da estratégia PCR-RFLP. Os níveis séricos de IL-1ß foi medido por meio de kit para ensaio imunoenzimático (ELISA). Testes para médias e estudos de associação foram executados considerando-se um nível de significância de 5%. Resultados: Não houve diferença estatística com relação a distribuição genotípica entre indivíduos caso e controle, e estes grupos não diferiram em relação às dosagens de citocina. Porém, os níveis de citocina aumentaram significativamente após a Iodoterapia, sendo que os portadores do genótipo CC apresentaram maior produção da proteína, mas este aumento não estava correlacionado com a dose de radiofármaco administrada. Conclusão: O polimorfismo IL1B -511 não foi associado à susceptibilidade ao CPT, porém os níveis séricos da citocina elevaram-se com o tratamento da iodoterapia, e esta elevação foi genótipo dependente

Objective: To associate the presence of SNP IL1B -511 (rs16944) with susceptibility to TLC, as well as to compare serum cytokine levels before and seven days after iodotherapy, along with other clinical characteristics of patients. Method: This is a case-control study, in which blood samples were obtained from 52 individuals (26 in each group). Genotyping was performed using the PCR-RFLP strategy. Serum IL-1ß levels were measured using an enzyme immunoassay kit (ELISA). Tests for means and association studies were performed considering a significance level of 5%. Results: There was no statistical difference regarding genotypic distribution between case and control individuals, and these groups did not differ in relation to cytokine dosages. However, cytokine levels increased significantly after iodine therapy, and patients with the CC genotype showed higher protein production, but this increase was not correlated with the administered radiopharmaceutical dose. Conclusion: IL1B-511 polymorphism was not associated with susceptibility to TLC, but serum cytokine levels increased with the treatment of iodotherapy, and this elevation was genotype dependent.

Objetivo: investigar la asociación entre el polimorfismo VNTR del gen IL4, localizado en la región intrón 3, en pacientes diagnosticados de accidente cerebrovascular hemorrágico (Stroke) o aneurisma intracerebral en una muestra del Distrito Federal. Método: Estudio observacional, retrospectivo, transversal, con 55 individuos, del cual se registraron las características clínicas de las historias clínicas y se realizó un análisis de genotipado mediante la estrategia de PCR. Las frecuencias genotípicas se estimaron mediante conteo directo. El nivel de significancia adoptado fue del 5% y la prueba estadística utilizada fue Chi-Cuadrado. Resultados: Se verificó que el genotipo más frecuente fue B1/B2 (50,9%; n=28), seguido del genotipo ancestral B1/B1 (27,3%, N=15), y el menos frecuente fue el genotipo B2/B2 (21,8%, N=12). No se encontró asociación estadística entre las variables hipertensión arterial sistémica, diabetes, tabaquismo y consumo de alcohol y la presencia de polimorfismo en el grupo estudiado. Conclusión: La presencia del polimorfismo IL4 INTRON 3 VNTR se asoció con la variable género, demostrando que en la muestra estudiada, AVEH es más frecuente en mujeres que en hombres, divergiendo de los estudios en los que los varones tienen más probabilidades de desarrollar una VENa.

The clinical value of dynamic detection of serum I-FABP, HBP, IL-1β in abdominal compartment syndrome patients secondary to severe acute pancreatitis / 中国医师杂志

Objective:To discuss the value of dynamic detection of serum intestinal fatty acid binding protein (I-FABP), heparin binding protein (HBP) and interleukin-1β(IL-1β) in early predicting and evaluating the severity of abdominal compartment syndrome (ACS) in severe acute pancreatitis (SAP) postoperative patients.Methods:The clinical data of 65 SAP patients treated in the Second Hospital of Anhui Medical University from July 2019 to Jan 2021 were retrospective analyzed. According to whether ACS has occurred, the patients were divided into non ACS group (48 cases) and ACS group (17 cases). The serum I-FABP, HBP and IL-1β of the two groups were dynamically monitored. Correlation analysis and receiver operating characteristic (ROC) curve were used to evaluate the efficacy and early prediction value of each observation index in evaluating the severity of SAP patients complicated with ACS.Results:There were no significant differences in age, sex, body mass index (BMI) and pathogenesis between the two groups (all P>0.05). The serum levels of C-reactive protein (CRP), white blood cell (WBC), Acute Physiology and Chronic Health Enquiry (APACHE-Ⅱ) score and intra-abdominal pressure (IAP) in ACS group were significantly higher than those in non ACS group (all P<0.05). The serum levels of I-FABP [(97.41±15.02)ng/ml vs (37.28±18.34)ng/ml, (103.32±18.40)ng/ml vs (56.96±19.12)ng/ml, (85.69±22.94)ng/ml vs (36.88±10.49)ng/ml], HBP [(92.19±14.59)ng/ml vs (24.56±10.96)ng/ml, (106.11±15.03)ng/ml vs (37.17±13.83)ng/ml, (128.11±16.43)ng/ml vs (68.94±15.91)ng/ml] and IL-1β[(15.78±1.44)pg/ml vs (11.26±1.34)pg/ml, (19.34±1.87)pg/ml vs (13.51±2.84)pg/ml, (20.95±1.96)pg/ml vs (16.03±1.04)pg/ml] on 1st, 4th, 7th day in ACS group were continuously and evidently higher than those in non ACS group ( P<0.01). Correlation analysis revealed that I-FABP, HBP and IL-1β were positively correlated with IAP ( r=0.745, 0.793, 0.770) and APACHE Ⅱ score ( r=0.510, 0.489, 0.445) (all P<0.01). ROC curve analysis showed that the AUC of early prediction by I-FABP, HBP and IL-1β on the occurrence of ACS were 0.846, 0.873 and 0.902 respectively, which were higher than the CRP (0.681), WBC (0.765) and APACHE Ⅱ score (0.795), the sensitivity and specificity can be significantly improved to 0.997 and 0.994 by parallel and series tests respectively combined with the three indicators. Conclusions:Dynamic detection of serum I-FABP, HBP and IL-1β has a certain clinical value in evaluating the severity of ACS in SAP patients. At the same time, early detection with serum I-FABP, HBP and IL-1β has high predictive power for ACS in SAP patients and the combined application of three has higher predictive value.

Long chain noncoding RNA FAM224B protects the lung tissue of rats with severe pneumonia and the underlying mechanism / 中国基层医药

Objective:To investigate the protective effects of overexpression of long-chain noncoding RNA FAM224B on lung tissue of rats with severe pneumonia and the underlying mechanism.Methods:From August 2020 to March 2021, we randomly allocated 20 rats into the pneumonia group (severe pneumonia modeling) and FAM224B group (severe pneumonia modeling + FAM224B plasmid), with 10 rats in each group. We performed a quantitative real-time polymerase chain reaction to detect the level of FAM224B in lung tissue and performed an enzyme-linked immunosorbent assay to detect the levels of tumor necrosis factor-alpha, interleukin-6, and interleukin-1β in lung tissue. We used the software starBase v2.0 to predict the target gene of FAM224B. We performed a quantitative real-time polymerase chain reaction to detect the expression of the target gene in lung tissue and performed a western blot assay to detect the protein expression of the nuclear factor-kappa B signal pathway in lung tissue.Results:FAM224B expression was (1.09 ± 0.23) and (10.12 ± 1.52) in the pneumonia and FAM224B groups, respectively. FAM224B expression was significantly lower in the pneumonia group compared with the FAM224B group ( t = 15.86, P < 0.01). The levels of tumor necrosis factor-alpha, interleukin-6, and interleukin-1β were (41.53 ± 2.46) μg/L, (34.01 ± 2.53) ng/L, (20.92 ± 1.95) μg/L in the pneumonia group and they were (21.71 ± 2.25) μg/L, (17.13 ± 3.01) ng/L, (11.97 ± 1.21) μg/L in the FAM224B group. There were significant differences in the levels of tumor necrosis factor-alpha, interleukin-6, and interleukin-1β between the two groups ( t = 15.94, 14.29, 13.89, all P < 0.01). FAM224B had complementary binding sites with miR-34b-5p. The expression level of miR-34b-5p in lung tissue was significantly lower in the FAM224B group compared with the pneumonia group ( t = 15.55, P < 0.01). The protein expression levels of phosphorylated nuclear factor-κB subunit (p-p65) and phosphorylated inhibitor of kappa B alpha in lung tissue were significantly lower in the FAM224B group compared with the pneumonia group. Conclusion:FAM224B overexpression reduces the inflammatory reaction in lung tissue of rats with severe pneumonia through inhibiting miR-34b-5p expression.

The role of TSG-6 in inhibiting the secretion of IL-1β by bone-marrow-derived macrophages / 中国职业医学

@#Objective To investigate the role of tumor necrosis factor alpha stimulated gene/inducible protein 6（TSG-6）on free silica（SiO2 ）-induced secretion of pro-inflammatory cytokine interleukin（IL）-1β by bone-marrow-derived macrophages （BMDMs）. Methods i）BMDMs isolated from bone marrow were divided into eight groups：the control group was untreated； lipopolysaccharide （LPS） group was stimulated by LPS with a concentration of 50 µg/L；The TSG-6 control group was stimulated by 100 µg/L of recombinant mouse TSG-6. SiO2 model group was pre-stimulated with LPS for four hours，and then stimulated with SiO2 suspension at a final concentration of 250 mg/L；Different dose of TSG-6 groups were firstly treated with above concentrations of LPS and SiO2 suspension，then 10，20，50 and 100 µg/L of recombinant mouse TSG-6 were added respectively；After 16 hours of culture，the cells were collected and the level of IL-1β in BMDMs supernatant was detected by enzyme-linked immunosorbent assay（ELISA）to screen optimal concentration of TSG-6. ii）The cells of the control group，LPS group，SiO2 model group，TSG-6 optimal concentration group and TSG-6 control group were collected. The expression of IL-1β and components of its related pathways in BMDMs was detected by Western blot，including IL-1β，pro-IL-1β，caspase-1，pro dcaspase-1，asc type amino acid transport and NOD-like receptor protein 3（NLRP3）. Results i）Compared with the control group，the expression of IL-1β in SiO2 model group was increased significantly（P<0.01）. Compared with SiO2 model group，the expression of IL-1β in 20，50，100 µg/L dose of TSG-6 groups were decreased significantly（all P<0.01），and the optimal concentration of TSG-6 was found to be 100 µg/L. ii）Compared with the control group and LPS group，the relative expression levels of IL-1β，caspase-1 and NLRP3 in SiO2 model group were increased significantly （all P<0.05）. Compared with SiO2 model group，the expression levels of IL-1β、caspase-1 and NLRP3 were decreased in 100 µg/L TSG-6 group（all P<0.05）. Conclusion TSG-6 could inhibit BMDMs to secret pro-inflammatory cytokine IL-1β by down-regulating the expression of NLRP3 and caspase-1.

Effect of SHP2 knockdown on the proliferation and osteogenic differentiation of human periodontal ligament stem cells under inflammatory environment / 口腔疾病防治

Objective @# The purpose of this study was to clarify the regulatory effect and mechanism of Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2) on human periodontal ligament stem cell (hPDLSC) proliferation and osteogenic differentiation under inflammatory environment and to provide a new target for the treatment of periodontitis. @*Methods@#SHP2 was knocked down in hPDLSCs, and the transfection efficiency of SHP2 was detected by RT-qPCR and Western blot. An in vitro inflammatory environment was created using tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). The effect of SHP2 knockdown on hPDLSC viability under normal and inflammatory conditions was detected by CCK-8, and the osteogenic capacity of hPDLSCs under normal and inflammatory conditions was detected by ALP staining, ALP activity, ARS staining, RT-qPCR and Western blot. The mechanism by which SHP2 knockdown affected the MAPK pathway and its downstream NF-κB pathway under inflammatory conditions was assessed by Western blot. @*Results@# Green fluorescence was observed after transfection for 72 h, and the titer of SHP2 shRNA recombinant lentivirus was 2.9×108 TU/mL. SHP2 expression was significantly downregulated in lentivirus-transfected cells, as demonstrated by Western blot and RT-qPCR (P<0.001). SHP2 knockdown inhibited hPDLSC proliferation to a certain extent and increased the expression of early osteogenic markers under normal conditions, including increased ALP activity and increased ALP and COL-1 expression (P<0.05). However, SHP2 knockdown exerted no effect on mineralized nodule formation. In the TNF-α- and IL-1β-induced inflammatory environment, SHP2 knockdown exerted no effect on hPDLSC proliferation (P>0.05). Osteogenic markers were upregulated (P<0.05), and mineralized nodules were significantly increased (P<0.05) after SHP2 knockdown. Western blot analysis showed that p65 phosphorylation and IκB-α degradation were reduced in SHP2-knockdown hPDLSCs in the inflammatory environment. Moreover, SHP2 knockdown significantly inhibited the expression of p-p38 and p-JNK MAPK, which represent pathways upstream of the NF-κB pathway (P<0.05). @*Conclusion @# SHP2 knockdown did not affect cell viability but promoted the osteogenic potential of hPDLSCs by inhibiting the MAPK/NF-κB-mediated signaling pathway under inflammatory environment.

Therapeutic effect of Yanghe decoction combined with Tounongpowder on patients with acute plasma cell mastitis and its influence on inflammatory factors / 中国医师进修杂志

Objective:To investigate the therapeutic effect of Yanghe decoction combined with Tounongpowder on patients with acute plasma cell mastitis and its influence on inflammatory factors.Methods:A total of 120 patients with acute plasma cell mastitis admitted to Yantai Affiliated Hospital of Binzhou Medical College from May 2019 to May 2020 were selected, and divided into control group (60 cases) and combination group (60 cases). The control group was treated with western medicine, and the combination group was treated with Yanghe decoction and Tounongpowder on the basis of the control group. Seven days was 1 course and a total of 4 courses were continued. The scores of symptoms and signs and clinical effects of the two groups before treatment and 1 month after treatment were compared. The serum interleukin(IL)-1β and IL-6 were measured by radioimmunoassay, and tumor necrosis factor-α(TNF-α) was measured by enzyme-linked immunosorbent assay.Results:After 1 month of treatment, the scores of breast swelling, breast lumps, breast pain, breast fistula symptoms and signs in the two groups were significantly decreased, the scores of above index in the combination group were significantly lower than those in the control group, and the differences were statistically significant ( P<0.05). The total effective rate in the combined group was higher than that in control group: 91.7%(55/60) vs. 76.7% (46/60), and the difference was statistically significant ( χ2 = 8.456, P<0.05). After 1 month of treatment, the serum levels of IL-1β, IL-6 and TNF-α in the two groups were significantly reduced, and the serum levels of above 3 index in the combination group were significantly lower than those in the control group: (3.24 ± 0.92) ng/L vs. (3.81 ± 1.02) ng/L, (1.12 ± 0.42) ng/L vs. (1.41 ± 0.35) ng/L, (32.27 ± 19.03) ng/L vs. (43.04 ± 21.58) ng/L, and the differences were statistically significant ( P<0.05). After treatment, the liver and kidney functions of the two groups were not abnormal, and the differences in adverse reactions such as headache, dizziness, nausea and vomiting were not statistically significant ( P>0.05). Conclusions:Yanghe decoction combined with Tounongpowder can significantly improve the clinical symptoms of patients with acute plasma cell mastitis, with a definite clinical effect. Its mechanism of action may be related to reducing the levels of IL-1β, IL-6, and TNF-α and reducing the inflammatory response.

Role of IL-1β/JNK pathway in sevoflurane-induced necroptosis of rat hippocampal neurons in vitro / 中华麻醉学杂志

Objective:To evaluate the role of interleukin 1β (IL-1β)/c-Jun N-terminal kinase (JNK) pathway in sevoflurane-induced necroptosis of rat hippocampal neurons in vitro. Methods:Primarily cultured hippocampal neurons of Sprague-Dawley rat fetuses were inoculated into 96-well plates (cell density: 1×10 4 cells/ml, 200 μl/hole) and 6-well plates (cell density: 1×10 6 cells/ml, 2 ml/hole). The cells were divided into 3 groups ( n=20 each) using a random number table method after being cultured for 7 days: control group (group C), sevoflurane group (group S) and IL-1 receptor antagonist group (group I). Group C received routine culture, IL-1 receptor antagonist IL-1ra 1 μg/μl was added, and the cells were incubated for 30 min in group I, and in addition the cells were placed in the incubator containing 2% sevoflurane and cultured for 5 h at 37 ℃ in S and I groups.The cells were collected for microscopic examination of the morphology of neurons (with an inverted microscope) and for determination of the cell necroptosis rate (by flow cytometry), cell viability (by MTT method), and expression of IL-1β, interleukin-1 receptor type I (IL-1RI), interleukin-1 receptor accessory protein (IL-1RAcP), phosphorylated JNK (p-JNK) ), receptor-interacting protein 1 (RIP1), RIP3 and phosphorylated mixed lineage kinase-like (p-MLKL) (by Western blot ). Results:Compared with group C, the cell viability was significantly decreased, the necroptosis rate was increased, and the expression of IL-1β, IL-1RI, IL-1RAcP, p-JNK, RIP1, RIP3 and p-MLKL was up-regulated in group S ( P<0.05). Compared with group S, the cell viability was significantly increased, the necroptosis rate was decreased, and the expression of IL-1β, IL-1RI, IL-1RAcP, p-JNK, RIP1, RIP3 and p-MLKL was down-regulated in group I ( P<0.05). There was no obvious abnormality in the morphology of neurons in group C. The cell body of neurons was shrunk, the processes were broken, and the network between processes was sparse in group S. The cell body was round, and the morphology was close to normal in group I. Conclusion:The mechanism by which sevoflurane induces necroptosis of rat hippocampal neurons in vitro is related to activation of IL-1β/JNK pathway.

Role of interleukin-1β in the pathogenesis of alcoholic liver disease / 临床肝胆病杂志

Alcoholic liver disease (ALD) has become the second largest liver disease after viral liver disease in China. Chronic alcohol exposure increases the production of proinflammatory factors including interleukin-1β (IL-1β), which is closely associated with the main symptoms of alcoholic hepatitis such as pyrexia and elevated white blood cell count. This article introduces the production and function of IL-1β; in ALD, it promotes hepatic steatosis and inflammation by acting on liver parenchymal cells and nonparenchymal cells and accelerates liver fibrosis by regulating the proliferation of hepatic stellate cells. It is pointed out that interference with the IL-1β pathway may become one of the treatment strategies for ALD in the future.

Relationship between the polymorphism in the interleukin 1-β and the treatment time of patients subjected to a modified piezocision technique / Relación entre el polimorfismo en la interleucina 1-β y el tiempo de tratamiento de pacientes sometidos a una técnica de piezocisión modificada

Abstract Aim: We aimed to evaluate the correlation between the polymorphism of the interleukin 1-Beta (IL1-β, +3954 C>T) and tooth movement, in a group of Colombian patients undergoing surgically accelerated orthodontic tooth movement. Methods: The study was nested to a controlled clinical trial. Blood samples were taken from 11 women and 29 healthy Colombian male volunteers between 18 and 40 years old, after 1 year of starting orthodontic treatment. The patients presented malocclusion class I, with grade II or III. To detect the genetic polymorphism of the nucleotide +3954 C to T in the IL-1β gene, we used a real-time PCR assay. Results: Eleven individuals presented the allele 2 (T) heterozygous with the allele 1 (T/C) and 19 individuals were homozygous for the allele 1 (C/C). When analyzing the presence of the SNP, no significant differences were found in any of the variables. The best treatment was reflected in Group 3 (selective upper and lower alveolar decortication and 3D collagen matrix) and Group 4 (only selective alveolar decortication in the upper arch, with 3D collagen matrix), with 27% and 35% more speed respectively than in the control group. Conclusions: Our analyses indicated that a reduction in the total treatment time can be mostly potentiated by using decortication and collagen matrices and not for the presence of the allele 2 in the IL-1β. Nevertheless, it is important that further studies investigate if the polymorphism could be associated with the speed of tooth movement and analyze the baseline protein levels.

Resumen Objetivo: Evaluar la correlación entre el polimorfismo de la interleucina 1-Beta (IL1-β, +3954 C> T) y el movimiento de los dientes, en un grupo de pacientes colombianos sometidos a un movimiento dental ortodóncico acelerado quirúrgicamente. Métodos: Este fue un estudio secundario derivado de un ensayo clínico aleatorio controlado. Se tomaron muestras de sangre de 11 mujeres y 29 voluntarios varones colombianos sanos entre 18 y 40 años, después de 1 año de comenzar el tratamiento de ortodoncia. Los pacientes presentaron maloclusión clase I, con grado II o III. Para detectar el polimorfismo genético del nucleótido +3954 C a T en el gen IL-1β, se usó un ensayo de PCR en tiempo real. Resultados: 11 individuos presentaron el alelo 2 (T) heterocigoto con el alelo 1 (T / C) y 19 individuos fueron homocigotos para el alelo 1 (C / C). Al analizar la presencia del SNP, no se encontraron diferencias significativas en ninguna de las variables. El mejor tratamiento se reflejó en el Grupo 3 (decorticación alveolar superior e inferior selectiva y matriz de colágeno 3D) y el Grupo 4 (solo decorticación alveolar selectiva en el arco superior, con matriz de colágeno 3D), con un 27% y un 35% más de velocidad, respectivamente, que en el grupo de control. Conclusiones: Los análisis indicaron que una reducción en el tiempo total de tratamiento puede potenciarse principalmente mediante el uso de decorticación y matrices de colágeno y no por la presencia del alelo 2 en la IL-1β. Sin embargo, es importante que otros estudios investiguen si el polimorfismo podría estar asociado con la velocidad del movimiento de los dientes y analizar los niveles de proteína de referencia.

Níveis Elevados de Netrina-1 e IL-1β em Mulheres Idosas com SCA: Pior Prognóstico no Acompanhamento de Dois Anos / High Serum Netrin-1 and IL-1β in Elderly Females with ACS: Worse Prognosis in 2-years Follow-up

Resumo Fundamento Vários marcadores têm sido avaliados quanto a um potencial impacto nas decisões clínicas ou na predição de mortalidade na síndrome coronariana aguda (SCA), incluindo Netrina-1 e IL-1β. Objetivo Examinamos o valor prognóstico de Netrina-1 e IL-1β em pacientes com SCA (2 anos de acompanhamento). Métodos Avaliamos Netrina-1, IL-1β e outros fatores de risco em amostras de soro de 803 pacientes. Curvas de Kaplan-Meier e regressão de Cox foram usadas para análise de óbito por todas as causas, óbito por doenças cardiovasculares (DCV) e desfecho combinado de infarto agudo do miocárdio (IAM) fatal ou novo IAM não fatal, considerando p < 0,05. Resultados Houve 115 óbitos por todas as causas, 78 óbitos por DCV e 67 eventos no desfecho combinado. Níveis de Netrina-1 acima da mediana (> 44,8 pg/mL) foram associados a pior prognóstico (óbito por todas as causas e por DCV) em mulheres idosas, mesmo após o ajuste do modelo (HR: 2,08, p = 0,038 e HR: 2,68, p = 0,036). Níveis de IL-1β acima da mediana (> 13,4 pg/mL) em mulheres idosas foram associados a risco aumentado para todos os desfechos após o ajuste (todas as causas - HR: 2,03, p = 0,031; DCV - HR: 3,01, p = 0,013; desfecho combinado - HR: 3,05, p = 0,029). Para homens, não foram observadas associações entre Netrina-1 ou IL-1β e os desfechos. Conclusão Níveis séricos elevados de Netrina-1 e IL-1β mostraram associação significativa com pior prognóstico em idosas do sexo feminino. Eles podem ser úteis como indicadores prognósticos em SCA. (Arq Bras Cardiol. 2020; 114(3):507-514)

Abstract Background Several markers have been evaluated for a potential impact on clinical decisions or mortality prediction in acute coronary syndrome (ACS), including Netrin-1 and IL-1β that have been associated with cardiovascular disease. Objective Our study examined the prognostic value of Netrin-1 and IL-1β in patients with ACS (2-year follow-up). Methods We evaluate Netrin-1, IL-1β and other risk factors in the serum sample of 803 patients. Kaplan-Meier curves and Cox regression were used for the analysis of all-cause mortality, cardiovascular mortality, and a combined outcome of fatal myocardial infarction (MI) or new non-fatal MI, considering p-value < 0.05. Results There were 115 deaths from all causes, 78 deaths due to cardiovascular causes and 67 events in combined outcomes. Netrin-1 levels above the median (>44.8 pg/mL) were associated with a worse prognosis (all-cause mortality and cardiovascular mortality) in elderly females, even after model adjustment (HR: 2.08, p = 0.038 and HR: 2.68, p = 0.036). IL-1β levels above the median (>13.4 pg/mL) in elderly females were associated with increased risk of all outcomes after adjustment (all-cause mortality - HR: 2.03, p = 0.031; cardiovascular mortality - HR: 3.01, p = 0.013; fatal MI or new non-fatal MI - HR: 3.05, p = 0.029). For males, no associations were observed between Netrin-1 or IL-1β and outcomes. Conclusion High serum levels of Netrin-1 and IL-1β showed significant association with worse prognosis in elderly females. They may be useful as prognostic indicators in ACS. (Arq Bras Cardiol. 2020; 114(3):507-514)

Niveles plasmáticos de la interlucina-1 ß (IL-1ß) en pacientes con diagnóstico de sepsis y choque séptico en la unidad de cuidados intensivos de una clínica en la ciudad de Cali (Colombia) / Plasmatic levels of Interleukin-1ß (IL-1ß) in Patients Diagnosed with Sepsis and Septic Shock in the Intensive Care Unit of a Clinic in the City of Cali (Colombia)

Objetivo: el objetivo del presente estudio fue evaluar los niveles plasmáticos de IL-1ß como biomarcador de sepsis bacteriana en pacientes de una clínica de la ciudad de Cali. Materiales y métodos: se realizó un estudio prospectivo en 62 pacientes con sepsis y 20 adultos sanos como control, empleando la técnica de ELISA para medir los niveles plasmáticos de las citocinas. Un análisis de regresión logística se utilizó para estimar Odds Ratio (OR), expresado con su 95% intervalos de confianza (IC del 95%) para el resultado de la sepsis en relación a los niveles de IL-1ß. La prueba de Chi-cuadrado y la U de Mann-Whitney se emplearon cuando correspondió, valores de p<0,05, fueron considerados significativos y se empleó el paquete estadístico SPSS. Vs 23.00. Resultados: la edad promedio de los pacientes fue de 53 años y de estancia en la UCI de 7,00 días, 59,7% de ellos eran hombres. El foco pulmonar (43,5%), la hipertensión arterial (41,9%) y bacterias Gram negativas (59,7%) fueron los más prevalentes con una mortalidad del 16,1%. Los altos niveles de IL-1ß se asoció al desarrollo de choque séptico (OR=28,050; IC95%5,512-142,740;p<0,05) y con padecer insuficiencia respiratoria (OR=9,009;IC95%:0,013-0,941; p<0,05). Conclusión: este estudio evidenció niveles plasmáticos significativamente altos de la IL-1ß durante las primeras 48 horas en pacientes con choque séptico. Los altos niveles de esta citosina se relacionaron con mayor riesgo de desarrollo de choque séptico..(AU)

Objective: the objective of the present study was to evaluate plasma levels of IL-1ß were evaluated as a biomarker of bacterial sepsis in patients from a clinic in the city of Cali. Materials and methods: a prospective study was conducted a prospective study in 62 patients with sepsis and 20 healthy adults as control, using the ELISA test to measure plasma levels of cytokines. The analysis of the odds ratio (OR), expressed with its 95% confidence intervals (95% CI) for the outcome of sepsis in relation to the levels of IL-1ß. The Chi-square test and the Mann-Whitney U test will be applied when appropriate, the p values <0.05, and the statistical data of the SPSS statistical package. Vs 23.00. Results: the average age of the patients were 53 years and they were in the ICU of 7.00 days, 59.7% of them were men. The pulmonary focus (43.5%), arterial hypertension (41.9%) and Gram negative bacteria (59.7%) were the most prevalent with a mortality of 16.1%. The high levels of IL-1ß were associated with the development of septic shock (OR = 28,050, 95% CI 5,512-142,740, p<0.05) and with respiratory failure (OR = 9,009, 95% CI: 0.013-0.941, p<0.05. Conclusion: this study evidenced significantly high levels of IL-1ß during the first 48 hours in patients with septic shock. High levels of this cytokine were associated with increased risk of septic shock development..(AU)

Clinical effect of monosialotetrahexosyl ganglioside in the treatment of neonatal intracranial hemorrhage / 中国基层医药

Objective To investigate the clinical effect of monosialotetrahexosyl ganglioside in the treatment of neonatal intracranial hemorrhage.Methods From January 2016 to December 2018,142 neonates with intracranial hemorrhage admitted to the Maternal and Child Health Hospital of Zhoushan were randomly divided into observation group (71 cases) and control group (71 cases) according to the digital table.The control group was treated with routine treatment,while the observation group was treated with ganglioside needle on the basis of the control group.Both two groups were treated for 14 days.The therapeutic effects,muscle tone recovery time,reflex recovery time and consciousness recovery time were compared.The changes of neurobehavioral assessment score (NABA score),TNF-αt,IL-1β,MMP-2,T IMP-1 and NSE levels before and after treatment were compared.Results The total effective rate of the observation group (92.96％) was higher than that of the control group (77.47％) (x2 =6.762,P ＜ 0.05).The recovery time of muscle tension,reflex and consciousness in the observation group [(7.68 ± 1.29) d,(6.83 ± 1.20) d and (8.34 ± 1.54) d] were shorter than those in the control group [(10.25 ± 2.31) d,(9.17 ±1.86) d and (10.53 ± 1.08) d] (t =8.185,8.908,9.811,all P ＜ 0.05).After treatment,the NABA score of the observation group [(40.37 ± 0.65) points] was higher than that of the control group [(37.16 ± 0.93) points] (t =23.838,P ＜ 0.05).The serum levels of TNF-α [(26.37 ± 4.25) pg/L],IL-1β [(16.74 ± 3.24) ng/L],MMP-2 [(78.39 ± 16.57)g/L],TIMP-1 [(179.32 ± 17.65) ng/mL] and NSE [(13.52 ± 2.19) g/L] in the observation group were lower than those in the control group [(53.21 ± 7.39) pg/L,(28.93 ± 5.64) ng/L,(97.42 ±12.63) g/L,(238.63 ± 28) ng/mL and (21.43 ± 2.89) μg/L] (t =26.529,15.792,7.696,14.938,1 8.381,all P ＜ 0.05).Conclusion Ganglioside has good therapeutic effect on neonatal intracranial hemorrhage.It can reduce the serum levels of TNF-α,IL-1β,MMP-2,TIMP-1 and NSE,and improve the neurobehavioral function of neonates.