Objective To summarize the research progress of programmed cell death protein 1 (PD-1)/programmed cell death protein-ligand 1 (PD-L1) inhibitors before liver transplantation of liver cancer. Method The literatures on the application of PD-1/PD-L1 inhibitors before liver transplantation of liver cancer were collected and reviewed. Results PD-1/PD-L1 inhibitors preoperatively treated liver transplantation recipients had a low incidence of postoperative rejection, and routine usage of hormone and immune tolerance induction therapy in liver transplantation recipients might reduce the incidence of rejection caused by PD-1/PD-L1 inhibitors. Conclusion Preoperative usage of PD-1/PD-L1 inhibitors have more benefits than risks for patients with advanced liver cancer.
Objective To summarize the clinical characteristics of interstitial pneumonia with autoimmune features (IPAF). Methods The interstitial lung disease (ILD) patients diagnosed in our department between January 2010 and August 2013 were retrospectively analyzed to screen out the patients with IPAF.The clinical manifestations, laboratory examination, imaging, pulmonary function and treatment were summarized. Results In 254 ILD patients, 25 patients met the diagnosis criteria of IPAF, and 26 patients were diagnosed with definite connective tissue diseases associated ILD (DCTD-ILD). There were differences in arthralgia, sicca symptoms, mechanic’s hand, positive antinuclear antibodies, anti-CCP antibodies and residual lung volume between the IPAF patients and the DCTD-ILD patients (all P < 0. 05). Five IPAF patients were revealed hug or “pancake” the diaphragm in their chest high resolution CT radiographs. The microscopic performance showed that diffuse thickened with collagen fiber, alveolar wall thickening with marked interstitial lymphocyte inflammatory cells infiltration, and granulation tissue that filled bronchiolar lumina. The patients were pathologically diagnosed with nonspecific interstitial pneumonia (NSIP) overlap organized pneumonia (OP). During following-up, the progression-free survival time of the IPAF patients was significant longer and that of the DCTD-ILD patients [(14.32±5.74)months vs. (10. 31± 3. 70) months, P < 0. 05]. Conclusions If an ILD patient has mechanic’s hand, positive antinuclear antibodies or NISP overlap OP in image, the diagnosis of IPAF should be considered. IPAF have slower disease progression and better prognosis than DCTD-ILD.
ObjectivesTo systematically review the efficacy of Bailing capsule for autoimmune antibodies in Hashimoto thyroiditis (HT).MethodsPubMed, EMbase, The Cochrane Library, CBM, WanFang Data and CNKI databases were electronically searched to collect the randomized controlled trials (RCTs) on Bailing capsule in treatment of HT from inception to January 2019. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies, then, meta-analysis was performed by using RevMan 5.3 software.ResultsA total of 7 RCTs involving 428 patients were included. The results of meta-analysis showed that the changes of TGAb and TPOAb in Bailing capsule combined with Euthyrox group were higher than that in control group (MD=−228.91, 95%CI −398.61 to −59.20, P=0.008; MD=−158.19, 95%CI −222.44 to −93.94, P<0.000 01); the changes of TGAb and TPOAb in Bailing capsule combined with Iodine modification diet group were higher than that in control group(MD=−499.27, 95%CI −540.39 to −458.15, P<0.000 01; MD=−407.37, 95%CI −448.60 to −366.14, P<0.000 01).ConclusionsCurrent evidence shows that Bailing capsule combined with other therapies can decrease the levels of TGAb and TPOAb in HT patients. Due to limited quality and quantity of the included studies, more high-quality studies are required to verify the above conclusion.
Objective Risk factors for real-word immune checkpoint inhibitor-related pneumonitis in patients with lung cancer were analyzed by systematic analysis. Methods Computerized retrieval of PubMed, EMbase, Web of Science, the Cochrane Library , WanFang Data, CNKI and VIP databases was carried out. Studies were collected from the database establishment to March 2023. Three researchers independently screened the literature, extracted data, and evaluated the risk of bias in the included studies. Meta-analysis was performed using RevMan5.4.1software. Results A total of 18 studies were included with a total of 4 990 patients. The results of meta-analysis showed that, interstitial pneumonia [odds ratio (OR)=9.32, 95% confidence interval (CI) 4.66 - 18.67, P<0.01], smoking history (OR=2.39, 95%CI 1.29 - 4.45, P<0.01), chronic obstructive pulmonary disease (COPD) (OR=5.54, 95%CI 2.96 - 10.36, P<0.01), chest radiotherapy (OR=2.74, 95%CI 1.80 - 4.19, P<0.01), pulmonary fibrosis (OR=7.46, 95%CI 4.25 - 13.09, P<0.01), high programmed death ligand 1 (PD-L1) expression (OR=2.98, 95%CI 1.71 - 5.22, P<0.01), high absolute eosinophil count (AEC) (OR=3.92, 95%CI 2.17 - 7.08, P<0.01) and pembrolizumab (OR=2.90, 95%CI 1.56 - 5.37, P<0.01) were independent risk factors for immune checkpoint inhibitor-related pneumonitis in lung cancer patients. Conclusions Interstitial pneumonia, smoking history, COPD, Chest radiotherapy, pulmonary fibrosis, high PD-L1expression, high AEC and pembrolizumab are independent risk factors for immune checkpoint inhibitor-related pneumonitis in lung cancer patients. Due to insufficient evidence on the risk factors of low albumin, more studies are needed to further identify it.
ObjectiveTo explore the combined application of neutrophil to lymphocyte ratio (NLR) and systemic immune inflammation index (SII) on the prognosis of hepatitis B-related hepatocellular carcinoma after resection.MethodsRetrospectively collected data of 180 patients with hepatitis B-related hepatocellular carcinoma who were hospitalized in the Department of Infectious Diseases and Hepatobiliary Surgery of the Affiliated Hospital of Southwest Medical University and received surgical treatment from January 2013 to December 2019, including general information, laboratory examination and abdominal CT or MRI results. NLR and SII values were measured at one week before operation, and their critical values of NLR and SII were determined by ROC curve analysis. Univariate and multivariate analysis were performed to determine the risk factors to predict the survival status of patients with hepatitis B-related hepatocellular carcinoma after hepatectomy.ResultsUnivariate analysis showed that AFP, platelets, TNM staging, portal vein tumor thrombus, tumor differentiation, NLR, SII, and NLR+SII combined score were significantly correlated with the prognosis of patients with hepatitis B-related hepatocellular carcinoma (P<0.05). Multivariate analysis showed that PLT [HR=1.791, 95%CI (1.124, 2.854), P=0.014], NLR [HR=4.289, 95%CI (2.571, 7.156), P<0.001], SII [HR=5.317, 95%CI (3.016, 9.374), P<0.001], and NLR+SII combined score [HR=7.901, 95%CI (4.124, 15.138), P<0.001] were independently correlated with the survival of patients with hepatitis B-related hepatocellular carcinoma.ConclusionsThe preoperative NLR+SII combined score can be used to evaluate the postoperative prognosis of patients with hepatitis B-related hepatocellular carcinoma. The higher the score, the lower the postoperative survival rate.
【Abstract】ObjectiveTo study Toll like receptor 4 (TLR4) expression on peripheral blood monocytes (PBMCs) during the early stage of human acute pancreatitis. MethodsThirty consecutive patients with acute pancreatitis admitted within 24 h of onset of abdominal pain were enrolled in this study. Another 20 healthy volunteers were included as control. Blood samples were collected by venipuncture on the day of admission and 3， 7 d after admission and PBMCs were isolated. TLR4 and CD14 expressions on PBMCs were detected by flow cytometry. Serum tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) were measured simultaneously. Correlations between these parameters were analyzed. ResultsTLR4 expression increased on the day of admission and then continued to decline for several days. On third day, TLR4 expression was almost normal compared with the normal control. The alteration of serum TNF-α was consistent with that of TLR4. ConclusionDuring the early stage of human acute pancreatitis, mononuclear-macrophages may be ignited through TLR4 (a door keeper of innate immune system), which lead to TNF-α production.
Alternative splicing plays an important role in the pathogenesis, diagnosis, treatment and prognosis of autoimmune diseases. Alternative splicing is universal and non-preferred in autoimmune diseases, and exon skipping is the most common type in alternative splicing types. The occurrence and development of autoimmune diseases can be influenced by the 5′ splicing, 3′ splicing, number change of exons, splicing affected by the single nucleotide polymorphism and the variance of gene expression levels. Moreover, different single nucleotide polymorphisms of the same gene can affect the development of various autoimmune diseases. This review summarizes the role of different forms of alternative splicing in various autoimmune diseases, and aims to provide a basis for further study of the conditions in different development stages of autoimmune diseases and the regulatory mechanism of different levels of splicing isoforms.
ObjectiveTo investigate the effect of interleukin (IL)-23 receptor (IL-23R) overexpression on the balance of T helper 17 (Th17 cells)/regulatory T cells (Treg cells) in experimental autoimmune uveitis (EAU) mice. MethodsTwelve 8-week-old female C57BL/6J mice were randomly divided into LV-Ctrl group and LV-IL-23R group, with 6 mice in each group. Two groups of mice were injected with LV-Ctrl and LV-IL-23Rlentiviruses through the tail vein, respectively; 7 days after injection, the EAU mouse model was established by active immunization with vitamin A-binding protein 1-20 between photoreceptors. Starting from 13 days after immunization, the fundus of the mice was observed by indirect ophthalmoscopy every 2 days and clinical scores were performed; 30 days after immunization, hematoxylin-eosin staining was used to observe the histopathological changes of mouse retina. The levels of IL-17 in serum of the two groups of mice were detected by enzyme-linked immunosorbent assay; the proportion of Th17 cells and Treg cells was detected by flow cytometry. The relative mRNA expression of IL-23R, IL-17, retinoic acid-related orphan receptor γt (RORγt), IL-10 and forkhead transcripyion factor p3 (Foxp3) were detected by real-time quantitative polymerase chain reaction. Comparisons between groups were performed using repeated measures analysis of variance, independent samples Mann-Whitney U test, and independent samples t test. ResultsCompared with the LV-Ctrlgroup, the retinal inflammatory reaction of the LV-IL-23R group was more severe. At 13 days after immunization, there was no significant difference in fundus inflammation scores between LV-IL-23R group and LV-Ctrl group (t=－2.001, P=0.058); 15-29 days after immunization. The fundus inflammation scores of LV-IL-23Rgroup were higher than those of LV-Ctrl group, and the difference was statistically significant (t=－4.429, －6.578, －7.768, －10.183, －6.325, －7.304, －4.841, －6.872; P＜0.001). Histopathological examination showed that the infiltration of inflammatory cells in the fundus increased, the retinal structure was damaged more seriously, and the histopathological score was significantly increased, and the difference was statistically significant (t=－4.339, P=0.001). Compared with the LV-Ctrl group, the relative expression of IL-23RmRNA in the spleen of the LV-IL-23R group was significantly increased, and the difference was statistically significant (Z=2.087, P=0.037). The relative expression of IL-17 and RORγt mRNA increased, while the relative expression of IL-10 and Foxp3 mRNA decreased, and the differences were statistically significant (t=－6.313,－5.922, 4.844, 7.572; P=0.003, 0.004, 0.008, 0.002). Compared with the LV-Ctrl group, the level of IL-17 in the serum of the mice in the LV-IL-23R group was significantly increased, and the difference was statistically significant (t=－5.423, P=0.002); the proportion of Th17 cells in the spleen and lymph nodes was significantly increased, whereas, the proportion of Treg cells was significantly reduced, and the difference was statistically significant (t=－4.290, 3.700; P=0.002, 0.006). ConclusionIL-23R overexpression can promote Th17/Treg imbalance in EAU mice, and aggravate the clinical and pathological manifestations of EAU.
ObjectiveTo analyze the correlations between the immune function and inflammatory factors levels of patients with hepatocellular carcinoma (HCC) and the results of in vitro high-throughput drug sensitivity, and to provide a reference for personalized drug selection for patients with HCC. MethodsThe patients with HCC who met the inclusion criteria from December 2019 to June 2021 in the First Affiliated Hospital of Chongqing Medical University were included. The HCC cells were used to perform in vitro high-throughput drug sensitivity screening, the result was classified into sensitive and insensitive. The correlations between drug sensitivity results and immune function and inflammatory factors levels of corresponding patients were analyzed, and the relation between these indexes (P<0.05) and drug sensitivity of HCC cells to drugs or combination regimen of drugs was further analyzed by univariate logistic regression. ResultsA total of 74 patients with HCC were included in this study. The results showed that the level of interleukin-6 was negatively correlated with sorafenib, caffezomib, gemcitabine, oxaliplatin + epirubicin + irinotecan + 5-fluorouracil, oxaliplatin + irinotecan + epirubicin, and oxaliplatin + epirubicin regimens on the inhibition rates of HCC in vitro (P<0.05), and positively correlated with bortezomib (P<0.05). However, the level of interleukin-6 was not related to the sensitivity of HCC cells to these single drugs or combined regimens (P>0.05). Meanwhile it was found that tumor necrosis factor (TNF)-α was negatively correlated with cabotinib, apatinib, caffezomib, and epirubicin on the inhibition rates of HCC in vitro (P<0.05), and positively correlated with epirubicin (P<0.05). But only it was found that tumor necrosis factor-α level was related to the sensitivity of HCC cells to epirubicin (P<0.05). ConclusionsTumor necrosis factor-α level in peripheral blood of patients with HCC has a certain relation with epirubicin on inhibition rate of HCC in vitro and it might have a certain value in predicting sensitivity of HCC cells to epirubicin. Meanwhile, although it is found that level of IL-6 is related to sorafenib, caffezomib, gemcitabine, or including combination regiems including oxaliplatin and epirubicin on inhibition rates of HCC in vitro, their value is not found in predicting sensitivity of HCC cells to these single drugs or combined regimens.
ObjectiveTo explore clinical effect of enteral nutrition (EN) through nasojejunal tube in severe acute pancreatitis (SAP).MethodsThe clinical and pathological data of 76 patients with SAP who met the inclusion criteria and treated in the Third People’s Hospital of Henan Province from June 2015 to December 2018 were retrospectively collected. According to the nutritional support therapy adopted in the course of treatment, the patients were divided into an EN group (n=44) and a parenteral nutrition group (PN group, n=32), the patients in the EN group were given the EN through the nasojejunal tube and the patients in the PN group were given the routine PN. The APACHE Ⅱ and SOFA scores, nutritional status, and immune function were observed before the treatment and on week 2 after the treatment in the two groups.ResultsThere were no significant differences in the general data of the gender, age, body mass index, etc. between the two groups (P>0.050). ① The score of APACHEⅡ or SOFA score on week 2 after the treatment in both groups was significantly lower than that before the treatment (P<0.050), which in the EN group was significantly lower than that in the PN group on week 2 after the treatment (P<0.050). ② The levels of albumin and prealbumin were increased significantly and the hemoglobin level was decreased (P<0.050) on week 2 after the treatment as compared with those before the treatment in the two groups (P<0.050), which in the EN group were significantly higher than those in the PN group on week 2 after the treatment (P<0.050). ③ The CD4, CD8, and CD4/CD8 and IgG, IgM, and IgA on week 2 after the treatment were significantly lower than those before the treatment in these two groups (P<0.050), which in the EN group were significantly higher than those in the PN group on week 2 after the treatment (P<0.050). ④ The levels of endotoxin, D-lactic acid, diamine oxidase, and serum high mobility group protein B1 on week 2 after the treatment were significantly lower than those before the treatment in the two groups (P<0.050), and which in the EN group were significantly lower than those of the PN group on week 2 after the treatment (P<0.050). ⑤ The complications rate in the EN group was significantly lower than that in the PN group [20.45% (9/44) versus 53.13% (17/32), χ2=8.786, P=0.003].ConclusionEN through nasojejunal tube has a good effect on patients with SAP, which is helpful to improve their immune and nutritional status.