Objective To construct expression vectors of human ribosomal protein S 3(RPS3) and RPS3Ser209 mutant in orcler to investigate the effect of RPS3Ser209 mutant on NF-κB signaling pathway and DNA binding capacity .Methods The vector RPS3-myc was amplified by polymerase chain reaction ( PCR) from the human liver cDNA and subcloned into pcDNA-3.1myc-HisB.RPS3S209A represented mutant RPS3 expression vectors, in which the designated amino acid was mutated to an alanine residue .Dual luciferase reporter gene assay was used to detect the NF-κB transcription activity in HEK293 cells,immunofluorescence to detect RPS3 location, and EMSA to examine NF-κB DNA-binding activity.Results The expression vectors of RPS3-myc and RPS3S209A-myc were constructed.Compared with wild-type RPS3,the nucleus translocation, transactivation activity of NF-κB and DNA binding ability of RPS3S290A were reduced significantly .Conclu-sion The impact of RPS3 on NF-κB signaling pathway depend on its serine 209.

Objective Acute liver failure is one of the significant causes of death clinically.It is important to explore new serum markers of liver injury for early diagnosis and prognosis prediction of severe liver disease.Hepassocin ( HPS) is a liver-specific mitogenic growth factor.Our study is intended to investigate the correlation between HPS serum levels and the degree of liver injury.Methods Firstly, a mouse model of acute liver injury was constructed via intraperitoneally injection with different doses of CCl4 .Then the survival rate, alanine aminotransferase ( ALT) , aspartate aminotransferase ( AST) and the pathological changes in the liver were detected.Meanwhile, ELISA assay was performed to detect the serum level of HPS.In addition, the mRNA level and protein level of HPS were detected by real-time PCR and Western blotting, respectively.Results The mortality rate was increased and the liver damage was aggravated with the increase of the CCl4 dose.Besides, the ALT and AST levels were also increased in a dose-dependent manner.Additionally, the mRNA and protein levels of HPS were significantly up-regulated and closely related to the degree of the liver injury in the model. Conclusion HPS can be used as a new marker of liver injury in mice.

Objective To investigate the regulation of T cells in the process of liver regeneration using a model of mice after 70% liver resection.Methods We performed 70% hepatectomy in T-cell-deficient mice and control mice.The liver mass and body mass ratio, BrdU infiltration level, proliferating cell nuclear antigen (PCNA),expression of M phase marker protein p-HDAC3, and serum transaminase levels were measured.Results The recovery of liver mass and body mass ratio of thymus-deficient mice occurred significantly later than that of control mice.The peak time of BrdU infiltration levels and the expression of PCNA and p-HDAC3 in T-cell-deficient mice were later than in control mice, but the degree of liver injury was lower.Conclusion T cells are involved in the regulation of liver regeneration, and the absence of T cells delays the process of liver regeneration.

OBJECTIVETo study the effect of E3 ubiquitin ligase RNF31 knockdown on nuclear factor-κB (NF-κB) pathway activation and cell apoptosis.

METHODSHuman RNF31 siRNA sequences were cloned into the lentiviral vector pGreenPuro and transiently transfected in HEK293T cells to screen the most effective fragments, which were co-transfected along with the packaging plasmids PMD and SPA in 293T cells. The cell supernatant was collected at 24 h and 48 h after the transfection and the viral titers were determined with flow cytometry. Real-time PCR and Western blotting were used to evaluate the effect of RNF31 knockdown on the expression of NF-κB downstream target genes and IκBα activity; the changes of NF-κB pathway transcriptional activity were assessed with dual luciferase reporter gene. Hochest dying was used to examine the influence of RNF31 down-regulation on cell apoptosis.

RESULTSRNF31 knockdown mediated by the lentiviral vector pGreenPuro-RNF31 suppressed the transcriptional activity of NF-κB and the downstream target genes in HEK293 cells stimulated with TNF-α. RNF31 knockdown also resulted in suppression of NF-κB-stimulated expression of pIκBα and in increased apoptosis of cells stimulated with TNF-α for 24 h.

CONCLUSIONRNF31 down-regulation inhibits NF-κB pathway activation induced by TNF-α.

Apoptosis ; Down-Regulation ; Gene Expression Regulation ; Genetic Vectors ; HEK293 Cells ; Humans ; I-kappa B Proteins ; metabolism ; Lentivirus ; NF-KappaB Inhibitor alpha ; NF-kappa B ; metabolism ; RNA, Small Interfering ; Real-Time Polymerase Chain Reaction ; Signal Transduction ; Transfection ; Tumor Necrosis Factor-alpha ; pharmacology ; Ubiquitin-Protein Ligases ; genetics ; metabolism

OBJECTIVETo explore the effect and mechanism of ginsenoside Rg3 (Shenyi Capsule) on the postoperative life span of patients with non-small cell lung cancer (NSCLC).

METHODSThe prospective, randomized, controlled method was adopted. One hundred and thirty-three patients with NSCLC were randomly assigned to 3 groups: Shenyi Capsule group (43 cases), combined therapy group (Shenyi Capsule plus chemotherapy, 46 cases), and chemotherapy group (44 cases). The survival rates, immune function and the correlation between vascular endothelial growth factor (VEGF) expression and clinical effect were analyzed in the three groups.

RESULTS(1) The 1-year survival rate in the Shenyi group, the combined group and the chemotherapy group was 76.7% (33/43), 82.6% (38/46), and 79.5% (35/44), respectively; the 2-year survival rate was 67.4% (29/43), 71.7% (33/46), and 70.5% (31/44), respectively; and the 3-year survival rate was 46.5% (20/43), 54.3% (25/46), and 47.7% (21/44), respectively. There was no significant difference among the 3 groups (P>0.05). (2) NK cells were increased to different degrees and the ratio of CD4/CD8 was normal in the Shenyi Capsule group and the combined group, while the ratio of CD4/CD8 was disproportional in the chemotherapy group. (3) In the chemotherapy group, the 3-year survival rate was lower in patients with positive expression of VEGF than in patients with negative expression (37.0% vs 64.7%, chi2=17.9, P<0.01), but no signifi cant statistical difference was shown in the other two groups (53.6% vs 55.6%, P>0.05; 44.4% vs 50.0%, P>0.05).

CONCLUSIONShenyi Capsule, especially in combination with chemotherapy, can improve the life span of patients with NSCLC after operation. The mechanism might be correlated with improving the immune function and anti-tumor angiogenesis

Adult ; Aged ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; immunology ; mortality ; Female ; Ginsenosides ; adverse effects ; pharmacology ; therapeutic use ; Humans ; Lung Neoplasms ; drug therapy ; immunology ; mortality ; Male ; Middle Aged ; Prospective Studies ; Survival Rate ; Vascular Endothelial Growth Factor A ; analysis

BACKGROUNDCan single-agent maintenance therapy be considered as an ideal strategy for non-small cell lung cancer (NSCLC) treatment to achieve prolonged survival and tolerated toxicity? A systematic review and meta-analysis was performed to elucidate this issue.

METHODSThe electronic databases were searched for RCTs comparing single-agent maintenance therapy with placebo, best support care or observation. The required data for estimation of response, survival and toxicity were extracted from the publications and the combined data were calculated.

RESULTSEleven RCTs involving 3686 patients were identified. We found a statistically significant higher probability of tumor response for patients with maintenance therapy versus control patients (OR: 2.80, 95%CI: 2.15 - 3.64). Patients receiving maintenance therapy had significantly longer progression-free survival (PFS) (HR: 0.67, 95%CI: 0.62 - 0.71) and overall survival (OS) (HR: 0.84, 95%CI: 0.78 - 0.90). However, maintenance therapy was associated with more severe toxicities (OR: 6.45, 95%CI: 4.61 - 9.01).

CONCLUSIONIn patients with advanced NSCLC, the use of single-agent maintenance therapy is associated with higher response rate and significantly prolongs PFS and OS despite of the risk of additional toxicity.

Antineoplastic Agents ; adverse effects ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; mortality ; Disease-Free Survival ; Humans ; Lung Neoplasms ; drug therapy ; mortality ; Publication Bias

OBJECTIVETo determine the pulmonary pathological changes in hematological malignancy patients with pulmonary complications.

METHODS17 hematological malignancy patients underwent surgical treatment were evaluated retrospectively. The pathological changes of all the surgical specimens were examined postoperatively by standard hematoxylin and eosin (HE) staining.

RESULTSPathological examination confirmed: aspergillus infection in 9 patients, sub-acute inflammation (fibrosis and hematoma formation) in 3, and each in 1 of pulmonary infarction with granulomatous tissue in the periphery; granulomatous inflammation with calcified tubercle; alveolar dilation and hemorrhage, interstitial fibrosis and focal vasculitis; intercostal neurilemmoma; and moderate-differentiated adenocarcinoma accompanied by intrapulmonary metastasis. And several operative complications (1 case of fungal implantation, 3 pleural effusion and adhesions and 2 pulmonary hematoma) were occurred. The coincidence rate of pre- and post-operative diagnosis was 9/14 (64.3%). After surgery, 8 patients were received hematopoietic stem cell transplantation (HSCT, allo-gene or autologous), with 7 succeeded. On effective secondary antifungal prophylaxis, 4 of 5 patients of aspergillosis succeeded in transplantation with free from mycotic relapse, one patient died from fungal relapse.

CONCLUSIONHematological malignancies with persistent and/or resistant pulmonary infection, hemoptysis, or unexplained lung diseases, should be treated in time by surgery operation to effectively eliminate residual disease and obtain a definitive diagnosis, so as to create a prerequisite condition for the following treatments. Moreover, the secondary antifungal prophylaxis can provide active roles for patients scheduled for chemotherapy and/or HSCT.

Aspergillosis ; diagnosis ; Hematologic Neoplasms ; Hematopoietic Stem Cell Transplantation ; Humans ; Lung Diseases ; Neoplasm Recurrence, Local

Objective: To explore the clinical efficacy and safety of modified Huqianwan in treatment of rheumatoid arthritis (RA) liver-kidney Yin deficiency syndrome, and investigate its possible mechanism. Method: A total of 184 patients with RA liver-kidney Yin deficiency syndrome were randomly divided into Chinese medicine group (62 cases), western medicine group (57 cases) and integrated Chinese and western medicine group (65 cases) according to the digital table method. The patients in Chinese medicine group were treated with Huqianwan; the patients in western medicine group were treated with methotrexate tablets and leflunomide tablets; and the patients in integrated Chinese and western medicine group received Huqianwan+methotrexate tablets and leflunomide tablets,with a treatment course of 12 weeks in all groups. The pain visual analog scale (VAS), swelling and tenderness scores of 28 joints (DAS28), average hands grip strength, morning stiffness time and liver-kidney Yin deficiency syndrome differentiation of traditional Chinese medicine (TCM) syndrome score were compared between groups before and after treatment. The changes of erythrocyte sedimentation rate (ESR), C reactive protein (CRP), immunoglobulin (Ig) G, tumor necrosis factor-alpha (TNF-α) and rheumatoid factor (RF) were detected in all groups after treatment. Clinical efficacy, and incidence of adverse reactions such as gastrointestinal response, liver injury, leukopenia, serum glutamate oxaloacetic aminotransferase (GOT) and platelet (PLT) level changes were compared between the groups, so as to investigate the efficiency and safety of the different medicines. Result: After 12 weeks of treatment, the total clinical effective rate was 79.0%, 80.7%, and 92.3% respectively in Chinese medicine group, western medicine group, and integrated Chinese and western medicine group; the integrated Chinese and western medicine group was significantly better than the Chinese medicine group and western medicine group (P<0.01), but there was no difference between the Chinese medicine group and western medicine group. Every treatment group can effectively improve liver and kidney Yin deficiency syndrome in RA patients (P<0.05), and the effect in integrated Chinese and western medicine group was superior to that in Chinese medicine group (P<0.05); the effect in Chinese medicine group was superior to that in western medicine group (P<0.05). The incidence of adverse reactions was Chinese medicine group (1.61%, 1/62)Conclusion: The efficacy in treating RA liver and kidney Yin deficiency syndrome shows no significant difference between modified Huqianwan and methotrexate tablets+leflunomide tablets. In the treatment of RA liver and kidney Yin deficiency syndrome, Huqianwan has fewer adverse reactions. Huqianwan combined with methotrexate tablets+leflunomide tablets is superior to that in methotrexate tablets+leflunomide tablets in treatment of RA liver-kidney Yin deficiency syndrome.

Anemia, Hemolytic ; chemically induced ; diagnosis ; Ceftriaxone ; adverse effects ; Child ; Cochlear Implantation ; adverse effects ; Hearing Loss, Sensorineural ; surgery ; Humans ; Male ; Vestibular Aqueduct

OBJECTIVE: To investigate the significance of anti-histidyl tRNA synthetase (Jo-1) antibody in idiopathic inflammatory myopathies (IIM) and its diseases spectrum. METHODS: We enrolled all the patients who were tested positive for anti-Jo-1 antibody by immunoblotting in Peking University People's Hospital between 2016 and 2022. And the patients diagnosed with anti-synthetase antibody syndrome (ASS) with negative serum anti-Jo-1 antibody were enrolled as controls. We analyzed the basic information, clinical characteristics, and various inflammatory and immunological indicators of the patients at the onset of illness. RESULTS: A total of 165 patients with positive anti-Jo-1 antibody were enrolled in this study. Among them, 80.5% were diagnosed with connective tissue disease. And 57.6% (95/165) were diagnosed with IIM, including ASS (84/165, 50.9%), immune-mediated necrotizing myopathy (7/165, 4.2%) and dermatomyositis (4/165, 2.4%). There were 23.0% (38/165) diagnosed with other connective tissue disease, mainly including rheumatoid arthritis (11/165, 6.7%), undifferentiated connective tissue disease (5/165, 3.0%), interstitial pneumonia with autoimmune features (5/165, 3.0%), undifferentiated arthritis (4/165, 2.4%), Sjögren's syndrome (3/165, 1.8%), systemic lupus erythematosus (3/165, 1.8%), systemic vasculitis (3/165, 1.8%), and so on. Other cases included 3 (1.8%) malignant tumor patients, 4 (2.4%) infectious cases and so on. The diagnoses were not clear in 9.1% (15 /165) of the cohort. In the analysis of ASS subgroups, the group with positive serum anti-Jo-1 antibody had a younger age of onset than those with negative serum anti-Jo-1 antibody (49.9 years vs. 55.0 years, P=0.026). Clinical manifestations of arthritis (60.7% vs. 33.3%, P=0.002) and myalgia (47.1% vs. 22.2%, P=0.004) were more common in the ASS patients with positive anti-Jo-1 antibody. With the increase of anti-Jo-1 antibody titer, the incidence of the manifestations of arthritis, mechanic hands, Gottron sign and Raynaud phenomenon increased, and the proportion of abnormal creatine kinase and α-hydroxybutyric dehydrogenase index increased in the ASS patients. The incidence of myalgia and myasthenia were significantly more common in this cohort when anti-Jo-1 antibody-positive ASS patients were positive for one and more myositis specific antibodies/myositis associated autoantibodies (P < 0.05). CONCLUSION The disease spectrum in patients with positive serum anti-Jo-1 antibody includes a variety of diseases, mainly ASS. And anti-Jo-1 antibody can also be found in many connective tissue diseases, malignant tumor, infection and so on.
Humans ; Middle Aged ; Myalgia ; Myositis/epidemiology* ; Autoantibodies ; Connective Tissue Diseases ; Arthritis, Rheumatoid ; Neoplasms