Objective:The tumorigenesis, progression, and metastasis of lung cancer are mostly governed by the immunosuppres-sive profile. This study aimed to explore the levels of various immunosuppressive inhibitory molecules in lung-cancer patients subject-ed to different chemotherapy cycles. Methods:Thirty-three patients with advanced lung cancer (ALC;stages III-IV) without receiving prior chemotherapy and 23 healthy subjects were enrolled in our study. Peripheral blood samples were collected from the patients be-fore each chemotherapy cycle. The inhibitory markers expressed in T cells such as TIM3, PD-1, and CTLA4 were analyzed by flow cy-tometry. Results:The percentages of CD4+TIM3+, CD8+TIM3+, CD4+PD-1+, CD8+PD-1+, CD4+CTLA-4+, and CD8+CTLA-4+T cells in the peripheral blood of the ALC patients were significantly higher compared to the controls. The percentage of CD4+TIM3+, CD8+TIM3+, CD4+PD-1+, and CD8+PD-1+T lymphocytes in the peripheral blood of patients (n=19) who achieved PR or SD significantly de-creased after five cycles of chemotherapy (P<0.05). Similarly, the percentages of CD4+CTLA-4+and CD8+CTLA-4+T cells in the pa-tients also decreased after five cycles of treatment. Conclusion:The immune status of ALC patients was evidently suppressed. Effec-tive chemotherapy successfully potentiated effective immune responses by downregulating inhibitory molecules in T cells.

OBJECTIVETo investigate the anti-oxidative stress and anti-fibrotic mechanisms of adiponectin by examining effects on oxidative stress levels and expression of fibrosis-related signaling factors, including transforming growth factor-beta 1 (TGFb1), collagen I (COL-1), and the adenosine monophosphate-activated protein kinase (AMPK) pathway by using an in vitro HSC-T6 cultured cell system.

METHODSActivated HSC-T6 cells were pre-treated with 1.0 mug/mL adiponectin for 0, 30, 60 and 120 min, or left untreated to serve as controls, and both groups were then exposed to 5 mumol/L H2O2; a portion of the adiponectin-treated oxidative stress-induced cells were treated with an AMPK inhibitor (Compound C). The effects on mRNA levels of TGFb1. and COL-1 were analyzed by real-time PCR, in the levels of secreted TGF-b1 and COL-1 were detected by enzyme-linked immunosorbent assay of supernatants, and in the phosphoAMPK and AMPK protein expressions were detected by Western blotting.

RESULTSCompared to the H2O2 group without adiponectin pre-treatment, the H2O2 group with adiponectin pre-treatment showed significantly increased activity of superoxide dismutase (SOD), decreased content of malondialdehyde (MDA), and decreased gene and protein expressions of TGF-b1 and COL-1 (P less than 0.05). Moreover, inhibition of the AMPK pathway inhibited these adiponectin-mediated effects. The H2O2 group with adiponectin pre-treatment also showed increased levels of phospho-AMPK protein expression, with the maximum effect detected after 120 min of the adiponectin pre-treatment (P less than 0.01).

CONCLUSIONInhibition of oxidative stress is one of the mechanisms of the anti-fibrotic effects of adiponectin. Adiponectin can attenuate oxidative stress levels, resulting in down-regulation of TGFb1 and COL-1 expression through activation of the AMPK pathway.

AMP-Activated Protein Kinases ; Adiponectin ; Cell Line ; Collagen Type I ; Down-Regulation ; Hepatic Stellate Cells ; Humans ; Hydrogen Peroxide ; Oxidative Stress ; RNA, Messenger ; Signal Transduction ; Transforming Growth Factor beta1

Objective:To investigate the expression of retinoic acid receptor responsive gene 2 (RARRES2), microtubule microfilament cross-linking factor 1 (MACF1), and core protein polysaccharide (DCN) in cerebrospinal fluid (CSF) of patients with neurosyphilis, and their diagnostic value for neurosyphilis.Methods:A total of 64 non neurosyphilis syphilis patients (syphilis group) and 78 neurosyphilis patients (neurosyphilis group) admitted to the Second Hospital of Nanjing between June 2020 and September 2022 were included. Among neurosyphilis patients, there were 48 early neurosyphilis patients (early group) and 30 late neurosyphilis patients (late group). Patients with neurosyphilis are treated with routine symptomatic therapy and antibiotic therapy to expel syphilis. The mRNA levels of RARRES2, MACF1, and DCN in CSF of patients with neurosyphilis before and after treatment were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The National Institutes of Health Stroke Scale (NIHSS) was used to evaluate the neurological function of patients with neurosyphilis before and after treatment. The diagnostic value of various indicators for neurosyphilis was analyzed using receiver operating characteristic (ROC) curves.Results:The mRNA levels of RARRES2, MACF1, and DCN in CSF of patients with neurosyphilis were higher than those in the syphilis group (all P<0.001). The mRNA levels of RARRES2, MACF1, and DCN in the CSF of patients with advanced neurosyphilis were higher than those in the early group (all P<0.001). Compared with before treatment, the NIHSS score and RARRES2, MACF1, and DCN mRNA levels of neurosyphilis patients decreased after treatment (all P<0.001). The area under the curve (AUC), sensitivity, and specificity of the combined diagnosis of RARRES2, MACF1, and DCN mRNA in CSF for neurosyphilis were 0.995%, 100.00%, and 93.75%, respectively. The AUC and sensitivity were higher than those of individual diagnosis. Conclusions:The expression of RARRES2, MACF1, and DCN is elevated in CSF of patients with neurosyphilis, and is associated with disease severity and treatment response. These three genes may be candidate biomarkers for diagnosing neurosyphilis.

Objective To evaluate the efficacy, safety and risk factors of endoscopic treatment for patients with early gastric cancer. Methods A retrospective study was conducted in a single center and data was collected from 186 early gastric cancers in 168 pathologically confirmed patients who received endoscopic treatment in Peking Union Medical College Hospital from January 2006 to December 2015. The cases were divided into different groups according to indications of endoscopic treatment. The curative resection rate and complication rate were analyzed. Post-resection outcomes were evaluated by long-term surveillance. Results The curative resection rate was 86. 9%( 73/84) in the group with absolute indications, 61. 7%(50/81)in the group with expanded indications, and 33. 3%(7/21) in the group beyond indications (P＜0. 01). Multivariate analysis revealed that the significant independent predictors for curative resection included lower third location of stomach, no ulceration,≤2 cm at diameter, no adhesion, and well-differentiation in histopathology. In the expanded indications group, discordance of differentiation type and deeper invasion mainly resulted in non-curative resection in en bloc lesions. The rate of bleeding and perforation was 4. 8%( 9/186) and 3. 8%( 7/186), respectively. The perforation rate was significantly lower in the lesions located in the lower third of stomach, without adhesion or performed by en bloc resection. During a median follow-up period of 22. 3 months, 154 patients were followed successfully. The incidence of synchronous and metachronous gastric cancers in curative resected lesions was 7. 5%( 8/106) and 0. 9%(1/106), respectively. Conclusion Endoscopic resection is an optimal treatment with high curative resection rate for early gastric cancer patients with absolute indications. Patients with expanded indications should take precise preoperative evaluation to avoid higher risk of non-curative resection endoscopically. Close follow-up is necessary for synchronous and metachronous gastric cancers after endoscopic resection.

To investigate the clinical manifestations and risk factors in patients with systemic lupus erythematosus (SLE) and cancers. From October 2010 to February 2019, 5 566 SLE patients hospitalized in the First Affiliated Hospital of Zhengzhou University were enrolled. A total of 69 cancer patients were identified, and the clinical characteristics and previous treatment were analyzed. Cervical carcinoma (21.74%, 15/69) and thyroid cancer (21.74%, 15/69) were the most common types of cancer. Most cancers were diagnosed in SLE patients with an age 40~50 years. The disease duration of SLE was from 60~120 months. SLE patients without cancers were usually diagnosed between 20~30 years with duration of symptoms less than 12 months. As to the previous treatment of SLE, the uses of glucocorticoid, cyclophosphamide, methotrexate and azathioprine were comparable between patients with cancers and without (P>0.05). However, the use of hydroxychloroquine was more frequent in SLE patients than in patients with cancers (P<0.01). Correlation analysis revealed significant correlation between disease course of SLE (OR=4.25, 95%CI 1.79~10.01,P<0.001), hydroxychloroquine (OR=0.26, 95%CI 0.12~0.59,P<0.001) and cancer risk. Long disease course may be a risk factor for SLE patients to develop cancer, whereas hydroxychloroquine could be a protective factor.