SOCS3 protein expression predicts the responses of advanced non-small cell lung cancer patients to platinum-based chemotherapy.

Background: This study sought to assess the relationship between suppressor of cytokine signaling 3 (SOCS3) expression, SOCS3 promoter methylation status, and platinum-based chemotherapy responses in advanced non-small cell lung cancer (NSCLC) patients. Methods: A total of 400 advanced NSCLC patients with inoperable disease were enrolled in this study. All the patients underwent platinum-based chemotherapy treatment, and the clinical and prognostic outcomes of these patients were analyzed. The SOCS3 protein expression and SOCS3 promoter methylation status of the tumor tissues in these patients were also tested by immunohistochemistry and polymerase chain reaction (PCR), respectively. In addition, we knocked down SOCS3 expression via small-interfering RNA (siRNA) in the lung cancer cell lines and conducted in vitro analyses to examine cell viability and apoptosis. Results: Patients with higher expression levels of SOCS3 were found to have a lower average tumor stage, higher average tumor differentiation, and higher rates of positive chemotherapy responses than those with lower expression levels of SOCS3. SOCS3 promoter methylation was also found to be correlated with chemotherapy responses in these patients. In the prognostic analyses, only SOCS3 expression, but not SOCS3 promoter methylation, was found to be predictive of outcomes in advanced NSCLC patients. We also found that the pro-apoptotic effects of SOCS3 were mediated by the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathways in the lung cancer cells. Conclusions: Currently, there is a lack of reliable biomarkers for predicting the responses of NSCLC patients to chemotherapy. Our results may aid in clinical evaluations of NSCLC patients.

[Mechanism of Xinfeng Capsules improving rheumatoid arthritis based on CD19~+B cells regulating FAK/CAPN/PI3K pathway].

To observe the effect of Xinfeng Capsules on rheumatoid arthritis (RA) B lymphocytes,inflammatory mediators,FAK/CAPN/PI3K pathway,in order to explore the mechanism of Xinfeng Capsules in improving clinical symptoms of RA.Joint and systemic symptoms of RA patients were observed,and laboratory indicators[hemoglobin (HGB),platelet count (PLT),erythrocyte sedimentation (ESR),immunoglobulin (Ig) G,Ig A,Ig M,rheumatoid factor (RF),anti-cyclic citrulline antibody (CCP-AB),C-reactive protein (CRP)]were detected.ELISA was used to detect serum interleukin (IL)-1ß，IL-10,IL-33,chemokine 5 (CCL5),and vascular endothelial growth factor (VEGF).CD3~-CD19~+B cells were measured by flow cytometry.Western blot was used to detect FAK,p-FAK,CAPN,PI3K protein.The results showed that Xinfeng Capsules could significantly alleviate RA joint and systemic symptoms and improve clinical efficacy.And Xinfeng Capsules could increase HGB,decrease PLT,CCP-AB,CRP,ESR index,upregulate IL-10 expression,and down-regulate IL-1ß，IL-33,CCL5,VEGF,CD3~-CD19~+B cells,FAK,p-FAK,CAPN,PI3K expressions (P<0.01).Based on the above results,Xinfeng Capsules may reduce the expression of CD3~-CD19~+,regulate the balance of inflammatory cytokines and chemokines,inhibit abnormal activation of FAK/CAPN/PI3K pathway,and improve clinical symptoms of RA.

Cost benefit analysis of portable chest radiography through glass: Initial experience at a tertiary care centre during COVID-19 pandemic.

INTRODUCTION: Portable chest radiography through glass (TG-CXR) is a novel technique, particularly useful during the COVID-19 (Coronavirus disease 2019) pandemic. The purpose of this study was to understand the cost and benefit of adopting TG-CXR in quantifiable terms. METHODS: Portable or bedside radiographs are typically performed by a team of two technologists. The TG-CXR method has the benefit of allowing one technologist to stay outside of the patient room while operating the portable radiography machine, reducing PPE use, decreasing the frequency of radiography machine sanitization and decreasing technologists' exposures to potentially infectious patients. The cost of implementing this technique during the current COVID-19 pandemic was obtained from our department's operational database. The direct cost of routinely used PPE and sanitization materials and the cost of the time taken by the technologists to clean the machine was used to form a quantitative picture of the benefit associated with TG-CXR technique. RESULTS: Technologists were trained on the TG-CXR method during a 15 min shift change briefing. This translated to a one-time cost of $424.88 USD. There was an average reduction of portable radiography machine downtime of 4 min and 48 s per study. The benefit of adopting the TG-CXR technique was $9.87 USD per patient imaged. This will result in a projected net cost savings of $51,451.84 USD per annum. CONCLUSION: Adoption of the TG-CXR technique during the COVID-19 pandemic involved minimal one-time cost, but is projected to result in a net-benefit of over $51,000 USD per annum in our emergency department.

[Effect of Triptolide on Cardiac Function in Arthritic Rats and Its Mechanism].

OBJECTIVE: To observe the changes of cardiac function in arthritic rats and the effect of triptolide on it. METHODS: Forty rats were divided in random into normal control (NC) group, model control (MC) group, leflunomide (LEF) group and triptolide (TP) group. Except for the normal group, rats in the other three groups were injected with Freund's complete adjuvant to create arthritic inflammation in the right hind paws, and the interventional drug was administered on the 12th day after the inflammation. By treating for 30 d, the cardiac function of rats was detected by left ventricular catheterization. The expressions of superoxide dismutase (SOD), malondialdehyde (MDA), reacitve oxygen species (ROS), total antioxidation (T-AOC), interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α) in serum were measured by enzyme-linked immunosorbent assay. The expressions of keap-like protein 1 ( Keap1), muscular aponeurotic fibrosarcom ( maf) and nuclear factor-E2 related factor2 ( Nrf2) mRNAs in cardiac tissue were detected by real-time PCR. The expressions of Keap1, maf and Nrf2 proteins in heart tissues were detected by Western blot. RESULTS: Comparing with the normal group, the heart rate (HR), heart index (HI), left ventricular systolic pressure (LVSP), and left ventricular end-diastolic pressure (LVEDP) of the model group were significantly increased, whereas the maximum change rate of ventricular pressure rise or decline (±dp/dtmax) was significantly decreased ( P<0.01). SOD, MDA, ROS, T-AOC, and TNF-α were all increased, and IL-10 was significantly decreased ( P<0.01). The mRNA and protein expressions of Keap1, maf and Nrf2 in heart tissues were increased ( P<0.01). Comparing with the model group, HR, HI, LVSP, and LVEDP in the triptolide group were significantly decreased, whereas the ±dp/dtmax was significantly increased ( P<0.01). SOD, MDA, T-AOC, ROS, TNF-α decreased while the IL-10 increased ( P<0.05, P<0.01). The expressions of Keap1, maf and Nrf2 mRNAs and proteins in the heart tissues of the triptolide group were decreased ( P<0.01). CONCLUSION: Triptolide could improve cardiac function in arthritic rats, and the mechanism may related to its ability of improving the anti-oxidationin cardiomyocytes, reducing oxidative stress damage, and inhibiting abnormal immune inflammatory response.

Xinfeng capsule for the treatment of rheumatoid arthritis patients with decreased pulmonary function--a randomized controlled clinical trial.

OBJECTIVE: To determine the effectiveness and safety of Xinfeng Capsules (XFC) for the treatment of rheumatoid arthritis (RA) patients with decreased pulmonary function. METHODS: This was a randomized controlled clinical trial of 80 RA patients. Participants were assigned to the trial group (40 cases) and the control group (40 cases) by block randomization. The trial group was treated with XFC, three pills each time three times daily for 2 months. The control group was treated with tripterygium glycoside (TPT), two pills each time three times daily for 2 months. Both groups were followed up after 2 months. The clinical effects, changes in joint and pulmonary function, and quality of life before and after treatment were observed; safety indices were also evaluated. RESULTS: Pain, swelling, tenderness, and duration of morning stiffness of joints were obviously decreased after treatment in both the trial and the control groups compared with baseline (P<0.01). Compared with before treatment, hand grip strength increased significantly after treatment in the trial group (P=0.0000); pulmonary function parameters such as forced expiratory volume in the first second of expiration/forced vital capacity (FEV1/FVC), 50% of the expiratory flow of forced vital capacity (FEF50), carbon monoxide diffusing capacity (DLco) were increased (P<0.01 or P<0.05); measures of quality of life such as role-physical, body pain, vitality and mental health were also improved after treatment in the trial group (all P<0.05). Joint swelling in the trial group decreased compared with the control group (P=0.0043), while hand grip strength was increased after treatment (P=0.0000). The increase in FEF50, DLco, and the dimensions of quality of life such as vitality and mental health were all significantly greater in the trial group than the control group (P<0.05 or P<0.01). CONCLUSIONS: XFC not only relieved joint pain in RA patients, but also significantly improved the ventilation and diffusion function of the lungs. Therefore, XFC could improve the whole body function and enhance the quality of life of RA patients.

Inhibition mechanism of Qingluo Tongbi Granule () on osteoclast differentiation induced by synovial fibroblast and monocytes co-culture in adjuvant-induced arthritic rats.

OBJECTIVE: To study the mechanism underlying the inhibitory effect of Qingluo Tongbi Granule (, QTG) on osteoclast differentiation in rheumatoid arthritis in rats. METHODS: Fibroblast and monocyte co-culture were used to induce osteoclast differentiation in adjuvant-induced arthritic (AIA) rats. Serum containing QTG was prepared and added to the osteoclasts, and activation of the tumor necrosis factor receptor-associated factor 6/mitogen-activated protein kinase/nuclear factor of activated T cells, cytoplasmic1 (TRAF6/MAPK/NFATc1) pathways was examined. RESULTS: The induced osteoclasts were multinucleated and stained positive for tartrate-resistant acid phosphatase (TRAP) staining. Serum containing QTG at 14.4, 7.2 or 3.6 g/kg inhibited the activation of TRAF6, extracellular regulated protein kinase (ERK)1/2, c-Jun N-terminal kinase (JNK) and p38 and decreased the percentage of cells with nuclear NFATc1 in a dose-dependent manner, the high and middle doses exhibited clear inhibitory activity (P<0.01 and P<0.05, respectively). After the addition of MAPK inhibitors, the NFATc1 expression showed no significant difference compared with the control group (P>0.05). CONCLUSIONS: Serum containing QTG could generally inhibit the TRAF6/MAPK pathways and possibly inhibit the NFATc1 pathway. In addition, QTG may regulate other signaling pathways that are related to osteoclast differentiation and maturation.

[Inhaled iloprost during acute pulmonary vasodilator testing for preoperative assessment of surgical operability of congenital heart disease with severe pulmonary hypertension].

OBJECTIVE: To evaluate the efficacy of iloprost in acute vasodilatation test during cardiac catheterization and to explore a useful hemodynamic indication regarding operability in the patients with severe pulmonary hypertension (PH) related to congenital heart disease (CHD). METHODS: The clinical data of 46 patients [mean age (12 ± 9) years] with severe PH related to CHD from June 2006 to December 2008 was retrospectively analyzed. All patients underwent standard right and left cardiac catheterization and a trial of inhaled iloprost test during cardiac catheterization. The mean pulmonary arterial pressure was (80 ± 13) mm Hg (1 mm Hg = 0.133 kPa) and pulmonary vascular resistance index was (17 ± 10) wood.m². A positive response to inhaled iloprost was defined as a decrease of at least 20% in pulmonary vascular resistance index (PVRI) without changes on systemic artery pressure. Patients with positive response to iloprost underwent cardiac surgical repair. The pulmonary artery pressure and PVRI was monitored by Swan-Ganz catheter postoperatively. RESULTS: Of the 46 patients, 29 (63.1%) showed a positive response after iloprost inhalation, defined by a significant reduction in PVRI from (15 ± 6) wood.m(2) at baseline to (9 ± 4) wood.m² in response to iloprost inhalation therapy (P < 0.05). The ratio of pulmonary to systemic resistance (Rp/Rs) decreased from 0.7 ± 0.2 to 0.4 ± 0.2 (P < 0.05). Seventeen patients (36.9%) didn't respond to iloprost displayed only little changes in PVRI [from (21 ± 10) wood.m(2) to (19 ± 9) wood.m²] and Rp/Rs (from 1.0 ± 0.5 to 0.9 ± 0.5). Out of 29 positive patients, 21 (72%) underwent successful cardiac surgical repair with a reduction of mean pulmonary arterial pressure (mPAP) to an average of (27 ± 10) mm Hg after the operation. Only 2 patients out of the 17 patients from the negative group were referred to surgery. Their mPAP was greater than 45 mm Hg. CONCLUSIONS: A significant reduction in pulmonary artery pressure after cardiac surgery was observed in patients with positive response to inhaled iloprost. Inhaled iloprost may be a valuable tool in the preoperative evaluation of patients with severe PH related to CHD.