BACKGROUND: This study aimed to investigate programmed death-ligand 1 tumor proportion score in predicting the safety and efficacy of PD-1/PD-L1 antibody-based therapy in treating patients with advanced non-small cell lung cancer (NSCLC) in a real-world setting. METHODS: This retrospective, multicenter, observational study enrolled adult patients who received PD-1/PD-L1 antibody-based therapy in China and met the following criteria: (1) had pathologically confirmed, unresectable stage III-IV NSCLC; (2) had a baseline PD-L1 tumor proportion score (TPS); and (3) had confirmed efficacy evaluation results after PD-1/PD-L1 treatment. Logistic regression, Kaplan-Meier analysis, and Cox regression were used to assess the progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) as appropriate. RESULTS: A total of 409 patients, 65.0% ( n = 266) with a positive PD-L1 TPS (≥1%) and 32.8% ( n = 134) with PD-L1 TPS ≥50%, were included in this study. Cox regression confirmed that patients with a PD-L1 TPS ≥1% had significantly improved PFS (hazard ratio [HR] 0.747, 95% confidence interval [CI] 0.573-0.975, P = 0.032). A total of 160 (39.1%) patients experienced 206 irAEs, and 27 (6.6%) patients experienced 31 grade 3-5 irAEs. The organs most frequently associated with irAEs were the skin (52/409, 12.7%), thyroid (40/409, 9.8%), and lung (34/409, 8.3%). Multivariate logistic regression revealed that a PD-L1 TPS ≥1% (odds ratio [OR] 1.713, 95% CI 1.054-2.784, P = 0.030) was an independent risk factor for irAEs. Other risk factors for irAEs included pretreatment absolute lymphocyte count >2.5 × 10 9 /L (OR 3.772, 95% CI 1.377-10.329, P = 0.010) and pretreatment absolute eosinophil count >0.2 × 10 9 /L (OR 2.006, 95% CI 1.219-3.302, P = 0.006). Moreover, patients who developed irAEs demonstrated improved PFS (13.7 months vs. 8.4 months, P <0.001) and OS (28.0 months vs. 18.0 months, P = 0.007) compared with patients without irAEs. CONCLUSIONS A positive PD-L1 TPS (≥1%) was associated with improved PFS and an increased risk of irAEs in a real-world setting. The onset of irAEs was associated with improved PFS and OS in patients with advanced NSCLC receiving PD-1/PD-L1-based therapy.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Lung Neoplasms/metabolism* ; Aged ; B7-H1 Antigen/metabolism* ; Programmed Cell Death 1 Receptor/metabolism* ; Adult ; Aged, 80 and over ; Immune Checkpoint Inhibitors/therapeutic use*

The role of glial scar after intracerebral hemorrhage(ICH)remains unclear.This study aimed to inves-tigate whether microglia-astrocyte interaction affects glial scar formation and explore the specific function of glial scar.We used a pharmacologic approach to induce microglial depletion during different ICH stages and examine how ablating microglia affects astrocytic scar formation.Spatial transcriptomics(ST)analysis was performed to explore the potential ligand-receptor pair in the modulation of microglia-astrocyte interaction and to verify the functional changes of astrocytic scars at different periods.During the early stage,sustained microglial depletion induced disorganized astrocytic scar,enhanced neutrophil infiltration,and impaired tissue repair.ST analysis indicated that microglia-derived insulin like growth factor 1(IGF1)modulated astrocytic scar formation via mechanistic target of rapamycin(mTOR)signaling activation.Moreover,repopulating microglia(RM)more strongly activated mTOR signaling,facilitating a more protective scar formation.The combination of IGF1 and osteopontin(OPN)was necessary and sufficient for RM function,rather than IGF1 or OPN alone.At the chronic stage of ICH,the overall net effect of astrocytic scar changed from protective to destructive and delayed microglial depletion could partly reverse this.The vital insight gleaned from our data is that sustained microglial depletion may not be a reasonable treatment strategy for early-stage ICH.Inversely,early-stage IGF1/OPN treatment combined with late-stage PLX3397 treatment is a promising therapeutic strategy.This prompts us to consider the complex temporal dynamics and overall net effect of microglia and astrocytes,and develop elaborate treatment strategies at precise time points after ICH.

AIM:To investigate whether specific small interfering RNA ( siRNA) targeting Toll-like receptor 4 ( TLR4) gene inhibits the proliferation of cervical cancer cell line HeLa through NF-κB signaling pathway and down-regula-tion of Bcl-2 expression.METHODS:Three specific TLR4 siRNAs and 1 negative siRNA were transfected respectively in-to HeLa cells.The expression of TLR4 at mRNA and protein levels was measured by reverse transcription-polymerase chain reaction ( RT-PCR) and Western blotting , respectively .The protein expression of p 65 and Bcl-2 was detected by Western blotting.The cell proliferation was determined by MTT assay and plate colony formation assay .The apoptotic rate of the cells and the cell cycle were analyzed by flow cytometry .RESULTS:In comparison with the other 2 kinds of TLR4 siR-NAs, TLR4-siRNA-003 demonstrated the strongest silencing effect on TLR4 gene expression in the HeLa cells at 48 h after transfection.The expression of TLR4 at mRNA and protein levels was reduced by 62% and 89%, respectively.The pro-tein levels of p65 and Bcl-2 significantly decreased .The growth rate of HeLa cells transfected with TLR 4-siRNA-003 was significantly inhibited .Moreover , the cell apoptotic rate increased significantly and the cell cycle was arrested at G 1 phase as the HeLa cells were transfected with TLR 4-siRNA-003 for 48 h.CONCLUSION:Specific TLR4 siRNA effectively in-hibits the expression of TLR4 and inhibits the proliferation of cervical cancer HeLa cells through NF-κB signaling pathway and down-regulation of Bcl-2 expression, indicating that TLR4 may be a new target for the treatment of cervical cancer .

Objective: To evaluate the therapeutic effects of Rituximab combined with CHOP on B cell non-Hodgkin's lymphoma. Methods: A prospective study with concurrent control group was carried out. A total of 60 cases of B cell non-Hodgkin's lympoma were divided into 2 groups. The 30 cases in the research group received Rituximab combined with CHOP regimen. The 30 cases in the control group were treated with CHOP regimen alone. CHOP regimen (Cyclophospham 600mg/m~2 IV, Vincristine 1.4mg/m~2 Ⅳ, and Adriamy-cin piarubicin 50mg/m~2 IV) was administered on the first day of chemotherapy course. Prednisone 100mg/m~2 was administered orally from the first day to the fifth day. The cycle was repeated every 21 days and the patients received at least 3-6 cycles of chemotherapy. The therapeutic effect was assessed. Results: The complete remission (CR) rate and total response rate were 66.7% (20/30) and 90.0% (27/30) in the research group and 39.97% (12/30) and 56.7% (17/30) in the control group. The therapeutic differences between the two groups showed a statistical significance (P＜0.05). Conclusion: Compared with CHOP regimen chemotherapy, Rituximab combined with CHOP regimen shows better therapeutic effect. The side effects in the research group are similar to those in the control group. Rituximab combined with CHOP regimen can be the first choice in the treatment for B cell non-Hodgkin's lymphoma.

Objective:To compare suicide attempters with community-based controls for more specific prevention strategies.Method:From the list of suicide attempters of three general hospitals 2 years before, 363 of 786 attempters (48.5%) were found. We collected a control group matched for sex, age and location of residence and compared the life events for the past two years, life quality, family cohesion and adaptability of the past month, and impulsivity and aggressiveness.Result:The two groups were similar in sex, age, family income, marital status, occupation and health insurance status. But the suicide attempt group had less education, had more prominent impulsive and aggressive in traits, had higher levels of hopelessness, more negative life events and greater distress from negative life events in the two years after their attempt. They had poorer life quality and lower family cohesion and adaptability for the past month. They had also more severe depressive symptoms in the prior week.Conclusion:Two years after their suicide attempt, the attempters still have substantial differences from normal controls. They are a distinct high-risk subgroup that deserves specific interventions.

To evaluate the effect of mobilization of peripheral blood stem cells (PBSC) with high dose cyclophosphamide combination chemotherapy and G-CSF in breast cancer patients, a new mobilization protocol was designed on the basis of standard combination chemotherapy regimen, in which the dose of cyclophosphamide was raised to 2 to 4 times, and G-CSF began to be used at the dose of 150 micro g twice everyday when white blood cell (WBC) decreased below 1.0 x 10(9)/L. PBSC collection was performed while WBC increased over 5.0 x 10(9)/L during bone marrow recovering. The PBSC mobilization protocol was completed in 10 patients, the median nadir of WBC was 0.8 (0.4 - 1.0) x 10(9)/L, the median time of PBSC collection was 2 (2 - 4), the median number of collected CD34(+) cells was 6.43 (1.99 - 8.75) x 10(6)/kg. The results showed that the protocol, high dose cyclophosphamide combination chemotherapy, was an optimal PBSC mobilization regimen in breast cancer patients.

Results of experimental studies with guinea pig showed that a strong blast may produce concussion of the vestibular apparatus. The parts injured include saccule and utricle and their maculas, semicircular canals and their cristas,and the nerves related to these organs.The most common pathological changes were hemorrhage, detachment of sensorial epithelium, collapse of membranous labyrinth, loss of oto-liths and degeneration of sensorial epithelial cells.The authors believe that these vestibular damages are produced by the combined action of strong noise and shock wave, being transmitted through the oral and round windows into the inner ear, producing a violent fluctuation of endolymph.