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.

Cerebrospinal fluid leakage is one of the common complications of spinal surgeries. The causes of the leak can be dural tears during surgery procedure and this is a medical problem.Cerebrospinal fluid is a physiological fluid that protects the brain and maintains intracranial pressure. If it's not handled properly, it will cause persistent headaches, nausea, vomiting, and carry an increased risk of meningitis. Correct and effective dural suture and repair are the basis of recovery. The repair of dura mater is difficult to be alleviated by medicine, so it is very important to identify and repair cerebrospinal fluid leakage in time. In this review, the relevant studies in recent years are summarized. We discuss the pathogenesis of dural tears, diagnosis, repair methods. We provide references for clinicians to avoid delayed wound healing, wound infection, spinal canal and intracranial infection, pseudodural cyst, spinal cord nerve compression and other serious complications. This paper aims to assist in delivering efficacious treatment and recovery for patients.

Objective:To investigate the role of p21 gene in the radiation-induced heart disease (RIHD) and to evaluate the effect on p21 gene knockout on RIHD phenotype in mouse models.Methods:p21 -/-mice were utilized in the experimental group, and p21 + /-mice were allocated in the control group. RIHD mouse models were established by exposure to 10 Gy whole heart irradiation by using a small animal radiation research platform. The heart samples were collected at 6 weeks after irradiation, the gross specimens were measured and subject to HE staining. The wall thickness and left ventricular ejection fraction of the mice were detected by the Vevo2100 ultrasound imaging system. The hypoxia in cardiac tissues was detected by the hypoxia probe method. The apoptosis of cardiac cells was determined by Tunel method. Results:Compared with the p21 + /-mice, the survival of p21 -/-mice was significantly shortened ( P=0.004), the interventricular septum was significantly thinned during the diastolic and systolic phases ( P=0.049, P=0.006), the left ventricular posterior wall was remarkably thickened ( P<0.001) and the left ventricular ejection fraction was significantly decreased ( P=0.004). The gross heart tissue was enlarged in the p21 -/-mice. HE staining showed the aggregation of inflammatory cells in cardiac tissues and disordered arrangement of myocardial cells. Significant hypoxia and apoptosis could be observed in the p21 -/-mouse heart tissues. Conclusions:p21 -/-mice are prone to more severe RIHD after irradiation, manifested with shortened cardiac survival, weakened cardiac function, abnormal cardiac structure, hypoxia and apoptosis of cardiac tissues. p21 plays an important role in the repair after cardiac irradiation.

In a previous study, we screened thousands of long non-coding RNAs (lncRNAs) to assess their potential relationship with congenital heart disease (CHD). In this study, uc.4 attracted our attention because of its high level of evolutionary conservation and its antisense orientation to the CASZ1 gene, which is vital for heart development. We explored the function of uc.4 in cells and in zebrafish, and describe a potential mechanism of action. P19 cells were used to investigate the function of uc.4. We studied the effect of uc.4 overexpression on heart development in zebrafish. The overexpression of uc.4 influenced cell differentiation by inhibiting the TGF-beta signaling pathway and suppressed heart development in zebrafish, resulting in cardiac malformation. Taken together, our findings show that uc.4 is involved in heart development, thus providing a potential therapeutic target for CHD.

Objective To investigate and design a coincidence detection system for an all-digital small animal PET scanner and evaluate its preliminary performance properties.Methods This coincidence module adopted a coincidence identification mode based on singles data in list-mode.Using digital signal processing technology,energy calibration,crystal identification,timing alignment and coincidence events extraction were performed on singles data in list-mode.The obtained data could be used for image reconstruction.Results The 13 × 13 crystal array was well recognized by the position histogram of one lutetium yttrium orthosilicate (LYSO) crystal block.In the coincidence timing histogram of the micro-Derenzo phantom,1.36 ns full width at half maximum was obtained.The rods with a diameter of 1.2 mm were clearly displayed in the reconstructed image of the micro-Derenzo phantom.Conclusion The coincidence module can provide satisfactory performance to meet the design needs of an all-digital small animal PET scanner.

OBJECTIVETo explore the relationship between abnormal expressions of positive cell cycle control factors and thyroid carcinoma occurrence and progression, and assess the value of these factors in evaluating tumor cell proliferation activity and the prognosis of the patients.

METHODSImmunohistochemical SP method was used to detect the expressions of MCM7, CDK2 and Ki-67 proteins in 50 cases of thyroid carcinoma, 30 cases of thyroid adenoma, 30 cases of nodular goiter and 20 cases of normal thyroid gland tissues.

RESULTSThe positive rates of MCM7, CDK2 and Ki-67 expressions in thyroid carcinoma were 100% (50/50), 80.00% (40/50) and 84.00% (42/50), significantly higher than the rates in thyroid adenoma, nodular goiter and normal thyroid tissue (P<0.01). In thyroid carcinoma tissues, positive correlations were observed between the expressions of MCM7 and CDK2 proteins (r=0.637, P<0.01), MCM7 and Ki-67 proteins (r=0.633, P<0.01), and CDK2 and Ki-67 proteins (r=0.862, P<0.01).

CONCLUSIONThe high expressions of MCM7, CDK2 and Ki-67 protein may contribute to the development of thyroid carcinoma, and their combined examination may serve as useful index for early diagnosis and prognostic evaluation of thyroid carcinoma. MCM7 is superior to Ki-67 in the evaluation of the thyroid tumor cell proliferation activity.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Case-Control Studies ; Cyclin-Dependent Kinase 2 ; metabolism ; Female ; Humans ; Ki-67 Antigen ; metabolism ; Male ; Middle Aged ; Minichromosome Maintenance Complex Component 7 ; metabolism ; Thyroid Neoplasms ; metabolism ; pathology ; Young Adult