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*

This research study focuses on addressing the limitations of current neuropathic pain (NP) treatments by developing a novel dual-target modulator, E0199, targeting both Na_V1.7, Na_V1.8, and Na_V1.9 and K_V7 channels, a crucial regulator in controlling NP symptoms. The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP. Through an experimental design involving both in vitro and in vivo methods, E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury (CCI) mouse model. The results demonstrated that E0199 significantly inhibited Na_V1.7, Na_V1.8, and Na_V1.9 channels with a particularly low half maximal inhibitory concentration (IC₅₀) for Na_V1.9 by promoting sodium channel inactivation, and also effectively increased K_V7.2/7.3, K_V7.2, and K_V7.5 channels, excluding K_V7.1 by promoting potassium channel activation. This dual action significantly reduced the excitability of dorsal root ganglion neurons and alleviated pain hypersensitivity in mice at low doses, indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically. The safety of E0199 was supported by neurobehavioral evaluations. Conclusively, E0199 represents a ground-breaking approach in NP treatment, showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe therapeutic option for NP. This study introduces a promising direction for the future development of NP therapeutics.

Objective To investigate the relationship between serum arginase-1(Arg-1),thrombomodulin motif 9(ADAMTS-9),Ectodysplasin A and cardiac function after percutaneous coronary intervention(PCI)in patients with acute myocardial infarction(AMI),and their predictive value for major adverse cardiovascular events(MACE).Methods A total of 102 AMI patients who underwent PCI in the Third Medical Center of People's Liberation Army General Hospital from January 2021 to December 2023 were selected as the AMI group,and 110 healthy people were recruited as the control group.The serum levels of Arg-1,ADAMTS-9 and Ectodysplasin A were detected by enzyme-linked immunosorbent assay.Echocardiography was performed by color Doppler ultrasound,and left ventricular mass index(LVMI)was calculated.Patients were divided into MACE group(n=32)and non-MACE group(n=70)according to the occurrence of MACE.Pearson correla-tion analysis was used to analyze the correlation between serum Arg-1,ADAMTS-9,Ectodysplasin A levels and LVMI after PCI in AMI patients.Receiver operating characteristic(ROC)curve was used to analyze the predictive value of serum Arg-1,ADAMTS-9 and Ectodysplasin A levels for MACE in AMI patients after PCI.Z test was used to compare the area under the curve(AUC).Multivariate Logistic regression analysis was used to analyze the influencing factors of MACE in patients with AMI.Results Compared with the con-trol group,the AMI group had significantly higher serum levels of Arg-1,ADAMTS-9 and Ectodysplasin A(P<0.05).The serum levels of Arg-1,ADAMTS-9 and Ectodysplasin A in patients with AMI were positively correlated with LVMI(P<0.05).There were no significant differences in gender,body mass index,systolic blood pressure,heart rate,history of diabetes,diastolic blood pressure,smoking history,time from onset to treatment,drinking history,age,course of disease,and LVMI between MACE group and non-MACE group(P>0.05).The serum levels of Arg-1,ADAMTS-9 and Ectodysplasin A in the MACE group were higher than those in the non-MACE group(P<0.05).Arg-1,ADAMTS-9 and Ectodysplasin A were independent risk factors for MACE in AMI patients(P<0.05).The AUC of serum Arg-1,ADAMTS-9 and Ectodysplasin A levels in predicting MACE in AMI patients were 0.821,0.779,0.818 and 0.950,respectively.The combined prediction value of the three was higher than that of individual prediction(Z=3.137,3.702,2.699,P=0.002,<0.001,0.007).Conclusion The serum levels of Arg-1,ADAMTS-9 and Ectodysplasin A are increased in AMI patients,and they have certain predictive value for the occurrence of MACE in AMI patients after PCI.

Experiential teaching is a practical, reflective, and situational teaching method. Based on the systematic review of literature published worldwide, this paper summarizes the characteristics and organizational forms of experiential teaching, with a focus on its current application and existing problems in teaching geriatric nursing. This review provides suggestions for the reform of teaching methods of geriatric nursing in China.

Purpose To study the clinical and pathological features of angiomatoid fibrous histocytoma(AFH)and to ex-plore its diagnosis,differential diagnosis and prognosis.Meth-ods The clinicopathological and follow-up data were analyzed in 14 cases of AFH,and the literatures were reviewed.Results There were 11 males and 3 females.The age ranged from 11 months to 12 years and 11 months,with average 5.9 years.3 cases were located in limbs,and 5 cases in trunk,5 cases in head and neck region,and 1 of intracranial tumor.Histological-ly,14 cases were composed of fibrous capsules and lymphocyte sheaths,and cell nucleus were vacuolar,forming fascicles with focal whirling and synteny.Intralesional pseudoangiomatous spaces were noted in 9 cases.Calcification was found in 2 ca-ses.2 cases showed high mitotic acticity(11/10 HPF).Scle-rosing and/or myxoid stroma was seen in 3 cases.Tumors were immunopositive for desmin(10/14),EMA(12/14),CD99(12/14),SMA(9/12),ALK(7/8),and the average of Ki67 index was 16％.7 cases harbored EWSR1 rearrangenent(part-ner gene not identified),2 cases had EWSR1-ATF1 fusion and 2 EWSR1-CREB1 fusion.Clinical follow-up information was a-vailable for 14 cases(average 46 months).All the 14 cases were alive without recurrence and metastasis.Conclusion AFH is a borderline or low-grade malignant tumor,often demon-strates indolent behavior in children,but rarely recurs and me-tastasizes.The diagnosis and differential diagnosis require a comprehensive analysis of clinical features,histopathologic changes,immunohistochemical finding and EWSR1 or FUS gene detection results.

Objective:To investigate the relationship between 1p/16q loss of heterozygosity (LOH) and 1p gain in Wilms tumor and their clinicopathologic characteristics and prognosis.Methods:A total of 175 Wilms tumor samples received from the Department of Pathology, Beijing Children′s Hospital from September 2019 to August 2022 were retrospectively analyzed. The histopathologic type and presence of lymph node involvement were evaluated by two pathologists. The clinical data including patients′gender, age, tumor location, preoperative chemotherapy, and tumor stage were summarized. Fluorescence in situ hybridization (FISH) was done to detect 1p/16q LOH and 1p gain and their correlation with the clinicopathological features and prognosis were analyzed.Results:Among the 175 samples, 86 cases (49.1%) were male and 89 (50.9%) were female. The mean age was (3.5±2.9) years, and the median age was 2.6 years. There were 26 (14.9%) cases with 1p LOH, 28 (16.0%) cases with 16q LOH, 10 (5.7%) cases of LOH at both 1p and 16q, and 53 (30.3%) cases with 1q gain. 1q gain was significantly associated with 1p LOH ( P<0.01) and 16q LOH ( P<0.01). There were significant differences ( P<0.01) between 1q gain, 1p LOH and 16q LOH among different age groups. The rate of 16q LOH in the high-risk histopathological subtype (50.0%) was significantly higher than that in the intermediate-risk subtype (13.6%, P<0.05). The frequency of 1q gain, 1p LOH, and 16q LOH in children with advanced clinical stages (Ⅲ and Ⅳ) was significantly higher than that in children with early clinical stages (Ⅰ and Ⅱ). 1q gain, 1p LOH, and 16q LOH showed no significant correlation with gender, unilateral or bilateral disease, chemotherapy, or lymph node metastasis. The progression-free survival (PFS) time for patients with 1q gain and 1p LOH was significantly shorter than those without these aberrations ( P<0.05). Additionally, the PFS time of patients with 16q LOH was slightly shorter than those with normal 16q, although the difference was not statistically significant. Patients with stage Ⅲ to Ⅳ disease exhibiting 1q gain or 1p LOH had a significantly higher relative risk of recurrence, metastasis, and mortality. Conclusions:1p/16q LOH and 1q gain are associated with age, high-risk histological type, and clinical stage in Wilms tumor. 1q gain and 1p LOH are significantly correlated with the prognosis of Wilms tumor.

Objective:To investigate the clinicopathological features, immunophenotype and molecular genetic characteristics of congenital spindle cell/sclerosing rhabdomyosarcoma.Methods:Sixteen cases (including 10 consultation cases) of congenital spindle cell/sclerosing rhabdomyosarcoma diagnosed at the Beijing Children′s Hospital, Capital Medical University, Beijing China, from April 2017 to January 2022 were collected. These cases were evaluated for clinical profiles, histomorphological features, immunophenotype and molecular characteristics.Results:Among the 16 patients, 9 were male and 7 were female. Five cases were present during maternal pregnancy and 11 cases were found immediately after birth. The tumors were located in the chest wall, low back, retroperitoneum, extremities or perineum. The tumors consisted of fasciculated spindle-shaped cells with localized mesenchymal sclerosis and vitreous metaplasia. Immunohistochemistry showed that the tumor cells expressed Desmin, Myogenin, MyoD1, SMA, CD56 and ALK to varying degrees, but not other markers such as CD34, CD99, pan-TRK, S-100 and BCOR. FISH analyses with NCOA2 (8q13) and VGLL2 (6q22) gene breakage probes revealed a breakage translocation in chromosome NCOA2 (8q13) in 4 cases (4/11). In the 6 cases subject to sequencing, a mutation at the p.L122R locus of MYOD1 gene was detected in 1 case (1/6). Two cases were examined by electron microscopy, which showed bundle-arranged myofilaments with some primitive myofilament formation. Five cases were resected with simple surgery, 2 cases were biopsied and followed up with observation only, and 9 cases were treated with surgery and adjuvant chemotherapy. Follow-up was available in 12 cases. At the end of the follow-up, 2 of the 12 patients developed local recurrences and 2 patients survived with disease.Conclusions:Congenital spindle cell/sclerosing rhabdomyosarcoma is a rare subtype of congenital rhabdomyosarcoma. It more commonly occurs in the chest, back and lower limbs of infants than other sites. NCOA2/VGLL2 gene fusion seems to be the most common genetic change. Its prognosis is better than other subtypes of rhabdomyosarcoma and those in adolescents and adults with the same subtype. Analysis and summary of its clinicopathological features can help differentiate it from other soft tissue tumors in infants and children and provide the information for appropriate treatments.

Objectives To explore the establishment and effects of a multilevel and inter-disciplinary management scheme for specialist nurses.Methods The multilevel and inter-disciplinary management scheme included establishing the pyramid hierarchical training model,exploring superimposed training mechanism for specialist nurses with horizontal expansion,vertical extension,and deep development,and constructing stereoscopic clinical evaluation and quantitative assessment system.Four hundred-forty two specialized nurses have been recruited to join the multilevel and inter-disciplinary management scheme from July 2021 to August 2023.The core competencies of specialized nurses were compared before and after the implementation of management scheme.Results The quality development of specialized nursing have been improved,and the total scores and the scores of 3 dimensions(research innovation,management,and professional development)in core competencies of specialized nurses after the intervention of multilevel and inter-disciplinary management scheme were higher than those before(P＜0.05).Conclusion The multilevel and inter-disciplinary management scheme can effectively improve the core competencies of specialized nurses,and promote the high-quality development of specialized nursing.

Objective    To analyze the risk factors for acute kidney injury (AKI) after off-pump coronary artery bypass grafting (OPCABG). Methods     The PubMed, EMbase, The Cochrane Library, Web of Science, Wanfang data, CBM, VIP, CNKI were searched by computer for researches on risk factors associated with the development of AKI after OPCABG from the inception to March 2022. The meta-analysis was performed using RevMan 5.4 software. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of included studies. Results    A total of 18 researches were included, involving 9 risk factors. The NOS score of all included studies was≥6 points. Meta-analysis results showed that age [OR=1.03, 95%CI (1.01, 1.06), P=0.020], body mass index (BMI) [OR=1.10, 95%CI (1.05, 1.15), P<0.001], history of hypertension [OR=1.45, 95%CI (1.27, 1.66), P<0.001], history of diabetes [OR=1.50, 95%CI (1.33, 1.70), P<0.001], preoperative serum creatinine level [OR=2.05, 95%CI (1.27, 3.32), P=0.003], low left ventricular ejection fraction [OR=4.51, 95%CI (1.39, 14.65), P=0.010], preoperative coronary angiography within a short period of time [OR=2.10, 95%CI (1.52, 2.91), P<0.001], perioperative implantation of intra-aortic balloon pump [OR=3.42, 95%CI (2.26, 5.16),  P<0.001], perioperative blood transfusion [OR=2.00, 95%CI (1.51, 2.65), P<0.001] were risk factors for AKI after OPCABG. Conclusion    Age, BMI, history of hypertension, history of diabetes, preoperative serum creatinine level, low left ventricular ejection fraction, preoperative coronary angiography within a short period of time, perioperative implantation of intra-aortic balloon pump, perioperative blood transfusion are risk factors for AKI after OPCABG. Medical staff should focus on monitoring the above risk factors and early identifying, in order to prevent or delay the onset of postoperative AKI and promote early recovery of patients.

Because the brain and kidneys share a common basis for small vessel lesions, the related research on cerebral microbleeds (CMBs) in patients with chronic kidney disease (CKD) is gradually increasing. The development of neuroimaging technology has significantly increased the detection rate of CMBs, but there is still controversy over whether CKD will increase the incidence of CMBs. This article reviews the relationship between CKD and CMBs, pathogenesis, biomarkers, and treatment.