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*

Background and objective Neoantigen reactive T cell(NRT)has the ability to inhibit the growth of tumors expressing specific neoantigens.However,due to the difficult immune infiltration and the inhibition of tumor micro en-vironment,the therapeutic effect of NRT in solid tumors is limited.In this study,we designed NRT cells(7×19 NRT)that can express both interleukin-7(IL-7)and chemokine C-C motif ligand 19(CCL19)in mouse lung cancer cells,and evaluated the difference in anti-tumor effect between 7×19 NRT cells and conventional NRT cells.Methods We performed next-generation sequencing and neoantigen prediction for mouse Lewis lung carcinoma(LLC),prepared RNA vaccine,cultured NRT cells,constructed retroviral vectors encoding IL-7 and CCL19,transduced NRT cells and IL-7 and CCL19 were successfully ex-pressed,and 7×19 NRT was successfully obtained.The anti-tumor effect was evaluated in vivo and in vitro in mice.Results The 7×19 NRT cells significantly enhanced the proliferation and invasion ability of T cells by secreting IL-7 and CCL19,achieved significant tumor inhibition in the mouse lung cancer and extended the survival period of mice.The T cell infiltration into tumor tissue and the necrosis of tumor tissue increased significantly after 7×19 NRT treatment.In addition,both 7×19 NRT treatment and conventional NRT treatment were safe.Conclusion The anti-solid tumor ability of NRT cells is significantly enhanced by the arming of IL-7 and CCL19,which is a safe and effective genetic modification of NRT.

AIM: To understand the publication status, research trends, and cutting-edge and hot topics in this field by conducting a bibliometrics analysis of relevant literatures on the pathogenesis of primary open angle glaucoma(POAG)in the past 30 a.METHODS:A total of 986 relevant literatures on the pathogenesis of POAG published on the core databases of China National Knowledge Infrastructure(CNKI)and Web of Science(WOS)from 1 September 1993 to 1 September 2023 were retrieved. CiteSpace(6.2.R.4)and VOSviewer(1.6.18)software were used to conduct knowledge graph analysis on the retrieved literature, including publication volume, author, research institution, country/region, and keywords.RESULTS:The United States(243 articles)has the highest number of publications, followed by China(121 articles). The foreign institution with the highest number of publications is Harvard University(37 articles), while domestic institutions such as Zhongshan Ophthalmic Center, Sun Yat-sen University, ophthalmology department of Xuanwu Hospital of Capital Medical University, and Peking University First Hospital tied for the highest number of publications. Louis R. Pasquale(21 articles)is the most prolific English author. Wang Ningli is the most active Chinese researcher in this field. Keywords include trabecular meshwork, intraocular pressure, aqueous humor, glucocorticoid, hemorheology, etc.CONCLUSION: The research on the pathogenesis of POAG is in a period of vigorous development. The United States has the largest number of publications in this field, and Harvard University is a leading institution in this field. The research focus in the field of POAG has shifted from the structural aspect to the genetic level, and gene research and traditional Chinese medicine treatment have broad application prospects in this field.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease caused by inflammatory cells. Various inflammatory cells involved in RA include fibroblast-like synoviocytes, macrophages, CD4⁺T-lymphocytes, B lymphocytes, osteoclasts and chondrocytes. The close interaction between various inflammatory cells leads to imbalance of immune response and disorder of the expression of mRNA in inflammatory cells. It helps to drive production of pro-inflammatory cytokines and stimulate specific antigen-specific T- and B-lymphocytes to produce autoantibodies which is an important pathogenic factor for RA. Competing endogenous RNA (ceRNA) can regulate the expression of mRNA by competitively binding to miRNA. The related ceRNA network is a new regulatory mechanism for RNA interaction. It has been found to be involved in the regulation of abnormal biological processes such as proliferation, apoptosis, invasion and release of inflammatory factors of RA inflammatory cells. Understanding the ceRNA network in 6 kinds of RA common inflammatory cells provides a new idea for further elucidating the pathogenesis of RA, and provides a theoretical basis for the discovery of new biomarkers and effective therapeutic targets.
Humans ; Arthritis, Rheumatoid/genetics* ; MicroRNAs/metabolism* ; Synoviocytes/pathology* ; Cytokines/metabolism* ; RNA, Messenger/metabolism* ; Fibroblasts/pathology* ; Cell Proliferation

ObjectiveTo evaluate the lipid-lowering activity of Quansanqi tablets（QSQ）， an innovative new drug of Panax notoginseng. MethodMice and golden hamsters were used to establish a hyperlipidemia model by injecting egg yolk milk and feeding high-fat diets. The levels of total cholesterol （TC），triglyceride （TG），low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） were detected， and liver function indicators ［alanine aminotransferase （ALT）， aspartate amino-transferase （AST）， and alkaline phosphatase （ALP）］ of golden hamsters were detected. Hematoxylin-eosin （HE） staining was used to observe the degree of liver injury. In the experiments， a normal group， a model group， an atorvastatin calcium group， and low-， medium-， and high-dose QSQ groups （0.32， 0.64， 1.28 g·kg^-1 for mice， and 0.16， 0.32， 0.64 g·kg^-1 for golden hamsters） were set up. ResultCompared with the normal group， the acute hyperlipidemia model mice showed increased TC， TG， and LDL-C levels （P<0.01）， and the hyperlipidemia model mice showed increased TC and LDL-C levels （P<0.01）. Additionally， the hyperlipidemia model golden hamsters showed increased serum TC， TG， LDL-C， ALT， AST， and ALP levels （P<0.05， P<0.01）. HE staining indicated the presence of fat accumulation in the liver， accompanied by inflammatory reactions. Compared with the model group， QSQ of various doses could reduce TC， TG， and LDL-C levels in acute hyperlipidemia model mice （P<0.05， P<0.01）， and the high-dose QSQ could reduce TC and LDL-C levels （P<0.01） and increase HDL-C level （P<0.05） in hyperlipidemia model mice， as well as reduce TC， TG， and LDL-C levels in hyperlipidemia model golden hamsters （P<0.05， P<0.01）， especially in the first two weeks. In addition， atorvastatin calcium could further increase ALT， AST， and ALP levels （P<0.05， P<0.01） and aggravate liver function damage， while low-dose QSQ could reduce ALT， AST， and ALP （P<0.05）， and medium- and high-dose QSQ did not cause further liver function damage. ConclusionQSQ have a significant lipid-lowering effect on different hyperlipidemia model animals and can improve liver function and liver injury.

Objective:To establish an ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for plasma caffeine concentration detection, and to explore the clinical value of caffeine therapeutic drug monitoring (TDM) in the treatment of premature infants with respiratory distress syndrome (RDS).Method:Take the plasma sample in a centrifuge tube, add the caffeine deuterated isotope internal standard, then add the protein precipitant, vortex the mixture thoroughly, and centrifuge the supernatant to enter the mass spectrometry analysis. The mobile phase were methanol and water, gradient elution; the column temperature was 45 ℃, the method was established using Shimadzu LC-30AD-CL liquid system and AB SCIEX 4500 QTRAP mass spectrometer, and the sensitivity, specificity, linearity, accuracy imprecision, matrix effect, and carry-over of the method were evaluated. Sample from 30 patients diagnosed with neonatal RSD were collected in the Department of Neonatology of Renmin Hospital of Wuhan University from February to April 2021, then detected the trough concentration of caffeine in premature infants with RDS after taking the same dose of caffeine to assess the impact of individual variation on caffeine drug concentration.Results:The detection limit of caffeine was 0.02 μg/ml, and the lowest limit of quantification was 0.05 μg/ml. It showed good linearity ( R2=0.9986, R>0.99) in the concentration range from 1.0 to 100.0 μg/ml, specificity (recovery rate of 85.52%-114.12%), accuracy (recovery rate 85.97%-114.53%), intra-day and inter-day imprecision ( CV 6.01%-11.28%), matrix effects and carryover pollution were negligible. The trough concentration of 30 preterm infants with RSD after taking the same dose of caffeine (10 mg/kg) was (25.45±11.61) μg/ml, and the coefficient of variation was 44.88%. Conclusion:This study established an accurate and reliable UPLC-MS/MS method with low sample consumption to monitor the blood concentration of caffeine; caffeine TDM has certain clinical application value, which can be used to assist RDS diagnosis and treatment and improve the efficacy of caffeine.

Objective:To understand the role of desktop deduction competition on improving nurses' ability of disaster nursing, explore new models of disaster nursing training.Methods:A purposive sampling method was used to recruit 12 nurses who participated in the desktop deduction competition and semi-structured interviews were conducted. Thematic analysis was used for data analysis.Results:After reading, analyzing, comparing and refining, five themes were extracted: raise the awareness of nurses' disaster nursing: recognize the importance of nurses participating in disaster rescue and mastering the disaster rescue related knowledge and skills; improve the nurses' preparedness of disaster nursing: reserve disaster knowledge, improve the skills of disaster rescue, and cultivate disaster management ability; improve the use of critical thinking and communication skills: in deciding the game to answer questions, each player of the team must independently consider the questions raised by the host and propose solutions. Then, the three players of the team communicated quickly to form the final answer of the team and express them in a reasonable language. Improved players ′ critical thinking and communication skills; enhance nurses ′ psychological quality: calm was the basis for successful competition as well as dealing with public emergencies and participating in disaster care and rescue. It was also a basis for relieving nurses' anxiety and reducing post-traumatic stress disorder; explore a new training model of disaster nursing. Conclusion:Emergent emergency medical rescue desktop deduction competition as a new disaster nursing training model, can effectively improve nurses' ability of disaster nursing.

Objective To analyze the current situation and influencing factors of disaster preparedness of emergency rescue nurses in Anhui Province. Methods Using the convenience sampling method, 261 emergency rescue nurses from 48 tertiary and secondary hospitals drawn from the Disaster Nursing and Practice Classes organized by the Anhui Provincial Nursing Association in November 2017 were selected as research subjects. The questionnaire was conducted by using the Chinese version of Nurses Disaster Preparedness Scale. Results The score of disaster preparedness degree of nurses was 180.00(164.50, 201.00), which level was middle to upper,among the three dimensions, the highest score of disaster knowledge item was 4.50(4.00, 5.50), the second was disaster management 4.20(3.50, 5.00), the lowest disaster technology score was 4.00(3.00, 5.00); the disaster management (H = 7.968-40.324, P<0.01 or 0.05), the qualification level of rescue nurses (H = 13.341-61.550, P <0.01), grade of hospital (Z =-3.927-1.202, P <0.01 or 0.05), disaster education score (H = 19.517-65.061, P < 0.01), and participation in disaster rescue (Z =-8.219--6.280, P <0.01) were the influencing factors of disaster preparedness for emergency rescue nurses. Conclusions The disaster preparedness level of emergency rescue nurses in Anhui Province is at the upper middle level, disaster nursing should be included in the regular emergency rescue nurses′continuing education programs to carry out special lectures and regular emergency drills to establish a team of emergency nursing personnel training emergency rescue nurses for training at the same time, disaster relief incidents collect and analyze so that the combat experience at the disaster rescue site can be shared and promoted.

Objective To investigate the safety and clinical value of using ExoSeal vascular closure device (VCD) in interventional management via antegrade femoral access.Methods Clinical and imaging data of 303 patients (316 affected limbs) who were received interventional procedure via antegrade femoral access closure were retrospectively analyzed.ExoSeal VCD (VCD group,n=127) and manual compression (MC group,n =176) were performed to make femoral artery puncture point hemostasis.The time of hemostasis,actual immobilization time,technical success rate and vascular related complications were recorded and compared between the two groups.Results In VCD group and MC group,the time of hemostasis were (3.68 ± 2.40) min and (18.32 ± 4.54) min,the actual immobilization time were (3.45±5.30) h and (10.44±14.68) h,the technical success rates were 98.52％ (133/135) and 93.92％ (170/181),and the complication rates were 2.22％ (3/135) and 8.84％ (16/181),respectively.There were statistically significant differences between two groups (all P＜0.05).In VCD group,there were 2 cases of subcutaneous hematomas,and 1 case of retroperitoneal hematoma.In MC group,there were 15 cases of subcutaneous hematomas and 1 case of acute thrombosis in the puncture side limb.Conclusion Regarding hemostasis of puncture site in interventional management via antegrade femoral access,the use of ExoSeal VCD is safe and effective.

Objective To summary the nursing points of adverse reactions of infliximab during treatment in patients with moderate-severe psoriasis. Methods According to the problems of 34 patients with psoriasis treated with infliximab, through statistical Methods to analyze the problem of coping strategies. Results Thirty-four patients with the best results,no recurrence of psoriasis happened during treatment. Fatigue, heart rate increasing, skin rash, fever, weight gain, muscle pain, abdominal pain, diarrhea and other adverse reactions occurred. Through the proper drug administration, strengthening observation of adverse reactions, and providing individualized nursing care to patients according to the severity to ensure the smooth progress of the treatment. Except 2 patients interrupting treatment for intolerance to the adverse reactions, other patients had accomplished the course of treatment smoothly. Conclusions Nursing staff should be familiar with the preservation of the drug, liquid preparation, infusion process,infusion process of each link,and do the patient's follow-up,reduce the problem.