Objective: To investigate the distribution of pupil diameter and its association with myopia in school age children, providing ideas into the mechanisms of the role of pupil diameter in the onset and development of myopia. Methods: Adopting a combination of stratified cluster random sampling and convenience sampling method, 3 839 children from six schools in Shandong Province were included in September 2021. Pupil diameters distribution was analyzed by age, sex, and myopic status. Pearson correlation analysis was used to assess the relationship between pupil diameter and cycloplegic spherical equivalent (SE), as well as axial length (AL) and other variables. Propensity score matching (PSM) was applied to match myopic and non myopic children at a 1∶1 ratio based on age and sex. A generalized linear model (GLM) was constructed with pupil diameter as the dependent variable to identify independent factors influencing pupil size and its association with myopia. Results: The mean pupil diameter of school age children was (5.77±0.80)mm. Pupil diameter exhibited a significant increasing trend with age ( F =49.34， P trend ＜ 0.01). Myopic children had a significantly larger mean pupil diameter [(6.10±0.73)mm] compared to non myopic children [(5.62±0.79)mm] with a statistically significant difference( t=18.10, P <0.01). Multivariable GLM analysis, adjusted for age, amplitude of accommodation, and uncorrected visual acuity, revealed a negative correlation between pupil diameter and cycloplegic SE (before PSM: β =-0.089, after PSM: β =-0.063, both P ＜0.01). Conclusions Myopic school age children exhibite larger pupil diameters than their non myopic counterparts. Pupil diameter may serve as a potential indicator for monitoring myopia development in school age children.

OBJECTIVE: To investigate the predictive value of oxygenation index (PaO₂/FiO₂) at intensive care unit (ICU) admission on 30-day mortality in patients with sepsis. METHODS: A retrospective study was conducted. Patients with sepsis who were hospitalized in the ICU of the Affiliated Hospital of Jining Medical University from April 2015 to October 2023 were enrolled. The demographic information, comorbidities, sites of infection, vital signs and laboratory test indicators at the time of admission to the ICU, disease severity scores within 24 hours of admission to the ICU, treatment process and prognostic indicators were collected. According to the PaO₂/FiO₂ at ICU admission, patients were divided into Q1 group (PaO₂/FiO₂ of 4.1-16.4 cmHg, 1 cmHg ≈ 1.33 kPa), Q2 group (PaO₂/FiO₂ of 16.5-22.6 cmHg), Q3 group (PaO₂/FiO₂ of 22.7-32.9 cmHg), and Q4 group (PaO₂/FiO₂ of 33.0-94.8 cmHg). Differences in the indicators across the four groups were compared. Multifactorial Cox regression analysis was used to assess the relationship between PaO₂/FiO₂ and 30-day mortality of patients with sepsis. The predictive value of PaO₂/FiO₂, sequential organ failure assessment (SOFA) and acute physiology and chronic health evaluation II (APACHE II) on 30-day prognosis of patients with sepsis was analyzed by receiver operator characteristic curve (ROC curve). RESULTS: A total of 1 711 patients with sepsis were enrolled, including 428 patients in Q1 group, 424 patients in Q2 group, 425 patients in Q3 group, and 434 patients in Q4 group. 622 patients died at 30-day, the overall 30-day mortality was 36.35%. There were statistically significant differences in age, body mass index (BMI), history of smoking, history of alcohol consumption, admission heart rate, respiratory rate, APACHE II score, SOFA score, Glasgow coma score (GCS), site of infection, Combined chronic obstructive pulmonary disease (COPD), blood lactic acid (Lac), prothrombin time (PT), albumin (Alb), total bilirubin (TBil), pH, proportion of mechanical ventilation, duration of mechanical ventilation, proportion of vasoactive medication used, and maximal concentration, length of ICU stay, hospital stay, incidence of acute kidney injury, in-hospital mortality, 30-day mortality among the four groups. Multivariate Cox regression analysis showed that after adjusting for confounding factors, for every 1 cmHg increase in PaO₂/FiO₂ at ICU admission, the 30-day mortality risk decreased by 2% [hazard ratio (HR) = 0.98, 95% confidence interval (95%CI) was 0.98-0.99, P < 0.001]. The 30-day mortality risk in the Q4 group was reduced compared with the Q1 group by 41% (HR = 0.59, 95%CI was 0.46-0.76, P < 0.001). The fitted curve showed that a curvilinear relationship between PaO₂/FiO₂ and 30-day mortality after adjustment for confounders. In the inflection point analysis, for every 1 cmHg increase in PaO₂/FiO₂ at PaO₂/FiO₂ < 28.55 cmHg, the risk of 30-day death in sepsis patients was reduced by 5% (HR = 0.95, 95%CI was 0.94-0.97, P < 0.001); when PaO₂/FiO₂ ≥ 28.55 cmHg, there was no statistically significant association between PaO2/FiO2 and the increase in the risk of 30-day death in sepsis (HR = 1.01, 95%CI was 0.99-1.02, P = 0.512). ROC curve analysis showed that the area under the curve (AUC) for the prediction of 30-day mortality by admission PaO₂/FiO₂ in ICU sepsis patients was 0.650, which was lower than the predictive ability of the SOFA score (AUC = 0.698) and APACHE II score (AUC = 0.723). CONCLUSION In patients with sepsis, PaO₂/FiO₂ at ICU admission is strongly associated with 30-day mortality risk, alerting healthcare professionals to pay attention to patients with low PaO₂/FiO₂ for timely interventions.
Humans ; Sepsis/mortality* ; Intensive Care Units ; Retrospective Studies ; Prognosis ; Hospital Mortality ; Oxygen ; Male ; Predictive Value of Tests ; Female ; Middle Aged ; Aged

Conventional cancer therapies, such as radiotherapy and chemotherapy, often damage normal cells and may induce new tumors. Oncolytic viruses (OVs) selectively target tumor cells while sparing normal cells. Most OVs used in clinical trials have been genetically engineered to enhance their ability to target tumor cells and activate immune responses. To develop a specific OV-based approach for treating cervical cancer, this study constructed an oncolytic adenovirus that delivered a base editor targeting oncogenes to achieve efficient killing of tumor cells through inhibiting tumor growth and directly lysing tumor cells. We utilized the human telomerase reverse transcriptase (TERT) promoter to drive the expression of adenovirus early region 1A (E1A) and successfully constructed the P-hTERT-E1A-GFP vector, which was validated for its activity in cervical cancer cells. Given the critical role of the MYC oncogene in the research of oncology, identifying efficient editing sites for the MYC oncogene is a key step in this study.Three MYC-targeting gRNAs were engineered and co-delivered with ABE8e base editor plasmids into HEK293T cells. Following puromycin selection, Sanger sequencing demonstrated differential editing efficiencies: MYC-1 (43%), MYC-2 (25%), and MYC-3 (35%), identifying MYC-1 as the most efficient editing locus. By constructing the P-ABEs-hTERT-E1A-GFP and P-MYC gRNA-hTERT-E1A-GFP vectors, we successfully packaged the virus and confirmed its specificity and efficacy. The experimental results demonstrate that this novel oncolytic adenovirus effectively inhibits the growth of HeLa cells in vitro, providing new experimental evidence and potential strategies for treating cervical cancer based on the HeLa cell model.
Humans ; Uterine Cervical Neoplasms/pathology* ; Oncolytic Viruses/genetics* ; Female ; HEK293 Cells ; Oncolytic Virotherapy/methods* ; Adenoviridae/genetics* ; Gene Editing/methods* ; Telomerase/genetics* ; Adenovirus E1A Proteins/genetics* ; Genetic Vectors/genetics* ; HeLa Cells

Tumor-associated macrophage(TAM)play a crucial role in the immune microenvironment of lung can-cer.Through changes in their phenotype and phagocytic functions,TAM contribute to the initiation and progression of lung cancer.By promoting the formation of an immune-suppressive microenvironment and accelerating the growth of abnormal tumor vasculature,TAM facilitate the invasion and metastasis of lung cancer.Macrophages can polarize into different subtypes with distinct functions and characteristics in response to various stimuli,categorized as anti-tumor M1 and pro-tumor M2 types.In tumor tissues,TAM typically polarize into the alternatively activated M2 phenotype,exhibiting inhibitory effects on tumor immunity.This article reviews the role of anti-angiogenic drugs in modulating TAM phenotypes,highlighting their po-tential to reprogram M2-type TAM into an anti-tumor M1 phenotype.Additionally,the functional alterations of TAM play a significant role in anti-angiogenic therapy and immunotherapy strategies.In summary,the regulation of TAM polarization and function opens up new avenues for lung cancer treatment and may serve as a novel target for modulating the immune microen-vironment of tumors.

Objective:To evaluate the accuracy and stability of Eye-Monitor, a smart wearable device, in quantifying environmental risks related to myopia.Methods:A diagnostic test study was conducted.Forty-two subjects aged 18-25 years old were recruited from Shandong University of Traditional Chinese Medicine in December 2021.Forty-two Eye-Monitors were selected from 80 devices using the simple random sampling method.Static and dynamic tests were carried out to compare environmental risks related to myopia.The static tests included measurements under different working distances, different head tilt angles when sitting, and different light intensities.The dynamic tests included measurements under different near-work time, different outdoor activity time, different time watching computers, and different phone viewing time.Eye-Monitor with the largest sum of absolute values of total relative error was selected, Spearman rank correlation analysis was used to analyze the correlation between the set values and Eye-Monitor measurements, and the accuracy of the objectively measured values was evaluated by Bland-Altman consistency analysis.The stability of the objectively measured values from Eye-Monitor was evaluated by the coefficient of variation.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of the Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine (No.HEC-KS-2021005KY). Written informed consent was obtained from each subject.Results:There were significant correlations between the measured values and setting values in the working distance, head tilt angle when sitting, indoor light intensity, total near-work time, average continuous near-work time, outdoor activity time, time watching computers, and time viewing phones ( rs=0.999, 0.998, 0.999, 0.998, 0.976, 0.959, 0.992, 0.997; all at P<0.001), with the 95% limits of agreement (LoA) of-1.23-2.32 cm, -1.49-4.24°, -13.90-26.90 lx, -6.46-0.11 minutes, -4.50-1.20 minutes, -4.01-1.34 minutes, -2.54-1.94 minutes and-2.15-0.45 minutes, respectively.More than 95% of dots were within the clinically acceptable LoA.The coefficients of variation of the measured values ranged from 1.23%-2.99%, 2.39%-8.25%, 0.87%-8.03%, 1.49%-12.52%, 6.63%-13.59%, 0.00%-14.15%, 1.20%-8.33 and 1.49%-12.51%, respectively, showing good stability.Eye-Monitor had good accuracy in measuring outdoor light intensity (95% LoA: -336.50-130.00 lx). Conclusions:The smart wearable device Eye-Monitor can be used to objectively monitor working distance, head tilt angle when sitting, indoor light intensity, total near-work time, average continuous near-work time, outdoor activity time, time watching computers, and time watching phones, which are with good accuracy and stability.

T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domain (TIGIT) is a newly discovered immune checkpoint molecule, mainly expressed on the surface of T cells and natural killer (NK) cells. By binding to cluster of differentiation 155 (CD155) and other ligands, it inhibits T cell and NK cell-mediated immune responses and affects the tumor microenvironment. Multiple preclinical studies have demonstrated that the TIGIT/CD155 pathway plays a role in a variety of solid and hematological tumors. Clinical trials investigating TIGIT inhibitors alone or in combination with programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors for lung cancer are currently underway.
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Humans ; Lung Neoplasms/drug therapy* ; Immunotherapy ; Thorax ; Immunologic Factors ; Receptors, Immunologic ; Tumor Microenvironment

Treatment of advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation with EGFR-tyrosine kinase inhibitors (EGFR-TKIs) can achieve good disease control, but it will inevitably produce drug resistance. About 3%-10% of the resistance mechanism is small cell transformation. Two cases of stage IV lung adenocarcinoma with EGFR mutation were reported and the disease was controlled after EGFR-TKIs treatment. In case 1, progression-free survival (PFS) before small cell carcinoma transformation was 16 months, and in case 2, PFS before small cell carcinoma transformation was 24 months. Subsequent biopsy after disease progression indicated a shift to small cell lung cancer. Case 1 PFS after small cell carcinoma transformation was 6 months, and case 2 PFS after small cell carcinoma transformation was 8 months, and overall survival (OS) was 36 months, which significantly prolonged the patient's survival. At the same time, the literature of such drug resistance mutations was reviewed. For patients with advanced NSCLC with sensitive mutations, it is necessary to conduct secondary histopathological tests after TKIs treatment resistance, and select subsequent treatment according to different resistance mechanisms for the whole course of disease management.
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Humans ; Carcinoma, Small Cell ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Adenocarcinoma/genetics* ; Small Cell Lung Carcinoma/genetics* ; ErbB Receptors/genetics*

The incidence of lung cancer is high worldwide, and lung cancer is the leading cause of death from malignant tumors in both men and women. Early diagnosis of lung cancer can significantly improve the patient's prognosis. Therefore, searching for specific markers to assist in the early diagnosis of lung cancer is urgent question. Exosomes are nano-sized microvesicles and contain various biomaterial, including nucleic acids, proteins, and lipids. Exosomes are important carriers of these biomaterial, serve important roles in intracellular communications and signal transduction among tissues. Due to its unique enrichment mechanism, it has the stability and specificity as a biomarker. Exosomes are not only involved in the formation of tumor microenvironment and new blood vessels in lung cancer, but also involved in chemotherapy, targeted therapy response and prognosis assessment. Many research advances bring new hope for prolonging the survival of lung cancer patients. This article reviews the value of exosome specific protein and microRNA (miRNA) in lung cancer in the diagnosis and prognosis of lung cancer.

[Abstract] Objective: To explore the effects of triptolide on immune function and tumor cell proliferation in patients with cervical cancer. Methods: Sixty-two patients with cervical cancer admitted in the Department of Obstetrics and Gynecology of the Second Affiliated Hospital of Hebei North College between July 2015 and April 2018 were randomly divided into the control group (n=31) and the observation group (n=31). All patients received routine treatment after laparoscopy, while those in the observation group received additional triptolide. The treatment efficacy, serum immune cells, inflammatory factors and the levels of cyclinD1, estrogen receptor α (ERα ) were observed and compared between the two groups. Results: The total remission rate of the patients in the observation group was 87.10%, significantly higher than 61.29% in the control group (P<0.05). After treatment, the levels of CD3+ and CD4+ T lymphocytes and CD4+ /CD8+ T lymphocytes in the two groups increased significantly, with more obvious increase in the observation group than that in the control group (P<0.01). The levels of CD8+ and programmed cell death-ligand 1 (PD-L1) T lymphocytes in the two groups decreased significantly after treatment, with a more obvious decrease in observation group than that in control group (P<0.01). After treatment, the levels of interleukin-6 (IL-6), IL-10 and tumor necrosis factor-α (TNF-α) in the two groups decreased, and those in the observation group were significantly lower than those in the control group (P<0.05). After treatment, the positive expression rate of cyclinD1 decreased and the positive expression rate of ER α increased in both groups (all P<0.05), with no significant difference between the two groups (all P>0.05). Conclusion: On the basis of routine surgical treatment, triptolide can effectively improve the immune function, reduce the inflammatory response, inhibit the proliferation of tumor cells and regulate the expression of cancer-related factors in patients with cervical cancer, which has a certain therapeutic effect on cervical cancer.