OBJECTIVE To compare the efficacy and safety of chemotherapy combined with tislelizumab or sintilimab in patients with advanced non-small cell lung cancer （NSCLC）， and to analyze the influential factors of prognostic. METHODS A retrospective study was conducted on 163 patients with advanced NSCLC who received chemotherapy combined with tislelizumab or sintilimab at the First People’s Hospital of Yunnan Province from September 1， 2021 to November 30， 2024. Among them， there were 90 patients in the tislelizumab group and 73 patients in the sintilimab group. The objective response rate （ORR）， disease control rate （DCR）， progression free survival （PFS）， and overall survival （OS） of two groups were observed， and the occurrence of adverse drug reactions in patients was evaluated. Kaplan-Meier method was used to plot PFS and OS survival curves， Log-rank test was applied for univariate analysis， and Cox regression model was used to evaluate the independent prognostic factors of PFS and OS. RESULTS The median PFS of patients in the tislelizumab group and the sintilimab group were 14.14 months （95%CI of 10.95-17.33） and 10.95 months （95%CI of 8.75-13.15）， respectively. The median OS was 25.89 months （95%CI of 22.67-29.11） and 24.25 months （95%CI of 19.34-29.16）， with ORR of 45.56% and 49.32%， DCR of 94.44% and 90.41%， and the incidence of adverse drug reactions of 84.44% and 79.45%， respectively， the differences were not statistically significant （P＞0.05）. Age ≥60 years （HR＝1.542， 95%CI of 1.044-2.278， P＝0.029） and systemic immune inflammatory nutritional index （SIINI）＞ 116.58 （HR＝1.541， 95%CI of 1.058-2.245， P＝0.024） were risk factors for PFS in NSCLC patients receiving immune checkpoint inhibitor therapy； the use of antibiotics may affect the overall survival of patients （P＝0.001）. CONCLUSIONS The efficacy and safety of chemotherapy combined with tislelizumab or sintilimab for advanced NSCLC are comparable； age≥60 years and SIINI ＞116.58 are risk factors for PFS in NSCLC patients， and the use of antibiotics may affect the patients’ OS.

Objective To screen the risk factors for hypoglycemia in adult intensive care unit(ICU)patients,construct a risk prediction model,and validate its predictive effect.Methods A retrospective study was conducted on adult critically ill patients admitted to the general ICU of Hospital of Chengdu University of Traditional Chinese Medicine from December 2023 to September 2024.Patients admitted from December 2023 to June 2024 served as the modeling group,and those from July to September 2024 as the validation group.A total of 928 patients were included,with 650 in the modeling group and 278 in the validation group.After literature review and expert consultation,27 potential risk factors for hypoglycemia in ICU patients were initially screened,and data were collected including general information[gender,age,acute physiology and chronic health evaluation Ⅱ(APACHEⅡ)score,sequential organ failure assessment(SOFA)score,nutrition risk in critically ill(NUTRIC)score,mechanical ventilation status,hemodialysis status,enteral nutrition status],disease data(sepsis,liver disease history,kidney disease history,diabetes history,hypoglycemia history),blood glucose-related indicators[mean blood glucose,blood glucose coefficient of variation,insulin dosage,intravenous insulin titration use,inotropic drug use,insulin secretagogues(Sulfonylureas and Glinides),and combined use of hypoglycemic drugs(two or more)],and laboratory indicators[serum creatinine(SCr),blood urea nitrogen(BUN),serum albumin(Alb),alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBil),glomerular filtration rate(GFR)].The patients were divided into a hypoglycemia group and a non-hypoglycemia group based on the occurrence of hypoglycemia.Univariate analysis and binary Logistic regression analysis were used to identify influencing factors of hypoglycemia in adult ICU patients,and a nomogram prediction model was constructed.The area under the receiver operator characteristic curve(AUC)and calibration curves were employed to evaluate the discrimination and calibration of the model.Results The modeling cohort included 552 non-hypoglycemic patients and 98 hypoglycemic patients,with an ICU hypoglycemia incidence rate of 15.1％.Compared with the hypoglycemia group,the non-hypoglycemia group showed significantly lower proportions of patients with renal disease history,diabetes history,hypoglycemia history,undergoing hemodialysis,using intravenous insulin titration,and combined use of hypoglycemic drugs,as well as lower blood glucose coefficient of variation,lower APACHEⅡ scores,and significantly elevated GFR(all P<0.05).Binary Logistic regression analysis was performed using the 9 variables with statistically significant differences in univariate analysis as independent variables and hypoglycemia occurrence as the dependent variable.The results indicated that a history of diabetes,a history of hypoglycemia,APACHEⅡ score,GFR,blood glucose coefficient of variation,and combined use of hypoglycemic drugs were independent risk factors for hypoglycemia in ICU patients[odds ratios(OR)were 1.761,2.095,1.048,0.990,1.029,and 1.975,respectively,and 95％confidence intervals(95％CI)were 1.052-2.949,1.220-3.600,1.022-1.074,0.982-0.997,1.013-1.046,and 1.145-3.408,respectively.The corresponding Pvalues were 0.031,0.007,0.000,0.009,<0.001,0.014].A nomogram prediction model for hypoglycemia in ICU patients was constructed using six independent predictors selected through binary logistic regression analysis.The ROC curve AUC for the modeling group was 0.884(95％CI 0.826-0.941,P=0.250),with a maximum Youden index of 0.713,sensitivity of 92.1％,and specificity of 79.2％.The validation cohort included 38 patients with hypoglycemia and 240 patients without hypoglycemia.Compared with the hypoglycemia group,the non-hypoglycemia group showed significantly lower proportions of patients with a history of diabetes,a history of hypoglycemia,and combined use of hypoglycemic drugs,as well as lower APACHEⅡ scores and lower blood glucose coefficient of variation,with significantly increased GFR(all P<0.05).The ROC curve AUC for the validation cohort was 0.803(95％CI was 0.757-0.849,P=0.138),indicating high discriminatory ability.The predicted probability at the diagnostic cutoff point was P=0.138.The model's diagnostic threshold for predicted probability was P=0.138,while the optimal cut-off value based on the Youden index was 0.513,yielding a sensitivity of 76.5％and specificity of 74.8％,indicating predictive value for hypoglycemia in adult ICU patients.The mean absolute error(MAE)results for the modeling group and validation group were<0.05.The calibration curves of both the modeling and validation groups showed close alignment with the ideal curve,indicating excellent calibration performance of the model.Conclusion The constructed hypoglycemia risk prediction model for adult ICU patients has good predictive performance,which can quickly identify high-risk populations of hypoglycemia in ICU and provide reference for clinical preventive nursing.

Objective To investigate the expression of serum micro ribonucleic acid(miR)-423-5p and fer-ritin in elderly osteoporosis(OP)and their relationship with hip fragility fracture.Methods A total of 79 eld-erly OP patients admitted to the hospital from March 2020 to March 2024 were selected as the observation group,and 62 healthy elderly patients with complete physical examination records and reports were selected as the control group during the same period.Patients in the observation group were divided into fracture group(42 cases)and non-fracture group(37 cases)according to the occurrence of hip fragility fracture.Serum miR-423-5p and ferritin levels were compared between the observation group and the control group and between the fracture group and the non-fracture group.The difference of bone mineral density(BMD)at different sites between the fracture group and the non-fracture group was compared.The correlation between serum miR-423-5p and ferritin and BMD at different sites was analyzed by Pearson,and the predictive value of serum miR-423-5p and ferritin in elderly hip fragility fractures was analyzed by receiver operating characteristic(ROC)curve.Results Serum miR-423-5p and ferritin in observation group were higher than those in control group,the differences were statistically significant(P＜0.05).The levels of serum miR-423-5p and ferritin in frac-ture group were higher than those in non-fracture group,and the differences were statistically significant(P＜0.05).Greater trochanteric BMD and total hip BMD in the non-fracture group were higher than those in the fracture group,and the differences were statistically significant(P＜0.05).According to Pearson correlation analysis,serum miR-423-5p and ferritin levels in elderly OP patients were negatively correlated with BMD de-tected in lumbar spine,femoral neck,greater trochanter,intertrochanter and total hip(P＜0.05).ROC curve analysis results showed that the sensitivity,specificity and the area under the curve(AUC)of serum miR-423-5p combined with ferritin were 0.786,0.892 and 0.818(95％CI:0.715-0.912),which were higher than the AUC predicted by the two alone and had higher predictive value(P＜0.05).Conclusion The combination of serum miR-423-5p and ferritin levels can predict the risk of hip fragility fracture in elderly OP patients.

Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.

Over the past few decades, tumor immunotherapy has revolutionized the landscape of cancer clinical treatment. There is a flourishing development of combination strategies to improve the anti-tumor efficacy of mono-immunotherapy. However, instead of a straightforward combination of multiple therapeutics, it is more preferable to pursue a synergistic effect by designing rational combinations as well as administration strategies, which are based on a comprehensive understanding of the physiological and pathological features. In this case, the timing and spatial distribution of the combination drugs become essential factors in achieving improved therapeutic outcomes. Therefore, the concept of Sequential Drug Delivery System (SDDS) is proposed to define the spatiotemporally programmed drug delivery/release through triggers of internal conditions and/or external interventions, thus complying with the dynamic disease evolution and the human immunity. This review summarizes the recent advancements in biomaterial-based SDDSs used for spatiotemporally-tuned combination tumor immunotherapy. Furthermore, the rationales behind various engineering strategies are discussed. Finally, an overview of potential synergistic mechanisms as well as their prospects for combination immunotherapy is presented.

Quality marker (Q-Marker) is an innovative concept and model for quality control of Traditional Chinese medicines (TCMs), which will navigate the new direction of quality development of TCMs. Yet, how to characterize the overall quality attributes of TCMs and their biological effects is still debating. In view of this key scientific issue, this paper proposes a research method based on mass spectrometry imaging (MSI) technology for the discovery and confirmation of TCMs Q-Marker. MSI is powerful in investigating the spatial distribution of molecules in a variety of samples, and visualizing the information obtained from MS. On this basis, combine with the five principles of TCMs Q-Marker validation, i.e., specificity, transmission and traceability, testability, prescription compatibility, and validity, were applied to confirm the finalized Q-Marker. It will lead the new direction of quality development of TCMs.

Senile trichiasis is primarily manifested by eyelid laxity, decreased horizontal elasticity and tension of the eyelids, leading to friction between the eyelashes and the cornea, which subsequently causes corneal damage and vision decline. Surgical intervention remains the most effective therapeutic approach for senile trichiasis. This article elaborates on the epidemiological characteristics, pathological mechanisms, and clinical manifestations of senile trichiasis and systematically reviews the surgical treatment method for upper and lower eyelid trichiasis, including traditional surgical techniques and emerging minimally invasive procedures combined with personalized therapies. Through a literature review, the effectiveness and recurrence rates of surgical treatment are summarized, emphasizing the importance of preoperative assessment and individualized treatment. Additionally, strategies and recommendations for preventing senile trichiasis are proposed.

Objective To explore the effects of Yin Yang 1(YY1)on the proliferation and migration of bladder cancer cells and investigate the underlying mechanisms,so as to provide reference for the prevention and treatment of this disease.Methods The expression patterns of YY1 in common genitourinary tumors and their associations with the prognosis were analyzed using data from The Cancer Genome Atlas(TCGA)and the Gene Expression Omnibus(GEO).The efficiency of YY1 knockdown and overexpression in bladder cancer cell lines(T24 and UM-UC-3)was confirmed with quantitative reverse transcription PCR(qRT-PCR)and Western blotting.Cell proliferation and migration were assessed using methylthiazolyldiphenyl-tetrazolium bromide(MTT)and Transwell assays.RNA sequencing followed by bioinformatics analyses,including Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG),and Gene Set Enrichment Analysis(GSEA),was conducted to predict potential mechanisms.The qRT-PCR and rescue experiments were performed to validate whether YY1 exerted its effects via the E2F1 signaling pathway.Results YY1 was significantly overexpressed in bladder cancer compared to other genitourinary tumors and was associated with higher tumor grade and poorer prognosis(P＜0.05).Functional assays demonstrated that YY1 promoted the proliferation and migration of bladder cancer cells.Transcriptome analyses revealed that YY1 might regulate these processes through the E2F signaling pathway.Moreover,overexpression of E2F1 partially reversed the inhibitory effects of YY1 knockdown on bladder cancer cell proliferation and migration.Conclusion YY1 is upregulated in bladder cancer and is closely associated with tumor grade and unfavorable prognosis.It may facilitate tumor cell proliferation and migration by modulating the E 2F1 signaling pathway.

Objective:To evaluate the application effect of a wearable visual field meter based on extended reality (XR) glasses for patients with macular disease.Methods:A self-controlled study was conducted.A total of 41 consecutive patients (41 eyes) with macular disease were recruited at Renmin Hospital of Wuhan University from October 2022 to October 2024.All patients underwent 10-2 center visual field test using a self-developed wearable visual field meter (XRVF), and the results were compared with those obtained using a traditional Humphrey field analyzer (HFA).The comparison parameters included mean retinal sensitivity (MS), false positive rate (FPR), false negative rate (FNR), and testing duration.A subject satisfaction questionnaire was administered.This study followed the Declaration of Helsinki.The study protocol was approved by the Medical Ethics Committee of Renmin Hospital of Wuhan University (No.WDRY2024-K263), and all subjects signed the informed consent form.Results:The retinal sensitivity of patients measured by HFA was (23.24±3.71)dB, which was higher than (22.01±3.45)dB by XRVF, showing a statistically significant difference ( t=4.924, P=0.036).The FPR measured by HFA and XRVF were (2.39±2.51)% and (2.59±3.29)%, respectively, and the FNR were (3.49±6.05)% and (3.74±5.38)%, respectively, showing no statistically significant difference ( t=-3.624, P=0.948; t=-1.241, P=0.519).The median test duration for HFA and XRVF was 6.15 (5.78, 6.65) and 5.98 (5.71, 6.69)minutes, respectively, without statistically significant difference ( Z=-1.987, P=0.953).92.6% of the subjects thought the device was comfortable, simple and practical. Conclusions:The XRVF has good consistency with the HFA, can effectively and reliably evaluate the visual field function of patients with macular disease, and is easily accepted by patients.