1.Applications of Optical Technology in Non-invasive Hemoglobin Detection
Yao PENG ; Xian-Long WANG ; Bi-Tie LAN ; Jian-Hai YU
Progress in Biochemistry and Biophysics 2026;53(6):1561-1580
Hemoglobin (Hb) concentration is a key clinical biomarker for diagnosing and managing anemia, ischemic stroke, perioperative blood loss, and chronic diseases such as renal failure. Traditional venous blood sampling remains the gold standard due to its high accuracy, but its invasive nature limits frequent testing, real time monitoring, and large scale screening. This has driven growing interest in non-invasive Hb detection technologies over the past decade. Among these, optical methods are the most promising because of their safety, potential for continuous monitoring, and compatibility with portable or wearable devices. This paper systematically reviews major advances in optical non invasive Hb detection from the last ten years. We focus on near-infrared spectroscopy branches—photoplethysmography (PPG) and dynamic spectrum (DS)—and also cover color analysis/RGB imaging, Raman spectroscopy, and photoacoustic spectroscopy. For each technology, we explain its detection principles, analyze advantages and limitations, and summarize optimization strategies reported in recent literature. PPG, based on pulsatile blood volume changes, underpins many commercial continuous monitors. However, its accuracy is constrained by motion artifacts, individual physiological variations (e.g., skin tone, tissue thickness), and low AC signal to noise ratio. In contrast, DS—an advanced derivative of PPG—uses a differential principle to extract absorbance changes between systolic and diastolic peaks. This theoretically eliminates interference from static tissues (skin, bone, venous blood) and common mode noise (e.g., ambient light), positioning DS as a more robust framework for high precision Hb quantification. Beyond spectral methods, color analysis/RGB imaging offers a hardware minimalist approach. By analyzing images of vascular rich, thin tissues (e.g., conjunctiva, nail beds, palms), it enables Hb estimation using smartphone cameras. Recent advances have shifted from manual RGB feature extraction to deep learning models and spectral super resolution that reconstruct hyperspectral data from RGB inputs, significantly improving screening accuracy. Our academic perspective emphasizes critical and integrative analysis. We highlight persistent challenges that hinder clinical translation: profound individual biological variability (skin optics, microvascular architecture), sensitivity to measurement conditions (pressure, ambient light), and a lack of standardized validation protocols and multi center trials. A central thesis is that no single optical method is universally superior; each involves trade offs between accuracy, complexity, cost, and practicality. Looking forward, we posit that the next performance leap will come from multimodal information fusion—combining PPG, electrocardiogram (ECG), bioimpedance, or different optical modalities to compensate for individual differences and environmental noise. AI and deep learning are essential not only for image analysis but also for automated, end to end feature extraction from complex waveforms like PPG sequences. Advancing hardware (tunable lasers, quantum dot LEDs, novel sensor designs) is crucial to improve signal fidelity and portability. Finally, we advocate for clinical scenario specific optimization and rigorous standardized evaluation frameworks to gain regulatory approval (e.g., FDA, NMPA) and achieve widespread clinical acceptance. In conclusion, this review synthesizes a decade of progress. Optical non-invasive Hb detection has evolved from proof of concept studies to emerging products and validated screening tools, but the journey toward reliable, clinic ready quantitative devices continues. The convergence of smarter algorithms, fused sensing modalities, and focused clinical validation offers the most promising path to transform this potential into routine medical practice, ultimately enabling personalized, continuous, and accessible hematological management.
2.Trend in disease burden of nasopharyngeal carcinoma among middle-aged and elderly population in China from 1994 to 2023
WU Shuang ; WANG Zhe ; LI Dongyang ; QIAO Jian ; MU Lan
Journal of Preventive Medicine 2026;38(8):790-793
Objective:
To analyze the trend in disease burden of nasopharyngeal carcinoma-related among middle-aged and elderly population in China from 1994 to 2023, so as to provide evidence for formulating targeted screening and intervention strategies.
Methods:
Data on prevalent cases, standardized prevalence, incident cases, standardized incidence, death cases, standardized mortality, disability-adjusted life years (DALY) and standardized DALY rate of nasopharyngeal carcinoma among the population aged ≥45?years in China were collected through the Global Burden of Disease (GBD) 2023 database. The average annual percent change (AAPC) was used to evaluate the trend in disease burden. A four-factor decomposition method was used to estimate the contributions of population size, age structure, prevalence variation and disease severity to the alterations in death cases and DALY caused by nasopharyngeal carcinoma.
Results:
The standardized prevalence of nasopharyngeal carcinoma among Chinese middle-aged and elderly population rose from 46.54/105 in 1994 to 59.81/105 in 2023, presenting an upward trend (AAPC=0.760%, 95%CI: 0.561%-0.973%). The standardized incidence, standardized mortality and standardized DALY rate decreased from 13.66/105, 10.90/105 and 318.79/105 to 10.75/105, 3.87/105 and 111.20/105, respectively, with declining trends (AAPC=-0.757%, 95%CI: -0.882% to -0.620%; AAPC=-3.554%, 95%CI: -3.681% to -3.419%; AAPC=-3.444%, 95%CI: -3.564% to -3.307%). In 2023, the standardized prevalence, incidence, mortality and DALY rate among males reached 86.96/105, 15.84/105, 5.88/105 and 172.49/105, which were higher than 33.45/105, 5.82/105, 1.92/105 and 51.66/105 in females. Decomposition analysis indicated that expanded population scale, population ageing and prevalence change exerted favourable effects on the reduction of death cases and DALY caused by nasopharyngeal carcinoma, whereas disease severity produced an offsetting adverse effect.
Conclusions
The overall disease burden of nasopharyngeal carcinoma among middle-aged and elderly population in China declined from 1994 to 2023, yet males suffered from a comparatively heavy burden. The beneficial impacts from population expansion, population ageing and prevalence change on burden reduction were partially counteracted by disease severity.
3.Feixin Decoction Treats Hypoxic Pulmonary Hypertension by Regulating Pyroptosis in PASMCs via PPARγ/NF-κB/NLRP3 Signaling Pathway
Junlan TAN ; Xianya CAO ; Runxiu ZHENG ; Wen ZHANG ; Chao ZHANG ; Jian YI ; Feiying WANG ; Xia LI ; Jianmin FAN ; Hui LIU ; Lan SONG ; Aiguo DAI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(18):1-9
ObjectiveTo investigate the mechanism by which Feixin decoction treats hypoxic pulmonary hypertension (HPH) by regulating the peroxisome proliferator-activated receptor gamma (PPARγ)/nuclear factor-kappa B (NF-κB)/NOD-like receptor pyrin domain containing 3 (NLRP3) signaling pathway. MethodsForty-eight male SD rats were randomly allocated into normal, hypoxia, and low-, medium- and high-dose (5.85, 11.7, 23.4 g·kg-1, respectively) Feixin decoction groups, with 8 rats in each group. Except the normal group, the remaining five groups were placed in a hypoxia chamber with an oxygen concentration of (10.0±0.5)% for 8 h per day, 28 days, and administrated with corresponding drugs during the modeling process. After 4 weeks of treatment, echocardiographic parameters [pulmonary artery acceleration time (PAT), pulmonary artery ejection time (PET), right ventricular anterior wall thickness (RVAWd), and tricuspid annular plane systolic excursion (TAPSE)] were measured for each group. The right ventricular systolic pressure (RVSP) was measured by the right heart catheterization method, and the right ventricular hypertrophy index (RVHI) was calculated by weighing the heart. The pathological changes in pulmonary arterioles were observed by hematoxylin-eosin staining. The co-localization of α-smooth muscle actin (α-SMA) with NLRP3, N-terminal gasdermin D (N-GSDMD), and cysteinyl aspartate-specific proteinase-1 (Caspase-1) in pulmonary arteries was detected by immunofluorescence. The protein levels of PPARγ, NF-κB, NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), N-GSDMD, interleukin-1β (IL-1β), interleukin-18(IL-18), and cleaved Caspase-1 in the lung tissue was determined by Western blot. The ultrastructural changes in pulmonary artery smooth muscle cells (PASMCs) were observed by transmission electron microscopy. ResultsCompared with the normal group, the hypoxia group showed increased RVSP and RVHI (P<0.01), decreased right heart function (P<0.01), increased pulmonary vascular remodeling (P<0.01), increased co-localization of α-SMA with NLRP3, N-GSDMD, and Caspase-1 in pulmonary arterioles (P<0.01), up-regulated protein levels of NF-κB, NLRP3, ASC, N-GSDMD, IL-1β, IL-18, and cleaved Caspase-1 in the lung tissue (P<0.05, P<0.01), a down-regulated protein level of PPARγ (P<0.05, P<0.01), and pyroptosis in PASMCs. Compared with the hypoxia group, Feixin decoction reduced RVSP and RVHI, improved the right heart function and ameliorated pulmonary vascular remodeling (P<0.05, P<0.01), decreased the co-localization of α-SMA with NLRP3, N-GSDMD, and Caspase-1 (P<0.05, P<0.01), down-regulated the protein levels of NF-κB, NLRP3, ASC, N-GSDMD, IL-1β, IL-18, and cleaved Caspase-1 in the lung tissue (P<0.05, P<0.01), up-regulated the protein level of PPARγ (P<0.05, P<0.01), and alleviated pyroptosis in PASMCs. ConclusionFeixin decoction can ameliorate pulmonary vascular remodeling and right heart dysfunction in chronically induced HPH rats by regulating pyroptosis in PASMCs through the PPARγ/NF-κB/NLRP3 pathway.
4.Optimization of extraction process for Shenxiong Huanglian Jiedu Granules based on AHP-CRITIC hybrid weighting method, grey correlation analysis, and BP-ANN.
Zi-An LI ; De-Wen LIU ; Xin-Jian LI ; Bing-Yu WU ; Qun LAN ; Meng-Jia GUO ; Jia-Hui SUN ; Nan-Yang LIU ; Hui PEI ; Hao LI ; Hong YI ; Jin-Yu WANG ; Liang-Mian CHEN
China Journal of Chinese Materia Medica 2025;50(10):2674-2683
By employing the analytic hierarchy process(AHP), the CRITIC method(a weight determination method based on indicator correlations), and the AHP-CRITIC hybrid weighting method, the weight coefficients of evaluation indicators were determined, followed by a comprehensive score comparison. The grey correlation analysis was then performed to analyze the results calculated using the hybrid weighting method. Subsequently, a backpropagation-artificial neural network(BP-ANN) model was constructed to predict the extraction process parameters and optimize the extraction process for Shenxiong Huanglian Jiedu Granules(SHJG). In the extraction process, an L_9(3~4) orthogonal experiment was designed to optimize three factors at three levels, including extraction frequency, water addition amount, and extraction time. The evaluation indicators included geniposide, berberine, ginsenoside Rg_1 + Re, ginsenoside Rb_1, ferulic acid, and extract yield. Finally, the optimal extraction results obtained by the orthogonal experiment, grey correlation analysis, and BP-ANN method were compared, and validation experiments were conducted. The results showed that the optimal extraction process involved two rounds of aqueous extraction, each lasting one hour; the first extraction used ten times the amount of added water, while the second extraction used eight times the amount. In the validation experiments, the average content of each indicator component was higher than the average content obtained in the orthogonal experiment, with a higher comprehensive score. The optimized extraction process parameters were reliable and stable, making them suitable for subsequent preparation process research.
Drugs, Chinese Herbal/analysis*
;
Neural Networks, Computer
5.Investigation of therapeutic effects and mechanisms of Shenqi Buqi Granules on patients with chronic heart failure of Qi deficiency based on proteomics.
Zhi-Bo WANG ; Ying LI ; Lan MIAO ; Jun-Guo REN ; Jian-Xun LIU
China Journal of Chinese Materia Medica 2025;50(11):3168-3179
This study explored the efficacy and mechanisms of Shenqi Buqi Granules in treating chronic heart failure(CHF) of Qi deficiency using proteomics and bioinformatics methods. A total of 18 healthy participants(health group) and 19 patients with Qi deficiency-type CHF(experimental group) were enrolled and treated with Shenqi Buqi Granules for 12 weeks. Clinical indicators, including Qi deficiency scores, complete blood count, biochemical parameters, lipid profiles, and cardiac function, were collected from pre-and post-experimental groups. Serum proteomics analysis was performed. Differential proteins were screened through differential analysis and K-means clustering. Further analyses, including subcellular localization, Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment, and protein-protein interaction(PPI) network construction, were conducted to identify pathways and proteins associated with Shenqi Buqi Granules treatment. Spearman correlation analysis focused on proteins most correlated with the core phenotype of CHF of Qi deficiency. The results show that Shenqi Buqi Granules treatment reduced Qi deficiency scores and brain natriuretic peptide levels of pre-experimental group. A total of 1 594 proteins were quantified in the proteomics analysis, with 98 proteins showing differential expression between healthy group and experimental group before and after treatment. Subcellular localization analysis revealed 6 protein sources, while KEGG pathway enrichment highlighted biological processes including angiogenesis, immune inflammation, calcium homeostasis, cytoskeletal regulation, protein synthesis, and energy metabolism. Core genes identified included CD34, CSF1, CALM1, CALML3, PPP1CA, PFN1, and 3 ribosomal large subunit proteins. Correlation analysis between core proteins and Qi deficiency scores revealed that CD34(r=-0.67, P<0.05) and PPP1CA(r=0.62, P<0.01) were most strongly associated with Qi deficiency scores. This study suggests that Shenqi Buqi Granules improves Qi deficiency scores and CHF symptoms by regulating angiogenesis, immune inflammation, calcium homeostasis, cytoskeletal regulation, protein synthesis, and energy metabolism. CD34 and PPP1CA are identified as core proteins involved in the therapeutic effects of Shenqi Buqi Granules on Qi deficiency.
Humans
;
Drugs, Chinese Herbal/therapeutic use*
;
Heart Failure/metabolism*
;
Male
;
Female
;
Proteomics
;
Middle Aged
;
Qi
;
Aged
;
Protein Interaction Maps/drug effects*
;
Adult
;
Chronic Disease
6.Glucocorticoid Discontinuation in Patients with Rheumatoid Arthritis under Background of Chinese Medicine: Challenges and Potentials Coexist.
Chuan-Hui YAO ; Chi ZHANG ; Meng-Ge SONG ; Cong-Min XIA ; Tian CHANG ; Xie-Li MA ; Wei-Xiang LIU ; Zi-Xia LIU ; Jia-Meng LIU ; Xiao-Po TANG ; Ying LIU ; Jian LIU ; Jiang-Yun PENG ; Dong-Yi HE ; Qing-Chun HUANG ; Ming-Li GAO ; Jian-Ping YU ; Wei LIU ; Jian-Yong ZHANG ; Yue-Lan ZHU ; Xiu-Juan HOU ; Hai-Dong WANG ; Yong-Fei FANG ; Yue WANG ; Yin SU ; Xin-Ping TIAN ; Ai-Ping LYU ; Xun GONG ; Quan JIANG
Chinese journal of integrative medicine 2025;31(7):581-589
OBJECTIVE:
To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM).
METHODS:
This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis.
RESULTS:
Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings.
CONCLUSIONS
RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult
;
Aged
;
Female
;
Humans
;
Male
;
Middle Aged
;
Arthritis, Rheumatoid/drug therapy*
;
Glucocorticoids/therapeutic use*
;
Medicine, Chinese Traditional
;
Retrospective Studies
7.Erratum: Author correction to "Generation of αGal-enhanced bifunctional tumor vaccine" Acta Pharm Sin B 12 (2022) 3177-3186.
Jian HE ; Yu HUO ; Zhikun ZHANG ; Yiqun LUO ; Xiuli LIU ; Qiaoying CHEN ; Pan WU ; Wei SHI ; Tao WU ; Chao TANG ; Huixue WANG ; Lan LI ; Xiyu LIU ; Yong HUANG ; Yongxiang ZHAO ; Lu GAN ; Bing WANG ; Liping ZHONG
Acta Pharmaceutica Sinica B 2025;15(2):1207-1207
[This corrects the article DOI: 10.1016/j.apsb.2022.03.002.].
8.Long-chain acylcarnitine deficiency promotes hepatocarcinogenesis.
Kaifeng WANG ; Zhixian LAN ; Heqi ZHOU ; Rong FAN ; Huiyi CHEN ; Hongyan LIANG ; Qiuhong YOU ; Xieer LIANG ; Ge ZENG ; Rui DENG ; Yu LAN ; Sheng SHEN ; Peng CHEN ; Jinlin HOU ; Pengcheng BU ; Jian SUN
Acta Pharmaceutica Sinica B 2025;15(3):1383-1396
Despite therapy with potent antiviral agents, chronic hepatitis B (CHB) patients remain at high risk of hepatocellular carcinoma (HCC). While metabolites have been rediscovered as active drivers of biological processes including carcinogenesis, the specific metabolites modulating HCC risk in CHB patients are largely unknown. Here, we demonstrate that baseline plasma from CHB patients who later developed HCC during follow-up exhibits growth-promoting properties in a case-control design nested within a large-scale, prospective cohort. Metabolomics analysis reveals a reduction in long-chain acylcarnitines (LCACs) in the baseline plasma of patients with HCC development. LCACs preferentially inhibit the proliferation of HCC cells in vitro at a physiological concentration and prevent the occurrence of HCC in vivo without hepatorenal toxicity. Uptake and metabolism of circulating LCACs increase the intracellular level of acetyl coenzyme A, which upregulates histone H3 Lys14 acetylation at the promoter region of KLF6 gene and thereby activates KLF6/p21 pathway. Indeed, blocking LCAC metabolism attenuates the difference in KLF6/p21 expression induced by baseline plasma of HCC/non-HCC patients. The deficiency of circulating LCACs represents a driver of HCC in CHB patients with viral control. These insights provide a promising direction for developing therapeutic strategies to reduce HCC risk further in the antiviral era.
9.Improvement effect of ginseng alcohol extract on sleep of aged drosophila and its mechanism
Jian LIU ; Lu XING ; Tianye LAN ; Fan YAO ; Wen WANG ; Yufu DONG ; Jinpu WU ; Ran BI ; Liwei SUN ; Xuenan CHEN ; Weimin ZHAO
Journal of Jilin University(Medicine Edition) 2025;51(4):896-903
Objective:To investigate the impact of ginseng alcohol extract(GEE)on improving sleep quality in the aged Drosophila model by regulating the redox balance,and to elucidate its associated mechanism.Methods:Thirty-two male drosophila melanogaster(7-days-old)were randomly selected as young group,while 64 male Drosophila melanogaster flies(35-days-old)were randomly assigned to aged model group(n=32)and GEE group(n=32).The sleep parameters,including total sleep duration,daytime sleep duration,night sleep duration,0-4 h of sleep duration after lights off(ZT0-4 sleep duration),deep sleep duration,sleep episodetimes,sleep fragmentation,and the activity parameters such as the total number of locomotor activity daytime locomotor activity amount and nighttime locomotor activity amount were analyzed using the DAM2 Drosophila behavioral analysis system 7 d after administration.The grouping of the drosophila was as above,and there were 100 drosophila ineach group.The differentially expressed proteins in drosophila brain tissue were screened,identified,and functionally analyzed using two-dimensional fluorescence difference gel electrophoresis(2D-DIGE)and matrix-assisted laser desorption/ionization time of flight mass spectrometry(MALDI-TOF/TOF-MS)proteomic methods.The grouping of the drosophila was as above,and there were 100 drosophila in each group.The activities of superoxide dismutase(SOD),catalase(CAT),and glutathione peroxidase(GSH-Px)and the levels of lipid peroxidation product(MDA)in brain tissue of the drosophila were determined using assay kits.Results:Compared with young group,the total sleep duration daytime sleep duration and night sleep cluration of the drosophila in agaed group were decreased(P<0.05 or P<0.01);and the sleep rhythm amplitude was shortened.Compared with aged group,the total sleep duration and daytime and nighttime sleep durations of the drosphila in GEE group were lengthened(P<0.01).Compared with young group,the ZT0-4 sleep duration deep sleep duration and sleep fragment of the drosophila in aged group were decreased(P<0.05 or P<0.01),and the sleep rhythm amplitude was shortened.Compared with young group,the ZT0-4 sleep duration,deep sleep duration,and single sleep fragment of the drosphila in GEE group were significantly prolonged(P<0.01),and the sleep amplitude was increased.Compared with young group,there was no significant difference in diurnal spontaneous activity or total spontaneous activity of the drosophila in aged group(P>0.05),while the nocturnal spontaneous activity was significantly increased(P<0.05).Compared with aged group,the diurnal spontaneous activity,nocturnal spontaneous activity,and total spontaneous activity of the drosophila in GEE group were significantly decreased(P<0.05 or P<0.01).A total of 47 differentially expressed proteins were selected in the 2D-DIGE electrophoretic mapping.Compared with young group,the expressions of 47 differentially expressed protein sites in aged group were down-regulated mainly including glutathione S-transferase,peroxiredoxin 1 and dihydrolipoic dehydrogenase,which were related to redox balance.Compared with young group,the activities of SOD,CAT and GSH-Px in brain tissue of the drosophila in aged group were decreased(P<0.05 or P<0.01),and the level of MDA was increased(P<0.01);compared with aged group,the activities of SOD,CAT and GSH-Px in brain tissue of the drosphila in GEE group were increased(P<0.05 or P<0.01),and the MDA level was decreased(P<0.05).Conclusion:GEE has improvement effect on the sleep quality of aged drosophila,and its possible mechanism may be related to upregulating the activities of antioxidant enzymes,inhibiting the accumulation of lipid peroxidation products,and maintaining redox balance.
10.Development and validation of clinical prediction model for post-treatment recurrence in high-risk non-muscle invasive bladder cancer after BCG intravesical instillation
Haitao WANG ; Weiming LUO ; Jian CHEN ; Jian ZHANG ; Qiang RAN ; Jing XU ; Junhao JIN ; Yangkun AO ; Yapeng WANG ; Junying ZHANG ; Qiubo XIE ; Weihua LAN ; Qiuli LIU
Journal of Army Medical University 2025;47(9):959-968
Objective To investigate the factors influencing the efficacy of intravesical Bacille Calmette-Guérin(BCG)instillation after transurethral resection of bladder tumor(TURBT)in patients with intermediate-and high-risk non-muscle invasive bladder cancer(NMIBC),and to construct a prediction model for recurrence after BCG treatment.Methods A retrospective cohort study was conducted on the subjected patients diagnosed with intermediate-and high-risk NMIBC undergoing TURBT followed by standard BCG instillation.The 110 patients treated in Department of Urology of Army Medical Center of PLA from January 2018 to December 2023 were assigned into a training set,while the 52 patients treated at Department of Urology of General Hospital of Central Theater Command from January 2015 to December 2020 were into an external validation set.A total of 17 variables were included and analyzed.Univariate and multivariate Cox regression analyses were performed to identify factors associated with recurrence after BCG instillation,and nomograms were plotted to predict 1-year,3-year,and 5-year recurrence-free survival(RFS).Calibration curve,decision curve analysis(DCA),and receiver operating characteristic(ROC)curve analysis were conducted for internal and external validation to evaluate the predictive performance and clinical utility of the model.Results In the training set,26 patients(23.64%)experienced recurrence during the follow-up period,with a median RFS of 32.00(18.00~50.50)months.Univariate Cox regression analysis suggested that platelet count,eosinophil to lymphocyte ratio(ELR),neutrophil to lymphocyte ratio(NLR),platelet to lymphocyte ratio(PLR),systemic immune inflammation(SII)index,and neutrophil-monocyte to lymphocyte ratio(NMLR),pathological T1 stage(pT1)tumor and hemoglobin,albumin,lymphocyte,and platelet(HALP)score were potential factors influencing recurrence after BCG instillation.Multivariate Cox regression analysis identified high HALP score(HR=0.185,95%CI:0.046~0.736,P=0.017)as an independent protective factor,while high ELR(HR=3.599,95%CI:1.505~8.608,P=0.004)and pT1 stage(HR=3.240,95%CI:1.191~8.818,P=0.021)were independent risk factors for recurrence.Based on this,a nomogram prediction model was constructed.The calibration curves demonstrated good agreement between predicted and actual 1-,3-,and 5-year recurrence risks.Decision curve analysis indicated clinical utility across a wide threshold probability range.In the training set,the model showed strong predictive performance for 1-(AUC=0.842),3-(AUC=0.847),and 5-year(AUC=0.887)recurrence risks,which was further validated in the external cohort.Conclusion Higher HALP score prior to BCG instillation therapy is a protective factor against tumor recurrence,while higher ELR and pT1 stage are risk factors.Our nomogram prediction model based on HALP score,ELR and pathological T stage,can identify individuals at high risk of recurrence after BCG instillation therapy.


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