Objective To evaluate the predictive ability and clinical application value of artificial intelligence (AI) systems in the benign and malignant differentiation and pathological type of pulmonary nodules, and to summarize clinical application experience. Methods A retrospective analysis was conducted on the clinical data of patients with pulmonary nodules admitted to the Department of Thoracic Surgery, Second Hospital of Lanzhou University, from February 2016 to February 2025. Firstly, pulmonary nodules were divided into benign and non-benign groups, and the discriminative abilities of AI systems and clinicians were compared. Subsequently, lung nodules reported as precursor glandular lesions (PGL), microinvasive adenocarcinoma (MIA), and invasive adenocarcinoma (IAC) in postoperative pathological results were analyzed, comparing the efficacy of AI systems and clinicians in predicting the pathological type of pulmonary nodules. Results In the analysis of benign/non-benign pulmonary nodules, clinical data from a total of 638 patients with pulmonary nodules were included, of which there were 257 males (10 patients and 1 patient of double and triple primary lesions, respectively) and 381 females (18 patients and 1 patient of double and triple primary lesions, respectively), with a median age of 55.0 (47.0, 61.0) years. Different lesions in the same patient were analyzed as independent samples. Univariate analysis of the two groups of variables showed that, except for nodule location, the differences in the remaining variables were statistically significant (P<0.05). Multivariate logistic regression analysis showed that age, nodule type (subsolid pulmonary nodule), average density, spicule sign, and vascular convergence sign were independent influencing factors for non-benign pulmonary nodules, among which age, nodule type (subsolid pulmonary nodule), spicule sign, and vascular convergence sign were positively correlated with non-benign pulmonary nodules, while average density was negatively correlated with the occurrence of non-benign pulmonary nodules. The area under the receiver operating characteristic curve (AUC) of the malignancy risk value given by the AI system in predicting non-benign pulmonary nodules was 0.811, slightly lower than the 0.898 predicted by clinicians. In the PGL/MIA/IAC analysis, clinical data from a total of 411 patients with pulmonary nodules were included, of which there were 149 males (8 patients of double primary lesions) and 262 females (17 patients of double primary lesions), with a median age of 56.0 (50.0, 61.0) years. Different lesions in the same patient were analyzed as independent samples. Univariate analysis results showed that, except for gender, nodule location, and vascular convergence sign, the differences in the remaining variables among the three groups of PGL, MIA, and IAC patients were statistically significant (P<0.05). Multinomial multivariate logistic regression analysis showed that the differences between the parameters in the PGL group and the MIA group were not statistically significant (P>0.05), and the maximum diameter and average density of the nodules were statistically different between the PGL and IAC groups (P<0.05), and were positively correlated with the occurrence of IAC as independent risk factors. The average AUC value, accuracy, recall rate, and F1 score of the AI system in predicting lung nodule pathological type were 0.807, 74.3%, 73.2%, and 68.5%, respectively, all better than the clinical physicians’ prediction of lung nodule pathological type indicators (0.782, 70.9%, 66.2%, and 63.7% respectively). The AUC value of the AI system in predicting IAC was 0.853, and the sensitivity, specificity, and optimal cutoff value were 0.643, 0.943, and 50.0%, respectively. Conclusion This AI system has demonstrated high clinical value in predicting the benign and malignant nature and pathological type of lung nodules, especially in predicting lung nodule pathological type, its ability has surpassed that of clinical physicians. With the optimization of algorithms and the adequate integration of multimodal data, it can better assist clinical physicians in formulating individualized diagnostic and treatment plans for patients with lung nodules.

Objective:To compare the characteristics of gait disorders between patients with idiopathic normal pressure hydrocephalus(iNPH)and Parkinson's disease(PD)patients.Methods:General clinical data and gait assessment results of 16 iNPH patients, 20 PD patients, and 23 healthy adults seeking treatment at Tianjin Huanhu Hospital between January 2020 and December 2020 were retrospectively analyzed.Gait analysis was conducted using the Mobility Lab? system with APDM Opal sensors from the US.Results:The 16 patients in the iNPH group had a mean age of(68.81±8.73), the 20 patients in the PD group had a mean age of(65.05±10.15), and the 23 adults in the control group had a mean age of(59.96±6.20).There was no significant difference in age between the iNPH group and the PD group( P>0.05).However, the iNPH group was older than the healthy control group( t=3.71, P<0.05).The disease duration of the iNPH group was(22.94±23.19)months, which was shorter than(92.60±53.70)months in the PD group( t=5.23, P<0.05).The mini-mental state examination(MMSE)score(17.13±7.08)and the Montreal Cognitive Assessment(MoCA)score(11.75±5.43)of the iNPH group were significantly lower than those in the PD group[(24.17±4.73), t=3.45, P<0.05、(21.29±5.82), t=4.86, P<0.05]and the control group[(26.70±1.61), t=5.31, P<0.05、(22.78±3.30), t=7.89, P<0.05].Compared with the PD group, the iNPH group had a significantly lower foot clearance[right: (1.65±0.76)cm vs.(2.56±1.30)cm]and smaller bilateral toe-off angles[left: (20.59±6.11)° vs.(28.43±6.36)°; right: (20.78±6.88)° vs.(28.12±7.49)°, t=3.74、3.02, respectively, all P<0.05].There were statistically significant differences in all gait parameters in iNPH patients compared with the control group( P<0.05). Conclusions:iNPH patients exhibit clear gait disturbance, which is more prominent than in PD patients.The wearable gait analysis system can accurately assess gait disorders in iNPH patients, and can be applied to gait assessment and the development of rehabilitation plans.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Aberrant activation of oncogenic signaling pathways in tumors can promote resistance to the antitumor immune response. However, single blockade of these pathways is usually ineffective because of the complex crosstalk and feedback among oncogenic signaling pathways. The enhanced toxicity of free small molecule inhibitor combinations is considered an insurmountable barrier to their clinical applications. To circumvent this issue, we rationally designed an effective tumor microenvironment-activatable prodrug nanomicelle (PNM) for cancer therapy. PNM was engineered by integrating the PI3K/mTOR inhibitor PF-04691502 (PF) and the broad spectrum CDK inhibitor flavopiridol (Flav) into a single nanoplatform, which showed tumor-specific accumulation, activation and deep penetration in response to the high glutathione (GSH) tumoral microenvironment. The codelivery of PF and Flav could trigger gasdermin E (GSDME)-based immunogenic pyroptosis of tumor cells to elicit a robust antitumor immune response. Furthermore, the combination of PNM-induced immunogenic pyroptosis with anti-programmed cell death-1 (αPD-1) immunotherapy further boosted the antitumor effect and prolonged the survival time of mice. Collectively, these results indicated that the pyroptosis-induced nanoplatform codelivery of PI3K/mTOR and CDK inhibitors can reprogram the immunosuppressive tumor microenvironment and efficiently improve checkpoint blockade cancer immunotherapy.

Purpose: Drug resistance is one of the main causes of chemotherapy failure in patients with small cell lung cancer (SCLC), and extensive biological studies into chemotherapy drug resistance are required. Materials and Methods: In this study, we performed lncRNA microarray, in vitro functional assays, in vivo models and cDNA microarray to evaluate the impact of lncRNA in SCLC chemoresistance. Results: The results showed that KCNQ1OT1 expression was upregulated in SCLC tissues and was a poor prognostic factor for patients with SCLC. Knockdown of KCNQ1OT1 inhibited cell proliferation, migration, chemoresistance and promoted apoptosis of SCLC cells. Mechanistic investigation showed that KCNQ1OT1 can activate transforming growth factor-β1 mediated epithelial-to-mesenchymal transition in SCLC cells. Conclusion Taken together, our study revealed the role of KCNQ1OT1 in the progression and chemoresistance of SCLC, and suggested KCNQ1OT1 as a potential diagnostic and prognostic biomarker in SCLC clinical management.

Objective:To investigate the application value of dynamic scintigraphy single-photonemission computed tomography (SPECT) 99m-technetium-galactosyl human serum albumin diethy-lenetriamine pentaacetic ( 99Tc m-GSA) scintigraphy in assessing liver function of perihilar cholangio-carcinoma after portal vein embolization (PVE). Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 16 patients with perihilar cholangiocarcinoma who underwent 99Tc m-GSA scintigraphy after PVE in Beijing Tsinghua Changgung Hospital Affiliated to Tsinghua University from October 2019 to January 2021 were collected. There were 8 males and 8 females, aged from 46 to 78 years, with a median age of 64 years. Observation indicators: (1) liver volume after PVE; (2) liver function after PVE; (3) typical case analysis. Measurement data with normal distribution were represented as Mean± SD. Count data were represented as absolute numbers or percentages. Comparison of data of the same patient was analyzed using the paired t test. Results:(1) Liver volume after PVE:the morphological liver volume and functional liver volume for the 16 patients were (1 420±211)mL and (389±112)mL. The morphological liver volume and functional liver volume were (636±143)mL and (234±106)mL of planning reserved lobe, (784±210)mL and (151±106)mL of planning resection lobe, respectively. The functional liver density (FLD) of planning reserved lobe and planning resection lobe were 0.36±0.12 and 0.19±0.11, showing a significant difference between them ( t=3.794, P<0.05). The planning resection rate of morpholo-gical liver volume and functional liver volume were 37.8%±0.6% and 54.8%±0.2%, showing a significant difference between them ( t=?3.720, P<0.05). (2) Liver function after PVE: 13 of 16 patients completed the indocyanine green (ICG) test, and 3 patients didn't complete the ICG test due to intolerance. For the 13 patients undergoing ICG test, the total ICG-K value was (0.15±0.03)/minutes, and the ICG-K value of planning reserved lobe was (0.07±0.02)/minutes. The total GSA-K value of 16 patients was (0.14±0.10)/minutes, and the GSA-K value of planning reserved lobe was (0.08±0.06)/minutes. (3) Typical case analysis: a 46-year-old male patient with type Bismuth Ⅲa perihilar cholangiocarcinoma was planned to perform perihilar hepatectomy combined with right hepatectomy. The imaging evaluation showed that the volume of reserved liver lobe accounted for 27% of the total liver volume. The serum total bilirubin was 256 μmol/L when admitted and decreased to 118 μmol/L on the day 5 after percutaneous transhepatic biliary drainage. The right anterior and right posterior branches of PVE was performed. SPECT 99Tc m-GSA examination was performed on the day 37 after PVE. The morphological liver volume was 559 mL of planned reserved lobe and 1 461 mL of the whole liver. The planned morphological liver volume resection rate was 61.7%. ICG-K was 0.12/minutes of the whole liver, and 0.04/minutes of planned reserved lobe. The functional liver volume was 134 mL of planned reserved lobe and 309 mL of the whole liver. The planned resection rate of functional liver volume was 56.6%. The GSA-K was 0.20/minutes of the whole liver and 0.09/minutes of planned reserved lobe. R 0 resection was achieved in perihilar hepatectomy combined with right hepatectomy and no liver failure occurred. The survival time of patients was 11 months. Conclusion:Dynamic SPECT 99Tc m-GSA scintigraphy can effectively evaluate the regional function of the reserved liver lobe in patients with perihilar cholangiocarcinoma after PVE.

Objective:To observe the expression levels of glial fibrillary acidic protein (GFAP), β-tubulin Ⅲ and synaptophsin, and explore the role of tripartite synapse in the mechanism of central nervous system (CNS) injury and the neuroprotective effect of chondroitin sulfate (CS).Methods:One month old clean grade, 48 female Sparague-Dawley rats and 48 male Sparague-Dawley rats, were randomly divided into 8 groups according to body weight (90 - 120 g) by random number table method, with 12 rats in each group, half male and half female. These rats were fed with water containing different concentrations of sodium fluoride (NaF) [ < 0.5 mg/L (control, CN), 10.0 mg/L (low dose fluoride, LF) and 50.0 mg/L (high dose fluoride, HF)]. Some rats were fed directly for 185 days (CN, LF and HF groups). In addition, rats of CN + normal saline (NS), LF + NS, HF + NS groups and LF + CS, HF + CS groups, were intraperitoneally injected with NS or 0.66 mg/kg CS for 5 consecutive days after 180 days of feeding. After the experiment, the pathological changes of hippocampal CA4 of brain tissue in each group were observed by hematoxylin eosin staining under light microscope, and the expression and distribution of GFAP, β-tubulin Ⅲ and synaptophsin in hippocampal CA4 of rats were detected by immunohistochemistry, the expression of GFAP, β-tubulin Ⅲ and synaptophsin at protein level in hippocampus of rats were detected by Western blotting.Results:Under light microscope, eosinophilic change, loss and irregular arrangement of neuron in the hippocampal CA4 were observed in LF, HF, LF + NS and HF + NS groups. The morphology of LF + CS and HF + CS groups was not significantly changed compared with CN group, but was significant changed compared with LF, HF, LF + NS and HF + NS groups. Immunohistochemical results showed that the rates of positive area of GFAP, β-tubulin Ⅲ and synaptophsin in female and male rats in LF and HF groups were significantly decreased than those in CN group ( P < 0.05); the positive area rates of female and male rats in LF + CS and HF + CS groups were higher than those in LF and HF groups, respectively ( P < 0.05). Western blotting results showed that the proten expression levels of GFAP, β-tubulin Ⅲ and synaptophsin of female and male rats in LF and HF groups (LF group: 0.90 ± 0.09, 0.82 ± 0.08, 1.43 ± 0.14, 0.92 ± 0.02, 1.21 ± 0.15, 0.87 ± 0.02, HF group: 0.58 ± 0.14, 0.73 ± 0.03, 0.63 ± 0.06, 0.67 ± 0.03, 0.87 ± 0.04, 0.70 ± 0.05) were lower than those in CN group (1.24 ± 0.08, 1.09 ± 0.10, 2.64 ± 0.30, 1.54 ± 0.09, 1.72 ± 0.10, 1.13 ± 0.06, P < 0.05). Conclusions:The tripartite synapse and extracellular matrix may take part in pathogenesis of the damages of CNS results from chronic fluorosis; CS may reduce the injury to a certain extent.

Objective To study the mechanism of central nervous system (CNS) injury in chronic fluorosis and the neuroprotective effect of chondroitin sulfate (CS).Methods Forty-eight female Sprague-Dawley rats weighting 90-120 g were divided into 8 groups according to body weight by random number table,6 rats in each group:control group,drinking tap water freely;low dose and high dose fluoride groups,freely drinking tap water with fluoride content of 10 and 50 mg/L,respectively;control + normal saline (NS),low dose fluoride + NS,and high dose fluoride + NS groups,each group was fed for 180 d,and treated with intraperitoneal injection of 0.66 mg/kg NS for 5 d (once a day);low dose fluoride + CS and high dose fluoride + CS groups,each group was fed for 180 d,0.66 mg/kg CS was injected intraperitoneally for 5 d (once a day).All groups were fed standard nutritive animal feed for 185 d and dissected for brain tissue.The pathologic change was observed after hematoxylin-eosin (HE)staining;the expression levels of phosphorylated extracellular signal-regulated protein kinase 1/2 (phospho-Erk1/2)and glutamate receptors 1,2 (GluR1,GluR2) in the brain cortex were detected by immunohistochemistry;the protein levels of Erk1/2,phospho-Erk1/2,GluR1,and GluR2 in the brain cortex were detected by Western blotting.Results Brain cortex of all rats in the fluoride groups showed eosinophilic degeneration,loss and disordered arrangement of neurons,and the brain morphological changes in each fluoride + CS groups were significantly improved compared with those in the fluoride groups.Immunohistochemistry results showed that compared with the control group [(0.44 ± 0.09)％,(1.49 ± 0.05)％,(2.51 ± 0.54)％],the expression levels of phospho-Erk1/2 [(1.47 ±0.09)％,(1.03 ± 0.05)％],and GluR2 [(2.37 ± 0.06)％,(3.38 ± 0.12)％] in the low dose and high dose fluoride groups were increased,and the expression levels of GluR1 [(1.49 ± 0.02)％,(0.99 ± 0.19)％] were decreased (P ＜ 0.05).Western blotting results showed that compared with the control group (1.00 ± 0.12,1.76 ± 0.33),the protein levels of Erk1/2 (3.10 ± 0.76,1.99 ± 0.01) and phospho-Erk1/2 (3.27 ± 0.25,2.67 ± 0.05) in low dose and high dose fluoride groups were significantly increased (P ＜ 0.05);compared with low dose fluoride group,the protein levels of Erk1/2,and phospho-Erk1/2 (1.30 ± 0.31,2.20 ± 0.34) in low dose fluoride + CS group decreased significantly (P ＜0.05).Compared with control group (1.86 ± 0.47,1.17 ± 0.27),the protein levels of GluR1 (1.09 ± 0.26,0.61 ± 0.14) in low dose and high dose fluoride groups decreased significantly,while the protein level of GluR2 (1.99 ± 0.42,3.38 ±0.27) increased significantly (P ＜ 0.05);compared with low dose and high dose fluoride groups,the protein levels of GluR2 in low dose fluoride + CS and high dose fluoride + CS groups (1.53 ± 0.41,2.65 ± 0.32) decreased significantly (P ＜ 0.05).The protein level of phospho-Erk1/2 was negatively correlated with GluR1 protein level (r =-0.975,-0.991,P ＜ 0.05) in low dose and high dose fluoride groups,and it was positively correlated with the protein level of GluR2 (r =0.986,0.993,P ＜ 0.05).Conclusion The CNS injury caused by chronic fluorosis may be related to GluR1 and GluR2 activated Erk1/2 signaling pathway,and CS has certain protection to the injury.

Objective To investigate the effect of vitamin D on platelet reactivity after combined treatment with aspirin and clopidogrel in elderly patients with ischemic stroke??Methods A total of 190 elderly patients with ischemic stroke treated with aspirin and clopidogrel in Beijing Bo′ai Hospital from June 2017 to August 2018 were enrolled in this study??Venous blood was collected for platelet aggregation rate,25?hydroxyvitamin D[25(OH)D] and clinical biochemical indexes during 1～2 weeks??According to 25 (OH) D quartile,the patients were further divided into Q1(≤7??18 μg／L) group ( n＝50),Q2: (＞7??18－≤9??39 μg／L) group (n＝50),Q3: (＞9??39－≤13??74 μg／L) group (50),Q4: (＞13??74 μg／L) (n＝40)??In order to evaluate the effect of calcitriol on platelet aggregation,platelet rich plasma ( PRP) in healthy group (15 cases) and clopidogrel resistance group (15 cases) were treated with calcitriol (10 nmol／L) and saline (37℃ pretreatment for 5 minutes),respectively,and to compare the difference of maximum platelet aggregation rate induced by ADP between the two treatments??Results There were significant differences in ADP? induced maximum platelet aggregation rate ( MPAR) (( 49??36 ± 23??34)%,( 48??80 ± 20??90)%, ( 37??02 ±18??24)%,(36??02± 14??46)%, F＝ 3??426, P＝ 0??018) and clopidogrel resistance ( CR)／ clopidogrel sensitive (CS) ratio (30／20,24／26,15／35,10／30,χ2＝15??119,P＝0??002) among the vitamin D quartiles (increasing)??Moreover, the MPAR and CR showed a decreasing trend with the increase of vitamin D concentration??Logistic regression analysis showed that serum 25( OH) D level was an independent inhibited factor for clopidogrel resistance in elderly patients with ischemic stroke ( Q4 vs Q1, OR＝0??699,95%CI 0??582～0??838,P＜0??001; Q3 vs Q1,OR＝0??848,95%CI 0??755－0??953,P＝0??006)??In vitro,compared with physiological saline,the aggregation rates of platelet in healthy group and CR group decreased after calcitriol pretreatment,and the difference was statistically significant ( healthy group: ( 69??8 ± 12??7 )% vs ( 58??6 ±11??5)%,t＝12??13,P＜0??001;CR group: ( 65??5 ± 8??3)% vs ( 56??3 ± 7??6)%, t＝11??48, P ＜0??001)??Conclusion Vitamin D reduces the high residual platelet reactivity after antiplatelet therapy??Further study is needed to determine whether vitamin D supplementation may improve the efficacy of clopidogrel??

Objective To explore the influences of protein kinase Cβ (PKC3) inhibitor LY333531 on oxidative injury and apoptosis of SH-SY5Y cells induced by fluorosis.Methods The SH-SY5Y cell model of fluorosis was established,and the experiment was divided into three groups:control group [0.0 mmol/L sodium fluoride (NaF) and 0.0 μmol/L LY333531],the fluoride group (0.5 mmol/L NaF and 0.0 μmol/L LY333531),and the PKCβ inhibitor group (0.5 mmol/L NaF and 0.2 μmol/L LY333531),n =3.Flow cytometry was used to detect the changes of reactive oxygen species (ROS) and apoptosis rate,fluorescent probe technique was used to detect mitochondrial membrane potential after each group for 48 h.Results Compared with the control group [(3.32 ± 0.29) × 103,0.60 ± 0.09,(7.58 ± 1.20)％],the level of ROS [(5.99 ± 0.32) × 103] was increased,mitochondrial membrane potential (0.28 ± 0.06) was decreased,and the apoptosis rate [(18.00 ± 2.32)％] was increased in the fluoride group (all P ＜ 0.05);compared with the fluoride group,the level of ROS [(5.12 ± 0.25) × 103] was decreased,mitochondrial membrane potential (0.42 ± 0.03) was increased,and the apoptosis rate [(11.79 ± 0.70)％] was decreased in the PKCβ inhibitor group (all P ＜ 0.05).Conclusions Excess fluoride could cause oxidative damage and apoptosis in cells.PKC3 inhibitor LY333531 has a protective effect in oxidative damage and apoptosis by fluorosis.