OBJECTIVES: Multiple myeloma (MM) is a highly heterogeneous hematologic malignancy, with disease progression driven by cytogenetic abnormalities and a complex bone marrow microenvironment. This study aims to construct a prognostic model for MM based on transcriptomic data and lipid metabolism related genes (LRGs), and to identify potential drug targets for high-risk patients to support clinical decision-making. METHODS: In this study, 2 transcriptomic datasets covering 985 newly diagnosed MM patients were retrieved from the Gene Expression Omnibus (GEO) database. Univariate Cox regression and 101 machine learning algorithms were used for gene selection. An LRG-based prognostic model was constructed using Stepwise Cox (both directions) and random survival forest (RSF) algorithms. The association between the prognostic score and clinical events was evaluated, and model performance was assessed using time-dependent receiver operating characteristic (ROC) curves and the C-index. The added predictive value of combining prognostic scores with clinical variables and staging systems was also analyzed. Differentially expressed genes between high- and low-risk groups were identified using limma and clusterProfiler and subjected to pathway enrichment analysis. Drug sensitivity analysis was conducted using the Genomics of Drug Sensitivity in Cancer (GDSC) database and oncoPredict to identify potential therapeutic targets for high-risk patients. The functional role of key LRGs in the model was validated via in vitro cell experiments. RESULTS: An LRG-based prognostic model (LRG17) was successfully developed using transcriptomic data and machine learning. The model demonstrated robust predictive performance, with area under the curve (AUC) values of 0.962, 0.912, and 0.842 for 3-, 5-, and 7-year survival, respectively. Patients were stratified into high- and low-risk groups, with high-risk patients showing significantly shorter overall survival (OS) and event-free survival (EFS) (both P<0.001) and worse clinical profiles (e.g., lower albumin, higher β2-microglobulin and lactate dehydrogenase levels). Enrichment analysis revealed that high-risk patients were significantly enriched for pathways related to chromosome segregation and mitosis, whereas low-risk patients were enriched for immune response and immune cell activation pathways. Drug screening suggested that AURKA inhibitor BMS-754807 and FGFR3 inhibitor I-BET-762 may be more effective in high-risk patients. Functional assays demonstrated that silencing of key LRG PLA2G4A significantly inhibited cell viability and induced apoptosis. CONCLUSIONS LRGs serve as promising biomarkers for prognosis prediction and risk stratification in MM. The overexpression of chromosomal instability-related and high-risk genetic event-associated genes in high-risk patients may explain their poorer outcomes. Given the observed resistance to bortezomib and lenalidomide in high-risk patients, combination therapies involving BMS-754807 or I-BET-762 may represent effective alternatives.
Humans ; Multiple Myeloma/mortality* ; Prognosis ; Lipid Metabolism/genetics* ; Transcriptome ; Machine Learning ; Male ; Female ; Gene Expression Profiling ; Algorithms

AIM: To assess the clinical efficacy of visual therapy in children with abnormal visual functions and asthenopia.METHODS: Retrospective case study. The data of 57 patients(114 eyes), aged 8.25±1.94 years, who underwent visual training at the optometry center of Xi'an Children's Hospital between January 2022 and April 2023, were collected. Patient assessments before and after training included refractive errors, a visual fatigue scale questionnaire, and visual function tests. These tests included the Worth 4 Dot for binocular vision, the Von Graefe method for measuring latent strabismus at distance and near, the gradient method for assessing the accommodative convergence/accommodation(AC/A)ratio, the push-up test for convergence near point, the negative lens method for amplitude of accommodation, the cross-cylinder test for accommodative response, and the flipper test for accommodative flexibility. Training programs were tailored based on the initial assessments of visual function and asthenopia. Comparisons were made between pre-training, 1 and 3 mo post-training evaluations.RESULTS: At baseline and 1 mo post-training, the visual fatigue scores were 26.00±6.77 and 19.57±8.90, respectively(P<0.05). Significant enhancements were observed in near phoria, convergence near point, and accommodative amplitude in both eyes, both negative relative accommodation(NRA)and positive relative accommodation(PRA), as well as accommodative flexibility in both eyes at 1 mo after therapy(all P<0.05), while no significant changes were found in distance phoria or accommodative response(all P>0.05). Furthermore, no significant differences were noted in the binocular amplitude of accommodation, NRA, PRA, and near phoria between 1 and 3 mo after training(all P>0.05). The visual function parameters of 30 patients with low myopia(SE: -1.99±1.22 D), 3 patients with low hyperopia(SE: +1.01±0.13 D)and 24 patients with emmetropia(SE: +0.25±0.11 D)were not statistically significant before training and at 1 mo after training(all P>0.05). Certain visual functions significantly improved at 1 mo after training, and most had returned normal by 3 mo.CONCLUSION: Vision therapy significantly enhances binocular visual function and alleviates symptoms of asthenopia in children with visual dysfunction. It is an effective, straightforward, and easily applicable method for relieving children's visual fatigue.

Pancreatic cancer,as a common malignant tumor of the digestive system,has a very low survival rate.In recent years,pancreatic cancer has made great progress in diagnostic methods,radiation therapy techniques,and systemic chemotherapy,but its therapeutic effect has not been considerably improved.As a new type of tumor research platform,organoids have made research progress in many fields.Constructing pancreatic cancer organoids is of great research value to guide the individualized treatment of pancreatic cancer.This article reviews the research and clinical application prospect of organoid model in radiotherapy of pancreatic cancer.

Organoids are in vitro-cultured three-dimensional (3D) miniature structures derived from human pluripotent stem cells or adult stem cells from healthy individuals or patients. Compared to traditional two-dimensional (2D) cell lines or animal models, organoids are regarded as more promising high-fidelity models, possessing unique advantages in terms of disease modeling, drug development, the establishment of living biobanks, and the exploration of personalized treatment. Over recent years, the rapid development of organoid technology has brought new hopes for innovating preclinical experimental tumor models and promoting clinical personalized diagnosis and treatment. This review is intended to introduce the development status and latest progress of organoids in the field of radiotherapy for tumors, explore the advantages and limitations of organoid models for cancer, and prospect for its application in the field of radiotherapy.

Objective:To evaluate the diagnostic efficacy and practicality of the Jaundice color card (JCard) as a screening tool for neonatal jaundice.Methods:Following the standards for reporting of diagnostic accuracy studies (STARD) statement, a multicenter prospective study was conducted in 9 hospitals in China from October 2019 to September 2021. A total of 845 newborns who were admitted to the hospital or outpatient department for liver function testing due to their own diseases. The inclusion criteria were a gestational age of ≥35 weeks, a birth weight of ≥2 000 g, and an age of ≤28 days. The neonate′s parents used the JCard to measure jaundice at the neonate′s cheek. Within 2 hours of the JCard measurement, transcutaneous bilirubin (TcB) was measured with a JH20-1B device and total serum bilirubin (TSB) was detected. The Pearson′s correlation analysis, Bland-Altman plots and the receiver operating characteristic (ROC) curve were used for statistic analysis.Results:Out of the 854 newborns, 445 were male and 409 were female; 46 were born at 35-36 weeks of gestational age and 808 were born at ≥37 weeks of gestational age. Additionally, 432 cases were aged 0-3 days, 236 cases were aged 4-7 days, and 186 cases were aged 8-28 days. The TSB level was (227.4±89.6) μmol/L, with a range of 23.7-717.0 μmol/L. The JCard level was (221.4±77.0) μmol/L and the TcB level was (252.5±76.0) μmol/L. Both the JCard and TcB values showed good correlation ( r=0.77 and 0.80, respectively) and agreements (96.0% (820/854) and 95.2% (813/854) of samples fell within the 95% limits of agreement, respectively) with TSB. The JCard value of 12 had a sensitivity of 0.93 and specificity of 0.75 for identifying a TSB ≥205.2?μmol/L, and a sensitivity of 1.00 and specificity of 0.35 for identifying a TSB ≥342.0?μmol/L. The TcB value of 205.2?μmol/L had a sensitivity of 0.97 and specificity of 0.60 for identifying TSB levels of 205.2 μmol/L, and a sensitivity of 1.00 and specificity of 0.26 for identifying TSB levels of 342.0 μmol/L. The areas under the ROC curve (AUC) of JCard for identifying TSB levels of 153.9, 205.2, 256.5, and 342.0 μmol/L were 0.96, 0.92, 0.83, and 0.83, respectively. The AUC of TcB were 0.94, 0.91, 0.86, and 0.87, respectively. There were both no significant differences between the AUC of JCard and TcB in identifying TSB levels of 153.9 and 205.2 μmol/L (both P>0.05). However, the AUC of JCard were both lower than those of TcB in identifying TSB levels of 256.5 and 342.0 μmol/L (both P<0.05). Conclusions:JCard can be used to classify different levels of bilirubin, but its diagnostic efficacy decreases with increasing bilirubin levels. When TSB level are ≤205.2 μmol/L, its diagnostic efficacy is equivalent to that of the JH20-1B. To prevent the misdiagnosis of severe jaundice, it is recommended that parents use a low JCard score, such as 12, to identify severe hyperbilirubinemia (TSB ≥342.0 μmol/L).

Objective:To observe the unfolding status of foldable acrylic intraocular lens (IOL) of different materials, designs and refractive powers implanted in the capsular bag during cataract surgery, and to investigate its influence on the IOL implantation procedure.Methods:An observational case series study was conducted.A total of 1 005 patients who underwent routine phacoemulsification and IOL implantation in Shaanxi Eye Hospital from February to August 2021 were enrolled.The status and unfolding time of the leading haptic, optical region, and trailing haptic of the IOL in the capsular bag and the surgeon were recorded in real-time intraoperative video.Of the 1 005 IOL implants, 681 were hydrophobic, 324 hydrophilic, 733 C-loop, 272 plate-haptic, 909 single-piece, 96 three-piece, 620 preloaded, and 385 non-preloaded.The differences in unconventional implantation factors and IOL unfolding time were compared.The factors influencing IOL implantation status were analyzed by multivariate logistic regression.Multivariate logistic regression was used to analyze the relevant factors affecting IOL implantation status.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Xi'an People's Hospital (Xi'an Fourth Hospital)(No.20200035). Written informed consent was obtained from each subject.Results:There were 14(1.4%) IOLs with unconventional leading haptic status during implantation, including 7 recurved, 4 folded, 2 twisted and 1 straightened.There were 101(10.0%) IOLs with unconventional trailing haptic status during implantation, including 49 stuck in the injector, 40 folded, 10 recurved and 2 broken.There were 22(2.2%) IOLs with overlapped leading and trailing haptic requiring additional separation.There were 4(0.4%) IOLs with reversed optical regions and 2(0.2%) with damaged optical regions.The occurrence rate of unconventional leading haptic status using C-loop IOL was higher than that using plate IOL, and the difference was statistically significant ( P<0.05). The occurrence rate of unconventional trailing haptic status using hydrophilic, non-preloaded, three-piece, and C-loop IOL was higher than that using hydrophobic, preloaded, single-piece, and plate IOL, respectively, and the differences were statistically significant ( χ2=9.100, 61.400, 81.885, 7.587; all at P<0.05). The 22(2.2%) IOLs with overlapped leading and trailing haptic were hydrophobic.The 4 (0.4%) IOLs with reversed optical region were non-preloaded.The results of multivariate logistic regression analysis showed that IOL material, loading method, design and surgeons were related to the unconventional trailing haptic status in implantation ( OR=9.894, 3.720, 6.810, 1.338; all at P<0.05). The average unfolding time of hydrophobic IOL was 26.12(21.21, 30.91)s, which was significantly longer than 3.03(2.16, 4.49)s of hydrophilic IOL ( Z=-25.603, P<0.05). The average unfolding time of C-loop IOL was 25.53(19.41, 30.25)s, which was significantly longer than 2.70(2.08, 3.69) s of plate IOL ( Z=-23.764, P<0.05). Conclusions:A variety of unconventional statuses of IOL can occur during implantation into the lens capsular bag.The use of hydrophobic, preloaded, single-piece, and plate IOLs can reduce the occurrence of unconventional status.The use of hydrophilic IOLs can reduce the overlap of leading and trailing haptic.The use of preloaded IOLs can reduce the occurrence of IOL optical region reversal.The use of hydrophilic and plate IOLs can shorten the operation time.

Objective:To assess the combination of conventional ultrasound with contrast-enhanced ultrasound(CEUS)in the diagnosis of urothelial carcinoma(UC)of the renal pelvis in elderly patients.Methods:Sixty-seven elderly patients with a histopathologic diagnosis of UC of the renal pelvis and surgically treated at our hospital between April 2015 and March 2023 were retrospectively analyzed.Characteristics of regular preoperative 2D ultrasound, color Doppler flow imaging(CDFI)and CEUS were examined.Results:Of 67 patients, 49(73.13%)were found to have localized lesions in the renal pelvis and renal calyces.Lesions in 53 patients(79.10%)could be clearly identified by conventional ultrasound, with 46(86.79%)being isoechoic or hypoechoic, and 7(13.21%)being hyperechoic.Analysis of tumor blood flow by CDFI found 22 cases(41.51%)with avascular lesions, 21(39.62%)with hypovascular lesions and 10(18.87%)with hypervascular lesions.The average value of the resistance index(RI)was 0.64.Enhancement was seen in 62 lesions(92.54%)by CEUS after injection of SonoVue.Compared with the cortex of the ipsilateral kidney, a slow enhancement pattern was observed in 46(74.19%), 14(22.58%)showed simultaneous enhancement, and 2(3.23%)showed fast enhancement.At peak enhancement, 43 lesions(69.35%)had hypo-enhancement, 10(16.13%)had iso-enhancement, and 9(14.52%)had hyper-enhancement, compared with the cortex.Concerning the homogeneity of enhancement, 16(25.81%)displayed heterogeneous enhancement, with tumor necrosis or hemorrhage, and 46(74.19%)had homogeneous enhancement.When the contrast agent washout rate was assessed, a fast washout pattern was observed in 53(85.48%), synchronous washout in 6(9.68%), and slow washout in 3(4.84%).Conclusions:UC of the renal pelvis mostly shows isoechoic and hypoechoic lesions on conventional ultrasound, avascular or hypo-vascular lesions on CDFI, and slow-in, fast-out and hypo-enhancement on CEUS, compared with the cortex.Conventional ultrasound combined with CEUS can help improve the diagnostic accuracy of UC of the renal pelvis.

Objective:Rapid assessment of the outcome after percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS) is an important clinical issue. In this study, an electrocardiogram (ECG) analysis method based on dynamic learning was proposed.Methods:A total of 203 patients with ACS after successful PCI were enrolled for prospective analysis at the Emergency Department of Qilu Hospital of Shandong University from April 2019 to December 2020. All patients were divided into group without ≥70% postoperative stenosis ( n=72) and group with ≥ 70% postoperative stenosis ( n=131) according to the presence of 70% or more stenosis after PCI. The clinical data of ACS patients were collected and analyzed by χ2 test, t-test, or Mann-Whitney test. ECGs were recorded before and 2 h after PCI, and were dynamically analyzed to generate cardiodynamicsgram (CDG) using dynamic learning. In the group without ≥ 70% postoperative stenosis, the model and CDG index for evaluating myocardial ischemia were obtained by training support vector machine (SVM) using 10 times 10-fold cross-validation. Results:There was no significant difference in clinical data between the two groups. The prediction accuracy and sensitivity of the support vector machine model for myocardial ischemia in group without≥70% postoperative stenosis were 73.61%, and 84.72% respectively. CDG transformed from disorderly to regular after PCI, and CDG index decreased significantly ( P<0.001): 90.28% (65) patients in group without≥70% postoperative stenosis, and 79.39% (104) patients in group with≥70% postoperative stenosis had lower CDG indexes than before PCI. Conclusions:In this study, CDG obtained by dynamic learning can intuitively and effectively evaluate the changes of myocardial ischemia before and after PCI, which is helpful to assist clinicians to formulate the next treatment plan.

The National Medical Products Administration has authorized sodium oligomannate for treating mild-to-moderate Alzheimer's disease.In this study,an LC-MS/MS method was developed and validated to quantitate sodium oligomannate in different biomatrices.The plasma pharmacokinetics,tissue distri-bution,and excretion of sodium oligomannate in Sprague-Dawley rats and beagle dogs were system-atically investigated.Despite its complicated structural composition,the absorption,distribution,metabolism,and excretion profiles of the oligosaccharides in sodium oligomannate of different sizes and terminal derivatives were indiscriminate.Sodium oligomannate mainly crossed the gastrointestinal epithelium through paracellular transport following oral administration,with very low oral bioavail-ability in rats(0.6％-1.6％)and dogs(4.5％-9.3％).Absorbed sodium oligomannate mainly resided in circulating body fluids in free form with minimal distribution into erythrocytes and major tissues.So-dium oligomannate could penetrate the blood-cerebrospinal fluid(CSF)barrier of rats,showing a con-stant area under the concentration-time curve ratio(CSF/plasma)of approximately 5％.The cumulative urinary excretion of sodium oligomannate was commensurate with its oral bioavailability,supporting that excretion was predominantly renal,whereas no obvious biliary secretion was observed following a single oral dose to bile duct-cannulated rats.Moreover,only 33.7％(male)and 26.3％(female)of the oral dose were recovered in the rat excreta within 96 h following a single oral administration,suggesting that the intestinal flora may have ingested a portion of unabsorbed sodium oligomannate as a nutrient.

Objective:To investigate the effect of psychological support during perithrombotic period on post-stroke depression (PSD) in patients with acute ischemic stroke (AIS).Methods:Patients with AIS received intravenous thrombolysis in the Affiliated Lianyungang Hospital of Xuzhou Medical University from January 1, 2021 to July 31, 2021 were enrolled prospectively. The intervention group received one-to-one individual psychological support therapy in the perithrombolytic period on the basis of receiving standard intravenous thrombolytic therapy. At 30 d after onset, Hamilton Depression Scale was used to assess whether PSD occurred. Multivariate logistic regression analysis was used to evaluate the independent influencing factor of PSD. Results:A total of 126 patients with AIS were enrolled, and 86 of them were male (68.25%). Their age was 63.65±10.46 years; 65 were in the intervention group and 61 were in the control group. The incidence of PSD in the intervention group was significantly lower than that in the control group (20.00% vs. 36.07%; χ2=4.049, P=0.044). Multivariate logistic regression analysis showed that psychological intervention (odds ratio [ OR] 0.333, 95% confidence interval [ CI] 0.132-0.838; P=0.020] was an independent protective factor for PSD, while ischemic heart disease ( OR 4.510, 95% CI 1.181-17.217; P=0.028), alcohol consumption ( OR 3.421, 95% CI 1.317-8.888; P=0.012), anticoagulation therapy ( OR 3.145, 95% CI 1.155-8.567; P=0.025) and modified Rankin Scale score before thrombolysis ( OR 1.627, 95% CI 1.142-2.317; P=0.007) were the independent risk factors for PSD. Conclusion:Perithrombolytic psychological support may reduce the incidence of PSD.