Objective:To develop radiomics score (RS) based on 18F-FDG PET/CT, and construct the machine learning model combining clinical and other relevant factors for personalized prediction of 2-year event-free survival (2-EFS) in patients with diffuse large B-cell lymphoma (DLBCL), and to perform interpretability analysis of the model. Methods:A total of 91 patients (49 males, 42 females; age (57.8±12.8) years) with pathologically confirmed DLBCL from December 2017 to December 2020 at the First Hospital of Shanxi Medical University were retrospectively analyzed. According to the ratio of 7∶3, patients were randomly divided into training set ( n=63) and test set ( n=28), and divided into non-progression group and progression group according to the follow-up results. The whole-body PET semi-quantitative parameters were calculated from the PET/CT images before treatment, and 328 radiomics features were extracted from the largest target lesions of patients. The least absolute shrinkage and selection operator (LASSO) was used to develop the RS. Clinical and PET characteristic difference analysis was performed through χ2 test and Mann-Whitney U test. Extreme gradient boosting (XGBoost) models were constructed based on clinical, PET radiomics features and RS, and the prediction efficiency of each model was evaluated by ROC AUC. The model interpretability was analyzed by using shapely additive explanation (SHAP). Results:Of all patients, 32 had disease progression and 59 did not. There were no significant differences in baseline characteristics between the training set and the test set ( χ2 values: 0.06-1.84, U values: 665.00-763.00, all P>0.05). The comparison between the progression group and non-progression group in the training set showed statistical differences in the international prognostic index (IPI) score ( χ2=4.87, P=0.027), myelocytomatosis viral oncogene (MYC) protein expression ( χ2=4.29, P=0.038), and metabolic tumor volume (MTV; U=307.00, P=0.038). Seven radiomics features were screened by LASSO. Among XGBoost models with different feature combinations, IPI score, MYC protein expression, MTV combined with RS had the highest predictive efficiency (training set: AUC=0.73; test set: AUC=0.70). Through SHAP analysis, RS was the most predictive feature in the optimal model. Conclusion:The machine learning integrated model of IPI score, MYC protein expression and MTV combined with RS can effectively predict the prognosis of DLBCL patients, and baseline 18F-FDG PET/CT radiomics can be used as a potential means to evaluate the prognosis of DLBCL patients.

Objective:A C57/BL6 mouse model of traumatic temporomandibular joint ankylosis (TTMJA) was established through composite trauma to lay the foundation for studying the pathophysiology of TTMJA.Methods:This study was conducted from January 2024 to February 2025. Forty-two 4-weeks old C57/BL6 mice, numbered 1 to 42, are randomly assigned to a control group ( n=21) and an experimental group ( n=21) using a computer-generated random number sequence. The experimental group undergoes modeling surgery on the left temporomandibular joint (TMJ), while the control group is routinely raised without special treatment. At 12 weeks post-surgery, the TMJ complex of both groups is assessed via body weight and mouth opening measurements, gross observation, micro-CT, and histological staining to evaluate model establishment. Results:At 12 weeks post-operation, in the experimental group, the body weight of mice [(27.75±1.08) g] did not show a significant difference compared with that of the control group [(30.80±0.29) g]( t=0.54, P=0.610). The maximum vertical passive mouth opening [(1.70±0.26) mm] in the experimental group was significantly lower than that in the control group [(3.43±0.21) mm]( t=8.92, P<0.001). Gross observation indicated that the right TMJ structure of the experimental-group mice was normal, while irregular hyperplasia occurred in the left TMJ complex. Micro-CT revealed that at 12 weeks post-operation, the right joint structure of the experimental-group mice was normal, with regular condyles and glenoid fossae. On the left side, a large amount of bone hyperplasia occurred on the lateral side of the joint in the condyles and glenoid fossae, forming two irregular bone masses, and there was an uncalcified radiolucent zone between the bone masses. In histological staining, no new cartilage or bone tissue was observed in the left joint space of the control-group mice, and the articular disc structure was normal. In the experimental-group mice, obvious new cartilage and calcified bone tissue were visible on the lateral side of the left joint space. A bone bridge was formed between the condyles and glenoid fossae, the articular disc structure disappeared, and bony ankylosis occurred. Conclusions:In this experiment, a TTMJA model of C57/BL6 mice was initially established by removing the articular disc and damaging part of the fibrous cartilage of the glenoid fossae and condyles, providing an experimental platform for further research on the pathogenesis of TTMJA.

Objective:To develop radiomics score (RS) based on 18F-FDG PET/CT, and construct the machine learning model combining clinical and other relevant factors for personalized prediction of 2-year event-free survival (2-EFS) in patients with diffuse large B-cell lymphoma (DLBCL), and to perform interpretability analysis of the model. Methods:A total of 91 patients (49 males, 42 females; age (57.8±12.8) years) with pathologically confirmed DLBCL from December 2017 to December 2020 at the First Hospital of Shanxi Medical University were retrospectively analyzed. According to the ratio of 7∶3, patients were randomly divided into training set ( n=63) and test set ( n=28), and divided into non-progression group and progression group according to the follow-up results. The whole-body PET semi-quantitative parameters were calculated from the PET/CT images before treatment, and 328 radiomics features were extracted from the largest target lesions of patients. The least absolute shrinkage and selection operator (LASSO) was used to develop the RS. Clinical and PET characteristic difference analysis was performed through χ2 test and Mann-Whitney U test. Extreme gradient boosting (XGBoost) models were constructed based on clinical, PET radiomics features and RS, and the prediction efficiency of each model was evaluated by ROC AUC. The model interpretability was analyzed by using shapely additive explanation (SHAP). Results:Of all patients, 32 had disease progression and 59 did not. There were no significant differences in baseline characteristics between the training set and the test set ( χ2 values: 0.06-1.84, U values: 665.00-763.00, all P>0.05). The comparison between the progression group and non-progression group in the training set showed statistical differences in the international prognostic index (IPI) score ( χ2=4.87, P=0.027), myelocytomatosis viral oncogene (MYC) protein expression ( χ2=4.29, P=0.038), and metabolic tumor volume (MTV; U=307.00, P=0.038). Seven radiomics features were screened by LASSO. Among XGBoost models with different feature combinations, IPI score, MYC protein expression, MTV combined with RS had the highest predictive efficiency (training set: AUC=0.73; test set: AUC=0.70). Through SHAP analysis, RS was the most predictive feature in the optimal model. Conclusion:The machine learning integrated model of IPI score, MYC protein expression and MTV combined with RS can effectively predict the prognosis of DLBCL patients, and baseline 18F-FDG PET/CT radiomics can be used as a potential means to evaluate the prognosis of DLBCL patients.

Objective:A C57/BL6 mouse model of traumatic temporomandibular joint ankylosis (TTMJA) was established through composite trauma to lay the foundation for studying the pathophysiology of TTMJA.Methods:This study was conducted from January 2024 to February 2025. Forty-two 4-weeks old C57/BL6 mice, numbered 1 to 42, are randomly assigned to a control group ( n=21) and an experimental group ( n=21) using a computer-generated random number sequence. The experimental group undergoes modeling surgery on the left temporomandibular joint (TMJ), while the control group is routinely raised without special treatment. At 12 weeks post-surgery, the TMJ complex of both groups is assessed via body weight and mouth opening measurements, gross observation, micro-CT, and histological staining to evaluate model establishment. Results:At 12 weeks post-operation, in the experimental group, the body weight of mice [(27.75±1.08) g] did not show a significant difference compared with that of the control group [(30.80±0.29) g]( t=0.54, P=0.610). The maximum vertical passive mouth opening [(1.70±0.26) mm] in the experimental group was significantly lower than that in the control group [(3.43±0.21) mm]( t=8.92, P<0.001). Gross observation indicated that the right TMJ structure of the experimental-group mice was normal, while irregular hyperplasia occurred in the left TMJ complex. Micro-CT revealed that at 12 weeks post-operation, the right joint structure of the experimental-group mice was normal, with regular condyles and glenoid fossae. On the left side, a large amount of bone hyperplasia occurred on the lateral side of the joint in the condyles and glenoid fossae, forming two irregular bone masses, and there was an uncalcified radiolucent zone between the bone masses. In histological staining, no new cartilage or bone tissue was observed in the left joint space of the control-group mice, and the articular disc structure was normal. In the experimental-group mice, obvious new cartilage and calcified bone tissue were visible on the lateral side of the left joint space. A bone bridge was formed between the condyles and glenoid fossae, the articular disc structure disappeared, and bony ankylosis occurred. Conclusions:In this experiment, a TTMJA model of C57/BL6 mice was initially established by removing the articular disc and damaging part of the fibrous cartilage of the glenoid fossae and condyles, providing an experimental platform for further research on the pathogenesis of TTMJA.

Objective:To prepare nanoprobes by using polydopamine (PDA) as a carrier which is modified with the sonosensitizer protoporphyrin Ⅸ (PpⅨ) and labeled with 131I, 99Tc m or 177Lu, and to explore the value of these new nanoprobes in diagnosis and combination therapy of breast cancer. Methods:PDA particles were synthesized by aqueous oxidation, and a layer of polyethylene glycol (PEG) and PpⅨ were modified on the surface to product PDA-PEG-PpⅨ. Then the nuclides 131I, 99Tc m and 177Lu were labeled on PDA, respectively, and the labeling yield and stability were determined. The cytotoxicity test was conducted by comparing the viabilities of 4T1 tumor cells in free 131I group and 131I-PDA-PEG-PpⅨ group. The 4T1 cells were divided into 7 groups according to different treatment methods: PDA-PEG-PpⅨ group, PDA-PEG-PpⅨ+ photothermal therapy (PTT) group, PDA-PEG-PpⅨ+ sonodynamic therapy (SDT) group, 131I-PDA-PEG-PpⅨ+ PTT group, 131I-PDA-PEG-PpⅨ+ SDT group, 131I-PDA-PEG-PpⅨ+ PTT+ SDT group (100 μg/ml PDA-PEG-PpⅨ, 925 kBq/ml 131I), and the control group (DMEM culture medium). The cell viabilities of those groups were compared to evaluate the therapeutic effect. 4T1 tumor bearing mouse models were established, then 99Tc m-PDA-PEG-PpⅨ was injected through the tail vein (29.6 MBq) or intratumorally (14.8 MBq) to perform gamma imaging. The independent-sample t test and one-way analysis of variance were used for data analysis. Results:The PDA particles were uniform in size, with a particle size of (160.0±1.5) nm. They had a good photothermal conversion effect. A characteristic peak consistent with PpⅨ (400 nm) appeared in the UV-Vis absorption spectrum of PDA-PEG-PpIX. In the cytotoxicity test, when the radioactivity was 1.850 or 3.700 or 7.400 MBq/ml, the cell viabilities of free 131I group and 131I-PDA-PEG-PpⅨ group were significantly different ((72.18±6.57)% vs (86.07±5.17)%, (59.31±9.06)% vs (80.85±4.21)%, (42.90±1.30)% vs (72.99±5.73)%; t values: 3.71, 4.82, 11.46, P values: 0.006, 0.001, <0.001). The 131I-PDA-PEG-PpⅨ+ PTT+ SDT combination therapy had a better killing effect on 4T1 tumor cells than the combination of 131I-PDA-PEG-PpⅨ+ PTT and 131I-PDA-PEG-PpⅨ+ SDT (cell viabilities: (10.09±2.50)% vs (16.04±2.63)%, (28.65±4.72)%; F=351.66, P<0.001). In vivo imaging showed that 99Tc m-PDA-PEG-PpⅨ was stable in mouse models and could be effectively enriched in tumors. Conclusions:A multifunctional nanoprobe based on PDA is successfully prepared. The radionuclide labeling method is simple and effective, with a good stability. 131I-PDA-PEG-PpⅨ can kill 4T1 cells efficiently. 99Tc m-PDA-PEG-PpⅨ has an obvious tumor concentration effect in mouse models.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Objective To assess the alterations of negative functional connectivity(FC),its relationship with clinical symptoms,and its potential value in schizophrenia(SZ).Methods Resting-state functional magnetic resonance imaging(rs-fMRI)data were acquired from patients with SZ and healthy controls(HC).For each participant,the whole brain image was first divided into 272 regions and then the FC between each pair of these regions was calculated using Pearson's correlation coefficient.Group-level negative FCs were identified using permutation test for each group.Each of the identified negative FCs was then compared between patients and controls to identify the altered negative FCs.Then,Spearman rank correlation was adopted to examine the relationship between the altered negative FCs and clinical variables.Finally,to evaluate the diagnostic value of negative FC in SZ,a multivariate pattern analysis(MVPA)was performed to distinguish between SZ and HC based on negative FCs.Results Ninety-one patients with SZ and 91 HC were included in this study,and 207 negative FCs in total were identified.Among the identified 207 negative FCs,12(constituting 5.80％of the total 207 negative FCs)were significantly altered in SZ compared with HC(Bonferroni correction,P<0.05),of which 11 were significantly decreased(i.e.,closer to 0)in SZ.The correlation analyses identified 2 significant associations-one was between a negative FC and the total score of the psychotic symptoms rating scales-auditory hallucinations(r=-0.24,P=0.02)and the other was between a negative FC and the weighted total score of the scale for the assessment of thought,language,and communication(r=0.26,P=0.01).Furthermore,the model for distinguishing between SZ and HC based on negative FCs achieved a classification accuracy of 72.6％that was significantly higher than chance-level accuracy(permutation test,P<0.001).Conclusion Negative FCs are altered in patients with SZ.Given that negative FCs are associated with clinical symptoms,thus they may serve as an imaging biomarker for assisting the diagnosis of SZ.

Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.

Objective:To investigate the diagnostic value of independent and combined subtests of the psychometric hepatic encephalopathy score (PHES) in mild hepatic encephalopathy(MHE) of patients with liver cirrhosis, so as to optimize the PHES.Methods:This was a prospective, multicenter and real-world study which was sponsored by the National Clinical Research Center of Infectious Diseases and the Portal Hypertension Consortium. Twenty-six hospitals from 13 provinces, autonomous regions and municipalities countrywide participated in this study, induding Tianjin Third Central Hospital, the Fourth People′s Hospital of Qinghai Province, the Second Affiliated Hospital of Baotou Medical College, the Third People′s Hospital of Taiyuan, the Fifth Medical Center of PLA General Hospital and so on. From October 2021 to February 2022, outpatients and hospitalized patients with liver cirrhosis and no obvious hepatic encephalopathy were consecutively enrolled. All patients received 5 PHES subjects in the same order: number connection test(NCT)-A, NCT-B, digit symbol test(DST), line tracing test(LTT) and serial dotting test(SDT), and the scores were calculated. The total score of PHES <-4 was taken as the cut-off value for diagnosing MHE. Compare the differences in each subtest between MHE group and non-MHE group. Receiver operating characteristic curve(ROC) and area under the curve(AUC) was performed to assess the diagnostic value of independent and combined subtests in MHE. Mann-Whitney U test and DeLong test were used for statistical analysis. Results:A total of 581 patients with liver cirrhosis were enrolled, 457 were diagnosed as MHE, and the incidence of MHE was 78.7%. The results of NCT-A, NCT-B, SDT, LTT, DST of MHE group were 60.00 s(47.01 s, 88.00 s), 90.45 s(69.32 s, 125.35 s), 74.00 s(57.65 s, 96.60 s), 74.72(60.00, 98.61) and 27.00(20.00, 36.00), respectively. Compared those of non-MHE group(34.00 s(29.15 s, 44.48 s), 50.00 s(40.98 s, 60.77 s), 50.00 s(41.07 s, 63.03 s), 46.23(38.55, 59.42) and 42.00(34.00, 50.75)), the differences were statistically significant( Z=12.37, 12.98, 9.83, 11.56, 10.66; all P<0.001). The AUC(95% confidence interval(95% CI)) of subtests of PHES NCT-B, NCT-A, LTT, DST and SDT alone in MHE diagnosis were 0.880(0.849 to 0.910), 0.862(0.828 to 0.896), 0.838(0.799 to 0.877), 0.812(0.772 to 0.851) and 0.788(0.743 to 0.832), respectively. The combination of 2 PHES subtests significantly increased the diagnostic efficacy. Among them the diagnostic efficacy of the combination of NCT-B and LTT was the best, the AUC(95% CI) was 0.924(0.902 to 0.947), the specificity was 91.9% and the sensitivity was 79.2%, which was better than a single PHES subtest (NCT-A, NCT-B, SDT, LTT and DST) and the combination of NCT-A and DST(AUC was 0.879, 95% CI0.847 to 0.910) which was recommended by guidelines on the management of hepatic encephalopathy in cirrhosis, the differences were statistically significant ( Z=3.78, 3.83, 5.57, 5.51, 5.38, 2.93; all P<0.01). Furthermore, compared between the combination of NCT-B and LTT and the combination of 3 subests of PHES, only the diagnostic efficacy of combination of NCT-B, LTT and SDT (AUC was 0.936, 95% CI 0.916 to 0.956) was better than that of the combination of NCT-B and LTT, the difference was statistically significant( Z=2.32, P=0.020). Conclusion:Based on the diagnostic efficacy and clinical feasibility of PHES subtests and their combinations, the combination of NCT-B and LTT is recommended for the diagnosis of MHE.

Objective:To compare the effect of different β values on the semi-quantitative accuracy and image quality of 68Ga-prostate specific membrane antigen (PSMA) PET/CT imaging after partial volume effect correction (PVC). Methods:In the model experiment, image reconstruction was carried out based on block sequential regularized expectation maximization algorithm (BSREMA) with the range of β values from 100 to 1 000. Recovery coefficient (RC), contrast recovery (CR) and background variability (BV) were measured to evaluate semi-quantitative accuracy and image quality. In the clinical study, image data of 21 prostate cancer patients (age 45-78 years) who underwent 68Ga-PSMA PET/CT examination in the First Hospital of Shanxi Medical University from March 2019 to February 2020 were retrospectively collected. A total of 29 abdominal imaging positive lymph nodes were divided into the small lymph node group (diameter <10 mm; n=12) and the large lymph node group (10 mm≤diameter≤30 mm; n=17). SUV parameters including SUV max, SUV mean and peak of SUV (SUV peak) and the influence of different β values on the SUV parameters were evaluated. The signal to noise ratio (SNR) and subjective scores were used to evaluate image quality. Independent-sample t test, Kappa test and Pearson correlation analysis were used to analyze data. Results:The model experiment showed that CR, RC and BV decreased with the increase of β values. The image quality, image clarity, lesion significance, and total image scores given by nuclear medicine physicians showed strong consistency ( Kappa values: 0.65-0.87, P values: 0.026-0.043). The small lymph node group had the highest score (13 and 14) with β value of 600, while the large lymph node group had the highest score (13 and 14) with β value of 700. SNR of the two groups increased steadily within β values from 100 to 600 ( t values: 2.49-8.99, P values: 0.023-0.038). When the β value was higher than 600, SNR of the small lymph node group reached a plateau ( t values: 1.28-2.00, P values: 0.072-0.098), while the SNR of the large lymph node group continued to increase ( t values: 2.98-4.63, P values: 0.012-0.029). Before PVC, there were significant negative correlations between SUV parameters and β values ( r values: from -0.94 to -0.64, P values: 0.039-0.046). After PVC, it was found that SUV mean and SUV max still had significant negative correlation with β values ( r values: from -0.78 to -0.68, P values: 0.035-0.042), while the SUV peak showed no significant correlation with β values ( r values: -0.22, -0.28, P values: 0.069, 0.126). Conclusions:Based on subjective scores and semi-quantitative indicators, 68Ga-PSMA PET/CT is superior to select β values of 600 and 700 for image reconstruction based on BSREMA. The SUV peak of small lesions is stable after PVC and the clinical value should be explored in further.