OBJECTIVE: To construct a predictive model for the reduction in methadone maintenance treatment (MMT) and evaluate the effects of different interventions and other clinical factors on methadone reduction using Shapley additive explanations (SHAP). METHODS: Two clinical trials of acupuncture for methadone reduction in MMT patients were analyzed, and the baseline data, MMT related information, intervention measures, the data related to dose-reduction outcomes were collected. The predictive model was constructed by means of 6 machine learning algorithms including support vector machine (SVM), K-nearest neighbors (KNN), logistic regression (LR), Naive Bayes (NB), random forest (RF) and categorical-boosting (CatBoost), and 2 integration methods, blending-ensemble method (Blending) and Stacking-ensemble method (Stacking). SHAP was employed for the interpretability analysis of the optimal model. RESULTS: A total of 251 MMT patients were included, 128 cases in the acupuncture group and 123 cases in the non-acupuncture group. CatBoost and Stacking performed optimally in the test set. CatBoost obtained an accuracy of 0.780 0±0.060 8, a precision of 0.500 0±0.120 0, a recall of 0.818 2±0.140 2, F1 score of 0.620 7±0.114 0, and receiver operating characteristic-area under curve (ROC-AUC) of 0.857 8±0.140 2 for the subjects. In MMT patients with acupuncture as an adjunctive therapy, the top 5 important features for methadone reduction, included intervention measures, body mass index (BMI), the duration of MMT, the history of opioid use and occupation; and SHAP values were 1.25, 0.36, 0.21, 0.19 and 0.12, respectively. The SHAP feature dependence plot showed that BMI, MMT duration and the history of opioid use presented a nonlinear negative correlation with the reduction effect. CONCLUSION In acupuncture as adjunctive therapy for methadone reduction, the clinical factors should be considered comprehensively; and the interpretable predictive model provides a scientific basis for it, which is conducive to the improvement of clinical strategy of acupuncture for methadone reduction and the development of personalized reduction scheme.
Humans ; Methadone/therapeutic use* ; Acupuncture Therapy ; Adult ; Female ; Male ; Machine Learning ; Middle Aged ; Opiate Substitution Treatment ; Young Adult

Neuropathic pain is frequently comorbidity with cognitive deficits. Neuralized1 (Neurl1)-mediated ubiquitination of CPEB3 in the hippocampus is critical in learning and memory. However, the role of Neurl1 in the cognitive impairment in neuropathic pain remains elusive. Herein, we found that lumbar 5 spinal nerve ligation (SNL) in male rat-induced neuropathic pain was followed by learning and memory deficits and LTP impairment in the hippocampus. The Neurl1 expression in the hippocampal CA1 was decreased after SNL. And this decrease paralleled the reduction of ubiquitinated-CPEB3 level and reduced production of GluA1 and GluA2. Overexpression of Neurl1 in the CA1 rescued cognitive deficits and LTP impairment, and reversed the reduction of ubiquitinated-CPEB3 level and the decrease of GluA1 and GluA2 production following SNL. Specific knockdown of Neurl1 or CPEB3 in bilateral hippocampal CA1 in naïve rats resulted in cognitive deficits and impairment of synaptic plasticity. The rescued cognitive function and synaptic plasticity by the treatment of overexpression of Neurl1 before SNL were counteracted by the knockdown of CPEB3 in the CA1. Collectively, the above results suggest that the downregulation of Neurl1 through reducing CPEB3 ubiquitination and, in turn, repressing GluA1 and GluA2 production and mediating synaptic plasticity impairment in hippocampal CA1 leads to the genesis of cognitive deficits in neuropathic pain.
Animals ; Male ; Neuralgia/metabolism* ; Rats ; Down-Regulation/physiology* ; Ubiquitination/physiology* ; Neuronal Plasticity/physiology* ; Rats, Sprague-Dawley ; CA1 Region, Hippocampal/metabolism* ; Cognitive Dysfunction/metabolism* ; RNA-Binding Proteins/metabolism* ; Receptors, AMPA/metabolism*

To effectively exploit the tumor microenvironment (TME), TME-responsive nanocarriers based on cascade reactions have received much attention. In this study, we designed a novel nanoparticle PB@SiO₂@MnO₂@P-Arg (PMP) to construct a cascade reaction nanoplatform. While using biosafety Prussian blue (PB) for photothermal therapy (PTT), this nanoplatform uses silica (SiO₂) as an intermediate layer to assemble Prussian blue and manganese dioxide (MnO₂) into a core-shell structure, which effectively enhances the response of the nanoplatform to TME and promotes the effect of chemodynamic therapy (CDT) resulting from glutathione (GSH) depletion and Fenton-like reaction. The released Mn²⁺ can also be used for magnetic resonance imaging (MRI). Through the cascade reaction, poly-l-arginine (P-Arg) coated on the surface of the nanoparticles can react with hydroxyl radical (•OH) obtained from the Fenton-like reaction to release nitric oxide (NO), which further reacts with O₂•^- to produce the more toxic peroxynitrite anion (ONOO^-). The photothermal effect of PB further enhances the effect of the cascade reaction while reducing the amount of heat required for treatment. In vitro and in vivo studies confirmed the antitumor effects of cascade reaction-based nanoplatforms in combined photothermal/chemodynamic/gas cancer therapies, providing new strategies for the design and fabrication of multifunctional nanoplatforms that integrate diagnostic and therapeutic functions, as well as the application of cascade reactions in multimodal synergistic therapy.

Objective:To investigate the value of intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) and texture analysis for predicting BRAF gene mutation in rectal cancer.Methods:The clinical diagnositic trial was conducted. The clinicopathological data of 36 rectal cancer patients who were admitted to the First People's Hospital of Shangqiu from January 2016 to June 2021 were collected. There were 28 males and 8 females, aged (50±4)years. All the 36 patients were confirmed by pathological examination. After genetic testing, 12 patients with BRAF mutant type of BRAF V600E mutation were allocated into the mutation group, and 24 patients with BRAF wild type were allocated into the non-mutation group. All patients underwent MRI scan before surgery, and IVIM related post-processing images were received by Function Tool post-processing software. Observation indicators: (1) consistency test between observers of IVIM para-meters and texture parameters; (2) comparison of IVIM parameters on MRI between the two groups; (3) comparison of texture parameters on MRI between the two groups; (4) diagnostic efficacy of IVIM and texture parameters. The intraclass correlation coefficient (ICC) was used to evaluate the consistency between observers, with ICC >0.80 as good consistency. The average values of para-meters with ICC >0.80 were included for further analysis. Measurement data with normal distribu-tion were represented as Mean± SD, and comparison between groups was analyzed by the indepen-dent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was analyzed by the chi-square test. Comparison of ordinal data was analyzed by the non-parameter rank sum test. The texture parameters were combined using the Logistic regression model. Receiver operating charac-teristic curve was used to analyze the predictive performance and calculate the sensitivity and specificity. Results:(1) Consistency test between observers of IVIM parameters and texture parameters: the ICCs between two observers of IVIM parameters including apparent diffusion coefficient, diffusion related coefficient, perfusion-related diffusion coefficient and perfusion-related parameter were 0.91, 0.90, 0.91, 0.89, respectively. The ICCs of texture parameters including the minimum value, the maximum value, the 10th percentile and the 25th percentile between two observers were <0.80 while the ICCs of texture parameters including mean value, the 50th percentile, the 75th percentile, the 90th percentile, energy, entropy, skewness and kurtosis between two observers were >0.80. (2) Comparison of IVIM parameters on MRI between the two groups: IVIM parameters of diffusion related coefficient and perfusion-related parameter on MRI were (0.70±0.13)×10 -3 mm 2/s and 0.39±0.30 for the mutation group, versus (0.79±0.12)×10 -3 mm 2/s and 0.17±0.10 for the non-mutation group, showing significant differences between the two groups ( t=-2.17, 2.46, P<0.05). (3) Comparison of texture parameters on MRI between the two groups: the texture parameters of mean value and energy on diffusion related coefficient image were 0.54±0.23 and 0.00(0.00,0.01) for the mutation group, versus 0.77±0.34 and 0.01(0.00,0.01) for the non-mutation group, showing significant differences between the two groups ( t=-2.12, Z=-1.35, P<0.05). (4) Diagnostic efficacy of IVIM and texture parameters: the areas under the curve (AUCs) of diffusion related coefficient, perfusion-related parameter, IVIM parameters combination, mean value of diffu-sion related coefficient image, energy value of diffusion related coefficient image, texture parameters combination were 0.69[95% confidence interval ( CI) as 0.52-0.84], 0.76(95% CI as 0.59-0.88), 0.79(95% CI as 0.62-0.91), 0.71(95% CI as 0.52-0.85), 0.79(95% CI as 0.62-0.91), 0.84(95% CI as 0.68-0.94), which were all lower than the AUC of IVIM and texture parameters combination as 0.92(95% CI as 0.79-0.99). Conclusions:IVIM parameters and texture parameters of MRI can non-invasively predict the mutation status of BRAF gene in rectal cancer. The combination of IVIM and texture parameters has a better predictive efficacy.

Objective: To assess the effect of percutaneous transluminal septal myocardial ablation (PTSMA) on mid- to long-term left ventricular diastolic function in patients with hypertrophic obstructive cardiomyopathy (HOCM) by real-time three-dimensional echocardiography (RT-3DE). Methods: A total of 46 HOCM patients who received 2DE and RT-3DE examination before and after (with the mean of 18.8 months) PTSMA were studied. The ratios of E/A and E/Ea were analyzed, RT-3DE was conducted to collect the images, to obtain 17-segmant volume-time curve and to calculate the parameters of rEDV, rESV, rSV and rPFR respectively. Results: The follow-up echocardiography in all 46 patients indicated that the ratio of E/Ea decreased after the operation (12.04 ± 3.29) vs (15.70 ± 5.68),P<0.001, the rSV of left ventricular anterior wall middle segment and anterior septal middle segment decreased after the operation,P<0.05, while the rPFR of anterior septal middle segment, rear septal middle segment and apical segment increased,P<0.05. Conclusion: PTSMA may improve local left ventricular diastolic function in HOCM patients, RT-3DE provides a new method and viewing angle for HOCM evaluation.

OBJECTIVETo characterize the role of tumor necrosis factor-α (TNF-α) and NF-κB play a role in macrophage-like THP-1 cells promoting coal tar pitch extract (CTPE)-induced tumorigenic transformation of human bronchial epithelial cells (BEAS-2B).

METHODSFrom passage 10, CTPE-induced BEAS-2B cells cocultured with THP-1 cells were treated with NF-κB inhibitor-Pyrrolidine dithiocarbamate (PDTC) every 3 passages and TNF-α antibody every passage. Alterations of cell cycle, karyotype and colony formation in soft agar of BEAS-2B cells at passages 20, indicative of tumorigenicity, were determined, respectively. In addition, mRNA and protein levels of TNF receptor associated factor2 (TRAF2) and Cyclin D1 in BEAS-2B cells were measured with Real Time-PCR and Western blot, respectively.

RESULTSThe percentages of S-phase BEAS-2B cells at passage 20 in PDTC group and TNF-α antibody group were (33.97±2.16)% and (34.29±2.04)% respectively, which were less than that in Co-culture+CTPE group of 20th passage [(44.46±0.83)%], P < 0.05; The number of cells with aneuploidy in 100 cells in 20th passage PDTC group and TNF-α antibody group were 40 and 37, and there were significantly different when comparing to that of 20th passage Co-culture+CTPE group (75); The number of colony formation and the rate of colony formation of BEAS-2B cells in soft agar at passage 20 in PDTC group were (15.17±2.48) and (1.51‰±0.25‰), (13.33±2.58)and (1.33‰±0.26‰) in TNF-α antibody group, which were less that those in 20th passage Co-culture+CTPE group [(172.33±12.09) and (17.23‰±1.20‰)], P < 0.05; at the same time, the mRNA and protein levels of TRAF2 and Cyclin D1 in BEAS-2B cells were decreased after PDTC and TNF-α antibody treatment.

CONCLUSIONTNF-α and NF-κB could play an important role in THP-1 cells promoting coal tar pitch extract-induced tumorigenic transformation of BEAS-2B cells by influencing the expression of TRAF2 and Cyclin D1.

Bronchi ; cytology ; Cell Line ; Cell Transformation, Neoplastic ; drug effects ; Coal Tar ; toxicity ; Cyclin D1 ; metabolism ; Epithelial Cells ; cytology ; Humans ; Macrophages ; cytology ; NF-kappa B ; metabolism ; TNF Receptor-Associated Factor 2 ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

Objective To investigate the risk factors for conversion of laparoscopic cholecystectomy (LC) to laparotomy.Methods In 1020 LC patients,36 patients with conversion of LC to laparotomy were chosen as the case group,108 patients with successful LC were chosen as the control group.Univariate analysis and Logistic multivariate regression model were used to analyze the risk factors for conversion of LC to laparotomy.Results Age ＞ 65 years (0R=3.234,95％ CI:0.532-6.853),course of disease ＞ 72h (OR =2.342,95％ CI:0.568 ～ 5.656),history of upper abdominal operation (OR =2.453,95％ CI:0.345-7.453),thickness of gallbladder wall ≥ 6 mm (OR =2.453,95％ CI:0.453-6.343),white bloodcell count ＞ 15.0 × 109/L (OR =4.532,95％ CI:0.535-8.329) were risk factors for conversion of LC to laparotomy.Conclusion Preoperative comprehensive evaluation the risk factors and selecting suitable program have important clinical significant in reducing the rate of conversion LC to laparotomy.

Objective To investigate the associated protein markers in urine of patients with chronic renal failure (CRF) based on surface enhanced laser desorption and ionization time of flight mass spectrometry (SELDI-TOF MS)technique.Methods Urine samples were taken from 150 CRF patients and 50 healthy people,and investigated by proteomic techniques with H4 gene chip.Results Compared to healthy group,141 different protein peaks were identified within the range of 1000 to 20 000 M/Z in the protein map of CRF group,whose differences were all significant (all P＜0.01).The decision tree model for CRF urine was constructed after bioinformation analysis to significantly differentiate between CRF and healthy group.The accuracy rate,sensitivity and specificity of the decision tree model were 96.0％,100.0％ and 94.7％ respectively.In CRF group and healthy group,the different protein peaks in urine were identified to probably be 17 proteins with reference to SwissProt database.Conclusions Candidate protein markers in urine are screened and prediction model of CRF urine is established.The markers are identified with the database which provides a more accurate prediction and solid evidence for early diagnosis of CRF.

father′s hypertension. Conclusion In addition to mother′s menses irregularity and father′s premature balding, father′s hypertension may also be an independent phenotype in families of women with PCOS.