Autonomic neural regulation in mediating the brain-bone axis: mechanisms and implications for regeneration under psychological stress.

Efficient regeneration of bone defects caused by disease or significant trauma is a major challenge in current medicine, which is particularly difficult yet significant under the emerging psychological stress in the modern society. Notably, the brain-bone axis has been proposed as a prominent new concept in recent years, among which autonomic nerves act as an essential and emerging skeletal pathophysiological factor related to psychological stress. Studies have established that sympathetic cues lead to impairment of bone homeostasis mainly through acting on mesenchymal stem cells (MSCs) and their derivatives with also affecting the hematopoietic stem cell (HSC)-lineage osteoclasts, and the autonomic neural regulation of stem cell lineages in bone is increasingly recognized to contribute to the bone degenerative disease, osteoporosis. This review summarizes the distribution characteristics of autonomic nerves in bone, introduces the regulatory effects and mechanisms of autonomic nerves on MSC and HSC lineages, and expounds the crucial role of autonomic neural regulation on bone physiology and pathology, which acts as a bridge between the brain and the bone. With the translational perspective, we further highlight the autonomic neural basis of psychological stress-induced bone loss and a series of pharmaceutical therapeutic strategies and implications toward bone regeneration. The summary of research progress in this field will add knowledge to the current landscape of inter-organ crosstalk and provide a medicinal basis for the achievement of clinical bone regeneration in the future.

[The application value of Gd-EOB-DTPA enhanced MRI based radiomics in the differential diagnosis of iso-or hyperintensity HCC and focal nodular hyperplasia in hepatobiliary phase].

Objective: To investigate the application value of Gd-EOB-DTPA enhanced MRI based radiomics model in the differential diagnosis of iso-or hyperintensity HCC and focal nodular hyperplasia (FNH) in hepatobiliary phase. Methods: A total of 88 patients with HCC or FNH confirmed by surgical or puncture pathology who underwent preoperative Gd-EOB-DTPA enhanced MRI (all lesions showed iso-or hyperintensity in hepatobiliary phase) between January 2015 and February 2023 in The First Affiliated Hospital of Soochow University and Nantong No.3 People's Hospital were retrospectively evaluated, which including 58 males and 30 females, aged [M(Q1, Q3)]56 (40, 67) years, including 61 patients with HCC and 27 patients with FNH. The included cases were divided into training (43 cases of HCC, 19 cases of FNH) and validation cohort (18 cases of HCC, 8 cases of FNH) in the ratio of 7∶3 using the random seeding method. A total of 1 781 radiomics features were extracted from Gd-EOB-DTPA enhanced MRI in the arterial, portal and hepatobiliary phases, respectively. The independent three phase models, combined three phases model and combined clinical-radiomics model was established using Auto-Encoder (AE) and Native Bayes (NB) classifier, respectively. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic performance of these models. DeLong test was used to compare the areas under curve (AUC). Results: In the validation cohort, the combined clinical-radiomics model had the highest AUC (AUC=0.938, 95%CI: 0.828-1.000). The AUC, accuracy, sensitivity, specificity of the clinical-radiomics combined model using AE classifier in the validation cohort were 0.896 (95%CI: 0.760-1.000), 88.5%, 88.9%, 87.5%. The AUC of the clinical-radiomics combined model using NB classifier in the validation cohort were 0.938 (95%CI: 0.828-1.000), 92.3%, 88.9%, 100.0%. Conclusion: Gd-EOB-DTPA enhanced MRI combined clinical-radiomics model has certain value in preoperative differentiation of iso-or hyperintensity in the hepatobiliary phase HCC and FNH, with a high accuracy, sensitivity and specificity.

[The value of machine learning models based on biparametric MRI for diagnosis of prostate cancer and clinically significant prostate cancer].

Objective: To evaluate the value of machine learning (ML) models based on biparametric magnetic resonance imaging (bpMRI) for diagnosis of prostate cancer (PCa) and clinically significant prostate cancer (csPCa). Methods: A total of 1 368 patients, aged from 30 to 92 (69.4±8.2) years, from 3 tertiary medical centers in Jiangsu Province were retrospectively collected from May 2015 to December 2020, including 412 cases of csPCa, 242 cases of clinically insignificant prostate cancer (ciPCa) and 714 cases of benign prostate lesions. The data of center 1 and center 2 were randomly divided into training cohort and internal testing cohort at a ratio of 7∶3 by random number sampling without replacement using Python Random package, and the data of center 3 were used as the independent external testing cohort. The training cohort includs 243 cases of csPCa, 135 cases of ciPCa and 384 cases of benign lesions, the internal testing cohort includs 104 cases of csPCa, 58 cases of ciPCa and 165 cases of benign lesions, and the external testing cohort includs 65 cases of csPCa, 49 cases of ciPCa and 165 cases of benign lesions. The radiomics features were extracted on T2-weighted imaging, diffusion-weighted imaging and apparent diffusion coefficient map, and optimal radiomics features were selected by using Pearson correlation coefficient method and analysis of variance. The ML models were built using two ML algorithms, including support vector machine and random forest (RF) and were further tested in the internal testing cohort and external testing cohort. Finally, the PI-RADS scores evaluated by the radiologists were adjusted by the ML models which had superior diagnostic performance, namely adjusted PI-RADS. The receiver operating characteristic (ROC) curves were used to evaluate the diagnostic performance of the ML models and PI-RADS. DeLong test was used to compare the areas under curve (AUC) of models with those of PI-RADS. Results: For PCa diagnosis, in internal testing cohort, the AUC of ML model using RF algorithm and PI-RADS were 0.869 (95%CI: 0.830-0.908) and 0.874 (95%CI: 0.836-0.913), respectively, and the difference between the model and PI-RADS did not reach to the statistical significance (P=0.793). In the external testing cohort, the AUC of model and PI-RADS were 0.845 (95%CI: 0.794-0.897) and 0.915 (95%CI: 0.880-0.951), respectively, and the difference was statistically significant (P=0.01). For csPCa diagnosis, the AUC of ML model using RF algorithm and PI-RADS were 0.874 (95%CI: 0.834-0.914) and 0.892 (95%CI: 0.857-0.927), respectively, in internal testing cohort, and the difference between the model and PI-RADS was not statistically significant (P=0.341). In the external testing cohort, the AUC of model and PI-RADS were 0.876 (95%CI: 0.831-0.920) and 0.884 (95%CI: 0.841-0.926), respectively, and the difference between the model and PI-RADS was not statistically significant (P=0.704). When PI-RADS assessment was adjusted with the assistance of ML models, the specificities increased from 63.0% to 80.0% in the internal testing cohort and from 92.7% to 93.3% in the external test group in diagnosing PCa. In diagnosing csPCa, the specificities increased from 52.5% to 72.6% in the internal testing cohort and from 75.2% to 79.9% in the external testing cohort. Conclusions: The ML models based on bpMRI showed comparable diagnostic performance to PI-RADS assessed by senior radiologists and achieved good generalization ability in both diagnosing PCa and csPCa. The specificities of the PI-RADS were improved by ML models.

RESOLVE-based radiomics in cervical cancer: improved image quality means better feature reproducibility?

AIM: To compare the reproducibility of apparent diffusion coefficient (ADC)-based radiomic features between readout-segmented echo-planar diffusion-weighted imaging (RESOLVE) and single-shot echo-planar diffusion-weighted imaging (SS-EPI DWI) in cervical cancer. MATERIALS AND METHODS: The RESOLVE and SS-EPI DWI images of 36 patients with histopathologically confirmed cervical cancer were collected retrospectively. Two observers independently delineated the whole tumour on RESOLVE and SS-EPI DWI, and then copied them to the corresponding ADC maps. Shape, first-order, and texture features were extracted from ADC maps in the original and filtered (Laplacian of Gaussian [LoG] and wavelet) images. Thereafter, 1,316 features were generated in each RESOLVE and SS-EPI DWI, respectively. The reproducibility of radiomic features was assessed using intraclass correlation coefficient (ICC). RESULTS: In the original images, RESOLVE showed 92.86%, 66.67%, and 86.67% of features with excellent reproducibility in shape, first-order, and texture features, while SS-EPI DWI showed 85.71%, 72.22%, and 60% of features with excellent reproducibility, respectively. In the LoG and wavelet filtered images, RESOLVE had 56.77% and 65.32% of features with excellent reproducibility and SS-EPI DWI had 44.95% and 61.96% of features with excellent reproducibility, respectively. CONCLUSION: Compared with SS-EPI DWI, the feature reproducibility of RESOLVE was better in cervical cancer, especially for texture features. The filtered images cannot improve the feature reproducibility compared with the original images for both SS-EPI DWI and RESOLVE.

[Safety and feasibility of stereotactic radiation therapy on porcine ventricular septum: a preliminary study].

Objective: To explore the safety and feasibility of stereotactic radiation therapy (SBRT) strategy for irradiating porcine ventricular septum, see if can provide a preliminary experimental evidence for clinical SBRT in patients with hypertrophic obstructive cardiomyopathy (HOCM). Methods: Five male pigs (39-49 kg, 6 months old) were used in this study. Pigs were irradiated at doses of 25 Gy (n=2) or 40 Gy (n=3). Delineation of the target volume was achieved under the guidance of 3-dimensional CT image reconstruction, and SBRT was then performed on defined target volume of porcine ventricular septum. Blood biomarkers, electrocardiogram and echocardiography parameters were monitored before and after SBRT. Pathological examination (HE staining, Masson staining) was performed on the target and non-target myocardium at 6 months post SBRT. Results: SBRT was successful and all animals survived to the designed study endpoint (6 months) after SBRT. Serum cardiac troponin T (cTnT) level was significantly higher than the baseline level at 1 day post SBRT, and reduced at 1 week after SBRT, but was still higher than the baseline level(P<0.05). Serum N-terminal pro-B type natriuretic peptide (NT-proBNP) was also significantly increased at 1 day post SBRT (P<0.05) and returned to baseline level at 1 week post SBRT. The serum NT-proBNP level was (249±78), (594±37) and (234±46) pg/ml, respectively, and the cTnT was (14±7), (240±40) and (46±34) pg/ml, respectively at baseline, 1 day and 1 week after SBRT in the 40 Gy dose group. The serum NT-proBNP level was (184±20), (451±49) and (209±36) pg/ml, respectively, the cTnT values ​​were (9±1), (176±29) and (89±27) pg/ml, respectively at baseline, 1 day and 1 week after SBRT in the 25 Gy dose group. Both NT-proBNP and cTnT values tended to be higher post SBRT in the 40 Gy dose group as compared with the 25 Gy dose group, but the difference was not statistically significant (P>0.05). The left ventricular ejection fraction and the left ventricular end-diastolic diameter remained unchanged before and after SBRT (P>0.05). The interventricular septum thickness showed a decreasing trend at 6 months after SBRT, but the difference was not statistically significant ((9.54±0.24) mm vs. (9.82±8.00) mm, P>0.05). The flow velocity of the left ventricular outflow tract, and the valve function and morphology were not affected by SBRT. At 6 months after SBRT, HE staining revealed necrosis in the irradiated target area of ​​the myocardium in the 40 Gy dose group and the 25 Gy dose group, and the degree of necrosis in the irradiated interventricular septum was more obvious in the 40 Gy dose group as compared with the 25 Gy group. The combined histological analysis of the two groups showed that the necrotic area of ​​the irradiated target area accounted for (26±9)% of the entire interventricular septum area, which was higher than that of the non-irradiated area (0) (P<0.05). There was no damage or necrosis of myocardial tissue outside the target irradiation area in both groups. The results of Masson staining showed that the percentage area of myocardial fibrosis was significantly higher in the irradiated target area than non-irradiated area ((12.6±5.3)% vs. (2.5±0.8)%, P<0.05). Conclusion: SBRT is safe and feasible for irradiating porcine ventricular septum.

[Effect of gender factor on the effective dose of oxycodone for inhibiting responses to laryngeal mask airway insertion in elderly patients undergoing ophthalmic surgery].

Objective: To evaluate the effect of gender factor on the effective dose of oxycodone for inhibiting responses to laryngeal mask airway (LMA) insertion in elderly patients undergoing ophthalmic surgery. Methods: From June to October 2021, 56 elderly patients, including 26 females and 30 males, aged from 65 to 80 (72±5) years, with a body mass index (BMI) of 18.5-24.9 kg/m2 and American Society of Anesthesiologists (ASA) physical status of Ⅰ or Ⅱ, who underwent elective ophthalmic surgery requiring LMA insertion in the Beijing Tongren Hospital affiliated to Capital Medical University were selected. Patients were divided into two groups according to gender: elderly female group and elderly male group. The modified Dixon sequential method was used. Oxycodone 0.10 mg/kg was injected intravenously in the first patient. Etomidate 0.2 mg/kg and cisatracurium 0.1 mg/kg were administrated 5 min later. After 3 min, the laryngeal mask was placed when the bispectral index (BIS) ≤60. The positive response to LMA insertion was defined as an increase in the maximum mean arterial pressure or the maximum heart rate>20% of the baseline value within 2 min after insertion. When the response to LMA insertion was positive, the dose of oxycodone was increased in the next patient, otherwise the dose was decreased, and the ratio of adjacent dose was 1.1. This process was repeated until the 7th turning point occurred. The half-maximal effective doses (ED50) and 95% confidence intervals (CI) of oxycodone for inhibiting laryngeal mask insertion were calculated and compared between the two groups. Meanwhile, the adverse reactions during anesthesia induction were observed. Results: All 26 patients in the elderly female group completed the test, but one patient in the elderly male group withdrew due to poor alignment of laryngeal mask, and finally 29 patients completed the study. There were 13 cases and 14 cases who had positive response to LMA insertion in the elderly female and male groups, respectively. The ED50 (95%CI) of oxycodone for inhibiting laryngeal mask insertion in the elderly male group was 0.096 (0.083-0.112) mg/kg, which was higher than that in the elderly female group [0.081 (0.073-0.098) mg/kg, P=0.008]. No adverse reactions such as choking cough, muscle tremor, hypoxemia, nausea, vomiting, reflux and aspiration occurred in 55 patients, except that one patient in the elderly female group had transient hypotension after induction, which improved after symptomatic treatment. Conclusion: The ED50 of oxycodone for inhibiting laryngeal mask insertion reaction in ophthalmic surgery is different in patients with different genders, which is 0.096 (0.083-0.112) mg/kg in the elderly male group and 0.081 (0.073-0.098) mg/kg in the elderly female group.

[Relationship between preoperative inflammatory indexes and prognosis of patients with rectal cancer and establishment of prognostic nomogram prediction model].

Objective: To compare the prognostic evaluation value of preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII) in rectal cancer patients. Nomogram survival prediction model based on inflammatory markers was constructed. Methods: The clinical and survival data of 585 patients with rectal cancer who underwent radical resection in the First Affiliated Hospital of Xi'an Jiao tong University from January 2013 to December 2016 were retrospectively analyzed. The optimal cut-off values of NLR, PLR, LMR, and SII were determined by the receiver operating characteristic (ROC) curve. The relationship between different NLR, PLR, LMR and SII levels and the clinic pathological characteristics of the rectal cancer patients were compared. Cox proportional risk model was used for univariate and multivariate regression analysis. Nomogram prediction models of overall survival (OS) and disease-free survival (DFS) of patients with rectal cancer were established by the R Language software. The internal validation and accuracy of the nomograms were determined by the calculation of concordance index (C-index). Calibration curve was used to evaluate nomograms' efficiency. Results: The optimal cut-off values of preoperative NLR, PLR, LMR and SII of OS for rectal cancer patients were 2.44, 134.88, 4.70 and 354.18, respectively. There was statistically significant difference in tumor differentiation degree between the low NLR group and the high NLR group (P<0.05), and there were statistically significant differences in T stage, N stage, TNM stage, tumor differentiation degree and preoperative carcinoembryonic antigen (CEA) level between the low PLR group and the high PLR group (P<0.05). There was statistically significant difference in tumor differentiation degree between the low LMR group and the high LMR group (P<0.05), and there were statistically significant differences in T stage, N stage, TNM stage, tumor differentiation degree and preoperative CEA level between the low SII group and the high SII group (P<0.05). The multivariate Cox regression analysis showed that the age (HR=2.221, 95%CI: 1.526-3.231), TNM stage (Ⅲ grade: HR=4.425, 95%CI: 1.848-10.596), grade of differentiation (HR=1.630, 95%CI: 1.074-2.474), SII level (HR=2.949, 95%CI: 1.799-4.835), and postoperative chemoradiotherapy (HR=2.123, 95%CI: 1.506-2.992) were independent risk factors for the OS of patients with rectal cancer. The age (HR=2.107, 95%CI: 1.535-2.893), TNM stage (Ⅲ grade, HR=2.850, 95%CI: 1.430-5.680), grade of differentiation (HR=1.681, 95%CI: 1.150-2.457), SII level (HR=2.309, 95%CI: 1.546-3.447), and postoperative chemoradiotherapy (HR=1.837, 95%CI: 1.369-2.464) were independent risk factors of the DFS of patients with rectal cancer. According to the OS and DFS nomograms predict models of rectal cancer patients established by multivariate COX regression analysis, the C-index were 0.786 and 0.746, respectively. The calibration curve of the nomograms showed high consistence of predict and actual curves. Conclusions: Preoperative NLR, PLR, LMR and SII levels are all correlated with the prognosis of rectal cancer patients, and the SII level is an independent prognostic risk factor for patients with rectal cancer. Preoperative SII level can complement with the age, TNM stage, differentiation degree and postoperative adjuvant chemoradiotherapy to accurately predict the prognosis of rectal cancer patients, which can provide reference and help for clinical decision.

[The prediction value of enhanced magnetic resonance imaging nomogram model for dual phenotype hepatocellular carcinoma].

Objective: To explore the value of enhanced magnetic resonance imaging nomogram model in the prediction of dual-phenotype hepatocellular carcinoma(DPHCC). Methods: Data of 116 patients of hepatocellular carcinoma (HCC) confirmed by postoperative pathology, who underwent preoperative enhanced MRI between January 2016 and March 2021 in the First Affiliated Hospital of Soochow University were retrospectively evaluated, of these, there are 87 males and 28 females, aged 30-79 (59±10) years, including 31 patients with DPHCC and 85 patients with non-DPHCC. The patients were randomly divided into training set(51 cases of non-DPHCC,19 cases of DPHCC)and validation set(34 cases of non-DPHCC, 12 cases of DPHCC) in a ratio of 6∶4, according to random number table,clinical and imaging characteristics of the two groups were compared. The statistically significant parameters were included in multivariate logistic regression to identify the independent predictors and for the establishment of the nomogram model. The receiver operating characteristic curves were used to evaluate the prediction ability of the models, the corrected curve was used to validate the model. Results: In the training group, the proportions of rim arterial phase hyperenhancement in the DPHCC was significantly higher than that of the non-DPHCC [47.4%(9/19)vs 7.8%(4/51),P<0.001]. Rim arterial phase hyper-enhancement and enhanced capsule were significant predictors for DPHCC[OR=10.17(1.70-60.80),0.17(0.03-0.93),all P<0.05]. In the training group, the area under curve (AUC), sensitivity and specificity of the nomogram were 0.888 (95%CI: 0.806-0.969), 78.9% and 86.3%. In the validation group, the above three indicators were 0.811(95%CI: 0.655-0.968), 75.0% and 82.4%. Conclusion: Enhanced MRI nomogram model has certain value in prediction of DPHCC, with high sensitivity and specificity.

Effects of early weaning on intestinal morphology, digestive enzyme activity, antioxidant status, and cytokine status in domestic pigeon squabs (Columba livia).

The aim of this study was to explore the effects of early weaning on growth performance, intestinal morphology, digestive enzyme activity, antioxidant status, and cytokine status in domestic pigeon squabs (Columba livia). The conclusion is based on body weight (BW) and average daily gain (ADG), length index and weight index of small intestine, small intestinal morphology, activity of digestive enzymes in duodenum content, the concentrations of jejunal antioxidant status and cytokines. A completely randomized design with 2 treatments, the control group (CON) and early weaning (EW) group, was utilized. Eight squabs per treatment were sampled at the age of 25 d. The results showed that early weaning reduced BW (P < 0.05), ADG (P < 0.05), ileac length index (P < 0.05), and weight index (P < 0.01). Compared with the CON group, small intestinal morphology was altered in the EW group. Ileac crypt depth (CD) increased significantly (P < 0.01). The villus area was decreased in the duodenum (P < 0.05), jejunum (P < 0.01), and ileum (P < 0.05). The ileac ratio of villus height to crypt depth (VCR) in the EW group was lower than the ileac ratio of villus height to VCR in the CON group (P < 0.01). The activity of trypsin (P < 0.05), sucrase (P < 0.01) and aminopeptidase-N (APN) (P < 0.01) in the duodenum was reduced. Jejunal malondialdehyde (MDA) (P < 0.01) was increased and total superoxide dismutase (T-SOD) (P < 0.01) was reduced significantly. Early weaning decreased the concentrations of interferon-γ (IFN-γ) (P < 0.01), interleukin-4 (IL-4) (P < 0.05) and interleukin-10 (IL-10) (P < 0.01) but induced significant upregulation of interleukin-2 (IL-2) (P < 0.05). In conclusion, our results suggested that early weaning did harm the BW and ADG, intestinal length index and weight index, intestinal morphology, activity of digestive enzymes, and antioxidant and cytokine status.

[Value of the application of enhanced CT radiomics and machine learning in preoperative prediction of microvascular invasion in hepatocellular carcinoma].

Objective: To explore the value of machine learning models in preoperative prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) based on dual-phase contrast-enhanced CT radiomics features. Methods: The data of 148 patients [106 males and 42 females, with an average age of (58±11) years] with HCC confirmed by pathology in the First Affiliated Hospital of Soochow University from January 2015 to May 2020 were retrospectively analyzed, including 88 cases of positive MVI and 60 cases of negative MVI. According to the ratio of 7∶3, the patients were randomly divided into the training and validation sets, respectively. The three-dimensional (3D) radiomics features of HCC in arterial phase (AP) and portal venous phase (PP) were extracted by MaZda software, and the optimal feature subset was obtained by combining three feature selection methods (FPM method) and Lasso regression. Then, six machine learning methods were used to build the prediction models. Receiver operating characteristic (ROC) curves were drawn to evaluate the prediction ability of the aforementioned models, and the area under the curve (AUC), accuracy, sensitivity and specificity were calculated. Results: Radiomics features of HCC in AP and PP were extracted by MaZda software, with 239 in each phase. There were 7 optimal features in AP and 14 optimal features in PP selected by FPM method and Lasso regression, respectively. The AUCs of decision tree, extreme gradient boosting, random forest, support vector machine (SVM), generalized linear model, and neural network based on the 7 optimal features in AP in the validation set were 0.736, 0.910, 0.913, 0.915, 0.897, 0.648, respectively. The SVM had the highest AUC in the validation set, with the accuracy, sensitivity and specificity of 95.35%, 95.83% and 94.74%, respectively. Likewise, the AUCs of machine learning models in prediction of MVI in HCC based on the 14 optimal features in PP in the validation set were 0.873, 0.876, 0.913, 0.859, 0.877, 0.834, respectively, and there were no significant differences (all P>0.05). The random forest had the highest AUC in the validation set, with the accuracy, sensitivity and specificity of 90.70%, 87.50% and 94.74%, respectively. Conclusion: Machine learning models based on dual-phase enhanced CT radiomics features can be used in preoperative prediction of MVI in HCC, particularly the SVM and random forest models have high prediction efficiency.

[Correlation between nUGT1A1 gene polymorphisms and adverse events of irinotecan plus S-1 for patients with recurrent or metastatic esophageal squamous cell carcinoma: a prospective, open-label, randomized controlled trial (ESWN 01)].

Objective: To investigate the correlation between UGT1A1 polymorphisms and the irinotecan plus S-1 regimen-induced toxicities in Chinese advanced esophageal squamous cell carcinoma (ESCC) patients. Methods: A total of 46 recurrent or metastatic ESCC patients selected from ESWN 01 trial were randomly assigned to irinotecan plus S-1 group [intravenous infusion of irinotecan (160 mg/m(2)) on day 1 and oral S-1 (80-120 mg) on days 1-10, repeated every 14 days]. Peripheral venous blood at baseline was collected and genomic DNA was extracted. The genetic polymorphisms of UGT1A1*6 and UGT1A1*28 were analyzed by polymerase chain reaction (PCR) amplification. Irinotecan plus S-1 regimen-induced toxicities of patients with different UGT1A1 polymorphisms were observed. The correlation between UGT1A1 polymorphisms and the adverse effects was analyzed. Results: Among the 46 patients, the numbers of UGT1A1*6 wild type genotype (GG), mutant heterozygote (GA) and mutant homozygote (AA) were 30, 15 and 1, while those with UGT1A1*28 wild type genotype (TA6/6), mutant heterozygote (TA6/7) and mutant homozygote (TA7/7) were 36, 8 and 2, respectively. Only one patient with UGT1A1*6 AA genotype occurred grade 3 diarrhea, while one of the 2 patients with UGT1A1*28 TA7/7 genotype occurred grade 4 diarrhea. No neutropenia was observed in the patient with UGT1A1*6 AA genotype, however, both of the two patients with UGT1A1*28 TA7/7 genotype occurred grade 3-4 neutropenia. Patients with UGT1A1*28 genetic polymorphism (TA 6/7 or TA7/7) had a higher response rate compared with wild-type TA6/6 carriers. (55.6% versus 26.5%). Conclusions: The homozygous genotype of UGT1A1*6 AA and UGT1A1*28 TA7/7 are rare (<5%) in Chinese ESCC population. Not all homozygous AA and TA7/7 carriers occur severe dose limited toxicities (DLT) when treated with irinotecan (160 mg/m(2)) plus S-1 regimen for 2 weeks. However, it's still necessary torigorously observe the occurrence of severe diarrhea and neutropenia in patients with UGT1A1*6 AA and UGT1A1*28 TA7/7 and adjust the dose timely.

[Early infantile epileptic encephalopathy caused by PACS2 gene variation: three cases report and literature review].

Objective: To explore the clinical features of three early-onset infantile epileptic encephalopathy (EIEE) patients with variations in phosphofurin acidic cluster sorting protein 2 (PACS2) gene and to review related literature. Methods: The clinical data and genetic features of three early infantile epileptic encephalopathy 66 (EIEE66) patients with a PACS2 gene variant diagnosed by the Department of Neurology, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, from January 2019 to January 2020 were retrospectively analyzed. A literature search with "PACS2 gene" "PACS2" "epileptic encephalopathy, early infantile, 66" and"early infantile epileptic encephalopathy 66" as key words was conducted at PubMed, China National Knowledge Infrastructure (CNKI), and Wanfang Data Knowledge Service Platform (up to July 2020). Case reports of patients with PACS2 gene variants and related clinical data were chosen and reviewed. Results: Case 1, a girl aged 2 years and 2 months was hospitalized because of repetitive seizures within more than two years and 6 convulsions within 2 days due to fever. The seizures occurred at the age of 7 days, characterized by focal seizures and generalized tonic-clonic seizures. Sometimes, the frequency of seizures increased with high fever. Regular treatment had not been implemented in the early stage, later seizures were controlled by valproic acid treatment. Case 2, a female 5 months of age, was admitted due to recurrent convulsions in nearly five months. Focal seizures occured at the age of 5 days. And the brain magnetic resonance imaging (MRI) confirmed abnormal cerebellar hemispheres and cerebellar vermis, as well as cerebellar dysplasia. Several antiepileptic drugs and ketogenic diet were ineffective in the early months, and later seizures were controlled with the treatment with levetiracetam and valproic acid. Case 3, a five-month-old girl, was admitted because of recurrent convulsions for nearly five months. At the age of 3 days, she had tonic seizures, and showed good response to levetiracetam and valproic acid. All the three cases were accompanied by development delay and dysmorphic facial appearance, and got seizure-free with the treatment with valproic acid. All copy-number variant analysis and trio whole exome sequencing revealed a recurrent heterozygous missense variant (c.625G>A) in PACS2 gene. No related reports were found in Chinese journals, while 4 reports were found in English literature, describing 17 patients in total. With these 3 patients included, 20 cases had only two missense PACS2 gene variants, in whom 19 cases carried the variant c. 625G>A (p.Glu209Lys) and 1 case carried the variant c. 631G>A (p.Glu211Lys). Epilepsy was the first reported symptom in all patients, and 17 cases had seizures during the first week of life. Out of the various seizure types observed, focal seizures were the predominant types (13 cases), whereas tonic, clonic, tonic-clonic seizures and non-motor seizures (such as facial flushing) were also reported. Almost all patients showed facial dysmorphism and developmental delay to different degrees. Total of 16 patients had abnormal brain MRI recordings, and 13 cases had cerebellar hypoplasia. More specifically, 7 cases showed inferior vermian hypoplasia, and 3 cases showed hypothalamic fusion anomaly. The treatment was mainly aimed to control the symptoms. And the recommended effective treatment for epilepsy has not been reported yet. Conclusions: PACS2-related early infantile epileptic encephalopathy is an autosomal dominant disease, characterized by seizure onset within the first week of life in most cases, dysmorphic facial appearance, and various degrees of developmental retardation. Treatment with valproic acid showed good effect.

[Comparison of the post-operative analgesic effect of ultrasound-guided serratus anterior plane block combined with pectoral nerves block â and thoracic paravertebral block in radical mastectomy].

Objective: To investigate the serratus anterior plane block combined with pectoral nerves block I can produce a non-inferior analgesic effect compared with thoracic paravertebral block for radical mastectomy. Methods: From October 2020 to February 2021, Sixty-four patients of Beijing Tongren Hospital, Capital Medical University scheduled for radical mastectomy with general anesthesia,were divided into two groups (n = 32 each) using a random number table method: thoracic paravertebral block group (TPVB group) and serratus anterior plane block combined with pectoral nerves block I group (S&P group). All patients received patient controlled intravenous analgesia (PCIA) postoperatively. The numerical rating scale (NRS) at post anesthesia care unit (PACU), 4, 8, 12, 24, 48 h after operation were compared between the two groups. Sufentanil cumulative dosage of PCIA in 24 h and 48 h, first press time after operation, total press times, the dosage of propofol, remifentanil and vasoactive drugs during operation, intraoperative blood pressure and heart rate, the operation time of block and adverse effects were all compared. Non-inferiority could be claimed if the difference of sufentanil cumulative dosage in 24 h between S&P group and TPVB group is higher than the negative value (-3.8) of the non-inferiority effect. Results: There was no significant difference in postoperative NRS at PACU, 4, 8, 12, 24, 48 h after operation, first press time after operation, total press times, propofol and remifentanil dosage, sufentanil cumulative dosage of PCIA in 24 h and 48 h, and adverse effects (all P>0.05). The sufentanil cumulative dosage of PCIA in 24 h of S&P group and of TPVB group were (15.8±4.7) µg and (15.2±3.2) µg. The 95% confidence interval (CI) of the difference between S&P group and of TPVB group was -1.478 to 2.694, and the lower limit was greater than non-inferiority margin -3.8. The mean arterial pressure of TPVB patients after induction and at the beginning of the operation were (63±7) mmHg and (70±7) mmHg, which were significantly lower than the (77±5) mmHg and (79±8) mmHg at the same time in the combination group (both P<0.05). The frequency of vasoactive drugs usage in TPVB group was 56.3%, which was statistically significant higher than the 18.8% in S&P group (P<0.01). Nerve block time in TPVB group was 10 (9, 11) min, which was significantly longer than 8 (6, 10) min in S&P group (P<0.01). Conclusion: The serratus anterior block combined with pectoral nerves block I can produce a non-inferior analgesic effect compared with thoracic paravertebral block for radical mastectomy, and the intraoperative hemodynamics is more stable and the block time is shorter than that of thoracic paravertebral block for radical mastectomy.

LncRNA DNAJC3-AS1 functions as oncogene in renal cell carcinoma via regulation of the miR-27a-3p/PRDM14 axis.

OBJECTIVE: Renal cell carcinoma (RCC) is one of the most common urological malignancies worldwide. Although great advances have been made in the diagnosis and management of RCC, its prognosis remains unsatisfactory. Long noncoding RNAs (lncRNAs) have been found to be essential factors in the initiation and development of cancer. The current study aimed to measure the expression and functions of lncRNA DNAJC3-AS1 in the progression of clear cell RCC (ccRCC). PATIENTS AND METHODS: The expression of lncRNA DNAJC3-AS1 was detected in 30 pairs of ccRCC tissues and in cell lines by RT-PCR, and its prognostic association with ccRCC was evaluated by the Kaplan-Meier method. The proliferation, migration, invasion and apoptosis of ccRCC cells were measured after silencing DNAJC3-AS1. The interaction between DNAJC3-AS1, miR-27a-3p and PRDM14 was identified by Dual-Luciferase reporter assay. The protein levels were measured by Western blotting. RESULTS: The expression of DNAJC3-AS1 was upregulated in ccRCC tissues and cell lines compared to their normal counterparts. In vitro, silencing DNAJC3-AS1 reduced the proliferation, migration and invasion of ccRCC cells. Downregulation of DNAJC3-AS1 also led to the apoptosis of ccRCC cells. Moreover, we also found that DNAJC3-AS1 acted as a sponge of miR-27a-3p and identified PRDM14 as a target of miR-27a-3p. CONCLUSIONS: LncRNA DNAJC3-AS1 acts as an oncogene and plays an essential role in the tumorigenesis of ccRCC, possibly via the regulation of the miR-27a-3p/PRDM14 axis.

CT-based radiomics model to distinguish necrotic hepatocellular carcinoma from pyogenic liver abscess.

AIM: To investigate the feasibility of a computed tomography (CT)-based radiomics model in distinguishing necrotic hepatocellular carcinoma (nHCC) from pyogenic liver abscess (PLA). MATERIAL AND METHODS: One hundred-four enrolled patients with nHCC (n=56) and PLA (n=48) were divided randomly into a training cohort (n=62) and validation cohort (n=42). ROI (region of interest) of the wall (ROI-wall) and ROI of the necrotic cavity (ROI-necrotic cavity) of the lesion were delineated from each arterial phase (AP) and portal venous phase (PP) image. The least absolute shrinkage and the selection operator logistic regression method was used to select radiomics features, and radiomics scores (R-scores) were calculated. Four radiomics models, including R-score (ROI-wall) in the AP, R-score (ROI-necrotic cavity) in the AP, R-score (ROI-wall) in the PP and R-score (ROI-necrotic cavity) in the PP, were constructed and evaluated by area under the curve (AUC) of receiver operating characteristic curve. RESULTS: The AUCs of R-score (ROI-wall) in the AP, R-score (ROI-necrotic cavity) in the AP, R-score (ROI-wall) in the PP, and R-score (ROI-necrotic cavity) in the PP were 0.935 and 0.917, 0.906 and 0.824, 0.985 and 0.928, 0.899 and 0.850, in the training and validation cohorts, respectively. In the training cohort, the AUC of R-score (ROI-wall) in the PP was higher than that of R-score (ROI-wall) in the AP (p=0.024) or R-score (ROI-necrotic cavity) in the AP (p=0.046) or R-score (ROI-necrotic cavity) in the PP (p=0.044). CONCLUSION: CT-based radiomics models can be used to distinguish nHCC from PLA.

Long non-coding RNA LINC00173 serves as sponge for miR-338-3p to promote prostate cancer progression via regulating Rab25.

OBJECTIVE: Long non-coding RNA LINC00173 (LINC00173) has been shown to facilitate the progression of a number of malignancies. In this study, we aimed to investigate the function of LINC00173 on prostate cancer (PCa) and discover the potential regulatory mechanism. PATIENTS AND METHODS: RT-PCR was used to determine the levels of LINC00173, miR-338-3p and Rab25 in PCa patients and cell lines. The clinical significance of LINC00173 was statistically analyzed in 124 PCa patients. CCK-8, colony formation, transwell, scratch wound, Ethynyldeoxyuridine (EdU) assays and flow cytometry assays were used to detect the proliferation, apoptosis, invasion and migration of PCa cells. The mechanism of LINC00173 action was explored through bioinformatics, RNA pull-down assays and Luciferase reporter assays. RESULTS: We observed that the expression of LINC00173 and Rab25 was distinctly upregulated in both PCa specimens and cell lines, while miR-338-3p expression was significantly down-regulated. High LINC00173 expression was associated with Gleason score, preoperative PSA level and reduced patient survivals. Functional assays revealed that knockdown of LINC00173 suppressed the proliferation, migration and invasion of PCa cells, and promoted apoptosis. Mechanistically, LINC00173 acted as a competitive endogenous RNA in PCa and increased Rab25 expressions via sponging miR-338-3p. Moreover, LINC00173 promoted PCa progression by interacting with miR-338-3p and Rab25. CONCLUSIONS: Our findings, for the first time, identified a novel PCa-related lncRNA, LINC00173 which might serve as an oncogene in PCa. The discovery of the LINC00173/miR-338-3p/Rab25 pathways provided new thinking for the treatments of PCa.

[The predictive value of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid enhanced MRI imaging features combined with quantitative parameters for the pathologic grading of hepatocellular carcinoma].

Objective: To investigate the predictive value of gadolinium-ethoxybenzyl- diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced MRI imaging features combined with quantitative parameters for the pathologic grading of hepatocellular carcinoma (HCC). Methods: Eighty patients (65 males, 15 females; range 30-74 years,average age (59±11) years old) with HCC who underwent curative resection or biopsy from June 2016 to June 2019 in the First Affiliated Hospital of Soochow University after Gd-EOB-DTPA-enhanced MRI were evaluated retrospectively.According to the pathological results of the postoperative pathology, eighty patients were divided into poorly differentiated group (26 cases, 22 males, 4 females) and moderately-well differentiated group (54 cases, 43 males, 11 females). In Gd-EOB-DTPA-enhanced MRI, qualitative parameters were assessed. Quantitative parameters including tumor size, tumor-to-liver signal intensity ratio(SIR) of arterial phase (AP), portal vein phase (PP), equilibrium phase (EP) and hepatobiliary phase (HBP), contrast enhancement ration AP (CER-AP)were measured and calculated. Clinical data and qualitative parameters between poorly differentiated group and moderately-well differentiated group were analyzed by using χ(2) test.Quantitative parameters were analyzed by using independent sample t test. Statistically significant qualitative parameters, quantitative parameters, qualitative combined with quantitative parameters and AFP combined with qualitative and quantitative parameters were included in binary logistic regression model. The receiver operating characteristic (ROC) curves were used to evaluate the diagnostic performance of the four prediction model for the pathologic grading of HCC. Results: There was a statistical difference between poorly differentiated group and moderately-well differentiated group in AFP, arterial peritumoral enhancement, arterial rim enhancement, peritumoral hypointensity on HBP and tumor signal (all P<0.05). In two groups, tumor size, SIR-AP and SIR-PP were (7.0±3.7) vs (3.9±2.4)cm,1.11±0.29 vs 1.31±0.32 and 0.89±0.21 vs 1.03±0.27 (all P<0.05). AUC of qualitative parameters, quantitative parameters, qualitative combined with quantitative parameters and AFP combined with qualitative and quantitative parameters were 0.805, 0.804, 0.855, 0.892.There was a statistical difference between qualitative parameters and qualitative combined with quantitative parameters in sensitivity(80.8% vs 92.3%, P<0.05). Conclusion: Gd-EOB-DTPA-enhanced MRI imaging features combined with quantitative parameters can be used to predict the pathologic grading of HCC preoperatively, which has a great applicative value.

[The value of analysis of quantitative radiomics based on DTI in predicting astrocytoma IDH1 mutation].

Objective: Non-invasive prediction of IDH1 mutations by establishing a quantitative radiographic model based on DTI-based whole-tumor texture analysis. Methods: Preoperative MRI images of patients with surgically confirmed astrocytoma were collected in the First Affiliated Hospital of Soochow University from February 2016 to June 2019, including T(1)WI, T(2)WI, DTI, and T(1)-contrast enhancement images.A total of 38 patients were included, consisting of 12 mutants and 26 wilds, 20 males and 18 females, the average age was (49±15) years old.The ROIs were drawn on each level of the T(2)WI image using MaZda software and copied to the ADC and FA maps to extract texture feature parameters. The LASSO regression was used to determine the best radiomics features, radiological scores were calculated, and binary Logistic regression was used to construct a prediction model, then the ROC curve was used to analyze the diagnostic efficiency and the calibration curve was used to evaluate model prediction performance. Results: The four most valuable radiomics features were determined by LASSO regression, and then the radiomics scores and Logistic regression models of each patient were established. The radiomics scores of the wild and mutant groups were 2.3±0.3 and 1.8±0.4. There were significant differences between the groups (P<0.05). The ROC curve analysis showed an AUC of 0.837 with sensitivity and specificity of 91.7% and 61.5%, respectively. The Logistic regression model had good predictive performance with AUC of 0.907, sensitivity and specificity of 91.7% and 84.6%. Conclusions: DTI-based whole tumor radiomics model is benefit for predicting astrocytoma IDH1 mutations.

[Short-term efficacy of robotic-assisted total mesorectal excision with and without lateral lymph node dissection for mid-low advanced rectal cancer: a propensity score matching analysis].

Objective: To evaluate the feasibility, safety and efficacy of robotic-assisted lateral lymph node dissection for mid-low advanced rectal cancer. Methods: A retrospective cohort study was performed. Inclusion criteria: (1) age between 18 and 80 years old; (2) rectal adenocarcinoma diagnosed by pathology; (3) without distant metastasis by preoperative CT or MRI; (4) patients underwent robotic-assisted total mesorectal resection (TME). Exclusion criteria: (1) conversion to open surgery; (2) multiple primary tumors; (3) patients underwent combined multiple organ resection. According to the above criteria, 137 patients undergoing robotic-assisted mid-low rectal cancer resection in the First Affiliated Hospital of Xi'an Jiaotong University from December 2016 to April 2019 were enrolled. Ninety-seven cases underwent robotic-assisted total mesorectal excision (TME group) and 40 underwent robotic-assisted total mesorectal resection with lateral lymph node dissection (LLND) (TME+LLND group, pelvic LLND was performed with neurovascular guidance to retain pelvic autonomic nerves in the order of the left side the first and then the right side). The propensity score matching of 1:1 was performed with R software, based on age, sex, BMI, ASA classification, distance from tumor to the anal verge, preoperative chemoradiotherapy history, preoperative abdominal surgery history, the size of tumors and TNM stage. The operative indicators, postoperative recovery, pathology and postoperative complications within 30 days were compared between the two groups. Results: A total of 72 cases were successfully matched (36 in each group), and there were no statistically significant differences in baseline data between the two groups (all P>0.05). The operation time of TME+LLND group was significantly longer than that of TME group [275.0 (180-405) minutes vs. 220.0 (140-320) minutes, Z=-3.680, P<0.001], while there were no statistically significant differences in blood loss during operation, time to postoperative first flatus, postoperative hospital stay, total hospital cost, tumor differentiation, and distal resection length of margin (all P>0.05). Circumferential resection margin was all negative in both groups. The number of harvested lymph modes in the TME+LLND groups was higher than that in the TME group [26 (18-37) vs. 14 (9-36), Z=-6.407, P<0.001]. In addition, there were no statistically significant differences in postoperative morbidity and Clavien-Dindo classification of complication within 30 days between the two groups (both P>0.05). Conclusions: Although robotic lateral lymph node dissection requires longer operation time, it is a feasible, safe and effective procedure.

[Analysis of factors affecting olfactory disfunctions in patients with chronic rhinosinusitis with nasal polyps].

Objective: To analyze the factors affecting olfactory disfunctions in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Methods: This was a retrospective analysis. Eighty-eight patients with CRSwNP who underwent endoscopic sinus surgery in Beijing Anzhen Hospital from 2014 to 2018 were enrolled, including 22 males and 66 females, with the age of (48.1±11.3) years old(Mean±SD). Sniffin' Sticks olfactory test, Lund-Mackay score and modified sinus CT olfactory cleft score, nasal resistance and acoustic reflex examination, blood routine and blood biochemistry test, serum specific IgE test were performed before surgery and nasal polyps of all patients were collected for eosinophil count during surgery. According to bilateral total TDI score, the patients were divided into normal olfactory function group and olfactory disfunction group. The clinical baseline data were compared between the two groups. According to the results of single factor analysis, factors which were significant different between the two groups and clinically useful indicators were further included in the multivariate Logistic regression model analysis, then a model predicting olfactory disfunction in patients with CRSwNP was initially established. P<0.05 was considered statistically significant. Results: Among 88 patients with CRSwNP, 32 (36.4%) patients were with normal olfaction and 56 (63.6%) patients were with olfactory disfunction, including 40 (45.5%) of hyposmia and 16 (18.2%) of anosmia. Tissue eosinophil count, blood eosinophil percentage and blood urea concentration had significant difference between the two groups (12.7[2.0, 52.3]/HP (M[P(25), P(75)]) vs 38.6[16.2, 87.0]/HP, 2.75[1.60, 4.80]% vs 4.35[2.50, 6.60]%, (5.56±1.15) mmol/L vs (4.98±1.33) mmol/L, all P<0.05). Modified sinus CT olfactory cleft score and Lund-Mackay score except for ostiomeatal complex score were statistically significant between the two groups (all P<0.05). Multivariate Logistic regression analysis showed that the bilateral and total olfactory cleft score and blood urea concentration were statistically significant, in addition, the bilateral and total olfactory cleft score was a risk factor (OR=2.108, 95%CI: 1.407-3.159, P<0.001) and blood urea within a certain concentration was a protective factor (OR=0.461, 95%CI: 0.240-0.884, P=0.020). Further studies found that the area under the ROC curve of the model with tissue eosinophil count, blood eosinophil percentage, bilateral and total olfactory cleft score, total inspiratory volume and blood urea concentration was 0.888 (P<0.01), which had good predictive value for olfactory disorders in CRSwNP. Conclusions: The modified sinus CT olfactory cleft score is closely related to the olfactory disorders in patients with CRSwNP. A certain degree of elevated blood urea concentration may have a protective effect on the olfactory function of patients with CRSwNP.