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Objectives: To construct a YOLOv3-based model for diatom identification in scanning electron microscope images, explore the application performance in practical cases and discuss the advantages of this model., Methods: A total of 25 000 scanning electron microscopy images were collected at 1 500× as an initial image set, and input into the YOLOv3 network to train the identification model after experts' annotation and image processing. Diatom scanning electron microscopy images of lung, liver and kidney tissues taken from 8 drowning cases were identified by this model under the threshold of 0.4, 0.6 and 0.8 respectively, and were also identified by experts manually. The application performance of this model was evaluated through the recognition speed, recall rate and precision rate., Results: The mean average precision of the model in the validation set and test set was 94.8% and 94.3%, respectively, and the average recall rate was 81.2% and 81.5%, respectively. The recognition speed of the model is more than 9 times faster than that of manual recognition. Under the threshold of 0.4, the mean recall rate and precision rate of diatoms in lung tissues were 89.6% and 87.8%, respectively. The overall recall rate in liver and kidney tissues was 100% and the precision rate was less than 5%. As the threshold increased, the recall rate in all tissues decreased and the precision rate increased. The F 1 score of the model in lung tissues decreased with the increase of threshold, while the F 1 score in liver and kidney tissues with the increase of threshold., Conclusions: The YOLOv3-based diatom electron microscope images automatic identification model works at a rapid speed and shows high recall rates in all tissues and high precision rates in lung tissues under an appropriate threshold. The identification model greatly reduces the workload of manual recognition, and has a good application prospect.

Background: Hepatectomy with tumor thrombectomy is the preferred treatment option for hepatocellular carcinoma (HCC) patients with bile duct tumor thrombus (BDTT); however, the impact of BDTT on their prognosis is unclear., Objective: We aimed to investigate the long-term surgical outcomes of HCC patients with BDTT., Methods: The data of HCC patients with and without BDTT who underwent hepatectomy were retrospectively reviewed and the long-term outcomes were compared. For propensity score matching (PSM) analysis, patients were matched in a 1:1 ratio. Subgroup analysis was conducted according to the American Joint Committee on Cancer (AJCC) staging system., Results: Before PSM, HCC patients with BDTT had more advanced tumor stages and adverse clinicopathological features. Recurrence-free survival (RFS) and overall survival (OS) were significantly higher in the non-BDTT group before PSM (RFS, p < 0.001; OS, p < 0.001), while after PSM, the BDTT group had significantly poorer RFS (p = 0.025). There was no difference in OS between the groups (p = 0.588). Subgroup analysis showed that RFS and OS in AJCC stage I-II patients were significantly poorer in the BDTT group; no differences were found in the AJCC stage III group before or after PSM. When the presence of BDTT was recommended to increase the AJCC staging system by one stage in AJCC stage I-II patients, the predictive ability for RFS and OS was higher., Conclusions: BDTT was associated with significantly poorer long-term surgical outcomes in AJCC stage I-II patients. A modified AJCC staging system including BDTT status in stage I-II might have a better prognostic ability., (© 2021. Society of Surgical Oncology.)

Psychosocial stress is a vital factor contributing to the pathogenesis and progression of inflammatory bowel disease (IBD). The contribution of intestinal macrophage autophagy to the onset and development of IBD has been widely studied. Herein, we investigated the underlying mechanism of psychosocial stress in an IBD mouse model pertaining to macrophage autophagy. Corticotropin releasing hormone (CRH) was peripherally administrated to induce psychosocial stress. For in vivo studies, dextran sulfate sodium (DSS) was used for the creation of our IBD mouse model. For in vitro studies, lipopolysaccharide (LPS) was applied on murine bone marrow-derived macrophages (BMDMs) as a cellular IBD-related challenge. Chloroquine was applied to inhibit autophagy. We found that CRH aggravated the severity of DSS-induced IBD, increasing overall and local inflammatory reactions and infiltration. The levels of autophagy in intestinal macrophages and murine BMDMs were increased under these IBD-related inflammatory challenges and CRH further enhanced these effects. Subsequent administration of chloroquine markedly attenuated the detrimental effects of CRH on IBD severity and inflammatory reactions via inhibition of autophagy. These findings illustrate the effects of peripheral administration of CRH on DSS-induced IBD via the enhancement of intestinal macrophage autophagy, thus providing a novel understanding as well as therapeutic target for the treatment of IBD., (© 2021. The Author(s).)

Background: Anatomic resection (AR) of the liver is generally recommended in hepatocellular carcinoma (HCC) patients. However, the benefits of AR and nonanatomic resection (NAR) in HCC patients with bile duct tumor thrombus (BDTT) are unknown. This study aimed to compare long-term outcomes of AR and NAR in HCC patients with BDTT after curative resection., Patients and Methods: A total of 175 consecutive HCC patients with BDTT after curative resection between April 2009 and December 2017 were included. One-to-one propensity score matching (PSM) was performed to minimize the influence of potential confounders. Recurrence-free survival (RFS) and overall survival (OS) were compared between the cohorts., Results: After PSM, 120 patients were analyzed. The AR group had better RFS than the NAR group (P = 0.010). Even though there was no statistically significant difference in OS (P = 0.140, power = 0.33), the 3- and 5-year OS rates in the AR group (52.4% and 44.2%, respectively) were obviously higher than those in the NAR group (35.4% and 30.4%, respectively). When patients were further stratified according to tumor size, better RFS and OS were observed in patients with small (≤ 5 cm) tumors after AR (P < 0.001 and P = 0.004, respectively). Multivariate analysis identified AR (P = 0.024) as an independent favorable prognostic factor for RFS in HCC patients with BDTT., Conclusions: AR is recommended for HCC patients with BDTT, especially in patients with small (≤ 5 cm) tumors., (© 2021. Society of Surgical Oncology.)

Background: Neuropathic pain is a debilitating disease with few effective treatments. Emerging evidence indicates the involvement of mitochondrial dysfunction and oxidative stress in neuropathic pain. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a potent regulator of the antioxidant response system. In this study, we investigated whether RTA-408 (RTA, a novel synthetic triterpenoid under clinical investigation) could activate Nrf2 and promote mitochondrial biogenesis (MB) to reverse neuropathic pain and the underlying mechanisms., Methods: Neuropathic pain was induced by chronic constriction injury (CCI) of the sciatic nerve. Pain behaviors were measured via the von Frey test and Hargreaves plantar test. The L4-6 spinal cord was collected to examine the activation of Nrf2 and MB., Results: RTA-408 treatment significantly reversed mechanical allodynia and thermal hyperalgesia in CCI mice in a dose-dependent manner. Furthermore, RTA-408 increased the activity of Nrf2 and significantly restored MB that was impaired in CCI mice in an Nrf2-dependent manner. Peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1 α ) is the key regulator of MB. We found that the PGC-1 α activator also induced a potent analgesic effect in CCI mice. Moreover, the antinociceptive effect of RTA-408 was reversed by the preinjection of the PGC-1 α inhibitor., Conclusions: Nrf2 activation attenuates chronic constriction injury-induced neuropathic pain via induction of PGC-1 α -mediated mitochondrial biogenesis in the spinal cord. Our results indicate that Nrf2 may be a potential therapeutic strategy to ameliorate neuropathic pain and many other disorders with oxidative stress and mitochondrial dysfunction., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2021 Jia Sun et al.)

Background: Bile duct invasion is a relatively rare event and is not well characterised in hepatocellular carcinoma (HCC). It remains very difficult to diagnose HCC with bile duct tumour thrombus (BDTT) before surgery. Increasing evidence has revealed that inflammation plays a critical role in tumorigenesis. This study aimed to develop nomograms based on systemic and hepatic inflammation markers to predict microscopic BDTT (micro-BDTT) before surgery in HCC., Methods: A total of 723 HCC patients who underwent hepatectomy as initial therapy between January 2012 and June 2020 were included in the study. Logistic regression analysis was used to identify independent risk factors for micro-BDTT. The nomograms were constructed using significant predictors, including α-fetoprotein (AFP), alkaline phosphatase (ALP), direct bilirubin (DB), prognostic nutritional index (PNI), and γ-glutamyl transferase (γ-GT)/alanine aminotransferase (ALT). The prediction accuracies of the nomograms were evaluated using the area under the receiver operating characteristic (ROC) curve., Results: AFP, ALP, DB, PNI, and γ-GT/ALT were independent risk factors for predicting micro-BDTT (P = 0.036, P = 0.004, P = 0.013, P = 0.012, and P = 0.006, respectively), which were assembled into the nomograms. The area under the ROC curve of the nomograms combining PNI and γ-GT/ALT for predicting micro-BDTT was 0.804 (95% confidence interval [CI]: 0.730-0.878). The sensitivity and specificity values when used in predicting micro-BDTT before surgery were 0.739 (95% CI: 0.612-0.866) and 0.781 (95% CI: 0.750-0.813), respectively., Conclusions: The nomogram based on combining systemic and hepatic inflammation markers is suitable for predicting micro-BDTT before surgery in HCC patients, leading to a rational therapeutic choice for HCC.

Feed-water valves are widely used in nuclear power plants to regulate the flow rate of the water supplying to steam generators, and thus holding the water level in steam generators at desired values. The flow rate characteristics of feed-water valves have important effects on the management quality of the water level in steam generators and therefore influence the safety and the efficiency of nuclear power plants. In this paper, the effects of throttling window shapes on the flow rate characteristics through feed-water valves are investigated in two aspects, the overall performances and the fluid dynamics. First of all, a dimensionless parameter defining throttling window shapes is proposed for the quantitative assessment. Then, for the analysis of overall performances, the rated flow coefficient, the loss coefficient, and the inherent valve characteristics are investigated. A revised fitting function is obtained to predict the inherent valve characteristics with different throttling window shapes for engineering applications. Finally, for the observation of the fluid dynamics, the velocity characteristics and the pressure characteristics are both discussed. The wear conditions are predicted at different relative travels and throttling window shapes. This paper provides a reference for researchers dealing with the design work of feed-water valves and is beneficial for the improvement of the whole water level control system., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 ISA. Published by Elsevier Ltd. All rights reserved.)

Chronic neuropathic pain poses a significant health problem, for which effective therapy is lacking. The current work aimed to investigate the potential antinociceptive efficacy of isorhynchophylline, an oxindole alkaloid, against neuropathic pain and elucidate mechanisms. Male C57BL/6J mice were subjected to chronic constriction injury (CCI) by loose ligation of their sciatic nerves. Following CCI surgery, the neuropathic mice developed pain-like behaviors, as shown by thermal hyperalgesia in the Hargreaves test and tactile allodynia in the von Frey test. Repetitive treatment of CCI mice with isorhynchophylline (p.o., twice per day for two weeks) ameliorated behavioral hyperalgesia and allodynia in a dose-dependent fashion (5, 15, and 45 mg/kg). The isorhynchophylline-triggered antinociception seems serotonergically dependent, since its antinociceptive actions on neuropathic hyperalgesia and allodynia were totally abolished by chemical depletion of spinal serotonin by PCPA, whereas potentiated by 5-HTP (a precursor of 5-HT). Consistently, isorhynchophylline-treated neuropathic mice showed escalated levels of spinal monoamines especially 5-HT, with depressed monoamine oxidase activity. Moreover, the isorhynchophylline-evoked antinociception was preferentially counteracted by co-administration of 5-HT 1A receptor antagonist WAY-100635. In vitro , isorhynchophylline (0.1-10 nM) increased the Emax (stimulation of [ 35 S] GTPγS binding) of 8-OH-DPAT, a 5-HT 1A agonist. Of notable benefit, isorhynchophylline was able to correct co-morbidly behavioral symptoms of depression and anxiety evoked by neuropathic pain. Collectively, these findings confirm, for the first time, the disease-modifying efficacy of isorhynchophylline on neuropathic hypersensitivity, and this effect is dependent on spinal serotonergic system and 5-HT 1A receptors., (Copyright © 2020 Gao, Zhao, Wang, Yu, Wu and Zhao.)

Inflammatory external root resorption (IERR) refers to the pathological process of dissolving the hard tissue on the outer surface of the tooth root by the body's own immune system under the stimulation of various physical and chemical factors such as infection, stress, trauma and orthodontic treatment. Severe IERR can lead to endodontic and periodontal diseases, and even the loss of teeth. Therefore, understanding the etiology and the pathogenic mechanism of IERR are of importance in its prevention and treatment. This article will review the etiology and the regulation mechanisms of IERR.

Objective: To investigate the association between the level of serum testosterone and atherosclerosis in middle-aged and elderly men., Methods: We conducted a population-based study of 413 males aged 40-75 years in a community in Guangzhou. We obtained the sociodemographic characteristics, clinical data, physical measurements, and laboratory results of sex hormones, blood glucose, and blood lipid of the subjects. We also measured the carotid intima media thickness (CIMT) by color Doppler ultrasonography., Results: The subjects were divided into a carotid atherosclerosis (CAS) group (CIMT ≥ 0.9 mm) and a non-CAS group (CIMT < 0.9 mm). The medians of free testosterone (FT) were 57.41 and 59.72 pmol/L in the CAS and non-CAS groups, respectively (P = 0.005), and no significant difference was found between the two groups in total testosterone (TT). The levels of serum FT and TT were negatively correlated to CIMT, with Spearman's rank correlation coefficients of -0.126 (P = 0.011) and -0.188 (P < 0.001), respectively. The incidence rates of CAS were 23.30, 13.46, 17.48, and 7.77% in the Q1, Q2, Q3, and Q4 groups, respectively according to the quartile of FT (P for trend = 0.008) and 17.48, 18.27, 16.50, and 9.71% respectively according to the quartile of TT (P for trend = 0.116). Based on the quartile of FT and after adjustment for age, waist circumference, systolic blood pressure, and HbAlc, the risk of CAS was significantly increased in the Q1 group as compared with Q4 (OR = 2.491, 95% CI 1.01-6.149), but no statistically significant differences were observed according to the quartile of TT., Conclusion: A low serum FT level may be a risk factor of atherosclerosis in Chinese men aged 40 years or older.

Objectives: To compare the sensitivity of mammogram and breast dedicated MRI in detecting ductal carcinoma in situ with microinvaion (DCIS-MI) and ductal carcinoma in situ (DCIS) lesions, and to further investigate the independent predictive factors of mammogram and MRI sensitivity., Methods: From August 2009 to November 2011, 122 consecutive confirmed breast cancer patients who had received operations were recruited for this clinical research. These patients were divided into two groups including DCIS (72 cases) and DCIS-MI (50 cases) based on pathologic reports. All the patients were female, with mean ages of 52.6 years and 54.4 years. Preoperative bilateral breast mammogram, breast dedicated MRI depictions and reports as well as histopathological reports were collected., Results: Sensitivity of MRI outstood mammogram in each subgroups: 84.7% vs. 42.4% in DCIS (χ(2) = 27.028, P = 0.000), 94.0% vs. 80.0% in DCIS-MI group (χ(2) = 4.540, P = 0.040). And further analysis showed that MRI was more sensitive to high nuclear grade DCIS and DCIS-MI lesions than low nuclear grade ones (OR = 3.471, P = 0.031)., Results: of logistic regression analysis proved microcalcification was an independent predictive factor of mammogram sensitivity (OR = 11.287, P = 0.001)., Conclusions: Sensitivity of breast dedicated MRI is superior to mammogram in detecting DCIS and DCIS-MI groups. Lesions with microcalcifiation is an independent predictive marker which meant that mammogram would achieve high detection rate in cancers presented calcification on mammogram image when compared with non-calcification. Diagnostic performance of breast MRI is less affected by clinical and pathological characteristics of the early stage breast cancer patients but further increased detection rate is observed in DCIS and DCIS-MI with high nuclear grade lesions which indicated that MRI could detect more early stage cancers with relative more aggression biological behaviour and provide these patients with early surgical interventions before possible progression to invasive breast cancers.

We investigated whether molecular subtype can predict the response and prognosis in Chinese locally advanced breast cancer (LABC) patients treated with preoperative therapy. LABC patients treated with preoperative therapy in Cancer Hospital, Fudan University between August 2001 and May 2008 were retrospectively analyzed. Molecular subtypes were constructed from the immunohistochemical results of hormonal receptors (HR) and HER2 status, which were classified as luminal (HR+/HER2-), triple negative (HR-/HER2-) and HER2 positive subtypes. Preoperative tumor parameters, chemotherapy regimens and response as well as outcome were compared among these subtypes. A total of 225 cases were included into analysis. Univariate and multivariate analysis showed that the pathological complete remission (pCR) independent predictive factors were molecular subtype and preoperative regimens. Compared with luminal subtype, patients with HER2 positive or triple negative tumor had significantly higher pCR rate, with odds ratio 3.02 (95% CI=1.07-8.07; P=0.037) and 3.10 (95% CI=1.01-9.52; P=0.048), respectively. However, HER2 positive or triple negative breast cancer patients were also associated with increased recurrence (P=0.072) and death rates (P=0.019) compared with luminal subtype in the whole population, and was especially worse in patients with residual disease after preoperative therapy with decreased disease-free survival (P=0.022) and overall survival (P=0.007). Our results show that molecular subtype can predict the response and prognosis of Chinese LABC patients treated with preoperative therapy. Compared with luminal subtype, patients with HER2 positive or triple negative disease had increased pCR rates, but associated with significantly worse survival, especially in those with residual disease after preoperative therapy.

Objective: To examine the effect of postoperative pregnancy upon the prognosis of young Chinese breast cancer patients., Methods: Four hundred and thirty-two female unilateral breast cancer patients aged 35 or younger were retrospectively reviewed. Kaplan-Meier analysis and Log Rank test were used for univariate analysis of factors predictive of disease-free survival (DFS) and overall survival (OS). Multivariate analysis was carried out using the Cox proportional hazards model., Results: Eighteen patients were identified to have postoperative pregnancy, including 5 full-term pregnancy and 13 abortions with the earliest pregnancy taking place at Month 17 post-operation. After a median follow-up of 62 months (6 - 237 months), the DFS and OS rates were 72.5% (313/432) and 88.7% (383/432) respectively. On multivariate analysis, postoperative pregnancy, clinical stage and number of pathologically involved axillary lymph node were significantly associated with DFS. And the axillary lymph node status was also predictive of OS. No death occurred in patient with postoperative pregnancy. There was no significant association between postoperative pregnancy and OS., Conclusion: Postoperative pregnancy has no adverse effect upon the prognosis of young breast cancer patients.

Objective: To identify predictive markers of the long-term outcome for neo-adjuvant chemotherapy (NC) in locally advanced breast cancer (LABC) treated with intravenous vinorelbine (V) and epirubicin (E) combination regimen., Methods: One hundred and nineteen patients with LABC were treated from September 2001 to May 2006. All patients were diagnosed as invasive breast cancer by 14G core needle biopsy and treated with three cycles of VE regimen before the operation. The patients were subjected to surgery and subsequently were given other three cycles of VE or cyclophosphamide+epirubicin+fluorouracil (CEF) regimen according to the clinical responses. Local-regional radiotherapy was applied to all patients after the chemotherapy and followed by hormone-therapy according to hormone receptor status. The impact of clinical, pathological, and immunohistochemical features on disease free survival (DFS) and overall survival (OS) was evaluated., Results: All patients were evaluable for responses: clinical complete response was documented in 27 patients (22.7%), 78 patients (65.5%) obtained partial clinical response. The pathological complete response was found in 22 cases (18.5%). Of the patients, 115 cases (96.6%) were followed-up for a median time of 63.4 months (range, 9-76 months), the 5-year DFS rate and OS rate was 58.7% and 71.3%, respectively. On multivariate analysis, high pre-Ki-67 (P=0.012) and post-Ki-67 expression (P=0.045), no pathological complete response after NC (P=0.034) were associated with the higher risk of disease relapse; high pre-Ki-67 (P=0.017) and post-Ki-67 expression (P=0.001), negative pre-ER (P=0.002) and no pathological complete response after NC (P=0.034) were associated with a shorter survival., Conclusion: Pathological response in primary tumor, pre-Ki-67 and post-Ki-67 expression, pre-ER expression are important predictors of long-term outcome for LABC patients with three cycles of VE regimen before operation.