Berberine ameliorates nonalcoholic fatty liver disease-induced bone loss by inhibiting ferroptosis.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) may contribute to osteoporosis. Berberine is a traditional Chinese medicine and was recently shown to be beneficial in NAFLD. However, little is known about its impact on bone loss induced by NAFLD. AIM: We aimed to explore the role of berberine in bone loss and determine its underlying mechanisms in NAFLD. METHODS: C57BL/6 mice were fed a high-fat high-fructose high-glucose diet (HFFGD) for 16 weeks to establish a NAFLD mouse model. The mice were administered berberine (300 mg/kg/d) by gavage, and fatty liver levels and bone loss indicators were tested. RESULTS: Berberine significantly improved HFFGD-induced weight gain, hepatic lipid accumulation and increases in serum liver enzymes, thereby alleviating NAFLD. Berberine increased trabecular number (Tb. N), trabecular thickness (Tb. Th), bone volume to tissue volume ratio (BV/TV), and decreased trabecular separation (Tb. Sp) and restored bone loss in NAFLD. Mechanistically, berberine significantly inhibited ferroptosis and 4-hydroxynonenal (4-HNE), prostaglandin-endoperoxide synthase 2 (PTGS2), and transferrin (TF) levels and increased ferritin heavy chain (FTH) levels in the femurs of HFFGD-fed mice. Moreover, berberine also activated the solute carrier family 7 member 11 (SLC7A11)/glutathione (GSH)/glutathione peroxidase 4 (GPX4) signaling pathway. CONCLUSION: Berberine significantly ameliorates bone loss induced by NAFLD by activating the SLC7A11/GSH/GPX4 signaling pathway and inhibiting ferroptosis. Therefore, berberine may serve as a therapeutic agent for NAFLD-induced bone loss.

A study on the radiomic correlation between CBCT and pCT scans based on modified 3D-RUnet image segmentation.

Purpose: The present study is based on evidence indicating a potential correlation between cone-beam CT (CBCT) measurements of tumor size, shape, and the stage of locally advanced rectal cancer. To further investigate this relationship, the study quantitatively assesses the correlation between positioning CT (pCT) and CBCT in the radiomics features of these cancers, and examines their potential for substitution. Methods: In this study, 103 patients diagnosed with locally advanced rectal cancer and undergoing neoadjuvant chemoradiotherapy were selected as participants. Their CBCT and pCT images were used to divide the participants into two groups: a training set and a validation set, with a 7:3 ratio. An improved conventional 3D-RUNet (CLA-UNet) deep learning model was trained on the training set data and then applied to the validation set. The DSC, HD95 and ASSD were calculated for quantitative evaluation purposes. Then, radiomics features were extracted from 30 patients of the test set. Results: The experiments demonstrate that, the modified model achieves an average DSC score 0.792 for pCT and 0.672 for CBCT scans. 1037 features were extracted from each patient's CBCT and pCT images, 73 image features were found to have R values greater than 0.9, including three features related to the staging and prognosis of rectal cancer. Conclusion: In this study, we proposed an automatic, fast, and consistent method for rectal cancer GTV segmentation for pCT and CBCT scans. The findings of radiomic results indicate that CBCT images have significant research value in the field of radiomics.

Identifying tumor markers-stratified subtypes (CA-125/CA19-9/carcinoembryonic antigen) in cervical adenocarcinoma.

OBJECTIVE: There is a lack of research evaluating the effect of tumor markers for prognosis in cervical adenocarcinoma. We aimed to develop and validate a preoperative tumor-marker-based model including clinicopathological factors to clarify the prognostic value of endocervical adenocarcinoma. METHODS: A total of 572 patients with cervical adenocarcinoma who were staged at the International Federation of Gynecology and Obstetrics (FIGO) IA-IIA were reviewed retrospectively. Preoperative serum carcinoembryonic antigen (CEA), carbohydrate antigen (CA)-125 and CA19-9 levels were measured. The survival and recurrence patterns were analyzed according to the tumor-marker-related stratification. The predictive values of biomarkers and clinical variables were assessed with Cox regression and competing risk models. RESULTS: Patients with elevated preoperative tumor markers had evidently poor overall survival and recurrence-free survival. The triple-elevated tumor marker (TETM) subgroup had the worst overall survival and progression-free survival than the triple-negative tumor marker (TNTM) subgroup and the single-elevated tumor marker (SETM) subgroup. The most important predictors for overall survival were elevated tumor markers, FIGO-stage, tumor differentiation, lymphovascular space invasion (LVSI) and lymph nodes metastasis. The most important predictors for recurrence-free survival were elevated tumor markers, FIGO-stage, tumor differentiation, LVSI and deep stromal invasion. Stratified analysis showed that elevated CA-125 and CA19-9 were significantly associated with postoperative distant metastasis. A decision curve analysis confirmed that a combination of tumor markers as predictors significantly outperformed the other common predictors used (FIGO-stage, intermediate and high-risk factors, tumor differentiation, lymph nodes). CONCLUSIONS: Elevated preoperative serum CEA, CA-125, and CA19-9 levels exhibited poor overall survival and recurrence-free survival in cervical adenocarcinoma patients. Combined preoperative serum CA-125 and CA19-9 independently predicted distant metastasis in patients with endocervical adenocarcinoma.

Evaluation of the role of postoperative radiotherapy in locally invasive thymoma: A propensity-matched study based on the SEER database.

OBJECTIVES: No consensus was reached on the efficacy of postoperative radiotherapy (PORT) in locally invasive thymomas because of the rarity of the thymic epithelial and the variations of study results. Therefore, we aimed to explore the efficacy of PORT in locally invasive thymomas using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: Patients diagnosed with thymomas from 2004 to 2016 were identified using the SEER database. Prognostic factors of cancer-specific survival (CSS) and overall survival (OS) were identified using univariate and multivariate Cox regression analyses.Propensity score matching (PSM) was performed to balance the baseline characteristics. RESULTS: A total of 700 eligible patients were identified. After PSM, 262 paired patients were selected from the two groups, those who received or did not receive PORT. Receiving PORT improved CSS and OS before and after PSM. In the matched population, the multivariate analyses showed that tumour invasion into adjacent organs/structures and non-utilisation of PORT were independent poor prognostic factors for CSS, whereas age ≥62 years,tumour invasion into adjacent organs/structures, and non-utilisation of PORT were independently associated with poorer OS. The subgroup analysis revealed that PORT improved CSS and OS in Masaoka-Koga stage III thymoma, but showed no OS benefit in Masaoka-Koga stage IIB thymoma. CONCLUSION: Based on the SEER database, we found that PORT provides a significant survival benefit in Masaoka-Koga stage III thymoma with complete or incomplete resection. The role of PORT in thymoma requires further evaluation.

Clinical Prognostic Factors During the Last One Month of Life in Terminally Ill Cancer Patients: A Retrospective Observational Study.

OBJECTIVE: To explore the trajectory of clinical symptoms and biomarkers in the last four weeks of life in terminally ill cancer patients. STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: Department of Oncology, Shijingshan hospital, Shijingshan Teaching Hospital of Capital Medical University, Beijing, China, between January 2017 and January 2020. METHODOLOGY: This study evaluated 173 terminally ill cancer patients. Seventeen symptoms and fifteen biomarkers were identified. For sequential analysis, the authors divided the final four weeks of life into four time periods from the date of death. Ordinal multiple logistic regression analysis was used to explore the association between the changes in clinical parameters and the risk of death in a given period. Changes in clinical parameters across different time periods were evaluated using the Wilcoxon signed rank test. RESULTS: Abnormal consciousness; elevated ECOG (Eastern Cooperative Oncology Group) scores, neutrophil-to-lymphocyte ratio (NLR), blood urea nitrogen (BUN) to creatinine ratio, C-reactive protein (CRP)-to-albumin ratio; and decreased platelet (PLT) counts were independent factors (p<0.05) for predicting closer death in the final month of life. All parameters above showed significant changes over time in the last month, although the starting time points for these changes varied. CONCLUSION: Abnormal consciousness, elevated ECOG scores, NLR, BUN-to-creatinine ratio, CRP-to-albumin ratio, and decreased PLT counts are potentially useful markers for approaching death in terminally ill cancer patients. These findings are valuable for understanding the biology of death in terminally ill cancer patients. And to some extent, they may help clinicians recognise that a patient will die in the near future. KEY WORDS: Cancer, Ordinal regression analysis, Death, Terminal illness, Biomarkers.

Prognostic Effect of Primary Recurrence Patterns in Squamous Cervical Carcinoma After Radical Surgery.

Objective: To examine the effect of primary recurrence patterns on the prognosis of squamous cervical cancer after initial treatment. Methods: Primary recurrence patterns and prognostic factors were examined in stage IB-IIA cervical cancer patients after initial treatment. Recurrence site (locoregional recurrence and distant metastasis or in-field and out-field recurrence for patients receiving adjuvant radiotherapy) and subtype (nodal and organ recurrence) were examined. Clinicopathological characteristics and survival rates were evaluated to generate a prognostic nomogram. Results: A total of 472 patients were included. The median follow-up period, 5-year overall (OS) rate, and median OS were 59.1 months, 33.7%, and 24.0 months, respectively. Overall, 38.8% and 61.2% of the patients had locoregional recurrence and distant metastasis, respectively, and survival rates were comparable in these groups. Patients with nodal recurrence had better OS than those with organ recurrence (38.3% vs 30.7%, respectively; P = 0.001). Patients not receiving adjuvant radiotherapy had increased risk of pelvic recurrence [odds ratio (OR) = 0.148; 95% confidence interval[(CI): 0.075-0.291, P = 0.000]. Positive lymph-vascular space invasion (OR= 1.928; 95% CI: 1.151-3.229, P = 0.013) and no chemotherapy (OR = 0.521; 95% CI: 0.317-0.733, P = 0.040) increased the risk of distant metastasis. Positive lymph node status after initial treatment were associated with nodal recurrence (OR = 3.729; 95% CI: 1.838-7.563, P = 0.000), while elevated preoperative squamous cell carcinoma antigen (SCC-Ag) levels were associated with organ recurrence (OR = 1.642; 95% CI: 1.325-2.265, P = 0.002). Recurrence subtype, therapy for relapse, the International Federation of Gynecology and Obstetrics stage, adjuvant radiotherapy, preoperative SCC-Ag levels, and risk subgroup were independently associated with OS. Conclusions: Primary recurrence patterns were associated with specific clinicopathological characteristics of cervical cancer. Recurrent cervical cancer prognosis was mainly affected by recurrence location and subtype.

Clinical Implication of Simultaneous Intensity-modulated Radiotherapy Boost to Tumor Bed for Cervical Cancer with Full-thickness Stromal Invasion.

OBJECTIVE: The objective of this study was to retrospectively explore the clinical implications of simultaneous intensity-modulated radiotherapy (IMRT) boost to the tumor bed in cervical cancer with full-thickness stromal invasion (FTSI). PATIENTS AND METHODS: Patients diagnosed with the International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB and IIA cervical cancer with confirmed FTSI were included. Patients received pelvic IMRT from a dose of 50.4 Gy in 28 fractions with (or without) a simultaneous integrated boost (SIB) to 58.8 Gy in 28 fractions for the tumor bed. The progression-free survival (PFS), overall survival (OS), and pelvic-PFS (p-PFS) were analyzed using the Kaplan-Meier method, and independent prognostic factors were explored by Cox regression analyses. RESULTS: Patients without a tumor bed boost had a poor prognosis. The 5-year OS was 81.3% versus 58.3% and the 5-year PFS rates were 75.0% versus 57.6% (boost vs non-boost). The FIGO stage, pathology, adjuvant chemotherapy, and tumor bed boost were independent factors affecting both the 5-year OS and PFS. Subgroup analysis showed that the SIB group had a higher 5-year OS, PFS, and p-PFS for different stages, lymph node status, and risk groups than the non-SIB group. Recurrence occurred in 268 of 910 (29.5%) patients without SIB and 49 of 293 (16.7%) with SIB. Among patients with recurrence, 113 of 282 (40.1%) in the non-boost group compared with 14 of 51 (23.0%) patients in the boost group had a pelvic recurrence. Tumor bed boost resulted in an increase in the mean radiation dose to the intestine, rectum, and bladder, although there were no differences in the rates of acute and late toxicities between the 2 groups. CONCLUSION: Tumor bed boost by external beam radiotherapy (EBRT) is an effective and safe method for patients with FTSI and risk factors. Compared with the standard prophylactic radiation, tumor bed boost by EBRT was not associated with increased acute and late toxicities.

Adjuvant radiotherapy shows benefit in selected stage I uterine sarcoma: A risk scoring system based on a population analysis.

BACKGROUND: The potential therapeutic benefit of adjuvant radiotherapy for patients with stage I uterine sarcoma has not been clear. In this study, we aimed to develop a risk scoring model to select the subgroup of patients with stage I uterine sarcoma who might benefit from adjuvant radiotherapy. METHODS: Patients with stage I uterine sarcoma from the Surveillance, Epidemiology, and End Results program from 2010 to 2014 were retrospectively included in this analysis. Cox proportional hazards models were performed to identify risk factors. RESULTS: A total of 947 stage I uterine sarcoma patients were included. The 5-year disease-specific survival (DSS) of the overall cohort was 75.81%. Multivariate analysis identified stage (p = 0.013), tumor grade (p <0.001) and histology (p = 0.043) as independent prognostic factors for DSS, and these factors were used to generate the risk scoring model. The low-risk group presented a better DSS than the high-risk group (95.51% vs. 49.88%, p < 0.001). The addition of radiotherapy to surgery significantly increased the DSS in the high-risk group compared with surgery alone (78.06% vs. 46.88%, p = 0.022), but no significant survival benefit was observed in the low-risk group (98.36% vs. 100%, p = 0.766). CONCLUSIONS: Our risk scoring model based on stage, tumor grade, and histology predicted the outcome of patients with stage I uterine sarcoma cancer. This system may help to select stage I uterine sarcoma cancer patients who might benefit from adjuvant radiotherapy.

All-Weather Thermal Simulation Methods for Concrete Maglev Bridge Based on Structural and Meteorological Monitoring Data.

Thermal energy exchange induces non-uniform temperature distribution on the concrete bridge structures, leading to variation of static and dynamic properties of structural systems. The finite element method can facilitate thermal simulation and predict the structural temperature distribution based on heat flow theories. Previous studies mainly focused on the daytime with sunny weather, and the effects of solar shadow distribution were not fully considered or even ignored. In this paper, a systematic all-weather thermal simulation method was proposed to investigate the temperature distributions of concrete maglev bridges. The solar shadow distribution on the bridge surface could be accurately simulated to determine the solar radiation-imposed range. A meteorological station and some thermocouples were installed on a real concrete maglev bridge to obtain the real-time structural temperatures and environmental conditions. Its temperature distribution is also simulated using the proposed method within the 27 monitoring days in Summer. Results show that the simulated structural temperature matches well with the measured results under various weather conditions, except that of the east structural surface. Moreover, the simulation method acquired a higher accuracy under overcast or rainy weather due to weaker solar radiation effects. Both the numerical results and experimental records illustrated that direct solar radiation dominates the thermal energy exchange under sunny or cloudy conditions. The proposed methodology for temperature field simulation is oriented by all-weather prediction of structural temperature, which is reliable for concrete bridge structures with the help of accurate measurement of real-time solar radiation.

Chemotherapy Plus Radiotherapy Versus Radiotherapy in Patients With Small Cell Carcinoma of the Esophagus: A SEER Database Analysis.

BACKGROUND: Small cell carcinoma of the esophagus is a rare malignant tumor. We aimed to explore the chemotherapeutic efficacy on the prognosis of patients with small cell carcinoma of the esophagus who received radiotherapy. METHODS: To identify the population of interest, Surveillance, Epidemiology, and End Results data from 1996 to 2016 were chosen. Univariate and multivariate analyses were used to probe into prognosis factors. Multivariate Cox regression analysis was conducted to identify factors related to overall survival and cancer-specific survival. RESULTS: Overall, data from 162 patients were analyzed in this study. Tumor size (P = 0.014), T staging (P = 0.028), and chemotherapy (P < 0.001) were independent prognostic factors affecting overall survival. Patients with regional disease (hazard ratio = 5.435, P < 0.001) and distant metastasis (hazard ratio = 2.183, P < 0.001) who received radiotherapy alone had worse survival than those receiving chemoradiotherapy. Tumor size (P = 0.004) and chemotherapy (P < 0.001) were independent prognostic factors affecting cancer-specific survival. Tumor size was an independent factor affecting cancer-specific survival for patients receiving chemoradiation. CONCLUSIONS: Age, T staging, tumor size, primary site, and chemotherapy are independent prognosis factors affecting overall survival and cancer-specific survival in patients with small cell carcinoma of the esophagus who receive radiotherapy. Chemotherapy might further improve cancer-specific survival in patients with small cell carcinoma of the esophagus receiving radiotherapy at all stages.

Delayed postoperative radiotherapy might improve the long-term prognosis of locally advanced esophageal squamous cell carcinoma.

OBJECTIVE: There is no consensus on the optimal timing of postoperative radiotherapy (PORT) for locally advanced esophageal squamous cell carcinoma (ESCC). We aimed to determine whether the timing of PORT affects the long-term prognosis of ESCC, and plotted nomograms to predict survival. METHODS: We retrospectively analyzed 351 ESCC patients who underwent radical surgery and PORT. Receiver operating characteristic curves were used to estimate the optimal cutoff point of the time interval between surgery and PORT. Cox proportional hazards regression was used to identify prognostic predictors. Overall survival (OS) and progression-free survival (PFS) were predicted using nomograms. RESULTS: The median follow-up was 53 months (range: 3-179 months). Compared to early PORT, PORT at >48 days after surgery was associated with better OS (adjusted hazard ratio [HR]: 1.406, p = 0.037) and PFS (adjusted HR: 1.475, p = 0.018). In the chemotherapy subgroup, incorporation of chemotherapy timing into the analysis suggested that 2-4 chemotherapy cycles followed by PORT was the optimal treatment schedule as compared to 0-1 chemotherapy cycle followed by PORT and concurrent chemoradiotherapy (5-year PFS: 65.9% vs. 51.0% vs. 50.1%; p = 0.049). The nomograms for OS and PFS were superior to the TNM classification (concordance indices: 0.721 vs. 0.626 and 0.716 vs. 0.610, respectively). CONCLUSIONS: Delayed PORT (>48 days) provides better survival benefit than early PORT among ESCC patients. PORT following 2-4 chemotherapy cycles might lead to the best survival rate. The nomogram plotted in this study effectively predicted survival and may help guide treatment.

Prognostic factors and treatment comparison in small cell neuroendocrine carcinoma of the uterine cervix based on population analyses.

OBJECTIVE: We aimed to assess the impact of the treatment modality on the outcome of small cell neuroendocrine cervical carcinoma (SCNEC) using the Surveillance Epidemiology and End Results (SEER) database. METHODS: Patients from the SEER program between 1981 and 2014 were identified. Significant factors for cancer-specific survival (CSS) and overall survival (OS) were analyzed using the Kaplan-Meier survival and Cox regression methods. RESULTS: A total of 503 SCNEC patients were identified. The 5-year CSS and OS were 36.6% and 30.6%, respectively. The International Federation of Gynecology and Obstetrics (FIGO) stage I to IV distributions was 189 (37.6%), 108 (21.5%), 95 (18.9%), and 111 patients (22.0%), respectively. Within the patients with known treatment strategies, 177 (45.9%) were treated with radical surgery and 209 (54.1%) underwent primary radiotherapy. Local treatment strategies were independent prognostic factor for CSS and OS. The 5-year CSS for radical surgery and primary radiotherapy was 50.0% and 27.9%, respectively (P < .001). The 5-year OS for those who received radical surgery and primary radiotherapy was 57.8%, and 29.6%, respectively (P < .001). In FIGO stage I SCNEC, patients treated with radical surgery had superior CSS (P = .001) and OS (P = .003) than those with primary radiotherapy. However, in FIGO stage II and III SCNEC, there were no differences in CSS and OS with respect to different local treatment strategies. Our results also found that the addition of brachytherapy impacted OS in the FIGO stage III SENCE (P = .002). The 5-year CSS and OS of patients with FIGO IV were only 11.7% and 7.1%, respectively. CONCLUSIONS: SCNEC is a rare disease with aggressive clinical behavior. The findings indicate that radical surgery should be suggested for early-stage SCNEC and combining radiation therapy with brachytherapy should be suitable for patients with advanced stage.

[Percutaneous endoscopic lumbar discectomy combined with epidural injection for prolapsed lumbar disc herniation].

OBJECTIVE: To assess the effect of percutaneous endoscopic lumbar discectomy (PELD) combined with epidural injection for prolapsed lumbar disc herniation(PLDH). METHODS: In this prospective randomized controlled study, the clinical data of 126 patients who had undergone a PELD because of a single-level PLDH from March 2014 to June 2015 were analyzed. There were 67 males and 59 females, ranging in age from 17 to 75 years old with an average of(41.0±13.5) years old, 9 cases were L3,4, 76 cases were L4,5 and 41 cases were L5S1. According to the random number table, the patients were randomized into two groups, with 63 patients in each group. Patients in group 1 were injected normal saline after PLED, patients in group 2 were subjected to an epidural injection of Diprospan, Lidocaine and Mecobalamine after PLED. All the patients were followed up from 6 to 20 months with the mean of 12.4 months. Complications, the postoperative hospital stay, the period of return to work, visual analogue scale (VAS) and Japanese Orthopedic Association (JOA) score were compared between two groups, and clinical outcomes were evaluated according to modified MacNab criteria. RESULTS: All the operations were successful, and no complications were found. The mean postoperative hospital stay and the period of return to work in group 1 were (4.61±1.25) days and (4.31±0.47) weeks, respectively, and in group 2 were (2.53±0.69) days and (3.14±0.52) weeks, there was significant differences between two groups(P=0.000). Postoperative VAS and JOA scores in two groups were obviously improved (P=0.000). At 1 day, 1 week, 1 month after operation, VAS, JOA scores in group 2 were better than that of group 1(P=0.000), and after 6 months, there was no significant difference between two groups(P>0.05). According to the modified MacNab criteria, 39 cases got excellent results, 21 good, 3 fair in group 1, and which in group 2 were 41, 20, 2, respectively, there was no significant difference between two groups(P=0.087). CONCLUSIONS: PELD is an mini-invasive technique for PLDH, it can fleetly reduce pain and improve function. And combination with epidural injection has the advantages of pain releasing and function improving in the short-term postoperative period, and it can decrease postoperative hospital stay and time of returning to work, and it is a safe and effective method.