BART-D2 subtype of EBV encoded BART miRNA cluster 1 region is strongly associated with endemic nasopharyngeal carcinoma.

Epstein-Barr virus (EBV)-encoded BamHI A rightward transcript (BART) microRNAs (miRNAs) play important roles in viral infection and tumorigenesis. The association of sequence variations in the BART miRNA cluster 1 region with diseases remains unclear. Herein, 6 types and 11 subtypes of BART cluster 1 were identified in 354 tumors and healthy donors (HDs) from nasopharyngeal carcinoma (NPC)-endemic and nonendemic China (genotyped data), and 905 EBV genomes retrieved from GenBank from diseased and normal people from around the world (archived data). The distributions of BART cluster 1 types/subtypes between NPC-endemic and nonendemic China; between Asian regions and Africa/Europe & Australia & United States; and among Asian regions (NPC-endemic China, NPC-nonendemic East Asia and Southeast Asia) were significantly different (p < 0.001). The subtype BART-D2 was not found outside Asia and was only common in NPC-endemic China. More importantly, BART-D2 had a higher frequency in NPCs than in HDs in NPC-endemic China (genotyped data, 78.0% vs. 44.1%, p < 0.001; achieved data, 89.3% vs. 43.7%, p < 0.001), and was also more frequent in NPCs than in HDs, gastric carcinomas, and lymphomas in NPC-nonendemic China (genotyped data, 27.9% vs. 1.9%, 2.4%, and 0.0%, p < 0.001). BART-D2 was preferentially linked with the high-risk subtypes for NPC previously reported, 162476C or 163364T, in the BALF2 gene, and was associated with NPC risk (p < 0.01). In vitro experiments showed that BART-D2 affected the expression of some mature BART miRNAs. These findings demonstrate geographically restricted variations of BART cluster 1 and identify distinct subtype that is confined to NPC-endemic China and is associated with NPC.

Intraoperative hypotension is associated with shortened overall survival after lung cancer surgery.

BACKGROUND: Intraoperative hypotension is associated with increased morbidity and mortality after surgery. We hypothesized that intraoperative hypotension might also be associated with worse long-term survival after cancer surgery. Herein, we analyzed the correlation between intraoperative hyper-/hypotension and overall survival after lung cancer surgery. METHODS: In this retrospective cohort study, 676 patients who received lung cancer surgery between January 1, 2006 and December 31, 2009 were reviewed. Intraoperative hyper- and hypotension were defined according to their correlation with long-term survival. The primary endpoint was overall survival. The association between episodes of intraoperative hyper-/hypotension and overall survival was analyzed with multivariable Cox proportional hazard models. RESULTS: Long-term follow-ups were completed in 515 patients with a median duration of 5.2 years. The estimated 5-year survival rates were 66.5, 61.3, 56.5, and 41.2% in patients with only hypertension (systolic blood pressure > 140 mmHg for ≥5 min), with both hyper- and hypotension (systolic blood pressure < 100 mmHg for ≥5 min), with neither hyper- nor hypotension, and with only hypotension during surgery, respectively. After adjusting confounding factors, intraoperative hypotension was significantly associated with shortened overall survival (compared with patients with only intraoperative hypertension, those with both hyper- and hypotension: hazard ratio [HR]1.033, 95% confidence interval [CI] 0.709 to 1.507, p = 0.864; those with neither hyper- nor hypotension: HR 0.952, 95% CI 0.608 to 1.489, p = 0.829; those with only hypotension: HR 1.736, 95% CI 1.218 to 2.475, p = 0.002). CONCLUSIONS: For patients undergoing lung cancer surgery, intraoperative hypotension, but not hypertension, was associated with shortened overall survival.

Sequence variations of Epstein-Barr virus-encoded BARF1 gene in nasopharyngeal carcinomas and healthy donors from southern and northern China.

The BamHI A rightward frame 1 (BARF1) gene of the Epstein-Barr virus (EBV) is involved in carcinogenesis and immunomodulation of EBV-associated malignancies. The geographical distributions and the disease associations of BARF1 variants remain unclear. In the current study, the BARF1 variants in nasopharyngeal carcinoma (NPC) cases and healthy donors from southern and northern China, the NPC endemic and non-endemic areas, as well as in 153 sequenced EBV genomes from diseased and normal people from around the world, were determined and compared among areas and populations. Only 1 consistent coding change, V29A, and several consistent silent mutations were identified. Two BARF1 types (B95-8 and V29A) and 2 B95-8 subtypes (B95-8t165545c and B95-8P ) were classified. For Chinese isolates, the B95-8 type was dominant in both southern and northern China, but the isolates from southern China showed a higher frequency of the B95-8t165545c subtype than the isolates from northern China (76.0%, 38/50 NPC cases and 50.7%, 37/73 healthy donors vs 26.4%, 24/91 NPC cases and 7.6%, 6/79 healthy donors, P < .0001). Furthermore, the B95-8t165545c subtype was more frequent in NPC cases than healthy donors in both southern China (P = .005) and northern China (P = .001). For EBV genomes, the B95-8P subtype was dominant in northern China, Europe, America, and Australia, while V29A was dominant in Africa. The B95-8t165545c subtype was only identified in Asia and demonstrated high frequency (81.2%, 26/32) in genomes from NPC cases in southern China. These results further reveal conservation and possibly geographically spread variations of BARF1 and may also indicate the preference of EBV strains with the B95-8t165545c subtype in NPC cases, without biological or pathogenic implications.

Perioperative Management May Improve Long-term Survival in Patients After Lung Cancer Surgery: A Retrospective Cohort Study.

BACKGROUND: Surgical resection is the main treatment for patients with non-small-cell lung cancer (NSCLC), but patients' long-term outcome is still challenging. The purpose of this study was to identify predictors of long-term survival in patients after lung cancer surgery. METHODS: Patients who underwent surgery for NSCLC from January 1, 2006, to December 31, 2009, were enrolled into this retrospective cohort study. The primary outcome was the survival length after surgery. Predictors of long-term survival were screened with the multivariable Cox proportional hazard model. RESULTS: Postoperative follow-up was completed in 588 patients with a median follow-up duration of 5.2 years (interquartile range, 2.0-6.8). Two hundred ninety-one patients (49.5%) survived at the end of follow-up with median survival duration of 64.3 months (interquartile range, 28.5-81.6). The overall survival rates were 90.8%, 70.0%, and 57.1% at the end of the first, third, and fifth year after surgery, respectively. Limited resection (hazard ratio [HR], 1.46; 95% confidence interval [CI], 1.08-1.98; P = .013) and large tumor size (HR, 1.29; 95% CI, 1.17-1.42; P < .001) were associated with short survival; whereas high body mass index grade (HR, 0.82; 95% CI, 0.69-0.97; P = .021), highly differentiated tumor (HR, 0.59; 95% CI, 0.37-0.93; P = .024), dissection of mediastinal lymph node during surgery (HR, 0.45; 95% CI, 0.30-0.67; P < .001), and perioperative use of dexamethasone (HR, 0.70; 95% CI, 0.54-0.90; P = .006) were associated with long survival. No association was found between perioperative use of flurbiprofen axetil and long survival (HR, 0.80; 95% CI, 0.62-1.03; P = .086). However, combined administration of dexamethasone and flurbiprofen axetil was associated with longer survival (compared to no use of both: adjusted HR, 0.57; 95% CI, 0.38-0.84; P = .005). CONCLUSIONS: Certain factors in particular perioperative dexamethasone and flurbiprofen axetil therapy may improve patients' long-term survival after surgery for NSCLC. Given the small sample size, these findings should be interpreted with caution, and randomized clinical trials are needed for further clarification.

Crystal nucleation and metastable bcc phase in charged colloids: A molecular dynamics study.

The dynamic process of homogenous nucleation in charged colloids is investigated by brute-force molecular dynamics simulation. To check if the liquid-solid transition will pass through metastable bcc, simulations are performed at the state points that definitely lie in the phase region of thermodynamically stable fcc. The simulation results confirm that, in all of these cases, the preordered precursors, acting as the seeds of nucleation, always have predominant bcc symmetry consistent with Ostwald's step rule and the Alexander-McTague mechanism. However, the polymorph selection is not straightforward because the crystal structures formed are not often determined by the symmetry of intermediate precursors but have different characters under different state points. The region of the state point where bcc crystal structures of large enough size are formed during crystallization is narrow, which gives a reasonable explanation as to why the metastable bcc phase in charged colloidal suspensions is rarely detected in macroscopic experiments.

Phase II Study of Hepatic Arterial Infusion Chemotherapy with Oxaliplatin and 5-Fluorouracil for Advanced Perihilar Cholangiocarcinoma.

Purpose To evaluate the efficacy and safety of hepatic arterial infusion (HAI) of oxaliplatin and 5-fluorouracil for advanced perihilar cholangiocarcinoma (PCC) in this prospective phase II study. Materials and Methods The protocol was approved by the local ethics committee, and all patients gave informed consent. Patients with nonresectable PCC were included in a prospective, open phase II study investigating HAI through interventionally implanted port catheters. HAI consisted of infusions of oxaliplatin 40 mg/m2 for 2 hours, followed by 5-fluorouracil 800 mg/m2 for 22 hours on days 1-3 every 3-4 weeks. A maximum of six cycles of HAI were applied for tumor control patients followed by maintenance with oral capecitabine until tumor progression. The primary end points were tumor response and progression-free survival (PFS). The secondary end points were local PFS, overall survival, and adverse events. Kaplan-Meier methodology and Cox regression analysis were used to evaluate the risk factors for survival. Results Between 2012 and 2015, 37 patients were enrolled. The overall response rate was 67.6% (25 of 37), and the disease control rate was 89.2% (33 of 37). Median PFS, local PFS, and overall survival were 12.2, 25.0, and 20.5 months, respectively. All three survival lengths in patients with periductal infiltrating pattern were found to be significantly longer than those in patients with mass-forming pattern (P < .001, hazard ratio < 0.2). Macroscopic growth patterns (P = .018) and number of HAI cycles (P < .001) were independent risk factors of survival. The most frequent adverse events were grades 1 and 2 gastrointestinal side effects and sensory neuropathy in 31 (83.8%) and 28 (75.7%) patients, respectively. Conclusion HAI with oxaliplatin and 5-fluorouracil may be an encouraging treatment choice for advanced PCC due to its high tumor control, survival benefit, and low toxicity, especially in patients with periductal infiltrating pattern. © RSNA, 2016.

[Prognostic analysis of 525 Chinese patients with diffuse large B cell lymphoma].

OBJECTIVE: To describe the clinical characteristics, overall survival as well as to evaluate the prognostic factors in Chinese diffuse large B cell lymphoma (DLBCL) patients. METHODS: DLBCL patients who were initially diagnosed and treated in Peking University Cancer Hospital from January 1995 to December 2008 were identified and analyzed,retrospectively.The 5-year OS rates were estimated with Kaplan-Meier. Log-rank test was used to compare the survival curves of the different groups. The multivariate analysis of prognostic factors was conducted with Cox regression model, which included all statistically significant prognostic factors in the univariate analyses. RESULTS: A total of 525 DLBCL patients were included in this retrospective analysis, of whom, 294 were male and 231 female (male:female=1.27:1). The median age at the initial diagnosis was 55 (range 16-90) years, and 37.0% (n=194) were 60 years and above. Regarding the clinical staging at the initial diagnosis, 54 patients (10.3%) were diagnosed as Stage I of the disease, 152 (28.9%) as Stage II, 117 (22.3%) as Stage III and 202 (38.5%) as Stage IV. The "B symptoms" and increased serum LDH were presented in 206 (39.2%) and 192 (36.6%) patients, respectively. A total of 197 (37.5%) patients were treated with rituximab (R). The survival follow-up continued till 31 January 2014 with a median follow-up time of 77.5 (range: 0-205) months. A total of 267 patients (50.9%) died during the follow-up period. The medial overall survival (OS) time was 84 months, and 5-year OS rate was 52.3%. There were six statistically significant prognostic factors that were identified in both univariate and multivariate analyses: gender, Ann Arbor stage, B symptom, serum LDH, age at initial diagnosis and rituximab treatment. The relative risk (RR) of these prognostic factors in the multivariate analyses were: age > 60 years / ≤ 60 years=1.380 (95%CI 1.078-1.765), male / female=1.315 (95%CI 1.025-1.687), stage III/stage I=3.034 (95%CI 1.667-5.522), stage IV/I=3.748(95%CI 2.102-6.681), with B symptoms/without B symptoms=1.278(95%CI 0.999-1.636), serum LDH increased/LDH not increased=1.351(95%CI 1.057-1.726), without R treatment / with R treatment=1.543 (95%CI 1.182-2.015).Compared with the IPI, age >50 years/ ≤ 50 years was a statistically significant factor in both univariate and multivariate analyses RR=1.478 (95%CI 1.148-1.902), P=0.002. CONCLUSION: Six factors were related to DLBCL survival: gender, Ann Arbor stage, B symptom, serum LDH, age at initial diagnosis and rituximab treatment. Compared with the IPI, several specific factors may predict a poor prognosis in Chinese DLBCL patients: male, age>50 years and the presence of "B symptoms". But this result is not conclusive until these factors are further tested.

Correlation between TyG index and coronary atherosclerosis assessed by CCTA in elderly male patients: a cross-sectional study.

BACKGROUND: Age is a major risk factor associated with the complexity of coronary artery disease (CAD), and the prognosis of elderly patients with coronary heart disease is relatively poor. Metabolic disturbances are prevalent in the elderly population and contribute to CAD morbidity and mortality. This study aimed to investigate the relationship between the triglyceride-glucose (TyG) index and total coronary atherosclerotic burden assessed non-invasively by Coronary Computed Tomography Angiogram (CCTA) in the elderly population. METHODS: This retrospective cross-sectional study involved 427 patients who underwent CCTA. The patients were divided into two groups based on their Leiden score: ≥5 and < 5. Comparisons between groups were conducted using t-tests or Mann-Whitney U tests for continuous variables and chi-square tests for categorical variables. The correlation between TyG and Leiden score was assessed using Spearman's rank correlation coefficient. Univariable and multivariable logistic regression analyses were performed to assess the role of TyG in atherosclerosis risk, using clinical variables previously shown to independently predict a high Leiden score. RESULTS: The levels of age and HbA1c% were significantly higher in patients with Leiden score ≥ 5. Patients with Leiden score ≥ 5 showed no significant difference in TyG index compared to those with Leiden score < 5. Pearson correlation analysis showed that HbA1c% (r = 0.44, p < 0.01), age (r = 0.34, p < 0.01), and FBG (r = 0.15, p = 0.01) were positively correlated with Leiden score, while TyG index had no correlation with Leiden score (r = 0.05, p = 0.42). Multiple linear regression analysis showed that HbA1c% (ß = 2.92, 95%CI: 2.25-3.56, P < 0.01) was positively correlated with Leiden score, while TyG index had no correlation with Leiden score (ß = 0.73, 95%CI: -3.27-4.72, P < 0.01). HbA1c% was found to be an influential factor for obstructive CVD (ß = 1.86, 95%CI: 1.50-2.29, P < 0.01), while TyG index was not an independent risk factor for obstructive CVD (ß = 0.39, 95%CI: 0.12-1.32, P = 0.13). CONCLUSION: The TyG index did not show any significant correlation with the Leiden score and obstructive CVD as a risk factor in elderly male population. On the other hand, HbA1c% was identified as an influential factor for both the Leiden score and obstructive CVD.

Impact of anesthetic factors on prognosis of patients with non-small cell lung cancer after surgery.

Background: Nowadays, the influence of anesthesia management on the prognosis of cancer patients has been widely concerned. The goal of this study is to assess the association between anesthetic factors and the prognosis of patients with non-small cell lung cancer (NSCLC) after surgery. Methods: Patients with NSCLC who underwent surgery from January 1, 2006, to December 31, 2009 were selected. Cox proportional hazards model and Logistic regression analysis model were used to screen the independent predictors of prognosis of patients. The primary endpoint was postoperative overall survival (OS), and the secondary endpoint was postoperative recurrence-free survival (RFS) and postoperative pulmonary complications (PPCs). Results: A total of 588 patients were included into the final analysis. The overall RFS was 4.4 [interquartile range (IQR), 1.1-10.1] years, and the OS was 6.2 (IQR, 2.4-10.2) years. Age ≥60 years, advanced tumor stage, and maximal tumor size >3 cm were associated with shortened survival, whereas high BMI grade, mediastinal lymph node dissection, perioperative fentanyl equivalents >28.2 µg/kg, and high tumor grade were associated with prolonged survival (P<0.05); perioperative glucocorticoid administration delayed recurrence (P<0.05); advanced tumor stage and perioperative fentanyl equivalents >28.2 µg/kg were associated with an increased PPCs risk (P<0.05). Conclusions: The findings from this study revealed that perioperative anesthetic factors may impact the prognosis of patients with NSCLC after surgery. Perioperative opioid and glucocorticoid exposure were independent predictors for outcomes. However, perioperative fentanyl equivalents over 28.2 µg/kg seemed to be beneficial to OS, but contribute to the occurrence of PPCs.

Association of blood pressure variability and CT-based Leiden score in hypertension patients.

Background: Blood pressure variability (BPV) obtained from ambulatory blood pressure monitoring (ABPM) has been demonstrated to accurately predict the risk of cerebrovascular events and death in hypertension patients, however, the association between BPV and the severity of coronary atherosclerotic plaque remains unclear. Methods: Patients with hypertension combined with suspected coronary artery disease (CAD) were collected, who underwent both ABPM and coronary computed tomographic angiography (CCTA) from December 2017 to March 2022. Patients were divided into three groups according to the Leiden score: low-risk group (Leiden score <5), medium-risk group (Leiden score 5-20), and high-risk group (Leiden score >20). The clinical characteristics of patients were collected and analyzed. Univariate Pearson correlation and multivariate Logistics regression were used to determine the association between BPV and the severity of coronary atherosclerotic plaque. Results: A total of 783 patients were included, with the average age of (62.85 ± 10.17) years and 523 males. Patients in the high-risk group had higher mean systolic blood pressure (SBP), nighttime mean SBP and SBP variability (P < 0.05). Leiden score with low risk was associated with 24 h-SBP variability (r = 0.35, P = 0.006) and 24 h-diastolic blood pressure (DBP) loading (r = -0.18, P = 0.027). Leiden score with medium and high risk was associated with nighttime mean SBP (r = 0.23, P = 0.005), 24 h-SBP variability (r = 0.32, P = 0.003), and the decrease of nighttime SBP (r = 0.24, P = 0.019). Multivariate Logistic analysis showed that smoking [odds ratio (OR) = 1.014, 95% confidential interval (CI): 1.0-1.07, P = 0.03], diabetes (OR = 1.43, 95% CI: 1.10-2.26, P = 0.01) and 24 h-SBP variability (OR = 1.35, 95% CI: 1.01-2.46, P = 0.01) were independently associated with Leiden score with medium and high risk. Conclusion: Larger SBP variability in hypertensive patients indicates the higher Leiden score and consequently the more serious coronary atherosclerotic plaque. Monitoring SBP variability has certain significance for predicting the severity of coronary atherosclerotic plaque and preventing its progression.

Different situations of identifying second primary malignant tumors in lymphoma patients with synchronous solid tumors.

BACKGROUND: To our knowledge, the different situations of identifying second primary malignant tumors (SPMTs) in lymphoma patients with synchronous solid tumors remain to be comprehensively investigated. METHODS: We retrospectively collected information pertaining to lymphoma patients with synchronous solid tumors (diagnosed within 6 months) at Peking University Cancer Hospital & Institute between 2009 and 2019. The non-parametric Aalen-Johansen estimator was applied to calculate cumulative incidence function in the competing risk model. Furthermore, propensity score-matched analysis was performed to compare survival differences in lymphoma patients with or without synchronous solid tumors. RESULTS: Thirty-eight patients were enrolled. There were three situations of identifying SPMTs. First, in 15 patients (39.5%), SPMTs were identified before the initiation of any treatment. Among them, priority was given to anti-lymphoma treatment in case of only three patients. Second, in 17 patients (44.7%), SPMTs were unexpectedly detected on surgical specimen assessment; of them, 13 received anti-lymphoma treatment after surgery. Third, in six patients (15.8%), SPMTs were identified after the outset of treatment for the primary tumor; in this population, three of four patients with lymphoma switched toward the treatment plan for SPMTs. The 5-year overall survival was 58.7%. The cumulative incidence function within 5 years was 26.6% for lymphoma and 14.7% for other solid tumors. The early identification of SPMTs was associated with better outcomes (p = 0.048). After balancing the baseline characteristics, no differences in survival were observed between lymphoma patients with and without synchronous solid tumors (p = 0.664). CONCLUSIONS: This is the first study to present the different situations of identifying SPMTs in lymphoma patients with synchronous solid tumors. In only <50% patients, SPMTs were identifiable at baseline. SPMT identification at different situations may make it difficult to choose the optimal therapeutic option, which may consequently impact patient survival.

Effect of autologous hematopoietic stem cell transplantation for patients with peripheral T-cell lymphoma in China: A propensity score-matched analysis.

Background: The role of consolidation therapy with autologous stem cell transplantation (ASCT) in patients with peripheral T-cell lymphoma (PTCL) in first complete remission (CR1) or partial remission (PR1) remains controversial. The existing data from China are limited. Therefore, we aimed to investigate the effect of ASCT on the survival of Chinese patients with PTCL showing response to induction chemotherapy at our hospital. Methods: We retrospectively reviewed the data of patients with PTCL (excluding Natural killer/T cell lymphoma) in CR1 or PR1 treated at Peking University Hospital &Institute from 1996 to 2020. Propensity score matching (PSM) was used to balance clinical characteristics between the ASCT and non-ASCT groups. The primary endpoints were event-free survival (EFS) and overall survival (OS). Results: Of the 414 selected patients, 73 received ASCT consolidation and 341 did not. Over a median follow-up of 5.7 years, survival was significantly better in the ASCT group than in the non-ASCT group (median EFS, 8.1 years vs. 2.8 years, P = 0.002; median OS, 14.9 years vs. 10.2 years, P = 0.007). The 5-year EFS and OS rates were 68.4% and 77.0% in ASCT group, and 43.2% and 57.6% in non-ASCT group, respectively. The survival benefit was confirmed in the propensity score matched cohort (46 patients who received ASCT and 84 patients who did not receive ASCT): P = 0.007 for median EFS and P = 0.022 for the median OS. Cox regression analysis showed that ASCT was independently associated with better survival: hazard ratio (HR) for EFS, 0.46 (95% CI: 0.28-0.76); HR for OS, 0.50 (95% CI: 0.31-0.84). Subgroup analysis showed that ASCT was more likely to benefit higher-risk patients and those with advanced disease. Among the subtypes of PTCL, the benefit was significant in angioimmunoblastic T-cell lymphoma (HR = 0.26 [95% CI: 0.10-0.66] for EFS and 0.29 [95% CI: 0.12-0.74] for OS), but not in the other subtypes. Conclusion: ASCT may improve the long-term survival of patients with PTCL in first CR or PR, especially for patients with angioimmunoblastic T-cell lymphoma. The specific groups most likely to benefit from upfront ASCT need to be clearly identified.

Effect of infection with hepatitis B virus on the survival outcome of diffuse large B-cell lymphoma in the prophylactic antiviral era.

Patients with lymphoma who are also infected with Hepatitis B virus (HBV) have a poor prognosis. This could be partly explained by the delay or premature termination of anti-tumor treatment because of HBV reactivation. However, there is limited data on the survival outcome of patients HBV-related lymphoma in the era of prophylactic antivirals. Data for 128 patients with HBV surface antigen-positive diffuse large B-cell lymphoma was collected. The median age was 54 years and the ratio of men to women was 1.2:1. All patients received immune-chemotherapy and prophylactic antiviral therapy. The median number of cycles of immune-chemotherapy was six. The overall response rate was 82%, with a complete remission rate of 75%. With a median follow-up of 58.4 months, the 5-year progression-free survival and overall survival rates were 75.7% and 74.7%, respectively. Nine patients experienced HBV reactivation but none experienced HBV-associated hepatitis. Patients with low and high HBV DNA loads had comparable survival outcomes. In conclusion, HBV infection had no negative effect on the prognosis of DLBCL in the era of prophylactic antiviral therapy.

Clinical significance and interrelations of PD-L1 expression, Ki-67 index, and molecular alterations in sporadic medullary thyroid carcinoma from a Chinese population.

Immunotherapy shows prospects in treating advanced medullary thyroid carcinoma although controversial reports are present. Recently, histological grading has been applied to medullary thyroid carcinoma by the Ki-67 index, mitotic figures, and tumor necrosis. However, the interrelation of PD-L1 expression, the Ki-67 index, and major genetic alterations of sporadic medullary thyroid carcinoma has not been fully reported. We examined the expression of PD-L1 (SP142 and 22C3) and the Ki-67 index immunohistologically and detected the major genetic alterations by next-generation sequencing in a cohort of sporadic medullary thyroid carcinomas, studied their survival impact, and discussed their interrelation. We identified that a high Ki-67 index (> 2%) and positive RET M918T mutation were correlated with poor disease-free survival but were not correlated with PD-L1 expression. All PD-L1 positive tumors were RET M918T mutation negative, and PD-L1 expression was positively correlated with HRAS mutation. The Ki-67 index was correlated with neither PD-L1 expression nor major genetic alterations. Our results indicate that immunotherapy targeting PD-L1/PD-1 might be more effective for patients with sporadic medullary thyroid carcinoma harboring HRAS mutations.

Pyrrolidine dithiocarbamate inhibits nuclear factor-κB pathway activation, and regulates adhesion, migration, invasion and apoptosis of endometriotic stromal cells.

The activation of nuclear factor-κB (NF-κB) has been implicated in the development and progression of endometriosis. The aim of this study is to investigate the potential application of pyrrolidine dithiocarbamate (PDTC), a potent NF-κB inhibitor, in the treatment of endometriosis. NF-κB-DNA-binding activity, IκB phosphorylation and expression of nuclear p65 protein in endometriotic ectopic stromal cells (EcSCs), endometriotic eutopic stromal cells (EuSCs) and normal endometrial stromal cells (NESCs) were detected by electrophoretic mobility shift assay and western blot analysis. Adhesion, migration, invasion and apoptosis of EcSCs were observed by means of adhesion, migration, invasion and terminal deoxynucleotidyl transferase-mediated dUDP nick-end labeling assay, respectively. Gene and protein expressions of CD44s, matrix metalloproteinase (MMP)-2, MMP-9 and survivin in EcSCs were measured by RT-PCR and western blot analysis. The results showed that PDTC in the absence or presence of interleukin (IL)-1ß showed stronger inhibitory effects on NF-κB-DNA-binding activity, IκB phosphorylation and expression of nuclear p65 protein in EcSCs than those in EuSCs or NESCs. PDTC enhanced apoptosis, and suppressed IL-1ß-induced cellular adhesion, migration and invasion of EcSCs. Pretreatment of EcSCs with PDTC attenuated IL-1ß-induced expressions of CD44s, MMP-2, MMP-9 and survivin at gene and protein levels. All these findings suggest that PDTC induces apoptosis and down-regulates adhesion, migration and invasion of EcSCs through the suppression of various molecules. Therefore, PDTC could be used as a therapeutic agent for the treatment of endometriosis.

Pyrrolidine dithiocarbamate attenuates nuclear factor-ĸB activation, cyclooxygenase-2 expression and prostaglandin E2 production in human endometriotic epithelial cells.

BACKGROUND: The nuclear factor-κB (NF-κB) pathway activates many of the target genes that are critical to the initiation and establishment of endometriosis. We sought to examine the potential application of pyrrolidine dithiocarbamate (PDTC), a potent NF-κB inhibitor, in the treatment of endometriosis. METHODS: The phosphorylation of IκB, expression of nuclear p65 protein and NF-κB DNA binding in endometriotic epithelial cells (EECs), endometriotic eutopic epithelial cells (EuECs) and normal epithelial cells (NECs) were detected by Western blot analysis and electrophoretic mobility shift assay. Cyclooxgenase-2 (COX-2) gene and protein expressions in EECs were measured by RT-PCR and Western blot analysis. Prostaglandin E(2) (PGE(2)) production of EECs was measured by ELISA. RESULTS: PDTC in the absence or presence of tumor necrosing factor-α (TNF-α) showed stronger inhibitory effects on IκB phosphorylation, expression of nuclear p65 protein and NF-κB DNA-binding activity in EECs than in EuECs or NECs. Pretreatment of EECs with PDTC resulted in a dose-dependent reduction in the TNF-α-induced expressions of COX-2 at gene and protein levels, as well as a reduction of PGE(2) synthesis. CONCLUSION: PDTC may represent a novel therapeutic strategy for treatment of endometriosis.

Conditional survival and hazards of death for peripheral T-cell lymphomas.

Typically, peripheral T-cell lymphoma (PTCLs) prognosis is estimated using overall survival before treatment. However, these estimates cannot show how prognosis evolves with the changing hazard rate over time. Patients (n = 650) with newly diagnosed PTCLs were enrolled retrospectively. After a median follow-up of 5.4 years, angioimmunoblastic T-cell lymphoma, peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) and NK/T cell lymphoma had initially lower 3-year conditional overall survival (COS3; i.e., the 3-year conditional overall survival was defined as the probability of surviving an additional 3 years) and higher hazards of death (26-44.3%). However, after 2 years, the COS3 increased and the death risk decreased over time, whereas anaplastic lymphoma kinase-positive anaplastic large-cell lymphoma constantly had a lower risk over time (0-19.5%). For patients with complete remission after initial treatment, prognosis varied by histological subtypes, with PTCL, NOS having a negative impact. Our data suggested that the risk stratification using the International Prognostic Index might not accurately predict the COS3 for survivors of PTCLs. The COS3 provided time-dependent prognostic information for PTCLs, representing a possible surrogate prognosis indicator for long-term survivors after systemic chemotherapy.

Effects of fucoidan on gut flora and tumor prevention in 1,2-dimethylhydrazine-induced colorectal carcinogenesis.

Colorectal cancer (CRC) is one of the major malignancies in humans. This study was designed to evaluate the effects of fucoidan on gut flora and tumor prevention in 1,2-dimethylhydrazine-induced colorectal carcinogenesis in rats. We found that dietary fucoidan treatment decreased the tumor incidence and mean tumor weight and increased cell apoptosis. Fucoidan treatment decreased the expression of ß-catenin C-Myc, CyclinD1 and Survivin, while the Hippo pathway was activated with increased phosphorylation levels of mammalian sterile 20-like kinase 1 and 2, large tumor suppressor 1 and 2, and Yes-associated protein. Compared with the model group, the levels of interleukin (IL)-17 and IL-23 were decreased, but the levels of interferon-γ, IL-4 and IL-10 were increased, in the fucoidan group. Fucoidan treatment increased natural killer cells in peripheral blood and the proportion of CD4+ T cells. Immunofluorescence detection of colorectal tumor tissues showed decreased expression of Foxp3 and up-regulated expression of CD68 in the fucoidan group. Moreover, fucoidan treatment decreased the levels of diamine oxidase and lipopolysaccharides and up-regulated the levels of tight junction proteins. 16S rDNA high-throughput sequencing revealed that fucoidan treatment decreased the abundance of Prevotella and increased the abundance of Alloprevotella. Fucoidan increased the levels of butyric acid and valeric acid compared to the model group. This study provides experimental evidence that dietary fucoidan may prevent colorectal tumorigenesis by regulating gut microecology and body immunity. Meanwhile, fucoidan activated the Hippo pathway and down-regulated the ß-catenin pathway to induce tumor cell apoptosis and suppress tumor growth.

Efficacy of transcutaneous electrical acupoint stimulation combined with general anesthesia for sedation and postoperative analgesia in minimally invasive lung cancer surgery: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Multimodal opioid-sparing analgesia is a key component of an enhanced recovery pathway after surgery that aims to improve postoperative recovery. Transcutaneous electrical acupoint stimulation (TEAS) is assumed to alleviate pain and anxiety and to modify the autonomic nervous system. This study aimed to determine the efficacy of TEAS for sedation and postoperative analgesia in lung cancer patients undergoing thoracoscopic pulmonary resection. METHODS: A total of 80 patients were randomized into two groups: the TEAS group and the sham TEAS combined with general anesthesia group. Postoperative pain levels at six, 24, 48 hours, and one month after surgery were measured using the visual analogue scale (VAS). Bispectral index (BIS) score during the TEAS prior to anesthetic induction, Observer's Assessment of Alertness/Sedation (OAAS) score, sufentanil consumption during postoperative patient-controlled intravenous analgesia (PCIA), number of total and effective attempts of PCIA pump use, and incidence of postoperative nausea and vomiting were recorded and analyzed statistically. RESULTS: Patients in the TEAS group had significantly lower VAS scores at six, 24, and 48 hours after surgery (P < 0.01); lower BIS scores at 10, 20, and 30 minutes before induction (P < 0.01); lower levels of postoperative sufentanil consumption; lower number of PCIA attempts and effective rates (P < 0.01); lower incidences of nausea at 0, six, 24, and 48 hours; and lower incidence of vomiting at 24 hours after surgery (P < 0.05). The postoperative OAAS scores were similar between the groups. CONCLUSIONS: TEAS could be a feasible approach for sedation and postoperative analgesia in thoracoscopic pulmonary resection.