Multi-frequency electromagnetic radiation induces anxiety in mice via inflammation in the cerebral cortex.

Modern life is filled with radiofrequency electromagnetic radiation (RF-EMR) in various frequency bands, while the health risks are not clear. In this study, mice were whole-body exposed to 0.9/1.5/2.65 GHz radiofrequency radiation at 4 W/kg for 2 h per day for 4 weeks to investigate the emotional effects. It was found that the mice showed anxiety but no severe depression. The ELISA results showed a significant decrease in amino acid neurotransmitters (GABA, DA, 5-HT), although acetylcholine (ACH) levels were not significantly altered. Furthermore, Western blot results showed that BDNF, TrkB, and CREB levels were increased in the cerebral cortex, while NF-κB levels were decreased. In addition, pro-inflammatory factors (IL-6, IL-1ß, TNF-α) were significantly elevated, and anti-inflammatory factors (IL-4, IL-10) tended to decrease. In conclusion, multi-frequency electromagnetic radiation induces an inflammatory response through the CREB-BDNF-TrkB and NF-κB pathways in the cerebral cortex and causes a decrease in excitatory neurotransmitters, which ultimately causes anxiety in mice.

Unexpected mutations occurred in CRISPR/Cas9 edited Drosophila analyzed by deeply whole genomic sequencing.

CRISPR/Cas9 possesses the most promising prospects as a gene-editing tool in post-genomic researches. It becomes an epoch-marking technique for the features of speed and convenience of genomic modification. However, it is still unclear whether CRISPR/Cas9 gene editing can cause irreversible damage to the genome. In this study, we successfully knocked out the WHITE gene in Drosophila, which governs eye color, utilizing CRISPR/Cas9 technology. Subsequently, we conducted high-throughput sequencing to assess the impact of this editing process on the stability of the entire genomic profile. The results revealed the presence of numerous unexpected mutations in the Drosophila genome, including 630 SNVs (Single Nucleotide Variants), 525 Indels (Insertion and Deletion) and 425 MSIs (microsatellite instability). Although the KO (knockout) specifically occurred on chromosome X, the majority of mutations were observed on chromosome 3, indicating that this effect is genome-wide and associated with the spatial structure between chromosomes, rather than being solely limited to the location of the KO gene. It is worth noting that most of the mutations occurred in the intergenic and intron regions, without exerting any significant on the function or healthy of the animal. In addition, the mutations downstream of the knockout gene well beyond the upstream. This study has found that gene editing can lead to unexpected mutations in the genome, but most of these mutations are harmless. This research has deepened our understanding of CRISPR/Cas9 and broadened its application prospects.

Tenofovir versus entecavir on the prognosis of hepatitis B-related hepatocellular carcinoma after surgical resection: a randomised controlled trial.

BACKGROUND: Nucleot(s)ide analog treatment (entecavir (ETV) and tenofovir (TDF)) is reported to be associated with decreased tumor recurrence and death in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients, yet further work is needed to evaluate the different efficacies of these two agents on the prognosis of early-stage HBV-related HCC patients after curative liver resection. MATERIAL AND METHODS: From July 2017 to January 2019, 148 patients with HBV-related HCC who underwent curative liver resection were randomized to receive TDF ( n =74) or ETV ( n =74) therapy. The primary end point was tumor recurrence in the intention-to-treat population. Overall survival and tumor recurrence of patients were compared by multivariable-adjusted Cox regression and competing risk analyses. RESULTS: During the follow-up with continued antiviral therapy, 37 (25.0%) patients developed tumor recurrence, and 16 (10.8%) patients died ( N =15) or received liver transplantation ( N =1). In the intention-to-treat cohort, the recurrence-free survival for the TDF group was significantly better than that for the ETV group ( P =0.026). In the multivariate analysis, the relative risks of recurrence and death/liver transplantation for ETV therapy were 3.056 (95% CI: 1.015-9.196; P =0.047) and 2.566 (95% CI: 1.264-5.228; P =0.009), respectively. Subgroup analysis of the PP population indicated a better overall survival and RFS of patients receiving TDF therapy ( P =0.048; hazard ratio (HR) =0.362; 95% CI: 0.132-0.993 and P =0.014; HR =0.458; 95% CI: 0.245-0.856). Additionally, TDF therapy was an independent protective factor against late tumor recurrence ( P =0.046; (HR)=0.432; 95% CI: 0.189-0.985) but not against early tumor recurrence ( P =0.109; HR =1.964; 95% CI: 0.858-4.494). CONCLUSION: HBV-related HCC patients treated with consistent TDF therapy had a significantly lower risk of tumor recurrence than those treated with ETV after curative treatment.

Assessment of age as different variable types for determining survival in differentiated thyroid cancer.

PURPOSE: The current tumor, node, metastasis (TNM) system uses an age of 55 years as a threshold for differentiated thyroid cancer (DTC). The aim of our study was to explore the concept of using age as a continuous variable. METHODS: A total of 36,559 patients with DTC in the Surveillance, Epidemiology, and End Results (SEER) database and 7491 patients in our centers were enrolled. Overall survival (OS) and cancer-specific survival (CSS) were compared. Furthermore, the different statistical model performance of the 6th edition TNM system and age cutoffs for papillary (PTC) and follicular thyroid cancer (FTC) were assessed. Then, a nomogram was built and validated to evaluate the efficacy of age as a continuous variable for predicting survival. RESULTS: The OS and CSS of patients with DTC were significantly increased in patients <55 years compared with those aged ≥55 years. However, no significant differences in prognosis were observed in certain groups as patients between 50 and 60 years were stratified by 1-year increments. Furthermore, the highest concordance index (C-index) was observed in the TNM staging without an age cutoff in SEER database (0.895), our two centers (0.877) and receiver operating characteristic (ROC) curves showed different age cutoffs for PTC and FTC. More importantly, the nomogram incorporating age as a continuous variable showed a favorable area under the ROC curve and calibration for training and validation groups. CONCLUSIONS: The utilization of age as a continuous variable is a rational approach for predicting outcome in DTC patients.

Prognostic implications of extranodal extension in papillary thyroid carcinomas: A propensity score matching analysis and proposal for incorporation into current tumor, lymph node, metastasis staging.

BACKGROUND: The current American Joint Committee on Cancer tumor, lymph node, metastasis cancer staging system for papillary thyroid carcinoma places low weight on extranodal extension. This study examined the prognostic implications of extranodal extension in papillary thyroid carcinoma patients and attempted to design a new staging system incorporating extranodal extension. METHODS: We reviewed data from 6,165 consecutive papillary thyroid carcinoma patients from 2012 to 2018. Patients with extrathyroidal extension or extranodal extension were included and then divided into 3 groups: extrathyroidal extension (papillary thyroid carcinoma with extrathyroidal extension but without extranodal extension, N = 457); extranodal extension (papillary thyroid carcinoma with extranodal extension but without extrathyroidal extension, N = 116); and extrathyroidal extension and extranodal extension (papillary thyroid carcinoma with both extrathyroidal extension and extranodal extension, N = 116). Recurrence-free survival and cancer-specific survival were compared before and after adjusting for differences using propensity score matching owing to observed heterogeneity in baseline characteristics in the original cohort. Recurrence-free survival and cancer-specific survival were also compared between patients with and without extranodal extension after matching at a 1:1 ratio. Cox proportional hazards regression analyses were used to identify the relationships of factors associated with structural recurrent disease in the node-positive subset. Then a new staging system incorporating extranodal extension was established, and the discrimination of the new staging system for recurrence-free survival and cancer-specific survival was investigated. RESULTS: Of the 6,165 patients with papillary thyroid carcinoma, extrathyroidal extension was found in 573 (9.3%) patients, and extranodal extension was observed in 232 (3.8%) patients. The recurrence-free survival and cancer-specific survival rates of patients with extranodal extension were similar to those of patients with extrathyroidal extension (all P > .05). Patients with extrathyroidal extension and extranodal extension experienced worse recurrence-free survival than patients with extrathyroidal extension or extranodal extension and even worse cancer-specific survival than patients with extrathyroidal extension (all P < .05). The recurrence-free survival and cancer-specific survival rates of patients with extranodal extension were worse than those of patients without extranodal extension (P = .003; P = .048). Cox proportional hazards regression analysis demonstrated that after propensity score matching, extranodal extension (hazard ratio 1.911; 95% confidence interval 1.568-3.609; P < .001) remained an independent predictor of structural recurrent disease in patients with node-positive papillary thyroid carcinoma. After incorporating extranodal extension into the current tumor, lymph node, metastasis classification, the new staging system presented a better discrimination for recurrence-free survival and cancer-specific survival for those with lymph node metastasis. CONCLUSION: Papillary thyroid carcinoma patients with extranodal extension present worse prognosis, and incorporating extranodal extension in tumor, lymph node, metastasis classification identifies poor-risk patients more accurately.

Intraoperative application of inactivated Pseudomonas aeruginosa in patients undergoing lateral neck dissection for metastatic thyroid cancer: A randomized, parallel group, placebo-controlled trial.

BACKGROUND: We hypothesize that the intraoperative, prophylactic application of Pseudomonas aeruginosa can decrease postoperative chylous fistula and enhance recovery after surgery in patients with thyroid cancer undergoing lateral neck lymph node dissection. METHOD: In this single-center trial, we assigned randomly 200 patients with thyroid cancer who had proven lateral lymph node metastasis to groups receiving either 2 mL Pseudomonas aeruginosa spray (Pseudomonas aeruginosa group) or 2 mL saline spray (control group) in the lateral cervical surgical field. The primary end points were the rate of chylous fistula, mean difference in the duration and volume of drainage fluid, days of postoperative hospital stay, and overall cost. The secondary end points included the red blood cell count and triglyceride level in the drainage, the white blood cell count in the blood, fever, local pain, development of a pleural effusion, and tumor recurrence. RESULTS: Patients treated with Pseudomonas aeruginosa had a decrease in macroscopic chylous fistula compared with controls (0 vs 6%, P = .025). There were fewer days to drain-tube removal, a less volume of drainage fluid, fewer postoperative days of hospital stay, and a lesser red blood cell count in the drainage fluid in the Pseudomonas aeruginosa group than in the control group (all P < .05). No severe side effects of the Pseudomonas aeruginosa spray with respect to fever, pain, or pleural effusion were observed. Pseudomonas aeruginosa spraying did not affect postoperative recurrence of the thyroid cancer. CONCLUSION: Intraoperative spraying of inactivated Pseudomonas aeruginosa in the lateral neck compartment can decrease the development of chylous fistula and enhance postoperative recovery.

Measuring inclusive wealth of China: Advances in sustainable use of resources.

The inclusive wealth approach is increasingly common to measure the sustainable development of the countries. It comprised the natural, human and produced capital of nations to measure social wellbeing. We measure the inclusive wealth of the provinces in China from 2000 to 2015 and reports the sustainable use of the resources. We identify that three types of capital have increased to varying degrees, with produced capital increasing by 615.6%, natural capital increasing by 33.8%, and human capital increased by 337.0%. The total amount of inclusive wealth has increased by 300.4% in the past 15 years. However, the provinces in China are still facing unbalanced development across the country compared to developed nations. The use of the natural capital, more specifically now-renewable resources, has been restricting the wealth growth in some provinces. Although ecological services account for a small proportion of the total inclusive wealth, more attention is essential for sustainable development. Meanwhile, the rapid growth of carbon damages posed threat to future wealth accumulation. Innovative, coordinated, green, open and shared development are the goals of China 13th and 14th five-year plan and our inclusive wealth of China will be key measurement tool of this achievement.

The use of The Bethesda System for Reporting Thyroid Cytopathology in a Chinese population: An analysis of 13 351 specimens.

AIMS: The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) has been widely adopted since its introduction. In this study, we aimed to report our experience using this reporting system at a College of American Pathologists (CAP)-accredited hospital laboratory in a large series of Chinese patients. METHODS: All patients who underwent preoperative ultrasound-guided thyroid fine-needle aspiration (FNA) from January 2011 to August 2016 were retrospectively analyzed. Thyroid FNAs were classified according to the Bethesda System. For patients who underwent subsequent surgery at our institution, the diagnostic performance of the preoperative FNA was further analyzed according to four different calculation criteria. All of the follicular variants of papillary thyroid carcinoma specimens were reviewed to exclude NIFTP (noninvasive follicular thyroid neoplasm with papillary-like nuclear features). RESULTS: A total of 13 351 thyroid FNAs were included in this analysis. Of the 12 530 sampled patients, 3594 (28.7%) underwent thyroidectomy, and the malignancy rates for each cytological category were as follows: 66.7% unsatisfactory, 14.2% benign, 53.5% undetermined significance, 30.2% follicular neoplasm, 82.0% suspicious, and 99.1% malignant. Only 12 (0.36% of all PTC) patients were reclassified as having NIFTP. The sensitivities of the preoperative FNAs were all above 95.0% and were as high as 99.0%. The specificities ranged from 50.3% to 63.9%, depending on which criteria were used. The positive predictive value was 95.4% for criteria 1 and 2 and was 94.2% for criteria 3 and 4. The negative predictive values ranged from 64.5% to 85.8%. The diagnostic accuracies all exceeded 90.0%, with the highest being 94.8%. CONCLUSION: This study revealed the great efficacy and accuracy of TBSRTC in a large Chinese population for the first time.

Using a nomogram based on preoperative serum fibrinogen levels to predict recurrence of papillary thyroid carcinoma.

BACKGROUND: Hyperfibrinogenemia is increasingly being recognized as an important risk factor related to cancer stage, development and outcomes. We evaluated whether preoperative serum fibrinogen levels predict recurrence of papillary thyroid carcinoma (PTC). METHODS: We retrospectively collected data for 1023 PTC patients who underwent surgery at our institution from Aug 2014 to Aug 2016. In total, 414 patients (from Aug 2014 to Dec 2015) were used as the training set to build the model, and 609 patients (from Jan 2016 to Aug 2016) were used as the testing set to validate the model. RESULTS: In the training set, PTC cases with high serum fibrinogen levels were more likely to have multiple PTCs (P = 0.001) and to exhibit surrounding tissue or organ invasion (both P < 0.01). Moreover, PTC patients with higher serum fibrinogen levels were also more likely to have an advanced tumor stage (T, P = 0.001) and distance metastasis (P < 0.001), and these patients had a significantly higher rate of postoperative PTC recurrence (P = 0.002). All of these findings were validated in the testing set. The results of univariate and multivariate analyses indicated that hyperfibrinogenemia was a risk factor for PTC recurrence. The identified risk factors were incorporated into a nomogram and validated using the testing set (C-index = 0.811, 95% CI: 0.762-0.871). CONCLUSION: PTC cases with hyperfibrinogenemia are more likely to have an advanced TNM stage and have a higher rate of PTC recurrence. Our nomogram could be used to objectively and accurately predict PTC recurrence in a clinical setting.

A Nomogram Based on the Characteristics of Metastatic Lymph Nodes to Predict Papillary Thyroid Carcinoma Recurrence.

BACKGROUND: The extent of metastatic lymph node (LN) invasion was not considered in the postoperative stratification of the recurrence risk of papillary thyroid carcinoma (PTC) in the 2015 American Thyroid Association (ATA) guidelines, and the recommended risk stratification cannot be applied to individuals. A nomogram based on these risk factors was developed based on the risk factors to predict individual recurrence risk. METHODS: Data from 1788 PTC patients at the West China Hospital and 306 cases from the Shang Jin Nan Fu Hospital between August 2013 and July 2015 were included in this study. The 1788 cases were randomized into two groups-the training set (896 cases) and the testing set (896 cases)-and 306 cases were used as the external evaluation set. RESULTS: Univariate and multivariate analyses identified the following independent prognostic factors associated with recurrence in the three independent sets and the combined set (p < 0.01): LN invasion in the capsule or organ, more than five metastatic LNs, and a largest metastatic LN diameter >3 cm. Importantly, PTC patients showed significantly different recurrence rates depending on the extent of LN invasion in the three sets and in the combined set (p < 0.001). The nomogram was developed based on the risk factors in the training set and was validated in the independent testing and validation sets. CONCLUSION: The largest LN metastasis diameter, number of metastatic LNs, and the extent of extranodal invasion had significant prognostic value for predicting the risk of recurrence. Based on the characteristics of the thyroidal PTC lesion and metastatic LNs, the nomogram showed good prediction of recurrence in individual PTC patients.

Independent predictors and lymph node metastasis characteristics of multifocal papillary thyroid cancer.

The multifocal papillary thyroid cancer (PTC), with more aggressive and poorer prognosis, is not rare in papillary histotype. Few studies evaluated risk factors and lymph node metastasis in multifocal PTC. The aim of this present study focusing on risk factors and lymph node metastasis characteristics in multifocal PTC was excepted to assist clinical decisions regarding surgery.It was a retrospective study. The 1249 consecutive patients with PTC were reviewed. Of these, 570 patients who met the criteria were selected: 285 with solitary papillary thyroid cancer and 285 with multifocal PTC. The risk factors and lymph node metastasis in multifocal PTC were investigated by univariate and multivariate analysis.Multifocal PTC showed a higher positive rate of capsular invasion, extrathyroidal extension, tumor size >10 mm, pathological T classification, N+ stage, local recurrence, and radioactive iodine ablation (RAI). Capsular invasion (hazard ratio [HR], 1.589; 95% confidence interval [CI],1.352-1.984), advanced pathological T classification (HR, 3.582; 95% CI, 2.184-5.870), and pathological N+ stage (HR, 1.872; 95% CI, 1.278-2.742) were related to increased risk of multifocality and there was a significant increased HR for central neck compartment involvement in male sex (HR, 2.694; 95% CI, 1.740-4.169), advanced pathological T classification (HR, 2.403; 95% CI, 1.479-3.907) and multifocality (HR, 1.988; 95% CI, 1.361-2.906).There is a significant association between capsular invasion, advanced pathological T classification, N+ stage, and multifocal PTC. Total thyroidectomy plus prophylactic bilateral central lymph node dissection should be recommended during surgery due to a stronger predilection for level VI lymph node metastasis in multifocal PTC.

Effects of high dose of anisodamine on the respiratory function of patients with traumatic acute lung injury.

The objective of this study is to observe the effects of high dose of anisodamine in the respiratory function of patients with acute lung injury (ALI) induced by trauma. Fifty cases of patients with complicated ALI after trauma were randomly divided into the anisodamine treatment group (n = 26) and the conventional treatment group (n = 24). Intravenous injection of high dose of anisodamine was administrated in the anisodamine treatment group on the basis of conventional treatment. Acute lung injury scores, oxygenation index, PaO2, respiratory mechanic index, mechanical ventilation time, and the occurrence of adverse reactions in the two groups were observed. Acute lung injury scores and respiratory parameters were all significantly improved in the two groups of patients after the treatment (P < 0.05); compared with the conventional treatment group, the improvements of respiratory function in the anisodamine treatment group were more obvious (P < 0.05), the mechanical ventilation time was shorter (P < 0.05), and there was no significant adverse reaction. In conclusion, high dose of anisodamine contributed to improve the respiratory function of the patients with traumatic ALI.