Comparison of the PADUA and IMPROVE scores in assessing venous thromboembolism risk in 42,257 medical inpatients in China.

Venous thromboembolism (VTE) is a major contributor to hospital mortality and disability-adjusted life-year (DALY) loss. Multiple guidelines recommend using the Padua or IMPROVE scores to stratify VTE risk in hospitalized medical patients. However, the IMPROVE score is not recommended in Chinese guidelines, and there is very little evaluation of its clinical application and effectiveness in the Chinese population. The objective of this study is to compare the efficacy of the Padua and IMPROVE scoring models for assessing VTE risk in Chinese medical inpatients. We conducted a retrospective analysis of the clinical characteristics and thrombotic risk of 42,257 medical inpatients at a tertiary hospital in Guangdong, China, between 2021 and 2022. Logistic regression was used to assess thrombotic risk factors. The Receiver Operating Characteristic (ROC) curves, Area Under the Curve (AUC), sensitivity, and specificity were employed to evaluate the performance of the two models. Of the 42,257 patients included, 948 (2.24%) experienced VTE during hospitalization. According to the Padua score, 3,7513 (88.78%) of patients were considered low risk, while 4,744 (18.22%) were classified as high risk. The IMPROVE score identified 20,744 (49.09%) of patients as low risk, 20799(49.22%) as intermediate risk, and 714(1.69%) as high risk. The AUC for the Padua score was 0.735 (95% CI: 0.717-0.753), with a sensitivity of 49.4% and specificity of 89.6%. For the IMPROVE score, the AUC was 0.711 (95% CI: 0.693-0.729), with a sensitivity of 32.5% and specificity of 99.0%. The DeLong test, used to compare the AUCs, yielded a z-value of 1.886 with a P-value of 0.059, indicating no statistical difference. When assessing VTE risk in patients with stroke, cancer, nephrotic syndrome, and critical illness (ICU/CCU stay), both scoring models showed comparable predictive performance with AUCs ranging between 0.7 and 0.8. Both the Padua score and IMPROVE score have good predictive ability for VTE events during hospitalization in medical patients. Among them, the IMPROVE score has objective assessment items, simpler operation, and more detailed risk stratification, which is beneficial for clinicians to take physical and pharmacological preventive measures at different levels.ChiCTR2200056903, February 22, retrospectively registered.

Two new antimicrobial monoterpenoid indole alkaloids from the roots of Rauvolfia yunnanensis.

Two new monoterpenoid indole alkaloids 3-hydroxylochnerine (1) and 10-hydroxyvinorine (2) were isolated from the roots of Rauvolfia yunnanensis. Their structures were elucidated based on the analysis of spectroscopic data and ECD calculation. Both compounds exhibited potent antimicrobial activity against Bacillus subtilis and Escherichia coli, and their activities were comparable to the well-known antibacterial drug berberine.

A high-throughput cell-based gaussia luciferase reporter assay for measurement of CYP1A1, CYP2B6, and CYP3A4 induction.

The induction of cytochrome P450s can result in reduced drug efficacy and lead to potential drug-drug interactions. The xenoreceptors-aryl hydrocarbon receptor (AhR), constitutive androstane receptor (CAR), and pregnane X receptor (PXR)-play key roles in CYP induction by xenobiotics. In order to be able to rapidly screen for the induction of three enzymes (CYP1A1, CYP2B6, and CYP3A4), we generated a stable AhR-responsive HepG2 cell line, a stable CAR-responsive HepG2 cell line, and a stable PXR-responsive HepG2 cell line.To validate these stable xenoreceptor-responsive HepG2 cell lines, we evaluated the induction of the different Gaussia reporter activities, as well as the mRNA and protein expression levels of endogenous CYPs in response to different inducers.The induction of luciferase activity in the stable xenoreceptor-responsive HepG2 cell lines by specific inducers occurred in a concentration dependent manner. There was a positive correlation between the induction of luciferase activities and the induction endogenous CYP mRNA expression levels. These xenoreceptor-responsive HepG2 cell lines were further validated with known CYP1A1, CYP2B6, and CYP3A4 inducers.These stable xenoreceptor-responsive HepG2 cell lines may be used in preclinical research for the rapid and sensitive detection of AhR, CAR, and PXR ligands that induce CYP450 isoforms.

Ultracompact optical fiber acoustic sensors based on a fiber-top spirally-suspended optomechanical microresonator.

Acoustic wave sensors with a high sensitivity and small size are highly desired for a wide variety of important and emerging applications such as photoacoustic gas sensing and bio-imaging. Here we present an ultracompact optical fiber acoustic sensor based on an optomechanical resonator that is directly in situ printed on the end face of a standard single-mode optical fiber by using an optical 3D µ-printing technology. The fiber-top optomechanical microresonator is composed of a microscale suspended polymer micro-disk that forms a Fabry-Perot interferometric cavity, together with the optical fiber end face, and acts as the acoustic wave-sensitive micromechanical resonator simultaneously. The microbeams for suspending the micro-disk are devised with a spiral structure to overcome the small-size imposed low deflection amplitude so as to improve its sensitivity to acoustic waves. The sensor with a high sensitivity of 118.3 mV/Pa and low noise equivalent acoustic signal level of 0.328µPa/Hz1/2 at audio frequency is experimentally demonstrated. Moreover, with a resonance amplification mechanism, the sensitivity can be enhanced by 40.1 times when the frequency of the acoustic wave matches with the natural resonance frequency of the optomechanical resonator. Such an ultrasmall fiber-tip acoustic sensor has not only a miniaturization-induced broad bandwidth, but also a structure-enhanced ultrahigh sensitivity and thus is very promising in various acoustic wave-based sensing, imaging, and testing applications.

Vinpocetine regulates levels of circulating TLRs in Parkinson's disease patients.

BACKGROUND: The pathogenesis of Parkinson's disease (PD) is complex; it includes mitochondrial dysfunction, oxidative stress, and neuroinflammation. Notably, Toll-like receptors (TLRs) may activate inflammatory or anti-inflammatory responses in Parkinson's disease. Vinpocetine has been tested as an anti-inflammatory in both animal and in vitro research. Thus, it is important to test whether the anti-inflammatory properties of vinpocetine may have a protective effect in PD patients. METHODS: Eighty-nine Parkinson's disease patients and 42 healthy controls were recruited for this study. All patients were randomly assigned to either the traditional therapy group (T PD group, n = 46) or the vinpocetine group (V PD group, n = 43), in a blinded manner. Both treatments were administered for 14 days. RESULTS: Administration of vinpocetine reduced mRNA levels of TLR2/4, as well as protein levels of the downstream signalling molecules, MyD88 and NF-κB; moreover, it lowered the expression levels of serum inflammatory cytokines, TNF-α and MCP-1. Notably, vinpocetine increased TLR3 mRNA levels, as well as protein levels of the downstream signalling molecules TRIF-ß and IRF-3, and serum levels of the anti-inflammatory cytokines IL-10 and IL-8. Furthermore, vinpocetine produced a robust increase in the Mini Mental State Examination score, compared to that achieved by using levodopa therapy. CONCLUSION: Vinpocetine treatment may exhibit anti-inflammatory activity and alleviate cognitive impairment.

Predictors of Occult Lymph Node Metastasis and Prognosis in Patients with cN0 T1-T2 Supraglottic Laryngeal Carcinoma: A Retrospective Study.

BACKGROUND: This work aimed to explore the predictors of lymph node metastasis (LNM) and analyze the prognosis of patients with clinically node-negative (cN0) T1-T2 supraglottic laryngeal carcinoma (SGLC). METHODS: Data for 130 patients with cN0 T1-T2 SGLC who initially underwent surgery were retrospectively reviewed. Occult LNM incidence, relevant factors, and prognosis were analyzed. RESULTS: Of the 130 patients with cN0 T1-T2 SGLC, 21 (16.2%) had occult LNM. Based on univariate and multivariable regression analyses, male sex and poor tumor differentiation predicted the incidence of occult LNM. The incidence of occult LNM was 20.9% in males and 5.1% in females (p = 0.035). Patients with poorly differentiated tumors had a higher incidence of occult LNM (42.9%) than patients with well-differentiated (10.3%) and moderately differentiated tumors (14.3%; p < 0.05). Thirteen patients (10%) had cervical recurrence, and all had T2 tumors (p = 0.02). The 5-year disease-specific survival rates were 70 and 90% for patients with and without LNM, respectively (p = 0.000). CONCLUSIONS: Sex and tumor differentiation are potential predictors of occult nodal disease. Female patients with cN0 T1-T2 SGLC are less likely than male patients to have neck metastasis. Poorly differentiated tumors are associated with the frequency of neck metastasis, and selective neck dissection is strongly recommended for these tumors.

C1206, a novel curcumin derivative, potently inhibits Hsp90 and human chronic myeloid leukemia cells in vitro.

4-(4-Pyridinyl methylene) curcumin (C1206) is a new derivative of curcumin that is more active than curcumin in inhibition of heat shock protein 90 (Hsp90) and antitumor action. In this study we investigated the relationship between C1206-induced inhibition of Hsp90 and its anti-leukemic effects. The fluorescence quenching experiments showed that C1206 seemed to bind the middle dimerization domain of Hsp90. The interaction between C1206 and Hsp90 was driven mainly by electrostatic interaction. In in vitro enzyme activity assay, C1206 dose-dependently inhibited Hsp90 ATPase activity with an IC50 value of 4.17 µmol/L. In both imatinib-sensitive K562 chronic myeloid leukemia cells and imatinib-resistant K562/G01 chronic myeloid leukemia cells, C1206 (0.4-3.2 µmol/L) dose-dependently caused the degradation of Hsp90 client proteins and downstream proteins (AKT, MEK, ERK, C-RAF, P-AKT, P-MEK and P-ERK). Furthermore, C1206 (0.4-3.2 µmol/L) dose-dependently induced apoptosis of K562 and K562/G01 cells through triggering mitochondrial pathway. Consistent with this result, C1206 inhibited the proliferation of K562 and K562/G01 cells with IC50 values of 1.10 and 0.60 µmol/L, respectively. These results suggest that C1206 is a novel Hsp90 inhibitor and a promising therapeutic agent for chronic myeloid leukemia.

Optofluidic tunable mode-locked fiber laser using a long-period grating integrated microfluidic chip.

An optofluidic tunable mode-locked fiber laser using a microfluidic chip integrated with long-period grating (LPG) is presented. The microfluidic chip enables ultrafine adjustment of the liquid's refractive index and, thus, LPG's spectrum via tuning the mixing ratio of the microfluidic flows. With such an optofluidic spectrum-tunable filter, the central wavelength of the mode-locked laser can be tuned continuously, while the mode-locking state is steadily maintained. The mode-locked pulses are measured with a pulse duration of 0.9 ps and repetition rate of 12.14 MHz, respectively. Moreover, bound solitons with variable soliton separations are experimentally demonstrated.

Neuronal filtering of multiplexed odour representations.

Neuronal activity patterns contain information in their temporal structure, indicating that information transfer between neurons may be optimized by temporal filtering. In the zebrafish olfactory bulb, subsets of output neurons (mitral cells) engage in synchronized oscillations during odour responses, but information about odour identity is contained mostly in non-oscillatory firing rate patterns. Using optogenetic manipulations and odour stimulation, we found that firing rate responses of neurons in the posterior zone of the dorsal telencephalon (Dp), a target area homologous to olfactory cortex, were largely insensitive to oscillatory synchrony of mitral cells because passive membrane properties and synaptic currents act as low-pass filters. Nevertheless, synchrony influenced spike timing. Moreover, Dp neurons responded primarily during the decorrelated steady state of mitral cell activity patterns. Temporal filtering therefore tunes Dp neurons to components of mitral cell activity patterns that are particularly informative about precise odour identity. These results demonstrate how temporal filtering can extract specific information from multiplexed neuronal codes.

TNF Receptor 1/2 Predict Heart Failure Risk in Type 2 Diabetes Mellitus Patients.

Inflammation plays an important role in heart failure and diabetes mellitus. Traditional serum markers have limited predictive value in heart failure and diabetes. TNFR1 and TNFR2 (TNFR1/2) have been proven to be strongly associated with heart failure and diabetes complications. This study aimed to assess the association of sTNFR1 and sTNFR2 levels and incidental HF risk in diabetes patients.We detected the mRNA, protein, and serum expression of TNFR1/2, their downstream signaling pathway protein NF-kB, and JNK expression and some traditional serum inflammatory markers in a heart failure group without diabetes mellitus or abnormal glucose tolerance (n = 84), a diabetes mellitus group without heart failure (n = 86), and a heart failure with diabetes mellitus group (n = 86).TNFR1/2 were significantly higher in patients with heart failure and diabetes mellitus based on mRNA expression to protein expression and serum expression. However, there were no differences in mRNA, protein, and serum levels of TNFR1/2 between the HF group and DM group. Furthermore, there were no differences between the groups in some traditional serum inflammatory markers.This study demonstrated higher expressions of TNFR, NF-kB, and JNK in patients with heart failure and diabetes mellitus. Compared with traditional serum markers, TNFR1 and TNFR2 are associated with heart failure risk in type 2 diabetes mellitus patients.

Cloning, expression, and characterization of a four-component O-demethylase from human intestinal bacterium Eubacterium limosum ZL-II.

Eubacterium limosum ZL-II was described to convert secoisolariciresinol (SECO) to its demethylating product 4,4'-dihydroxyenterodiol (DHEND) under anoxic conditions. However, the reaction cascade remains unclear. Here, the O-demethylase being responsible for the conversion was identified and characterized. Nine genes encoding two methyltransferase-Is (MT-I), two corrinoid proteins (CP), two methyltransferase-IIs (MT-II), and three activating enzymes (AE) were screened, cloned, and expressed in Escherichia coli. Four of the nine predicted enzymes, including ELI_2003 (MT-I), ELI_2004 (CP), ELI_2005 (MT-II), and ELI_0370 (AE), were confirmed to constitute the O-demethylase in E. limosum ZL-II. The complete O-demethylase (combining the four components) reaction system was reconstructed in vitro. As expected, the demethylating products 3-demethyl-SECO and DHEND were both produced. During the reaction process, ELI_2003 (MT-I) initially catalyzed the transfer of methyl group from SECO to the corrinoid of ELI_2004 ([CoI]-CP), yielding demethylating products and [CH3-CoIII]-CP; then ELI_2005 (MT-II) mediated the transfer of methyl group from [CH3-CoIII]-CP to tetrahydrofolate, forming methyltetrahydrofolate and [CoI]-CP. Due to the low redox potential of [CoII]/[CoI], [CoI]-CP was oxidized to [CoII]-CP immediately in vitro, and ELI_0370 (AE) was responsible for catalyzing the reduction of [CoII]-CP to its active form [CoI]-CP. The active-site residues in ELI_2003, ELI_2005, and ELI_0370 were subsequently determined using molecular modeling combined with site-directed mutagenesis. To our knowledge, this is the first study on the identification and characterization of a four-component O-demethylase from E. limosum ZL-II, which will facilitate the development of method to artificial synthesis of related bioactive chemicals.

Expression of hypoxia-inducible factor 1 alpha ameliorate myocardial ischemia in rat.

Hypoxia-inducible factor 1 alpha (HIF-1a), the upstream regulator of Vascular endothelial growth factor (VEGF), is the vital hypoxia related gene expression control factor. To evaluate HIF-1a therapeutic efficacy to acute myocardial infarction, the HIF-1a expressing recombinant Adeno-associated virus (rAAV) was constructed. The Wistar rat ischemic heart animal model was established with left anterior descending coronary artery ligation. The ischemic rats were treated with HIF-1a expressing and GFP expressing rAAVs respectively. Four weeks post the injection, the cardiac function of treated rat was compared by TM_WAVE system; size of infracted area was calculated by Evan's blue stain and capillary density was determined by CD31 immunohistochemical staining. Compare to the control group, the rats received HIF-1a expressing rAAV have smaller infracted heart size, the better heart function and higher capillary density than vehicle control group. The results show that the injection of HIF1a expressing rAAV can improve cardiac function and ameliorate acute myocardial ischemia (AMI) in rats.

Mitophagy-regulated Necroptosis plays a vital role in the nephrotoxicity of Fumonisin B1 in vivo and in vitro.

Fumonisin B1 (FB1), one of the most widely distributed mycotoxins found in grains and feeds as contaminants, affects many organs including the kidney once ingested. However, the nephrotoxicity of FB1 remains to be further uncovered. The connection between necroptosis and nephrotoxicity of FB1 has been investigated in this study. The results showed that mice exposed to high doses of FB1 (2.25 mg/kg b.w.) developed kidney damage, with significant increases in proinflammatory cytokines (Il-6, Il-1ß), kidney injury-related markers (Ngal, Ntn-1), and gene expressions linked to necroptosis (Ripk1, Ripk3, Mlkl). The concentration-dependent damage effects of FB1 on PK-15 cells contain cytotoxicity, cellular inflammatory response, and necroptosis. These FB1-induced effects can be neutralized by pretreatment with the necroptosis inhibitor Nec-1. Additionally, FB1 caused mitochondrial damage and mitophagy in vivo and in vitro, whereas Mdivi-1, a mitophagy inhibitor, prevented these effects on PK-15 cells as well as, more crucially, necroptosis. In conclusion, the RIPK1/RIPK3/MLKL signal route of necroptosis, which may be controlled by mitophagy, mediated nephrotoxicity of FB1. Our findings clarify the underlying molecular pathways of FB1-induced nephrotoxicity.

3D-printed near-infrared-light-responsive on-demand drug-delivery scaffold for bone regeneration.

Although several bioactive 3D-printed bone scaffolds loaded with multiple kinds of biomolecules for enhanced bone regeneration have been recently developed, the manipulation of on-demand release profiles of different biomolecules during bone regeneration remains challenging. Herein, a 3D-printed dual-drug-loaded biomimetic scaffold to regulate the host stem cell recruitment and osteogenic differentiation in a two-stage process for bone regeneration was successfully fabricated. First, a chemotactic small-molecule drug, namely, simvastatin (SIM) was directly incorporated into the hydroxyapatite/collagen bioink for printing and could be rapidly released during the early stage of bone regeneration. Further, near-infrared (NIR)-light-responsive polydopamine-coated hydroxyapatite nanoparticles were designed to deliver the osteogenic drug, i.e., pargyline (PGL) in a controllable manner. Together, our scaffold displayed an on-demand sequential release of those two drugs and could optimize their therapeutic effects to align with the stem cell recruitment and osteoblastic differentiation, thereby promoting bone regeneration. The results confirmed the suitable mechanical strength, high photothermal conversion efficiency, good biocompatibility of our scaffold. The scaffold loaded with SIM could efficiently accelerate the migration of stem cells. In addition, the scaffold with on-demand sequential release promoted alkaline phosphatase (ALP) activity, significantly upregulated gene expression levels of osteogenesis-related markers, and enhanced new-bone-formation capabilities in rabbit cranial defect models. Altogether, this scaffold not only offers a promising strategy to control the behavior of stem cells during bone regeneration but also provides an efficient strategy for controllable sequential release of different biomolecule in bone tissue engineering.

Is the expression of different discrete emotions related to time? Evidence from online Chinese reviews using sentiment analysis and human behavior dynamics.

Objectives: The online behavior of online users has taken on complex and diverse characteristics, and posting product reviews on e-commerce platforms is no exception. In fact, reviews contain rich and multi-dimensional discrete emotional information, and whether there is a relationship between the expression of these different discrete emotions and the time interval between product purchase and review posting as well as their related characteristics are the issues that this study needs to analyze and solve in depth. Methods: Based on the OCC model (named after three proposers) of psychological emotional cognitive evaluation theory as the basis for emotion classification, the study used the massive amounts of Chinese reviews of mobile phones on the Chinese e-commerce platform Jingdong Mall as the research object, applied supervised machine learning methods to classify discrete emotions, and constructed a large corpus containing satisfaction, disappointment, admiration, reproach, love, and hate; then the study delved into the distribution and behavioral dynamics characteristics of consumers' comments containing the different discrete emotions at different "purchase-comment" time intervals. Results: The results showed that the first peak of the distribution curves of the six discrete emotions at different "purchase-comment" time intervals occurs on the first day after purchase and then decreases gradually but at different rates. The three curves for satisfaction, love, and hate emotions also show a second peak on the eleventh day, which is more similar to the bimodal distribution, implying that the corresponding product reviews are more objective. In addition, the distribution of reviews containing the six discrete emotions at different "purchase-comment" time intervals follows a power-law distribution and has the temporal characteristics of human behavioral dynamics, that is, "strong paroxysms and weak memory". However, the reviews containing the admiration and reproach emotions were most intensively written by consumers after the purchase, indicating that the service provided by the seller, logistics, and e-commerce platform stimulates more consumers to give quick responses and detailed reviews. Conclusion: This study is not only of great significance for exploring the internal mechanisms of consumer discrete emotional expression but also provides important decision-making references for potential consumer purchasing decisions, product updates for developers, marketing strategy formulation for marketing teams, and service improvement for sellers, logistics companies, and e-commerce platforms.

Dopaminergic modulation of mitral cells and odor responses in the zebrafish olfactory bulb.

In the olfactory bulb, the modulatory neurotransmitter dopamine (DA) is coexpressed with GABA by local interneurons, but its role in odor processing remains obscure. We examined functions of DA mediated by D2-like receptors in the olfactory bulb of adult zebrafish by pharmacology, whole-cell recordings, calcium imaging, and optogenetics. Bath application of DA had no detectable effect on odorant-evoked sensory input. DA directly hyperpolarized mitral cells (MCs) via D2-like receptors and slightly increased their response gain. Consistent with this effect on input-output functions of MCs, small odorant responses were suppressed, whereas strong responses were enhanced in the presence of DA. These effects increased the root-mean-square contrast of population activity patterns but did not reduce their correlations. Optical stimulation of interneurons expressing channelrhodopsin-2 evoked fast GABAergic inhibitory currents in mitral cells but failed to activate D2 receptor-mediated currents when stimuli were short. Prolonged stimulus trains, however, activated a slow hyperpolarizing current that was blocked by an antagonist of D2-like receptors. GABA and DA are therefore both released from interneurons by electrical activity and hyperpolarize MCs, but D2-dependent dopaminergic effects occur on slower timescales. Additional effects of DA may be mediated by D1-like receptors. These results indicate that DA acts on D2-like receptors via asynchronous release and/or volume transmission and implicate DA in the slow adaptation of circuit function. The shift of the membrane potential away from spike threshold could adapt mitral cells to background input without compromising their sensitivity.

Risk factors for dementia with type 2 diabetes mellitus among elderly people in China.

OBJECTIVE: to investigate the prevalence and risk factors of diabetes to dementia and its subtypes such as Alzheimer disease (AD) and vascular dementia (VD) among the Chinese elderly population. METHODS: among 8,213 Chinese people aged 65 years and older, 1,109 subjects with type 2 diabetes millitus (T2DM) were ascertained by interview and direct glucose testing. All diabetic subjects were initially screened with the "DSM-IV criteria" for dementia and its subtypes. We compared the prevalence of dementia in diabetic patients with that in ordinary subjects, and analyzed the association of the status of diabetes with dementia including AD and VD. Logistic regression was used to assess OR of dementia and its subtypes with T2DM. RESULTS: after a comprehensive geriatric and cognitive assessment, 132 diabetic subjects were diagnosed with all-cause dementia. The prevalence rate for dementia with T2DM was 1.61%. Of demented subjects, 37 subjects had AD, 30 subjects had VD. The prevalence rates for AD with T2DM and VD with T2DM were 4.51% and 3.65%, respectively. In the univariate analyses, among all diabetic subjects, compared with cognitive intactly subjects, the demented subjects, including AD and VD subjects, were older, more female had higher percentage of current smoking, had a greater duration of diabetes, took more frequent use of diabetes medications, and stronger effect of APOE ε4 status. In multivariate logistic regression analyses, variables including age, APOE ε4 allele, duration from onset of diabetes, using oral hypoglycemic agents, HMG-CoA reductase (statins) were significantly associated with increased risk for dementia with T2DM (all P < 0.05). CONCLUSIONS: the present study shows that T2DM is associated with dementia and its subtypes amongst elderly people in the Chinese population.

Management of nasopharyngeal adenoid cystic carcinoma.

PURPOSE: Nasopharyngeal adenoid cystic carcinomas (NACCs) are rare. No clear consensus is available regarding clinical characteristics and management approaches. The aim of this study was to summarize the clinical characteristics and evaluate the management approaches of NACC. MATERIALS AND METHODS: The experience of 1 institution with this tumor and the outcomes of treatment were examined. The medical records of 36 patients with NACC at 1 institution from 1963 through 2006 were reviewed. RESULTS: After a median follow-up of 65.8 months (1.8 to 245.2 mo), the 5- and 10-year overall survival, locoregional failure-free survival, and distant metastasis failure-free survival rates were 70.2% and 31.6%, 63.4% and 49.1%, and 65.0% and 59.6%, respectively. No significant differences were found in locoregional failure-free survival, distant metastasis failure-free survival, or overall survival rates between the group that received radiotherapy alone and the group that received combined modality therapy (radiotherapy plus surgery or surgery plus radiotherapy). CONCLUSIONS: NACC is a malignancy with a generally favorable prognosis. Radiotherapy alone or a combined modality therapy (radiotherapy plus surgery or surgery plus radiotherapy) is effective in the treatment of NACC.

[Significance of selective neck dissection in patients with cN0 thyroid carcinoma].

OBJECTIVE: To investigate the significance of selective neck dissection in patients with cN0 thyroid carcinoma who have a high-risk of lateral neck lymph node metastasis. METHODS: Sixty three patients with cN0 thyroid carcinoma who have a high-risk of lateral neck lymph node metastasis were prospectively studied at the Department of Head and Neck Surgery, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between August 2006 and June 2011. The patients with cN0 thyroid carcinoma easy to occur neck lymph node metastasis include: The maximum diameter of primary tumor is ≥ 2 cm; The primary tumor invaded the thyroid capsule; Lymph node metastasis in level VI is found; Lymph node enlargement in level III or/and IV were detected preoperatively by ultrasonography, but not considered as metastasis. The surgical procedure is that the selective neck dissection in level III and IV is performed depending on the collar incision of thyroid surgery. The lymph node chosen from the specimen has a frozen section. If lymph node metastasis is found in the frozen section, a functional neck dissection should be performed through prolonging the collar incision. RESULTS: All cases were pathologically confirmed as thyroid papillary carcinoma. The occult metastasis rate of lateral neck lymph nodes was 39.7%. According to the univariate analysis, the patients with thyroid capsule invasion and lymph node metastasis in level VI were more likely to have lateral neck lymph node metastasis, and the occult metastasis rate was 46.9% and 54.3%, respectively (P = 0.028, P = 0.008), and there were statistically no significant difference in the primary tumor size and the preoperative neck lymph node status by ultrasonography with occult metastasis of lateral neck lymph nodes (P = 0.803 and P = 0.072). According to the multivariate analysis, there was a significant correlation only between the lymph node metastasis in level VI and occult metastasis of lateral neck lymph nodes (P = 0.017), but there was no significant correlation with the thyroid capsule invasion, primary tumor size and neck lymph node status by preoperative ultrasonography in prediction of occult metastasis of lateral neck lymph nodes (all P > 0.05). CONCLUSIONS: Selective neck dissection is feasible for the patients with cN0 thyroid carcinoma who have a high-risk lateral neck lymph node metastasis and the lateral occult metastatic lymph node can be promptly found and removed. We suggest that the selective neck dissection for level III and IV should be routinely performed in cN0 thyroid carcinoma patients with thyroid capsule invasion and lymph node metastasis in level VI.

Oxidative Stress and Pyroptosis in Doxorubicin-Induced Heart Failure and Atrial Fibrillation.

Patients undergoing doxorubicin (Dox) chemotherapy often develop new-onset atrial fibrillation and heart failure. Recent studies indicate that the TLR4/MyD88/NLRP3 pyroptosis signaling pathway plays a key role in the occurrence and development of cancer, heart failure, and atherosclerosis. However, few studies investigated the role of oxidative stress and pyroptosis in doxorubicin-induced heart failure and new-onset atrial fibrillation. In this study, we recruited 84 healthy subjects, 112 patients undergoing Dox chemotherapy showing heart failure (HF), and 62 patients undergoing Dox treatment who manifested atrial fibrillation (AF). The mRNA and protein levels of TLR4 expression, several downstream pyroptosis-associated proteins (cleaved caspase-1, NLRP3, GSDMD-N, and HMGB-1), serum inflammatory factors, and oxidative stress were detected at the beginning of chemotherapy and after 3 months of Dox chemotherapy. Oxidative stress and downstream pyroptosis-associated proteins tended to increase in the Dox-baseline group to the Dox-HF group. However, virtually no change in the expression of either oxidative stress or pyroptosis-associated proteins was detected in patients after three months of Dox chemotherapy compared with those at baseline. This study suggests that the prolonged oxidative stress and high levels of pyroptosis-associated proteins contribute to cardiac systolic dysfunction, suggesting TLR4 as a novel biomarker and a potential treatment target for doxorubicin-induced heart failure.