Synthesis and characterization of microencapsulated paraffin with melamine-urea-formaldehyde shell modified with lignin.

The study aims to fabricate MUF/paraffin microcapsules with lignin nanoparticles (LNPs)/ melamine-urea-formaldehyde (MUF) resin as hybrid shell material with different LNPs addition were synthesized in oil-in-water emulsion stabilized synergistically by styrene/maleic anhydride (SMA) and LNPs. The morphological characterization of LNPs was observed by transmission electron microscopy (TEM). The particle size of LNPs, the mean particle size and ξ potentials of SMA/LNPs mixture at pH =4.5 were investigated by zeta potential measurement. Field emission scanning electron microscopy (FE-SEM), Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), thermogravimetric analyzer (TGA), and differential scanning calorimetry (DSC) were characterized the morphologies, crystallography, chemical component, thermal stability and phase change properties of MUF/paraffin microcapsules with different LNPs addition. The results showed that MUF/paraffin microcapsules were spherical. The LNPs did not influence the chemical structure or crystal type of MUF/paraffin microcapsules. When the LNPs addition was 0.15 g, the melting enthalpy and crystallization enthalpy is respectively 130.03 and 121.92 J/g and the encapsulation efficiency of MicroC-15 is 61.04 %.

A blinded-endpoint, randomized controlled trial of Sanyrene with natural active ingredient for prophylaxis of radiation dermatitis in patients receiving radiotherapy.

BACKGROUND: Randomized controlled study was conducted to evaluate the efficacy of Sanyrene® vs. control intervention (DaBao®, a complex of hyaluronic acid and Vitamin E) for acute radiation dermatitis in patients receiving radiotherapy. METHODS: Patients with breast cancer or head and neck cancer undergoing radiotherapy (≥ 50 Gy) were eligible. Participants were randomly assigned to either Sanyrene arm or control intervention arm in a ratio of 1:1. The primary endpoint was incidence rate of ≥ grade 2 radiation induced dermatitis. (Trial Registration: ChiCTR2100050910, registration date: 9/7/2021) RESULTS: A total of 102 eligible patients were randomly assigned into the study. The rate of ≥ grade 2 radiation dermatitis was 22% in Sanyrene group, as compared with 67.3% in the control intervention group (P<0.001). The incidence of grade 3 radiation dermatitis was 20.4% and 8.0% in control intervention group and Sanyrene group, respectively (P = 0.076). Patients in Sanyrene group had a longer median time to reach ≥ grade 2 radiation dermatitis compared to these in control intervention group, with hazard ratio of 0.231 (95%CI:0.116-0.458, p < 0.001). Mean score of SD-16 were much higher in control intervention group than Sanyrene group at end of radiotherapy (25 vs.8.3), 2 weeks after radiotherapy (22.9 vs. 0.5) and 4 weeks after radiotherapy (4.2 vs.0), with significantly statistical difference between two groups. CONCLUSIONS: This trial suggests that Sanyrene is effective on preventing serious radiation dermatitis and improving skin related quality of life in patients with breast cancer or head and neck cancer receiving radiotherapy.

The effect of accompanying anxiety and depression on patients with different vestibular syndromes.

Objective: This study aims to investigate the situation of vertigo disorder combined with anxiety and depression in patients with different types of vestibular syndrome. Methods: A total of 330 patients with vertigo in otolaryngology outpatient department were selected, and clinical information such as age, gender, and scores of Dizziness handicap inventory (DHI), Generalized anxiety disorder-7 (GAD-7), and Patient Health Questionnaire-9 (PHQ-9) were collected. Analyzed the differences among acute vestibular syndrome (AVS), episodic vestibular syndrome (EVS) and chronic vestibular syndrome (CVS) in terms of age, gender, comorbid anxiety and depression, and the multivariate ordered logistic regression analysis was used to evaluate the relationship between the above factors and the degree of vertigo disorder. Results: The three types of vestibular syndrome had no significant difference in age composition, sex composition, anxiety and depression. There was no significant difference in the probability of anxiety and depression among vertigo patients of different ages and genders. The total score of vertigo disorder and each sub-item score were higher in patients with anxiety and depression. Patients with anxiety mainly manifested in EVS and CVS, while patients with depression mainly manifested in EVS and AVS. The probability of increased vertigo in anxious patients was 4.65 times that of non-anxious patients, and the probability of increased vertigo in depressed patients was 3.49 times that of non-depressed patients. Age and gender had no statistically significant effect on the degree of vertigo. In patients with EVS, anxiety and depression had a significant effect on the degree of vertigo; in patients with CVS, anxiety had a significant effect on the degree of vertigo, but depression had no significant effect. Conclusion: Age and gender do not significantly affect the degree of vertigo disorder and mental state in various vestibular syndromes. Instead, anxiety and depression are the risk factors for aggravating the degree of vertigo disorder, and manifest differently in each type of vestibular syndrome. Therefore, it is necessary to use a quick scale tool to conduct a standardized screening of the psychological status of patients with vertigo.

Prevalence of pharmaceuticals and personal care products, microplastics and co-infecting microbes in the post-COVID-19 era and its implications on antimicrobial resistance and potential endocrine disruptive effects.

The COVID-19 (coronavirus disease 2019) pandemic's steady condition coupled with predominance of emerging contaminants in the environment and its synergistic implications in recent times has stoked interest in combating medical emergencies in this dynamic environment. In this context, high concentrations of pharmaceutical and personal care products (PPCPs), microplastics (MPs), antimicrobial resistance (AMR), and soaring coinfecting microbes, tied with potential endocrine disruptive (ED) are critical environmental concerns that requires a detailed documentation and analysis. During the pandemic, the identification, enumeration, and assessment of potential hazards of PPCPs and MPs and (used as anti-COVID-19 agents/applications) in aquatic habitats have been attempted globally. Albeit receding threats in the magnitude of COVID-19 infections, both these pollutants have still posed serious consequences to aquatic ecosystems and the very health and hygiene of the population in the vicinity. The surge in the contaminants post-COVID also renders them to be potent vectors to harbor and amplify AMR. Pertinently, the present work attempts to critically review such instances to understand the underlying mechanism, interactions swaying the current health of our environment during this post-COVID-19 era. During this juncture, although prevention of diseases, patient care, and self-hygiene have taken precedence, nevertheless antimicrobial stewardship (AMS) efforts have been overlooked. Unnecessary usage of PPCPs and plastics during the pandemic has resulted in increased emerging contaminants (i.e., active pharmaceutical ingredients and MPs) in various environmental matrices. It was also noticed that among COVID-19 patients, while the bacterial co-infection prevalence was 0.2-51%, the fungi, viral, protozoan and helminth were 0.3-49, 1-22, 2-15, 0.4-15% respectively, rendering them resistant to residual PPCPs. There are inevitable chances of ED effects from PPCPs and MPs applied previously, that could pose far-reaching health concerns. Furthermore, clinical and other experimental evidence for many newer compounds is very scarce and demands further research. Pro-active measures targeting effective waste management, evolved environmental policies aiding strict regulatory measures, and scientific research would be crucial in minimizing the impact and creating better preparedness towards such events among the masses fostering sustainability.

Effects of Processing Conditions on the Properties of Monoammonium Phosphate Microcapsules with Melamine-Formaldehyde Resin Shell.

To develop monoammonium phosphate (MAP) as a novel acid source for durable intumescent fire retardants (IFR), MAP microcapsules (MCMAPs) containing MAP as the internal core and melamine-formaldehyde (MF) as the external shell were prepared by in situ polymerization in this study. The influences of synthesis conditions (including reaction temperature, polymerization time, and reaction pH value) on the properties of obtained MCMAPs (MAP content, yield, morphologies, and thermal properties) were then investigated systematically. The morphologies, chemical structures, and thermal properties were characterized by optical microscopy, scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), Fourier transform infrared (FTIR) spectroscopy, and thermogravimetry analyzer (TGA). The results show that MAP was well encapsulated by MF resin. No microcapsules are obtained at <55 °C or with polymerization times <1 h. Optimal preparation conditions of reaction temperature, polymerization time, and reaction pH value are 75 °C, 3 h, and 5.5, respectively. Those results provide process reference and theoretical basis for preparing MCMAPs and could promote the application of MAP microcapsules in wood flame-retardant materials.

Adsorptive removal of ciprofloxacin and sulfamethoxazole from aqueous matrices using sawdust and plastic waste-derived biochar: A sustainable fight against antibiotic resistance.

We produced carbon-negative biochar from the pyrolysis of sawdust biomass alone (SB) and from the co-pyrolysis of sawdust and plastic waste (SPB). The co-pyrolysis approach in this study was driven by several hypothetical factors, such as increased porosity, surface chemistry, stability, as well as waste management. We applied pyrolyzed and co-pyrolyzed biochars for the removal of ciprofloxacin (CFX) and sulfamethoxazole (SMX). Due to its more alkaline and amorphous nature, SB showed better removal efficiencies compared to SPB. The maximum removals of CFX and SMX with SB were observed as ∼95% and >95%, respectively whereas with SPB were 58.8%, and 34.9%, respectively. The primary mechanisms involved in the adsorption process were H-bonding, electrostatic and π-π electron donor-acceptor interactions. Homogenously and heterogeneously driven adsorption of both antibiotics followed the pseudo-second-order kinetic model, implying electron sharing/transfer (chemisorption) mediated adsorption. The work is highly pertinent in the context of emerging concerns related to drivers that promote antimicrobial resistance.

Characterization and commissioning of a new collaborative multi-modality radiotherapy platform.

TaiChi, a new multi-modality radiotherapy platform that integrates a linear accelerator, a focusing gamma system, and a kV imaging system within an enclosed O-ring gantry, was introduced into clinical application. This work aims to assess the technological characteristics and commissioning results of the TaiChi platform. The acceptance testing and commissioning were performed following the manufacturer's customer acceptance tests (CAT) and several AAPM Task Group (TG) reports/guidelines. Regarding the linear accelerator (linac), all applicable validation measurements recommended by the MPPG 5.a (basic photon beam model validation, intensity-modulated radiotherapy (IMRT)/volumetric-modulated arc therapy (VMAT) validation, end-to-end(E2E) tests, and patient-specific quality assurance (QA)) were performed. For the focusing gamma system, the absorbed doses were measured using a PTW31014 ion chamber (IC) and PTW60016 diode detector. EBT3 films and a PTW60016 diode detector were employed to measure the relative output factors (ROFs). The E2E tests were performed using PTW31014 IC and EBT3 films. The coincidences between the imaging isocenter and the linac/gamma mechanical isocenter were investigated using EBT3 films. The image quality was evaluated regarding the contrast-to-noise ratio (CNR), spatial resolution, and uniformity. All tests included in the CAT met the manufacturer's specifications. All MPPG 5.a measurements complied with the tolerances. The confidence limits for IMRT/VMAT point dose and dose distribution measurements were achieved according to TG-119. The point dose differences were below 1.68% and gamma passing rates (3%/2 mm) were above 95.1% for the linac E2E tests. All plans of patient-specific QA had point dose differences below 1.79% and gamma passing rates above 96.1% using the 3%/2 mm criterion suggested by TG-218. For the focusing gamma system, the differences between the calculated and measured absorbed doses were below 1.86%. The ROFs calculated by the TPS were independently confirmed within 2% using EBT3 films and a PTW60016 detector. The point dose differences were below 2.57% and gamma passing rates were above 95.3% using the 2%/1 mm criterion for the E2E tests. The coincidences between the imaging isocenter and the linac/gamma mechanical isocenter were within 0.5 mm. The image quality parameters fully complied with the manufacturer's specifications regarding the CNR, spatial resolution, and uniformity. The multi-modality radiotherapy platform complies with the CAT and AAPM commissioning criteria. The commissioning results demonstrate that this platform performs well in mechanical and dosimetry accuracy.

Therapeutic Evaluation of Induction Chemotherapy for Locoregionally Advanced Nasopharyngeal Carcinoma With Low-risk N Stage : A Multicenter Retrospective Study From Nonendemic Region of China.

OBJECTIVES: The role of induction chemotherapy (IC) remains ambiguous in a patient with T3-4N0-1 nasopharyngeal carcinoma (NPC) according to data from the endemic area of China. Here, we conducted a multicenter retrospective study to investigate the value of adding IC to concurrent chemoradiotherapy (CCRT) for T3-4N0-1 NPC from Northwest China. METHODS: Data were extracted in 3 hospitals from Northwest China between May 1, 2010 and August 30, 2018. The Kaplan-Meier method was used to estimate the endpoints. Survival curves were compared using the log-rank test. Initial propensity matching was conducted with a 1:1 match of IC + CCRT to CCRT. The primary endpoint of this study was overall survival (OS). RESULTS: A total of 108 patients with staging T3-4N0-1 were included in this study. The median follow-up time was 50 months (range: 6 to 118 months). IC followed by CCRT did not significantly improve OS compared with CCRT in the whole cohort (89.5% vs 77.6%, hazard ratio: 0.41, 95% CI: 0.16-1.04, P = 0.100). But significantly better OS was found when a well-balanced propensity score-matched cohort was analyzed. Adjusted 4-year OS was 89.5% for IC followed by CCRT versus 71.1% for CCRT (hazard ratio: 0.30, 95% CI: 0.11-0.80, P = 0.027). No significant differences were detected in side effects between the two groups. CONCLUSION: This study suggested IC followed by CCRT had the potential to further improve OS in patients with T3-4N0-1M0 NPC from Northwest China compared with CCRT. However, prospective studies with a large sample are warranted to confirm the results.

The epidemiological characteristics of neurogenic limb deformity disorder in China: a national-based study from Qin Sihe orthopedic center.

BACKGROUND: Neurogenic limb deformity disorder (NLDD) refers to limb deformity disorders caused by various neurogenic disorders. However, there are no studies to systematically summarize and analyze these diseases in China, and we first proposed the concept of NLDD. We describe the epidemiological characteristics of NLDD in China based on the largest case database of limb orthopedics in China. METHODS: This study analyzed parameters from the Qin Sihe Orthopedic Surgery Case Data (QSHOSCD). The database is based on the Rehabilitation Hospital affiliated to National Research Center for Rehabilitation, which has collected nearly 37,000 patients to date and includes a wide variety of limb deformities. The types of diseases are summarized and classified for all patients studied. Statistical analysis was based on the type of etiology, age, regional distribution, and historical surgical volume. Partial outcomes were statistically analyzed separately by common diseases (polio and cerebral palsy) and rare diseases (37 other diseases). RESULTS: From 1979 to 2019, 30,194 patients with NLDD were treated surgically for 39 neurogenic disorders. The male to female ratio was 1.48:1, the mean age was 19.65 years, and most patients (82.38%) were aged between 6 and 30 years. Patients included from 32 provinces and cities across China, mainly concentrated in populous central provinces and Heilongjiang Province. The peak of annual surgical procedures was from 1988 to 1994, and the number of annual surgical procedures for common diseases gradually decreased from 1994 onwards, but the trending is opposite for rare diseases. CONCLUSIONS: This study is the first to demonstrate the disease types, population characteristics and incidence trends of NLDD in China. It suggests that the prevention and treatment of NLDD should focus on the adolescent population and enhance the treatment of neurogenic diseases that cause limb deformities. The growth and adaption of the Ilizarov technique and its practice in Chinese orthopedic benefits the treatment of neurogenic limb deformity disorders.

Cadmium distribution and transformation in leaf cells involved in detoxification and tolerance in barley.

Barley is a diagnostic plant that often used in the research of soil pollution by heavy metals, our research explored the detoxification and tolerance mechanism of cadmium(Cd) in barley through pot experiment. We investigated subcellular distribution, chemical forms and oxidative damage of Cd in barley leaves, combing with the transmission electron microscopy and Fourier-transform infrared spectroscopy(FT-IR) to further understand the translocation, transformation characteristics and toxic effect of Cd in cells. The results showed that, the bioaccumulation factors in roots and shoots of barley were ranged of 4.03-7.48 and 0.51-1.30, respectively. Barley reduces the toxic effects by storing Cd in the roots and reducing its transport to the shoots. Compared to the control treatment (0 mg/kg), the percentage of Cd in the cell wall fractions of leaves in 300 mg/kg Cd treatment increased from 34.74 % to 38.41 %; the percentage of the organelle fractions increased from 24.47 % to 56.02 %; and the percentage of soluble fraction decreased from 40.80 % to 5.57 %. We found that 69.13 % of the highly toxic inorganic Cd and water-soluble Cd were converted to less toxic pectates and protein-integrated Cd (50.20 %) and undissolved Cd phosphates (18.93 %). This conversion of Cd was mainly due to its combination with -OH, -NH, -CN, -C-O-C, and -C-O-P groups. Excessive Cd induced a significant (P < 0.05) increase in the levels of peroxidase, malondialdehyde, and cell membrane permeability, which damaged the cell membrane and allowed Cd to enter the organelles. The chloroplasts and mitochondria were destroyed, and eventually the metabolism of intracellular substances was affected, resulting in symptoms of toxicity. Our research provides cellular-scale insight into the mechanisms of Cd tolerance in barley.

Low expression of microRNA-125b enhances the expression of STAT3 and contributes to cholesteatoma growth.

Introduction: MicroRNA-125b has been found to be down-regulated in many types of malignant tumours and diseases with excessive proliferation of keratinocytes, such as cutaneous squamous cell carcinoma and psoriasis. Cholesteatoma, which is mainly composed of keratinocytes, also has characteristics of abnormal proliferation similar to a malignant tumour. However, the expression and regulatory mechanisms of miR-125b and its downstream genes in cholesteatoma have not been clarified. Material and methods: Real time fluorescence quantitative PCR was applied to detect the expression of miR-125b in the cholesteatoma and corresponding retroauricular skin. Immunohistochemical staining and western blot were used to detect signal transducers and activators of transcription 3 (STAT3) and the downstream gene cyclin D1, survivin, and vascular endothelial growth factor (VEGF) in the cholesteatoma and corresponding retroauricular skin. The targeted regulatory relationship between miR-125b and STAT3 was confirmed by dual luciferase reporter assay. Proliferation and apoptosis of transfected HaCaT cells were detected by MTS, cell cycle, and apoptosis assays. Results: We observed down-regulation of miR-125b and up-regulation of STAT3, cyclin D1, survivin, and VEGF in cholesteatoma tissues. STAT3 was a direct target gene of miR-125b. Inhibition of miR-125b enhanced STAT3 and its downstream genes expression, promoted HaCaT cell proliferation, and inhibited apoptosis. Conclusions: The results of this study demonstrate that miR-125b can influence the growth of cholesteatoma by targeting STAT3 and its downstream genes, including cyclin D1, survivin, and VEGF, thus providing an opportunity to establish new medical therapy strategies and facilitating further study of the pathogenesis of cholesteatoma.

The influence of cerebral small vessel diseases on the efficacy of repositioning therapy and prognosis of benign paroxysmal positional vertigo.

Background: Although vascular risk factors have been found to be closely related to the development of benign paroxysmal positional vertigo (BPPV), the relationship between BPPV and cerebral small vessels diseases (CSVDs) has rarely been discussed in literature. This study set out to investigate the efficacy of repositioning therapy and prognosis among BPPV patients with CSVDs. Methods: We enrolled 553 BPPV patients who had undergone brain MRI, and categorized them into two groups based on the presence or absence of CSVDs. After controlling for other confounders using a propensity score matching (PSM) approach, we compared the incidence of recurrence and residual dizziness (RD). Then, we analyzed the recurrence rate and RD incidence in 176 BPPV patients with CSVDs, and assessed potential risk factors. Results: White matter hyperintensity (WMH, 72.2%) and lacunar infarction (LI, 65.9%) were the two CSVDs that were present in the highest proportion among the BPPV patients. The incidence of RD in patients with CSVDs was significantly higher compared to subjects without CSVDs. Patients with RD (n=100, 56.8%) were older, had more severe WMH, and had a higher incidence of brain atrophy; age and higher Fazekas score were independent risk factors. Among the recurrent patients (n=61, 34.7%), the ages were older, the Fazekas score of WMH was higher, and number of LIs was increased; age was the sole independent risk factor. Conclusion: BPPV patients with a combination of CSVD comorbidities, especially elderly patients with WMHs, are more likely to develop RD, which needs to be paid more attention.

GAF domain is essential for nitrate-dependent AtNLP7 function.

Nitrate is an essential nutrient and an important signaling molecule in plants. However, the molecular mechanisms by which plants perceive nitrate deficiency signaling are still not well understood. Here we report that AtNLP7 protein transport from the nucleus to the cytoplasm in response to nitrate deficiency is dependent on the N-terminal GAF domain. With the deletion of the GAF domain, AtNLP7ΔGAF always remains in the nucleus regardless of nitrate availability. AtNLP7 ΔGAF also shows reduced activation of nitrate-induced genes due to its impaired binding to the nitrate-responsive cis-element (NRE) as well as decreased growth like nlp7-1 mutant. In addition, AtNLP7ΔGAF is unable to mediate the reduction of reactive oxygen species (ROS) accumulation upon nitrate treatment. Our investigation shows that the GAF domain of AtNLP7 plays a critical role in the sensing of nitrate deficiency signal and in the nitrate-triggered ROS signaling process.

Final Overall Survival Analysis of Gemcitabine and Cisplatin Induction Chemotherapy in Nasopharyngeal Carcinoma: A Multicenter, Randomized Phase III Trial.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically on the based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We previously reported significantly improved failure-free survival using gemcitabine plus cisplatin induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma. Here, we present the final overall survival (OS) analysis. In this multicenter, randomized trial, patients were assigned to be treated with concurrent chemoradiotherapy alone (standard therapy, n = 238) or gemcitabine and cisplatin induction chemotherapy before concurrent chemoradiotherapy (n = 242). With a median follow-up of 69.8 months, the induction chemotherapy group had a significantly higher 5-year OS (87.9% v 78.8%, hazard ratio, 0.51 [95% CI 0.34 to 0.78]; P = .001) and a comparable risk of late toxicities (≥ grade 3, 11.3% v 11.4%). Notably, the depth of the tumor response to induction chemotherapy correlated significantly and positively with survival (complete response v partial response v stable/progressive disease, 5-year OS, 100% v 88.4% v 61.5%, P = .005). Besides, patients with a low pretreatment cell-free Epstein-Barr virus DNA load (< 4,000 copies/mL) might not benefit from induction chemotherapy (5-year OS, 90.6% v 91.4%, P = .77). In conclusion, induction chemotherapy before concurrent chemoradiotherapy improved OS significantly in patients with locally advanced nasopharyngeal carcinoma, without increasing the risk of late toxicities. Tumor response to induction chemotherapy and pretreatment cell-free Epstein-Barr virus DNA might be useful to guide individualized treatment.

A New Nomogram for Predicting the Risk of Intracranial Hemorrhage in Acute Ischemic Stroke Patients After Intravenous Thrombolysis.

Background: We aimed to develop and validate a new nomogram for predicting the risk of intracranial hemorrhage (ICH) in patients with acute ischemic stroke (AIS) after intravenous thrombolysis (IVT). Methods: A retrospective study enrolled 553 patients with AIS treated with IVT. The patients were randomly divided into two cohorts: the training set (70%, n = 387) and the testing set (30%, n = 166). The factors in the predictive nomogram were filtered using multivariable logistic regression analysis. The performance of the nomogram was assessed based on the area under the receiver operating characteristic curve (AUC-ROC), calibration plots, and decision curve analysis (DCA). Results: After multivariable logistic regression analysis, certain factors, such as smoking, National Institutes of Health of Stroke Scale (NIHSS) score, blood urea nitrogen-to-creatinine ratio (BUN/Cr), and neutrophil-to-lymphocyte ratio (NLR), were found to be independent predictors of ICH and were used to construct a nomogram. The AUC-ROC values of the nomogram were 0.887 (95% CI: 0.842-0.933) and 0.776 (95% CI: 0.681-0.872) in the training and testing sets, respectively. The AUC-ROC of the nomogram was higher than that of the Multicenter Stroke Survey (MSS), Glucose, Race, Age, Sex, Systolic blood Pressure, and Severity of stroke (GRASPS), and stroke prognostication using age and NIH Stroke Scale-100 positive index (SPAN-100) scores for predicting ICH in both the training and testing sets (p < 0.05). The calibration plot demonstrated good agreement in both the training and testing sets. DCA indicated that the nomogram was clinically useful. Conclusions: The new nomogram, which included smoking, NIHSS, BUN/Cr, and NLR as variables, had the potential for predicting the risk of ICH in patients with AIS after IVT.

Ilizarov technology in China: a historic review of thirty-one years.

PURPOSE: To summarize the evolution of Ilizarov technology in China, highlight important milestones, introduce the atmosphere of the era concerning the first uses and development of this technology, and share Chinese modification and experience in this field. METHOD: A thorough interview with senior ASAMI members of China and literature search and physical books in libraries was undertaken to summarize the history of Ilizarov technology in China. RESULTS: The formal development of Ilizarov technology began when professor Ilizarov himself came to Beijing (1991) and gave a speech. In the following 31 years, his technology was rapidly developed through China, with many symposiums held and associations established including ASAMI China (2003) and ILLRS China (2015). Today, Ilizarov technology has become the main treatment of complex fractures, defects, nonunion, infections, deformities, and chronic ischemic ulcers of the limbs. In those years, Chinese scholars also developed some special treatment methods and made many modifications to Ilizarov external fixators. CONCLUSION: Ilizarov technology has developed in China for 31 years. It revolutionized the treatment of complex limb traumas, deformities, and diseases. In the treatment of millions of patients, Chinese scholars had many unique experiences and made modifications to this technology which is worthy to share with the world.

miR-139/PDE2A-Notch1 feedback circuit represses stemness of gliomas by inhibiting Wnt/ß-catenin signaling.

Rationale: The malignant phenotypes of glioblastomas (GBMs) are primarily attributed to glioma stem cells (GSCs). Our previous study and other reports have suggested that both miR-139 and its host gene PDE2A are putative antitumor genes in various cancers. The aim of this study was to investigate the roles and mechanisms of miR-139/PDE2A in GSC modulation. Methods: Clinical samples were used to determine miR-139/PDE2A expression. Patient-derived glioma stem-like cells (PD-GSCs) were stimulated for immunofluorescent staining, sphere formation assays and orthotopic GBM xenograft models. Bioinformatic analysis and further in vitro experiments demonstrated the downstream molecular mechanisms of miR-139 and PDE2A. OX26/CTX-conjugated PEGylated liposome (OCP) was constructed to deliver miR-139 or PDE2A into glioma tissue specifically. Results: We demonstrated that miR-139 was concomitantly transcribed with its host gene PDE2A. Both PDE2A and miR-139 indicated better prognosis of gliomas and were inversely correlated with GSC stemness. PDE2A or miR-139 overexpression suppressed the stemness of PD-GSCs. FZD3 and ß-catenin, which induced Wnt/ß-catenin signaling activation, were identified as targets of miR-139 and mediated the effects of miR-139 on GSCs. Meanwhile, PDE2A suppressed Wnt/ß-catenin signaling by inhibiting cAMP accumulation and GSK-3ß phosphorylation, thereby modulating the self-renewal of PD-GSCs. Notably, Notch1, which is also a target of miR-139, suppressed PDE2A/miR-139 expression directly via downstream Hes1, indicating that miR-139 promoted its own expression by the miR-139-Notch1/Hes1 feedback circuit. Expectedly, targeted overexpression miR-139 or PDE2A in glioma with OCP system significantly repressed the stemness and decelerated glioma progression. Conclusions: Our findings elaborate on the inhibitory functions of PDE2A and miR-139 on GSC stemness and tumorigenesis, which may provide new prognostic markers and therapeutic targets for GBMs.

Residual Volume of Lymph Nodes During Chemoradiotherapy Based Nomogram to Predict Survival of Nasopharyngeal Carcinoma Patient Receiving Induction Chemotherapy.

PURPOSE: To accurately stratify nasopharyngeal carcinoma (NPC) patients who were benefit from induction chemotherapy (IC) followed by chemoradiotherapy (CCRT), we established residual volume of lymph nodes during chemoradiotherapy based nomogram to predict survival for NPC patients. METHODS: Cox regression analysis were used to evaluate predictive effects of tumor volume parameters. Multivariate Cox regression analysis was used to identify the prognostic factors, and nomogram models were developed to predict survival of NPC patients receiving IC followed by CCRT. RESULTS: Compared with other tumor volumetric parameters, midRT GTVnd was the best predictive factor for OS (HR: 1.043, 95%CI: 1.031-1.055), PFS (HR: 1.040, 95%CI: 1.030- 1.051), and DMFS (HR: 1.046, 95%CI: 1.034 - 1.059) according to the HR of Cox regression analysis. Based on multivariate analysis, three nomograms included midRT GTVnd were constructed to predict 4-year survival. The C-index of nomograms for each survival endpoints were as follow (training cohort vs. validation cohort): 0.746 vs. 0.731 for OS; 0.747 vs. 0.735 for PFS; 0.768 vs. 0.729 for DMFS, respectively. AUC showed a good discriminative ability. Calibration curves demonstrated a consistence between actual results and predictions. Decision curve analysis (DCA) showed that the nomograms had better clinical predictive effects than current TNM staging system. CONCLUSION: We identified the best volumetric indicator associated with prognosis was the residual volume of lymph nodes at the fourth week of chemoradiotherapy for patients receiving IC followed by CCRT. We developed and validated three nomograms to predict specific probability of 4-year OS, PFS and DMFS for NPC patient receiving IC followed by CCRT.

Long-term survival outcomes and adverse effects of nasopharyngeal carcinoma patients treated with IMRT in a non-endemic region: a population-based retrospective study.

OBJECTIVES: To evaluate the long-term survival outcomes and adverse effects of intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC) and to summarise the experiences of IMRT in NPC in the past few decades in non-endemic northwest China. DESIGN: A population-based retrospective study. SETTING: An experience of using IMRT in non-endemic region of China. PARTICIPANTS: The study included 792 newly diagnosed and non-metastatic NPC patients who received IMRT from January 2006 to September 2018 in Xijing Hospital. OUTCOME MEASURES: The survival outcomes, adverse effects and failure patterns were evaluated by univariate, multivariate and subgroup analyses. RESULTS: With a median follow-up time of 46.2 months, the 5-year local recurrence-free survival, regional recurrence-free survival, distant metastasis-free survival, disease-free survival (DFS) and overall survival (OS) rates were 90.8%, 97.0%, 82.8%, 69.6% and 78.0%, respectively. Multivariate analysis showed that age, N stage, clinical stage, pathological type and primary tumour volume of more than 23 cm3 were the independent prognosis factors for DFS (all p<0.05); age, N stage, pathological type, cervical lymph node necrosis, and anaemia were significantly associated with OS (all p<0.05). The most common acute toxicities of IMRT were dermatitis, mucositis and dysphagia. Xerostomia and hearing impairment were the top two late toxicities. The main failure patterns were distant metastasis and local and/or regional relapses. CONCLUSIONS: Similar survival, toxicities and failure patterns have been observed in patients treated with IMRT in a non-endemic area of China when compared with that in endemic areas. Induction chemotherapy combined with concurrent chemoradiotherapy may benefit locally advanced NPC in non-endemic areas of China.

Detailed analysis of recovery process of cranial nerve palsy after IMRT-based comprehensive treatment in nasopharyngeal carcinoma.

BACKGROUND: Cranial nerve (CN) palsy due to cancer involvement has been considered as an unfavorable prognostic factor for patients with nasopharyngeal carcinoma (NPC). We assessed the role of IMRT based treatment on the recovery of CN palsy and investigated the prognostic value of complete recovery of CN palsy. METHODS: A total of 115 NPC patients with cancer-related CN palsy were included in the study. We referred CTCAE version 5.0 to evaluate the grade of CN palsy. RESULTS: All patients with grade 1 CN palsy recovered completely during the 2 years of follow-up after definite treatment. Most grade 2 palsy could change gradually to grade 1 palsy or complete recovery during 2 years of follow-up. Patients with more than 2 symptoms of CN palsy had poor 3-year disease-free survival (DFS) than these with 1 or 2 symptoms (60.3% vs. 84.9%, HR 0.25, 95% CI 0.07-0.89, P = 0.001). There were no significant differences for PFS, OS, DMFS and LRFS between patients with complete recovery and non-complete recovery from CN palsy after receiving IMRT based comprehensive treatment. CONCLUSIONS: IMRT based comprehensive treatment could effectively promote the recovery of tumor-related CN palsy for NPC patient. More than 2 symptoms of CN palsy was a poor prognostic factor for DFS of NPC patients. The prognostic role of complete recovery of CN palsy was not identified in our study.