A portable smartphone detection of ctDNA using MnB2 nanozyme and paper-based analytical device.

The development of point-of-care testing (POCT) for circulating tumor DNA (ctDNA) is meaningful for the non-invasive cancers screening and diagnosis, particularly in resource-limited settings. The microfluidic paper-based analytical device (µPAD) provides an ideal platform, its application in ctDNA assays remains underexplored. In this work, a multifunctional µPAD was manufactured, which can enhance the efficiency and reduce the cost of ctDNA sensing. Additionally, a smartphone-based application analysis was fabricated for convenient, portable detection and colorimetric signal readout. Moreover, the novel oxidase-like MnB2 nanozyme was introduced in the sandwiches sensing strategy, utilizing its catalytic properties to effectively generate a colorimetric signal. The use of MnB2 nanozyme in sensing application is relatively novel, and its catalytic performance and mechanism was thoroughly evaluated via experiment and density functional theory (DFT) calculations. After optimizing the detection conditions, the proposed biosensor exhibited satisfactory results. Furthermore, the method was successfully used to detect ctDNA in tumor cell lysates and peripheral blood samples from tumor-bearing mice. The results were consistent with standard qPCR method, affirming the reliability of our POCT analysis device in ctDNA detection. Thus, this work not only provides a paper-based POCT device and intelligent analysis tool for portable cancers diagnosis, but it also paves a new application path for MnB2 nanozyme in the sensing filed.

Tinnitus pitch does not always fall within the frequency range of hearing loss - a cross-sectional study on the mechanism of tinnitus production.

BACKGROUND: Clinically, we find that tinnitus patients often have hearing loss. According to the most accepted mechanism of tinnitus, that is, the spontaneous discharge and abnormal synchronization of neurons after afferent reduction, tinnitus frequency is closely related to the frequency of hearing loss. OBJECTIVE: The purpose of this study was to investigate the correlation of tinnitus pitch with the frequency of hearing loss. MATERIALS AND METHODS: A total of 500 patients with unilateral or bilateral chronic tinnitus were enrolled in this study. All patients underwent pure tone audiometry (PTA) and tinnitus acoustic examination. Hearing loss levels and frequencies were recorded. The relationship between tinnitus pitch and hearing loss level and frequency was statistically analyzed. RESULTS: Our results showed that 96.6% of the 500 tinnitus patients had hearing loss. Statistical analysis showed that low frequency (LF) tinnitus was correlated with LF hearing loss, but moderate frequency & high frequency (MF&HF) tinnitus was not significantly associated with MF&HF hearing loss. The coincidence of tinnitus pitch with the highest hearing threshold correlated with the degree of hearing loss. CONCLUSION AND SIGNIFICANCE: The vast majority of patients with chronic subjective tinnitus had hearing loss, and the frequency of tinnitus correlated with the degree and frequency of hearing loss but not exactly fall within the frequency range of hearing loss.

A sensitive sandwich-type electrochemical aptasensing platform based on Ti3C2Tx/MoS2/MWCNT@rGONR composites for simultaneous detection of kanamycin and chloramphenicol in food samples.

A Ti3C2Tx/MoS2/MWCNT@rGONR nanocomposite was prepared for the first time for building a sensitive electrochemical aptasening platform to simultaneously detect kanamycin (Kana) and chloramphenicol (Cap). Owing to their accordion-like structure, rich surface groups, and high charge mobility, Ti3C2Tx/MoS2/MWCNT@rGONR composites provided a spacious covalent immobilization surface and a better electrochemical aptasensing platform. The aptamers of Kana and Cap used in sensors enhance the selectivity. Furthermore, TiP, an ion exchanger, was used for loading more different metal ions functioning as labels to form a sandwich-type sensor together with Ti3C2Tx/MoS2/MWCNT@rGONR, improving the electrochemical sensitivity and obtaining a highly distinguishable signal readout. Under the optimized conditions, the sensor has good detection limits of 0.135 nmol L-1 and 0.173 nmol L-1 for Kana and Cap, respectively, at the same linearity concentration of 0.5-2500 nmol L-1. Finally, it was successfully applied for detection in milk and fish meat, and the results were compared with the standard method HPLC, indicating its great potential for food safety monitoring.

Role of polyferric sulfate and ferric chloride on anaerobic fermentation of sludge from novel two-stage process for resource recovery.

Polyferric sulfate (PFS) and ferric chloride (FC) were compared for their efficiencies in capturing organic carbon and phosphorus, and their effects on the anaerobic fermentation process of sludge from a pilot-scale two-stage reactor were studied. Both PFS and FC promoted organic carbon and phosphorus capture. Further study revealed that PFS-based sludge with a dosage of 18 mg Fe/Lsewage showed a better volatile fatty acids (VFAs) production performance (202.97 ± 2.38 mg chemical oxygen demand (COD)/g volatile solids (VS)) than that of FC-based sludge (169.25 ± 1.56 mg COD/g VS). Besides, the high dosage of PFS effectively promoted the activities of the α-glucosidase and proteases. The dissimilatory iron reduction process enhanced sludge flocs disintegration and the conversion of carbohydrates and proteins to VFAs. Non-hydroxyapatite phosphorus predominated in the total phosphorus of all samples. This study contributes to developing strategies for optimizing iron-based sludge management and high-value product recovery.

Label-free fluorescent sensor for sensitive detection of ctDNA based on water stabilized CsPbBr3 nanosheet.

The detection of circulating tumor DNA (ctDNA), as a practical liquid biopsy technique, was of great significance for the study of cancer diagnosis and prognosis. However, reported methods for detection ctDNA still have some limitations, such as tedious process and high cost. In this study, CsPbBr3 nanosheet (CsPbBr3 NS) with high water stability was prepared by etching, and its fluorescence intensity could be stably stored for 1 year. The Ti3C2Tx possessed high quenching efficiency for CsPbBr3 NS and the HOMO-LUMO orbital study revealed that the PET mechanism was responsible for fluorescence quenching. And the Ti3C2Tx showed stronger affinity towards single-stranded DNA (ssDNA), as compared with double-stranded DNA (dsDNA). The probe ssDNA could be adsorbed on the surface of Ti3C2Tx through π-π stacking. After the targets were recognized by probe ssDNA to form dsDNA, its affinity with Ti3C2Tx decreased and the active site of Ti3C2Tx recovered, causing a high quenching efficiency on CsPbBr3 NS. Based on this, a label-free fluorescent biosensor was designed for the sensitive detection of ctDNA (EGFR 19 Dels for non-small cell lung cancer, NSCLC). Under the optimal experimental conditions, this biosensor exhibited a detection limit of 180 fM and a linear range of 50 pM-350 pM with amplification of magnetic beads through strand displacement reaction. In addition, this sensor was applied to the detection of ctDNA in serum samples and cells lysates. This method for ctDNA detection was expected to have great potential for biomarker detection in the field of liquid biopsy.

Anterior Talofibular Ligament Repair in Combination With Anterior Tibiofibular Ligament Distal Fascicle Transfer for The Treatment of Chronic Lateral Ankle Instability: A Finite Element Analysis.

In recent years, anterior tibiofibular ligament-distal fascicle transfers for anterior talofibular ligament augmentation repair have proposed. However, a comprehensive biomechanical study on the anterior tibiofibular ligament-distal fascicle transfer is still lacking. We are established four distinct groups, namely the normal, the anterior talofibular ligament rupture, the anterior talofibular ligament repair, and the anterior talofibular ligament repair + anterior tibiofibular ligament-distal fascicle transfer. We assessed the anterior drawer test and varus stress test of the ankle in each group. Moreover, we employed the model to simulate and compute the total displacement and von-Mises stress of the talus cartilage at varying gait phases, including foot strike, tibia vertical, and toe-off phases. The results of the anterior drawer test and varus stress test revealed that the anterior talofibular ligament repair + anterior tibiofibular ligament-distal fascicle transfer group exhibited greater closeness to the normal group. Regarding von-Mises stress in cartilage, the three gait instants had higher values in the anterior talofibular ligament repair + anterior tibiofibular ligament-distal fascicle transfer group than the other groups. Nevertheless, regarding total displacement, the toe-off phases exhibited higher values in the anterior talofibular ligament repair + anterior tibiofibular ligament-distal fascicle transfer group than the other groups. Using ATiFL-DF transfer to augment ATFL repair is a potential feasible procedure. However, this procedure could potentially compromise the anterior tibiofibular ligament's contribution to the dynamic stability of the ankle. Therefore, we recommend conducting further in-depth research to ensure the suitability and success of this technique in a clinical environment.

Comparative Evaluation of Metallic and Biodegradable Suture Anchors in Arthroscopic Repair of Anterior Talofibular Ligament Injury: A Short-term Study on Clinical and Functional Outcomes.

BACKGROUND With the development of arthroscopy and suture anchor, the modified BrostrÓ§m technique has made remarkable progress. However, it is unclear which material is most suitable for treating anterior talofibular ligament injury (ATFL). This study evaluated the short-term efficacy of 2 suture anchors (metal vs biodegradable materials) in arthroscopic ATFL repair. MATERIAL AND METHODS From January 2018 to December 2019, 82 patients with ankle disorders (51 men and 31 women) with ATFL injury received arthroscopic repair with suture anchor through the BrostrÓ§m-Gould procedure. The mean age was 38.70±9.35 years (range, 18-54 years). Each patient was followed up. American Orthopedic Foot and Ankle Society score (AOFAS), Karlsson Ankle Functional Score (KAFS), and the Visual Analogue Scale (VAS) were used to evaluate functional status and pain. RESULTS All patients were followed up for 21.21±2.19 months (range, 18-25 months). No complications were found either group. Preoperative clinical and functional scores in both groups had no significant difference (P>0.05). The functional score increased significantly in both groups (P<0.001). At the last follow-up, the mean AOFAS score was 93.00 (90.00, 96.00) in the Biodegradable group and 93.50 (91.00, 96.00) in the Metallic group (P=0.31). The mean KAFS score was 91.50 (85.00, 95.00) in the Biodegradable group and 93.00 (90.00, 95.50) in the Metallic group (P=0.10); the mean VAS score was 1.50 (1.00, 1.80) in the Biodegradable group and 1.30 (0.98, 1.70) in the Metallic group (P=0.22). CONCLUSIONS Arthroscopic repair of ATFL injury with suture anchors can improve the prognosis of CAI. There were no statistically significant differences in clinical and functional outcomes with metal or biodegradable suture anchors at short-term follow-up.

Recent advances on cyclodepsipeptides: biologically active compounds for drug research.

Cyclodepsipeptides are a large family of peptide-related natural products consisting of hydroxy and amino acids linked by amide and ester bonds. A number of cyclodepsipeptides have been isolated and characterized from fungi and bacteria. Most of them showed antitumor, antifungal, antiviral, antimalarial, and antitrypanosomal properties. Herein, this review summarizes the recent literatures (2010-2022) on the progress of cyclodepsipeptides from fungi and bacteria except for those of marine origin, in order to enrich our knowledge about their structural features and biological sources.

In Different Gender Groups, What Is the Impact of the Fibular Notch on the Severity of High Ankle Sprain: A Retrospective Study of 360 Cases.

OBJECTIVES: The role of the distal tibiofibular ligament in the occurrence of high ankle sprain (HAS) has been widely studied. But previous studies have overlooked the physiological and anatomical differences between males and females and have not further refined gender. Therefore, the impact of the anatomical morphology of fibular notch (FN) on HAS in different genders is still unclear. This study aimed to explore the impact of different types of FN on the severity of HAS and to estimate the prognosis of patients with HAS while excluding anatomical differences caused by gender. METHODS: One hundred and eighty patients with HAS were included in this study as the experimental group (i.e., HAS group). They were further divided into four groups according to gender and FN depth, with deep concave FN ≥ 4 mm and shallow flat FN < 4 mm. Another 180 normal individuals were set as the control group. The FN morphological indicators, tibiofibular distance (TFD), and ankle mortise indexes were measured and compared with those in HAS group. The independent t-test was used to compare continuous variables between groups, the intraclass correlation coefficient (ICC) was used to analyze the reliability of intra-observer measurement, and the Pearson correlation coefficient was used to verify the correlation between FN and the severity of HAS. RESULTS: In males with shallow flat type, the measurements of anterior tibiofibular distance (aTFD), middle tibiofibular distance (mTFD), posterior tibiofibular distance (pTFD), front ankle mortise width (fAMW), middle ankle mortise width (mAMW), posterior ankle mortise width (pAMW), and depth of ankle mortise (DOAM) in HAS group were significantly larger than those in normal group (p < 0.05). In male patients with deep concave type, the measurements of aTFD, mTFD, fAMW, mAMW, and DOAM were significantly larger than those in normal group (p < 0.05). Among female patients with shallow flat type, the measurements of aTFD, mTFD, pTFD, fAMW, mAMW, pAMW, and DOAM were found to be significantly larger than those in normal group (p < 0.05). Among female patients with deep concave type, the measurements of mTFD, pTFD, fAMW, mAMW, and DOAM were found to be significantly larger than those of the normal group (p < 0.05). The depth of FN was negatively correlated with TFD, and the AOFAS score of patients with shallow flat type was significantly lower than that of patients with deep concave type after treatment (p < 0.05). CONCLUSIONS: In different gender groups, compared with the normal controls, the TFD and partial ankle mortise indices were significantly different in HAS patients. Moreover, FN depth was negatively correlated with TFD, and the AOFAS score of shallow flat patients was significantly lower than that of deep concave patients. These suggested that shallow flat FN may be associated with more severe distal tibiofibular ligament injury and ankle mortise widening, leading to poorer prognosis. This should be taken seriously in clinical practice.

Association between the distal tibiofibular syndesmosis morphology classification and ankle osteoarthritis: a retrospective study.

BACKGROUND: Syndesmosis injury is proposed to contribute to ankle stability and osteoarthritis (OA). However, whether distal tibiofibular syndesmosis structure is closely related to ankle OA is unclear. We hypothesized that different DTS morphology classifications would affect the biomechanics properties in ankle OA. The study aimed to determine the association between the distal tibiofibular syndesmosis (DTS) morphological classification and ankle OA. METHODS: This is a retrospective study examining imaging data of 147 patients (87 males and 60 females) with ankle OA. Magnetic resonance imaging was used to access the DTS morphological classification, according to measuring various parameters. Joint space narrowing and osteophytes were measured using ankle weight-bearing radiography. The classification and parameters were analyzed to determine the relationship between the syndesmosis classification and the abnormality of ankle OA. RESULTS: Five morphological classifications of the DTS, including Chevron (19.6%), Widow's peak (16.2%), Flat (22.3%), Trapezoid (32.0%), and Crescent (19.6%), were shown. There were statistical differences between DTS classification and tibial angle surface angle (TAS) (P = .009) and talar tilt angle (TTA) (P = .014). The TAS (degree) of the Crescent (86.47 ± 3.21) was less than Chevron (88.75 ± 2.72) (P = .006), Widow's peak (89.26 ± 3.15) (P = .001), Flat (88.83 ± 3.62) (P = .003) and Trapezoid (88.11 ± 2.62) (P = .041), respectively. The TTA (degree) of Crescent (86.83 ± 5.30) was less than Chevron (89.28 ± 2.46) and Widow's peak (89.82 ± 3.41). The men were greater than women for TAS (P = .008) and angle (P = .003), which are consistent with osteophyte (P = .019) and the modified Kellgren-Lawrence grades (P = .041) between gender. CONCLUSIONS: DTS morphological classification might affect the biomechanics properties in TAS and TTA in ankle OA. In clinical practice, surgeons should pay attention to the effects of DTS on ankle OA. LEVEL OF EVIDENCE: Level III, retrospective study.

A label-free fluorescent sensor for rapid and sensitive detection of ctDNA based on fluorescent PDA nanoparticles.

Technological advances in the detection of circulating tumor DNA (ctDNA) have made new options available for diagnosis, classification, biological studies, and treatment selection. However, effective and practical methods for analyzing this emerging class of biomarkers are still lacking. In this work, a fluorescent biosensor was designed for the label-free detection of ctDNA (EGFR 19 del for non-small cell lung cancer, NSCLC). The biosensor was based on the fact that MnO2 nanosheets (MnO2 NSs) have stronger affinity towards single-stranded DNA (ssDNA), as compared with double-stranded DNA (dsDNA). As a high-performance nanoenzyme, MnO2 NSs could oxidize dopamine (DA) into fluorescent polydopamine nanoparticles (FL-PDA NPs), which could be used as a fluorescence signal. The probe ssDNA could be adsorbed on the surface of MnO2 NSs through π-π stacking, and the active site would be masked, causing a lower fluorescence. After the targets were recognized by probe ssDNA to form dsDNA, its affinity for MnO2 NSs decreased and the active site recovered, causing a restored fluorescence. It was verified that Mn ions, •OH radicals and electron transfer were the important factors in the catalytic oxidation of DA. Under the optimal experimental conditions, this biosensor exhibited a detection limit of 380 pM and a linear range of 25-125 nM, providing reliable readout in a short time (45 min). This sensor exhibited outstanding specificity, stability and reproducibility. In addition, this sensor was applied to the detection of ctDNA in serum samples and cell lysates. It is demonstrated that FL-PDA NPs can be used as a fluorescence signal for easy, rapid and label-free detection of ctDNA without any other amplification strategies, and the proposed strategy has great potential for biomarker detection in the field of liquid biopsy.

An ultrasensitive ratiometric electrochemical aptasensor based on metal-organic frameworks and nanoflower-like Bi2CuO4 for human epidermal growth factor receptor 2 detection.

An ultra-sensitive ratiometric electrochemical aptasensor was constructed based on metal-organic frameworks (MOFs) and bimetallic oxides for the detection of the human epidermal growth factor receptor 2 (HER2), a breast cancer marker. The aluminum metal-organic framework (Al-MOF) and cerium-metal-organic framework (Ce-MOF) have higher specific surface area, which is conducive to load more aptamers or complementary DNA (cDNA), and realize the amplification of internal reference signal Fc. Furthermore, nanoflower-like bismuth copper oxide (Bi2CuO4) with abundant active sites was introduced to modify more aptamers on its surface, which were then fixed to the glassy carbon electrode (GCE) to amplify the detection signal. The quantitative detection of HER2 was achieved by differential pulse voltammetry (DPV), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The materials were characterized by scanning electron microscope, transmission electron microscope, Zeta potential analyzer, X-ray diffraction and X-ray photoelectron spectroscopy. The ratiometric electrochemical aptasensor based on nanomaterial and chain displacement signal amplification technology could discern HER2 in a very wide range (0.001-20.0 ng/mL) with an extremely low detection limit (0.049 pg/mL) and has demonstrated good performance in clinical serum analysis. This strategy also provides a feasible idea for sensitive analysis of other clinical tumor markers.

Porous-nanozyme-based colorimetric sensor for rapid detection of kanamycin in foods under neutral condition.

Most colorimetric methods based on nanozymes need to have excellent performance under acidic condition, so they are currently facing some challenges in the field of food hazard detection. Herein, a facile and rapid colorimetric sensor for kanamycin (KAN) detection in foods under neutral condition has been designed using the peroxidase-mimic activity of porous nanozyme like Co3 O4 nanodisk. Further investigations showed that the interaction mechanism between porous Co3 O4 nanodisk and substrates belongs to a ping-pong model, and the inhibition type of KAN on the peroxidase-mimic activity is noncompetitive inhibition. The constructed sensor has good sensitivity for KAN with the limit of 57 nM, and the color changes can be discerned visually when KAN exceeds 0.5 µM. Besides, the colorimetric sensor obtains excellent recovery results in chicken serum, milk, honey, and pork, which shows that the proposed sensing strategy can provide a rapid and convenient detection method for KAN in foods under neutral condition. PRACTICAL APPLICATION: The established sensing strategy can rapidly distinguish whether KAN residue exceeds the permissible level within 10 min, which meets the requirement for on-site monitoring of antibiotics in foods, and also open up a new idea for other hazards detection under neutral condition.

Efficacy and factors influencing outcomes of customized music therapy combined with a follow-up system in chronic tinnitus patients.

BACKGROUNDS: Tinnitus is a meaningless sound signal perceived by the patients in the absence of auditory stimuli. Due to the complex etiology and unclear mechanism, specific therapies for tinnitus are still in the exploratory stage. In recent years, personalized and customized music therapy has been proposed as an effective method for tinnitus treatment. The aim of this study was to explore the efficacy of customized therapy with a well-designed follow-up system in the treatment of tinnitus through a large sample one arm study and to identify the relevant factors affecting the treatment outcome. METHODS: The study investigated a total of 615 patients with unilateral or bilateral chronic tinnitus who received personalized and customized music therapy for 3 months. A complete follow-up system was designed by the professionals. Questionnaires of Tinnitus Handicap Inventory (THI), Hospital Anxiety and Depression Scale (HADS) and Visual Analogue Scale (VAS) were used to evaluate the therapeutic effects and relevant factors affecting the efficacy of therapy. RESULTS: The results showed a decreasing trend in THI and VAS scores after 3 months of therapy, with statistically significant differences between pre- and post-therapy time points (P < 0.001). All patients were divided into 5 groups according to THI scores, and the mean reduction score in catastrophic, severe, moderate, mild and slight group was 28, 19, 11, 5, 0 respectively. The proportion of tinnitus patients with anxiety was higher than that with depression (70.57% and 40.65%, respectively), and there were statistically significant differences between HADS-A/D scores pre- and post-therapy. Binary logistic regression showed that the baseline of THI, VAS scores, the duration of tinnitus and the state of anxiety prior to therapy were significant influencing factors of therapeutic efficacy. CONCLUSIONS: The magnitude of reduction in THI scores after music therapy depended on the severity of the patients' tinnitus, the higher the initial THI scores, the greater the potential for improvement in tinnitus disorders. Music therapy also reduced the anxiety and depression levels of tinnitus patients. Therefore, personalized and customized music therapy with a comprehensive follow-up system may be an effective treatment option for chronic tinnitus patients.

Distribution and risk assessment of microplastics in Liujiaxia Reservoir on the upper Yellow River.

Microplastics (MPSs) distribution in global freshwater systems is extensively reported, but the distribution of MPSs in reservoirs of the Yellow River has rarely been studied. To fill in this gap, we systematically investigated the distribution of MPSs in surface water and bank sediments gleaned from Liujiaxia Reservoir of the upper Yellow River for the first time and conducted an ecological risk assessment in succession in this work. The results showed that the main polymer types of MPSs in the surface water and bank sediments of Liujiaxia Reservoir were polyethylene terephthalate (PET), polystyrene (PS), and polypropylene (PP), and the abundance of MPSs in the reservoir surface water and bank sediments ranged from 4.48 to 12.09 item/L and 447.27 to 1543.80 item/kg (dry weight), respectively. Further physical morphology analysis of MPSs in the samples revealed that MPSs in the surface water and bank sediments of Liujiaxia Reservoir were predominantly fibrous with small particle sizes (<1 mm), and there was abundant color, mainly exhibiting transparent, black, and blue. The results of the MPS pollution load index (PLI>1) and the hazard ranking of MPSs (HZone = 10.20 for surface water and HZone = 14.06 for bank sediments) yielded a hazard class II for MPS pollution in Liujiaxia Reservoir, the combined pollution risk index (PRIZone = 17.05 for surface water and PRIZone = 31.25 for bank sediments) stated clearly the potential ecological risk in the Liujiaxia Reservoir. Briefly, this study supplemented and enriched the data on the distribution of MPSs in the reservoirs of the Yellow River basin, and provide a benchmark for future pollution control and management in the reservoir area.

Conductive metal-organic framework based label-free electrochemical detection of circulating tumor DNA.

An ultrasensitive electrochemical biosensor was designed for the rapid label-free detection of circulating tumor DNA (ctDNA, EGFR 19 Dels for non-small cell lung cancer, NSCLC). We linked the highly conjugated tricatecholate, 2,3,6,7,10,11-hexahydroxytriphenylene (HHTP) with Ni(II) ions into the two-dimensional porous conductive metal-organic frameworks (MOFs), which is termed Ni-catecholates (Ni-CAT). Then, the AuNPs/Ni-catecholates/carbon black/polarized pencil graphite electrode (AuNPs/Ni-CAT/CB/PPGE) was obtained by electrodeposition of AuNPs on the surface of PPGE modified with Ni-CAT/CB composite materials. The AuNPs/Ni-CAT/CB/PPGE were used for label-less detection of ctDNA, with a total detection time of only 30 min. Under optimal detection conditions, the AuNPs/Ni-CAT/CB/PPGE sensor exhibited excellent detection performance with good linear response to ctDNA over a wide concentration range and the detection limit down to the femtomolar level. The sensor was applied to the determination of ctDNA in serum samples with high sensitivity. This simple, efficient, and expeditious method has practical value in liquid biopsy of ctDNA and has potential for development in early detection, treatment, and prognosis of tumors. Herein, an ultrasensitive electrochemical biosensor was designed for the rapid label-free detection of ctDNA (EGFR 19 Dels for non-small cell lung cancer, NSCLC). We linked the highly conjugated tricatecholate, 2,3,6,7,10,11-hexahydroxytriphenylene (HHTP) with Ni(II) ions into the two-dimensional porous conductive metal-organic frameworks (MOFs), which is termed as Ni-catecholates (Ni-CAT). Then, the AuNPs/Ni-catecholates/carbon black/polarized pencil graphite electrode (AuNPs/Ni-CAT/CB/PPGE) was obtained by electrodeposition of AuNPs on the surface of PPGE modified with Ni-CAT/CB composite materials. The AuNPs/Ni-CAT/CB/PPGEs were used for label-less detection of ctDNA, with a total detection time of only 30 min. Under optimal detection conditions, the AuNPs/Ni-CAT/CB/PPGE sensor exhibited excellent detection performance with good linear response to ctDNA in the concentration range of 1 × 10-15 M to 1 × 10-6 M and with a detection limit as low as 0.32 fM. The sensor was applied for determination of ctDNA in serum samples and gave high sensitivity. This simple, efficient and expeditious method has practical value in liquid biopsy of ctDNA and has potential for development in early detection, treatment and prognosis of tumors.

Novel nitrogen-doped carbon dots for "turn-on" sensing of ATP based on aggregation induced emission enhancement effect.

In this work, a nitrogen-doped carbon dots (CDs) was successfully synthesized by hydrothermal synthesis of polyethylenimine (PEI) and citric acid. The as-prepared CDs suffered from aggregation-caused quenching (ACQ) with a high concentration, but after adding adenosine triphosphate (ATP), the CDs aggregated. The generation of aggregates caused the rotation of the surface groups on CDs and reduced the non-radiation decay. The QY of CDs in water was 9.25 %, and increased to 16.60 % and 63.38% in the addition of 100 and 1000 µM ATP. And then, the enhancement of the radiation rate led to the aggregation induced enhancement effect (AIEE). Moreover, we also found that the proportion of precursors for CDs synthesis was a key factor in the occurrence of AIEE. Therefore, such CDs would be excellent candidates as fluorescent probes for the label-free detection of ATP. Our proposed method exhibited simple and easy preparation of nanoprobe, quick response (3 min), wide range of linear rage (1-2000 µM) and eco-friendly. In addition, the method performed successfully as a "turn-on" sensor for detection of ATP in the tablet with a recovery of 100.1~106.9% and RSD below 3.5%.

[Extracranial/intracranial vascular bypass to control carotid artery blowout in postirradiated nasopharyngeal carcinoma patients].

Objective:To summarize and analyze the effect of extracranial/intracranial vascular bypass in the treatment of internal carotid artery burst hemorrhage after radiotherapy for nasopharyngeal carcinoma（NPC）. Methods:A retrospective analysis of the data of 9 patients with nasopharyngeal carcinoma and carotid artery blowout syndrome（CBS） who underwent extracranial/intracranial vascular bypass. Collected patient demographics, treatment course and dose of radiotherapy, analyze the effect of extracranial/intracranial vascular bypass on the prognosis of patients with internal carotid artery burst hemorrhage, including perioperative stroke and death, overall survival rate, and rebleeding rate. Results:Nine patients were included in the study. The average age is 53.5 years. The pathological types were all non-keratinizing squamous cell carcinoma, undifferentiated, stage Ⅳ; 7 cases of local NPC recurrence, 2 cases of skull base osteonecrosis; all 9 cases had internal carotid artery hemorrhage, including 7 cases of petrous carotid artery and 2 cases of cervical carotid artery; 3 cases of typeⅠthreatened CBS（33.3%）, 2 cases of type Ⅱ impending CBS（22.2%）, and 4 cases of type Ⅲ acute CBS（44.45%）. All patients underwent extracranial/intracranial vascular bypass surgery, and there were no perioperative deaths and strokes. The mean follow-up was 16.7 months. The median overall survival time of the patients was 22.1 months and the 90-day, 1-year and 2-year survival rates were 100.0%, 75.0% and 30.0%, respectively. Conclusion:Patients with internal carotid artery burst hemorrhage after radiotherapy for nasopharyngeal carcinoma can be safely treated by extracranial/intracranial vascular bypass surgery and obtain a longer survival rate.

Extracranial/Intracranial Vascular Bypass in the Treatment of Head and Neck Cancer - Related Carotid Blowout Syndrome.

OBJECTIVE/HYPOTHESIS: To investigate the endovascular intervention or extracranial/intracranial (EC/IC) vascular bypass in the management of patients with head and neck cancer-related carotid blowout syndrome (CBS). STUDY DESIGN: Retrospective case series. METHODS: Retrospective analysis of clinical data of patients with head and neck cancer-related CBS treated by endovascular intervention and/or EC/IC vascular bypass, analysis of its bleeding control, neurological complications, and survival results. RESULTS: Thrity-seven patients were included. Twenty-five were associated with external carotid artery (ECA); twelve were associated with internal or common carotid artery (ICA/CCA). All patients with ECA hemorrhage were treated with endovascular embolization. Of the 12 patients with ICA/CCA hemorrhage, 9 underwent EC/IC bypass, 1 underwent endovascular embolization, and 3 underwent endovascular stenting. For patients with ECA-related CBS, the median survival was 6 months, and the 90-day, 1-year, and 2-year survival rates were 67.1%, 44.7%, and 33.6%, respectively; the estimated rebleeding risk at 1-month, 6-month, and 2-year was 7.1%, 20.0%, and 31.6%, respectively. For patients with ICA/CCA-related CBS, the median survival was 22.5 months, and the 90-day, 1-year, and 2-year survival rates were 92.3%, 71.8%, and 41.0%, respectively; the estimated rebleeding risk at 1 month, 6 months, and 2 years is 7.7%,15.4%, and 15.4%, respectively. ICA/CCA-related CBS patients have significantly longer survival time and lower risk of rebleeding, which may be related to the more use of EC/IC vascular bypass as a definite treatment. CONCLUSIONS: For patients with ICA/CCA-related CBS, if there is more stable hemodynamics, longer expected survival, EC/IC vascular bypass is preferred. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:1548-1556, 2021.

Ketamine ameliorates hypoxia-induced endothelial injury in human umbilical vein endothelial cells.

OBJECTIVES: Hypoxia leads to endothelial cell inflammation, apoptosis, and damage, which plays an important role in the complications associated with ischemic cardiovascular disease. As an oxidoreductase, p66Shc plays an important role in the regulation of reactive oxygen species (ROS) production and apoptosis. Ketamine is widely used in clinics. This study was designed to assess the potential protective effect of ketamine against hypoxia-induced injury in human umbilical vein endothelial cells (HUVECs). Moreover, we explored the potential mechanism by which ketamine protected against hypoxia-induced endothelial injury. METHODS: The protective effects of ketamine against hypoxia-induced injury was assessed using cell viability and adhesion assays, quantitative polymerase chain reaction, and western blotting. RESULTS: Our data showed that hypoxia reduced HUVEC viability, increased the adhesion between HUVECs and monocytes, and upregulated the expression of endothelial adhesion molecules at the protein and mRNA levels. Moreover, hypoxia increased ROS accumulation and upregulated p66Shc expression. Furthermore, hypoxia downregulated sirt1 expression in HUVECs. Alternatively, ketamine was shown to reverse the hypoxia-mediated reduction of cell viability and increase in the adhesion between HUVECs and monocytes, ameliorate hypoxia-induced ROS accumulation, and suppress p66Shc expression. Moreover, EX527, a sirt1 inhibitor, reversed the protective effects of ketamine against the hypoxia-mediated reduction of cell viability and increase in adhesion between HUVECs and monocytes. CONCLUSION: Ketamine reduces hypoxia-induced p66Shc expression and attenuates ROS accumulation via upregulating sirt1 in HUVECs, thus attenuating hypoxia-induced endothelial cell inflammation and apoptosis.