Distinguishable Magnetic Reporter Coordination with Buoyancy-Magnetism Separation for Immobilization-Free Dual-Target Electrochemical Immunosensing.

Simultaneous sensitive and precise determination of multibiomarkers is of great significance for improving detection efficiency, reducing diagnosis and treatment expenses, and elevating survival rates. However, the development of simple and portable biosensors for simultaneous determination of multiplexed targets in biological fluids still faces challenges. Herein, a unique and versatile immobilization-free dual-target electrochemical biosensing platform, which combines distinguishable magnetic signal reporters with buoyancy-magnetism separation, was designed and constructed for simultaneous detection of carcinoembryonic (CEA) and α-fetoprotein (AFP) in intricate biological fluids. To construct such distinguishable magnetic signal reporters with signal transduction, amplification, and output, secondary antibodies of CEA and AFP were respectively functionalized on methylene blue (MB) and 6-(ferrocenyl)hexanethiol (FeC) modified Fe3O4@Au magnetic nanocomposites. Meanwhile, a multifunctional flotation probe with dual target recognition, capture, and isolation capability was prepared by conjugating primary antibodies (Ab1-CEA, Ab1-AFP) to hollow buoyant microspheres. The target antigens of CEA and AFP can trigger a flotation-mediated sandwich-type immunoreaction and capture a certain amount of the distinguishable magnetic signal reporter, which enables the conversion of the target CEA and AFP quantities to the signal of the potential-resolved MB and FeC. Thus, the MB and FeC currents of magnetically adsorbed distinguishable magnetic reporters can be used to determine the CEA and AFP targets simultaneously and precisely. Accordingly, the proposed strategy exhibited a delightful linear response for CEA and AFP in the range of 100 fg·mL-1-100 ng·mL-1 with detection limits of 33.34 and 17.02 fg·mL-1 (S/N = 3), respectively. Meanwhile, no significant nonspecific adsorption and cross-talk were observed. The biosensing platform has shown satisfactory performance in the determination of real clinical samples. More importantly, the proposed approach can be conveniently extended to universal detection just by simply substituting biorecognition events. Thus, this work opens up a new promising perspective for dual and even multiple targets and offers promising potential applications in clinical diagnosis.

The French multicentric molecular analysis platforms and personalized medicine trials MOST, MOST Plus and MEGAMOST.

BACKGROUND AND PURPOSE: In this manuscript we describe the academic French multicentric molecular analysis platforms including PROFILER, promoted by Centre Léon Berard, and the multicentric personalized medicine trials MOST, MOST Plus and MEGAMOST. PATIENTS/MATERIAL AND METHODS: MOST, MOST Plus and MEGAMOST comprise 14 cohorts with different targeted agents and immunotherapies. RESULTS AND INTERPRETATION: PROFILER has recruited 5,991 patients in 10 years, MOST and MOST Plus 875 patients since 2014 and MEGAMOST 172 patients since 2020, and are still ongoing. We provide a description of the local, national and international implications of these initiatives, and we review the results of the sorafenib and olaparib cohorts.

The Effect of Dexmedetomidine as a Local Anesthetic Adjuvant for Iliac Fascia Compartment Block on Postoperative Delirium in Elderly Patients Undergoing Elective Hip Surgery.

INTRODUCTION: We analyzed the effect of dexmedetomidine (DEX) as a local anesthetic adjuvant on postoperative delirium (POD) in elderly patients undergoing elective hip surgery. METHODS: In this study, 120 patients undergoing hip surgery were enrolled and randomly assigned to two groups: fascia iliaca compartment block with DEX + ropivacaine (the Y group, n = 60) and fascia iliaca compartment block with ropivacaine (the R group, n = 60). The primary outcomes: presence of delirium during the postanesthesia care unit (PACU) period and on the first day (D1), the second day (D2), and the third day (D3) after surgery. The secondary outcomes: preoperative and postoperative C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), occurrence of insomnia on the preoperative day, day of operation, D1 and D2; HR values of patients in both groups before iliac fascia block (T1), 30 min after iliac fascia block (T2), at surgical incision (T3), 20 min after incision (T4), when they were transferred out of the operating room (T5) and after leaving the recovery room (T6) at each time point; VAS for T1, PACU, D1, D2; the number of patients requiring remedial analgesics within 24 h after blockade and related complications between the two groups. RESULTS: A total of 97 patients were included in the final analysis, with 11 and 12 patients withdrawing from the R and Y groups, respectively. The overall incidence of POD and its incidence in the PACU and ward were all lesser in the Y group than in the R group (p < 0.05). Additionally, fewer cases required remedial analgesia during the PACU period, and more vasoactive drugs were used for maintaining circulatory system stability in the Y group as compared to the R group (p < 0.05). At the same time, the incidence of intraoperative and postoperative bradycardia in the Y group was higher than that in the R group, accompanied by lower postoperative CRP and ESR (all p < 0.05). CONCLUSION: Ultrasound-guided high fascia iliaca compartment block with a combination of ropivacaine and DEX can reduce the incidence of POD, the use of intraoperative opioids and postoperative remedial analgesics, and postoperative inflammation in elderly patients who have undergone hip surgery, indicating that this method could be beneficial in the prevention and treatment of POD.

Fascinating Immobilization-Free Electrochemical Immunosensing Strategy Based on the Cooperation of Buoyancy and Magnetism.

Rapid and accurate detection of biomolecules is of vital importance for the diagnosis of disease and for performing timely treatments. The point-of-care analysis of cancer biomarkers in the blood with low cost and easy processing is still challenging. Herein, an advanced and robust strategy, which integrates the buoyant recognition probe with the magnetic reporter probe in one solution, was first proposed for immobilization-free electrochemical immunosensing. The tumor marker of alpha fetoprotein (AFP) can be captured immune-buoyantly, and then a multifunctional magnetic reporter probe in pseudo-homogeneous solution was further captured to fulfill a sandwich-type immunoreaction. The residual magnetic reporter probe can be firmly and efficiently attracted on a magnetic glassy carbon electrode to fulfill the conversion of the target AFP amount into the residual magnetic electrochemical signal indicator. As a result, the electrochemical signal of methylene blue can accurately reflect the original level of target antigen AFP concentration. By integrating buoyancy-driven quasi-homogenous biorecognition with magnetism-mediated amplification and signal output, the proposed immobilization-free electrochemical immunosensing strategy displayed a wide range of linear response (100 fg mL-1 to 10 ng mL-1), low detection limit (14.52 fg mL-1), and good reproducibility, selectivity, and stability. The designed strategy manifests remarkable advantages including assay simplicity, rapidness, and high sensitivity owing to the in-solution instead of on-electrode biorecognition that could accelerate and improve the biorecognition efficiency. To the best of our knowledge, this is the first cooperation of buoyancy-driven biorecognition with magnetism-mediated signal output in bioanalysis, which would be attractive for rapid clinic biomedical application. Thus, this work provides a fresh perspective for convenient and favorable immobilization-free electrochemical biosensing of universal biomolecules.

Ratiometric Electrochemiluminescence Sensing of Carcinoembryonic Antigen Based on Luminol.

Ratiometric electrochemiluminescence (ECL) sensors can efficiently remove environmental interference to attain precise detection. Nonetheless, two eligible luminophores or coreactants were usually needed, increasing the complexity and restricting their practical application. In this study, a single luminophore of luminol with a single coreactant of H2O2 was employed to construct a dual-potential ratiometric ECL sensor for the detection of carcinoembryonic antigen (CEA). The produced palladium nanoclusters (Pd NCs) employing a DNA duplex as a template could not only stimulate luminol to produce cathodic ECL (Icathodic) but also quench its anodic ECL (Ianodic). During the detection process, CEA could damage the double-stranded structure and reduce the Pd NCs' amount, triggering a significant decrease in the ratio of Icathodic to Ianodic (Icathodic/Ianodic) and thereby achieving sensitive CEA's detection. Furthermore, the Icathodic/Ianodic was independent of the H2O2 concentration, which avoided a prejudicial effect from H2O2 decomposition and considerably enhanced the detection's reliability. The developed ratiometric ECL sensor demonstrated a sensitive detection toward CEA with a wide linear range from 100 ag/mL to 10 ng/mL and a detection limit of 87.1 ag/mL (S/N = 3). In conclusion, this study offers a new idea for constructing ratiometric ECL sensors based on a single luminophore and technical support for cancer's early diagnosis.

Thermally Hypsochromic or Bathochromic Emissions? The Silver Nuclei Does Matter.

Structural modulation of core-shell silver nanoclusters from the inside is a huge challenge but of great importance in their syntheses. Herein, two silver nanoclusters [Ag3 S9 @Ag42 ] (SD/Ag45b) and [Ag9 S9 @Ag42 ] (SD/Ag51a) are isolated in the presence of different kinds of sulfonic acids. Uniquely, SD/Ag45b and SD/Ag51a show typical core-shell structures with the similar Ag42 shell but different cores. The outer shell of 42 silver atoms comprises two Ag3 trigons at two poles encircled by three equatorial distorted square cupolas (J4 , Ag12 ). The core in SD/Ag45b is a silver trigon ligated by nine S2- ions (Ag3 S9 ), while a tricapped triangular prismatic Ag9 also ligated by the same amount of S2- ions (Ag9 S9 ) is observed in the inner core of SD/Ag51a. The electrospray ionization mass spectrometry (ESI-MS) indicates that the introduction of p-toluenesulfonic acid can realize the transformation from SD/Ag45b to Ag51 . SD/Ag45b and SD/Ag51a show inverse luminescence thermochromic behaviors in the near-infrared (NIR) region, mainly dictated by the inner silver cores. This work not only realizes the synthesis of new silver nanoclusters by core modulation but also provides a prototype to get molecular-level insight into the correlation between structure and luminescence thermochromism.

CHMFL-26 is a highly potent irreversible HER2 inhibitor for use in the treatment of HER2-positive and HER2-mutant cancers.

Oncogene HER2 is amplified in 20%-25% of human breast cancers and 6.1%-23.0% of gastric cancers, and HER2-directed therapy significantly improves the outcome for patients with HER2-positive cancers. However, drug resistance is still a clinical challenge due to primary or acquired mutations and drug-induced negative regulatory feedback. In this study, we discovered a potent irreversible HER2 kinase inhibitor, CHMFL-26, which covalently targeted cysteine 805 of HER2 and effectively overcame the drug resistance caused by HER2 V777L, HER2 L755S, HER2 exon 20 insertions, and p95-HER2 truncation mutations. CHMFL-26 displayed potent antiproliferation efficacy against HER2-amplified and mutant cells through constant HER2-mediated signaling pathway inhibition and apoptosis induction. In addition, CHMFL-26 suppressed tumor growth in a dose-dependent manner in xenograft mouse models. Together, these results suggest that CHMFL-26 may be a potential novel anti-HER2 agent for overcoming drug resistance in HER2-positive cancer therapy.

Value Of Anteroposterior-To-Transverse Ratio in Ultrasonic Diagnosis of Thyroid Nodule in Different Locations.

PURPOSE: To investigate the value of anteroposterior-to-transverse ratio (ATR) and the effect on features of nodules in ultrasound (US) diagnosis of thyroid nodules in different locations.  Methods: The nodules were divided into three groups according to the different nodule location: isthmus group; upper and lower poles of bilobed thyroid group; and the middle of the bilobed thyroid group. The diameters of the nodules were recorded, and ATR of the nodule was calculated on the transverse and longitudinal sections. The transverse and the longitudinal sections of ATR of thyroid nodules in different groups were compared.  Result: The transverse section of ATR was significantly different among the three groups (p = 0.001). In addition, there are significant differences in many US features among three groups, including nodule composition, thyroid parenchyma, morphology, echogenicity, shape, calcifications, vascularity, nodule ACR TI-RADS and histopathologic (all p < 0.05). In the group of upper and lower poles of bilobed thyroid, significant difference was found between the transverse and the longitudinal section of ATR (p = 0.019). The cut-off values of transverse section and longitudinal section of ATR were 0.967 and 0.750, respectively.  Conclusion: The transverse section of ATR at different location of thyroid may be a predictor for malignancy with clinical diagnostic significance.

Efficacy and safety of different drug treatments in patients with spinal-cord injury-related neuropathic pain: a network meta-analysis.

STUDY DESIGN: Systematic review with network meta-analysis. OBJECTIVE: We explored the efficacy and safety of different drug treatments in patients with spinal-cord injury (SCI)-related neuropathic pain. We investigated which treatment is most suitable for such patients by judging the efficacy and safety of these drugs. METHODS: We searched the PubMed, Medline, Embase and Cochrane databases from inception to 31 August 2020. The quality of the included studies was assessed. We selected the proportion of patients whose pain was reduced by ≥50% and the prevalence of adverse effects as the outcome indicators of efficacy and safety, respectively. RESULTS: We included 15 randomized controlled clinical trials involving five interventions (anticonvulsants, antidepressants, anesthetics, opioids and botulinum toxin A). Based on the proportion of patients with pain reduction ≥50%, the order (from highest to lowest) was anticonvulsants > anesthetics > antidepressants > botulinum toxin A > opioids > placebo. With regard to the prevalence of adverse effects, the order of safety (from highest to lowest) was placebo > antidepressants > botulinum toxin A > anticonvulsants > opioids > anesthetics. Analyzes of efficacy and safety revealed that anticonvulsant, antidepressant and botulinum toxin A have good efficacy and safety. CONCLUSION: The efficacy of anticonvulsants, anesthetics, antidepressants, opioids and botulinum toxin A was greater than that of placebo for treatment of SCI-related neuropathic pain. However, the prevalence of adverse effects associated with use of these drugs was also higher than that of placebo. Further analyses based on efficacy and safety revealed anticonvulsants to be more suitable for such patients. In addition, antidepressant and botulinum toxin A may be promising treatments for SCI-related neuropathic pain, however, their effects still need to be further explored due to the small sample size.

Fingerprint combining with quantitative analysis of multi-components by single marker for quality control of Chenxiang Huaqi tablets.

BACKGROUND: Chenxiang Huaqi tablets (CXHQTs) are a traditional Chinese medicine (TCM) commonly used to treat stomach-related diseases. Currently, the ministerial standards do not provide detailed guidance and regulations on the content determination of CXHQTs, and the reported studies only use individual active components as indicators for determining effective ingredients. OBJECTIVE: The present study aimed to propose a methodology for quality control of CXHQTs based on high-performance liquid chromatography (HPLC) fingerprinting combined with the quantitative analysis of multi-components by single marker (QAMS) method. METHODS: HPLC method was used to determine seven active ingredients and performed fingerprint analysis of CXHQTs. To further process chemometric assessment, technical analysis-model including similarity analysis (SA), hierarchical clustering analysis (HCA), principal components analysis (PCA) and orthogonal partial least squares discrimination analysis (OPLS-DA) was set up to differentiate and classify the 20 batches of samples. RESULTS: After comparing the results of QAMS method with the external standard method (ESM), we found there is no significant difference. Besides, the fingerprint of CXHQT was also established. CONCLUSION: HPLC fingerprint combined with the QAMS could be an efficient and selective analysis technique to achieve a qualitative and quantitative evaluation of executing quality processes.

Effects of B-azolemiteacrylic on life-history traits and demographic parameters of two-spotted spider mite, Tetranychus urticae (Acari: Tetranychidae).

The present study was conducted to evaluate sublethal effects of B-azolemiteacrylic on the two-spotted spider mite, Tetranychus urticae Koch (Acari: Tetranychidae). Female adults of T. urticae were exposed to LC10 and LC30 of the acaricide, and the effects on treated females and their offspring were evaluated. The results showed that the fecundity of F0 female adults treated with LC10 and LC30 of B-azolemiteacrylic was reduced by 30.9 and 39.2%, respectively. Longevity and oviposition period of the females were significantly reduced as well. The developmental duration of egg and deutonymph stage of the F1 generation were not significantly different from that of the control. The protonymph stage after LC30 treatment lasted significantly longer, whereas the larva, deutonymph and female stage were significantly shorter than the control. The oviposition period of the F1 generation was significantly shortened, the fecundity of each female decreased significantly, and the ratio of female-to-male was reduced too. Moreover, the average generation period of T. urticae after LC10 and LC30 treatments was shorter than that of the control, and the net production rate (R0), intrinsic rate of increase (rm) and finite rate of increase (λ) were all reduced by 33.3, 7.5 and 1.9% (LC10 treatment) and by 51.3, 14.8 and 3.6% (LC30 treatment), respectively. The population doubling time was prolonged by 7.5 and 14.8% after LC10 and LC30 treatments, respectively, compared with the control. These results indicate that B-azolemiteacrylic may effectively inhibit the development rate of the F0 and F1 populations of T. urticae, which will help design integrated strategies for the comprehensive control of T. urticae and rational use of pesticides in the field.

A novel ratiometric electrochemical biosensing strategy based on T7 exonuclease-assisted homogenous target recycling coupling hairpin assembly-triggered double-signal output for the multiple amplified detection of miRNA.

A novel ratiometric electrochemical biosensing strategy based on T7 exonuclease (T7 Exo)-assisted homogenous target recycling coupling hairpin assembly triggered dual-signal output was proposed for the accurate and sensitive detection of microRNA-141 (miRNA-141). Concretely, in the presence of target miRNA, abundant signal transduction probes were released via the T7 Exo-assisted homogenous target recycling amplification, which could be captured by the specially designed ferrocene-labeled hairpin probe (Fc-H1) on -electrode interface and triggered the nonenzymatic catalytic hairpin assembly (Fc-H1 + MB-H2) to realize the cascade signal amplification and dual-signal output. Through such a conformational change process, the electrochemical signal of Fc (IFc) and MB (IMB) is proportionally and substantially decreased and increased. Therefore, the signal ratio of IMB/IFc can be employed to accurately reflect the true level of original miRNA. Benefiting from the efficient integration of the T7 Exo-assisted target recycle, nonenzymatic hairpin assembly and dual-signal output mode, the proposed sensor could realize the amplified detection of miRNA-141 effectively with a wide detection range from 1 fM to 100 pM, and a detection limit of 200 aM. Furthermore, it exhibits outstanding sequence specificity to discriminate mismatched RNA, acceptable reproducibility and feasibility for real sample. This strategy effectively integrated the advantages of multiple amplification and ratiometric output modes, which could provide an accurate and efficient method in biosensing and clinical diagnosis.

Graphene-PtPd nanocomposite for low-potential-driven electrochemiluminescent determination of carcinoembryonic antigen using Ru(bpy)32.

As well known, the electrochemiluminescence (ECL) of tris(2,2'-bipyridine)ruthenium(II) (Ru(bpy)32+) heavily relies on highly positive or negative triggered voltage, prejudicing the detection toward the bio-molecules. In this work, Ru(bpy)32+ could generate enhanced and stable ECL at a low potential of 0.05 V (vs. Ag/AgCl) on graphene-PtPd hybrid, attributing to its excellent electrocatalysis from the synergistic effect between Pt and Pd. The obtained low-potential-driven ECL could be quenched by MoS2 nanoflowers. Based on the quenching effect, a sandwich "signal-off" ECL immunosensor was fabricated to sensitively detect carcinoembryonic antigen (CEA). A linear calibration curve from 1 fg mL-1 to 1 ng mL-1 was obtained along with a low detection limit of 0.54 fg mL-1 (S/N = 3) under optimal conditions. The sensor showed satisfactory specificity, stability, and reproducibility and was successfully applied to determine CEA in actual samples. The recoveries ranged from 98.80 to 100.23%, and the relative standard deviation (RSD) was lower than 5%. Above all, this work explored new materials in low-potential-driven ECL system and provided a reliable sensing strategy for clinical applications.

Phospholipase C inhibits apoptosis of porcine oocytes cultured in vitro.

Oocyte apoptosis can be used as an indicator of oocyte quality and development competency. Phospholipase C (PLC) is a critical enzyme that participates in phosphoinositide metabolic regulation and performs many functions, including the regulation of reproduction. In this study, we aimed to explore whether PLC participates in the regulation of apoptosis in porcine oocytes and investigated its possible mechanism. In porcine oocytes, 0.5 µM U73122 (the PLC inhibitor) was considered to be the best concentration to facilitate maturation, and 0.5 µM m-3M3FBS (the PLC activator) was regarded as the most appropriate concentration to inhibit maturation. The percentage of cleavage and blastocysts treated with 0.5 µM U73122 was lower than that of the control group. Furthermore, the percentage of cleavage and blastocysts treated with 0.5 µM m-3M3FBS was higher than that of the control group. The relative PLC messenger RNA (mRNA) expression tested by a quantitative real-time polymerase chain reaction was found to be inhibited by 0.5 µM U73122 or activated by 0.5 µM m-3M3FBS. The relative mRNA abundance of BAK, BAX, CASP3, CASP8, and TP53 and protein abundance of Bak, cleaved caspase-3, caspase-8, and P53 was activated by U73122 or inhibited by m-3M3FBS, while the relative mRNA and protein level of BCL6 showed the opposite trend. The intracellular Ca2+ concentration increased and the expression of PLCB1 protein also increased in porcine oocytes when they were cultured with 0.5 µM m-3M3FBS for 44 hours. The abundance of proteins PKCß and CAMKIIα and the expression of several downstream genes (CDC42, NFATc1, NFATc2, NFκB, and NLK) were activated by m-3M3FBS or inhibited by U73122. Our findings indicate that PLC inhibits apoptosis and maturation in porcine oocytes. The intracellular Ca2+ concentration, two Ca2+ -sensitive proteins, and several downstream genes were positively regulated by PLC.

Preliminary exploration of atmospheric water vapor, liquid water and ice water by ultraviolet Raman lidar.

Water is the only atmospheric component with three phases. In this work, ultraviolet Raman lidar is developed for synchronous measurements of water vapor, liquid water and ice water in Xi'an (34.233°N, 108.911°E), China. Different interference filters are designed to construct individual water Raman channels, and the corresponding central wavelength and bandwidth are determined by 399.0 nm (3.1 nm), 403.0 nm (5.0 nm) and 407.6 nm (0.6 nm) in ice water, liquid water and water vapor Raman channels, respectively. The mutual interference effect originating from the overlapping characteristics of water Raman spectra is further analyzed, and an accurate retrieval method based on linear simultaneous equations and mutual interference degrees is proposed for synchronous three-phase water mixing ratio profiles. Preliminary measurements are carried out in the Centre for lidar remote sensing research of Xi'an University of Technology, and representative measurement examples are obtained and validated for the performance of the Raman lidar system. Synchronous mixing ratio profiles in water vapor, liquid water and ice water are retrieved, and the corresponding extinction coefficient and relative humidity profiles are also combined to reveal the variation characteristics in three-phase waters. The possible aerosol fluorescence are analyzed as well, and it is inferred that the aerosol fluorescence might affect (possibly overestimate) the derived mixing ratio values of the liquid water and ice water. The effective detection can reach up to a height of 5 km under cloudy weather, and synchronized growth in water vapor and liquid water content is obtained in cloud layers. Continuous observations are also made under hazy weather conditions, and the temporal and spatial evolution trends of three-phase waters in clouds are successfully realized. Preliminary exploration and results validate the feasibility of ultraviolet Raman lidar for synchronous measurements of atmospheric water vapor, liquid water and ice water.

Modifications to Expose Porta Hepatis for Laparoscopic Portoenterostomy Easier in Biliary Atresia.

BACKGROUND: Laparoscopic Kasai portoenterostomy (LKPE) is generally regarded to have a poorer outcome for surgical treatment of uncorrectable biliary atresia. We herein described our initial experience of some modifications to make LKPE easier in the treatment of type III biliary atresia (BA). METHODS: During the period July 2012-October 2016, a total of 25 infants with type III BA were treated with a modified LKPE technique. A percutaneous suture was introduced just below the xiphoid process to snare the round ligament and retract the liver; other percutaneous stay sutures were then introduced to the fundus and neck of the gallbladder to elevate the liver and expose the porta hepatis. In 15 cases, part of the hepatic lobus quadratus was removed laparoscopically to expose the porta hepatis. The two elastic rubber bands were put around the portal vein and hepatic artery, and the porta hepatis was exposed by stretching the two rubber bands laterally to facilitate laparoscopic portoenterostomy. RESULTS: Patients were divided into two groups according to their ages at operation: group I: age between 30 and 75 days (n = 18), and group II: age between 76 and 85 days (n = 8). There were no operative deaths, but two patients died of repeated cholangitis and liver failure. Blood loss during operation was minimal and no blood transfusions were required. Operating times varied from 210 to 270 min (mean 232.4 ± 19.0 min). Among the two groups, there were no differences in blood loss (P > 0.05), but there were differences in operating time (P < 0.05). All patients survived the surgery without any intraoperative complications, and the median follow-up time was 25.3 months. Total bilirubin dropped to normal in 18 patients with an additional 5 patients showing a significant overall drop after surgery. CONCLUSIONS: With the original concepts of Kasai portoenterostomy, perfect laparoscopic skills and some key modifications to expose the porta hepatis, our LKPE can be performed safely and successfully with improved outcome for infants with type III BA.

Etiology and Clinical Characteristics of Community-Acquired Pneumonia with Airway Malacia in Children.

Objective: The objective of this article is to study the etiology of community-acquired pneumonia in children with airway malacia. Methods: We retrospectively reviewed the medical records of 428 pneumonia patients. All patients underwent bronchoscopy, and bronchoalveolar lavage samples were processed for microbiological assessment. Results: In a total of 428 cases reviewed, 60 were found to have airway malacia. Pathogens were identified in 44 of the 60 specimens (73.3%), with 32 being single-pathogen infections. The most common pathogen was respiratory syncytial virus (RSV; 20%). Mixed-pathogen infections were observed in 12 patients. Airway malacia patients were younger than those without malacia (10.5 vs. 50 months, respectively; p < 0.001). Compared with those without airway malacia, wheezing, cyanosis and admission to the pediatric intensive care unit were more common in children with airway malacia and their hospital stay was longer. Conclusion: RSV was the most common pathogen in those with airway malacia. Airway malacia was found to aggravate infectious pneumonia.

Evaluating photographic scales of facial pores and diagnostic agreement of tests using latent class models.

BACKGROUND: Ordinal severity scales illustrated by photographs have been widely developed to help dermatologists in evaluating skin problems or improvements. Numerous scales have been published, and none of them were used for assessing facial pores. METHODS: A five-point photographic scale of facial pores was formulated, and photographs of pores on nasal ala from 128 female volunteers were acquired. Five dermatologists with similar experiences rated the 128 photographs independently using the reference photographs. Latent Class Models (LCM) were used to analyze the data. Firstly, we hypothesized that the conditional probabilities of the five dermatologists were identical to build the first LCM and without the restriction to formulate the second LCM. Conditional probability and posterior probability were also calculated. RESULTS: The five-point scales were ambiguous as the raters actually had difficulties in distinguishing between some adjacent categories. Adjacent categories were pooled for reanalyzing, and the model fitted well. CONCLUSIONS: The newly developed photographic scale of Chinese facial pores should be redefined to improve their quality and reproducibility in future studies. Standardized scales for the measurement of aging and response to cosmetic therapy were essential for assessing diagnostic experiment. The LCM can effectively deal with diagnostic test of agreement and reproducibility.

Treatment of CD33-directed chimeric antigen receptor-modified T cells in one patient with relapsed and refractory acute myeloid leukemia.

We conducted a clinical trial to assess the feasibility and efficacy of CD33-directed chimeric antigen receptor-modified T cells (CART-33) for the treatment of refractory acute myeloid leukemia (AML). A 41-year-old male patient with AML was enrolled and received a total of 1.12 × 10(9) autologous CART-33 cells, of which ~38% were transduced with CAR. The CART-33 infusion alone induced rigorous chills and fevers; drastic fluctuations of his preexisting pancytopenia; elevated serum cytokine levels, including interleukin (IL)-6, IL-8, tumor necrosis factor-α, and interferon-γ; slight transient hyperbilirubinemia within 2 weeks; a subsequent intermittent moderate fever; and reversed fluctuation of the pancytopenia. A marked decrease of blasts in the bone marrow was observed on examination 2 weeks after therapy, and there was a gradual increase until florid disease progression occurred at 9 weeks after the cell infusion. These observations warrant further research on CART-33 treatment in refractory AML and may spur efforts to extend the CART-33-induced tumor burden to the preparation of other intensive strategies, such as hematopoietic stem cell transplantation. This study is registered at www.ClinicalTrials.gov as NCT01864902.

A Novel Method for Detection the Deafness-Associated Mitochondrial A1555G and C1494T Mutations.

BACKGROUND: To develop a novel method for molecular detection of deafness-associated mitochondrial A1555G and C1494T mutations. METHODS: We designed four primers that specifically bind to human mitochondrial 12S rRNA. PCR amplification of DNA samples including the A1555G, C1494T, and healthy controls is performed. The products are analyzed by the electrophoresis. RESULTS: We found that the PCR products of DNA samples with A1555G mutation consisted of two specific bands: 226 bp and 736 bp. While amplification of DNA samples with the C1494T mutation resulted in two fragments: 488 bp and 736 bp. CONCLUSIONS: Our study establishes a convenient, accurate, and cost-effective method for molecular diagnosis of deafness-associated mitochondrial A1555G and C1494T mutations.