Effective Enzyme Coimmobilization and Synergistic Catalysis on Hierarchically Porous Inorganic/Organic Hybrid Microbeads Fabricated Via Droplet‐Based Microfluidics

In this paper, a novel and robust droplet‐based microfluidic method to fabricate poly(ε‐caprolactone)/silica (PCL/SiO₂) hybrid microbeads with hierarchically porous architecture is described and their performance as multienzyme carriers for cascade catalysis is further investigated in detail. In addition to the precise control on size and monodispersity of PCL/SiO₂ microbeads enabled by the microfluidic method, the presence of ammonia as a catalyst for the hydrolysis and condensation of tetraethylorthosilicate makes it possible to manipulate the competition between sol–gel process and solvent extraction and thus adjust the surface porosity of hybrid microbeads, which eliminates the use of porogens/templates and also the complicated post‐treatment. Isothiocyanate‐immunoglobulin G/cyanine 3‐bovine serum albumin (FITC‐IgG/Cy3‐BSA) and superoxide dismutase/chloramphenicol acetyltransferase (SOD/CAT) are coimmobilized, respectively onto hierarchically porous PCL/SiO₂ hybrid microbeads via either physical adsorption or covalent binding. Fluorescence intensity of coimmobilized FITC‐IgG/Cy3‐BSA proves that the proteins/enzymes immobilization amount via covalent binding is much higher than physical adsorption. The enhanced enzymatic activity, total antioxidant capacity, and reusability assay reveal that coimmobilized SOD/CAT exhibits better performance compared with the mono‐immobilized ones, mainly due to their mutual synergistic effect. The excellent results achieved in the work indicate that hierarchically porous PCL/SiO₂ hybrid microbeads are very promising carriers for multienzymatic catalysis.     

A preliminary review of studies on adaptogens: comparison of their bioactivity in TCM with that of ginseng-like herbs used worldwide

Modern studies have shown that adaptogens can non-specifically enhance the resistance of human body under a wide range of external stress conditions with a multi-targeted and multi-channel network-like manner, especially by affect the immune-neuro-endocrine system and the hypothalamic–pituitary–adrenal axis. This review article draws the attention to the relationships of adaptogens, tonics from traditional Chinese medicine (TCM) and ginseng-like herbs worldwide, which all have similar plant sources and clinical applications. To clarify the sources and pharmacological mechanisms of these plant-originated adaptogens, which will provide useful information for the utilization of adaptogens to improve the human health. Meanwhile, the TCMs and the world-wide ginseng-like herbs from each region’s ethnopharmacology will be beneficial modernization and globalization.     

Pathogenic gene screening in 91 Chinese patients with short stature of unknown etiology with a targeted next-generation sequencing panel

Background

Dwarfism is a common severe growth disorder, but the etiology is unclear in the majority of cases. Recombinant human growth hormone may be a treatment option, but it has limited efficacy. The currently known laboratory assays do not meet the precision requirements for clinical diagnosis. Here, we have constructed a targeted next-generation sequencing (NGS) panel of selected genes that are suspected to be associated with dwarfism for genetic screening.

Methods

Genetic screening of 91 children with short stature of unknown etiology was performed with the help of the NGS panel. All the coding regions and exon-intron boundaries of 166 genes were included in the panel. To clarify the pathogenicity of these mutations, their clinical data were reviewed and analyzed.

Results

The assay identified p.A72G, p.I282V, and p.P491S variants of the PTPN11 gene and a p.I437T variant of the SOS1 gene in 4 cases with Noonan syndrome. A frameshift mutation (p.D2407fs) of the ACAN gene was identified in a case of idiopathic short stature with moderately advanced bone age. A p.R904C variant of the COL2A1 gene was found in a patient, who was accordingly diagnosed with Stickler syndrome. Severe short stature without limb deformity was associated with a p.G11A variant of HOXD13. In addition, we evaluated evidence that a p.D401N variant of the COMP gene may cause multiple epiphyseal dysplasia.

Conclusions

Our findings suggest that syndromes, particularly Noonan syndrome, may be overlooked due to atypical clinical features. This gene panel has been verified to be effective for the rapid screening of genetic etiologies associated with short stature and for guiding precision medicine-based clinical management.

     

Lentiviral Vectors and Adeno‐Associated Virus Vectors: Useful Tools for Gene Transfer in Pain Research

Pain, especially chronic pain, has always been a heated point in both basic and clinical researches since it puts heavy burdens on both individuals and the whole society. A better understanding of the role of biological molecules and various ionic channels involved in pain can shed light on the mechanism under pain and advocate the development of pain management. Using viral vectors to transfer specific genes at targeted sites is a promising method for both research and clinical applications. Lentiviral vectors and adeno‐associated virus (AAV) vectors which allow stable and long‐term expression of transgene in non‐dividing cells are widely applied in pain research. In this review, we thoroughly outline the structure, category, advantages and disadvantages and the delivery methods of lentiviral and AAV vectors. The methods through which lentiviral and AAV vectors are delivered to targeted sites are closely related with the sites, level and period of transgene expression. Focus is placed on the various delivery methods applied to deliver vectors to spinal cord and dorsal root ganglion both of which play important roles in primary nociception. Our goal is to provide insight into the features of these two viral vectors and which administration approach can be chosen for different pain researches. Anat Rec, 301:825–836, 2018. © 2017 The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists.     

Fiberoptic Bronchoscopy-Assisted Endotracheal Intubation in a Patient With a Large Tracheal Tumor

In the event of a high degree of airway obstruction, endotracheal intubation can be impossible and even dangerous, because it can cause complete airway obstruction, especially in patients with high tracheal lesions. However, a smaller endotracheal tube under the guidance of a bronchoscope can be insinuated past obstructive tumor in most noncircumferential cases. Here we report a case of successful fiberoptic bronchoscopy-assisted endotracheal intubation in a patient undergoing surgical resection of a large, high tracheal tumor causing severe tracheal stenosis. A 42-year-old Chinese man presented with dyspnea, intermittent irritable cough, and sleep deprivation for one and a half years. X-rays and computed tomography scan of the chest revealed an irregular pedunculated soft tissue mass within the tracheal lumen. The mass occupied over 90% of the lumen and caused severe tracheal stenosis. Endotracheal intubation was done to perform tracheal tumor resection under general anesthesia. After several failed conventional endotracheal intubation attempts, fiberoptic bronchoscopy-assisted intubation was successful. The patient received mechanical ventilation and then underwent tumor resection and a permanent tracheostomy. This case provides evidence of the usefulness of the fiberoptic bronchoscopy-assisted intubation technique in management of an anticipated difficult airway and suggests that tracheal intubation can be performed directly in patients with a tracheal tumor who can sleep in the supine position, even if they have occasional sleep deprivation and severe tracheal obstruction as revealed by imaging techniques.Key words: Tracheal tumors, Fiberoptic bronchoscopy, Difficulty intubation, Difficult airwayPrimary tumors of the trachea, mostly malignant, are rare, accounting for fewer than 0.1% of all tumors.¹ Surgical resection is the major option that has the potential to cure all patients with benign and low-grade tumors and most patients with malignant tracheal tumors.¹ Since surgical procedure often requires the airway to be shared by the anesthetist and the surgeon, patients who undergo tracheal tumor resection often present with a considerable degree of airway obstruction, which makes anesthetic management during surgical resection challenging.² In the event of a high degree of airway obstruction, endotracheal intubation can be impossible and even dangerous because it can cause complete airway obstruction, especially in patients with high tracheal lesions.³ However, tumors are not circumferential in most cases, and a small endotracheal tube can be insinuated past a highly obstructive tumor under the guidance of bronchoscopy.³ Here we report a case of successful fiberoptic bronchoscopy-assisted endotracheal intubation in a patient undergoing surgical resection of a large, high tracheal tumor causing severe tracheal stenosis.     

A Promising Method for Repairing Low-Level Biliary Strictures After Cholecystectomy

The purpose of this study is to introduce and evaluate a new technique of repairing bile ducts by the tubular gastric wall with a vascularized pedicle. Both the end-to-end bile duct repair and Roux-en-Y hepatoenterostomy have limitations in the treatment of benign bile duct strictures after cholecystectomy. There are no other good choices to manage these cases, especially the bile duct transection injuries or partly missing common bile duct or hepatic duct. Eleven patients with partly missing common bile ducts in the Chinese People''s Liberation Army General Hospital between January 2007 and December 2012 were retrospectively analyzed. The study comprised 8 females and 3 males, whose age ranged from 29 to 56 years. All patients underwent successful bile duct repair. The time of operations ranged from 210 minutes to 240 minutes. The maximal blood loss was less than 220 ml. There was no perioperative mortality and no case of gastric fistula. Postoperative complications occurred in 3 patients, including wound infection, bile leakage, and erosive gastritis. All complications were cured by conservative treatment. The mean follow-up time was 42 months. One patient was classified as Terblanche''s grade II and 10 patients were classified as Terblanche''s grade I. The observations indicate that this technique is a feasible and effective choice to manage low level biliary stricture after cholecystectomy, especially suitable to repair bile duct transection injuries or partly missing common bile duct or hepatic duct.Key words: Tubular gastric wall with a vascularized pedicle, Biliary injury, Benign biliary strictureIt is a great challenge for surgeons to manage benign biliary strictures (BBSs) after cholecystectomy. BBS patients often survive for a long time, so surgeons pursue a long-term treatment for BBSs and minimize the effect on the patients'' quality of life as they are able. Traditionally, surgery has been used as a means to treat BBSs, and the common procedure includes end-to-end bile duct repair and biliary-enteric anastomosis. However, current studies suggest that the former has a limited role in the treatment of benign bile duct strictures due to its narrow indications and poor long-term outcome.^1,2 The latter emphasizes the anatomy and treatment of proximal bile ducts. This approach misses the important “sphincter of Oddi” function of an antireflux device, and therefore, cannot avoid the incidence of reflux cholangitis, which increases not only the pain but also the risk of cholangiocarcinoma in long-term follow-up patients. Moreover, a biliary-enteric anastomosis alters the normal bile flow, changing the physiologic conditions of the gastrointestine and leading to the disorder of gastrointestinal hormone release. Hence, it increases the incidence of postoperative duodenal ulcer and inhibits fat metabolism and absorption due to the lack of bile between the duodenum and jejunum.^3–5New technologies should be developed to overcome the above disadvantage of current surgery, and the method of biliary reconstruction should be improved. The ideal surgical procedure for BBSs should be technically simple and should preserve both the physiologic passage of bile and the function of sphincter of Oddi.⁶ This article introduced a new method using the tubular gastric wall with a vascularized pedicle to repair iatrogenic biliary strictures based on this idea.