Design and synthesis of JNK1-targeted PROTACs and research on the activity.

Kinase dysregulation is greatly associated with cell growth, proliferation, differentiation and apoptosis, which indicates their great potential as therapeutic targets for treatment of numerous progressive disorders, including inflammatory, metabolic and autoimmune disorders, organ fibrosis and cancer. The c‑Jun N‑Terminal Kinase (JNK), as a member of MAPK family, is proved to be a potential target for the treatment of pulmonary fibrosis, which is the most common progressive and fatal fibrotic lung disease. As a new strategy, small-molecule-mediated targeted protein degradation pathway has the advantages of catalytic properties, overcoming drug resistance and expanding target space, which can circumvent the limitations associated with kinase inhibitors.

Structure Optimization of c-Jun N-terminal Kinase 1 Inhibitors for Treating Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease with an elusive etiology. Aberrant activation of c-Jun N-terminal kinase 1 (JNK1) has been implicated in its pathogenesis. Through a combination of structure-based drug design and structure-activity relationship (SAR) optimization, a series of pyrimidine-2,4-diamine scaffold derivatives have been developed as potent JNK1 inhibitors.

Comparison of the Retention Rates of Synthetic and Natural Astaxanthin in Feeds and Their Effects on Pigmentation, Growth, and Health in Rainbow Trout ().

The coloring efficiency and physiological function of astaxanthin in fish vary with its regions. The aim of this study was to compare the retention rates of dietary astaxanthin from different sources and its effects on growth, pigmentation, and physiological function in . Fish were fed astaxanthin-supplemented diets (LP: 0.

Development and evaluation of the Cantonese matrix sentence test.

Objective: To develop the Cantonese matrix (YUEmatrix) test according to the international standard procedure and examine possible different outcomes in another tonal language.

Design: A 50-word Cantonese base-matrix was established. Word-specific speech recognition functions, speech recognition thresholds (SRT), and slopes were obtained.

Dissolved trace element concentrations and fluxes in the Irrawaddy, Salween, Sittaung and Kaladan Rivers.

The Irrawaddy (Ayeyarwaddy) and Salween (Thanlwin) globally rank among the largest rivers for supplying dissolved and particulate material to the ocean. Along with the Sittaung and Kaladan rivers they have societal importance to Myanmar in terms water sources and food production. Despite their importance for global biogeochemical cycles and the ~50 million people who live in their catchments, the chemistry of these rivers is poorly known.

Cascade Wolff Rearrangement/Acylation: A Metal-Free and Eco-Friendly Approach for 4-Hydroxy-pyrazolo[3,4-]pyridin-6-ones and -Pyrazole Amides Synthesis from 5-Aminopyrazoles and α-Diazoketones.

A highly chemoselective cascade Wolff rearrangement/acylation reaction between 5-aminopyrazoles and diazo compounds has been developed. The protocol can facilitate the switchable synthesis of 4-hydroxy-pyrazolo[3,4-]pyridin-6-ones and -pyrazole amides with the merits of a broad substrate scope, high functional group compatibility, and green and sustainable performance manner. All reactions proceeded efficiently without any catalyst and additives (acid and base) and resulted in the release of benign N, wherein diethyl carbonate served as a green benign solvent.

Intracranial Stenting as Rescue Therapy After Failure of Mechanical Thrombectomy for Basilar Artery Occlusion: Data From the ANGEL-ACT Registry.

Studies on rescue therapy for acute posterior circulation stroke due to basilar artery occlusion (BAO) are limited in the modern era of mechanical thrombectomy (MT). The aim of this study was to evaluate the safety and efficacy of rescue stenting (RS) following MT failure in patients with BAO. Data were collected from the Endovascular Treatment Key Technique and Emergency Work Flow Improvement of Acute Ischemic Stroke (ANGEL-ACT) prospective registry in China.

KILT (Kidney and IVC Abnormalities with Leg Thrombosis) Syndrome in a 41-Years-Old Man with Loin Pain and Fever.

KILT syndrome is a rare condition composing the triad of kidney and inferior vena cava anomaly and extensive venous thrombosis. We present a case of newly diagnosed KILT syndrome in a 41-years-old gentleman presenting with loin pain and fever. Reviewing previous case reports, KILT syndrome is usually an incidental finding on imaging studies and there is a wide scope of initial clinical presentations.

A 55-Year-Old Man with Right Testicular Pain: Too Old for Torsion?

Testicular torsion is predominantly a disease of adolescence, but age itself should not be an exclusion criterion for the diagnosis. A lack of suspicion for testicular torsion in older patients may result in a missed or delayed diagnosis which jeopardizes the chance of testicular salvage. In this article, we report a case of testicular torsion in a 55-year-old Chinese man.

Asymmetric Acute Motor Axonal Neuropathy With Unilateral Tongue Swelling Mimicking Stroke.

A 60-year-old man presented with acute onset of left hemiparesis and left hypoglossal nerve palsy with ipsilateral tongue swelling. He then progressed to tetraparesis in a few days. Cerebrospinal fluid showed cell protein dissociation.

Oral Prednisolone in the Treatment of Acute Gout: A Pragmatic, Multicenter, Double-Blind, Randomized Trial.

Background: Two recent double-blind, randomized, controlled trials (RCTs) showed that oral steroids and nonsteroidal anti-inflammatory drugs have similar analgesic effectiveness for management of gout, but the trials had small sample sizes and other methodological limitations.

Objective: To compare the effectiveness and safety of oral prednisolone versus oral indomethacin in patients presenting to emergency departments (EDs) with acute gout.

Design: Multicenter, double-blind, randomized equivalence trial.

Differential expression of vascular endothelial growth factor angiogenic factors in different endometrial compartments in women who have an elevated progesterone level before oocyte retrieval, during in vitro fertilization-embryo transfer treatment.

Objective: To investigate the relationship between endometrial expressions of angiogenic factors around the time of embryo implantation and P level before oocyte retrieval during IVF-ET treatment.

Design: Retrospective study.

Setting: University Assisted Reproductive Unit.

Inflammatory myofibroblastic tumours of the urinary bladder: multi-centre 18-year experience.

Objective: To review a series of inflammatory myofibroblastic tumours (IMTs) of the urinary bladder in 10 hospitals in Hong Kong.

Methods: A database search in the pathology archives of 10 hospitals in Hong Kong from 1995 to 2013 was performed using the key words 'inflammatory myofibroblastic tumour', 'inflammatory pseudotumour' and 'spindle cell lesion'. Patient characteristics, clinical features, histological features, immunohistochemical staining results and treatment outcomes were reviewed.

Primary yolk sac tumour of the urinary bladder: A case report and review of the literature.

We present a case of rare primary yolk sac tumour of the urinary bladder in adulthood. A 31-year-old female patient presented with a history of chronic ketamine abuse, which has not previously been shown to be associated with malignancy development. The final diagnosis was established only after radical cystectomy.

Ambulatory care program for patients presenting with acute urinary retention secondary to benign prostatic hyperplasia.

Objective: We analyze the clinical and economical outcomes of an ambulatory care program for the management of patients presenting to the emergency department with acute urinary retention (AUR).

Method: A standardized ambulatory care program for managing male patients presenting with AUR was established in October 2007. Prospective data collected in 194 ambulatory patients from January to December 2008 were compared to a historical cohort of 168 patients who were managed by in-patient care from October 2006 to September 2007 for their clinical and economic outcomes.

Upper gastrointestinal problems in inhalational ketamine abusers.

Objective: To study the association between upper gastrointestinal (GI) problems and inhalational ketamine abuse.

Methods: This is a retrospective study of 64 ketamine abusers treated from 2001 to 2008. Variables studied included clinical presentations, findings of upper GI endoscopy, abstinence from ketamine and relief of epigastric pain.

Oral prednisolone is more cost-effective than oral indomethacin for treating patients with acute gout-like arthritis.

Objectives: Acute gouty arthritis is often treated with NSAIDs, but recent studies have suggested that treatment with prednisolone has at least equivalent analgesic efficacy and fewer adverse effects. No formal economic analysis has been performed earlier. In this study, we aimed to compare the economic impact of oral indomethacin therapy and oral prednisolone therapy in the treatment of acute gout in patients presenting to an emergency department in Hong Kong.

Comparison of oral prednisolone/paracetamol and oral indomethacin/paracetamol combination therapy in the treatment of acute goutlike arthritis: a double-blind, randomized, controlled trial.

Study Objective: We compare the analgesic efficacy and adverse effects of oral prednisolone/acetaminophen and oral indomethacin/acetaminophen combination therapy in the treatment of acute goutlike arthritis in patients presenting to an emergency department (ED).

Methods: This is a double-blind, randomized, controlled study in a university hospital emergency department (ED) in the New Territories of Hong Kong. Patients older than 17 years and presenting between February 1, 2003, and June 30, 2004, with a clinical diagnosis of goutlike arthritis were randomized to receive either oral prednisolone/acetaminophen or oral indomethacin/acetaminophen combination therapy.

Impact of SARS on an emergency department in Hong Kong.

Objective: To report on the impact of a Severe Acute Respiratory Syndrome (SARS) outbreak on the attendances of a major teaching hospital ED.

Methods: Two periods were studied. The first was prior to the closure of the ED due to SARS and the second was after re-opening of the ED.