Publications by authors named "Lily Li"

71 Publications

Efficacy of Traditional Chinese Medicine on COVID-19: Two Case Reports.

Med Acupunct 2021 Feb 16;33(1):92-102. Epub 2021 Feb 16.

Hallam Institute of TCM, Sheffield, United Kingdom.

Severe acute respiratory syndrome coronavirus 2-infected pneumonia (novel coronavirus-infected pneumonia [NCIP]) is a new viral illness initially identified in the central Chinese city of Wuhan in December 2019. According to the daily report on the epidemic situation of coronavirus disease (COVID-19) issued by the National Health and Family Planning Commission of the People's Republic of China on March 23, 2020: COVID-19 is highly infectious, causing extremely high incidence of NCIP throughout Wuhan and has spread swiftly to 34 provinces within China and >100 other countries around the world between January and March 2020. Up to August 11, 2020, there have been 89,383 cases diagnosed as coronavirus-infected pneumonia; and 4,696 deaths in China (mortality rate of 5.25%) and worldwide reports have confirmed 19,936,210 cases and 732,499 deaths. These figures have been increasing daily. The treatment of viral conditions is well established within the context of Chinese Medicine. We report 2 successful cases in this study showing the patient's chest computed tomography scans and temperature charts made on before, during, and after treatment to demonstrate proof of the positive benefits achieved. Traditional Chinese Medicine (TCM) demonstrates a positive effect in the treatment for COVID-19. It is highly recommended that TCM be incorporated early on in the treatment schedule for COVID-19.
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http://dx.doi.org/10.1089/acu.2020.1432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894045PMC
February 2021

Reported drug allergies among patients with opioid use disorder: Role for allergy evaluation and intervention.

Ann Allergy Asthma Immunol 2020 Dec 30. Epub 2020 Dec 30.

Division of Allergy and Clinical Immunology, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.

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http://dx.doi.org/10.1016/j.anai.2020.12.017DOI Listing
December 2020

Impact of reported NSAID "allergies" on opioid use disorder in back pain.

J Allergy Clin Immunol 2020 Sep 9. Epub 2020 Sep 9.

Division of Allergy and Clinical Immunology, Department of Medicine, Brigham and Women's Hospital, Boston, Mass; Harvard Medical School, Boston, Mass.

Background: It is crucial to identify patients at highest risk for opioid use disorder (OUD) and to address challenges in reducing opioid use. Reported nonsteroidal anti-inflammatory drug (NSAID) allergies may predispose to use of stronger pain medications and potentially to OUD.

Objective: We sought to investigate the clinical impact of reported NSAID allergy on OUD in patients with chronic back pain.

Methods: We conducted a retrospective study of adults receiving care at a tertiary health care system from January 1, 2013, to December 31, 2018. Back pain and OUD were identified using administrative data algorithms. We used propensity score matching and logistic regression to estimate the impact of self-reported NSAID adverse drug reactions (ADRs) on risk of OUD, adjusting for other relevant clinical information.

Results: Of 47,114 patients with chronic back pain, 3,620 (7.7%) had a reported NSAID ADR. In an adjusted propensity score-matched analysis, patients with NSAID ADRs had higher odds (odds ratio, 1.34; 95% CI, 1.07-1.67) of developing OUD as compared with those without NSAID ADRs. Additional risk factors for OUD included younger age, male sex, Medicaid insurance, Medicare insurance, higher number of inpatient and outpatient visits in the previous year, and comorbid anxiety and depression. Patients with listed NSAID ADRs also had higher odds of a documented opioid prescription during the study period (odds ratio, 1.22; 95% CI, 1.11-1.34).

Conclusions: Adults with chronic back pain and reported NSAID ADRs are at a higher risk of developing OUD and receiving opioid analgesics, even after accounting for comorbidities and health care utilization. Allergy evaluation is critical for potential delabeling of patients with reported NSAID allergies and chronic pain.
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http://dx.doi.org/10.1016/j.jaci.2020.08.025DOI Listing
September 2020

Hip fractures.

Br J Hosp Med (Lond) 2020 Aug;81(8):1-10

Department of Trauma and Orthopaedics, Chelsea and Westminster NHS Foundation Trust, London, UK.

In the UK the incidence of hip fractures is nearly 76 000 cases per year, with the vast majority of these fractures occurring in patients over the age of 70 years. Most patients who sustain a hip fracture will have significant comorbidities and up to 40% will have cognitive impairment. For patients, sustaining a hip fracture can potentially be a devastating event. This article provides an overview of the presentation, assessment and management of hip fractures for core surgical, acute care common stem and emergency medicine trainees.
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http://dx.doi.org/10.12968/hmed.2020.0215DOI Listing
August 2020

Impact of the COVID-19 pandemic on paediatric orthopaedic trauma workload in central London: a multi-centre longitudinal observational study over the "golden weeks".

Acta Orthop 2020 Dec 24;91(6):633-638. Epub 2020 Aug 24.

Imperial College Healthcare NHS Trust, London.

Background and purpose - The COVID-19 pandemic has been recognised as an unprecedented global health crisis. This study assesses the impact on a large acute paediatric hospital service in London, evaluating the trends in the acute paediatric orthopaedic trauma referral caseload and operative casemix before (2019) and during (2020) COVID-19 lockdown. Patients and methods - A longitudinal retrospective observational prevalence study of both acute paediatric orthopaedic trauma referrals and operative caseload was performed for the first 6 "golden weeks" of lockdown. These data were compared with the same period in 2019. Statistical analyses included median (± median absolute deviation), risk and odds ratios as well as Fisher's exact test to calculate the statistical significance, set at p ≤ 0.05. Results - Acute paediatric trauma referrals in 2020 were reduced by two-thirds compared with 2019 (n = 302 vs. 97) with a halving risk (RR 0.55) and odds ratios (OR 0.43) of sporting-related mechanism of injuries (p = 0.002). There was a greater use of outpatient telemedicine in the COVID-19 period with more Virtual Fracture Clinic use (OR 97, RR 84, p < 0.001), and fewer patients being seen for consultation and followed up face to face (OR 0.55, RR 0.05, p < 0.001). Interpretation - The impact of the COVID-19 pandemic has led to a decline in the number of acute paediatric trauma referrals, admissions, and operations during the COVID period. There has also been a significant change in the patient pathway with more being reviewed via the means of telemedicine to reduce the risk of COVID-19 transmission and exposure. More work is required to observe for similar trends nationwide and globally as the pandemic has permanently affected the entire healthcare infrastructure.
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http://dx.doi.org/10.1080/17453674.2020.1807092DOI Listing
December 2020

Thorium chelators for targeted alpha therapy: Rapid chelation of thorium-226.

J Labelled Comp Radiopharm 2020 Oct 13;63(12):502-516. Epub 2020 Sep 13.

Department of Radiation Oncology, University of Washington, Seattle, Washington, USA.

One of the main challenges in targeted alpha therapy is assuring delivery of the α-particle dose to the targeted cells. Thus, it is critical to identify ligands for α-emitting radiometals that will form complexes that are very stable, both in vitro and in vivo. In this investigation, thorium-227 (t = 18.70 days) chelation of ligands containing hydroxypyridinonate (HOPO) or picolinic acid (pa) moieties and the stability of the resultant complexes were studied. Chelation reactions were followed by reversed-phased HPLC and gamma spectroscopy. Studies revealed that high Th chelation yields could be obtained within 2.5 h or less with ligands containing four Me-3,2-HOPO moieties, 1 (83%) and 2 (65%), and also with ligands containing pa moieties, H octapa 3 (65%) and H py4pa 6 (87%). No reaction occurred with H neunpa-p-Bn-NO 4, and the chelation reaction with another pa ligand H pypa 5 gave inconsistent yields with a very broad radio-HPLC peak. The ligands spermine-(Me-3,2-HOPO) 1, H octapa 3, and H py4pa 6 had high stability (i.e., 87% of Th still bound to the ligand) in phosphate-buffered saline at room temperature over a 6-day period. Preliminary studies with ligand 6 demonstrated efficient chelation of thorium-226 (t = 30.57 min) when heated to 80°C for 5 min.
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http://dx.doi.org/10.1002/jlcr.3875DOI Listing
October 2020

Disparities in United States hospitalizations for serious infections in patients with and without opioid use disorder: A nationwide observational study.

PLoS Med 2020 08 7;17(8):e1003247. Epub 2020 Aug 7.

Harvard Medical School, Boston, Massachusetts, United States of America.

Background: Patients with opioid use disorder (OUD) who are hospitalized for serious infections requiring prolonged intravenous antibiotics may face barriers to discharge, which could prolong hospital length of stay (LOS) and increase financial burden. We investigated differences in LOS, discharge disposition, and charges between hospitalizations for serious infections in patients with and without OUD.

Methods And Findings: We utilized the 2016 National Inpatient Sample-a nationally representative database of all discharges from US acute care hospitals. The population of interest was all hospitalizations for infective endocarditis, epidural abscess, septic arthritis, or osteomyelitis. The exposure was OUD, and the primary outcome was LOS until discharge, assessed by using a competing risks analysis to estimate adjusted hazard ratios (aHRs). Adjusted odds ratio (aOR) of discharge disposition and adjusted differences in hospital charges were also reported. Of 95,470 estimated hospitalizations for serious infections (infective endocarditis, epidural abscess, septic arthritis, and osteomyelitis), the mean age was 49 years and 35% were female. 46% had Medicare (government-based insurance coverage for people age 65+ years), and 70% were non-Hispanic white. After adjustment for potential confounders, OUD was associated with a lower probability of discharge at any given LOS (aHR 0.61; 95% CI 0.59-0.63; p < 0.001). OUD was also associated with lower odds of discharge to home (aOR 0.38; 95% CI 0.33-0.43; p < 0.001) and higher odds of discharge to a post-acute care facility (aOR 1.85; 95% CI 1.57-2.17; p < 0.001) or patient-directed discharge (also referred to as "discharge against medical advice") (aOR 3.47; 95% CI 2.80-4.29; p < 0.001). There was no significant difference in average total hospital charges, though daily hospital charges were significantly lower for patients with OUD. Limitations include the potential for unmeasured confounders and the use of billing codes to identify cohorts.

Conclusions: Our findings suggest that among hospitalizations for some serious infections, those involving patients with OUD were associated with longer LOS, higher odds of discharge to post-acute care facilities or patient-directed discharge, and similar total hospital charges, despite lower daily charges. These findings highlight opportunities to improve care for patients with OUD hospitalized with serious infections, and to reduce the growing associated costs.
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http://dx.doi.org/10.1371/journal.pmed.1003247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413412PMC
August 2020

The impact of COVID-19 on the future of orthopaedic training in the UK.

Acta Orthop 2020 12 31;91(6):627-632. Epub 2020 Jul 31.

Department of Trauma and Orthopaedics, Chelsea and Westminster NHS Foundation Trust, London, UK.

The COVID-19 pandemic has had a major impact on global healthcare systems, has drastically affected patient care, and has had widespread effects upon medical education. As plans are being devised to reinstate elective surgical services, it is important to consider the impact that the pandemic has had and will continue to have on surgical training. We describe the effect COVID-19 has had at all levels of training in the UK within trauma and orthopaedics and evaluate how training might change in the future. We found that the COVID-19 pandemic has significantly impacted trainees within trauma and orthopaedics at all levels of training. It had led to reduced operative exposure, cancellations of examinations and courses, and modifications to speciality recruitment and annual appraisals. This cohort of trainees is witnessing novel methods of delivering orthopaedic services, which will continue to develop and become part of routine practice even once the pandemic has resolved. It will be important to observe the extent to which the rapid changes currently being introduced will impact the personal health, safety, and career progression of current trainees.
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http://dx.doi.org/10.1080/17453674.2020.1795790DOI Listing
December 2020

Clavicle fractures.

Br J Hosp Med (Lond) 2020 Jul 30;81(7):1-7. Epub 2020 Jun 30.

Department of Trauma and Orthopaedics, Chelsea and Westminster NHS Foundation Trust, London, UK.

Clavicle fractures account for approximately 2-5% of all fractures in adults and 10-15% in children. There is a bimodal distribution, with two peaks occurring in patients <25 years of age as a result of direct trauma and in those >55 years of age secondary to a fall onto an outstretched arm. Approximately two-thirds of all clavicle fractures occur in men. This article provides an overview of the presentation, assessment and management of clavicle fractures for both core surgical trainees and acute care common stem/emergency medicine trainees.
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http://dx.doi.org/10.12968/hmed.2020.0158DOI Listing
July 2020

Improving Allergy Documentation: A Retrospective Electronic Health Record System-Wide Patient Safety Initiative.

J Patient Saf 2020 Jun 1. Epub 2020 Jun 1.

From the Division of Allergy and Clinical Immunology, Department of Medicine, Brigham and Women's Hospital.

Objectives: Documentation of allergies in a coded, non-free-text format in the electronic health record (EHR) triggers clinical decision support to prevent adverse events. Health system-wide patient safety initiatives to improve EHR allergy documentation by specifically decreasing free-text allergy entries have not been reported. The goal of this initiative was to systematically reduce free-text allergen entries in the EHR allergy module.

Methods: We assessed free-text allergy entries in a commercial EHR used at a multihospital integrated health care system in the greater Boston area. Using both manual and automated methods, a multidisciplinary consensus group prioritized high-risk and frequently used free-text allergens for conversion to coded entries, added new allergen entries, and deleted duplicate allergen entries. Environmental allergies were moved to the patient problem list.

Results: We identified 242,330 free-text entries, which included a variety of environmental allergies (42%), food allergies (18%), contrast media allergies (13%), "no known allergy" (12%), drug allergies (2%), and "no contrast allergy" (2%). Most free-text entries were entered by medical assistants in ambulatory settings (34%) and registered nurses in perioperative settings (20%). We remediated a total of 52,206 free-text entries with automated methods and 79,578 free-text entries with manual methods.

Conclusions: Through this multidisciplinary intervention, we identified and remediated 131,784 free-text entries in our EHR to improve clinical decision support and patient safety. Additional strategies are required to completely eliminate free-text allergy entry, and establish systematic, consistent, and safe guidelines for documenting allergies.
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http://dx.doi.org/10.1097/PTS.0000000000000711DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704710PMC
June 2020

Buoctapa-alkyl-NHS for metalloradiopeptide preparation.

Dalton Trans 2020 Jun;49(22):7605-7619

Medicinal Inorganic Chemistry Group, Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, British Columbia V6T 1Z1, Canada.

The peptide is an important class of biological targeting molecule; herein, a new bifunctional octadentate non-macrocyclic H4octapa, tBu4octapa-alkyl-NHS, which is compatible with solid-phase peptide synthesis and thus useful for radiopeptide preparation, has been synthesized. To preserve denticity, the alkyl-N-hydroxylsuccinimide linker was covalently attached to the methylene-carbon on one of the acetate arms, yielding a chiral carbon center. According to density-functional theory (DFT) calculations using [Lu(octapa-alkyl-benzyl-ester)]- as a simulation model, the chirality has minimal effects on the complex geometry; regardless of the S-/R-stereochemistry, DFT calculations revealed two possible geometric isomers, distorted bicapped trigonal antiprism (DBTA) and distorted square antiprism (DSA), due to the asymmetry in the chelator. To evaluate the biological behavior of the new bifunctionalization, two well-studied PSMA (prostate-specific membrane antigen)-targeting peptidomimetics of varying hydrophobicity were chosen as proof-of-principle targeting vector molecules. Radiolabeling both bioconjugates with lutetium-177 was highly efficient at room temperature in 15 min at micromolar chelator concentration pH = 7. Both the in vitro serum challenge and the lanthanum(iii) challenge studies revealed complex lability, and notably, progressive bone accumulation was only observed with the more hydrophobic linker (i.e. H4octapa-alkyl-PSMA617). This in vivo result informs potential alterations exerted by the linker on the complex geometry and stability, with an appropriate biological targeting vector adopted for such evaluations.
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http://dx.doi.org/10.1039/d0dt00845aDOI Listing
June 2020

Effects of inorganic trace minerals replaced by complexed glycinates on reproductive performance, blood profiles, and antioxidant status in broiler breeders.

Poult Sci 2020 May 26;99(5):2718-2726. Epub 2020 Mar 26.

BASF SE, Nutrition & Health Division, Ludwigshafen 78354, Germany.

This study was conducted to investigate the effects of replacing inorganic trace minerals (ITM) with organic trace minerals (OTM; complexed glycinates) on reproductive performance, blood profiles, and antioxidant status in broiler breeders. A total of 648, 23-week-old healthy broiler breeders (ZhenNing), with similar body weight (1.40 ± 0.002 kg), were randomly divided into 4 groups with 6 replicates in each group (27 hens/replicate) and fed the respective experimental diets for 14 wk (including 2 wk for adaptation). The experimental treatments consisted of T1: Cont., commercially recommended levels of ITM (Cu, Zn, Fe, and Mn sulfates); T2: Mix, half trace minerals (TM) were provided from ITM and half from OTM (glycinates); T3: M-OTM, TM were provided from glycinates and reduced to 70% of T1; T4: L-OTM, TM were provided from glycinates and reduced to 50% of T1. The results showed that commercial level of inorganic trace minerals replaced by low-dose complexed glycinates (T3 and T4) exhibited no significant effects on laying performance, 50% ITM replaced by complexed glycinates (T2) numerically improved laying rate by 1.23% than cont. treatment (T1). Broiler breeders fed complexed glycinates tended to produce more qualified eggs (P = 0.05) in T3, with better yolk color (P < 0.01) and eggshell thickness (P = 0.05) in T2 treatment. Replacement of low-dose complexed glycinates reduced fertilization rate (P < 0.01), while it did not affect hatchability. There were no significant differences in serum reproductive hormones such as estrogen and progesterone among the treatments. Serum total protein, albumin, and phosphorus were increased respectively with the replacement of ITM by low-dose OTM from complexed glycinates (P < 0.05). Total liver antioxidant capacity in M-OTM and L-OTM treatment was higher than that of Cont. and Mix treatments (P < 0.01). In conclusion, replacement of high levels of ITM by lower levels of OTM in the form of complexed glycinates is beneficial for egg quality and liver antioxidant status in broiler breeders during the peak laying period.
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http://dx.doi.org/10.1016/j.psj.2019.11.058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7597384PMC
May 2020

The impact of the novel coronavirus on trauma and orthopaedics in the UK.

Br J Hosp Med (Lond) 2020 Apr 10;81(4):1-6. Epub 2020 Apr 10.

Department of Trauma and Orthopaedics, Chelsea and Westminster NHS Foundation Trust, London, UK.

At first glance, the novel coronavirus pandemic and orthopaedic surgery appear separate entities. Orthopaedic surgeons are not generally considered front-line staff in terms of the treatment of the disease that the novel coronavirus causes compared with anaesthetic and medical colleagues. However, the impact that the novel coronavirus is likely to have on the musculoskeletal injury burden and the morbidity associated with chronic musculoskeletal disease is significant. This article summarises the strategies currently being developed for the remodelling of orthopaedic services in the UK and the emergency British Orthopaedic Association Standards for Trauma and Orthopaedic guidelines released on 24 March 2020 in managing urgent orthopaedic patients during the novel coronavirus pandemic.
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http://dx.doi.org/10.12968/hmed.2020.0137DOI Listing
April 2020

Coordination chemistry of [Y(pypa)] and comparison immuno-PET imaging of [Sc]Sc- and [Y]Y-pypa-phenyl-TRC105.

Dalton Trans 2020 May 9;49(17):5547-5562. Epub 2020 Apr 9.

Medicinal Inorganic Chemistry Group, Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, British Columbia V6T 1Z1, Canada.

Both scandium-44 and yttrium-86 are popular PET isotopes with appropriate half-lives for immuno-positron emission tomography (immuno-PET) imaging. Herein, a new bifunctional Hpypa ligand, Hpypa-phenyl-NCS, is synthesized, conjugated to a monoclonal antibody, TRC105, and labeled with both radionuclides to investigate the long-term in vivo stability of each complex. While the Sc-labeled radiotracer exhibited promising pharmacokinetics and stability in 4T1-xenograft mice (n = 3) even upon prolonged interactions with blood serum proteins, the progressive bone uptake of the Y-counterpart indicated in vivo demetallation, obviating Hpypa as a suitable chelator for Y ion in vivo. The solution chemistry of [Y(pypa)] was studied in detail and the complex found to be thermodynamically stable in solution with a pM value 22.0, ≥3 units higher than those of the analogous DOTA- and CHX-A''-DTPA-complexes; the Y-result in vivo was therefore most unexpected. To explore further this in vivo lability, Density Functional Theory (DFT) calculation was performed to predict the geometry of [Y(pypa)] and the results were compared with those for the analogous Sc- and Lu-complexes; all three adopted the same coordination geometry (i.e. distorted capped square antiprism), but the metal-ligand bonds were much longer in [Y(pypa)] than in [Lu(pypa)] and [Sc(pypa)], which could indicate that the size of the binding cavity is too small for the Y ion, but suitable for both the Lu and Sc ions. Considered along with results from [Y][Y(pypa-phenyl-TRC105)], it is noted that when matching chelators with radionuclides, chemical data such as the thermodynamic stability and in vitro inertness, albeit useful and necessary, do not always translate to in vivo inertness, especially with the prolonged blood circulation of the radiotracer bound to a monoclonal antibody. Although Hpypa is a nonadentate chelator, which theoretically matches the coordination number of the Y ion, we show herein that its binding cavity, in fact, favors smaller metal ions such as Sc and Lu and further exploitation of the Sc-pypa combination is desired.
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http://dx.doi.org/10.1039/d0dt00437eDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7222037PMC
May 2020

Diabetes Mellitus Increases Risk of Incident Dementia in APOEɛ4 Carriers: A Meta-Analysis.

J Alzheimers Dis 2020 ;74(4):1295-1308

School of Psychology & Public Health, La Trobe University, Melbourne, Victoria, Australia.

Background: Dementia is a devastating condition for older adults, with both modifiable (e.g., diabetes mellitus) and unmodifiable risk factors (e.g., APOEɛ4 allele). It remains unclear how, and to what extent, diabetes impacts dementia risk via both cerebrovascular and amyloid-β pathways.

Objective: We conducted a quantitative meta-analysis to investigate the contribution of diabetes to incident dementia risk in people with ɛ4 and, based on the vascular-related neuropathology of diabetes, whether the combination of these factors increases risk for vascular dementia versus Alzheimer's disease (AD).

Methods: Systematic literature searches were conducted using EMBASE, MEDLINE, PsycINFO, and CINAHL databases. Pooled relative risk (RR) estimates were calculated using a random effects model, and subgroup analyses conducted across dementia subtypes.

Results: Twelve studies were included, with a total of 16,200 participants. Considered concurrently, diabetes increased incident dementia risk an additional 35% for those with ɛ4 (RR = 1.35, 95% CI = 1.13-1.63). Similar patterns were observed for AD and vascular dementia.

Conclusion: Interventions to prevent co-morbid diabetes, and diabetes-related complications and neuropathological changes, may be one way of modifying dementia risk in the vulnerable ɛ4 population.
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http://dx.doi.org/10.3233/JAD-191068DOI Listing
January 2020

LIMD1-AS1 suppressed non-small cell lung cancer progression through stabilizing LIMD1 mRNA via hnRNP U.

Cancer Med 2020 06 2;9(11):3829-3839. Epub 2020 Apr 2.

Respiratory Medicine Department, Liaocheng People's Hospital, Liaocheng, China.

Background: Non-small cell lung cancer (NSCLC) occupies the majority of lung cancer cases and is notorious for the awful prognosis. LIM domains-containing 1 (LIMD1) is suggested as a tumor suppressor in lung cancer, but its mechanism in NSCLC remains elusive. Present study aimed to uncover the mechanism of LIMD1 in NSCLC.

Methods: qRT-PCR was performed to analyze the level of LIMD1. The functions of LIMD1 in NSCLC cells were evaluated by CCK-8, EdU, and caspase-3 activity assays. RIP and pull-down assays were applied to determine the interaction of LIMD1 with heterogeneous nuclear ribonucleoprotein U (hnRNP U) and LIMD1-AS1.

Results: LIMD1 was downregulated in NSCLC samples and cells. Functionally, LIMD1 hindered proliferation and drove apoptosis in NSCLC cells. Moreover, long noncoding RNA (lncRNA) LIMD1 antisense RNA 1 (LIMD1-AS1) was downregulated in NSCLC samples and cell lines. LIMD1-AS1 knockdown abrogated NSCLC cell growth in vitro and in vivo. Mechanistically, LIMD1-AS1 stabilized LIMD1 mRNA through interacting with hnRNP U. Rescue experiments suggested that LIMD1-AS1 repressed NSCLC progression through LIMD1.

Conclusions: LIMD1-AS1 suppressed NSCLC progression through stabilizing LIMD1 mRNA via hnRNP U, providing new thoughts for the improvement of molecular-targeted therapy for NSCLC.
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http://dx.doi.org/10.1002/cam4.2898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286462PMC
June 2020

Ac-Hpy4pa for Targeted Alpha Therapy.

Bioconjug Chem 2020 Apr 9. Epub 2020 Apr 9.

Medicinal Inorganic Chemistry Group, Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, British Columbia V6T 1Z1, Canada.

Herein, we present the syntheses and characterization of a new undecadendate chelator, Hpy4pa, and its bifunctional analog Hpy4pa-phenyl-NCS, conjugated to the monoclonal antibody, Trastuzumab, which targets the HER2+ cancer. Hpy4pa possesses excellent affinity for Ac (α, = 9.92 d) for targeted alpha therapy (TAT), where quantitative radiolabeling yield was achieved at ambient temperature, pH = 7, in 30 min at 10 M chelator concentration, leading to a complex highly stable in mouse serum for at least 9 d. To investigate the chelation of Hpy4pa with large metal ions, lanthanum (La), which is the largest nonradioactive metal of the lanthanide series, was adopted as a surrogate for Ac to enable a series of nonradioactive chemical studies. In line with the H NMR spectrum, the DFT (density functional theory)-calculated structure of the [La(py4pa)] anion possessed a high degree of symmetry, and the La ion was secured by two distinct pairs of picolinate arms. Furthermore, the [La(py4pa)] complex also demonstrated a superb thermodynamic stability (log ∼ 20.33, pLa = 21.0) compared to those of DOTA (log ∼ 24.25, pLa = 19.2) or Hmacropa (log = 14.99, pLa ∼ 8.5). Moreover, the functional versatility offered by the bifunctional py4pa precursor permits facile incorporation of various linkers for bioconjugation through direct nucleophilic substitution. In this work, a short phenyl-NCS linker was incorporated to tether Hpy4pa to Trastuzumab. Radiolabeling studies, serum stability, and animal studies were performed in parallel with the DOTA-benzyl-Trastuzumab. Both displayed excellent stability and tumor specificity.
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http://dx.doi.org/10.1021/acs.bioconjchem.0c00171DOI Listing
April 2020

Effects of Replacing Inorganic with Respective Complexed Glycinate Minerals on Apparent Mineral Bioavailability and Deposition Rate in Tissues of Broiler Breeders.

Biol Trace Elem Res 2020 Dec 12;198(2):654-660. Epub 2020 Mar 12.

BASF SE, 78354, Ludwigshafen, Germany.

The study was conducted to evaluate the effects of replacing inorganic trace minerals (ITMs) with respective low-dose complexed glycinate minerals (CGMs) on their bioavailability and retention during peak laying period of broiler breeders. In this experiment, 648 ZhenNing broiler breeders (23 weeks old) were randomly allocated to four treatments with six replicates (27 birds/replicate) and fed for 14 weeks including 2 weeks adaptation period. The treatments were T1-ITM, commercially recommended levels of ITMs (Cu, Zn, Fe, and Mn sulphates); T2-MIX, half of the minerals were supplemented with ITMs and half with CGMs; T3-L-CGMs, minerals were supplemented with CGMs (50% level of T1); and T4-M-CGMs, minerals were supplemented with CGMs (70% level of T1). The results showed that birds fed on ITM had lower bioavailability of Fe, Mn, and Zn (P < 0.05) than those fed on L-CGMs, but the highest (P < 0.01) bioavailability of Cu was found in those fed on MIX. Mineral retention (in serum, muscle, bone, and tissues) was not affected by reducing supplementation levels of trace minerals up to 50% of ITMs, but Zn (in serum, liver, kidney, heart, and albumen) and Fe (in serum and the yolk) retention was negatively affected (P < 0.05). In conclusion, replacing dietary ITMs with low-dose complexed glycinate minerals increases the apparent bioavailability of Fe, Mn, and Zn without compromising the mineral retention rates in most of the tissues tested.
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http://dx.doi.org/10.1007/s12011-020-02102-1DOI Listing
December 2020

[Sc(pypa)]: Thermodynamic Stability, Radiolabeling, and Biodistribution of a Prostate-Specific-Membrane-Antigen-Targeting Conjugate.

Inorg Chem 2020 Feb 24;59(3):1985-1995. Epub 2020 Jan 24.

Department of Molecular Oncology , BC Cancer , 675 West 10th Ave , Vancouver , British Columbia V5Z 1L3 , Canada.

Sc is an attractive positron-emitting radionuclide for PET imaging; herein, a new complex of the Sc ion with nonmacrocyclic chelator Hpypa was synthesized and characterized with high-resolution electrospray-ionization mass spectrometry (HR-ESI-MS), as well as different nuclear magnetic resonance (NMR) spectroscopic techniques (H, C, H-C HSQC, H-C HMBC, COSY, and NOESY). In aqueous solution (pH = 7), [Sc(pypa)] presented two isomeric forms, the structures of which were predicted using density functional theory (DFT) calculation with a small energy difference of 22.4 kJ/mol, explaining their coexistence. [Sc(pypa)] was found to have superior thermodynamic stability (pM = 27.1) compared to [Sc(AAZTA)] (24.7) and [Sc(DOTA)] (23.9). In radiolabeling, [Sc][Sc(pypa)] formed efficiently at RT in 15 min over a range of pH (2-5.5), resulting in a complex that is highly stable (>99%) in mouse serum over at least six half-lives of scandium-44. Similar labeling efficiency was observed with the PSMA (prostate-specific membrane antigen)-targeting Hpypa-C7-PSMA617 at pH = 5.5 (RT, 15 min), confirming negligible disturbance from the bifunctionalization on scandium-44 scavenging. Moreover, the kinetic inertness of the radiocomplex was proved Surprisingly, the molar activity was found to have profound influence on the pharmacokinetics of the radiotracers where lower molar activity drastically reduced the background accumulations, particularly, kidney, and thus, yielded a much higher tumor-to-background contrast.
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http://dx.doi.org/10.1021/acs.inorgchem.9b03347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408314PMC
February 2020

Acupuncture and Chinese Herbal Medicine Effects on Assisted Reproductive Technology: Six Cases and Their Clinical Significance.

Med Acupunct 2019 Dec 13;31(6):395-406. Epub 2019 Dec 13.

Lincoln College, Lincoln, United Kingdom.

Assisted reproductive technology (ART) is the routine treatment for infertility. The success rate for individual sessions is generally not high, and many patients need to undergo several cycles. To increase their chances of success, many patients turn to acupuncture to complement ART. Many clinical trials of acupuncture helping fertilization (IVF) have focused only on IVF-embryo transfer (ET). In some difficult cases, when even IVF cannot be offered, acupuncture and Chinese herbs can improve the patients' conditions to reach a level at which ART can be successful. Six cases showed how acupuncture and Traditional Chinese Medicine (TCM), using Chinese herbs, can make IVF possible in difficult cases and how they can also help prevent miscarriage afterward. The cases included patients with amenorrhea, sperm disorders, polycystic ovary syndrome, diminished ovarian reserve (DOR), tubal blockage, premenopause, and premature ovarian insufficiency. Acupuncture and Chinese herbs worked together to help make ART possible or easier. The ART used for these patients included intrauterine insemination, IVF, IVF with a donor egg, and introcytoplasmic sperm injection. In 3 cases, IVF was not initially successful but was successful after TCM treatment. These 6 cases demonstrated the positive effect of a combined approach, using acupuncture and herbs to reduce DOR and regulate hormonal disorders, creating sustainable environments for conceiving and maintaining pregnancy, thus, translating into clinical success. Clinical observation of these cases sheds new light on designing future clinical trials and practice of TCM for practitioners who provide infertility treatments.
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http://dx.doi.org/10.1089/acu.2019.1338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6918531PMC
December 2019

Ten-Year Average Full Follow-up and Evaluation of a Contoured Focal Resurface Prosthesis (HemiCAP) in Patients in the United Kingdom.

J Knee Surg 2020 Oct 24;33(10):966-970. Epub 2019 May 24.

Department of Trauma and Orthopaedic Surgery, Queen Elizabeth II Hospital, Howlands, Welwyn Garden City, Hertfordshire, United Kingdom.

A significant number of patients are affected by localized articular damage that is appropriate neither for traditional arthroplasty nor for biological repair. A focal resurfacing system using a matched contoured articular prosthetic (HemiCAP) has been introduced for the treatment of such cases. Independent long-term results of these implants are limited. We retrospectively evaluated the use of this resurfacing system in 14 patients (13 males, 1 female), with a mean age of 40.3 years (range: 28-49), with focal femoral condyle defects. The same consultant orthopaedic surgeon performed all procedures. Our primary outcome measure was revision rate. Secondary outcome measures included radiographic evaluation (prosthesis migration signs, radiolucency), patient-reported functional evaluation (knee injury and osteoarthritis outcome scores), and complications. A total of 10 patients were treated on the medial femoral condyle, 2 were treated on the lateral condyle, and 2 received bicondylar implants (14 in total). Average follow-up was 107 months (range: 59-135). Three patients were lost to follow-up at the time of study. One patient was excluded from the study. Of the 10 left, 2 had to be revised, leading the survival rate to be 80% at 9.4 years. In four contactable patients, average Knee injury and Osteoarthritis Outcomes score at 121 months postsurgery (9.75 years) was 92.9 (as compared with 57.7 preoperatively). There were no complications. This series demonstrates that focal resurfacing is a safe, suitable, and useful temporizing step in knee arthroplasty surgery. The use of the focal resurfacing implant in this way allows the delay in transition to knee arthroplasty. This series shows an excellent functional outcome for remaining implants at average 10 years, with low complication rates.
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http://dx.doi.org/10.1055/s-0039-1688921DOI Listing
October 2020

Cross-reactivity and tolerability of celecoxib in adult patients with NSAID hypersensitivity.

J Allergy Clin Immunol Pract 2019 Nov - Dec;7(8):2891-2893.e4. Epub 2019 May 14.

Division of Rheumatology, Allergy and Immunology, Department of Medicine, Brigham and Womens Hospital, Boston, MA.

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http://dx.doi.org/10.1016/j.jaip.2019.04.042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328117PMC
October 2020

Functionally Versatile and Highly Stable Chelator for In and Lu: Proof-of-Principle Prostate-Specific Membrane Antigen Targeting.

Bioconjug Chem 2019 05 5;30(5):1539-1553. Epub 2019 May 5.

Department of Molecular Oncology , BC Cancer , 675 West 10th Avenue , Vancouver , British Columbia V5Z 1L3 , Canada.

Here, we present the synthesis and characterization of a new potentially nonadentate chelator Hpypa and its bifunctional analogue Bupypa-C7-NHS conjugated to prostate-specific membrane antigen (PSMA)-targeting peptidomimetic (Glu-urea-Lys). Hpypa is very functionally versatile and biologically stable. Compared to the conventional chelators (e.g., DOTA, DTPA), Hpypa has outstanding affinities for both In (EC, t ≈ 2.8 days) and Lu (β,γ, t ≈ 6.64 days). Its radiolabeled complexes were achieved at >98% radiochemical yield, RT within 10 min, at a ligand concentration as low as 10 M, with excellent stability in human serum over at least 5-7 days (<1% transchelation). The thermodynamic stabilities of the [M(pypa)] complexes (M = In, Lu, La) were dependent on the ionic radii, where the smaller In has the highest pM value (30.5), followed by Lu (22.6) and La (19.9). All pM values are remarkably higher than those with DOTA, DTPA, Hoctapa, Hoctox, and Hneunpa. Moreover, the facile and versatile bifunctionalization enabled by the p-OH group in the central pyridyl bridge of the pypa scaffold (compound 14) allows incorporation of a variety of linkers for bioconjugation through easy nucleophilic substitution. In this work, an alkyl linker was selected to couple Hpypa to a PSMA-targeting pharmacophore, proving that the bioconjugation sacrifices neither the tumor-targeting nor the chelation properties. The biodistribution profiles of In- and Lu-labeled tracers are different, but promising, with the Lu analogue particularly outstanding.
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http://dx.doi.org/10.1021/acs.bioconjchem.9b00225DOI Listing
May 2019

Lessons From Reporting National Performance Measures in a Regional Setting: Washington State Community Cancer Care Report.

J Oncol Pract 2018 12;14(12):e801-e814

Fred Hutchinson Cancer Research Center, Seattle, WA; Premera Blue Cross, Mountlake Terrace, WA; and University of Washington School of Medicine, Seattle, WA.

Regional public reporting of performance measures in oncology can facilitate local decision making across stakeholders, but small numbers of patients and clinics pose a challenge to creating statistically robust measures. In this article, we describe our development of the Community Cancer Care in Washington State: Quality and Cost Report, the first publicly available report showing clinic-level quality and cost measures at the regional level. We learned key lessons in how to adapt national performance reporting to our regional setting using a registry-linked multipayer claims database. In short, limited numbers of eligible patients for some nationally recognized metrics led us to group metrics and use a 3-year performance window. After completing clinic attribution and other requirements of metric construction, the final metrics included between 62.9% and 88.4% of the eligible patients. To link total costs to some quality measures, we had to define a treatment and surveillance episode of care. Risk adjustment was challenged by the ability to include a limited number of risk adjustors and their potential concentration in a few clinics. We used a different quality score than national performance reporting to account for variation in the range of risk-standardized rates. Current methodology does not permit us to determine whether clinically meaningful differences in quality or costs exist, which inhibits value comparisons. Stakeholder engagement was critical for providing methodologic feedback. In conclusion, we found that refining national metrics was necessary to facilitate public reporting in a regional setting. Further methodologic development can strengthen public reporting and future applications.
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http://dx.doi.org/10.1200/JOP.18.00410DOI Listing
December 2018

Co-delivery of paclitaxel and cetuximab by nanodiamond enhances mitotic catastrophe and tumor inhibition.

Sci Rep 2017 08 29;7(1):9814. Epub 2017 Aug 29.

Department and Institute of Biological Science and Technology, National Chiao Tung University, Hsinchu, 30068, Taiwan.

The poor intracellular uptake and non-specific binding of anticancer drugs into cancer cells are the bottlenecks in cancer therapy. Nanocarrier platforms provide the opportunities to improve the drug efficacy. Here we show a carbon-based nanomaterial nanodiamond (ND) that carried paclitaxel (PTX), a microtubule inhibitor, and cetuximab (Cet), a specific monoclonal antibody against epidermal growth factor receptor (EGFR), inducing mitotic catastrophe and tumor inhibition in human colorectal cancer (CRC). ND-PTX blocked the mitotic progression, chromosomal separation, and induced apoptosis in the CRC cells; however, NDs did not induce these effects. Conjugation of ND-PTX with Cet (ND-PTX-Cet) was specifically binding to the EGFR-positive CRC cells and enhanced the mitotic catastrophe and apoptosis induction. Besides, ND-PTX-Cet markedly decreased tumor size in the xenograft EGFR-expressed human CRC tumors of nude mice. Moreover, ND-PTX-Cet induced the mitotic marker protein phospho-histone 3 (Ser10) and apoptotic protein active-caspase 3 for mitotic catastrophe and apoptosis. Taken together, this study demonstrated that the co-delivery of PTX and Cet by ND enhanced the effects of mitotic catastrophe and apoptosis in vitro and in vivo, which may be applied in the human CRC therapy.
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http://dx.doi.org/10.1038/s41598-017-09983-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5575327PMC
August 2017

Effect of Chinese Herbal Medicine on Male Infertility.

Int Rev Neurobiol 2017 12;135:297-311. Epub 2017 Apr 12.

Institute of Pharmaceutical Science, King's College, London, United Kingdom.

Male infertility normally refers a male's inability to cause pregnancy in a fertile female partner after 1 year of unprotected intercourse. Male infertility in recent years has been attracting increasing interest from public due to the evidence in decline in semen quality. There are many factors contributing to the male infertility including abnormal spermatogenesis; reproductive tract anomalies or obstruction; inadequate sexual and ejaculatory functions; and impaired sperm motility, imbalance in hormone levels, and immune system dysfunction. Although conventional treatments such as medication, surgical operation, and advanced techniques have helped many male with infertility cause pregnancy in their female partners, effectiveness is not satisfactory and associated with adverse effects. Chinese herbal medicine (CHM) has been used to improve male infertility in China for a very long time and has now been increasingly popular in Western countries for treating infertility. In this chapter we summarized recent development in basic research and clinical studies of CHM in treating male infertility. It has showed that CHM improved sperm motility and quality, increased sperm count and rebalanced inadequate hormone levels, and adjusted immune functions leading to the increased number of fertility. Further, CHM in combination with conventional therapies improved efficacy of conventional treatments. More studies are needed to indentify the new drugs from CHM and ensure safety, efficacy, and consistency of CHM.
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http://dx.doi.org/10.1016/bs.irn.2017.02.014DOI Listing
April 2018

Treatment of Chinese Herbal Medicine for Female Infertility.

Int Rev Neurobiol 2017 12;135:233-247. Epub 2017 Apr 12.

Neurodegenerative Disease Research Group, Institute of Pharmaceutical Science, Faculty of Life Sciences & Medicine, King's College, London, United Kingdom.

Female infertility is when a woman of reproductive age and sexual active, without contraception, cannot get pregnant after a year and more or keeps having miscarriages. Although conventional treatments for infertility such as hormone therapy, in vitro fertilization and many more, helped many female patients with infertility get pregnant during past a few decades, it is far from satisfactory with prolonging treatment time frames and emotional and financial burden. In recent years, more patients with infertile problems are seeking to alternative and complementary medicines to achieve a better outcome. In particular, Chinese herbal medicine (CHM) is increasingly popular for treating infertility due to its effectiveness and complimentary with conventional treatments. However, the mechanisms of action of CHM in treating female infertility are not well understood. In this chapter authors reviewed research development of CHM applied in many infertile models and CHM clinical studies in many conditions associated with female infertility, published in past 15 years. The data of review showed that CHM has either specific target mechanisms of action or multitarget mechanisms of action, via regulating relevant hormone levels in female reproductive system, improving ovary function, enhancing uterine receptivity. More studies are warranted to explore the new drugs from CHM and ensure safety, efficacy, and consistency of CHM.
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http://dx.doi.org/10.1016/bs.irn.2017.02.011DOI Listing
April 2018

An Enhancer's Length and Composition Are Shaped by Its Regulatory Task.

Front Genet 2017 23;8:63. Epub 2017 May 23.

Department of Developmental and Cell Biology, University of California, IrvineIrvine, CA, United States.

Enhancers drive the gene expression patterns required for virtually every process in metazoans. We propose that enhancer length and transcription factor (TF) binding site composition-the number and identity of TF binding sites-reflect the complexity of the enhancer's regulatory task. In development, we define regulatory task complexity as the number of fates specified in a set of cells at once. We hypothesize that enhancers with more complex regulatory tasks will be longer, with more, but less specific, TF binding sites. Larger numbers of binding sites can be arranged in more ways, allowing enhancers to drive many distinct expression patterns, and therefore cell fates, using a finite number of TF inputs. We compare ~100 enhancers patterning the more complex anterior-posterior (AP) axis and the simpler dorsal-ventral (DV) axis in and find that the AP enhancers are longer with more, but less specific binding sites than the (DV) enhancers. Using a set of ~3,500 enhancers, we find enhancer length and TF binding site number again increase with increasing regulatory task complexity. Therefore, to be broadly applicable, computational tools to study enhancers must account for differences in regulatory task.
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http://dx.doi.org/10.3389/fgene.2017.00063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5440464PMC
May 2017