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Introduction: Zoster-associated pain (ZAP), which may cause anxiety, depression, and sleep disorders and reduce quality of life, is often refractory to current standard treatments. Studies have shown that pulsed radiofrequency (PRF) can alleviate ZAP and reduce the incidence of postherpetic neuralgia (PHN). This study aimed to explore the clinical characteristics associated with PRF responsiveness, develop a model for identifying risk factors of inadequate PRF management, and help clinicians make better decisions. Methods: Patients who underwent PRF for ZAP between January 2017 and October 2020 in our hospital were included in this study. Patients were evaluated using the numerical rating scale (NRS), Insomnia Severity Index, Patient Health Questionnaire-9, and 36-Item Short Form Health Survey (SF-36) before and 3 months after the procedure. Patient demographic data and blood test results were also collected. We defined the effectiveness of PRF for ZAP as relief of > 50% in NRS scores compared to pre-PRF. Least absolute shrinkage and selection operator (LASSO) regression analyses were subsequently performed to identify factors related to the therapeutic effect of PRF in patients with ZAP. The performance of the prediction model was assessed by the area under the receiver operating characteristic curve (AUC). Results: The effectiveness of PRF in patients with ZAP was 69.6% (total 313 patients) after 3 months. LASSO regression analysis extracted the seven most powerful features in the developed prediction model: sex, stage of herpes zoster (HZ), pregabalin dose, bodily pain indicators of SF-36, lymphocyte count, and low-density lipoprotein cholesterol (LDLC) and complement C4 in peripheral blood. Model = 1.586 + 0.148 × lymphocyte + (−0.001) × bodily pain indicators of SF-36 + (−0.001) × pregabalin dose + 0.028 × LDLC + 0.001 × C4 + (−0.508) × sex + (−0.128) × stage of HZ. We generated the ROC curve for the prediction model, and the final AUC was 0.701. The sensitivity, specificity, and overall accuracy of the model were 90%, 33%, and 73%, respectively. Conclusions: Seven factors were significantly associated with poor PRF outcome: male sex, advanced stage of HZ, higher pregabalin dose, higher bodily pain indicators of SF-36, and lower lymphocyte count, LDLC, and complement C4 in the peripheral blood. PRF should be applied to patients with ZAP as early as possible to achieve satisfactory outcomes.

Surface biotinylation has been widely adapted in profiling the cellular proteome associated with the plasma membrane. However, the workflow is subject to interference from the cytoplasmic biotin-associated proteins that compete for streptavidin-binding during purification. Here we established a bioorthogonal conjugation-assisted purification (BCAP) workflow that utilizes the Staudinger chemoselective ligation to label and isolate surface-associated proteins while minimizing the binding of endogenous biotin-associated proteins. Label-free quantitative proteomics demonstrated that BCAP is efficient in isolating cell surface proteins with excellent reproducibility. Subsequently, we applied BCAP to compare the surface proteome of proliferating and senescent mouse embryonic fibroblasts (MEFs). Among the results, EHD2 was identified and validated as a novel protein that is enhanced at the cell surface of senescent MEFs. We expect that BCAP will have broad applications in profiling cell surface proteomes in the future.

A zinc(ii) phthalocyanine (ZnPc) was conjugated to doxorubicin (Dox) viaan acid-labile hydrazone linker. The resulting ZnPc–Dox conjugate was then encapsulated into polymeric micelles formed through self-assembly of a block copolymer of poly(ethylene glycol) and poly(d,l-lactide) both in the absence and presence of the hypoxia-activated prodrug tirapazamine (TPZ) to give ZnPc–Dox@micelles and ZnPc–Dox/TPZ@micelles respectively. These polymeric micelles exhibited an excellent stability in aqueous media, but underwent disassembly in an acidic environment. Upon internalisation into HT29 human colorectal carcinoma cells, fluorescence due to ZnPc and Dox could be observed in the cytoplasm and nucleus respectively for both nanosystems. This observation suggested the disassembly of the polymeric micelles and the cleavage of the hydrazone linker in ZnPc–Dox in the acidic intracellular compartments. These micelles were slightly cytotoxic against HT29 cells in the dark due to the chemotherapeutic effect of Dox and/or TPZ. Upon light irradiation, ZnPc–Dox@micelles showed higher cytotoxicity. The IC50value under a normoxic condition (0.35 μM based on ZnPc–Dox) was significantly lower than that under hypoxia (>1 μM). With an additional therapeutic component, ZnPc–Dox/TPZ@micelles exhibited higher photocytotoxicity with IC50values of 0.20 μM and 0.78 μM under normoxia and hypoxia respectively. It is believed that the photodynamic action of this nanosystem consumed the intracellular oxygen and hence triggered the hypoxia-mediated chemotherapeutic action of TPZ. The multimodal antitumor effects of these polymeric micelles were also validated on HT29 tumour-bearing nude mice.

Epigenetic reader proteins interpret histone epigenetic marks to regulate gene expression. Given their vital roles and the link between their dysfunction and various diseases, these proteins present compelling targets for therapeutic interventions. Nevertheless, designing selective inhibitors for these proteins poses significant challenges, primarily due to their unique properties such as shallow binding sites and similarities with homologous proteins. To overcome these challenges, we propose an innovative strategy that uses phage display with a genetically encoded noncanonical amino acid (ncAA) containing an epigenetic mark. This ncAA guides binding to the reader protein’s active site, allowing the identification of peptide inhibitors with enhanced affinity and selectivity. In this study, we demonstrate this novel approach’s effectiveness by identifying potent inhibitors for the ENL YEATS domain that plays a critical role in leukemogenesis. Our strategy involved genetically incorporating Nε-butyryl-l-lysine (BuK), known for its binding to ENL YEATS, into a phage display library for enriching the pool of potent inhibitors. One resultant hit was further optimized by substituting BuK with other pharmacophores to exploit a unique π–π–π stacking interaction with ENL YEATS. This led to the creation of selective ENL YEATS inhibitors with a KDvalue of 2.0 nM and a selectivity 28 times higher for ENL YEATS than its close homologue AF9 YEATS. One such inhibitor, tENL-S1f, demonstrated robust cellular target engagement and on-target effects to inhibit leukemia cell growth and suppress the expression of ENL target genes. As a pioneering study, this work opens up extensive avenues for the development of potent and selective peptidyl inhibitors for a broad spectrum of epigenetic reader proteins.

Objective. To compare the efficacy and side effects of patient-controlled intravenous analgesia (PCIA) with hydromorphone, sufentanil, and oxycodone on the management of advanced cancer patients with pain. Methods. Patients allocated to receive PCIA between January 2015 and December 2016 were chosen for this study. After reviewing medical records, we verified if hydromorphone, sufentanil, or oxycodone for PCIA could equally provide effective pain relief. A numeric rating scale (NRS) of cancer pain was applied before PCIA, at 4 hours after PCIA, and at the discontinuation of PCIA. Secondary, the incidence of clinical side effects attributed to PCIA was observed. Results. A total of 85 medical records were reviewed. PCIA with hydromorphone (n=30), sufentanil (n=34), and oxycodone (n=21) was used for cancer pain management. PCIA successfully improved pain control in 97.6% of the patients. The most common side effects were constipation (11.8%), nausea (8.2%), and sedation (5.9%). Drug addiction, delirium, or respiratory depression associated with PCIA was not reported in this case series study. No significant intergroup difference was observed in NRS at any of the abovementioned time points. There was no significant difference of analgesic effect among the hydromorphone, sufentanil, or oxycodone. Conclusion. PCIA provided timely, safe, and satisfactory analgesia for advanced cancer patients with pain and may be useful for titration of opioids, management of severe breakthrough pain, and conversion to oral analgesia. There was no significant difference of analgesic effect and side effect among the hydromorphone, sufentanil, and oxycodone.