Comprehensive analysis of tertiary lymphoid structures-related genes for prognostic prediction, molecular subtypes and immune infiltration in gastric cancer.

Gastric cancer (GC) is a highly heterogeneous malignancy and survival rates of advanced GC patients are unsatisfactory. Tertiary lymphoid structures (TLS) are recently identified as lymphoid-like structures that are directly related to tumor prognosis and immune response. However, the association of tertiary lymphoid structures-related genes (TLS-RGs) with prognosis and immune response in GC remains unclear. In our study, a comprehensive analysis of the role of TLS-RGs in GC was performed based on public data, and the difference of TLS-RGs expression, TLS-RGs mutation frequency, pathway enrichment, differentially expressed gene, immune landscape, immunotherapy and drug sensitivity was analyzed. We found that TLS-RGs were altered in GC in terms of expression and mutation. The difference of survival, immune landscape and enrichment pathway exists between TLS clusters. Immune checkpoint differences were also evident between gene clusters. The grouping by TLS score indicated that patients in the low TLS score group had a better prognosis and a lower degree of immune escape. For immunotherapy, the low TLS score group showed better outcomes than the high TLS score group. Sensitivity to chemotherapeutic agents differed between TLS score groups. In conclusion, we comprehensively analyzed the role of TLS-RGs in GC, constructed nomogram that can accurately predict the prognosis of GC patients, and the TLS score can reflect the immune landscape of patients, providing the possibility of personalized design of immunotherapy and targeted drug therapy for GC patients.

Nano transdermal system combining mitochondria-targeting cerium oxide nanoparticles with all-trans retinoic acid for psoriasis.

Psoriasis is an inflammatory skin disease that is intricately linked to oxidative stress. Antioxidation and inhibition of abnormal proliferation of keratinocytes are pivotal strategies for psoriasis. Delivering drugs with these effects to the site of skin lesions is a challenge that needs to be solved. Herein, we reported a nanotransdermal delivery system composed of all-trans retinoic acid (TRA), triphenylphosphine (TPP)-modified cerium oxide (CeO2) nanoparticles, flexible nanoliposomes and gels (TCeO2-TRA-FNL-Gel). The results revealed that TCeO2 synthesized by the anti-micelle method, with a size of approximately 5 nm, possessed excellent mitochondrial targeting ability and valence conversion capability related to scavenging reactive oxygen species (ROS). TCeO2-TRA-FNL prepared by the film dispersion method, with a size of approximately 70 nm, showed high drug encapsulation efficiency (>96%). TCeO2-TRA-FNL-Gel further showed sustained drug release behaviors, great transdermal permeation ability, and greater skin retention than the free TRA. The results of in vitro EGF-induced and H2O2-induced models suggested that TCeO2-TRA-FNL effectively reduced the level of inflammation and alleviated oxidative stress in HaCat cells. The results of in vivo imiquimod (IMQ)-induced model indicated that TCeO2-TRA-FNL-Gel could greatly alleviate the psoriasis symptoms. In summary, the transdermal drug delivery system designed in this study has shown excellent therapeutic effects on psoriasis and is prospective for the safe and accurate therapy of psoriasis.

Cell-surface photochemistry mediated calcium overload for synergistic tumor therapy.

Calcium (Ca2+) is essential for mitochondrial homeostasis and function coordination, particularly in cancer cells that metabolize frequently to sustain their growth. Photochemistry mediated calcium overload has attracted lots of attention as an effective way to achieve tumor suppression. Herein, we developed a photonanomedicine to synergistically induce calcium overload via cell-surface photochemistry and thus tumor suppression. Specifically, the photosensitizer, protoporphyrin IX (PpIX) was loaded onto upconversion nanoparticles (UCNP), which was subsequently modified by a polymer bearing photo-crosslinking cinnamate (CA) groups. The resulting nanoparticle was further functionalized by anti-CD20 aptamers (Apt), to give photonanomedicine. The interaction between CD20 receptors and anti-CD20 aptamers allowed photonanomedicine to accurately attach onto the Raji cell surface after an intravenous injection. Following the local application of a 980 nm NIR laser, the photonanomedicine was able to capture the NIR light and convert it into ultraviolet (UV) light. On one hand, the converted UV light led the crosslinking of cinnamate groups in photonanomedicine, further stimulating the clustering of CD20 receptors and causing Ca2+ influx. On the other hand, the UV light could simultaneously excited PpIX to generate reactive oxygen species (ROS) in situ to break down the integrity of cell membrane and lead to an influx of Ca2+. The synergistic Ca2+ overload mediated by photonanomedicine exhibited an enhanced and superior anti-tumor efficacy. We believe this photonanomedicine expands the toolbox to manipulate intracellular Ca2+ concentration and holds a great potential as an anti-tumor therapy.

Efficacy and safety of pulsed radiofrequency combined with pregabalin for herpetic neuralgia: A systematic review and meta-analysis.

BACKGROUND: Pulsed radiofrequency (PRF), as a new technique, is used to treat a variety of chronic pain syndromes, but it has a high recurrence rate for herpetic neuralgia and is often combined with drugs therapy. The aim of this study was to comprehensively evaluate the efficacy and safety of PRF combined with pregabalin in the treatment of herpetic neuralgia. METHODS: The electronic databases, including CNKI, Wanfang data, PubMed, Embase, web of science, and Cochrane Library were searched from inception to January 31, 2023. The outcomes were pain scores, sleep quality and side effects. RESULTS: Fifteen studies with 1817 patients were included in this meta-analysis. PRF combined with pregabalin significantly reduced the visual analogue scale/score in patients with postherpetic neuralgia or herpes zoster neuralgia when compared with pregabalin or PRF monotherapy [P < .00001, standardized mean difference (SMD) = -2.01, confidence intervals (CI) = -2.36 to -1.66; P < .00001, SMD = -0.69, CI = -0.77 to -0.61]. Compared with pregabalin monotherapy, PRF combined with pregabalin significantly decreased the pittsburgh sleep quality index score, the dosage and number of days of using pregabalin (P < .00001, SMD = -1.68, CI = -2.19 to -1.17; P < .00001, SMD = -0.94, CI = -1.25 to -0.64; P < .00001, SMD = -1.52, CI = -1.85 to -1.19). However, there was no significant difference in the effect of PRF combined with pregabalin versus PRF alone on pittsburgh sleep quality index score in patients with postherpetic neuralgia (P = .70, SMD = -1.02, CI = -6.11 to 4.07). In addition, PRF combined with pregabalin could significantly decrease the incidence of dizziness, somnolence, ataxia and pain at puncture site when compared with pregabalin monotherapy (P = .0007, odds ratio [OR] = 0.56, CI = 0.40 to 0.78; P = .008, OR = 0.60, CI = 0.41 to 0.88; P = .008, OR = 0.52, CI = 0.32 to 0.84; P = .0007, OR = 12.39, CI = 2.87 to 53.43), but no significant difference was observed when compared with PRF alone. CONCLUSIONS: PRF combined with pregabalin can effectively alleviate the pain intensity and improve sleep quality in patients with herpetic neuralgia, and the incidence of complications was low, so it was worthy of clinical application.

PANoptosis-related prognostic signature predicts overall survival of cutaneous melanoma and provides insights into immune infiltration landscape.

Cutaneous melanoma (CM) is a highly malignant tumor originating from melanocytes, and its metastasis and recurrence are the major causes of death in CM patients. PANoptosis is a newly defined inflammatory programmed cell death that crosstalk pyroptosis, apoptosis, and necroptosis. PANoptosis participates in the regulation of tumor progression, especially the expression of PANoptosis related genes (PARGs). Although pyroptosis, apoptosis, and necroptosis have received attention in CM, respectively, the link between them remains elusive. Therefore, this study aimed to investigate the potential regulatory role of PANoptosis and PARGs in CM and the relationship among PANoptosis, PARGs and tumor immunity. We identified 3 PARGs associated with prognosis in CM patients by The Cancer Genome Atlas. Risk model and nomogram were established. Enrichment analysis of differentially expressed genes indicated that CM was immune-related. Subsequent analyses indicated that prognosis-related PARGs were associated with immune scores and infiltration of immune cells in CM patients. In addition, immunotherapy and drug sensitivity results indicated an association between prognosis-related PARGs and drug resistance in CM patients. In conclusion, PARGs play a key role in the progression of tumors in CM patients. PARGs can be used not only for risk assessment and OS prediction in CM patients, but also reflect the immune landscape of CM patients, which can provide a novel reference for individualized tumor treatment.

Metabolomics strategy of Pikang oral liquid in the treatment of psoriasis.

This study aimed to investigate the effect of Pikang oral liquid (PK) on psoriasis and analyze its possible mechanism from the perspective of metabolism. A psoriasis-form mouse model established using imiquimod (IMQ) was used to evaluate the anti-psoriatic effects of PK. The serum samples were analyzed by high-resolution nuclear magnetic resonance (1 H NMR)-based metabonomics. Nine amino acids were further quantitatively analyzed by ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS). This study suggested that PK treatment markedly attenuated IMQ-induced psoriasis in a dose-dependent manner. 1 H NMR-based multivariate trajectory analysis revealed that PK had a certain regression effect on eight differential metabolites. The quantitative results showed that PK could significantly regulate the serum levels of alanine, histidine and arginine to healthy control levels. The anti-psoriasis mechanism of PK may be associated with the restoration of the disturbance in the amino acid metabolism, energy metabolism and lipid metabolism and so on. Quantitative results further confirmed that amino acid metabolism play an key role in the pathogenesis of psoriasis. Our investigation provided a holistic view of PK for intervention psoriasis and provided the scientific information in vivo about a clinical value of PK for psoriasis.