Efficacy and safety of concurrent immune checkpoint inhibitors combined with radiotherapy or chemoradiotherapy for advanced non-small cell lung cancer: A systematic review and single-arm meta-analysis.

BACKGROUND: The recent usage of immunotherapy combined with chemoradiotherapy has improved survival in advanced non-small cell lung cancer (NSCLC) patients. However, determining the most effective therapy combination remains a topic of debate. Research suggests immune checkpoint inhibitors (ICIs) post-chemoradiotherapy enhance survival, but the impact of concurrent ICIs during chemoradiotherapy on rapid disease progression is unclear. This meta-analysis aims to assess the effectiveness and safety of concurrent ICIs with radiotherapy or chemoradiotherapy in advanced non-small cell lung cancer. METHODS: We searched PubMed, Embase, the Cochrane Library, and Web of Science for relevant studies, extracting data on overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs). RESULTS: The analysis included ten studies with 490 participants. Stage III NSCLC ORR was 81.8%, while Stage IV ORR was 39.9%. One-year PFS and OS for Stage III were 68.2% and 82.6%, compared to 27.9% and 72.2% for Stage IV. Common adverse events included anemia (46.6%), nausea (47.6%), rash (36.4%), and radiation pneumonitis (36.3%). CONCLUSIONS: Our meta-analysis shows concurrent ICIs with chemoradiotherapy are effective and safe in advanced NSCLC, particularly in stage III patients at risk of progression before starting ICIs after chemoradiotherapy. The findings support further phase III trials. The review protocol was registered on PROSPERO (CRD42023493685) and is detailed on the NIHR HTA programme website.

Efficient Alcoholysis of Poly(ethylene terephthalate) by Using Supercritical Carbon Dioxide as a Green Solvent.

In order to reduce the environmental impact of poly(ethylene terephthalate) (PET) plastic waste, supercritical fluids were used to facilitate effective recovery via improved solvent effects. This work focuses on the mechanisms of supercritical CO2 (ScCO2) during the alcoholysis processing of PET using systematic experiments and molecular dynamics (MD) simulations. The results of the alcoholysis experiment indicated that PET chips can be completely depolymerized within only an hour at 473 K assisted with ScCO2 at an optimal molar ratio of CO2/ethanol of 0.2. Random scission of PET dominates the early stage of the depolymerization reaction process, while specific scission dominates the following stage. Correspondingly, molecular dynamics (MD) simulations revealed that the solubilization and self-diffusion properties of ScCO2 facilitate the transportation of alcohol molecules into the bulk phase of PET, which leads to an accelerated diffusion of both oligomers and small molecules in the system. However, the presence of excessive CO2 has a negative impact on depolymerization by weakening the hydrogen bonding between polyester chain segments and ethanol, as well as decreasing the swelling degree of PET. These data provide a deep understanding of PET degradation by alcohols and the enhancement of ScCO2. It should be expected to achieve an efficient and high-yield depolymerization process of wasted polyesters assisted with ScCO2 at a relatively low temperature.

MicroRNA 421 induces the formation of high-invasive cell subsets of ovarian cancer from low-invasive cell subsets mediated by exosomes by activating the PI3K/AKT pathway.

Intratumoral heterogeneity (ITH) results in treatment failure in ovarian cancer (OC). Exosomes are related to the formation of a heterogeneous tumor microenvironment, and microRNAs play a crucial role in the progression of OC. Therefore, we aimed to explore the effect of exosomes and microRNA 421 (miR-421), which is mediated by exosomes, on ITH and the diagnosis of OC. Exosomes derived from A2780 cells with the highest (AHC) or lowest (ALC) invasive/migratory capacity cells (AHE/ALE) were extracted by differential centrifugation. We conducted a series of experiments to verify the role of AHE and miR-421 in promoting the transformation of low-invasive cells to high-invasive cells by regulating the PI3K/AKT pathway, and we also measured the levels of CA125 in serum exosomes. The results of assays showed that the AHE and miR-421, mediated by exosomes, significantly increased the malignancy of ALC cells by activating the PI3K/AKT pathway. The expression of miR-421 was significantly increased in the serum exosomes derived from high-grade serous ovarian cancer (HGSOC) patients. Our findings indicate that MiR-421, mediated by exosomes, could induce the transformation of highly invasive cell subpopulations from subpopulations of OC cells with low invasive potential by activating the PI3K/AKT signaling pathway.

Correlation analysis and clinical significance of changes in upper thoracic vertebra tilt and clavicle angle pre- and post-operation.

The imbalance of the lateral shoulder is reflected by the clavicle angle (CA) in radiology. It remains unclear how to achieve postoperative lateral shoulder balance (LSB) after spinal deformity correction surgery. A retrospective analysis was conducted on AIS patients who underwent surgery by the same spine surgeon at our hospital from 2016 to 2020. A total of 110 patients with spinal deformity were included in the study to verify the correlation between the T1-T5 tilt angle and CA before and after surgery, as well as the relation-ship between the change in T1-T5 tilt angle before and after surgery and the change in CA before and after surgery. By comparing the correlation coefficients, it was found that there may not be a direct relationship between the pre- and postoperative tilt angles of T1-5 and CA, but their changes were closely related to the changes in CA. The change in T1 tilt angle after orthopaedic surgery was significantly correlated with the change in CA, with a correlation coefficient of 0.976, indicating a close relationship between T1 and the clavicle. As the vertebrae moved down, the correlation gradually decreased. In summary, this study suggests that there is a close relationship between T1-T5 and the clavicle and that the change in T1 tilt angle after spinal scoliosis correction surgery is significantly correlated with CA, which decreases as the vertebra moves down.

Biosynthesis of NIR-II Ag2 Se Quantum Dots with Bacterial Catalase for Photoacoustic Imaging and Alleviating-Hypoxia Photothermal Therapy.

Developing the second near-infrared (NIR-II) photoacoustic (PA) agent is of great interest in bioimaging. Ag2 Se quantum dots (QDs) are one kind of potential probe for applications in NIR-II photoacoustic imaging (PAI). However, the surfaces with excess anions of Ag2 Se QDs, which increase the probability of nonradiative transitions of excitons benefiting PA imaging, are not conducive to binding electron donor ligands for potential biolabeling and imaging. In this study, Staphylococcus aureus (S. aureus) cells are driven for the biosynthesis of Ag2 Se QDs with catalase (CAT). Biosynthesized Ag2 Se (bio-Ag2 Se-CAT) QDs are produced in Se-enriched environment of S. aureus and have a high Se-rich surface. The photothermal conversion efficiency of bio-Ag2 Se-CAT QDs at 808 and 1064 nm is calculated as 75.3% and 51.7%, respectively. Additionally, the PA signal responsiveness of bio-Ag2 Se-CAT QDs is ≈10 times that of the commercial PA contrast agent indocyanine green. In particular, the bacterial CAT is naturally attached to bio-Ag2 Se-CAT QDs surface, which can effectively relieve tumor hypoxia. The bio-Ag2 Se-CAT QDs can relieve heat-initiated oxidative stress while undergoing effective photothermal therapy (PTT). Such biosynthesis method of NIR-II bio-Ag2 Se-CAT QDs opens a new avenue for developing multifunctional nanomaterials, showing great promise for PAI, hypoxia alleviation, and PTT.

Biosynthesis of CuTe Nanorods with Large Molar Extinction Coefficients for NIR-II Photoacoustic Imaging.

Photoacoustic imaging (PAI) in the second near-infrared region (NIR-II), due to deeper tissue penetration and a lower background interference, has attracted widespread concern. However, the development of NIR-II nanoprobes with a large molar extinction coefficient and a high photothermal conversion efficiency (PCE) for PAI and photothermal therapy (PTT) is still a big challenge. In this work, the NIR-II CuTe nanorods (NRs) with large molar extinction coefficients ((1.31 ± 0.01) × 108 cm-1·M-1 at 808 nm, (7.00 ± 0.38) × 107 cm-1·M-1 at 1064 nm) and high PCEs (70% at 808 nm, 48% at 1064 nm) were synthesized by living Staphylococcus aureus (S. aureus) cells as biosynthesis factories. Due to the strong light-absorbing and high photothermal conversion ability, the in vitro PA signals of CuTe NRs were about 6 times that of indocyanine green (ICG) in both NIR-I and NIR-II. In addition, CuTe NRs could effectively inhibit tumor growth through PTT. This work provides a new strategy for developing NIR-II probes with large molar extinction coefficients and high PCEs for NIR-II PAI and PTT.

SOD3 regulates FLT1 to affect bone metabolism by promoting osteogenesis and inhibiting adipogenesis through PI3K/AKT and MAPK pathways.

Osteoporosis is a chronic disease that seriously affects the quality of life and longevity of the elderly, so exploring the mechanism of osteoporosis is crucial for drug development and treatment. Bone marrow mesenchymal stem cells are stem cells with multiple differentiation potentials in bone marrow, and changing their differentiation direction can change bone mass. As an extracellular superoxide dismutase, Superoxide Dismutase 3 (SOD3) has been proved to play an important role in multiple organs, but the detailed mechanism of action in bone metabolism is still unclear. In this study, the results of clinical serum samples ELISA and single cell sequencing chip analysis proved that the expression of SOD3 was positively correlated with bone mass, and SOD3 was mainly expressed in osteoblasts and adipocytes and rarely expressed in osteoblasts in BMSCs. In vitro experiments showed that SOD3 can promote osteogenesis and inhibit adipogenesis. Compared with WT mice, the mice that were knocked out of SOD3 had a significant decrease in bone mineral density and significant changes in related parameters. The results of HE and IHC staining suggested that knocking out SOD3 would lead to fat accumulation in the bone marrow cavity and weakened osteogenesis. Both in vitro and in vivo experiments indicated that SOD3 affects bone metabolism by promoting osteogenesis and inhibiting adipogenesis. The results of transcriptome sequencing and revalidation showed that SOD3 can affect the expression of FLT1. Through in vitro experiments, we proved that FLT1 can also promote osteogenesis and inhibit adipogenesis. In addition, through the repeated experiments, the interaction between the two molecules (SOD3 and FLT1) was verified again. Finally, it was verified by WB that SOD3 regulates FLT1 to affect bone metabolism through PI3K/AKT and MAPK pathways.

Lenvatinib plus Immune Checkpoint Inhibitors versus Lenvatinib monotherapy as treatment for advanced hepatocellular carcinoma: a meta-analysis.

Lenvatinib, an FDA-approved first-line oral multi-kinase inhibitor for advanced hepatocellular carcinoma (aHCC), has demonstrated promise for treatment. Nevertheless, findings from the Leap-002 study suggest that the addition of anti-vascular drugs to Lenvatinib may not yield significant improvements in survival rate. This meta-analysis aims to comprehensively assess the effectiveness of Lenvatinib, both as a standalone treatment and in combination with immune checkpoint inhibitors (ICIs), in managing advanced aHCC patients. We retrieved relevant studies published up to March 1, 2023, from databases such as PubMed, the Cochrane Library, Web of Science, and Embase. Subsequently, we conducted an analysis using REVMAN 5.3 and Stata MP 14.0 software, following quality assessment and data extraction procedures. A random effects model was employed to calculate the risk ratio (HR) using a 95% confidence interval (CI). The initial literature search yielded 921 results. However, after multiple rounds of exclusion and the removal of unrelated studies, 26 papers met the screening criteria. After a thorough examination of the full texts, we found that 8 studies met the analysis criteria. The combination of Lenvatinib with ICIs demonstrated significant improvement in overall survival (OS) (HR=1.53, 95% CI: 1.34-1.74; P<0.001) and progression-free survival (PFS) (HR=1.51, 95% CI: 1.34-1.72; P<0.001). Furthermore, subgroup analysis, categorized by the duration of follow-up, revealed that for the 3-year combined OS (HR=2.21, 95% CI: 1.79-2.73; Z=7.40, P<0.05), the combination therapy significantly outperformed monotherapy, leading to a 2.21-fold increase in OS for patients during the 3-year follow-up period. Nevertheless, for non-3-year combinations (HR=1.206, 95% CI: 1.020-1.425; Z=2.19, P<0.05), there was merely a 1.206-fold increase in effectiveness compared to single therapy for follow-ups of both longer and shorter durations. This might be attributed to the insufficient representation of HBV-related aHCC cases and the Asian population in the study, along with the increased availability of second-line treatment options for advanced cancer, which can influence the observed effectiveness of immunotherapy.

Expanding the role of combined immunochemotherapy and immunoradiotherapy in the management of head and neck cancer (Review).

Immunotherapy has become one of the most promising approaches in tumor therapy, and there are numerous associated clinical trials in China. As an immunosuppressive tumor, head and neck squamous cell carcinoma (HNSCC) carries a high mutation burden, making immune checkpoint inhibitors promising candidates in this field due to their unique mechanism of action. The present review outlines a comprehensive multidisciplinary cancer treatment approach and elaborates on how combining immunochemotherapy and immunoradiotherapy guidelines could enhance clinical efficacy in patients with HNSCC. Furthermore, the present review explores the immunology of HNSCC, current immunotherapeutic strategies to enhance antitumor activity, ongoing clinical trials and the future direction of the current immune landscape in HNSCC. Advanced-stage HNSCC presents with a poor prognosis, low survival rates and minimal improvement in patient survival trends over time. Understanding the potential of immunotherapy and ways to combine it with surgery, chemotherapy and radiotherapy confers good prospects for the management of human papillomavirus (HPV)-positive HNSCC, as well as other HPV-positive malignancies. Understanding the immune system and its effect on HNSCC progression and metastasis will help to uncover novel biomarkers for the selection of patients and to enhance the efficacy of treatments. Further research on why current immune checkpoint inhibitors and targeted drugs are only effective for some patients in the clinic is needed; therefore, further research is required to improve the overall survival of affected patients.

Prevalence of psoriatic arthritis in Chinese population with psoriasis: A multicenter study conducted by experienced rheumatologists.

BACKGROUND: Reports on the prevalence of psoriatic arthritis (PsA) among Chinese patients with psoriasis are very limited. This study, conducted by rheumatologists, estimated the prevalence of PsA in a large number of Chinese patients with psoriasis. METHODS: Consecutive patients with a confirmed diagnosis of psoriasis attending nine dermatology clinics in five hospitals were recruited. All psoriasis patients were asked to complete a questionnaire comprising 16 questions to identify possible cases of PsA. All patients with one or more positive answers to the questionnaire were evaluated by two experienced rheumatologists. RESULTS: A total of 2434 psoriasis patients, including 1561 males and 873 females, were enrolled. Both the questionnaire and rheumatologists' examinations were completed in the dermatology clinics. The results identified 252 patients with PsA, comprising 168 males and 84 females. The overall prevalence of PsA among psoriasis patients was 10.4% (95% confidence interval [95% CI], 9.1%-11.7%). By sex, the prevalence was 10.8% (95% CI, 9.2%-12.5%) for males and 9.6% (95% CI, 7.7%-11.9%) for females and there was no significant sex difference in the prevalence of PsA (P = 0.38). Of the 252 PsA patients, 125 (49.6%, 95% CI, 41.3%-59.1%) were newly diagnosed by rheumatologists. Consequently, the prevalence of undiagnosed PsA among psoriasis patients was 5.2% (95% CI, 4.4%-6.2%). CONCLUSION: The prevalence of PsA in the Chinese population with psoriasis is about 10.4%, which is almost double that of previous reports in the Chinese population, but lower than that in Caucasians.

Risk of Erectile Dysfunction in Male Patients with Gout Treated with Febuxostat or Allopurinol: A Propensity Score-Matched Cohort Study.

OBJECTIVE: To evaluate and compare the risk of erectile dysfunction (ED) associated with the use of allopurinol and febuxostat in adult male gout patients. METHODS: We conducted a cohort study using TriNetX (Cambridge, MA, USA), a global federated health research network that provides real-time electronic medical record datasets. We analyzed and compared the associated risk of ED in gout patients who started taking allopurinol or febuxostat within 12 months. Propensity score matching was performed to adjust for demographic variables, comorbidities, and medication use. Kaplan-Meier analysis was used to estimate the probability of the outcome of interest. The hazard ratio (HR) and associated confidence intervals were calculated along with the proportionality test using R's Survival Package v3.2-3. RESULTS: We identified 679,862 patients with gout among 107,517,445 patients in the database. Of these patients, 24,000 were treated with febuxostat and 299,726 with allopurinol. After propensity matching, 9075 patients receiving febuxostat without allopurinol (febuxostat group) and 9075 corresponding patients receiving allopurinol without febuxostat (allopurinol group) were analyzed for comparison. Among all male patients over 19 years of age, febuxostat was associated with a significantly higher risk of ED versus allopurinol (HR 1.354; 95% confidence interval (CI) 1.003-1.829; log rank test, p = 0.047). After subgroup analysis, in gout patients aged 19-64 years, a significantly higher incidence of ED was observed in the febuxostat group than in the allopurinol group (HR 2.002, 95% CI 1.282-3.126). The risk of ED did not differ significantly between the allopurinol and febuxostat groups in gout patients older than 65 years. CONCLUSIONS: Febuxostat may be associated with a higher risk of ED than allopurinol in adult male patients with gout. Future large-scale prospective studies are warranted to confirm our results.

A New Index Based on Serum Creatinine and Cystatin C Can Predict the Risks of Sarcopenia, Falls and Fractures in Old Patients with Low Bone Mineral Density.

As new screening tools for sarcopenia, the serum sarcopenia index (SI) and creatinine/cystatin C ratio (CCR) had not been confirmd in a population with a high fragility fracture risk. This study aimed to evaluate whether SI and CCR indicators are useful for diagnosing sarcopenia and to determine their prediction values for future falls and fractures. A total of 404 hospitalized older adults were enrolled in this longitudinal follow-up study (mean age = 66.43 ± 6.80 years). The receiver operating curve (ROC) was used to assess the diagnostic accuracy of SI and CCR. Backward-selection binary logistic regression was applied to develop the optimal models for the diagnosis of new falls and fractures. SI had a significantly higher area under the curve (AUC) than CCR for predicting sarcopenia. The optimal models had acceptable discriminative powers for predicting new falls and fractures. Lower SI and CCR are the independent risks for sarcopenia, new falls, and fractures in the low-BMD population. SI and CCR, as easily accessible biochemical markers, may be useful in the detection of sarcopenia and in predicting the occurrence of new falls and fractures in patients with low BMD who have not previously experienced falls or fractures. However, further external validations are required.

A meta-analysis of adjuvant EGFR-TKIs for patients with EGFR mutation of resected non-small cell lung cancer.

BACKGROUND: The role of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKIs) in improving the prognostic outcome of non-small cell lung cancer (NSCLC) cases harboring EGFR mutation following radical surgery is still controversial. This work focused on comparing EGFR-TKIs and adjuvant chemotherapy (ACT) or placebo in treating NSCLC cases, specifically on those with EGFR-mutant, being in the stage of IB-IIIA and possibly gained benefits from the above treatment after radical resection. METHODS: The Cochrane Library, MEDLINE, and Embase databases were searched to identify eligible clinical trials; two authors were responsible for screening the results. The primary outcomes were evaluated by disease-free survival (DFS) and overall survival (OS) based on hazard ratios (HRs) and a relevant 95% confidence interval (CI). RESULTS: The literature search yielded twelve eligible studies, including four retrospective cohort studies and eight randomized controlled trials (RCTs) that enrolled 1694 cases and were of acceptable quality. In patients receiving adjuvant EGFR-TKIs compared with ACT or placebo treatment, HR regarding DFS was 0.47 (95% CI: 0.40, 0.55), whereas the OS rate was 0.74 (95% CI: 0.58, 0.95). For patients who received adjuvant EGFR-TKIs in combination with conventional chemotherapy compared to chemotherapy, the efficiency was significantly enhanced, with the HR for DFS being 0.29 (95% CI: 0.15, 0.58) and that for OS being 0.51 (95% CI: 0.25, 1.04), separately. CONCLUSION: For NSCLC cases who had EGFR mutations and surgery, adjuvant EGFR-TKI combined with chemotherapy achieved superior effect over chemotherapy or placebo with reference to DFS and may prolong the OS up to some extent.

Methylation-driven gene DLL3 is a potential prognostic biomarker in ocular melanoma correlating with metastasis.

Background: Ocular melanoma is an aggressive malignancy with a high rate of metastasis and poor prognosis. Increasing evidence indicated that DNA methylation plays an important role in the occurrence and development of ocular melanoma. Hence, exploring new diagnostic and prognostic biomarkers at the genetic level may be beneficial to the prognosis of patients with ocular melanoma. Methods: We collected DNA methylation and gene expression profiles of human UM (uveal melanoma) and CM (conjunctival melanoma) samples from various datasets. We conducted differential methylation and expression analyses to screen the potential biomarkers. Correlation analysis was performed to investigate the relationships between the expression level of DLL3 (delta-like protein 3) and the methylation level of its corresponding CpGs. We explored the prognostic and diagnostic value of DLL3 in UM and CM. Functional annotation and GSEA (gene set enrichment analysis) were applied to get insight into the possible biological roles of DLL3. A cohort of 60 ocular melanoma patients as well as UM and CM cell lines were used to validate our findings in bioinformatic analyses. Results: We found that DLL3 was a methylation-driven gene correlating with UM metastasis. The CpGs of DLL3 are mainly located in the gene body and their methylation level positively correlated to DLL3 expression. Multivariate Cox regression analysis revealed that DLL3 was an independent protective factor for UM patients. High DLL3 expression significantly prolonged the overall survival and disease-free survival of UM patients. DLL3 also showed a promising power to distinguish CM from normal tissues. Functional annotation exhibited that DLL3 may suppress UM progression through modulating immune activities and down-regulating various signaling pathways. External datasets, biospecimens, and cell lines further validated the aberrant expression and prognostic role of DLL3 in ocular melanoma. Conclusion: Methylation-driven gene DLL3 could serve as a new potential diagnostic and prognostic biomarker in ocular melanoma. Our findings may contribute to improving the clinical outcomes of patients with UM or CM.

Comparison of clinical outcomes and risk factors for COVID-19 infection in cancer patients without anticancer treatment and noncancer patients.

Background: Previous studies have shown that cancer patients have higher rates of coronavirus disease 2019 (COVID-19) infection and mortality than noncancer patients. However, the differences between cancer patients undergoing regular follow-up without anticancer treatment and noncancer patients with COVID-19 have remained insufficiently investigated. Methods: A retrospective case-control study of 52 patients with COVID-19 infection was performed with a 1:3 matched proportion of cancer patients undergoing regular follow-up without anticancer treatment and noncancer patients. The demographic characteristics, clinical data, laboratory tests, treatment, and complications of patients were collected from medical records. Chi-square tests and univariate and multivariate regressions were performed to assess the differences between these two cohorts of COVID-19 patients with and without cancer and risk factors for severe events in COVID-19 patients. Results: Increased C-reactive protein (CRP) (>4 mg/L) (p = 0.015) and lactate dehydrogenase (LDH) (>243 IU/L) (p = 0.038) were identified as risk factors for severe events in all enrolled COVID-19 patients based on multivariate analysis, but cancer as a chronic disease (p = 1.000) was not identified as an independent risk factor for severe events in COVID-19 patients. Compared with noncancer patients, cancer patients had a significantly longer median hospitalization time (29 days vs. 19 days, p = 0.048) and a higher incidence of hypoalbuminemia complications (84.6 vs. 46.2%, p = 0.016). Conclusions: Increased CRP and LDH were risk factors for severe events in all enrolled COVID-19 patients, and an increased incidence of hypoalbuminemia complications and longer hospitalization were noted in COVID-19 cancer patients undergoing regular follow-up without anticancer treatment compared with noncancer patients.

Silk Fibroin-Induced Gadolinium-Functionalized Gold Nanoparticles for MR/CT Dual-Modal Imaging-Guided Photothermal Therapy.

The development of multifunction nanoplatforms integrating accurate diagnosis and efficient therapy is of great significance for the precise treatment of tumors. Gold nanoparticles (AuNPs) possessing hallmark features of computed tomography (CT) imaging and photothermal conversion capability hold great potential in tumor theranostics. In this study, taking the advantages of outstanding biocompatibility, interesting anti-inflammatory and immunomodulatory properties, and abundant amino acid residues of silk fibroin (SF), a multifunctional Gd-hybridized AuNP nanoplatform was constructed using SF as a stabilizer and reductant via a facile one-pot biomimetic method, denoted as Gd:AuNPs@SF. The obtained Gd:AuNPs@SF possessed fascinating biocompatibility and excellent photothermal conversion efficiency. Functionalized with Gd, Gd:AuNPs@SF exhibited super tumor-contrasted imaging performance in magnetic resonance (MR) and CT imaging modalities. Moreover, Gd:AuNPs@SF, with strong NIR absorbance, demonstrated that it could effectively kill tumor cells in vitro, and was also proved to successfully ablate tumor tissues through MR/CT imaging-guided photothermal therapy (PTT) without systemic toxicity in Pan02 xenograft C57BL/6 mouse models. We successfully synthesized Gd:AuNPs@SF for MR/CT dual-mode imaging-guided PTT via a facile one-pot biomimetic method, and this biomimetic strategy can also be used for the construction of other multifunction nanoplatforms, which is promising for precise tumor theranostics.

Characterization of Immune-Related Molecular Subtypes and a Prognostic Signature Correlating With the Response to Immunotherapy in Patients With Gastric Cancer.

Gastric cancer (GC) is a disease characterized by high molecular and phenotypic heterogeneity and represents a leading cause of cancer-related death worldwide. The tumor immune microenvironment (TIME) affects the response to immunotherapy and the prognosis of patients with GC. Explorations of the TIME in GC and characterization of molecular subtypes might enhance personalized treatment and facilitate clinical decision-making. In this study, two molecular subtypes were defined through unsupervised consensus clustering based on immune-related dysregulated genes. Then, patients with different molecular subtypes of GC were shown to have distinct differences in sensitivity to immune checkpoint blockers (ICBs). The immune-related prognostic signature was established utilizing least absolute shrinkage and selection operator (LASSO)-Cox regression analysis. Three independent external cohorts and the IMvigor210 cohort were introduced to validate the robustness of IPRS. scRNA-seq data of GC samples were used to decipher the underlying mechanisms of how IPRS contributes to the TIME. GC biospecimens were collected for RT-qPCR to further validate our findings. In summary, we characterized the abnormal TIME of GC and constructed a reliable immune-related prognostic signature correlating with the response to immunotherapy. This study may provide new strategies for developing individualized treatments for patients with GC.

Primary ewing sarcoma in the uterine cervix with multiple bone metastases.

A 45-year-old female (G1, P1) with HPV-52 infection and low-grade cervical cytology presented to our clinic with an asymptomatic cervical mass. She suffered amenorrhea for the past 3 years due to medication for thyroid cancer. Magnetic resonance imaging revealed a mass sized 7.1 × 6.3 × 5.7 cm in the cervix with local invasion, and multiple lesions in the left ilium and femur. Histologically blue small round cells, positive for CD99 and FLI-1, obtained by cervical biopsy and the EWSR1 gene rearrangement detected by Fluorescence in situ hybridization confirmed the diagnosis of Ewing sarcoma. However, prior to the first cycle of systemic chemotherapy, the patient developed a sudden onset of lower extremities paraplegia, with PET/CT detecting extensive metastatic lesions in multiple bones including cervical 4 and thoracic 10 vertebral bodies. Although we performed emergency spinal canal decompression and excision of a thoracic 10 metastasis, the patient's condition deteriorated rapidly and died three months later.

Clinical analysis and artificial intelligence survival prediction of serous ovarian cancer based on preoperative circulating leukocytes.

Circulating leukocytes are an important part of the immune system. The aim of this work is to explore the role of preoperative circulating leukocytes in serous ovarian carcinoma and investigate whether they can be used to predict survival prognosis. Routine blood test results and clinical information of patients with serous ovarian carcinoma were retrospectively collected. And to predict survival according to the blood routine test result the decision tree method was applied to build a machine learning model.The results showed that the number of preoperative white blood cells (p = 0.022), monocytes (p < 0.001), lymphocytes (p < 0.001), neutrophils (p < 0.001), and eosinophils (p < 0.001) and the monocyte to lymphocyte (MO/LY) ratio in the serous ovarian cancer group were significantly different from those in the control group. These factors also showed a correlation with other clinicopathological characteristics. The MO/LY was the root node of the decision tree, and the predictive AUC for survival was 0.69. The features involved in the decision tree were the MO/LY, differentiation status, CA125 level, neutrophils (NE,) ascites cytology, LY% and age.In conclusion, the number and percentage of preoperative leukocytes in patients with ovarian cancer is changed significantly compared to those in the normal control group, as well as the MO/LY. A decision tree was built to predict the survival of patients with serous ovarian cancer based on the CA125 level, white blood cell (WBC) count, presence of lymph node metastasis (LNM), MO count, the MO/LY ratio, differentiation status, stage, LY%, ascites cytology, and age.