BackgroundDefinitive concurrent chemoradiotherapy (dCCRT) is suggested as the standard treatment for cervical esophageal squamous cell carcinoma (CESCC). This retrospective propensity study compared the 8-year survival outcomes and acute treatment toxicities of these patients treated with elective nodal irradiation (ENI) versus involved-field irradiation (IFI).Materials and methodsPatients with stage II–IV CESCC treated with dCCRT at the Fourth Hospital of Hebei Medical University between January 1, 2007 and December 31, 2020 were enrolled in the study. All the patients were restaged according to the American Joint Commission 8th edition criteria. The propensity score matching (PSM) was used to minimize the effects of treatment selection bias and potential confounding factors including sex, age, ECOG score, clinical T stage, clinical N stage, clinical TNM stage and radiation dose between the ENI group and IFI group. Survival and the prognostic factors were evaluated.ResultsThe 131 eligible patients underwent ENI (60 patients, 45.8%) or IFI (71 patients, 54.2%). The median follow-up time was 91.1 months (range, 23.8–182.0 months) for all the patients. The median OS, 1-, 3-, 5-, and 8-year OS rates were 44.4 months, 87.8%, 55.1%, 38.3%, and 27.2%, respectively. After PSM, there were 49 patients in each group. The median OS, 1-, 3-, 5-, and 8-year OS rates for ENI and IFI group were 32.0 months, 83.7%, 48.5%, 38.5% and 31.1% versus 45.2 months, 89.8%, 52.5%, 37.5%, 26.1%, respectively (P = 0.966; HR 0.99, 95% CI 0.61–1.61). Similar locoregional control was obtained in both groups. The tendency of leukocytopenia and neutropenia was higher in ENI than in IFI (59.2% vs. 38.8%; P = 0.068 and 30.6% vs. 14.3%; P = 0.089) at the end of dCCRT.ConclusionCervical esophageal squamous cell carcinoma patients undergoing definitive concurrent chemoradiotherapy has a satisfactory prognosis with organ conservation. The involved-field irradiation might be a better alternative owing to similar overall survival outcomes and local control with less toxicity of myelosuppression.

ObjectiveTo compare the clinical efficacy of surgical treatment for multilevel cervical spondylotic myelopathy (MCSM) between the hybrid procedure, posterior endoscopic decompression (PED) combined with anterior cervical discectomy fusion (ACDF), and posterior cervical laminectomy and fusion (PCLF).MethodsA retrospective analysis was performed on 38 patients who received surgical treatment for MCSM from January 2018 to December 2021, including 19 cases in hybrid procedure group (13 males and 6 females), followed up for 10 to 22 (12.8 ± 10.3) months, and 19 cases in PCLF group (15 males and 4 females), followed up for 10 to 21 (11.7 ± 8.9) months. Perioperative information, including operation time, intraoperative blood loss, length of hospitalization, and complications, were compared between two groups. Visual analogue scale (VAS) of pain, neck disability index (NDI) and Japanese Orthopaedic Association (JOA) score were recorded to evaluate clinical efficacy. Cervical lordosis was calculated by radiographic examination.ResultsIntraoperative blood loss, length of hospital stay were less in hybrid group than PCLF group, while operation time is longer in hybrid group, with a statistically significant difference (p < 0.05). Increased lordosis was better in hybrid group. There was no significant difference in preoperative VAS, JOA and NDI at pre-operation and final follow-up between two groups. But at post-operation and final follow-up, VAS was less in hybrid group than PCLF group (p < 0.05). There were 2 cases of neurostimulation symptoms in hybrid group, 2 cases of C5 nerve root palsy, 2 cases of subcutaneous fat necrosis and 1 case of dural tear in PCLF group, and all patients relieved with symptomatic treatment.ConclusionThe hybrid procedure of PED combined with ACDF showed satisfied clinical outcome, with less intraoperative blood loss, shorter length of hospitalization and lower post-operative neck pain than PCLF. It is an effective surgical treatment for MCSM.

BackgroundThe metastasis of breast cancer (BC) is a complex multi-step pathological process, strictly dependent on the intrinsic characteristics of BC cells and promoted by a predisposing microenvironment. Although immunotherapy has made important progress in metastasis BC, the heterogeneity of PD-L1 in tumor associated macrophages (TAMs) in BC and the underlying mechanisms in the metastasis development of BC are still not completely elucidated. Small extracellular vesicles (sEVs) represent essential interaction mediators between BC cells and TAMs. It is worth noting to explore the underlying mechanisms typical of sEVs and their role in the metastasis development of BC.MethodsThe structure of sEVs was identified by TEM, while the particle size and amounts of sEVs were detected by BCA and NTA analysis. The specific PD-L1 + CD163 + TAM subpopulation in metastasis BC was identified by scRNA-seq data of GEO datasets and verified by IHC and IF. The function of TAMs and sEVs in metastasis BC was explored by RT-qPCR, WB, IF, flow cytometry and in vivo experiment. The expression profiles of plasma sEVs-miRNA in relation to BC metastasis was analyzed using next-generation sequencing. Further detailed mechanisms of sEVs in the metastasis development of BC were explored by bioinformatics analysis, RT-qPCR, WB and luciferase reporter assay.ResultsIn this study, we identified that the immunosuppressive molecule PD-L1 was more abundant in TAMs than in BC cells, and a specific PD-L1 + CD163 + TAM subpopulation was found to be associated with metastasis BC. Additionally, we found that BC cells-derived sEVs can upregulate the PD-L1 expression and induce the M2 polarization, enhancing the metastasis development both in vitro and in vivo. Also, Clinical data showed that sEV-miR-106b-5p and sEV-miR-18a-5p was in relation to BC metastasis development and poor prognosis of BC patients. Further mechanistic experiments revealed that BC-derived sEV-miR-106b-5p and sEV-miR-18a-5p could synergistically promoted the PD-L1 expression in M2 TAMs by modulating the PTEN/AKT and PIAS3/STAT3 pathways, resulting in the enhancement of the BC cells invasion and metastasis.ConclusionsOur study demonstrated that BC-derived sEVs can induce metastasis in BC through miR-106b-5p/PTEN/AKT/PD-L1 and miR-18a-5p/PIAS3/STAT3/PD-L1 pathways in TAMs. Therefore, the inhibition of these specific interactions of signaling pathways would represent a promising target for future therapeutic strategies for treatment of BC.

The majority of these existing prognostic models of head and neck squamous cell carcinoma (HNSCC) have unsatisfactory prediction accuracy since they solely utilize demographic and clinical information. Leveraged by autophagy-related epigenetic biomarkers, we aim to develop a better prognostic prediction model of HNSCC incorporating CpG probes with either main effects or gene–gene interactions. Based on DNA methylation data from three independent cohorts, we applied a 3-D analysis strategy to develop An independently validated auTophagy-related epigenetic prognostic prediction model of HEad and Neck squamous cell carcinomA (ATHENA). Compared to prediction models with only demographic and clinical information, ATHENA has substantially improved discriminative ability, prediction accuracy and more clinical net benefits, and shows robustness in different subpopulations, as well as external populations. Besides, epigenetic score of ATHENA is significantly associated with tumor immune microenvironment, tumor-infiltrating immune cell abundances, immune checkpoints, somatic mutation and immunity-related drugs. Taken together these results, ATHENA has the demonstrated feasibility and utility of predicting HNSCC survival (http://bigdata.njmu.edu.cn/ATHENA/).

PurposeTo investigate the binocular summation (BiS) of visual acuity (VA) and contrast sensitivity (CS) in children with intermittent exotropia (IXT) before and after surgery and to probe the relationship between the two BiS phenomena and corresponding influencing factors.MethodsThis prospective study included 21 IXT children (11 males and 10 females; aged 6–13 years) who underwent strabismus surgery in Tianjin Eye Hospital from January to April 2022. The visual function was assessed preoperatively and 2.95 ± 0.14 months postoperatively, including monocular/ binocular visual acuity (MVA/BVA) at 100% contrast and 2.5% contrast as well as monocular/binocular contrast sensitivity (MCS/BCS), deviation, near and distant stereopsis, and fusion.ResultsAll patients had postoperative deviation ranging from 0 to -4 PD. Either preoperative or postoperative BVA at 2.5% contrast was superior to the MVA. The postoperative BiS at 2.5% contrast was significantly superior to the preoperative BiS for 2.5% contrast and postoperative BiS for 100% contrast (P < 0.05). Except for 3 c/d, the MCS and BCS at 6 c/d, 12 c/d and 18 c/d spatial frequencies were all notably improved postoperatively. The postoperative binocular summation ratio of CS (BSR) was highest while interocular difference ratio of CS (IOR) was the lowest at 6 c/d among 4 spatial frequencies. The deviation, distant and near stereopsis, and fusion performance were all remarkably improved after surgery (p = 0.001; p = 0.041; p = 0.000), all of which were not related to BVA at 2.5% contrast, BiS, BSC and BSR. The BCS at middle and high frequencies (6 c/ds, 12 c/ds, and 18 c/ds) was significantly negatively correlated with the BVA at 2.5% contrast, and BSR was irrelevant to the corresponding IOR across different spatial frequencies.ConclusionBVA at low contrast and BCS examinations were not equivalent to stereopsis and fusion status, which contributed to the evaluation of binocular function in the real environment and in the different aspects. BVA in 2.5% contrast is related with BCS in moderate and high spacial frequencies (especially 18c/d) but BCS in 6c/d presents more binocular summation of contrast sensitivity. MCS, BCS and the BSR persist inhibition at 3c/d after surgery. The improvement of BCS is better than that of BSR to evaluate the binouclar function in IXT. Those two methods showed different sensitivities to impairment and rehabilitation of binocular summation and inhibition.

BackgroundAlthough observational studies have established some socioeconomic traits to be independent risk factors for pelvic organ prolapse (POP), they can not infer causality since they are easily biased by confounding factors and reverse causality. Moreover, it remains ambiguous which one or several of socioeconomic traits play predominant roles in the associations with POP risk. Mendelian randomization (MR) overcomes these biases and can even determine one or several socioeconomic traits predominantly accounting for the associations.ObjectiveWe conducted a multivariable Mendelian randomization (MVMR) analysis to disentangle whether one or more of five categories of socioeconomic traits, “age at which full-time education completed (abbreviated as “EA”)”, “job involving heavy manual or physical work (“heavy work”)”, “average total household income before tax (income)”, “Townsend deprivation index at recruitment (TDI)”, and “leisure/social activities” exerted independent and predominant effects on POP risk.MethodsWe first screened single-nucleotide polymorphisms (SNPs) as proxies for five individual socioeconomic traits and female genital prolapse (FGP, approximate surrogate for POP due to no GWASs for POP) to conduct Univariable Mendelian randomization (UVMR) analyses to estimate causal associations of five socioeconomic traits with FGP risk using IVW method as major analysis. Additionally, we conducted heterogeneity, pleiotropy, and sensitivity analysis to assess the robustness of our results. Then, we harvested a combination of SNPs as an integrated proxy for the five socioeconomic traits to perform a MVMR analysis based on IVW MVMR model.ResultsUVMR analyses based on IVW method identified causal effect of EA (OR 0.759, 95%CI 0.629–0.916, p = 0.004), but denied that of the other five traits on FGP risk (all p > 0.05). Heterogeneity analyses, pleiotropy analyses, “leave-one-out” sensitivity analyses and MR-PRESSO adjustments did not detect heterogeneity, pleiotropic effects, or result fluctuation by outlying SNPs in the effect estimates of six socioeconomic traits on FGP risk (all p > 0.05). Further, MVMR analyses determined a predominant role of EA playing in the associations of socioeconomic traits with FGP risk based on both MVMR Model 1 (OR 0.842, 95%CI 0.744–0.953, p = 0.006) and Model 2 (OR 0.857, 95%CI 0.759–0.967, p = 0.012).ConclusionOur UVMR and MVMR analyses provided genetic evidence that one socioeconomic trait, lower educational attainment, is associated with risk of female genital prolapse, and even independently and predominantly accounts for the associations of socioeconomic traits with risk of female genital prolapse.