Case report: Innovative treatment for one metastatic thyroid-like follicular carcinoma of the kidney with ATM and POLE mutations.

Thyroid-like follicular renal cell carcinoma (TLFRCC), also known as thyroid-like follicular carcinoma of the kidney or thyroid follicular carcinoma like renal tumor, is an exceedingly rare variant of renal cell carcinoma that has only recently been acknowledged. This neoplasm exhibits a distinct follicular morphology resembling that of the thyroid gland. Immunohistochemical analysis reveals positive expression of PAX8, Vimentin, and EMA, while thyroid-specific markers TG and TTF1 are consistently absent. Furthermore, there is a notable absence of any concurrent thyroid pathology on clinical evaluation. Previous reports have suggested that TLFRCC is an indolent, slow-growing malignancy with infrequent metastatic potential. In this report, we present a case of TLFRCC characterized by remarkable ossification and widespread metastasis, including multifocal pulmonary lesions, involvement of the abdominal wall, and infiltration into the psoas muscle. To our knowledge, this represents only the third documented instance of distant metastasis in thyroid follicular renal carcinoma. The current case demonstrates a therapeutic approach that combines radiotherapy with the utilization of toripalimab, a programmed cell death 1 (PD-1) receptor inhibitor, and pazopanib. This treatment regimen was tailored based on comprehensive genomic profiling, which identified mutations in the POLE (catalytic subunit of DNA polymerase epsilon) and ATM (ataxia-telangiectasia mutated) genes, both of which have been implicated in the pathogenesis of various malignant tumors. These findings represent a novel discovery, as such mutations have never been reported in association with TLFRCC. Thus far, this therapeutic approach has proven to be the most efficacious option for treating metastatic TLFRCC among previously reported, and it also marks the first mention of the potential benefits of radiotherapy in managing this particular subtype of renal cell carcinoma.

UAV-based modelling of vegetation recovery under extreme habitat stresses in the water level fluctuation zone of the Three Gorges Reservoir, China.

Impoundment of the Three Gorges Reservoir on the upper Yangtze River has remarkably altered hydrological regime within the dammed reaches, triggering structural and functional changes of the riparian ecosystem. Up to date, how vegetation recovers in response to compound habitat stresses in the water level fluctuation zone remains inexplicitly understood. In this study, plant above-ground biomass (AGB) in a selected water level fluctuation zone was quantified to depict its spatial and temporal pattern using unmanned aerial vehicle (UAV)-derived multispectral images and screened empirical models. The contributions of multiple habitat stressors in governing vegetation recovery dynamics along the environmental gradient were further explored. Screened random forest models indicated relatively higher accuracy in AGB estimation, with R2 being 0.68, 0.79 and 0.62 during the sprouting, growth, and mature periods, respectively. AGB displayed a significant linear increasing trend along the elevational gradient during the sprouting and early growth period, while it showed an inverted U-shaped pattern during late growth and mature period. Flooding duration, magnitude and timing were found to exert greater negative effects on plant sprouting and biomass accumulation and acted as decisive factors in governing the elevation-dependent pattern of AGB. Localized spatial variations in AGB were modulated by other stressors such as sediment burial, soil erosion, soil moisture and nutrient content. Occurrence of episodic summer floods and vegetation distribution were responsible for an inverted U-shaped pattern of AGB during the late growth and mature period. Generally, AGB reached its peak in August, thereafter an obvious decline by an unprecedent dry-hot climatic event. The water level fluctuations with cumulative flooding effects exerted substantial control on AGB temporal dynamics, while climatic condition played a secondary role. Herein, further restorative efforts need to be directed to screening suitable species, maintaining favorable soil condition, and improving vegetation pattern to balance the many trade-offs.

Computed tomography perfusion deficit volume predicts the functional outcome of endovascular therapy for basilar artery occlusion.

OBJECTIVES: To investigate the relationship between baseline computed tomography perfusion deficit volumes and functional outcomes in patients with basilar artery occlusion (BAO) undergoing endovascular therapy. METHODS: This was a single-center study in which the data of 64 patients with BAO who underwent endovascular therapy were retrospectively analyzed. All the patients underwent multi-model computed tomography on admission. The posterior-circulation Acute Stroke Prognosis Early Computed Tomography Score was applied to assess the ischemic changes. Perfusion deficit volumes were obtained using Syngo.via software. The primary outcome of the analysis was a good functional outcome (90-day modified Rankin Scale score ≤ 3). Logistic regression and receiver operating characteristic curves were used to explore predictors of functional outcome. RESULTS: A total of 64 patients (median age, 68 years; 72 % male) were recruited, of whom 26 (41 %) patients achieved good functional outcomes, while 38 (59 %) had poor functional outcomes. Tmax > 10 s, Tmax > 6 s, and rCBF < 30 % volume were independent predictors of good functional outcomes (odds ratio range, 1.0-1.2; 95 % confidence interval [CI], 1.0-1.4]) and performed well in the receiver operating characteristic curve analyses, exhibiting positive prognostic value; the areas under the curve values were 0.85 (95 % CI, 0.75-0.94), 0.81 (95 % CI, 0.70-0.90), and 0.78 (95 % CI, 0.67-0.89). CONCLUSION: Computed tomography perfusion deficit volume represents a valuable tool in predicting high risk of disability and mortality in patients with BAO after endovascular treatment.

Demethylase FTO-Mediated m6A Modification of lncRNA MEG3 Activates Neuronal Pyroptosis via NLRP3 Signaling in Cerebral Ischemic Stroke.

Neuronal death following ischemia is the primary cause of death and disability in patients with ischemic stroke. N6-methyladenosine (m6A) modification plays essential role in various physiological and pathological conditions, but its role and mechanism in ischemic neuronal death remain unclear. In the present study, neuronal pyroptosis was an important event in brain injury caused by ischemic stroke, and the upregulation of long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3) following cerebral ischemia was a key factor in activating ischemic neuronal pyroptosis via NLRP3/caspase-1/GSDMD signaling. Moreover, we first demonstrated that the demethylase fat mass and obesity-associated protein (FTO), which was decreased following ischemia, regulated MEG3 expression in an m6A-dependent manner by affecting its stability, thereby activating neuronal pyroptosis via NLRP3/caspase-1/GSDMD signaling, and ultimately leading to ischemic brain damage. Therefore, the present study provides new insights for the mechanism of ischemic stroke, and suggests that FTO may be a potential therapeutic target for ischemic stroke.

The value of computed tomography perfusion deficit volumes in acute isolated brainstem infarction.

Purpose: Diagnosis of acute isolated brainstem infarction is challenging owing to non-specific, variable symptoms, and the effectiveness of non-contrast computed tomography (NCCT) is poor owing to limited spatial resolution and artifacts. Computed tomography perfusion (CTP) imaging parameters are significantly associated with functional outcomes in posterior circulation acute ischemic stroke; however, the role of CTP in isolated brainstem infarction remains unclear. We aimed to determine the value of CTP imaging parameters in predicting functional outcomes for affected patients. Methods: In total, 116 consecutive patients with isolated pontine/midbrain hypoperfusion who underwent CTP and follow-up by magnetic resonance imaging (MRI) between January 2018 and March 2022, were retrospectively analyzed. Perfusion deficit volumes on all maps, and the final infarction volume (FIV) on MRI were quantified. "Good" functional outcome was defined as a 90-day modified Rankin Scale score of 0 and 1. Statistical analysis included uni- and multivariate regression analyses, binary logistic regressions, and receiver operating characteristics (ROC) analyses. Results: In total, 113 patients had confirmed isolated pontine/midbrain infarction on follow-up MRI. Onset-to-scan time, visibility of ischemic lesions on NCCT, the baseline National Institutes of Health Stroke Scale (NIHSS) score, and perfusion deficit volumes on all CTP maps were significantly associated with FIV (p < 0.05). In a multivariate linear regression model, adjusted for age, sex, NIHSS score, onset-to-scan time, and visibility of NCCT, perfusion deficit volumes remained significantly associated with FIV. In binary logistic regression analyses, perfusion deficit volumes on all CTP maps remained independent predictors of a good functional outcome. In ROC analyses, the cerebral blood flow deficit volume showed a slightly higher discriminatory value with the largest area under the curve being 0.683 [(95% CI, 0.587-0.780), p = 0.001]. Conclusion: Perfusion deficit volumes of CTP imaging could reflect the FIV and contain prognostic information on functional outcomes in patients with acute isolated brainstem infarction.

A novel role for astrocytic fragmented mitochondria in regulating morphine addiction.

Chronic morphine exposure causes the development of addictive behaviors, accompanied by an increase in neuroinflammation in the central nervous system. While previous researches have shown that astrocytes contribute to brain diseases, the role of astrocyte in morphine addiction through induced neuroinflammation remain unexplored. Here we show that morphine-induced inflammation requires the crosstalk among neuron, astrocyte, and microglia. Specifically, astrocytes respond to morphine-induced neuronal activation by increasing glycolytic metabolism. The dysregulation of glycolysis leads to an increased in the generation of mitochondrial reactive oxygen species and causes excessive mitochondrial fragmentation in astrocytes. These fragmented, dysfunctional mitochondria are consequently released into extracellular environment, leading to activation of microglia and release of inflammatory cytokines. We also found that blocking the nicotinamide adenine dinucleotide salvage pathway with FK866 could inhibit astrocytic glycolysis and restore the mitochondrial homeostasis and effectively attenuate neuroinflammatory responses. Importantly, FK866 reversed morphine-induced addictive behaviors in mice. In summary, our findings illustrate an essential role of astrocytic immunometabolism in morphine induced neural and behavioral plasticity, providing a novel insight into the interactions between neurons, astrocytes, and microglia in the brain affected by chronic morphine exposure.

Corrigendum: Comparison of peripheral blood regulatory T cells and functional subsets between ocular and generalized myasthenia gravis.

[This corrects the article DOI: 10.3389/fmed.2022.851808.].

Characterization of cerebrovascular changes in mice treated with alcohol by photoacoustic imaging.

Alcohol has complex effects on cerebrovascular health. Monitoring the pathology of alcohol induced cerebrovascular changes in vivo is essential for understanding the mechanism and developing potential treatment strategies. Here, photoacoustic imaging was employed to examine cerebrovascular changes in mice under the treatment of alcohol at different doses. By analyzing the association of cerebrovascular structure, hemodynamics, neuronal function and corresponding behavior, we found that alcohol affected brain function and behavior in a dose-dependent manner. Low dose of alcohol increased cerebrovascular blood volume and activated neurons, without addictive behaviors and cerebrovascular structure changes. With the dose increased, cerebrovascular blood volume gradually decreased, triggering obviously progressive effects on the immune microenvironment, cerebrovascular structure and addictive behavior. These findings will provide further insights into the characterization of the biphasic effects of alcohol.

Intravenous Thrombolysis for Acute Ischemic Stroke in Patients With Cardiac Myxoma: A Case Series and Pooled Analysis.

Background and Purpose: Acute ischemic stroke (AIS) is a major life-threatening consequence of cardiac myxoma (CM) and leads to a poor prognosis. Although intravenous thrombolysis (IVT) is the first-line treatment for AIS, its efficacy and safety in CM-AIS have not been established. Currently, there are only limited data from case reports. Our study aimed to investigate the clinical characteristics of CM-AIS and evaluate the safety and efficacy of IVT for CM-AIS patients. Methods: Fourteen CM-AIS patients who received IVT between January 2016 and December 2021 were identified from our multicenter stroke registry databases. Clinical, neuroimaging and outcome data were analyzed. We then performed a pooled analysis of the published literature from inception to December 2021. Results: Of the 14 CM-AIS patients, nine were treated with IVT alone, and five were treated with bridging therapy (BT). The median age was 51.5 years, and 57.1% were female. The median onset-to-needle time was 160 min. The median National Institute of Health Stroke Score (NIHSS) decreased from 15.5 at presentation to 13 24 h after IVT. Very early neurological improvement (VENI) was observed in one patient. Hemorrhagic transformation (HT) was observed in five (35.7%) patients, and only one patient was symptomatic (7.1%). Three-month favorable outcomes were achieved in six patients (66.7%) who underwent IVT alone and three patients (60%) who received BT, which resulted in a total proportion of favorable outcomes of 64.3%. None of the patients died at 3 months follow-up. Forty-seven cases (15 BT patients) were included for the pooled analysis. The median NIHSS score was 16.5, and VENI was observed in 10 (21.3%) patients. HT was detected in 11 patients (23.4%), and four (8.5%) patients were symptomatic. Favorable outcomes at 3 months were achieved in 61.7% of patients, 56.3% of patients who underwent IVT alone, and 73.3% of patients who received BT. The 3-month mortality rate was 4.3%. Conclusions: IVT is a potentially safe and efficient treatment for CM-AIS patients. Further studies with larger sample sizes are required to provide more evidence on the safety and efficacy of IVT and BT in CM-AIS patients.

Comparison of Peripheral Blood Regulatory T Cells and Functional Subsets Between Ocular and Generalized Myasthenia Gravis.

Purpose: This study aims to discuss the function mechanism of regulatory T cells and its subsets in the pathogenic process of myasthenia gravis by contracting the activation levels of those cells in peripheral blood among healthy people, patients with ocular myasthenia gravis (oMG) and patients with generalized myasthenia gravis (gMG). Method: Healthy people, newly diagnosed oMG patients, and gMG patients were enrolled in this study. The percentage of the CD3+CD4+CD25+ Treg cells, CD3+CD4+CD25+Foxp3+ Treg cells, CD3+CD4+CD25+Foxp3hi CD45RA-aTreg cells, CD3+CD4+CD25+Foxp3loCD45RA-n-sTreg cells, and CD3+CD4+CD25+ Foxp3loCD45RA+rTreg cells in the peripheral blood were examined by flow cytometry. And then analyzed the differences of Treg cells and its subsets among the study members. Results: The percentage of the CD4+CD25+Treg cells in the peripheral blood of oMG patients and gMG patients were both lower than that of healthy people (p < 0.05), the percentage of patients with oMG had no distinct difference with that of patients with gMG (p = 0.475), however. Also, the percentage of CD3+CD4+CD25+Foxp3+Treg cells in the oMG and gMG patients' group were both lower than that of healthy group. And the percentage of CD25+Foxp3+Treg cells in the peripheral blood of patients with oMG and healthy people were both higher than that of patients with gMG (p < 0.05). The percentage of rTreg in the CD3+CD4+CD25+Treg of the peripheral blood for both gMG and oMG patients' group were lower than healthy group (p < 0.05), but there was no statistical significance between the oMG and gMG patients' group (p = 0.232). The percentage of the aTreg cells in the CD3+CD4+CD25+Treg cells of the peripheral blood for the oMG patients was higher than that of gMG patients (p < 0.05), but both of them were lower than healthy group (p < 0.05). The percentage of n-sTreg cells in the peripheral blood descended among the gMG patients' group, oMG patients' group, and healthy group (p < 0.05). Conclusion: The changes in the number and function of Treg cells and its subsets can cause the impairment of negative immune regulation, which may mediate the triggering of oMG and its progression to gMG.

Case Report: Interferon-Alpha-Induced Neuromyelitis Optica Spectrum Disorder.

Background and Objectives: To describe a new case of neuromyelitis optica spectrum disorder (NMOSD) induced by the administration of interferon-alpha (IFNα) and to raise awareness of this rare drug-induced disease of IFNα treatment. Methods: A single case study and comprehensive literature review of eight cases. Results: A 24-year-old man was diagnosed with cerebral venous thrombosis and essential thrombocythemia. He had been undergoing IFNα treatment (IFNα-2b, 3 million IU per day) without any side effects for 18 months, at which point the patient developed persistent hiccups, nausea, urinary retention, and numbness. Spinal magnetic resonance imaging revealed a longitudinal abnormality extending from the medulla to the entire spinal cord. The patient was positive for anti-aquaporin-4 antibody (AQP4-IgG) in both the serum and cerebrospinal fluid (CSF), which confirmed the diagnosis of NMOSD. Thus, recombinant IFNα-2b was suspended immediately. Because his condition did not improve after 6-day treatment of methylprednisolone pulse therapy (1,000 mg for 3 days, then 500 mg for 3 days), intravenous immunoglobulin (0.4 g/kg/day for 5 days) was administered. The patient gradually improved. Low-dose prednisolone and mycophenolate mofetil were subsequently administered as a long-term treatment. The patient was discharged with subtle limb numbness and their expanded disability status score (EDSS) was 1. At the 1-year follow-up, the patient had not relapsed and tested negative for AQP4-IgG. We further identified the eight patients with IFNα-induced NMOSD. The median onset age was 59 years, and the median time of IFNα exposure was 18 months. Optic neuritis was the most common initial symptom (five, 55.6%), followed by myelitis in three patients and area postrema syndrome in one patient. More than half (five, 55.6%) of the patients were monophasic. After IFNα discontinuation and immunotherapy, most (seven, 77.8%) patients remained relapse-free. However, only one patient was free of sequelae. Conclusion: This study highlights the potential pathogenic risk of NMOSD of IFNα treatment. Given the high disability rates of this rare drug-induced disease, it is crucial to monitor the early manifestations of NMOSD during IFNα treatment.

Mechanical Thrombectomy for Acute Ischemic Stroke in Patients With Cardiac Myxoma: A Case Series and Pooled Analysis.

Background and Purpose: Acute ischemic stroke (AIS) is a common and life-threatening complication of patients with cardiac myxoma (CM). The role of the mechanical thrombectomy (MT) technique in CM-AIS patients remains unclear, and no guidelines exist for this population. Therefore, we conducted a case series study of MT in CM-AIS patients to investigate its safety and efficacy via a pooled analysis of published literature. Methods: Eleven CM-AIS patients who underwent MT between 2016 and 2021 were screened from multicenter stroke databases. Clinical, procedural, and outcome data were obtained from medical records. A systematic review was conducted to identify additional cases from published studies by searching PubMed and China National Knowledge Infrastructure databases. We then performed a pooled analysis of the published cases. Results: In the case series study, most patients were male (81.8%), with a median age of 51 years. All patients had CM located in the left atrium. The rate of successful reperfusion using the first-line thrombectomy technique was 100% with stent retriever (SR) and 66.7% with direct aspiration (DA), which resulted in overall successful reperfusion in 94.1% of all occlusions. The retrieved emboli of the five patients who underwent histopathology examination were identified as myxoma components. Hemorrhagic transformation was observed in five (45.5%) patients, of whom one was symptomatic (9.1%). Three-month favorable functional outcomes were achieved in five (45.5%) patients with a 3-month mortality rate of 18.2%. For the literature review, 35 cases with 51 target vessel occlusions were identified and included in the pooled analysis. The rate of successful reperfusion following first-line thrombectomy did not differ between SR (30 patients, 90.9%) and DA (10 patients, 83.3%). The overall successful reperfusion rate was 91.8% of all occlusions. Three-month favorable functional outcomes were achieved in 21 (60.0%) patients, and the mortality rate was 8.6%. Conclusions: Our findings suggest that MT is not only an effective technique but also a safe option for CM-AIS patients with large vessel occlusion. MT has several advantages for this population, which include a high recanalization rate, low bleeding risk, and the ability to evaluate the source of emboli and the etiology of stroke.

Multimodal Imaging-Guided Photothermal Immunotherapy Based on a Versatile NIR-II Aggregation-Induced Emission Luminogen.

Synergistic photothermal immunotherapy has captured great attention owing to the mutually strengthening therapeutic outcomes towards both original tumors and abscopal tumors. Herein, a versatile theranostic agent displaying aggregation-induced emission, namely TPA-BT-DPTQ, was designed and prepared based on benzo[c]thiophene unit as a building block; it can be used for simultaneous fluorescence imaging (FLI) in the second near-infrared (NIR-II) window, photoacoustic imaging (PAI), photothermal imaging (PTI), and thermal eradication of tumors. Further experiments validate that photothermal therapy (PTT) mediated by TPA-BT-DPTQ nanoparticles not only destroys the primary tumor but also enhances immunogenicity for further suppressing the growth of tumors at distant sites. Furthermore, PTT combining a programmed death-ligand 1 (PD-L1) antibody prevents the metastasis and recurrence of cancer by potentiating the effect of immunotherapy.

[Effects of Intravitreal Injection of Anti-vascular Endothelial Growth Factor Drugs on Ocular Blood Vessels and Blood Flow in Patients with Diabetic Retinopathy].

Diabetic retinopathy(DR)is the major microvascular disease in diabetic patients,and it is also one of the main blinding eye diseases in the current population.The typical pathological change of DR in the eyes is vascular endothelial growth factor(VEGF)-mediated neovascularization induced by retinal ischemic stimulation.Therefore,anti-VEGF drugs have gradually become one of the mainstream methods to treat DR and DR-induced diseases such as diabetic macular edema.Recent studies have proved that anti-VEGF drugs have certain effects on ocular blood vessels and blood flow in patients with DR,while the specific mechanism has not been fully elucidated.This article summarizes the research progress on the effects of intravitreal injection of anti-VEGF drugs on the ocular blood vessels and blood flow in patients with DR.

miR-21 regulates ischemic neuronal injury via the p53/Bcl-2/Bax signaling pathway.

Focal cerebral ischemia leads to a large number of neuronal apoptosis, and secondary neuronal death is the main cause of cerebral infarction. MicroRNA-21 (miR-21) has been shown to be a strong anti-apoptosis and pro-survival factor in ischemia. However, the precise mechanism of miR-21 in ischemic neuroprotection remains largely unknown. In this study, miR-21 was down-regulated while p53 was up-regulated following ischemia in vitro and in vivo. Overexpression of miR-21 in vitro and in vivo substantially inhibited the expression of p53 following ischemia, while inhibition of miR-21 in vitro and in vivo promoted p53 expression following ischemia. Moreover, the miR-21/p53 axis regulated the expression of Bcl-2/Bax and abolished OGD/R-induced neuronal injury in vitro. Furthermore, overexpression of miR-21 in vivo reduced neuronal death, protected against ischemic damage, and improved neurological functions by inhibiting p53/Bcl-2/Bax signaling, while inhibition of miR-21 enhanced the p53/Bcl-2/Bax signaling and aggravated the ischemic neuronal injury in vivo. Our data uncover a novel mechanism of miR-21 in regulating cerebral ischemic neuronal injury by inhibiting p53/Bcl-2/Bax signaling pathway, which suggests that miR-21/p53 may be attractive therapeutic molecules for treatment of ischemic stroke.

Central Role of T Follicular Helper Cells in Myasthenia Gravis.

Myasthenia gravis (gMG) is a critical autoimmune disease, which has a serious impact on the life and survival of patients. Ocular Myasthenia Gravis (oMG) is often the initial manifestation of MG and has the potential to progress to gMG. However, to date no distinct mechanism has been found to clarify the pathogenesis of conversion from oMG to gMG. Recent studies have shown that the development and clinical progression of MG is closely associated with the abnormal function of follicular helper T (Tfh) cells. Thus, this article reviews the recently achieved research progress on the involvement of Tfh cells in MG immunopathogenesis and focuses on the role of Tfh cells and related-factors (IL-21, CXCL13, CXCR5, bcl-6 etc.) in germinal center formation and antibody production in MG immune response.

1-O-Hexyl-2,3,5-Trimethylhydroquinone Ameliorates the Development of Preeclampsia through Suppression of Oxidative Stress and Endothelial Cell Apoptosis.

1-O-Hexyl-2,3,5-trimethylhydroquinone (HTHQ), a potent nuclear factor-E2-related factor 2 (Nrf2) activator, has potent antioxidant activity by scavenging reactive oxygen species (ROS). However, the role of HTHQ on the development of preeclampsia (PE) and the underlying mechanisms have barely been explored. In the present study, PE model was induced by adenovirus-mediated overexpression of soluble fms-like tyrosine kinase 1 (sFlt-1) in pregnant mice. The results showed that HTHQ treatment significantly relieved the high systolic blood pressure (SBP) and proteinuria and increased the fetal weight and fetal weight/placenta weight in preeclamptic mice. Furthermore, we found that HTHQ treatment significantly decreased soluble endoglin (sEng), endothelin-1 (ET-1), and activin A and restored vascular endothelial growth factor (VEGF) in preeclamptic mice. In addition, HTHQ treatment inhibited oxidative stress and endothelial cell apoptosis by increasing the levels of Nrf2 and its downstream haemoxygenase-1 (HO-1) protein. In line with the data in vivo, we discovered that HTHQ treatment attenuated oxidative stress and cell apoptosis in human umbilical vein endothelial cells (HUVECs) following hypoxia and reperfusion (H/R), and the HTHQ-mediated protection was lost after transfected with siNrf2. In conclusion, these results suggested that HTHQ ameliorates the development of preeclampsia through suppression of oxidative stress and endothelial cell apoptosis.

Cancer photo-immunotherapy: from bench to bedside.

Targeted therapy and immunotherapy in combination is considered the ideal strategy for treating metastatic cancer, as it can eliminate the primary tumors and induce host immunity to control distant metastases. Phototherapy, a promising targeted therapy, eradicates primary tumors using an appropriate dosage of focal light irradiation, while initiating antitumor immune responses through induced immunogenic tumor cell death. Recently, phototherapy has been employed to improve the efficacy of immunotherapies such as chimeric antigen receptor T-cell therapy and immune checkpoint inhibitors. Phototherapy and immunoadjuvant therapy have been used in combination clinically, wherein the induced immunogenic cell death and enhanced antigen presentation synergy, inducing a systemic antitumor immune response to control residual tumor cells at the treatment site and distant metastases. This review summarizes studies on photo-immunotherapy, the combination of phototherapy and immunotherapy, especially focusing on the development and progress of this unique combination from a benchtop project to a promising clinical therapy for metastatic cancer.

The prognostic value of tumor-stromal ratio combined with TNM staging system in esophagus squamous cell carcinoma.

Background: Tumor stroma is a crucial component of the tumor environment that interacted with tumor cells and modulated tumor cell proliferation, immune evasion, and metastasis. Tumor-stromal ratio (TSR) has been confirmed as an influential independent prognostic factor for diverse types of cancer, but it was seldom discussed in esophagus squamous cell carcinoma (ESCC). Methods: In present study, pathological sections from the most invasive part of the ESCC of 270 patients were analyzed for their TSR by visual inspection and software. The TSR was combined with the TNM staging system to further explain its predictive value of prognosis. The 57 cases ESCC from TCGA database also were included as an independently validated cohort. Results: Our results indicated that TSR was a robust prognostic factor for ESCC patients. TSR by visual inspection was dependable to reflect the stroma percent of the tumor compared to software calculation. Compared with stroma-low groups, the risk of death increased by 153.1% for patients in the stroma-high group [HR=2.531 (95%CI 1.657-3.867), P<0.001]. The results of ROC analysis in two cohorts indicated that TSNM staging system had better resolving ability with the largest area under the curve [0.698 95%CI (0.635-0.760), 0.691 95%CI (0.555-0.807)], compare to TNM. The novel TSNM staging system revealed strong predictive performance (P<0.001). Conclusion: TSR was a reliable dependent indicator for ESCC prognosis. The TSNM staging system has a better discriminative ability than the conventional TNM staging system, especially for III stage patients.

The Role of Serum Inflammation-Based Factors in Anti-Vascular Endothelial Growth Factor Treatment for Macular Edema Secondary to Retinal Vein Occlusion and Its Subtypes.

OBJECTIVE: The aim of this work was to evaluate the association between pretreatment inflammation-based factors and outcomes in patients with macular edema (ME) secondary to retinal vein occlusion (RVO) and its subtypes after intravitreal ranibizumab or conbercept implant. METHODS: This retrospective observational study included patients who were diagnosed with ME secondary to RVO at the First Affiliated Hospital of Nanchang University between January 2017 and January 2019, and who subsequently received intravitreal anti-vascular endothelial growth factor (VEGF) treatment. Blood-based parameters were measured before treatment, and correlations between best-corrected visual acuity (BCVA) and each of 3 parameters - neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) - were analyzed to identify predictors of effective intravitreal injection treatment outcomes. RESULTS: A total of 315 treatment-naïve eyes treated with anti-VEGF drugs for RVO-ME were retrospectively analyzed in this study. The mean PLR value was significantly different in the effective and ineffective group for RVO-ME (138.03 ± 48.61 vs. 106.79 ± 27.28), branch RVO (BRVO)-ME (216.47 ± 53.04 vs. 185.94 ± 51.47), and central RVO (CRVO)-ME (231.07 ± 66.05 vs. 196.20 ± 60.44). The cutoff value of the PLR was 97.92, the area under the curve was 0.70, and the sensitivity and specificity were 81.5 and 44.3%, respectively. The mean NLR value was significantly different in the effective and ineffective groups for RVO-ME (2.20 ± 1.40 vs. 1.92 ± 0.89), and BRVO-ME (2.01 ± 0.80 vs. 1.82 ± 0.84), but not in patients with CRVO-ME (2.51 ± 2.02 vs. 2.12 ± 0.95). There are no significant differences between BRVO-ME and its subtype groups in MLR values. But the mean MLR value was significantly higher in the conbercept group than in the ranibizu-mab group among patients in the effective group (0.27 ± 0.11 vs. 0.25 ± 0.14). CONCLUSION: Higher pretreatment PLR was associated with BCVA in patients with RVO-ME and its subtypes who were treated with anti-VEGF drugs. The PLR may be used as a predictive and prognostic tool for effective intravitreal injection treatment outcomes.