CircFAM64A enhances cellular processes in triple-negative breast cancer by targeting the miR-149-5p/CDT1 axis.

Triple-negative breast cancer (TNBC) is a breast cancer subtype without targeted treatment options. Accumulating evidence has demonstrated the roles of circular RNAs in cancer. This study aimed to investigate the expression and function of circFAM64A in TNBC. The GSE101124 dataset from the GEO database was examined to identify the differentially expressed circular RNAs in TNBC. RT-qPCR and western blot analyses were performed to measure gene expression. TNBC cell proliferation, migration, invasion, and cell cycle were assessed using cell counting kit-8, EdU, flow cytometry, wound healing, and transwell invasion experiments. Bioinformatics analysis, RIP, RNA pulldown, and luciferase reporter assays were used to investigate the regulatory mechanism of circFAM64A. In this study, CircFAM64A expression was significantly upregulated in TNBC tissues and cells compared with normal tissues and cells. Overexpression of circFAM64A increased the proliferative, migratory, and invasive capacities of TNBC cells and promoted cell cycle progression. Mechanistically, circFAM64A acted as a molecular sponge for miR-149-5p, and miR-149-5p directly targeted the Cdc10-dependent transcript 1 (CDT1) 3'UTR. Moreover, the high expression of CDT1 is associated with a poor prognosis in patients with breast cancer. Rescue experiments demonstrated that circFAM64A sponged miR-149-5p to increase CDT1 expression, thereby promoting cellular processes in TNBC. Overall, CircFAM64A plays an oncogenic role in TNBC by interacting with miR-149-5p to increase CDT1 expression.

Tumor-derived biomimetic nanozyme with immune evasion ability for synergistically enhanced low dose radiotherapy.

High doses of radiation can cause serious side effects and efficient radiosensitizers are urgently needed. To overcome this problem, we developed a biomimetic nanozyme system (CF) by coating pyrite (FeS2) into tumor-derived exosomes for enhanced low-dose radiotherapy (RT). CF system give FeS2 with immune escape and homologous targeting abilities. After administration, CF with both glutathione oxidase (GSH-OXD) and peroxidase (POD) activities can significantly lower the content of GSH in tumor tissues and catalyze intracellular hydrogen peroxide (H2O2) to produce a large amount of ·OH for intracellular redox homeostasis disruption and mitochondria destruction, thus reducing RT resistance. Experiments in vivo and in vitro showed that combining CF with RT (2 Gy) can provide a substantial suppression of tumor proliferation. This is the first attempt to use exosomes bionic FeS2 nanozyme for realizing low-dose RT, which broaden the prospects of nanozymes.

Diagnostic accuracy of ultrasonographic features for lymph node metastasis in papillary thyroid microcarcinoma: a single-center retrospective study.

BACKGROUND: Whether sonography is an appropriate imaging modality for cervical lymph nodes in patients with papillary thyroid microcarcinoma (PTMC) remains unclear. Hence, this study aimed to evaluate the diagnostic value of ultrasonography (US) features for lymph node metastasis in PTMC. METHODS: Seven hundred twelve patients with PTMC who underwent conventional ultrasonography examinations of the cervical lymph nodes were included. All included cases underwent total thyroidectomy plus prophylactic central lymph node dissection. The included lymph nodes were marked superficially, and the corresponding lymph nodes were completely removed and sent for pathological examination. The US features of lymph nodes with and without metastasis were compared, and the odds ratios of the suspicious US features were determined with univariate and multivariate analyses. RESULTS: Round shape, loss of an echogenic fatty hilum, cystic change, calcification, and abnormal vascularity were significantly more common in metastatic than nonmetastatic lymph nodes, whereas the boundary and echo did not significantly differ. Multivariate logistic regression analysis showed that round shape, loss of echogenic fatty hilum, cystic change, calcification, and abnormal vascularity were independent predictive factors for the assessment of metastatic lymph nodes. Round shape had the highest sensitivity of all variables, while loss of an echogenic fatty hilum had the highest specificity and accuracy. The area under the receiver operating characteristic curve, which was calculated to verify the relationship between the various US features and metastatic lymph nodes, was 0.793. CONCLUSIONS: Our study found that the US features of round shape, cystic change, calcification, loss of echogenic fatty hilum, and abnormal vascularity were useful sonographic criteria for differentiating between cervical lymph nodes with and without metastasis.

Treatment for papillary thyroid microcarcinoma.

AIM OF THE STUDY: The treatment for papillary thyroid microcarcinoma (PTMC), which is a tumor measuring less than 1 cm, is still a subject of controversy. The aim of this study is to retrospectively evaluate the patients diagnosed with PTMC in terms of their clinical and histopathological features. MATERIAL AND METHODS: A total of 153 consecutive patients with PTMC were treated, and their clinical and histopathological characteristics were reviewed. The tumor diameter was observed to range from 1.0 mm to 10 mm (mean of 5.8 mm). Histologically, 138 (90.2%) cases of classical papillary carcinoma and 15 (9.8%) cases of the follicular variant were noted. Multicentric tumors were found in 37 (24.2%) patients, of whom 12 (7.8%) had more than one PTMC on the same side and 25 (16.3%) displayed bilateral PTMC. RESULTS: The proportions of capsular invasion and lymph node metastasis were 11.8% (18/153) and 48.1% (39/81), respectively. One patient showed distant metastasis during follow-up and died fifteen months after the operation. PTMC showed a high incidence of multifocality and lymph node metastasis in the level VI central compartment. The optimal surgical strategy for PTMC was total thyroidectomy and central compartment node dissection. CONCLUSIONS: Frozen tissue sections should be made for the prompt diagnosis of PTMC in all the thyroid nodules, except when the malignant diagnosis was already confirmed by cytology.

Cu-Hemin Nanosheets and Indocyanine Green Co-Loaded Hydrogel for Photothermal Therapy and Amplified Photodynamic Therapy.

Near-infrared (NIR) organic small molecule indocyanine green (ICG) could respond well to 808 nm laser to promote local high temperature and ROS generation for realizing photothermal therapy (PTT)/photodynamic therapy (PDT). However, the high content of GSH in the tumor microenvironment (TME) limited the further therapeutic performance of ICG. Herein, injectable agarose in situ forming NIR-responsive hydrogels (CIH) incorporating Cu-Hemin and ICG were prepared for the first time. When CIH system was located to the tumor tissue through local injection, the ICG in the hydrogel could efficiently convert the light energy emitted by the 808 nm laser into thermal energy, resulting in the heating and softening of the hydrogel matrix, which releases the Cu-Hemin. Then, the over-expressed GSH in the TME could also down-regulated by Cu-Hemin, which amplified ICG-mediated PDT. In vivo experiments validated that ICG-based PDT/PTT and Cu-Hemin-mediated glutathione depletion could eliminate cancer tissues with admirable safety. This hydrogel-based GSH-depletion strategy is instructive to improve the objective response rate of PDT.

Nanozyme Hydrogels for Self-Augmented Sonodynamic/Photothermal Combination Therapy.

Sonosensitizer-mediated sonodynamic therapy (SDT) has emerged as a promising anti-tumor strategy. However, this strategy of continuous oxygen consumption further exacerbates the hypoxic tumor microenvironment, which limits its therapeutic efficacy. In this study, we designed a multifunctional hydrogel (PB+Ce6@Hy) that simultaneously co-delivers nanozyme prussian blue (PB) and sonosensitizer chlorin e6 (Ce6) for the realization of photothermal therapy (PTT) and enhanced SDT. When the hydrogel reaches the tumor tissue through local injection, the 808 nm laser can induce the hydrogel to warm up and soften, thereby triggering the release of PB and Ce6. PB can interact with endogenous H2O2 in situ and generate sufficient oxygen to promote the Ce6-mediated SDT effect. Besides, due to the good encapsulation ability of the hydrogel, the nanomaterials can be released in a controlled manner by changing laser parameter, irradiation time, etc. The experimental results show that the PB+Ce6@Hy system we developed can generate a large amount of reactive oxygen species (ROS), which can be combined with the photothermal effect to kill tumor cells, as a result, tumor proliferation has been adequately inhibited. This combined PTT/SDT dynamic strategy provides a new perspective for Ce6-induced cancer therapy, showing great potential for clinical application.

Case Report: Implantation of Dedifferentiated to Poorly Differentiated Thyroid Carcinoma After Endoscopic Thyroid Surgery.

Background: Endoscopic thyroidectomy is widely accepted for its advantages. However, implant metastasis remains a significant complication of endoscopic thyroidectomy. Methods: This is the first report of breast implantation diagnosed with poorly differentiated thyroid carcinoma following endoscopic thyroidectomy. Results: We present a case of a 35-year-old woman who was initially diagnosed with a 3.0 cm conventional papillary thyroid carcinoma after endoscopic thyroidectomy via total areola. Two years later, she was reported to have recurring poorly differentiated thyroid carcinoma in the right areola. Implantation after endoscopic thyroidectomy is rare, and even rarer is dedifferentiated papillary thyroid carcinoma around the implant site. Conclusions: Stringently evaluated endoscopic surgery indications, appropriate preoperative evaluation, meticulous surgical technique, and adequate protective measures can significantly reduce the incidence of local implantation or recurrence.

Injectable Hydrogel System for Camptothecin Initiated Nanocatalytic Tumor Therapy With High Performance.

Single photothermal therapy (PTT) has many limitations in tumor treatments. Multifunctional nanomaterials can cooperate with PTT to achieve profound tumor killing performance. Herein, we encapsulated chemotherapeutic drug camptothecin (CPT) and pyrite (FeS2) with dual enzyme activity (glutathione oxidase (GSH-OXD) and peroxidase (POD) activities) into an injectable hydrogel to form a CFH system, which can improve the level of intratumoral oxidative stress, and simultaneously realize FeS2-mediated PTT and nanozymes catalytic treatment. After laser irradiation, the hydrogel gradually heats up and softens under the photothermal agent FeS2. The CPT then released from CFH to tumor microenvironment (TME), thereby enhancing the H2O2 level. As a result, FeS2 can catalyze H2O2 to produce ·OH, and cooperate with high temperature to achieve high-efficiency tumor therapy. It is worth noting that FeS2 can also deplete excess glutathione (GSH) in the cellular level, further amplifying oxidative stress. Both in vivo and in vitro experiments show that our CFH exhibits good tumor-specific cytotoxicity. The CFH we developed provides new insights for tumor treatment.

The Delineation and Ecological Connectivity of the Three Parallel Rivers Natural World Heritage Site.

Landscape connectivity refers to the degree of continuity between the spatially structured units of a landscape. Ecological connectivity can characterise the degree to which ecological functional areas are connected in terms of function and ecological processes. In this study, the landscape pattern index and ecosystem service values were used to evaluate the ecological functional resistance of each landscape type, taking the Three Parallel Rivers Natural World Heritage Site as an example and the habitat distribution and population size of the Yunnan snub-nosed monkey as a reference. The minimum cost distance model, combined with the barrier impact index (BEI) and ecological connectivity index (ECI), was used to determine the degree of barrier impact on the study area and the ecological connectivity of the core reserve of the heritage site in both 2000 and 2020. The resistances of the different land types and landscape heterogeneity to the ecological function of species migration between the core protected areas of the heritage site were, in descending order, those of the forest, shrubs and grass, water, unused land, cultivated land, and built-up land. In 2020, the study area had a large BEI, with areas such as built-up areas, major roads, the sides of large rivers, and arable land being significant contributors to the blockage of landscape connectivity. The overall landscape connectivity in the study area was generally low, with clear spatial differentiation and a three-column parallel distribution pattern influenced by the topography and landscape. With the adjustment of the core reserve boundaries of the heritage site, the proportion of areas with high connectivity (ECI = 4-5) increased from 11.31% in 2000 to 34.36% in 2020. This increased landscape connectivity was conducive to the migration and reproduction of large terrestrial animals, such as the Yunnan snub-nosed monkey, with increasing numbers of populations and individuals. This study provides theoretical and methodological insights into the delineation and conservation of natural heritage sites and landscape connectivity.

TSH-TSHR axis promotes tumor immune evasion.

BACKGROUND: Hormones are identified as key biological variables in tumor immunity. However, previous researches mainly focused on the immune effect of steroid hormones, while the roles that thyroid-stimulating hormone (TSH) played in the antitumor response were far from clear. METHODS: The source of TSH was determined using single-cell transcriptomic, histologic, quantitative PCR, and ELISA analysis. The influence of TSH on tumor proliferation, invasion, and immune evasion was evaluated in multiple cell lines of thyroid cancer, glioma, and breast cancer. Then transcriptomic sequencing and cellular experiments were used to identify signaling pathways. TSH receptor (TSHR) inhibitor was injected into homograft mouse tumor models with or without anti-programmed cell death protein-1 antibody. RESULTS: Monocyte-derived dendritic cells (moDCs) highly expressed TSHα and TSHß2 and were the primary source of TSH in the tumor microenvironment. TSH released by moDCs promoted proliferation and invasion of tumors with high TSHR expressions, such as thyroid cancers and glioma. TSH also induced tumor programmed death-ligand 1 (PD-L1) expression through the TSHR-AC-PKA-JNK-c-JUN pathway. TSHR inhibitors reversed tumor immune evasion by inhibiting PD-L1 expression in tumor and myeloid cells and enhancing Teff activation. CONCLUSIONS: TSH-TSHR axis promotes tumor evasion in thyroid cancers and glioma. TSH suppression therapy is an effective therapeutic strategy for combination in immune checkpoint blockades.

SnFe2O4 Nanozyme Based TME Improvement System for Anti-Cancer Combination Thermoradiotherapy.

High doses of radiotherapy (RT) are associated with resistance induction. Therefore, highly selective and controllable radiosensitizers are urgently needed. To address this issue, we developed a tin ferrite (SFO)-based tumor microenvironment (TME)-improved system (SIS) that can be used in combination with low-dose radiation. The SIS was delivered via intratumoral injection directly to the tumor site, where it was stored as a ration depot. Due to the photothermal properties of SFO, SIS steadily dissolved under near-infrared (NIR) laser irradiation. Simultaneously, the dual glutathione oxidase (GSH-OXD) and catalase (CAT) activities of the SFO nanozyme significantly lowered the content of GSH in tumor tissues and efficiently catalyzed the conversion of intracellular hydrogen peroxide to produce a large amount of oxygen (O2) for intracellular redox homeostasis disruption, thus reducing radiotherapy resistance. Our in vivo and in vitro studies suggested that combining the SIS and NIR irradiation with RT (2Gy) significantly reduced tumor proliferation without side effects such as inflammation. To conclude, this study revealed that SFO-based nanozymes show great promise as a catalytic, radiosensitizing anti-tumor therapy.

LRP6 as a biomarker of poor prognosis of breast cancer.

BACKGROUND: Recently, low-density lipoprotein receptor (LDLR)-related protein 6 (LRP6) has been the focus of molecular targeted therapy for breast cancer; however, its role in breast cancer is still controversial. The purpose of this study was to investigate the effect of LRP6 overexpression on the prognosis of breast cancer. METHODS: We used immunohistochemistry to detect the expression of LRP6 via tissue microarrays in breast cancer samples, Chi-square test analyze the relationship between LRP6 expression and clinicopathological features of breast cancer, the Kaplan-Meier method to perform survival analysis, and the Cox proportional hazards regression model to explore the potential risk factors of breast cancer. The role of LRP6 in the proliferation, invasion, and metastasis of breast cancer was studied by colony formation, Transwell migration and invasion assay and scratch assay. The tumor-bearing model of LRP6 knockdown was established using MCF-7 cells, and corresponding negative control was set up to observe the growth rate of the two models. RESULTS: High expression of LRP6 was observed in 89 out of 150 (59.3%) breast cancer cases, as detected by microarray of breast cancer tissue. Chi-square tests showed no significant correlation between LRP6 expression and tumor size, lymph node staging, or mitosis. Survival analysis showed that the overall survival rate of tumor patients with high LRP6 expression was significantly lower than that of patients with low LRP6 expression. Univariate and multivariate regression analyses revealed that LRP6 was an independent risk factor for breast cancer and was negatively correlated with the prognosis of breast cancer. Compared with the control group, small interference RNA (si-RNA) knockdown of LRP6 significantly reduced the clonogenic rate as well as the migration and invasion abilities of MCF-7 cells. In the scratch experiment, the wound healing ability of the LRP6 knockdown was significantly weaker than that of the control group. There were significant differences in tumor growth weight and volume between lentivirus transfected LRP6 knockdown MCF-7 cell line and control MCF-7 cell line in nude mice. CONCLUSIONS: LRP6 could be a useful biomarker of poor prognosis of breast cancer, as it plays an important role in tumor growth, migration, and invasion.

The diagnostic value of a non-contrast computed tomography scan-based radiomics model for acute aortic dissection.

ABSTRACT: To investigate the diagnostic value of a computed tomography (CT) scan-based radiomics model for acute aortic dissection.For the dissection group, we retrospectively selected 50 patients clinically diagnosed with acute aortic dissection between October 2018 and November 2019, for whom non-contrast CT and CT angiography images were available. Fifty individuals with available non-contrast CT and CT angiography images for other causes were selected for inclusion in the non-dissection group. Based on the aortic dissection locations on the CT angiography images, we marked the corresponding regions-of-interest on the non-contrast CT images of both groups. We collected 1203 characteristic parameters from these regions by extracting radiomics features. Subsequently, we used a random number table to include 70 individuals in the training group and 30 in the validation group. Finally, we used the Lasso regression for dimension reduction and predictive model construction. The diagnostic performance of the model was evaluated by a receiver operating characteristic (ROC) curve.Fourteen characteristic parameters with non-zero coefficients were selected after dimension reduction. The accuracy, sensitivity, specificity, and area under the ROC curve of the prediction model for the training group were 94.3% (66/70), 91.2% (31/34), 97.2% (35/36), and 0.988 (95% confidence interval [CI]: 0.970-0.998), respectively. The respective values for the validation group were 90.0% (27/30), 94.1% (16/17), 84.6% (11/13), and 0.952 (95% CI: 0.883-0.986).Our non-contrast CT scan-based radiomics model accurately facilitated acute aortic dissection diagnosis.

Reevaluation of Criteria and Establishment of Models for Total Thyroidectomy in Differentiated Thyroid Cancer.

INTRODUCTION: After the publication of the 2015 American Thyroid Association (ATA) guidelines, the indication for total thyroidectomy (TT) was reported to be underestimated before surgery, which may lead to a substantial rate of secondary completion thyroidectomy (CTx). METHODS AND MATERIALS: We retrospectively analyzed differentiated thyroid cancer patients from Wuhan Union Hospital (WHUH). Univariate analysis was performed to evaluate all preoperative and intraoperative factors. New models were picked out by comminating and arranging all significant factors and were compared with ATA and National Comprehensive Cancer Network (NCCN) guidelines in the multicenter prospective Differentiated Thyroid Cancer in China (DTCC) cohort. RESULTS: A total of 5,331 patients from WHUH were included. Pre- and intraoperative criteria individually identified 906 (17.0%) and 213 (4.0%) patients eligible for TT. Among all factors, age <35 years old, clinical N1, and ultrasound reported local invasion had high positive predictive value to predict patients who should undergo TT. Accordingly, we established two new models that minorly revised ATA guidelines but performed much better. Model 1 replaced "nodule size >4 cm" with "age <35 years old" and achieved significant increase in the sensitivity (WHUH, 0.711 vs. 0.484; DTCC, 0.675 vs. 0.351). Model 2 simultaneously demands the presence of "nodule size >4 cm" and "age <35 years old," which had a significant increase in the specificity (WHUH, 0.905 vs. 0.818; DTCC, 0.729 vs. 0.643). CONCLUSION: All high-risk factors had limited predictive ability. Our model added young age as a new criterion for total thyroidectomy to get a higher diagnostic value than the guidelines.

Clinical Characteristics-Assisted Risk Stratification for Extent of Thyroidectomy in Patients With 1-4 cm Solitary Intrathyroidal Differentiated Thyroid Cancer.

Background: Differentiated thyroid cancer (DTC) is the most common type of thyroid cancer. The 2015 American Thyroid Association (ATA) guidelines recommend that lobectomy is suitable for solitary intrathyroidal DTC (SI-DTC) of 1-4 cm. However, some SI-DTC patients with other high-risk characteristics still have poor prognosis and require more aggressive surgical methods. This study aimed to explore the clinical characteristics that are important for the identification and treatment of high-risk patients with SI-DTC of 1-4 cm. Methods: The study cohort was obtained from the SEER database, consisting of data between 2004 and 2013. The outcome measures were thyroid carcinoma-specific mortality (CSM) and all-cause mortality (ACM). Patient survival curves were examined using Kaplan-Meier analyses with log-rank tests and Cox proportional hazards regression analyses. Hazard ratios (HRs) were used to show the magnitude of the effect of disease stage on DTC-specific patient mortality. Results: The study included 55,947 patients with SI-DTC of 1-4 cm and 4,765 patients with DTC >4 cm. Tumor size, surgical approach, age, sex, race, and radiation exposure were independent risk factors for CSM and ACM. SI-DTC patients with female, age ≤45, and 1 cm< tumor size ≤2 cm were at low risk of CSM [HR = 0.014 (0.002-0.115)] and ACM [HR = 0.115 (0.077-0.171)] when stratified by age, sex, and tumor size. Compared to T3 patients, CSM was not significantly different in male patients, age >45, 2 cm< tumor size ≤3 cm [HR = 0.839 (0.414-1.700)] and male patients, age >45, 1 cm< tumor size ≤2 cm [HR = 0.751 (0.410-1.377)]. Furthermore, compared to T3 patients without extrathyroidal extension (ETE) and lymph node metastasis (LNM), more subgroups of SI-DTC of 1-4 cm had a similar prognosis. In addition, patients with SI-DTC of 1-4 cm showed similar rates of CSM and ACM to T3 patients without ETE, LNM, and distant metastasis (DM). Similar results were obtained when we set the age cut-off value as 55 years, according to the 8th edition of AJCC TNM system. Conclusions: Our study demonstrated that sex, age, and tumor size clearly differentiate SI-DTC of 1-4 cm into low-and high-risk categories. Survival rates were significantly lower in subgroups containing old males with larger tumors compared to younger females with small tumors. Total thyroidectomy may be favored in these high-risk subgroup patients.

Metaplastic breast cancer: Treatment and prognosis by molecular subtype.

BACKGROUND: Metaplastic breast cancer (MBC) is a rare and aggressive subtype of breast. However, the effect of molecular subtype on treatment and prognosis of MBC remains unclear. PATIENTS AND METHODS: The Surveillance, Epidemiology, and End Results database was used to analyze patients with MBC between 2010 and 2016. Molecular subtype was stratified to TN group (ER and PR-/HER2-), HER2 group (ER and PR-/HER2+, ER/PR+ and HER2+), and HR group (ER/PR+ and HER2-). The breast cancer-specific survival (BCSS) differences were estimated using multivariate Cox regression model and Kaplan-Meier curves. RESULTS: We included 1665 patients with median follow-up time of 27 months (range 0-83 months). 1154 (69.3%), 65 (3.9%), and 446 (26.8%) patients presented in TN group, HER2 group, and HR group, respectively. On multivariate Cox analysis, the prognosis was related to age, tumor size, regional node metastasis, and surgery. Molecular subtype remained no impact on BCSS. Radiotherapy (RT) was associated with better prognosis. Patients cannot benefit from chemotherapy. In Kaplan-Meier curve, triple-negative (P = 0.047) and HR-positive (P = 0.006) patients receiving RT had a superior BCSS than that not RT. HER2-positive patients cannot benefit from RT. However, adjusted Kaplan-Meier survival model showed that triple-negative (P = 0.019) but not HER2-positive (P = 0.575) or HR-positive (P = 0.574) patients receiving RT had a superior BCSS than that not RT. CONCLUSIONS: Molecular subtype is not associated with the better prognosis of MBC. Patients could benefit from RT. However, triple-negative but not HR-positive or HER2-positive patients have superior survival after receiving RT.

The biologically functional identification of a novel TIM3-binding peptide P26 in vitro and in vivo.

PURPOSE: Recent studies have shown that TIM3 plays an important role in T-cell failure, which is closely related to the resistance to anti-programmed cell death protein 1 (PD-1) treatment. However, there have been no reports on the application of peptide blockers to TIM3. In this study, we endeavored to identify the in vitro and in vivo anti-tumor activities of a TIM3-targeting peptide screened from the phage peptide library. METHODS: Phage display peptide library technology, surface plasmon resonance, flow cytometry, and mixed lymphocyte reaction were utilized to screen and demonstrate the bioactivities of P26, a TIM3-targeting peptide. Meanwhile, tumor growth assay was performed to evaluate the anti-tumor effect of P26. RESULTS: In terms of affinity, we demonstrated that P26 specifically binds to TIM3 at the cellular and molecular levels, which therefore blocks the interaction between TIM3 and Galectin-9 (Gal-9) and competes with Gal-9 to bind TIM3. Additionally, P26 significantly increases T-cell activity and elevates IFN-γ and IL-2 levels in a dose-dependent manner. Notably, P26 also counteracts Gal-9-mediated T-cell suppression. More importantly, P26 can inhibit growth of MC38-hPD-L1 tumor in mice. CONCLUSIONS: P26, as a novel TIM3-binding peptide, has the ideal bioactivity connecting to TIM3 and the potential prospect of application in immunotherapy as an alternative or adjuvant to existing agents.

Combination of serum lactate dehydrogenase and sex is predictive of severe disease in patients with COVID-19.

Elevated serum lactate dehydrogenase (LDH) was commonly reported in COVID-19 patients. However, the relationship between LDH and the incidence of severe cases has not been characterized in those patients.We retrospectively analyzed the characteristics of patients from a designated isolation medical center for COVID-19 patients diagnosed from February 6 to March 1. Variables accessed within 48 hours on admission were compared between patients with and without the severe disease. Logistic model analyses were performed to examine the prognostic value of LDH for predicting severe disease.52 (28.6%) patients later developed severe disease. Comparing to non-severe cases, severe cases had a higher level of serum LDH (321.85 ±â€Š186.24 vs 647.35 ±â€Š424.26, P < .001), neutrophils (5.42 ±â€Š3.26 vs 9.19 ±â€Š6.33, P < .001), and C-reactive protein (38.63 ±â€Š43.14 vs 83.20 ±â€Š51.01, P < .001). The patients with severe disease tended to be male (44.6% vs 80.8%, P < .001), lower level of serum albumin (31.41 ±â€Š6.20 vs 27.18 ±â€Š5.74, P < .001), and SpO2 (96.30 ±â€Š2.75 vs 92.37 ±â€Š8.29, P < .001). In the multivariate analysis model, LDH and sex remained independent risk factors for severe disease. The serum LDH predicted severe cases with an area under the curve (AUC) of 0.7999. A combination of serum LDH and sex predicted severe cases with an AUC of 0.849. A combination of serum LDH accessed on admission and sex had a better predictive performance than the serum LDH (P = .0238).Serum LDH on admission combined with sex is independently associated with severe disease in COVID-19.

Columnar cell papillary thyroid carcinoma prognosis: findings from the SEER database using propensity score matching analysis.

BACKGROUND: Columnar cell papillary thyroid carcinoma (CCPTC) is a rare variant of papillary thyroid carcinoma (PTC), whose prognosis, as defined by the American Thyroid Association (ATA) guidelines, is considered poor, although available evidence is insufficient for reliable assessment. This study aimed to investigate the CCPTC prognosis using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: Data of thyroid cancer patients, recorded from 2004 to 2013, were extracted to assess the CCPTC prognosis. All-cause and cancer-specific mortality rates associated with thyroid cancer types were evaluated using the Kaplan-Meier method and Cox proportional hazards regression. Propensity score matching analysis was used to adjust for potential confounders. RESULTS: Cancer-specific mortality per 1000 person-years was higher for CCPTC than for classic papillary thyroid cancer (CPTC) and follicular thyroid cancer (FTC). The multivariate Cox regression model revealed that the cancer-specific and all-cause mortality rates were higher for CCPTC than for CPTC but not FTC. However, propensity score matching analysis demonstrated a significantly lower survival for CCPTC than for both CPTC and FTC. CONCLUSIONS: Our findings provide evidence to support the poor prognosis associated with CCPTC. These findings may serve to improve the diagnosis of CCPTC, provide reliable reference data for clinical use, and increase the comprehensiveness of current guidelines.

Protective effects of dexmedetomidine on lung in rats with one-lung ventilation.

Protective effect of dexmedetomidine (DEX) on the lungs of one-lung ventilation (OLV) rat model and its effect on inflammatory factors were investigated. Ninety-two rats were selected and divided into groups A, B, C and D (n=23) according to the principle of similar body weight. OLV rat model was established. Before modeling (15 min), rats in group C were injected with sodium chloride. Rats in group D were injected with DEX at a speed of 5 µg/kg/h. Group A rats were ventilated in both lungs for 2 h. Rats in groups B and C (0.9% sodium chloride injection + OLV) and in group D (DEX + OLV) were subjected to OLV for 2 h and bilateral ventilation for 10 min. Concentrations of interleukin (IL)-6, IL-10 and tumor necrosis factor-α (TNF-α) in lung tissue of rats were detected by ELISA. The malondialdehyde (MDA) concentration and superoxide dismutase (SOD) activity in rat lung tissue were detected by radioimmunoassay. Wet weight (W)/dry weight (D) of lung tissue was calculated and indexes of the four groups of rats were compared. Compared with group A, IL-6, TNF-α and MDA concentrations and W/D of lung tissue of rats in groups B, C and D were significantly increased (p<0.05); SOD activity and IL-10 concentration were significantly decreased (p<0.01). Compared with groups B and C, the concentrations of IL-6, TNF-α and W/D in rats of group D were significantly decreased (p<0.01), but IL-10 significantly increased (p<0.01). Compared with groups B and C, the MDA concentration in lung tissue of rats in group D was significantly decreased (p<0.01), but SOD activity significantly increased (p<0.01). DEX can inhibit the production of inflammatory factors in the development and progression of pulmonary inflammation. It can inhibit lipid peroxidation, relieve pulmonary edema, and reduce lung injury after OLV, sin order to protect the lung.