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Background The composition of the population of immune‐related long non‐coding ribonucleic acid (irlncRNA) generates a signature, irrespective of expression level, with potential value in predicting the survival status of patients with invasive breast carcinoma. Methods The current study uses univariate analysis to identify differentially expressed irlncRNA (DEirlncRNA) pairs from RNA‐Seq data from The Cancer Genome Atlas (TCGA). 36 pairs of DEirlncRNA pairs were identified. Using various algorithms to construct a model, we have compared the area under the curve and calculated the 5‐year curve of Akaike information criterion (AIC) values, which allows determination of the threshold indicating the maximum value for differentiation. Through cut‐off point to establish the optimal model for distinguishing high‐risk or low‐risk groups among breast cancer patients. We assigned individual patients with invasive breast cancer to either high risk or low risk groups depending on the cut‐off point, re‐evaluated the tumor immune cell infiltration, the effectiveness of chemotherapy, immunosuppressive biomarkers, and immunotherapy. Results After re‐assessing patients according to the threshold, we demonstrated an effective means of distinguish the severity of the disease, and identified patients with different clinicopathological characteristics, specific tumor immune infiltration states, high sensitivity to chemotherapy,wellpredicted response to immunotherapy and thus a more favorable survival outcome. Conclusions The current study presents novel findings regarding the use of irlncRNA without the need to predict precise expression levels in the prognosis of breast cancer patients and to indicate their suitability for anti‐tumor immunotherapy., The manuscript is an immune‐related lncRNA pairing strategy to construct a risk assessment model. We did not use precise expression levels of the target lncRNAs in the signature.

Background Compared with conventional open surgery, endoscopic thyroidectomy via the oral vestibular approach (ETVOA) and endoscopic thyroidectomy via the areola approach (ETAA) avoided scarring of the skin, which may help patients achieve a better quality of life (QOL). However, the benefit of the QOL from this technique has not been adequately investigated, therefore this study compared the QOL outcomes between ETVOA and ETAA. Methods 131 patients were enrolled in this study. ETAA surgery and ETVOA surgery were performed in 74 patients and 57 patients, respectively. These patients were followed up at 2 weeks, 4 weeks, and 8 weeks, and their QOL was evaluated using a thyroid surgery-specific questionnaire and a short-form health survey (SF-36). Results There were no differences in clinical characteristics such as gender, age, body mass index (BMI), and tumor size between the two groups. The volume of intraoperative blood loss, cost of hospitalization, and complications between the two procedures showed no differences. Compared with ETAA, ETVOA has a longer operation time, no drainage, and shorter hospital stay. In the QOL questionnaire, several parameters in ETVOA were better. The satisfaction scores of patients undergoing ETVOA were higher. In addition, the cosmetic satisfaction in patients who received ETOVA was significantly better than that of patients who underwent ETAA. The degree of neck movement disorder in patients with ETVOA was milder. Patients who received ETVOA had higher score on the SF-36. Conclusions The trans-oral endoscopic approach can acquire better cosmetic results and achieved high-level QOL.

Objective To determine the feasibility of endoscopic thyroidectomy with level Vb dissection using a chest-breast approach. Methods Lateral neck level Vb dissection by endoscopic surgery using a chest-breast approach was performed as an update to the previously reported endoscopic selective lateral neck dissection. The demographic data, surgical outcomes, and adverse events were analyzed. Results A total of 12 cases were performed successfully, and no patient was converted to the open procedure. The sex ratio was 16/2 (female/male). The average age and primary lesion diameter were 36.3±5.8 years old, and 1.97±0.58 cm, respectively. The average total and lateral lymph nodes dissection time of duration was 154.6±17.0 and 276.3±19.2 minutes, respectively. The lymph node ratio (mean number of metastasis/total number of dissected nodes) at levels II, III+IV, VI, and Vb were 1.6±1.4/6.8±2.0, 5.8±2.4/14.4±3.6, 3.2±1.1/6.5±1.9, and 0.8±0.9/5.8±1.6, respectively. One of 12 patients had lymphatic leakage and 2 of 12 patients had transient hypocalcemia. There was no incidence of uncontrolled bleeding, mental nerve injury, permanent hypoparathyroidism, permanent recurrent laryngeal nerve injury, skin bruise on neck, infection, asphyxia/dyspnea, large blood vessel injury or other complications like tracheal injury, esophageal injury, etc., nor was there any death or recurrence in either of the 2 groups during a short follow-up period. Conclusions It is feasible to perform endoscopic thyroidectomy with level Vb dissection using a chest-breast approach. Such strategy represents another option for selective papillary thyroid carcinoma patients with levels II, III, IV, and Vb lymph node metastasis.

PurposeThe present study aimed to evaluate the efficacy and safety of capsular thyroid injection therapy under ultrasound guidance for treating subacute thyroiditis.MethodsSeventy-three patients with subacute thyroiditis were divided into groups A (n=48) and B (n=25). Group A was treated with ultrasound-guided capsular injection consisting of a mixture of dexamethasone (DEX) and lidocaine in the thyroid lesion area, while patients in group B received oral prednisolone (PSL). The duration of pain relief, duration of treatment, time of thyroid function recovery, recurrence rates, hypothyroidism, and side effects between the two groups were compared.ResultsAfter 12 months of follow-up, the duration of pain relief, duration of treatment and thyroid function recovery in group A were significantly shorter than those in group B (P0.05). Weight gain in patients was significantly higher in group A than in group B at the end of treatment (P

Objectives: Long non-coding RNAs (lncRNAs) serve pivotal roles in heart disease, while the role of lncRNA hypoxia-inducible factor 1α-antisense RNA 1 (HIF1A-AS1) is rarely mentioned. Therefore, the objective of this study was to investigate the mechanism of lncRNA HIF1A-AS1 regulating suppressor of cytokine signaling 2 (SOCS2) expression by adsorption of microRNA-204 (miR-204) on ventricular remodeling after myocardial ischemia-reperfusion (I/R) injury in mice. Methods: The mouse model of I/R was established by left coronary artery occlusion. The expression of HIF1A-AS1, miR-204 and SOCS2 was determined. The mice were injected with HIF1A-AS1-siRNA, miR-204 mimics or their controls to investigate their effects on cardiac function and ventricular remodeling of mice after I/R injury. The binding relationship between HIF1A-AS1 and miR-204 as well as between miR-204 and SOCS2 were verified. Results: HIF1A-AS1 and SOCS2 were upregulated and miR-204 was downregulated in myocardial tissues in mice after I/R injury. LVEDD, LVEDS, LVEDP, LVMI and RVMI expression reduced while LVEF, LVFS, +dp/dt max and – dp/dt max increased through knockdown HIF1A-AS1 and upregulated miR-204. The expression of BNP, cTnI, LDH, CK, TNF-α, IL-1β, IL-6 and β-MHC reduced, and the expression of α-MHC increased when HIF1A-AS1 was poorly expressed and miR-204 was highly expressed. Silencing HIF1A-AS1 and upregulating miR-204 inhibited apoptosis of cells. LncRNA HIF1A-AS1 could act as ceRNA to adsorb miR-204 to suppress miR-204 expression and elevate SOCS2 expression. Conclusion: Our study provides evidence that downregulation of HIF1A-AS1 and upregulation of miR-204 could alleviate ventricular remodeling and improve cardiac function in mice after myocardial I/R injury via regulating SOCS2.

Multiple DNA repair pathways may be involved in the removal of the same DNA lesion caused by endogenous or exogenous agents. Although distinct DNA repair machinery fulfill overlapping roles in the repair of DNA lesions, the mechanisms coordinating different pathways have not been investigated in detail. Here, we show that Ku70, a core protein of nonhomologous end-joining (NHEJ) repair pathway, can directly interact with DNA polymerase-β (Pol-β), a central player in the DNA base excision repair (BER), and this physical complex not only promotes the polymerase activity of Pol-β and BER efficiency but also enhances the classic NHEJ repair. Moreover, we find that DNA damages caused by methyl methanesulfonate (MMS) or etoposide promote the formation of Ku70-Pol-β complexes at the repair foci. Furthermore, suppression of endogenous Ku70 expression by small interfering RNA reduces BER efficiency and leads to higher sensitivity to MMS and accumulation of the DNA strand breaks. Similarly, Pol-β knockdown impairs total-NHEJ capacity but only has a slight influence on alternative NHEJ. These results suggest that Pol-β and Ku70 coordinate 2-way crosstalk between the BER and NHEJ pathways.—Xia, W., Ci, S., Li, M., Wang, M., Dianov, G. L., Ma, Z., Li, L., Hua, K., Alagamuthu, K. K., Qing, L., Luo, L., Edick, A. M., Liu, L., Hu, Z., He, L., Pan, F., Guo, Z. Two-way crosstalk between BER and c-NHEJ repair pathway is mediated by Pol-β and Ku70.

Lactational breast abscess is a serious complication of mastitis and commonly diagnosed in breast‐feeding women. The traditional drainage of breast abscess was often performed with incisive technique which may result in prolonged healing time, regular dressings, dressing pain, interfering with breastfeeding and unsatisfactory cosmetic outcome. As minimal invasive alternatives to incisive drainage, needle aspiration or percutaneous catheter placement cannot completely replace incisive drainage for the inability to treat large, multiloculated or chronic abscess. Vacuum‐assisted breast biopsy system (VABB) has been successfully applied in the treatment of benign breast diseases with satisfactory cosmetic outcomes. Among VABB devices, EnCor system has some distinctive features that make it an appropriate candidate for the treatment of lactational breast abscesses. In this study, for the first time, we investigated the feasibility, efficacy, and cosmetic results of surgical drainage of lactational breast abscess with US‐guided Encor VABB system. Our data suggests this procedure could serve as a promising alternative for women with lactational breast abscess who require incisive intervention with high cure rate, relatively short healing time, low recurrence rate, few complications, satisfactory cosmetics outcome and without interfering with breastfeeding.

ObjectivesPrognostication of spinal cord injury (SCI) is vital, especially for critical patients who need intensive care. The study aims to develop machine-learning (ML) classifiers for discharge prediction of SCI patients in the intensive care unit (ICU).MethodsClinical data of patients diagnosed with SCI were extracted from the publicly available ICU database. A total of 105 ML classifiers were initially developed to predict the discharge destination (dead, further medical care, home), and then the top 3 classifiers with the best performance were stacked into an ensemble classifier (Esb-Clf). To balance the accuracy and the feasibility, the complete Esb-Clf was finally simplified with top 10 features (simplified Esb-Clf). The micro-average area under the curve (AUC) was used to compare the prediction performance of difference ML classifiers and 6 doctors’ artificial prediction.ResultsA total of 1485 SCI patients were used for the early and the recent prediction of discharge destination. In the early prediction, the micro-average AUC of the Esb-Clf and the simplified Esb-Clf was 0.846 and 0.835 during the independent testing, respectively. While in the recent prediction, the micro-average AUC of the Esb-Clf and the simplified Esb-Clf was 0.898 and 0.892. Performance of both the Esb-Clf and the simplified Esb-Clf were superior to the doctors’ in the early and the recent prediction.ConclusionsML classifiers can discriminate the discharge destination of SCI patients with high accuracy, feasibility and interpretability. Whether the simplified Esb-Clf as an online predictive tool is applicable to guiding clinical management needs further verification.

Background: Breast cancer (BC) surpassed lung cancer as the most frequent malignant tumour in women. In recent years, pyroptosis has revealed itself as an inflammatory form of programmed cell death. However, it is unclear as to the expression of genes associated with pyroptosis in BC and its relationship to prognosis. Results: In this study, we identified 31 pyroptosis regulators that are differentially expressed between BC and normal breast. The differently expressed genes (DEG) allow BC patients to be divided into three subtypes. Through single-factor and multi-factor COX regression and the application of least absolute contraction and selection operator (LASSO) Cox regression method, the survival prognostic value of each gene related to pyroptosis in The Cancer Genome Atlas (TCGA) cohort was evaluated, and a 4-gene signature was constructed. BC patients of the TCGA cohort are divided into low-risk or high-risk groups by risk score. The survival of the low-risk group was significantly higher than the high-risk group (P Conclusions: In conclusion, pyroptosis-related genes are important for tumour immunity and can be used to predict the prognosis of BC.

OBJECTIVE: To compare the efficacy and safety of ultrasound-guided local injection of the mixture of dexamethasone(DEX) with lidocaine and oral prednisolone(PSL) in treating patients with subacute thyroiditis. METHODS: Ninety-three patients with subacute thyroiditis were divided into group A(n=48) and Group B(n=45). Group A was treated with ultrasound-guided subcapsular injection in thyroid lesion area, while group B was treated with oral medication. The pain relief time, the duration of treatment, thyroid function recovery, recurrence rate, concurrent hypothyroidism, and drug side effects were compared between the two groups. RESULTS: After 6 months of follow-up, the pain relief time, the duration of treatment and thyroid function recovery in group A were significantly shorter than those in group B (P

Background: Endoscopic thyroidectomy via the oral vestibular approach (ETVOA) and endoscopic thyroidectomy via the areola approach (ETAA) are becoming more favored in China. Compared with conventional open surgery, both methods avoid the scarring on the neck, but only ETVOA obviates scarring of the skin, which may helps patients achieve a better quality of life (QOL). However, the benefit of the QOL from this technique has not been adequately investigated, therefore this study compared the QOL outcomes between ETVOA and ETAA. Methods: We enrolled 131 patients in this study. ETAA surgery and ETVOA surgery were performed in 74 patients and 57 patients, respectively. These patients were followed up at 2 weeks, 4 weeks, and 8 weeks, and their QOL was evaluated using a thyroid surgery-specific questionnaire and a short-form health survey (SF-36). Results: There were no differences in clinical characteristics such as gender, age, body mass index (BMI), and tumor size between the two groups. The volume of intraoperative blood loss, cost of hospitalization, and complications between the two procedures showed no differences. Compared with ETAA, ETVOA has a longer operation time, no drainage, and shorter hospital stay. In the QOL questionnaire, several parameters in ETVOA were better. The satisfaction scores of patients undergoing ETVOA were higher. In addition, the cosmetic satisfaction in patients who received ETOVA was significantly better than that of patients who underwent ETAA. The degree of neck movement disorder in patients with ETVOA was milder. Patients who received ETVOA had higher score on the SF-36. Conclusions: Compared with ETAA, ETVOA can acquire better cosmetic results and make patients quick return to normal life.Patients who underwent ETVOA achieved high-level QOL.

With the growing popularity of endoscopic thyroid surgery for treatment of thyroid diseases, this study aimed to summarize our experience of endoscopic thyroidectomy (ETE), and evaluate the feasibility and safety of ETE, in our institute. Five hundred patients underwent ETE via the areola approach. The learning curve, clinicopathologic characteristics, cosmetic satisfaction, complications, and so on were analyzed. Among the 500 cases, 497 were successfully managed with ETE, and 3 were converted to open procedure. The score of cosmetic satisfaction, average operation time, tumor diameter, mean total intra-operative blood loss, hospital stay, drainage time, and age were 9.4 ± 0.5, 142 ± 20 min, 2.6 ± 1.2 cm, 34 ± 12 ml, 11.4 ± 3.6 days, 3.3 ± 0.7 days, and 44.2 ± 11.9 years, respectively. Pathological types of the tumor included papillary thyroid carcinoma (PTC; n = 87), nodular goiters (n = 283), follicular adenoma (n = 84), and others (n = 46). The complications included transient recurrent laryngeal nerve (RLN) palsy (n = 15, 3.0%), transient superior laryngeal nerve (SLN) palsy (n = 3, 0.6%), transient hypoparathyroidism (n = 32, 6.4%), tracheal injury (n = 1, 0.2%), swallowing discomfort (n = 20, 4.0%), infection (n = 7, 1.4%), and others (n = 15, 3.0%). No patients experienced permanent RLN injury or SLN injury, asphyxia/dyspnea, esophagus injury, bleeding, chylous fistula, or death. Among the cases of PTC, 76 (87.4%) cases underwent the central lymph node dissection. The mean number of retrieved lymph nodes was 6.4 ± 2.1, while the mean number of metastatic central lymph nodes was 1.2 ± 2.3. The ratios of capsule invasion, central lymph node metastasis, and extrathyroidal extension were 10.3, 26.4, and 3.4%. ETE via areola approach is safe, feasible, and cosmetic, with good operative results and low complication rates. It provides an effective choice for treating patients.

Studies on cervical cancer are urgently required to improve clinical outcomes. As a major anticancer drug for cervical cancer, paclitaxel has been used for many years in clinical therapy but its therapeutic efficacy is limited by common obstacle from cancer cells. The enhanced DNA repair pathways of cancer cells have been proved to survive DNA damage induced by chemotherapeutic drug. Inhibitors of specific DNA repair pathway can sensitize cancer cells to the treatment of chemotherapeutic drugs. In this paper we found that the effect of paclitaxel can be significantly improved when used in combination with FEN1 inhibitor SC13, suggesting a synergistic mechanism between the two compounds. Our studies suggest that FEN1 inhibition could be a novel strategy of tumor-targeting therapy for cervical cancer. Our work also revealed that paclitaxel demonstrates stronger synergistic effect with SC13 than other common used chemical drugs such as doxorubicin, carboplatin or camptothecin on cervical cancer cells.

microRNAs (miRNAs) usually act post-transcriptionally to suppress the expression of many targeted genes. However, the response of miRNAs to nanoplastics is still unclear. We here employed Caenorhabditis elegans to investigate the response of miRNAs to 100 nm nanopolystyrene at a predicted environmental concentration (1 μg/L). After exposure from L1-larvae to adult day-3, we found that 7 miRNAs (4 down-regulated (mir-39, mir-76, mir-794, and mir-1830) and 3 up-regulated (mir-35, mir-38, and mir-354)) were dysregulated by nanopolystyrene. Expressions of these 7 miRNAs were dose-dependent in nematodes exposed to 1–100 μg/L nanopolystyrene. Among these 7 miRNAs, we found that only mir-35, mir-38, mir-76, mir-354, and mir-794 were involved in the regulation of response to nanopolystyrene based on phenotypic analysis of both transgenic strains and mutant nematodes. Overexpression of mir-35, mir-38, or mir-354 induced a resistance to nanopolystyrene toxicity, and overexpression of mir-76 or mir-794 induced a susceptibility to nanopolystyrene toxicity, which suggested that these 5 miRNAs mediated a protective response to nanopolystyrene. Gene ontology and KEGG analysis further implied that mir-35, mir-38, mir-76, mir-354, and mir-794 were associated with various biological processes and signaling pathways. Our results suggest the crucial role of a certain number of miRNAs in response to nanopolystyrene after long-term and low-dose exposure in organisms.

Protein methylation has an important role in the regulation of chromatin, gene expression and regulation. The protein methyl transferases are genetically altered in various human cancers. The enzymes that remove histone methylation have led to increased awareness of protein interactions as potential drug targets. Specifically, Lysine Specific Demethylases (LSD) removes methylated histone H3 lysine 4 (H3K4) and H3 lysine 9 (H3K9) through formaldehyde-generating oxidation. It has been reported that LSD1 and its downstream targets are involved in tumor-cell growth and metastasis. Functional studies of LSD1 indicate that it regulates activation and inhibition of gene transcription in the nucleus. Here we made a discussion about the summary of histone lysine demethylase and their functions in various human cancers.

Lung cancer is one of the leading causes of cancer mortality worldwide. The therapeutic effect of chemotherapy is limited due to the resistance of cancer cells, which remains a challenge in cancer therapeutics. In this work, we found that flap endonuclease 1 (FEN1) is overexpressed in lung cancer cells. FEN1 is a major component of the base excision repair pathway for DNA repair systems and plays important roles in maintaining genomic stability through DNA replication and repair. We showed that FEN1 is critical for the rapid proliferation of lung cancer cells. Suppression of FEN1 resulted in decreased DNA replication and accumulation of DNA damage, which subsequently induced apoptosis. Manipulating the amount of FEN1 altered the response of lung cancer cells to chemotherapeutic drugs. A small-molecule inhibitor (C20) was used to target FEN1 and this enhanced the therapeutic effect of cisplatin. The FEN1 inhibitor significantly suppressed cell proliferation and induced DNA damage in lung cancer cells. In mouse models, the FEN1 inhibitor sensitized lung cancer cells to a DNA damage-inducing agent and efficiently suppressed cancer progression in combination with cisplatin treatment. Our study suggests that targeting FEN1 may be a novel and efficient strategy for a tumor-targeting therapy for lung cancer.

In the environment, nanoplastic particles, such as nanopolystyrene, potentially cause toxicity on organisms at various aspects. We here employed endpoints of lifespan and aging-related phenotypes to further investigate the possible long-term effects of nanopolystyrene (100 nm) in Caenorhabditis elegans. After exposure from L1-larvae to adult day-3, nanopolystyrene at high concentrations (100 and 1000 μg/L) reduced the lifespan. Although nanopolystyrene (1 or 10 μg/L) did not affect the lifespan, nanopolystyrene (1 or 10 μg/L) could induce the more severe intestinal reactive oxygen species (ROS) production and decrease in locomotion behavior during the aging process compared with control. Moreover, nanopolystyrene exposure could cause the severe decrease in expressions of some immune response genes, hsp-6 gene, and genes encoding manganese-superoxide dismutases (Mn-SODs) during aging process, suggesting the severe suppression in innate immune response, inhibition in antioxidation defense system, and suppression in mitochondrial unfolded protein response (mt UPR) by nanopolystyrene. Our results highlight the potential of long-term nanopolystyrene exposure in reducing longevity and in affecting health state during the aging process in environmental organisms.

Caenorhabditis elegans is an important non-mammalian alternative assay model for toxicological study. Previous study has indicated that exposure to multi-walled carbon nanotubes (MWCNTs) dysregulated the transcriptional expression of mir-259. In this study, we examined the molecular basis for mir-259 in regulating MWCNTs toxicity in nematodes. Mutation of mir-259 induced a susceptible property to MWCNTs toxicity and MWCNTs exposure induced a significant increase in mir-259::GFP in pharyngeal/intestinal valve and reproductive tract, implying that mir-259 might mediate a protection mechanisms for nematodes against MWCNTs toxicity. RSKS-1, a putative ribosomal protein S6 kinase, acted as the target for mir-259 in regulating MWCNTs toxicity and mutation of rsks-1 suppressed the susceptible property of mir-259 mutant to MWCNTs toxicity. Moreover, mir-259 functioned in pharynx-intestinal valve and RSKS-1 functioned in pharynx to regulate MWCNTs toxicity. Furthermore, RSKS-1 regulated MWCNTs toxicity by suppressing the function of AAK-2-DAF-16 signaling cascade. Our results will strengthen our understanding the microRNAs mediated protection mechanisms for animals against the toxicity from certain nanomaterials.

The screenshots of the pathway enrichment analysis results based on the 309 target proteins of drug ZINC218147572 and the set of 681 aging-related genes in GenAge, respectively. (DOCX 383 kb)

The present study examined plasma lipid profiles in thirty patients suffered from acute viral hepatitis. Patients' blood samples were collected at both the debut and recovery of diseases. Thirty sex and age matched normal subjects were included as controls. Plasma total triglycerides (TG), total cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein AI (ApoAI), apolipoprotein B (ApoB), lipoprotein (a) (Lp(a)), blood coagulation status including prothrombin complex activity and activated partial tromboplastin time (APTT), and hepatic functions were determined by the automatic biochemical analytical instrument. It demonstrated that plasma levels of total cholesterol, HDL-C and apoAI were significantly lower in the patients at the acute phase of hepatitis than those in normal subjects, whereas plasma levels of TG and LDL-C were obviously higher in the patients than in normal subjects (P < 0.05). Moreover, we demonstrated that patients' plasma levels of total cholesterol, LDL-C, HDL-C and apoAI were lower at the active phase of the diseases than at the recovering phase, which indicating that acute liver damage could significant influence lipid metabolism in vivo. No pathological changes of blood coagulation status occurred in these patients during the study as all selected patients had moderate hepatitis. It may conclude that examinations of plasma lipid profile could be considered as a clinical index to reflect liver damage in the active phase of hepatitis.