Immune-related long noncoding RNA zinc finger protein 710-AS1-201 promotes the metastasis and invasion of gastric cancer cells.

BACKGROUND: Gastric cancer (GC) is a prevalent malignant tumor of the gastrointestinal system. ZNF710 is a transcription factor (TF), and zinc finger protein 710 (ZNF710)-AS1-201 is an immune-related long noncoding RNA (lncRNA) that is upregulated in GC cells. AIM: To assess the correlation between ZNF710-AS1-201 and immune microenvironment features and to investigate the roles of ZNF710-AS1-201 in the invasion and metastasis processes of GC cells. METHODS: We obtained data from The Cancer Genome Atlas and Wujin Hospital. We assessed cell growth, migration, invasion, and programmed cell death using cell counting kit-8, EdU, scratch, Transwell, and flow cytometry assays. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to identify the potential downstream targets of ZNF710-AS1-201. RESULTS: In GC tissues with low ZNF710-AS1-201 expression, immunoassays detected significant infiltration of various antitumor immune cells, such as memory CD8 T cells and activated CD4 T cells. In the low-expression group, the half-maximal inhibitory concentrations (IC50s) of 5-fluorouracil, cisplatin, gemcitabine, and trametinib were lower, whereas the IC50s of dasatinib and vorinostat were higher. The malignant degree of GC was higher and the stage was later in the high-expression group. Additionally, patients with high expression of ZNF710-AS1-201 had lower overall survival and disease-free survival rates. In vitro, the overexpression of ZNF710-AS1-201 greatly enhanced growth, metastasis, and infiltration while suppressing cell death in HGC-27 cells. In contrast, the reduced expression of ZNF710-AS1-201 greatly hindered cell growth, enhanced apoptosis, and suppressed the metastasis and invasion of MKN-45 cells. The expression changes in ZNF710 were significant, but the corresponding changes in isocitrate dehydrogenase-2, Semaphorin 4B, ARHGAP10, RGMB, hsa-miR-93-5p, and ZNF710-AS1-202 were not consistent or statistically significant after overexpression or knockdown of ZNF710-AS1-201, as determined by qRT-PCR. CONCLUSION: Immune-related lncRNA ZNF710-AS1-201 facilitates the metastasis and invasion of GC cells. It appears that ZNF710-AS1-201 and ZNF710 have potential as effective targets for therapeutic intervention in GC. Nevertheless, it is still necessary to determine the specific targets of the ZNF710 TF.

A novel method for assessing cardiac function in patients with coronary heart disease based on wrist pulse analysis.

BACKGROUND: The timely assessment of B-type natriuretic peptide (BNP) marking chronic heart failure risk in patients with coronary heart disease (CHD) helps to reduce patients' mortality. OBJECTIVE: To evaluate the potential of wrist pulse signals for use in the cardiac monitoring of patients with CHD. METHODS: A total of 419 patients with CHD were assigned to Group 1 (BNP < 95 pg/mL, n = 249), 2 (95 < BNP < 221 pg/mL, n = 85), and 3 (BNP > 221 pg/mL, n = 85) according to BNP levels. Wrist pulse signals were measured noninvasively. Both the time-domain method and multiscale entropy (MSE) method were used to extract pulse features. Decision tree (DT) and random forest (RF) algorithms were employed to construct models for classifying three groups, and the models' performance metrics were compared. RESULTS: The pulse features of the three groups differed significantly, suggesting different pathological states of the cardiovascular system in patients with CHD. Moreover, the RF models outperformed the DT models in performance metrics. Furthermore, the optimal RF model was that based on a dataset comprising both time-domain and MSE features, achieving accuracy, average precision, average recall, and average F1-score of 90.900%, 91.048%, 90.900%, and 90.897%, respectively. CONCLUSIONS: The wrist pulse detection technology employed in this study is useful for assessing the cardiac function of patients with CHD.

Current status and advances of immunotherapy in nasopharyngeal carcinoma.

The general immune landscape of nasopharyngeal carcinoma (NPC) renders immunotherapy suitable for patients with NPC. Immune checkpoint inhibitors (ICIs) based on programmed death-1/programmed death ligand-1 (PD-1/PD-L1) blockade have made a breakthrough with the approval of PD-1 inhibitor for refractory recurrence and/or metastatic (R/M NPC) and the approval of PD-1 inhibitor in combination with gemcitabine and cisplatin as first line for R/M NPC in 2021 in China. The incorporation of ICIs into the treatment paradigms of NPC has become a clinical hot spot and many prospective clinical studies are ongoing. In this review, we provide a comprehensive overview of the rationale for immunotherapy in NPC and current status, advances and challenges of immunotherapy in NPC based on published clinical data, and ongoing trials. We focus on the clinical application and advances of PD-1 inhibitor monotherapy and its combination with chemotherapy and summarize the clinical explorations of other immunotherapy approaches, for example, combination of PD-1/PD-L1 inhibitors with antiangiogenic inhibitor with molecular targeted agents, cancer vaccines, adaptive immunotherapy, and new ICI agents beyond PD-1/PD-L1 inhibitors in R/M NPC. We also describe the clinical studies' status and challenges of ICIs-based immunomodulatory strategies in local advanced NPC and pay attention to the biomarker application for personalized immunotherapy of NPC in the hope to provide insights for clinical practice and future clinical studies.

Characteristics of Pulse Parameters in Patients with Polycystic Ovary Syndrome Varied at Different Body Mass Index Levels.

Objective: To analyze the characteristics of pulse graph parameters in patients with polycystic ovary syndrome (PCOS) varied at different body mass index (BMI) levels and to provide pulse diagnosis basis for syndrome differentiation and treatment of PCOS. Methods: Pulse graph parameters of 152 patients with PCOS (26 lean patients, 63 patients with moderate weight, and 63 overweight patients) were measured by a Z-BOX pulse meter, and the pulse graph parameters of patients with PCOS varied at different BMI levels were analyzed. Results: Fine pulse, slippery pulse, and string-like pulse were the most common pulse conditions in patients with PCOS. The common pulse conditions of patients with PCOS varied at different BMI levels. The order of pulse conditions was as follows: lean group: fine pulse > string-like pulse > slippery pulse; moderate group: fine pulse > slippery pulse > string-like pulse; and overweight group: slippery pulse > fine pulse > sunken pulse. Compared to the overweight group, the pulse graph parameters h1, h3, h4, h5, h4/h1, As, and Ad increased in the moderate group (P < 0.05), and the parameters h1, h3, and Ad increased (P < 0.05) and the parameter t1 decreased (P < 0.05) in the lean group. Conclusion: Pulse graph parameters among patients with PCOS varied at different BMI levels, which can probably provide pulse diagnosis basis for syndrome differentiation and treatment of PCOS by traditional Chinese medicine (TCM).

Association of Plasma Epstein-Barr Virus DNA With Outcomes for Patients With Recurrent or Metastatic Nasopharyngeal Carcinoma Receiving Anti-Programmed Cell Death 1 Immunotherapy.

IMPORTANCE: Anti-programmed cell death 1 (anti-PD-1) immunotherapy features a durable response and improved survival in a small subset of patients with recurrent or metastatic nasopharyngeal carcinoma (RM-NPC). The association between plasma Epstein-Barr virus (EBV) DNA titer dynamics and efficacy of anti-PD-1 monotherapy has been reported, while its value in predicting long-term outcomes and monitoring disease progression is unclear for patients with RM-NPC who are receiving anti-PD-1 monotherapy. OBJECTIVE: To evaluate the role of plasma EBV DNA titers in prognosis prediction and surveillance of disease progression for patients with RM-NPC who are receiving anti-PD-1 monotherapy. DESIGN, SETTING, AND PARTICIPANTS: Patients with RM-NPC from the POLARIS-02 prospective clinical trial, the largest cohort to receive anti-PD-1 monotherapy, were included in this study. From December 22, 2016, to February 19, 2019, 17 participating centers in China screened 279 patients with RM-NPC; 190 patients were enrolled and followed up until February 19, 2020. Plasma EBV DNA was detected before treatment and every 4 weeks until disease progression. MAIN OUTCOMES AND MEASURES: Plasma EBV DNA as a predictor for progression-free survival (PFS), overall survival (OS), durable clinical benefit (defined as PFS of ≥6 months), and disease progression. RESULTS: Of 179 patients with RM-NPC receiving anti-PD-1 therapy, 148 (82.7%) were men, and the median age was 46 years (range, 22-71 years). A higher baseline EBV DNA titer was associated with shorter median OS (hazard ratio, 1.88; 95% CI, 1.22-2.89; P = .004). Patients with a ratio of the EBV DNA titer at week 4 to that at baseline (W4 to baseline ratio) greater than 0.5 had shorter median OS (hazard ratio, 2.18; 95% CI, 1.30-3.65; P < .001) than those with a W4 to baseline ratio of 0.5 or less. Patients with higher baseline EBV DNA titers had a lower durable clinical benefit rate than those with lower baseline EBV DNA titers (19 of 97 [19.6%] vs 27 of 71 [38.0%]; P = .01). Similarly, patients with a W4 to baseline ratio greater than 0.5 had a lower durable clinical benefit rate than those with a W4 to baseline ratio of 0.5 or less (9 of 86 [10.5%] vs 32 of 54 [59.3%]; P < .001). In addition, a significant EBV DNA titer increase was present at a median of 2.6 months (IQR, 0.9-4.5 months) prior to radiographic progression. CONCLUSIONS AND RELEVANCE: This study of plasma EBV DNA in patients with RM-NPC who are receiving anti-PD-1 monotherapy suggests that plasma EBV DNA could be a useful biomarker for outcomes and monitoring disease progression.

Status and prospect of international standardization of TCM diagnosis.

The present study aimed to review the current status and development of international standards in the domain of traditional Chinese medicine (TCM) diagnosis. Moreover, the roles and relevant work of different organizations in developing such standards were explored, and the difficulties and challenges encountered were analyzed. The study further elaborated on the approaches to establish a complete set of international standards on TCM diagnosis. It also provided a promising solution for the development of international standards on TCM diagnosis.

Identifying Coronary Artery Lesions by Feature Analysis of Radial Pulse Wave: A Case-Control Study.

BACKGROUND: Cardiovascular diseases have been always the most common cause of morbidity and mortality worldwide. Health monitoring of high-risk and suspected patients is essential. Currently, invasive coronary angiography is still the most direct and accurate method of determining the severity of coronary artery lesions, but it may not be the optimal clinical choice for suspected patients who had clinical symptoms of coronary heart disease (CHD) such as chest pain but no coronary artery lesion. Modern medical research indicates that radial pulse waves contain substantial pathophysiologic information about the cardiovascular and circulation systems; therefore, analysis of these waves could be a noninvasive technique for assessing cardiovascular disease. OBJECTIVE: The objective of this study was to analyze the radial pulse wave to construct models for assessing the extent of coronary artery lesions based on pulse features and investigate the latent value of noninvasive detection technology based on pulse wave in the evaluation of cardiovascular disease, so as to promote the development of wearable devices and mobile medicine. METHOD: This study included 529 patients suspected of CHD who had undergone coronary angiography. Patients were sorted into a control group with no lesions, a 1 or 2 lesion group, and a multiple (3 or more) lesion group as determined by coronary angiography. The linear time-domain features and the nonlinear multiscale entropy features of their radial pulse wave signals were compared, and these features were used to construct models for identifying the range of coronary artery lesions using the k-nearest neighbor (KNN), decision tree (DT), and random forest (RF) machine learning algorithms. The average precision of these algorithms was then compared. RESULTS: (1) Compared with the control group, the group with 1 or 2 lesions had increases in their radial pulse wave time-domain features H2/H1, H3/H1, and W2 (P < 0.05), whereas the group with multiple lesions had decreases in MSE1, MSE2, MSE3, MSE4, and MSE5 (P < 0.05). (2) Compared with the 1 or 2 lesion group, the multiple lesion group had increases in T1/T (P < 0.05) and decreases in T and W1 (P < 0.05). (3) The RF model for identifying numbers of coronary artery lesions had a higher average precision than the models built with KNN or DT. Furthermore, average precision of the model was highest (80.98%) if both time-domain features and multiscale entropy features of radial pulse signals were used to construct the model. CONCLUSION: Pulse wave signal can identify the range of coronary artery lesions with acceptable accuracy; this result is promising valuable for assessing the severity of coronary artery lesions. The technique could be used to development of mobile medical treatments or remote home monitoring systems for patients suspected or those at high risk of coronary atherosclerotic heart disease.

Preliminary study on phonetic characteristics of patients with pulmonary nodules.

OBJECTIVE: Pulmonary nodules (PNs) are one of the imaging manifestations of early lung cancer screening, which should receive more attention. Traditional Chinese medicine believes that voice changes occur in patients with pulmonary diseases. The purpose of this study is to explore the differences in phonetic characteristics between patients with PNs and able-bodied persons. METHODS: This study explores the phonetic characteristics of patients with PNs in order to provide a simpler and cheaper method for PN screening. It is a case-control study to explore the differences in phonetic characteristics between individuals with and without PNs. This study performed non-parametric statistics on acoustic parameters of vocalizations, collected from January 2017 to March 2018 in Shanghai, China, from these two groups; it explores the differences in third and fourth acoustic parameters between patients with PNs and a normal control group. At the same time, computed tomography (CT) scans, course of disease, combined disease and other risk factors of the patients were collected in the form of questionnaire. According to the grouping of risk factors, the phonetic characteristics of the patients with PNs were analyzed. RESULTS: This study was comprised of 200 patients with PNs, as confirmed by CT, and 86 healthy people that served as a control group. Among patients with PNs, 43% had ground glass opacity, 32% had nodules with a diameter ≥ 8 mm, 19% had a history of smoking and 31% had hyperlipidemia. Compared with the normal group, there were statistically significant differences in pitch, intensity and shimmer in patients with PNs. Among patients with PNs, patients with diameters ≥ 8 mm had a significantly higher third formant. There was a significant difference in intensity, fourth formant and harmonics-to-noise ratio (HNR) between smoking and non-smoking patients. Compared with non-hyperlipidemia patients, the pitch, jitter and shimmer of patients with PNs and hyperlipidemia were higher and the HNR was lower; these differences were statistically significant. CONCLUSION: This measurable changes in vocalizations can be in patients with PNs. Patients with PNs had lower and weaker voices. The size of PNs had an effect on the phonetic formant. Smoking may contribute to damage to the voice and formant changes. Voice damage is more pronounced in individuals who have PNs accompanied by hyperlipidemia.

[Effect of acupoint catgut embedding on levels of PG-related factors and NF-κB proteins in ute-rine tissues of rats with primary dysmenorrhea].

OBJECTIVE: To observe the effect of acupoint catgut embedding on levels of prostaglandin F2α(PGF2α), cyclooxygenase-2(COX-2) and nuclear factor kappa B(NF-κB) in the uteruses of rats with primary dysmenorrhea (PD), so as to explore its mechanisms underlying improvement of PD. METHODS: Forty female SD rats were randomly divided into normal, model, acupoint catgut embedment and medication groups, with 10 rats in each group. The PD model was established by subcutaneous injection of estradiol benzoate (0.5 mg on the 1st day, and 0.2 mg thereafter) once daily for 10 days, followed by i．p. of oxytocin 2 U(0.5 mg•5 U－1•mL－1) on the 11th day. Catgut embedment was applied to "Guanyuan"(CV4) and "Sanyinjiao"(SP6) on day 1 and 5 while modeling, and rats of the medication group received gavage of ibuprofen (1.25 mg/mL, 0.8 mL/rat) once daily for 10 d. The level of PGF2αin the uterus tissuewas assayed by ELISA, and the expression levels of uterine COX-2, phospho (p)-NF-κB p65, NF-κB p65 proteins were detected by Western blot. RESULTS: Compared with the normal group, the levels of PGF2α， COX-2, p-NF-κB p65 and NF-κB p65 in the uterine tissues were significantly increased in the model group (P<0.05). Compared with the model group, the levels of PGF2α and COX-2 in both catgut embedment and medication groups as well as p-NF-κB p65 in the catgut embedment group were significantly decreased (P<0.05). Compared with the medication group, the level of p-NF-κB 65 in the catgut embedment group was significantly decreased (P<0.05). CONCLUSION: The analgesic effect of acupoint catgut embedding may be related to its effects in down-regulating the expression of p-NF-κB and the levels of COX-2 and PGF2αin uteruses of PD rats.

[Material basis and molecular mechanism of Dachengqi Decoction in treatment of acute pancreatitis based on network pharmacology].

The network pharmacology was used to investigate the material basis and molecular mechanism of Dachengqi Decoction(DCQD) in the treatment of acute pancreatitis(AP). Potential targets of components from DCQD and relevant pathogenic genes of AP were identified through database retrieval. Then, crucial targets were verified with relevant active chemical components via molecular docking. DAVID database was used to explore the functions and pathways involved in the treatment of AP. A total of 108 components were correlated with 28 targets. Molecular docking showed a strong binding ability of key targets and their corresponding compounds. DAVID enrichment analysis showed 438 biological process, 31 molecular functions, 17 cellular components and 96 KEGG pathways. DCQD may achieve its pharmacological effects through anti-inflammatory and anti-oxidative effects, negative regulation of apoptosis and regulation of pancreatic secretion, involving multiple signals, such as IL-17, TNF and NF-κB signaling pathway. In this study, it is the first time to use the method of network pharmacology to reveal the molecular mechanism of DCQD in the treatment of AP by multiple components and multi-signaling pathways, which provides a basis for further biological experiments of AP.

[Acupoint catgut embedding improves dysmenorrhea by suppressing activation of NLRP3 inflammasomes in uterine tissues in primary dysmenorrhea rats].

OBJECTIVE: To observe the effect of acupoint catgut embedding on the expression of nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome, interleukin (IL)-1ß and IL-18 in the uterine tissue of primary dysmenorrhea (PD) rats, so as to explore its underlying mechanisms in improving PD. METHODS: Forty female SD rats were randomly divided into control, model, acupoint catgut embedding and medication groups (n＝10 in each group). The PD model was established by subcutaneous injection of Estradiol Benzoate (0.5 mg/rat on the 1st and 10thday, and 0.2 mg/rat from 2nd to 9thday) and Oxytocin (2 U/rat, i．p.). The catgut embedding was applied to bilateral "Sanyinjiao" (SP6) and "Guanyuan" (CV4) on the 1st and 5th day after modeling. Rats of the medication group were treated by intragastric perfusion of Fenbid (0.8 mL/rat, 125 mg/100 mL) once daily for 10 days. The body writhing times in 30 min were recorded. The histopathological changes of the uterine were observed by H．E. staining. Western blot was used to detect the expression of NLRP 3, caspase-1, IL-1ß and IL-18 in uterine tissues. RESULTS: The body writhing times were notably more in the model group than in the control group (P<0.01), and obviously fewer in both medication and catgut embedding groups than in the model group (P<0.05, P<0.01). After modeling, the rats' endometrium was extensively exfoliated and got swelling, the histopathological score and the expression levels of NLRP3, caspase-1, IL-1ß and IL-18 proteins in the uterus tissue were evidently increased in the model group relevant to the control group (P<0.01). Following the treatment, the degree of endometrial exfoliation and edema of the uterus tissue was lightened, the pathological score was significantly reduced (P<0.01), and the expression levels of caspase-1, IL-1ß and IL-18 protein in uterus tissue were markedly decreased in both acupoint catgut embedding and medication groups (P<0.01, P<0.05). The NLRP3 protein expression was significantly decreased in the acupoint catgut embedding group compared with that in the model group (P<0.01). The therapeutic effect of acupoint catgut embedding was significantly superior to that of medication in reducing writhing times and down-regulating expression of NLPR3 protein (P<0.01). No significant differences were found between catgut embedding and medication in histopathological score, and expression levels of caspase-1, IL-1ß and IL-18 proteins (P>0.05). CONCLUSION: The acupoint catgut embedding can significantly alleviate the symptoms and pathological damage in PD rats, which may be related to its effect in inhibiting the activation of NLRP3 inflammasome in the uterine tissue.

Effect of neoadjuvant chemotherapy followed by radical surgery for FIGO stage IB2/IIA2 cervical cancer: A multi-center retrospective clinical study.

This study compared the efficacy of neoadjuvant chemotherapy (NACT) followed by radical surgery (RS) vs primary surgical treatment (PST) in patients diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage IB2/IIA2 cervical cancer.Data of 303 cervical cancer patients who received primary therapy for stage IB2/IIA2 cervical cancer at 7 medical centers in Beijing, China between January 1, 2009 and December 31, 2016 and followed through December 31, 2017 were collected retrospectively. The response rates, surgical characteristics, and overall survival (OS) durations of patients who received NACT followed by RS were compared to those of patients who received PST.An improved short-term complete response rate was observed among patients who received intra-arterial chemotherapy compared with patients who had intravenous chemotherapy (18.3% vs 4.1%, Pdifference = .020). Patients who received NACT were more likely to undergo laparoscopic surgery and to have a lower blood loss volume (555.4 ±â€Š520.2 ml vs PST, 682.5 ±â€Š509.8 ml; P = .036) and increased estimated operative time (249.9 ±â€Š101.9 vs PST, 225.1 ±â€Š76.5 min; P = .022). No differences in high-risk factors (HRFs), the effects of supplemental treatment, or 5-year OS were observed between patients who received NACT and PST.Our findings indicate that patients who received NACT for FIGO stage IB2/IIA2 cervical cancer were more likely to undergo laparoscopic surgery. These findings have important implications regarding treatment with curative intent for stage IB2/IIA2 cervical cancer and warrant a further analysis of treatment strategies to ensure adequate treatment and patient-centered care.

Inhibition of ferroptosis attenuates tissue damage and improves long-term outcomes after traumatic brain injury in mice.

AIMS: Ferroptosis, a new form of iron-dependent programmed cell death, has been shown to be involved in a range of diseases. However, the role of ferroptosis in traumatic brain injury (TBI) has yet to be elucidated. We aimed to investigate whether ferroptosis is induced after TBI and whether the inhibition of ferroptosis would protect against traumatic brain injury in a controlled cortical impact injury (CCI) mouse model. METHODS: After establishing the TBI model in mice, we determined the biochemical and morphological changes associated with ferroptosis, including iron accumulation with Perl's staining, neuronal cell death with Fluoro-Jade B (FJB) staining, iron metabolism dysfunction with Western blotting, reactive oxygen species (ROS) accumulation with malondialdehyde (MDA) assays, and shrunken mitochondria with transmission electron microscopy. Furthermore, a specific inhibitor of ferroptosis, ferrostatin-1(fer-1), was administrated by cerebral ventricular injection after CCI. We used cresyl violet (CV) staining to assess lesion volume, along with the Morris water maze and beam walk test to evaluate long-term outcomes. RESULTS: TBI was followed by iron accumulation, dysfunctional iron metabolism, the upregulation of ferroptosis-related genes, reduced glutathione peroxidase (GPx) activity, and the accumulation of lipid-reactive oxygen species (ROS). Three days (d) after TBI, transmission electron microscopy (TEM) confirmed that the mitochondria had shrunk a typical characteristic of ferroptosis. Importantly, the administration of Fer-1 by cerebral ventricular injection significantly reduced iron deposition and neuronal degeneration while attenuating injury lesions and improving long-term motor and cognitive function. CONCLUSION: This study demonstrated an effective method with which to treat TBI by targeting ferroptosis.

Circular RNA Expression Profiles Alter Significantly after Traumatic Brain Injury in Rats.

Circular RNAs (circRNAs) are involved in a variety of diseases. However, the roles of circRNAs in traumatic brain injury (TBI) remain unknown. In this study, circRNA microarray was used to profile the altered circRNAs in the rat hippocampus following TBI. A total of 192 circRNAs were observed to be differentially expressed (fold change [FC] ≥1.5 and p < 0.05) after TBI, including 98 upregulated and 94 downregulated. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that many messenger RNAs (mRNAs) transcribed from the host genes of altered circRNAs were implicated in brain damage and neural regeneration. CircRNA/microRNA (miRNA) interaction was predicted using Arraystar's homemade miRNA target prediction software based on TargetScan and miRanda. Thus, our studies have demonstrated altered circRNA expression pattern in the rat hippocampus after TBI, which may play important roles in post-TBI physiological and pathological processes. These findings may provide not only a new direction for studying the molecular mechanisms underlying TBI but also a new possibility for the treatment of TBI by modulating circRNAs.

Linc00152 promotes Cancer Cell Proliferation and Invasion and Predicts Poor Prognosis in Lung adenocarcinoma.

Background: The long non-coding RNA Linc00152 stimulates tumor progression in cancer. However, its clinical significance and biological functions in lung adenocarcinoma remains unknown. We evaluate the expression of Linc00152 in lung adenocarcinoma and its possible correlation with clinicopathologic features and patient survival to reveal its biological effects in cancer progression and prognosis. Methods: Total RNA extraction was performed on 110 pairs of lung adenocarcinoma and adjacent normal tissue samples, and then RT-qPCR was conducted. Chi-square test analysis was used to calculate the correlation between pathological parameters and the Linc00152 mRNA levels. Kaplan-Meier and Cox proportional hazards analyses were used to analyze the overall survival (OS) and disease-free survival (DFS) rates. We also detected the potential functional effects of overexpression and knockdown of Linc00152 in vitro cell proliferation, tumor cell invasion and migration, as well as in vivo nude mouse xenograft and metastasis models. Results: The Linc00152 expression levels were higher in lung adenocarcinoma samples than in the adjacent normal tissues. Linc00152 expression levels tightly correlated with lymph node metastasis station, remote metastasis and TNM staging. The Kaplan-Meier analysis suggested that high Linc00152 expression caused significantly poorer OS and DFS rates, and a multivariate analysis revealed that Linc00152 was an independent risk factor for both DFS and OS. Overexpression of Linc00152 in lung cancer cells stimulated proliferation, tumor cell invasion and migration. Knockdown of Linc00152 inhibited cell growth and cell invasion and migration. Finally, Linc00152 knockdown inhibited lung tumor growth and tumor metastasis in nude mice models. Conclusions: Our study suggests that Linc00152 independently predicts poor prognosis and promotes tumor progression in lung adenocarcinoma. Linc00152 needs to be considered as a potential molecular target in future cancer pharmacology.

Classifying syndromes in Chinese medicine using multi-label learning algorithm with relevant features for each label.

OBJECTIVE: To develop an effective Chinese Medicine (CM) diagnostic model of coronary heart disease (CHD) and to confifirm the scientifific validity of CM theoretical basis from an algorithmic viewpoint. METHODS: Four types of objective diagnostic data were collected from 835 CHD patients by using a self-developed CM inquiry scale for the diagnosis of heart problems, a tongue diagnosis instrument, a ZBOX-I pulse digital collection instrument, and the sound of an attending acquisition system. These diagnostic data was analyzed and a CM diagnostic model was established using a multi-label learning algorithm (REAL). RESULTS: REAL was employed to establish a Xin (Heart) qi defificiency, Xin yang defificiency, Xin yin defificiency, blood stasis, and phlegm fifive-card CM diagnostic model, which had recognition rates of 80.32%, 89.77%, 84.93%, 85.37%, and 69.90%, respectively. CONCLUSIONS: The multi-label learning method established using four diagnostic models based on mutual information feature selection yielded good recognition results. The characteristic model parameters were selected by maximizing the mutual information for each card type. The four diagnostic methods used to obtain information in CM, i.e., observation, auscultation and olfaction, inquiry, and pulse diagnosis, can be characterized by these parameters, which is consistent with CM theory.

Antiangiogenic therapy using endostatin increases the number of ALDH+ lung cancer stem cells by generating intratumor hypoxia.

Antiangiogenic therapy is becoming a promising option for cancer treatment. However, many investigations have recently indicated that these therapies may have limited efficacy, and the cancers in most patients eventually develop resistance to these therapies. There is considerable recently acquired evidence for an association of such resistance with cancer stem-like cells (CSLCs). Here, we used xenograft tumor murine models to further suggest that antiangiogenic agents actually increase the invasive and metastatic properties of lung cancer cells. In our experiments with murine lung cancer xenografts, we found that the antiangiogenic agent endostatin increased the population of ALDH+ cells, and did so by generating intratumoral hypoxia in the xenografts. We further showed endostatin to cause an increase in the CSLC population by accelerating the generation of tumor hypoxia and by recruiting TAMs, MDSCs and Treg cells, which are inflammatory and immunosuppressive cells and which can secrete cytokines and growth factors such as IL-6, EGF, and TGF-ß into the tumor microenvironment. All these factors are related with increased CSLC population in tumors. These results imply that improving the clinical efficacy of antiangiogenic treatments will require the concurrent use of CSLC-targeting agents.

Prenatal choline supplementation attenuates spatial learning deficits of offspring rats exposed to low-protein diet during fetal period.

Prenatal intake of choline has been reported to lead to enhanced cognitive function in offspring, but little is known about the effects on spatial learning deficits. The present study examined the effects of prenatal choline supplementation on developmental low-protein exposure and its potential mechanisms. Pregnant female rats were fed either a normal or low-protein diet containing sufficient choline (1.1g/kg choline chloride) or supplemented choline (5.0g/kg choline chloride) until delivery. The Barnes maze test was performed at postnatal days 31-37. Choline and its metabolites, the synaptic structural parameters of the CA1 region in the brain of the newborn rat, were measured. The Barnes maze test demonstrated that prenatal low-protein pups had significantly greater error scale values, hole deviation scores, strategy scores and spatial search strategy and had lesser random search strategy values than normal protein pups (all P<.05). These alterations were significantly reversed by choline supplementation. Choline supplementation increased the brain levels of choline, betaine, phosphatidylethanolamine and phosphatidylcholine of newborns by 51.35% (P<.05), 33.33% (P<.001), 28.68% (P<.01) and 23.58% (P<.05), respectively, compared with the LPD group. Prenatal choline supplementation reversed the increased width of the synaptic cleft (P<.05) and decreased the curvature of the synaptic interface (P<.05) induced by a low-protein diet. Prenatal choline supplementation could attenuate the spatial learning deficits caused by prenatal protein malnutrition by increasing brain choline, betaine and phospholipids and by influencing the hippocampus structure.

Long non-coding RNA Linc00152 is a positive prognostic factor for and demonstrates malignant biological behavior in clear cell renal cell carcinoma.

Accumulating evidence demonstrates that lncRNAs play important roles in regulating gene expression and are involved in various pathological processes. In the present study, we screened the lncRNAs profile in clear cell renal cell carcinoma (ccRCC) from The Cancer Genome Atlas (TCGA) database, and got linc00152, a differentially expressed lncRNA that haven't been reported in ccRCC. To further explore its role in ccRCC, the level of Linc00152 was detected in 77 paired ccRCC tissues and renal cancer cell lines by qRT-PCR, and its association with overall survival was assessed by statistical analysis. Linc00152 expression was significantly up-regulated in cancerous tissues and cell lines compared with normal counterparts, and high Linc00152 expression was closely associated with advanced TNM stage. Moreover, Linc00152 was found to be able to serve as an independent predictor of overall survival. Further experiments demonstrated that overexpression of Linc00152 can significantly promote cell proliferation and invasion, inhibit cell cycle arrest in G1 phase and dramatically decrease apoptosis in both 786O and Caki-2 cell lines, whereas the opposite results were observed with attenuated Linc00152 expression. Our data suggest that Linc00152 is a novel molecule involved in ccRCC progression as well as a potential prognostic biomarker and therapeutic target.

Upregulation of the Non-Coding RNA OTUB1-isoform 2 Contributes to Gastric Cancer Cell Proliferation and Invasion and Predicts Poor Gastric Cancer Prognosis.

BACKGROUND: The deubiquitinase OTUB1 plays critical oncogenic roles and facilitates tumor progression in cancer. However, less is known regarding the aberrant expression, clinical significance and biological functions of the non-coding RNA OTUB1-isoform 2. We aimed to evaluate the OTUB1-isoform 2 levels in gastric cancer and their possible correlation with clinicopathologic features and patient survival to reveal its biological effects in gastric cancer progression. METHODS: Total RNA extraction was performed on 156 gastric cancer case samples, and RT-qPCR was conducted. Chi-square test analysis was used to calculate the correlation between pathological parameters and the OTUB1-isoform 2 mRNA levels. Kaplan-Meier and Cox proportional hazards analyses were used to analyze the overall survival (OS) and disease-free survival (DFS) rates. Nuclear and cytoplasmic RNAs were isolated to detect the subcellular localization of OTUB1-isoform 2. We also assessed whether overexpression of OTUB1-isoform 2 influenced in vitro cell proliferation, cell cycle progression, tumor cell invasion and migration, as well as in vivo nude mouse xenograft and metastasis models. RESULTS: The OTUB1-isoform 2 expression levels were higher in the gastric cancer samples than in the paratumorous gland samples. OTUB1-isoform 2 expression levels tightly correlated with tumor size, lymph node metastasis and TNM staging. Higher OTUB1-isoform 2 expression levels led to significantly poorer OS and DFS rates, and a multivariate analysis revealed that OTUB1-isoform 2 was an independent risk factor for DFS. OTUB1-isoform 2 was predominantly localized in the cell nucleus. Ectopic overexpression of OTUB1-isoform 2 in gastric cancer cells stimulated proliferation by inducing G1-S transition, suppression of cell apoptosis and promotion of tumor cell invasion and migration. Finally, OTUB1-isoform 2 overexpression promoted tumor growth and tumor metastasis in nude mice models. CONCLUSIONS: Our study suggests that OTUB1-isoform 2 independently predicts poor prognosis and promotes tumor progression in gastric cancer. The non-coding RNA OTUB1-isoform 2 should be targeted in future molecular therapies.