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Purpose: The aim of this study was to compare patterns of recurrence in 2009 FIGO Stage IB‐IIA (T1bN0M0‐T2aN0M0) cervical cancer patients with cN0 and cN1. Methods: The epidemiological and clinical data of 1352 patients who had undergone radical hysterectomy and systematic lymphadenectomy with cervical cancer treated from January 2008 to April 2019 at a tertiary teaching hospital were retrospectively collected. The primary aim was to discover the lymph node status‐dependent patterns and time of recurrence. Results: Tumor recurrence and death were significantly less common in patients with cN0 than cN1. In addition, the length of time to recurrence (median 60 months cN0 vs. 43 months cN1, p < 0.001) and death (median 84 months cN0 vs. 68 months cN1 p < 0.001) were significantly longer in cN0 versus cN1 patients. The cumulative rate of relapse also showed a significant difference between cN0 and cN1 groups, especially the 1‐year relapse rate (2.14% vs. 10.78%). Of the patients who recurred, there was no difference in number of recurrent sites between cN0 and cN1 groups (solitary metastases:35.8% of cN0 and 35.6% of cN1; multiple metastases: 64.2% of cN0 and 64.4% of cN1). Similarly, there was no statistical difference in recurrence sites of cervical cancer between cN0 and cN1 groups based on three categories, (p = 0.646). However, in the six categories, patients' vaginal vaults with negative lymph nodes were more prone to recurrence, while the distribution of other recurrence sites showed no significant difference between the two groups. Conclusions: There is a significant improvement of relapse‐free survival in the cN0 group, and the recurrence time of cN0 patients is significantly delayed than cN1 group. However, except for the risk of metastasis of the vaginal vault, the site of relapse remains similar. [ABSTRACT FROM AUTHOR]

Background: This study aimed to compare the survival outcomes between squamous cell carcinoma (SCC) and adenocarcinoma/adenosquamous carcinoma (AC/ASC) of the cervix after radical radiotherapy and chemotherapy.Methods: Propensity score matching (1:4) was used to compare overall survival (OS) and disease-free survival (DFS) in cervical cancer patients with SCC and AC/ASC in China.Results: Five thousand four hundred sixty-six patients were enrolled according to the criteria. The 5-year OS and DFS in the SCC group (n = 5251) were higher than those in the AC/ASC group (n = 215). After PSM (1:4), the 5-year OS and DFS in the SCC group were higher than those in the AC/ASC group (72.2% vs 56.9%, p < 0.001, HR = 1.895; 67.6% vs 47.8%, p < 0.001, HR = 2.056). In stage I-IIA2 patients, after PSM (1:4), there was no significant difference in 5-year OS between the SCC group (n = 143) and the AC/ASC group (n = 34) (68.5% vs 67.8%, P = 0.175). However, the 5-year DFS in the SCC group was higher than that in the AC/ASC group (71.0% vs 55.7%, P = 0.045; HR = 2.037, P = 0.033). In stage IIB-IV patients, after PSM (1:4), the 5-year OS and DFS in the SCC group (n = 690) were higher than those in the AC/ASC group (n = 173) (70.7% vs 54.3% P < 0.001 vs 1.940%, P < 0.001 vs 45.8%, p < 0.001).Conclusions: For stage I-IIA2, there was no significant difference in 5-year survival time, but patients with AC/ASC were more likely to relapse. In the more advanced IIB-IV stage, the oncological outcome of radical radiotherapy and chemotherapy of cervical AC/ASC was worse than that of SCC. [ABSTRACT FROM AUTHOR]

Flexible electronic printing technology is a scientific technology that uses an "ink" material with conductive, dielectric, or semiconductor properties printed on a flexible web substrate to achieve precise preparation of flexible electronic devices, which are widely used in information, energy, medical, and military fields. In the preparation of the printing process of flexible printed electron webs under complex working conditions, the moving web will experience substantial unstable nonlinear dynamic behavior, such as divergence, flutter, bifurcation, and chaos. Accordingly, because of the coupling effects of the complex working conditions of the magnetic field, air and nonlinear electrostatic field forces, it is indispensable to explore the nonlinear dynamic equation of the flexible printed electron web in motion. The theory of multiphysics dynamics establishes a nonlinear vibration equation for the flexible printed electron web under multiphysics conditions. The discrete nonlinear vibration equation of state space equation was obtained by the Bubnov–Galerkin method. Utilizing the Runge–Kutta technique of the fourth-order, Poincaré maps, phase-plane diagrams, power spectra, bifurcation graphs, and time history diagrams of the moving flexible printed electron web were obtained. The influences of the velocity, electrostatic field, magnetic induction intensity, and follower force on the flexible printed electron web were analyzed. In addition, the Ansoft Maxwell finite element simulation software was used to simulate the magnetic field distribution of the moving web during roll-to-roll transmission. This paper determines the stable working range of the moving flexible printed electron web, which provides a theoretical basis for the preparation of flexible printed electronic webs. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC) is a prevalent form of lung cancer. Patients with advanced NSCLC are currently being treated with various therapies, including traditional radiotherapy, chemotherapy, molecular targeted therapies and immunotherapy. However, a considerable proportion of advance patients who cannot benefit from them. Consequently, it is essential to identify a novel research target that offers an encouraging perspective. The stimulator of interferon genes (STING) has emerged as such a target. At present, it is confirmed that activating STING in NSCLC tumor cells can impede the proliferation and metastasis of dormant tumor cells. This review focuses on the role of STING in NSCLC treatment and the factors influencing its activation. Additionally, it explores the correlation between STING activation and diverse therapy modalities for NSCLC, such as radiotherapy, chemotherapy, molecular targeted therapies and immunotherapy. Furthermore, it proposes the prospect of innovative therapy methods involving nanoparticles, with the aim of using the features of STING to develop more strategies for NSCLC therapy. [ABSTRACT FROM AUTHOR]

Amelogenesis is a complicated process that concerns the interaction between growing hydroxyapatite crystals and extracellular proteins, which requires the tight regulation of pH. In dental fluorosis, the balance of pH regulation is broken, leading to abnormal mineralization. The current review focuses on the electrolyte transport processes associated with pH homeostasis, particularly regarding the changes in ion transporters that occur during amelogenesis, following exposure to excessive fluoride. Furthermore, the possible mechanism of fluorosis is discussed on the basis of acid hypothesis. There are two main methods by which F− accelerates crystal formation in ameloblasts. Firstly, it induces the release of protons, lowering the pH of the cell microenvironment. The decreased pH stimulates the upregulation of ion transporters, which attenuates further declines in the pH. Secondly, F− triggers an unknown signaling pathway, causing changes in the transcription of ion transporters and upregulating the expression of bicarbonate transporters. This results in the release of a large amount of bicarbonate from ameloblasts, which may neutralize the pH to form a microenvironment that favors crystal nucleation. The decreased pH stimulates the diffusion of F− into the cytoplasm of amelobalsts along the concentration gradient formed by the release of protons. The retention of F− causes a series of pathological changes, including oxidative and endoplasmic reticulum stress. If the buffering capacity of ameloblasts facing F− toxicity holds, normal mineralization occurs; however, if F− levels are high enough to overwhelm the buffering capacity of ameloblasts, abnormal mineralization occurs, leading to dental fluorosis. [ABSTRACT FROM AUTHOR]

Background: Effective identification and development of new molecular methods for the diagnosis, treatment and prognosis of lung adenocarcinoma (LUAD) remains an urgent clinical need. DNA methylation patterns at cytosine bases in the genome are closely related to gene expression, and abnormal DNA methylation is frequently observed in various cancers. The ten-eleven translocation (TET) enzymes oxidize 5-methylcytosine (5mC) and promote locus-specific DNA methylation reversal. This study aimed to explore the role of the TET2 protein and its downstream effector, 5-hmC/5-mC DNA modification, in LUAD progression. Methods: The expression of TET2 was analysed by real-time PCR, Western blotting and immunohistochemistry. The 5-hmC DNA content was determined by a colorimetric kit. Activation of the cGAS-STING signalling pathway was evaluated by Western blotting. CCK-8, wound healing and Transwell assays were performed to evaluate the effect of TET2 on cell proliferation, migration and invasion abilities. A xenograft model was used to analyse the effect of TET2 on the tumorigenic ability of A549 cells. Results: TET2 overexpression decreased proliferation and metastasis of A549 and H1975 cells in vitro and in vivo. However, TET2 knockdown dramatically enhanced the proliferation, migration and invasion of A549 and H1975 cells. Mechanistically, activation of the cGAS-STING signalling pathway is critical for the TET2-mediated suppression of LUAD cell tumorigenesis and metastasis. Conclusion: In this study, we demonstrate a tumour suppressor role of TET2 in LUAD, providing new potential molecular therapeutic targets and clinical therapies for patients with non-small cell lung cancer. [ABSTRACT FROM AUTHOR]

Mutations in mitochondrial (mt)transfer (t)RNA (mt-tRNA) have been reported to serve important roles in hypertension. To determine the underlying molecular mechanisms of mt-tRNA mutations in hypertension, the present study screened for mt-tRNA mutations in a Chinese family with a high incidence of essential hypertension. Sequence analysis of the mt-tRNA genes in this family revealed the presence of an A4401G mutation in the glycine-and methionine-tRNA genes, and a G5821A mutation in the cysteine-tRNA (tRNACys) gene. The G5821A mutation was located at a position conserved in various species, and disrupted G6-C67 base-pairing. It was hypothesized that the G5821A mutation may decrease the baseline expression levels of tRNACys, and consequently result in failure of tRNA metabolism. The A4401G mutation was reported to cause the mitochondrial dysfunction responsible for hypertension. Thus, the combination of G5821A and A4401G mutations may contribute to the high incidence of hypertension in this family. Mt-tRNA mutations may serve as potential biomarkers for hypertension. [ABSTRACT FROM AUTHOR]

Strawberry fruits (cv. Benihoppe, Tochiotome, Sachinoka, and Guimeiren) were harvested and evaluated the flavor and nutritional parameters. By principal component analysis and hierarchical clustering analysis, differences were observed based on the volatile compounds composition, sugar and acid concentration, sweetness, and total soluble sugars/total organic acids of the four varieties. A total of 37, 48, 65, and 74 volatile compounds were identified and determined in cv. Benihoppe, Tochiotome, Sachinoka, and Guimeiren strawberry fruits extracted by head-space solid-phase microextraction ( HS- SPME), respectively. Esters significantly dominated the chemical composition of the four varieties. Furaneol was detected in cultivars of Sachinoka and Guimeiren, but mesifuran was only found in cv. Tochiotome. Tochiotome and Sachinoka showed higher content of linalool and (E)-nerolidol. Sachinoka showed the highest content of total sugars and total acids. Guimeiren showed higher sweetness index than the other three cultivars. Firmness of Tochiotome was highest among all the varieties. The highest total soluble solids TSS value was found in cv. Sachinoka, followed by the Guimeiren and Tochiotome varieties. Sachinoka had the highest titratable acidity TA value. The content of ascorbic acid (AsA) of cv. Tochiotome was higher than the others, but there was no significant difference in cultivars of Benihoppe, Tochiotome, and Sachinoka. Fructose and glucose were the major sugars in all cultivars. Citric acid was the major organic acid in cv. Tochiotome, cv. Sachinoka, and cv. Guimeiren. Tochiotome had higher ratios of TSS/ TA and total sugars/total organic acids than others, arising from its lower acid content. The order of the comprehensive evaluation score was Sachinoka>Guimeiren>Tochiotome>Benihoppe. [ABSTRACT FROM AUTHOR]

Background. Sciatica is one of the most frequently reported complaints; it affects quality of life and reduces social and economic efficacy. Clinical studies on the efficacy of acupuncture therapy in sciatica are increasing, while systematic reviews assessing the efficacy of acupuncture therapy are still lacking. Objective. This study aims to assess the effectiveness of acupuncture therapy for sciatica. Methods. Comprehensive searches of 8 databases were conducted up until April 2015. Outcomes included effectiveness (proportion of patients who improved totally or partly in clinical symptoms), pain intensity, and pain threshold. Effect sizes were presented as risk ratio (RR) and mean difference (MD). Pooled effect sizes were calculated by fixed effects or random effects model. Results. A total of 12 studies (involving 1842 participants) were included. Results showed that acupuncture was more effective than conventional Western medicine (CWM) in outcomes effectiveness (RR 1.21, 95% CI: 1.16–1.25), pain intensity (MD −1.25, 95% CI: −1.63 to −0.86), and pain threshold (MD: 1.08, 95% CI: 0.98–1.17). Subgroup and sensitivity analysis found that the results did not change in different treatment method and drug categories substantially. The reported adverse effects were acceptable. Conclusions. Acupuncture may be effective in treating the pain associated with sciatica. [ABSTRACT FROM AUTHOR]

The purpose of this study is to employ a nonlinear dynamic evaluation method to assess the tourism sustainability of Tibet Autonomous Region (TAR), China, a new emerging tourism destination. The methodology draws on system dynamics and Back Propagation (BP) neural network. According to 7 setting principles, this study identifies 13 tourism sustainability indicators including conventional tourism income, tourism resources stock, pollution stock, etc., as well as specific residents’ tourism cognition, seasonal difference, accessibility, etc. Then a system dynamics model including the 13 indicators (variables) and other relevant auxiliary variables is established. Based on the numerical simulation, using a three layers BP neural network optimized by genetic algorithm and particle swarm algorithm, this study evaluates the future sustainability dynamically and compares the sustainability evolution from 2014 to 2050 under different development strategies. The research results not only provide information useful for the dynamic control and scientific management of the future sustainable tourism development, but also provide a systems approach to evaluate regional tourism sustainability. [ABSTRACT FROM AUTHOR]

Dental fluorosis is a global issue. Although there are multiple causes of dental fluorosis, the precise mechanism remains controversial. Previous studies have demonstrated that extracellular fluoride may promote an accumulation of fluoride ions in ameloblasts, which may induce oxidative and endoplasmic reticulum stresses, leading to dental fluorosis. However, the exact process by which fluoride ions enter cells has not been determined. In the present study, intracellular fluoride concentration was determined using a newly developed specific fluorescent probe called probe 1. Under high extracellular fluoride concentrations, the fluorescence intensity of the ameloblasts increased, however, exogenous transforming growth factor-β1 (TGF-β1) was able to inhibit the increase. Furthermore, changes in the expression of the voltage-gated chloride channels 5 and 7 (ClC5 and ClC-7), which are responsible for the transport of fluoride were investigated. The results indicated that fluoride reduced the expression of endogenous TGF-β1 and increased the expression of ClC-5 and ClC-7. Additionally, exogenous TGF-β1 reduced the expression of ClC-5 and ClC-7. The results of the present study indicate that exogenous TGF-β1 may prevent accumulation of fluoride in ameloblasts through the regulation of ClC-5 and ClC-7 under high extracellular fluoride concentrations. [ABSTRACT FROM AUTHOR]

Despite recent advancements in cancer treatment, this disease still poses a serious threat to public health. Vaccines play an important role in preventing illness by preparing the body's adaptive and innate immune responses to combat diseases. As our understanding of malignancies and their connection to the immune system improves, there has been a growing interest in priming the immune system to fight malignancies more effectively and comprehensively. One promising approach involves utilizing nanoparticle systems for antigen delivery, which has been shown to potentiate immune responses as vaccines and/or adjuvants. In this review, we comprehensively summarized the immunological mechanisms of cancer vaccines while focusing specifically on the recent applications of various types of nanoparticles in the field of cancer immunotherapy. By exploring these recent breakthroughs, we hope to identify significant challenges and obstacles in making nanoparticle-based vaccines and adjuvants feasible for clinical application. This review serves to assess recent breakthroughs in nanoparticle-based cancer vaccinations and shed light on their prospects and potential barriers. By doing so, we aim to inspire future immunotherapies for cancer that harness the potential of nanotechnology to deliver more effective and targeted treatments. [ABSTRACT FROM AUTHOR]

Objective. To identify the biological function and metabolic pathway of differential metabolites in follicular fluid of senile patients with kidney qi deficiency undergoing in vitro fertilization-embryo transfer (IVF-ET) and observe the effect of kidney-invigorating herbs on IVF outcomes in senile patients. Methods. A total of 95 women undergoing IVF treatment were recruited and divided into three groups, including 34 cases in the treatment group (the senile patients with kidney qi deficiency after the intervention of Chinese medicine), 31 cases in the experiment group (the senile patients with kidney qi deficiency of no intervention of Chinese medicine), and 30 cases in the control group (young women with infertility due to male factor). The three groups of women were treated with long protocol ovarian hyperstimulation; the treatment group was given Qi-Zi-Yu-Si decoction on the day of HCG downregulation. Their IVF clinical outcomes were observed. The metabolites changes of kidney qi deficiency syndrome were analyzed in follicular fluid metabolomics using liquid chromatography-mass spectrometry (UPLC-MS/MS). Results. The syndrome score of kidney qi deficiency syndrome in the treatment group was significantly improved after treatment (P < 0.01). Compared with the experiment group, the available embryo rate and implantation rate were increased, and the difference was statistically significant (P < 0.05). Progesterone, indoleacrylic acid, 2-propenyl 1-(1-propenylsulfinyl) propyl disulfide, N-acetyltryptophan, decanoylcarnitine, 20a-dihydroprogesterone, testosterone acetate, eicosatrienoic acid, 1H-indole-3-carboxaldehyde, choline, phosphorylcholine, and tryptophan were downregulated in the treatment group. Through pathway analysis, glycerophospholipid metabolism and steroid hormone biosynthesis were regulated in senile patients with kidney qi deficiency after Qi-Zi-Yu-Si decoction intervention. Conclusion. Qi-Zi-Yu-Si decoction can effectively improve the IVF outcome and clinical symptoms of senile patients. Follicular fluid metabolites were significantly changed in senile infertile women with kidney qi deficiency, and the mechanism by which kidney-invigorating herbs improve IVF treatment outcomes may be related to glycerophospholipid metabolism and steroid hormone biosynthesis. This study was registered in the Chinese Clinical Trials Registry Platform (ChiCTR1800014422). [ABSTRACT FROM AUTHOR]

Background: The aim of the current study was to investigate the long non-coding RNA (lncRNA) expression profiles in psoriatic arthritis (PSA) patients by RNA sequencing, and to further explore potential biomarkers that were able to predict PSA risk and activity. Methods: LncRNA and mRNA expression profiles in peripheral blood mononuclear cells (PBMC) of 4 PSA patients and 4 normal controls (NCs) were detected by RNA sequencing, followed by comprehensive bioinformatic analyses. Subsequently, 3 top upregulated and 2 top downregulated lncRNAs were chosen for further validation in 93 PSA patients and 93 NCs by quantitative polymerase chain reaction (qPCR) assay. Results: Totally 76 upregulated and 54 downregulated lncRNAs, as well as 231 upregulated and 102 downregulated mRNAs were discovered in PSA patients compared with NCs. Enrichment analyses revealed that they were mostly associated with nucleosome, extracellular exosome and extracellular matrix, and the top enriched pathways were systemic lupus erythematosus (SLE), alcoholism and viral carcinogenesis. qPCR assay showed that lnc-RP11-701H24.7 and lnc-RNU12 were upregulated in PSA patients compared with NCs, and they could predict PSA risk with high area under curves. Besides, lnc-RP11-701H24.7 was positively associated with ESR, SJC, TJC and pain VAS score while lnc-RNU12 was positively correlated with PASI score, CRP and PGA score, implying that both of them were positively correlated with disease activity. Conclusion: Our study facilitates comprehensive understanding of lncRNA expression profiles in PSA pathogenesis, and discovers that lnc-RP11-701H24.7 and lnc-RNU12 might be served as novel biomarkers for PSA risk and activity. [ABSTRACT FROM AUTHOR]

Background: There is growing evidence discussing the role of long non-coding RNAs (lncRNAs) in cervical cancer (CC). We performed this study to explore the impact of exosomal lncRNA urothelial cancer-associated 1 (UCA1) in CC stem cells by sponging microRNA-122-5p (miR-122-5p) and regulating SOX2 expression.Methods: CC stem cells (CD133+CaSki) and exosomes were extracted and identified. The synthesized UCA1- and miR-122-5p-related sequences were transfected into CaSki cells, CaSki cells-derived exosomes were extracted and then co-cultured with CD133+CaSki cells. The functional roles of UCA1 and miR-122-5p in self-renewal and differentiation ability of CC stem cells were determined using ectopic expression, knockdown/depletion and reporter assay experiments. An in vivo experiment was performed to verify the in vitro results.Results: Up-regulated UCA1 and SOX2 and down-regulated miR-122-5p were found in CaSki-Exo. Exosomes promoted invasion, migration, proliferation and restrained apoptosis of CD133+CaSki cells. Silencing UCA1 or up-regulating miR-122-5p degraded SOX2 expression, and reduced invasion, migration and proliferation of CD133+CaSki cells while advanced apoptosis and suppressed the tumor volume and weight in nude mice.Conclusion: Our study provides evidence that CaSki-Exo can promote the self-renewal and differentiation ability of CC stem cells while silencing UCA1 or up-regulating miR-122-5p restrains self-renewal and differentiation of CC stem cells. [ABSTRACT FROM AUTHOR]

Tumor cells primarily employ the PD-1/PD-L1 pathway to thwart the anti-tumor capabilities of T lymphocytes, inducing immunosuppression. This occurs through the direct interaction of PD-L1 with PD-1 on T lymphocyte surfaces. Recent research focusing on the tumor microenvironment has illuminated the pivotal role of immune cells, particularly tumor-associated macrophages (TAMs), in facilitating PD-L1-mediated immunosuppression. Exosomes, characterized by their ability to convey information and be engulfed by cells, significantly contribute to promoting TAM involvement in establishing PD-L1-mediated immunosuppression within the tumor microenvironment. Exosomes, characterized by their ability to convey information and be engulfed by cells, significantly contribute to promoting TAM involvement in establishing PD-L1-mediated immunosuppression within the tumor microenvironment. In addition to receiving signals from tumor-derived exosomes that promote PD-L1 expression, TAMs also exert control over PD-L1 expression in tumor cells through the release of exosomes. This paper aims to summarize the mechanisms by which exosomes participate in this process, identify crucial factors that influence these mechanisms, and explore innovative strategies for inhibiting or reversing the tumor-promoting effects of TAMs by targeting exosomes. [ABSTRACT FROM AUTHOR]

Background: Interleukin-33 (IL-33) is an effective inducer of pro-inflammatory cytokines regulating innate and adaptive immunity. Inflammation could be a double-edged sword, promoting or inhibiting tumour growth. To date, the roles and mechanisms of IL-33 in tumours remain controversial. Here, we examined the effect of exogenous IL-33 on the biological characteristics of hepatocellular carcinoma (HCC) and the possible mechanism of action.Methods: In this study, IL-33 expression in the tissues of 69 HCC patients was detected and its relationship with prognosis was evaluated. After establishing a mouse HCC model and IL-33 treatment operation, the infiltration of splenic myeloid-derived suppressor (MDSCs), dendritic (DCs), regulatory T, and natural killer (NK) cells was detected by flow cytometry analysis, and the vascular density of the tumour tissues was detected by immunohistochemistry to reveal the mechanism of IL-33 in HCC proliferation. Finally, the Cancer Genome Atlas database was used to analyse Gene Ontology terms the and Kyoto Encyclopaedia of Genes and Genomes pathway. Moreover, the chi-square test, two-tailed unpaired Student's t-test, and multiple t-tests were performed using SPSS version 23.0 and GraphPad Prism 8.0 software.Results: The IL-33 expression level was negatively correlated with the overall survival of HCC patients, suggesting its potential clinical significance in the prognosis of HCC. We found that systemic IL-33 administration significantly promoted the tumour size in vivo. Furthermore, the IL-33-treated mice presented decreased frequencies of tumouricidal NK and CD69+ CD8+ T cells. After IL-33 treatment, the incidence of monocytic MDSCs and conventional DCs increased, while that of granulocytic MDSCs decreased. Moreover, IL-33 promoted the formation of intracellular neovascularization. Therefore, IL-33 accelerated HCC progression by increasing the accumulation of immunosuppressive cells and neovascularization formation. Finally, we found that the transcription of IL-33 was closely related to the PI3K-Akt and MAPK pathways in Gene Set Enrichment Analysis plots, which were involved in the tumourigenesis and pathogenesis of HCC.Conclusions: Taken together, IL-33 may be a key tumour promoter of HCC proliferation and tumourigenicity, an important mediator, and a potential therapeutic target for regulating HCC progression. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiotherapy followed by surgery has been recommended as standard treatment in patients with locally advanced esophageal cancer (LAEC). But the risk of tumor recurrence still remained, and many patients refused or abandoned radiotherapy because of the intolerable adverse effects in China. Neoadjuvant immunochemotherapy (nICT) followed by surgery has become an emerging treatment in patients with esophageal cancer. There was still no consensus on whether nICT was superior to nCT alone in patients with esophageal cancer. Methods: In this retrospective study, patients with resectable esophageal cancer who received surgery after nICT (n=26, 40%) or nCT alone (n=39, 60%) were included. The patients were classified as nICT or nCT arm. The primary endpoints were pathological tumor response (PTR) and event-free survival (EFS). The different clinic-pathological features were compared by the Kruskal-Wallis test for continuous variables and the Chi-square (χ2) test for categorical variables. Kaplan-Meier curves were used to estimate EFS from the date of treatment to recurrence or death. All tests were 2-sided with a significative P-value defined <.05. Results: Three (11.5%) of the 26 patients achieved pathological complete remission (pCR) in the nICT group, and four (10.3%) of the 39 patients achieved pCR in the nCT group, respectively (P=1.000). Six (23.1%) of the 26 patients achieved major pathological response (MPR) in the nICT group, and 11 (28.2%) of the 39 patients achieved MPR in the nCT group, respectively (P=0.645). Downstaging was achieved in 13 (44.8%) patients in the nICT group and 16 (55.2%) patients in the nCT group, respectively (P=0.732). To verify the tumor regression grade (TRG) results, we compared them with MPR and pCR, which showed a significant dependency (P< 0.001). Patients who achieved downgrading showed better MPR and pCR rates (P<0.001 and P =0.010). There was no significant difference in EFS between the nICT and nCT groups (HR=1.011, 95% CI: 0.421–2.425, P = 0.981). Conclusions: Neoadjuvant PD-1 blockade combined with chemotherapy was not superior to chemotherapy alone for patients with resectable locally advanced esophageal carcinoma. However, more studies with long-term follow-up were needed to confirm this result. [ABSTRACT FROM AUTHOR]

CIK cells therapy has been evaluated as an adoptive cell immunotherapy for cancer patients, but there still have not been any standardized systems for evaluating the antitumor efficacy yet. The WHO and RECIST criteria have already been established for a few years but not sufficient to fully characterize the activity of immunotherapy. Based on these two criteria, the irRC was proposed for evaluating the efficacy of immunotherapy. A variety of bioassays for immune monitoring including the specific and non-specific methods, have been established. We recommend detect levels of various immunocytes, immune molecules and soluble molecules to find the correlations among them and clinicopathological characteristics to establish criteria for immunological classification. We also recommend a paradigm shift for the oncologists in the evaluation of immune therapies to ensure assessment of activity based on clinically relevant criteria and time points. [ABSTRACT FROM AUTHOR]

Background: Implants immediately loaded full-arch prosthesis in maxilla is always a challenge, especially when the zone 2 is extremely defected. To achieve a satisfying result, different therapeutic alternatives have been proposed, such as zygomatic implant, pterygoid implant; however, precise surgical skills limited its application. Case presentation: This study reported a case that an edentulous patient was treated with a new technique, two axial implants and four tilted implants supporting an immediate fixed denture, extruding the cortical bone of the anterior wall of the maxillary sinus to establish the primary stability. Conclusions: Two-year follow-up proves that it is a viable choice. Meanwhile, a reliable method for its saving time and money and low level of discomfort for patients is presented. [ABSTRACT FROM AUTHOR]

Background: Existing studies for ferroptosis and prognosis in colorectal cancer (CRC) were limited. In this study, we aim to investigate the prognostic role of ferroptosis markers in patients with CRC and exploration of its micro‐environmental distributions. Methods: Immunohistochemical staining was performed for CRC patients' tissue microarray. Selection and prognostic validation of markers were based on mRNA data from the cancer genome atlas (TCGA) database. Gene Set Enrichment Analysis (GSEA) was performed to indicate relative immune landmarks and hallmarks. Ferroptosis and immune contexture were examined by CIBERSORT. Survival outcomes were analyzed by Kaplan‐Meier analysis and cox analysis. Results: A panel of 42 genes was selected. Through mRNA expression difference and prognosis analysis, GPX4, NOX1 and ACSL4 were selected as candidate markers. By IHC, increased GPX4, decreased NOX1 and decreased FACL4 indicate poor prognosis and worse clinical characteristics. Ferroptosis score based on GPX4, NOX1 and ACSL4 was constructed and validated with high C‐index. Low ferroptosis score can also demonstrate the better progression free survival and better adjuvant chemotherapy (ACT) responsiveness. Moreover, tumor with low ferroptosis score tend to be infiltrated with more CD4+ T cells, CD8+ T cells and less M1 macrophage. Finally, we found that IFN‐γ was potentially the central molecule at the crossroad between ferroptosis and onco‐immune response. Conclusion: Ferroptosis plays important role on CRC tumor progression, ACT response and prognosis. Ferroptosis contributes to immune‐supportive responses and IFN‐γ was the central molecule for this process. [ABSTRACT FROM AUTHOR]

Background: Mikania micrantha is a vine with strong invasion ability, and its strong sexual reproduction ability is not only the main factor of harm, but also a serious obstacle to control. M. micrantha spreads mainly through seed production. Therefore, inhibiting the flowering and seed production of M. micrantha is an effective strategy to prevent from continuing to spread. Result: The flowering number of M. micrantha is different at different altitudes. A total of 67.01 Gb of clean data were obtained from nine cDNA libraries, and more than 83.47% of the clean reads were mapped to the reference genome. In total, 5878 and 7686 significantly differentially expressed genes (DEGs) were found in E2 vs. E9 and E13 vs. E9, respectively. Based on the background annotation and gene expression, some candidate genes related to the flowering pathway were initially screened, and their expression levels in the three different altitudes in flower bud differentiation showed the same trend. That is, at an altitude of 1300 m, the flower integration gene and flower meristem gene were downregulated (such as SOC1 and AP1), and the flowering inhibition gene was upregulated (such as FRI and SVP). Additionally, the results showed that there were many DEGs involved in the hormone signal transduction pathway in the flower bud differentiation of M. micrantha at different altitudes. Conclusions: Our results provide abundant sequence resources for clarifying the underlying mechanisms of flower bud differentiation and mining the key factors inhibiting the flowering and seed production of M. micrantha to provide technical support for the discovery of an efficient control method. [ABSTRACT FROM AUTHOR]

Background: Targeted therapy has revolutionized the treatment of patients with malignancies harboring mutations in driver genes and has brought a favorable survival benefit to the population with actionable oncogenic mutations. In recent years, the MET exon14 skipping mutation has been recognized as a potentially promising therapeutic target in non-small cell lung cancer (NSCLC). These changes are mutually exclusive with molecular drivers such as EGFR, KRAS, HER-2, BRAF, ALK and ROS1. The prevalence rate of coexisting MET exon 14 mutations and EGFR sensitive mutations (L858R, exon 19 deletions) in Chinese population was reported to be 0.2% (3/1590). However, the coexistence of MET exon 14 mutations with EGFR exon 20 insertion mutations has never been reported and the management of this subtype is not identified. Case presentation: A 69-year-old male with a right lung adenocarcinoma (T4N2M0, IIIB) was confirmed to be positive for MET exon 14 skipping (c.3028_3028+1delGGinsTT, 44.4%), MET amplification (copy number 4.4), and EGFR exon 20 insertion (p. N771_H773dup, 22.1%) mutations. After the progression of one cycle of chemotherapy (Pemetrexed 0.8 g d1), the patient was subsequently accepted treatment with Crizotinib (250 mg twice a day) and achieved an important clinical remission for six months until the development of brain metastases. Then, he was submitted to a cycle of anti-programmed cell death-1 (PD-1) therapy after failure of Crizotinib and eventually acquired resistance despite of the high expression of programmed death ligand-1 (PD-L1) and tumor mutational burden (TMB) status. Conclusion: This case report provides treatment strategies for epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs)-untreated lung adenocarcinoma patients simultaneously carrying MET alterations and EGFR exon 20 insertion mutations. In addition, the signatures of PD-L1 or TMB expression were not the candidate for predicting the efficacy of immunotherapy in this context. [ABSTRACT FROM AUTHOR]

Using chicken feathers as bait, Acremonium globosisporum sp. nov. and Acremonium curvum sp. nov. were collected from the soil of Yuncheng East Garden Wildlife Zoo and Zhengzhou Zoo in China. They were identified by combining the morphological characteristics and the two-locus DNA sequence (LSU and ITS) analyses. In the phylogenetic tree, both new species clustered into separate subclades, respectively. They were different from their allied species in their morphology. The description, illustrations, and phylogenetic tree of the two new species were provided. [ABSTRACT FROM AUTHOR]

Many survival and ecological problems have emerged in Pinus yunnanensis pure pine forest plantations that are usually assumed to be solved by creating mixed plantations. On this basis, we determined the physicochemical properties and enzyme activities of three soil layers in pure and three types of mixed P. yunnanensis plantation stands (admixed species: Alnus nepalensis, Celtis tetrandra, and Quercus acutissima) in Southwest China. We used one-way ANOVA with Tukey's test to analyze the effects of plantation type and depth on the soil's properties and variations among different depths. Principal component analysis combined with cluster analysis was used to evaluate the soil quality of different forest types comprehensively. The results showed that the stand with a mixing proportion of 2:1 of P. yunnanensis and A. nepalensis, C. tetrandra, and Q. acutissima had higher total porosity, moisture content, total nitrogen, available phosphorus, total phosphorus, sucrase, urease, and catalase enzyme activities than other proportions of mixed forest and P. yunnanensis pine pure forest. In general, the mixed P. yunnanensis plantation could improve the soil quality, especially its chemical properties and enzymes. This study provides a basis for creating a mixed-mode of P. yunnanensis and other tree species that can not only improve the economy of forest land but also enhance the ecological value. [ABSTRACT FROM AUTHOR]

The study aims to investigate if low-level laser therapy (LLLT) combined with eccentric exercises could more effectively treat patellar tendinopathy than LLLT alone and eccentric exercises alone. Twenty-one patients with patellar tendinopathy were randomized to three groups: laser alone, exercise alone, or laser plus exercise, with seven in each group. Laser irradiations were administered at the inferior pole of the patella and the two acupoints of Extra 36 (Xiyan) with the intensity of1592 mW/cm². Eccentric training program consisted of three sets of 15 repetitions of unilateral squat on level ground. All patients received six treatments per week for four weeks. Knee pain and function and quadriceps muscle strength and endurance were evaluated at baseline and the end of treatment. After the 4-week intervention, all groups showed significant improvements in all the outcomes (P < 0.01). The laser + exercise group had significantly greater improvements in all the outcomes than the other two groups (P < 0.05), except nonsignificant difference in pain relief between the laser + exercise group and the laser group. In conclusion, LLLT combined with eccentric exercises is superior to LLLT alone and eccentric exercises alone to reduce pain and improve function in patients with patellar tendinopathy. [ABSTRACT FROM AUTHOR]

This paper studied an asset and liability management problem with stochastic interest rate, where interest rate is assumed to be governed by an affine interest rate model, while liability process is driven by the drifted Brownian motion. The investors wish to look for an optimal investment strategy to maximize the expected utility of the terminal surplus under hyperbolic absolute risk aversion (HARA) utility function, which consists of power utility, exponential utility, and logarithm utility as special cases. By applying dynamic programming principle and Legendre transform, the explicit solutions for HARA utility are achieved successfully and some special cases are also discussed. Finally, a numerical example is provided to illustrate our results. [ABSTRACT FROM AUTHOR]

Background: The optimal time at which to perform a frozen-thawed embryo transfer (FET) following a failed in-vitro fertilization-embryo transfer (IVF-ET) attempt remains elusive to most reproductive experts. Physicians often delay the introduction of FET due to concerns related to potential residual effects of ovarian hyperstimulation which may interfere with the regular menstrual cycle. Moreover, given that most of the published studies on the topic are retrospective and have inconsistent findings, it is crucial to develop evidence-based randomized control guides for clinical practice. Therefore, this well-designed randomized controlled trial (RCT) was conducted to determine whether it is necessary to delay FET for at least one menstrual cycle after the failure of fresh embryo transfer. Methods: Infertile women eligible for IVF-ET were invited to participate in this multicenter, randomized, non-inferiority, parallel-group, unblinded, controlled trial at the academic fertility centers of four public hospitals in Chinese Mainland. Infertile women scheduled to receive their first FET cycle after a failed IVF-ET attempt were randomly assigned to either (a) the immediate FET group in which FET was performed in the first menstrual cycle following the failed IVF-ET cycle (n = 366) or (b) the delayed FET group in which FET was performed in the second or subsequent menstrual cycle following the failed IVF-ET cycle (n = 366). All FET cycles were performed during hormone replacement cycles for endometrial preparation. The primary outcome was the ongoing pregnancy, defined as a detectable fetal heart beat beyond twelve weeks of gestation. Secondary outcomes were other pregnancy-related outcomes, maternal and neonatal complications. Analysis was performed by both intention-to-treat and per-protocol principles. Results: A total of 646 FETs were completed. The frequency of moderate to severe depression and high stress level prior to FET in delayed FET group were significantly higher than that in immediate FET group (10.6% vs 6.1%, p = 0.039; 30.3% vs 22.4%, p = 0.022, respectively). Immediate FET resulted in a higher frequency of clinical pregnancy than did delayed FET (41.7% vs 34.1%), for a relative risk (RR) of 1.23 (95% confidence interval [CI], 1.00–1.50; p = 0.045). Women who underwent immediate FET also had a lower frequency of biochemical pregnancy loss (11.7% vs. 30.6%), with a RR of 0.28 (95% CI 0.23–0.63, p < 0.001), and a higher frequency of embryo implantation (25.2% vs. 20.2%), with a RR of 1.25 (95% CI 1.01–1.53; p = 0.038). Although the ongoing pregnancy and live birth rates did not differ significantly between the immediate FET and delayed FET groups (37.1% vs 30.3%, RR 1.22, 95% CI 0.99–1.52, p = 0.067; 36.5% vs 30.0%, RR 1.22, 95% CI 0.98–1.52, p = 0.079, respectively), a multivariate logistic regression analysis adjusted for potential confounders such as depression and stress levels revealed that the immediate FET group had a significantly higher ongoing pregnancy and live birth rates than the delayed FET group (odds ratio 0.68, 95% CI 0.47–0.99, p = 0.041; odds ratio 0.67, 95% CI 0.46–0.96, p = 0.031). The risks of maternal and neonatal complications were comparable between the two groups. Conclusions: In women with a previous failed IVF-ET attempt, immediate FET resulted in higher ongoing pregnancy and live birth rates than delayed FET. These findings warrant caution in the indiscriminate application of a delayed FET strategy when apparent risk of high stress level is perceived. Trial registration: ChiCTR2000033313. [ABSTRACT FROM AUTHOR]

Effective and complete control of the invasive weed Mikania micrantha is required to avoid increasing damages. We exogenously applied indole 3-acetic acid (IAA), gibberellin (GA), and N -(2-Chloro-4-pyridyl)- N′ -phenylurea (CPPU), and their combinations i.e. IAA + CPPU (IC), GA + CPPU (GC), and GA + IAA + CPPU (GIC), at 5, 10, 25, 50, and 75 ppm against distilled water as a control (CK), to examine their effects on the weed. The increasing concentrations of these hormones when applied alone or in combination were fatal to M. micrantha and led towards the death of inflorescences and/or florets. CPPU and GIC were found as the most effective phytohormones. Transcriptome analysis revealed differential regulation of genes in auxin, cytokinin, gibberellin and abscisic acid signaling pathways, suggesting their role in the prohibition of axillary bud differentiation. Collectively, CPPU and GIC at a high concentration (75 ppm) could be used as a control measure to protect forests and other lands from the invasion of M. micrantha. • Investigation on an environment friendly approach to control Mikania micrantha. • CPPU and GIC (75 ppm) were the most effective phytohormones against Mikania micrantha. • Alterations in phytohormone signaling pathways affect Mikania micrantha reproduction. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is a global pandemic associated with a high mortality. Our study aimed to determine the clinical risk factors associated with disease progression and prolonged viral shedding in patients with COVID-19. Consecutive 564 hospitalized patients with confirmed COVID-19 between January 17, 2020 and February 28, 2020 were included in this multicenter, retrospective study. The effects of clinical factors on disease progression and prolonged viral shedding were analyzed using logistic regression and Cox regression analyses. 69 patients (12.2%) developed severe or critical pneumonia, with a higher incidence in the elderly and in individuals with underlying comorbidities, fever, dyspnea, and laboratory and imaging abnormalities at admission. Multivariate logistic regression analysis indicated that older age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.02-1.06), hypertension without receiving angiotensinogen converting enzyme inhibitors or angiotensin receptor blockers (ACEI/ARB) therapy (OR, 2.29; 95% CI, 1.14-4.59), and chronic obstructive pulmonary disease (OR, 7.55; 95% CI, 2.44-23.39) were independent risk factors for progression to severe or critical pneumonia. Hypertensive patients without receiving ACEI/ARB therapy showed higher lactate dehydrogenase levels and computed tomography (CT) lung scores at about 3 days after admission than those on ACEI/ARB therapy. Multivariate Cox regression analysis revealed that male gender (hazard ratio [HR], 1.22; 95% CI, 1.02-1.46), receiving lopinavir/ritonavir treatment within 7 days from illness onset (HR, 0.75; 95% CI, 0.63-0.90), and receiving systemic glucocorticoid therapy (HR, 1.79; 95% CI, 1.46-2.21) were independent factors associated with prolonged viral shedding. Our findings presented several potential clinical factors associated with developing severe or critical pneumonia and prolonged viral shedding, which may provide a rationale for clinicians in medical resource allocation and early intervention. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is a global pandemic associated with a high mortality. Our study aimed to determine the clinical risk factors associated with disease progression and prolonged viral shedding in patients with COVID-19. Consecutive 564 hospitalized patients with confirmed COVID-19 between January 17, 2020 and February 28, 2020 were included in this multicenter, retrospective study. The effects of clinical factors on disease progression and prolonged viral shedding were analyzed using logistic regression and Cox regression analyses. 69 patients (12.2%) developed severe or critical pneumonia, with a higher incidence in the elderly and in individuals with underlying comorbidities, fever, dyspnea, and laboratory and imaging abnormalities at admission. Multivariate logistic regression analysis indicated that older age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.02-1.06), hypertension without receiving angiotensinogen converting enzyme inhibitors or angiotensin receptor blockers (ACEI/ARB) therapy (OR, 2.29; 95% CI, 1.14-4.59), and chronic obstructive pulmonary disease (OR, 7.55; 95% CI, 2.44-23.39) were independent risk factors for progression to severe or critical pneumonia. Hypertensive patients without receiving ACEI/ARB therapy showed higher lactate dehydrogenase levels and computed tomography (CT) lung scores at about 3 days after admission than those on ACEI/ARB therapy. Multivariate Cox regression analysis revealed that male gender (hazard ratio [HR], 1.22; 95% CI, 1.02-1.46), receiving lopinavir/ritonavir treatment within 7 days from illness onset (HR, 0.75; 95% CI, 0.63-0.90), and receiving systemic glucocorticoid therapy (HR, 1.79; 95% CI, 1.46-2.21) were independent factors associated with prolonged viral shedding. Our findings presented several potential clinical factors associated with developing severe or critical pneumonia and prolonged viral shedding, which may provide a rationale for clinicians in medical resource allocation and early intervention. [ABSTRACT FROM AUTHOR]

Malignant solid tumors are the leading cause of death in humans, and epigenetic regulation plays a significant role in studying the mechanism of human solid tumors. Recently, histone lysine methylation has been demonstrated to be involved in the development of human solid tumors due to its epigenetic stability and some other advantages. The 90-kb protein methyltransferase nuclear receptor SET domain-containing 2 (NSD2) is a member of nuclear receptor SET domain-containing (NSD) protein lysine methyltransferase (KMT) family, which can cause epigenomic aberrations via altering the methylation states. Studies have shown that NSD2 is frequently over-expressed in multiple types of aggressive solid tumors, including breast cancer, renal cancer, prostate cancer, cervical cancer, and osteosarcoma, and such up-regulation has been linked to poor prognosis and recurrence. Further studies have identified that over-expression of NSD2 promotes cell proliferation, migration, invasion, and epithelial–mesenchymal transformation (EMT), suggesting its potential oncogenic role in solid tumors. Moreover, Gene Expression Profiling Interactive Analysis (GEPIA) was searched for validation of prognostic value of NSD2 in human solid tumors. However, the underlying specific mechanism remains unclear. In our present work, we summarized the latest advances in NSD2 expression and clinical applications in solid tumors, and our findings provided valuable insights into the targeted therapeutic regimens of solid tumors. [ABSTRACT FROM AUTHOR]

Rapid metastasis contributes significantly to the high mortality rates in lung adenocarcinoma. The present study reports a rare case of primary lung adenocarcinoma with concomitant gastric, duodenal, bone, and mediastinal lymph node metastases. A large gene panel based on the next-generation sequencing was used to detect gene mutations in different metastatic sites and blood. The results showed that the gene mutation spectrums among different metastatic foci were roughly similar. The mutation abundance was highest in mediastinal lymph nodes. Unique mutation sites were detected only in mediastinal lymph nodes, bone, and gastric metastatic foci. Despite partial heterogeneity, there are currently no applicable targeted drugs to adopt. In addition, tumor mutation burden (TMB) showed that blood, gastric, bone, and mediastinal lymph node metastases were all TMB-High, while the duodenal metastasis was TMB-Low. This study is the first to report a rare case of newly diagnosed lung adenocarcinoma with concomitant gastrointestinal metastases and to perform mutation analyses on all metastatic foci. Large sample sizes with similar cases are required to gain deeper insights. [ABSTRACT FROM AUTHOR]

Beta-amyloid (Aβ) oligomers are strongly associated with the cascade of harmful events leading to neurodegeneration in Alzheimer's disease (AD). Elimination of Aβ oligomers or inhibition of Aβ assembly is a valuable therapeutic approach for the treatment of AD. Here, we obtained a mimotope of Aβ oligomers, AOEP2, by screening a peptide library using oligomer-specific antibodies. The antibodies induced by AOEP2 specifically recognize Aβ oligomers rather than monomers and fibrils. Interestingly, the AOEP2 peptide binds to Aβ monomers and inhibits the formation of Aβ oligomers and β-sheet structure, reduces Aβ42-induced neurotoxicity, and decreases the release of proinflammatory cytokines. Taken together, AOEP2, a novel multifunctional peptide directly or indirectly targeting Aβ, has promising therapeutic potential for AD. [ABSTRACT FROM AUTHOR]

The present study aimed to evaluate the impact of total extracorporeal circulation on hemodynamics and placental function in an ovine fetal model. Mid-term ovine fetuses (n=6) underwent extracorporeal circulation (30 min), cardioplegic arrest (20 min) and monitoring (120 min). The ascending aorta and umbilical cords of the fetuses were occluded during the bypass and an extracorporeal membrane oxygenator was used as the oxygen source. Biventricular intracardiac pressures, echocardiographic data, blood gas levels and placental function variables were recorded, and statistical analysis was performed using the repeated-measure analysis of variance test. The data indicated that fetal heart rate and blood pressure at 30, 60, 90 and 120 min following the bypass were stable relative to pre-arrest baseline (pre-bypass) values (P>0.05). However, end diastolic pressures in the ovine right ventricles post-bypass were significantly increased at 30, 60, 90 and 120 min relative to pre-bypass pressures (P<0.05). The pulsatility index also increased at 30 min post-bypass relative to the pre-bypass score (0.91±0.06 vs. 0.61±0.14; P=0.007). The mean resistivity index at all time points post-bypass was consistent with the pre-bypass score (P>0.05), while the mean Tei index values for the left and right ventricles post-bypass were significantly higher at all time points relative to pre-bypass values (P<0.05). The pre-bypass fetal blood pH, SaO2, base excess and lactate values were maintained during arrest (P>0.05). Fetal hemodynamics and placental function additionally remained stable for up to 2 h upon reperfusion following total extracorporeal circulation and cardioplegic arrest. Collectively these data suggest that the reproducible ovine fetal model may be useful in the evaluation of fetal cardiac surgery. [ABSTRACT FROM AUTHOR]

Purpose: This phase II/III, non-randomized clinical trial aimed to determine the efficacy and safety of the combination of radiofrequency ablation (RFA) and cytokine-induced killer (CIK) cells transfusion for patients with colorectal liver metastases (CRLMs). Experimental Design: A total of 60 eligible patients with CRLMs were enrolled and divided into Group A (RFA alone, n = 30) and Group B (RFA plus CIK, n = 30), and following enzyme-linked immunosorbent spot assay was performed in 8 patients with CEA > 50 ng/mL pre-RFA and 7 days post-RFA and CIK treatment, respectively. Results: The median progression-free survival (PFS) times of Group A and Group B were 18.5 months and 23 months, respectively (P = 0.0336). The 3-year progression-free rates were 13.3% in Group A and 20.3% in Group B, respectively. The median overall survival time was 43 months in Group A, and not reached in Group B. The 3-year survival rates were 64.6% in Group A and 81.0% in Group B, respectively (P = 0.1187). Among the 8 patients with CEA > 50ng/mL, 6 had increase of circulating CEA-specific T cells after RFA (P = 0.010). After CIK cell therapy, the number of CEA-specific T cells increased in all the 8 patients comparing with that pre-treatment (P = 0.001) and in 7 patients comparing with that post-RFA (P = 0.028). Conclusions: We firstly confirm that the combination of RFA and CIK cells boosts CEA-specific T cell response and shows to be an efficacious and safe treatment modality for patients with CRLMs. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the Bmi-1 expression and the clinical significance in colon cancer (CC). Patients and Methods: Bmi-1 expression in tumor tissue and the corresponding normal tissue was detected using immunohistological staining. The correlations between Bmi-1 expression and clinicopathological characteristics and the overall survival (OS) time were analyzed. Results: The median H-scores of Bmi-1 in CC tissues and the corresponding tissues were 80.0 (0-270) and 5.0 (0-90), with no statistically significant difference (Z=-13.7, P<0.001). Bmi-1 expression in CC tissues was not statistically correlated with any characteristics. The median OS times for CC patients with high or low Bmi-1 expression were 53.7 months and 44.9 months, respectively, with no statistically significant difference (P = 0.123). The survival rates of patients with low Bmi-1 expression were higher than those of patients with high Bmi-1 expression but the differences were not statistically significant. Conclusion: Bmi-1 expression in CC tissue is significantly higher than that in corresponding normal tissue. While there may be a trend towards improved survival, this is not statistically significant. [ABSTRACT FROM AUTHOR]

MicroRNAs have been appreciated in various cellular functions, including the regulation of angiogenesis. Mesenchymal-stem-cells (MSCs) transplanted to the MI heart improve cardiac function through paracrine-mediated angiogenesis. However, whether microRNAs regulate MSC induced angiogenesis remains to be clarified. Using microRNA microarray analysis, we identified a microRNA expression profile in hypoxia-treated MSCs and observed that among all dysregulated microRNAs, microRNA-377 was decreased the most significantly. We also validated that vascular endothelial growth factor (VEGF) is a target of microRNA-377 using dual-luciferase reporter assay and Western-blotting. Knockdown of endogenous microRNA-377 promoted tube formation in human umbilical vein endothelial cells. We then engineered rat MSCs with lentiviral vectors to either overexpress microRNA-377 (MSCmiR-377) or knockdown microRNA-377 (MSCAnti-377) to investigate whether microRNA-377 regulated MSC-induced myocardial angiogenesis, using MSCs infected with lentiviral empty vector to serve as controls (MSCNull). Four weeks after implantation of the microRNA-engineered MSCs into the infarcted rat hearts, the vessel density was significantly increased in MSCAnti-377-hearts, and this was accompanied by reduced fibrosis and improved myocardial function as compared to controls. Adverse effects were observed in MSCmiR-377-treated hearts, including reduced vessel density, impaired myocardial function, and increased fibrosis in comparison with MSCNull-group. These findings indicate that hypoxia-responsive microRNA-377 directly targets VEGF in MSCs, and knockdown of endogenous microRNA-377 promotes MSC-induced angiogenesis in the infarcted myocardium. Thus, microRNA-377 may serve as a novel therapeutic target for stem cell-based treatment of ischemic heart disease. [ABSTRACT FROM AUTHOR]

Isoliquiritigenin (ISL), a simple chalcone-type flavonoid, is derived from licorice compounds and is mainly present in foods, beverages, and tobacco. Reactive oxygen species (ROS) is a critical factor involved in modulating cardiac stress response signaling during ischemia and reperfusion. We hypothesize that ISL as a natural antioxidant may protect heart against ischemic injury via modulating cellular redox status and regulating cardioprotective signaling pathways. The fluorescent probe H2DCFDA was used to measure the level of intracellular ROS. The glucose uptake was determined by 2-deoxy-D-glucose-³H accumulation. The IonOptix System measured the contractile function of isolated cardiomyocytes. The results demonstrated that ISL treatment markedly ameliorated cardiomyocytes contractile dysfunction caused by hypoxia. ISL significantly stimulated cardioprotective signaling, AMP-activated protein kinase (AMPK), and extracellular signal-regulated kinase (ERK) signaling pathways. The ROS fluorescent probe H2DCFDA determination indicated that ISL significantly reduced cardiac ROS level during hypoxia/reoxygenation. Moreover, ISL reduced the mitochondrial potential (Δψ) of isolated mouse cardiomyocytes. Taken together, ISL as a natural antioxidant demonstrated the cardioprotection against ischemic injury that may attribute to the activation of AMPK and ERK signaling pathways and balance of cellular redox status. [ABSTRACT FROM AUTHOR]

Purpose: To determine the long-term efficacy of adjuvant immunotherapy with autologous cytokine-induced killer (CIK) cells for locally advanced gastric cancer patients. Experimental design: One hundred and fifty-one patients with stage III/IV gastric cancer who had undergone gastrectomy were enrolled, assigned to two groups (immunotherapy group versus no immunotherapy group/or control group), and followed. Results: The 5-year overall survival (OS) and 5-year disease-free survival (DFS) rates for immunotherapy versus control group were 32.4 versus 23.4 % ( P = 0.071) and 28.3 versus 10.4 % ( P = 0.044), respectively. For patients with intestinal-type tumors, the 5-year OS and DFS rates were significantly higher for immunotherapy (OS, 46.8 vs. 31.4 % and P = 0.045; DFS, 42.4 vs. 15.7 % and P = 0.023). In the immunotherapy group, the mean CD3 level, CD4 level, and CD4/CD8 ratio increased from 50.8, 26.5, and 0.9 %, respectively, at baseline to 62.6, 35.0, and 1.4 %, respectively, 1 week after the first CIK-cell treatment, returned to baseline after 2 months, and maintained a higher level (60.7 ± 8.2 %, 34.2 ± 7.1 %, and 1.3 ± 0.3 %, respectively) 2 months after 3 cycles of immunotherapy. Conclusions: Adjuvant immunotherapy with CIK cells prolongs DFS in patients with locally advanced gastric cancer and significantly improves OS in patients with intestinal-type tumors. Intestinal-type tumors could be selected as an important indication for CIK-cell therapy. This treatment may help improve T-lymphocyte subset distribution and improve the host's immune functions, but multiple cycles are necessary for long-term therapeutic efficacy. [ABSTRACT FROM AUTHOR]

Background: Locoregional recurrence is the typical pattern of recurrence in gastric cancer, and cannot be removed by surgery in most of the patients. We aimed to evaluate the feasibility and efficacy of computed tomography (CT)-guided brachytherapy for patients with locoregional recurrent gastric cancer. Materials and methods: We reviewed the case histories of 28 patients with locoregional recurrent gastric cancer that were selected for CT- guided brachytherapy by a multidisciplinary team. The clinical data of the patients including patient characteristics, treatment parameters, short-term effects, and survival data were collected and analyzed. Results: 15-75 125I seeds were implanted into each patient to produce a minimal peripheral dose (MPD) 100- 160 Gy. Median day 0 dosimetry was significant for the following: V100 (the volume treated with the prescription dose) 95.8% (90.2-120.5%) and D90 (prescription dose received by at least 90% of the volume) 105.2% (98.0-124.6%) of prescription dose. No serious complications occurred during the study. Two months after brachytherapy, complete response, partial response and progressive disease were observed in 50.0%, 28.6% and 21.4% of patients, respectively. The median survival time was 22.0 ± 5.2 months, and the 1, 2,and 3-year survival rate was 89 ± 6%, 52 ± 10% and 11 ± 7%, respectively. A univariate analysis showed that the tumor size was a significant predictor of overall survival (P = 0.034). Patients with tumors <3 cm had relatively higher complete response rate (66.7%), compared to those with tumors >3 cm (30.8%). The PTV (planning target volume) smaller than 45 cm3 was significantly correlated with achieving complete tumor eradication in the treated region (P = 0.020). Conclusions: For selected patients with limited locoregional recurrent gastric cancer, CT-guided brachytherapy using 125I seeds implantation can provide a high local control rate, with minimal trauma. [ABSTRACT FROM AUTHOR]

The article discusses a sensitive and rapid method based on liquid chromatography-tandem mass spectrometry (LC-MS-MS) method for measuring olopatadine concentration in human plasma. The study used protein precipitation to carry out sample preparations, followed by liquid-liquid extraction (LLE) with ethyl acetate/dichloromethane. It states that the method has sensitivity with a lower limit of quantification (LLOQ) of 0.2 ng/mL and was used for the pharmacokinetic studies of olopatadine.

Background: Unprecedented durable responses are identified in clinical studies to target the signaling of programmed cell death protein-1 (PD-1) as well as its ligand (PD-L1) in patients with squamous-cell non-small cell lung cancer (NSCLC). However, factors predicting the patient subtypes that are responsive to PD-1/PD-L1inhibitors have not been fully understood yet. Biomarkers, like PD-L1 expression, tumor mutational burden(TMB), DNA mismatch repair deficiency (dMMR), and tumor-infiltrating lymphocytes (TILs), have been utilized to select patients responsive to PD-1/PD-L1inhibitors in the clinic, but each of them has limited use. Lung adenocarcinoma patients with a mutation of TP53 or KRAS, particularly those with co-mutations of TP53 and KRAS, can benefit from anti–PD-1 treatment. Case presentation: In this study, the co-mutations of TP53 and KRAS in a 64-year-old non-smoking man with squamous-cell NSCLC patient was described using the next-generation sequencing (NGS) technology. The patient was treated with the pembrolizumab combined with gemcitabine as the salvage therapy, and a marked partial response could be attained, which had persisted for over 7 months. Conclusion: In addition to testing common driving genes, like EGFR, ALK, ROS1 and BRAF, both TP53, and KRAS should also be considered in advanced or metastatic squamous-cell NSCLC.TP53 and KRAS co-mutations in squamous-cell NSCLC can be a potential factor to assess possible response to PD-1 blockade immunotherapy, but further studies with more cases are needed to confirm the prediction power. [ABSTRACT FROM AUTHOR]

Comparative studies of subspecies under different ecological environments offer insights into intraspecies evolutionary adaptive mechanisms. Golden snub-nosed monkeys (Rhinopithecus roxellana) include three subspecies in China classified mainly by their morphological variations: R. r. roxellana (Sichuan and Gansu province), R. r. qinlingensis (Shaanxi province) and R. r. hubeiensis (Hubei province). These three subspecies live in three isolated area with different environments. Past works focused on the last two subspecies, but little information of habitat and behaviors of the nominated subspecies (R. r. roxellana) is available to date. We conducted a two-year study on the diet, activity budget, home range and social organization of 4 herds of R. r. roxellana, based on a total of 106 days’ observation in Laohegou (LHG) Nature Reserve, Sichuan province. By using scan sampling method, our results suggest that the R. r roxellana feeds predominantly on leaves (77.5%), and spends more time feeding (40.0%) and resting (27.0%) while compared to the other two subspecies. Kernel Density Estimation Method based on GPS technology confirms that R. r roxellana has relatively larger home ranges (49.1 km2). The unit size (8.3 ± 3.5 individuals) of R. r roxellana is also smaller. Therefore, it is possible that differences in food availability in relation to habitats have important impacts on the feeding strategy and social system of the golden snub-nosed monkey. These results provide data to further explore intraspecific adaptations of living primates. [ABSTRACT FROM AUTHOR]

Miller Fisher's syndrome (MFS) commonly presents in the fourth and fifth decades and are rare in people over 70 years. An 85-year-old female with no significant medical history presented with upper extremity anesthesia, ptosis, and unsteady gait. The patient had a history of hypertension and diabetes mellitus. Physical examination showed bilateral total external ophthalmoplegia, areflexia, and cerebellar ataxia. Radiological and laboratory studies were unremarkable. Lumbar puncture showed albuminocytological dissociation. The combined history, physical examination, and lumbar puncture results established a presumptive diagnosis of MFS. Intravenous immunoglobulin was given for 5 days. The patient gradually improved 10 days after the onset of symptoms. Ophthalmoplegia had fully recovered after 6 months. To the best of our knowledge, this case represented the oldest patient with MFS. [ABSTRACT FROM AUTHOR]

Background: Anti-N-methyl-D-aspartate receptor encephalitis is an increasingly common autoimmune disorder mediated by antibodies to certain subunit of the N-methyl-D-aspartate receptor. Recent literatures have described anti-thyroid and infectious serology in this encephalitis but without follow-up.Case Presentation: A 17-year-old Chinese female patient presented with psychiatric symptoms, memory deficits, behavioral problems and seizures. She then progressed through unresponsiveness, dyskinesias, autonomic instability and central hypoventilation during treatment. Her conventional blood work on admission showed high titers of IgG antibodies to thyroglobulin, thyroid peroxidase and IgM antibodies to Epstein-Barr virus viral capsid antigen. An immature ovarian teratoma was found and removal of the tumor resulted in a full recovery. The final diagnosis of anti-N-methyl-D-aspartate receptor encephalitis was made by the identification of anti-N-methyl-D-aspartate receptor antibodies in her cerebral spinal fluid. Pathology studies of the teratoma revealed N-methyl-D-aspartate receptor subunit 1 positive ectopic immature nervous tissue and Epstein-Barr virus latent infection. She was discharged with symptoms free, but titers of anti-thyroid peroxidase and anti-thyroglobulin antibodies remained elevated. One year after discharge, her serum remained positive for anti-thyroid peroxidase and anti-N-methyl-D-aspartate receptor antibodies, but negative for anti-thyroglobulin antibodies and IgM against Epstein-Barr virus viral capsid antigen.Conclusions: Persistent high titers of anti-thyroid peroxidase antibodies from admission to discharge and until one year later in this patient may suggest a propensity to autoimmunity in anti- N-methyl-D-aspartate receptor encephalitis and support the idea that neuronal and thyroid autoimmunities represent a pathogenic spectrum. Enduring anti-N-methyl-D-aspartate receptor antibodies from admission to one year follow-up but seroreversion of Epstein-Barr virus viral capsid antigen IgM may raise the important issue of elucidating the triggers and boosters of anti- N-methyl-D-aspartate receptor encephalitis. [ABSTRACT FROM AUTHOR]