Kaempferol efficacy in metabolic diseases: Molecular mechanisms of action in diabetes mellitus, obesity, non-alcoholic fatty liver disease, steatohepatitis, and atherosclerosis.

The incidence of metabolic diseases has progressively increased, which has a negative impact on human health and life safety globally. Due to the good efficacy and limited side effects, there is growing interest in developing effective drugs to treat metabolic diseases from natural compounds. Kaempferol (KMP), an important flavonoid, exists in many vegetables, fruits, and traditional medicinal plants. Recently, KMP has received widespread attention worldwide due to its good potential in the treatment of metabolic diseases. To promote the basic research and clinical application of KMP, this review provides a timely and comprehensive summary of the pharmacological advances of KMP in the treatment of four metabolic diseases and its potential molecular mechanisms of action, including diabetes mellitus, obesity, non-alcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH), and atherosclerosis. According to the research, KMP shows remarkable therapeutic effects on metabolic diseases by regulating multiple signaling transduction pathways such as NF-κB, Nrf2, AMPK, PI3K/AKT, TLR4, and ER stress. In addition, the most recent literature on KMP's natural source, pharmacokinetics studies, as well as toxicity and safety are also discussed in this review, thus providing a foundation and evidence for further studies to develop novel and effective drugs from natural compounds. Collectively, our manuscript strongly suggested that KMP could be a promising candidate for the treatment of metabolic diseases.

Network meta-analysis of 7 acupuncture therapies for knee osteoarthritis.

OBJECTIVE: With the progression of society aging demographic, the prevalence of knee osteoarthritis (KOA) continues to rise steadily, exerting a significant impact on individuals' quality of life. Acupuncture therapy has garnered extensive utilization in the management of osteoarthritis; however, a comprehensive systematic review integrating acupuncture with traditional Chinese medicine remains absent. This study compared the clinical efficacy of 7 acupuncture methods (electroacupuncture, conventional acupuncture, warm needle, floating needle, fire needle, needle knife, and silver needle) for the treatment of KOA through a network meta-analysis. METHODS: This study examined the databases-PubMed, EMbase, The Cochrane Library, the China Biology Medicine, Chinese Journal Full-text Database, Wanfang Database, and VIP Database-for randomized controlled trials of the 7 methods for KOA treatment. The search time spanned from the database establishment to March 5, 2022. The primary outcome indicator was the total effective rate, and the secondary outcome indicator was the visual analog scale. After the layer-by-layer screening, the quality of the literature was assessed using the Cochrane systematic reviewer manual 5.1.0 bias risk assessment tool for randomized controlled trials. After data extraction, the R4.0.1 software was used for network meta-analysis. RESULTS: Based on the network meta-analysis, the ranking of interventions based on the surface under the cumulative ranking curve for the total effective rate is as follows: silver needle (0.99) > floating needle (0.97) > needle knife (0.66) > fire needle (0.56) > warm needle (0.44) > conventional acupuncture (0.35) > electroacupuncture (0.13). Regarding the improvement in visual analog scale scores, the surface under the cumulative ranking curve ranking is as follows: silver needle (0.97) > conventional acupuncture (0.67) > needle knife (0.64) > floating needle (0.51) > warm needle (0.44) > fire needle (0.14) > electroacupuncture (0.09). CONCLUSION: Based on the network meta-analysis, silver needle therapy emerged as the most efficacious and analgesic intervention for KOA. Nevertheless, given the notable variations in the quality and quantity of studies encompassing diverse treatment modalities, the findings of this research necessitate further substantiation through forthcoming high-quality multicenter, large-sample, randomized double-blind trials.

Prognostic model for the prediction of cancer-specific survival in elderly patients with stage I-III gastric cancer.

Elderly patients with gastric cancer (GC) exhibit unique physiological conditions and population characteristics. However, no efficient predictive tools have been developed for this patient subgroup. We extracted data on elderly patients diagnosed with stage I-III GC between 2010 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database, and applied Cox regression analysis to examine factors associated with cancer-specific survival (CSS). A prognostic model was developed and validated to predict CSS. We assessed the performance of the prognostic model and stratified patients based on their prognostic scores. Notably, 11 independent prognostic factors, including age, race, grade, the tumor-node-metastasis (TNM) stage, T-stage, N-stage, operation, tumor size, regional nodes, radiation, and chemotherapy, associated with CSS were identified using multivariate Cox regression. A nomogram was constructed based on these predictors. The C-index score of the nomogram was 0.802 (95% (confidence interval) [CI]: 0.7939-0.8114), which is superior to the American Joint Commission on Cancer (AJCC) TNM staging prediction ability in the training cohort (C-index: 0.589; 95% CI: 0.5780-0.6017). Based on the receiver operating characteristic (ROC) and calibration curve, the predicted value of the nomogram demonstrated a satisfactory accuracy with the actual observation value. Additionally, decision curve analysis (DCA) showed that the nomogram had a more ideal clinical net benefit than TNM staging. Survival analysis of the different risk groups confirmed the noteworthy clinical and statistical utility of the nomogram in prognosis stratification. This retrospective study reports the successful creation and validation of a nomogram for predicting CSS at 1-, 3- and 5-years in elderly patients with stage I-III GC. This nomogram critically guides personalized prognostic assessments and may contribute to clinical decision-making and consultation for postoperative survival.

Evaluating Efficacy and Safety of Tacrolimus Treatment in Membranous Nephropathy: Results of a Retrospective Study of 182 Patients.

Purpose: Tacrolimus is recommended by KDIGO Clinical Practice Guidelines as an initial therapy for the treatment of membranous nephropathy (MN). However, little is known about the factors that influence response and recurrence of the disease after tacrolimus therapy, and there are limited data regarding the duration of tacrolimus treatment. Here, we present a real-world retrospective cohort study of 182 MN patients treated with tacrolimus, aiming to assess the efficacy and safety of tacrolimus in the treatment of MN. Patients and Methods: The clinical data of 182 patients with MN treated with tacrolimus and followed up for at least one year were analyzed retrospectively for the efficacy and safety of tacrolimus. Results: The mean follow-up period was 27.3 (19.3-41.6) months. A total of 154 patients (84.6%) achieved complete or partial remission, and 28 patients (15.4%) did not. Multivariate Cox regression analysis showed that male and higher baseline BMI were independently associated with lower, while higher serum albumin was associated with higher probability of remission. Among the responders, 56 patients (36.4%) relapsed. After adjustments for age and sex, Cox regression analysis revealed that the longer period of full-dose tacrolimus was administered, the lower the incidence of relapse. However, high levels of serum creatinine and proteinuria at the onset of tacrolimus discontinuation were risk factors for relapse. During the treatment of tacrolimus, a decline in renal function (≥50% increase in serum creatinine after the onset of tacrolimus treatment) was the most common adverse reaction, observed in 20 (11.0%) patients, followed by elevated blood glucose and infection, but the latter two occurred mostly during treatment with tacrolimus plus corticosteroids. Conclusion: Tacrolimus is effective in the treatment of MN, but the relapse rate is high. Clinical studies with larger sample sizes are needed to further explore the use of tacrolimus in the treatment of membranous nephropathy.

Epigenetic modifications and metabolic memory in diabetic retinopathy: beyond the surface.

Epigenetics focuses on DNA methylation, histone modification, chromatin remodeling, noncoding RNAs, and other gene regulation mechanisms beyond the DNA sequence. In the past decade, epigenetic modifications have drawn more attention as they participate in the development and progression of diabetic retinopathy despite tight control of glucose levels. The underlying mechanisms of epigenetic modifications in diabetic retinopathy still urgently need to be elucidated. The diabetic condition facilitates epigenetic changes and influences target gene expression. In this review, we summarize the involvement of epigenetic modifications and metabolic memory in the development and progression of diabetic retinopathy and propose novel insights into the treatment of diabetic retinopathy.

Anchoring super-enhancer-driven oncogenic lncRNAs for anti-tumor therapy in hepatocellular carcinoma.

Super-enhancer (SE) plays a vital role in the determination of cell identity and fate. Up-regulated expression of coding genes is frequently associated with SE. However, the transcription dysregulation driven by SE, from the viewpoint of long non-coding RNA (lncRNA), remains unclear. Here, SE-associated lncRNAs in HCC are comprehensively outlined for the first time. This study integrally screens and identifies several novel SE-associated lncRNAs that are highly abundant and sensitive to JQ1. Especially, HSAL3 is identified as an uncharacterized SE-driven oncogenic lncRNA, which is activated by transcription factors HCFC1 and HSF1 via its super-enhancer. HSAL3 interference negatively regulates NOTCH signaling, implying the potential mechanism of its tumor-promoting role. The expression of HSAL3 is increased in HCC samples, and higher HSAL3 expression indicates an inferior overall survival of HCC patients. Furthermore, siHSAL3 loaded nanoparticles exert anti-tumor effect on HCC in vitro and in vivo. In conclusion, this is the first comprehensive survey of SE-associated lncRNAs in HCC. HSAL3 is a novel SE-driven oncogenic lncRNA, and siHSAL3 loaded nanoparticles are therapeutic candidates for HCC. This work sheds lights on the merit of anchoring SE-driven oncogenic lncRNAs for HCC treatment.

Upregulation of Superenhancer-Driven LncRNA FASRL by USF1 Promotes De Novo Fatty Acid Biosynthesis to Exacerbate Hepatocellular Carcinoma.

Superenhancers drive abnormal gene expression in tumors and promote malignancy. However, the relationship between superenhancer-associated long noncoding RNA (lncRNA) and abnormal metabolism is unknown. This study identifies a novel lncRNA, fatty acid synthesis-related lncRNA (FASRL), whose expression is driven by upstream stimulatory factor 1 (USF1) through its superenhancer. FASRL promotes hepatocellular carcinoma (HCC) cell proliferation in vitro and in vivo. Furthermore, FASRL binds to acetyl-CoA carboxylase 1 (ACACA), a fatty acid synthesis rate-limiting enzyme, increasing fatty acid synthesis via the fatty acid metabolism pathway. Moreover, the expression of FASRL, USF1, and ACACA is increased, and their high expression indicates a worse prognosis in HCC patients. In summary, USF1 drives FASRL transcription via a superenhancer. FASRL binding to ACACA increases fatty acid synthesis and lipid accumulation to mechanistically exacerbate HCC. FASRL may serve as a novel prognostic marker and treatment target in HCC.

A Novel Cuprotosis-Related Gene FDX1 Signature for Overall Survival Prediction in Clear Cell Renal Cell Carcinoma Patients.

Background: Ferredoxin 1 (FDX1) is a newly discovered gene regulating cuprotosis. However, the effect of FDX1 expression on clear renal cell carcinoma (ccRCC) is unknown. Methods: Gene expression profiles and clinical data of ccRCC patients were downloaded from the Cancer Genome Atlas (TCGA) database. The differences in FDX1 expression between ccRCC and nonneoplastic tissues adjacent to cancer were analyzed by R software. The results were validated by GEO data, quantitative real-time polymerase chain reaction (qRT-PCR), western blotting (WB), and immunohistochemistry (IHC). Chi-square test was used to analyze the clinical pathological parameters. Kaplan-Meier survival analysis and Cox proportional hazard regression model selection were used to evaluate the effect of FDX1 expression on overall survival. Protein interaction networks were used to analyze other proteins that interact with FDX1. Signal pathway analysis was performed for possible FDX1 enrichment using GSEA and ssGSEA algorithms. Pan-cancer analysis of FDX1 was carried out through TCGA database. Results: The FDX1 expression in nontumor tissues was significantly higher than that in ccRCC, and the expression difference was verified by GEO data, qRT-PCR, WB, and IHC. The high expression of FDX1 was significantly related to the well overall survival rate (P < 0.05). The chi-square test showed that the high expression of FDX1 was related to gender, TNM stage, T stage, lymph node metastasis, and pathological grade. Additionally, the FDX1 expression level was different in groups classified based on pathological grade, gender, TNM stage, T stage, lymph node metastasis, and distant metastasis (P < 0.05). The multivariate analysis revealed the high expression of FDX1 as an important independent predictor for overall survival. STRING database results showed that LIAS and LIPT1 may interact with FDX1 in the PPI network, which are also involved in the regulation of cuprotosis. The GSEA and ssGSEA results showed that the FDX1 was enriched in the anticancer pathway. The FDX1 high expression is associated with better prognosis in many cancers, as revealed by pan-cancer analysis. Conclusion: FDX1 may play a role in the progression of ccRCC as a tumor suppressor gene. It can be used as a potential prognostic indicator and therapeutic target of ccRCC. However, the cuprotosis regulatory role in the development of ccRCC needs to be further verified.

Anti-VEGF reduces inflammatory features in macular edema secondary to retinal vein occlusion.

AIM: To investigate the anti-inflammatory effect of intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) in patients with macular edema secondary to retinal vein occlusion (RVO-ME). METHODS: Twenty-eight eyes from twenty-eight treatment-naïve patients (14 males and 14 females) with RVO-ME were included in this retrospective study. The retinal vein occlusion (RVO) was comprised of both central retinal vein occlusion (CRVO, n=14) and branch retinal vein occlusion (BRVO, n=14). Intravitreal injection of anti-VEGF reagents were administered monthly for three consecutive months, in which 18 patients were injected with ranibizumab and 10 patients were injected with conbercept. All eyes were imaged with optical coherence tomography angiography (OCTA) at baseline and 1wk after monthly intravitreal anti-VEGF injection. The visual acuity (VA), central macular thickness (CMT), the number of hyperreflective foci (HRF) recognized as an inflammatory sign in OCT images, and non-perfusion area (NPA), were compared before and after anti-VEGF treatments. RESULTS: The mean interval between baseline and follow-up was 29.4±0.79 (range, 27-48)d. Compared with the baseline, the VA improved (logMAR 1.5±0.1 vs 0.8±0.1, P<0.05) and CMT decreased (460±34.0 µm vs 268.8±12.0 µm, P<0.05), significantly, after anti-VEGF treatment. The number of HRF was decreased significantly (76.5±4.8 vs 47.8±4.3, P<0.05) after anti-VEGF treatment. CONCLUSION: Anti-VEGF therapy is effective in treating RVO-ME. The mechanisms for the decreased HRF and the reduction of NPA by anti-VEGF therapy merits further exploration.

eccDNAdb: a database of extrachromosomal circular DNA profiles in human cancers.

Extrachromosomal circular DNA (eccDNA) elements are circular DNA molecules that are derived from but are independent of chromosomal DNA. EccDNA is emerging as a rising star because of its ubiquitous existence in cancers and its crucial role in oncogene amplification and tumor progression. In the present study, whole-genome sequencing (WGS) data of cancer samples were downloaded from public repositories. Afterwards, eccDNAs were identified from WGS data via bioinformatic analyses. To leverage database coverage, eccDNAs were also collected by manual curation of literatures. Gene expression and clinical data were downloaded from TCGA and CCLE and then used to investigate the roles of eccDNAs in cancers. Finally, the first integrated database of eccDNAs, eccDNAdb, was developed. eccDNAdb currently includes 1270 eccDNAs, which were identified in 480 samples (of 42 cancers) after analyzing a total number of 3395 tumor samples (of 57 cancers) including patient tissues, patient-derived xenografts, and cancer cell lines. A total number of 54,901 eccDNA genes were annotated and included in the database as well. With the integration of gene expression, clinical information and chromatin accessibility data, eccDNAdb enables users to easily determine the biological function and clinical relevance of eccDNAs in human cancers. In conclusion, eccDNAdb is freely accessible at http://www.eccdnadb.org . To our knowledge, eccDNAdb is the first database in the eccDNA research field. It is expected to provide insight for novel cancer therapies.

Is Iba-1 protein expression a sensitive marker for microglia activation in experimental diabetic retinopathy?

AIM: To investigate the changes of Iba-1 and other potential markers for microglia activation in experimental diabetic retinopathy (DR). METHODS: Male Sprague-Dawley rats were rendered diabetes via intraperitoneal injection of streptozotocin. The retinas were harvested at 1 to 24wk after diabetes onset. Hypoxia-treated mouse microglial cell line (BV2 cells) was employed as the in vitro model to mimic diabetic condition. The expressions of Iba-1, CD11b, ICAM-1 as well as the inflammatory factors were examined with real-time polymerase chain reaction, Western blot and immunofluorescence both in vivo and in vitro. RESULTS: Compared with age-matched normal control, the number of microglia (Iba-1 positive immunostaining) in diabetic rat retinas was increased from 1 to 24wk of diabetes, which was most obvious at 12wk of diabetes. Iba-1 protein expression detected by Western blot was increased slightly in diabetic rat retinas compared with that in age-matched normal control; however, there was statistically significant between two groups only at 2wk after diabetes onset. The mRNA expression of Iba-1 was decreased significantly at 2 and 4wk of diabetic rat retinas, and remained unchanged at 8 and 12wk of diabetes. In BV2 cells, there was no significant change for the Iba-1 protein expression between normoxia and hypoxia groups; however, its mRNA level was decreased significantly under hypoxia. To further characterize microglial activation, F4/80, CD11b and inflammatory factors were detected both in vivo and in vitro. Compared with normal control, the expressions of F4/80 and CD11b as well as the inflammatory factors, such as ICAM-1, iNOS, COX2, IL-1ß and IL-6, were increased significantly both in vivo and in vitro. CONCLUSION: Iba-1 protein expression might not be a sensitive marker to evaluate the activation of microglia in experimental DR. However, Iba-1 immunostaining, in combination with other markers like CD11b and ICAM-1, could be well reflect the activation of microglia. Thus, it is of great importance to explore other potential marker to evaluate the activation of microglia.

Method used to establish a large animal model of drug-induced acute kidney injury.

Acute kidney injury is a serious health hazard disease due to its complex etiology and lack of effective treatments, resulting in high medical costs and high mortality. At present, a large number of basic research studies on acute kidney injury have been carried out. However, acute kidney injury models established in rodents sometimes do not simulate the course of human disease well. Research in large animal models of acute kidney injury is relatively rare, and methods to build a mature model of acute kidney injury have failed. Because its kidney anatomy and morphology are very similar to those in humans, the mini pig is an ideal animal in which to model kidney disease. Nephrotoxic drug-induced acute kidney injury has a high incidence. In this study, we established models of acute kidney injury induced by two drugs (gentamicin and cisplatin). Finally, the model of cisplatin-induced acute kidney injury was developed successfully, but we found the model of gentamycin-induced acute kidney injury was not reproducible. Compared to other models, these models better represent acute kidney injury caused by antibiotics and chemotherapeutic drugs and provide a basis for the study of new treatments for acute kidney injury in a large animal model.

Kinetic study on elemental mercury release from fly ashes and hydrated fly ash cement pastes.

The kinetics of elemental mercury (Hg0) release from fly ashes and hydrated fly ash cement pastes was investigated using a homemade Hg measurement system. Three types of fly ash (FA) and ordinary Portland cement (OPC) were used to prepare cement pastes. After standard curing for 28 days, the hydrated cement paste (HCP) was ground into a fine powder for Hg emission measurements. Detectable Hg0 was found released from both fly ashes and hydrated fly ash cement pastes. The results show that elevated temperatures and evaporation of the capillary pore water in wet HCP samples accelerate Hg0 release. Both desorption of Hg0 from the particle surface of HCP powder and migration of Hg0 from the inner pores contribute to Hg0 release. The kinetic calculation indicates that the hydration products of hydrated fly ash cement have little immobilization effect on Hg0, which is mainly physically encapsulated in the HCP particles by hydration products.

Role of protein S-nitrosylation in regulating beef tenderness.

This research aimed to explore the role of protein S-nitrosylation in regulating the tenderness of postmortem beef, from the perspective of µ-calpain autolysis and protein proteolysis. Five bovine semimembranosus muscles were incubated with three treatments including S-nitrosoglutathione (GSNO, nitric oxide donor), normal saline and Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME, nitric oxide synthase inhibitor). The results showed that the level of protein S-nitrosylation was improved by GSNO treatment and reduced by L-NAME treatment (p < 0.05). Compared to the control, GSNO treatment had higher shear force while L-NAME treatment presented lower shear force at 7 d postmortem (p < 0.05). In addition, µ-calpain autolysis, myofibrillar protein and desmin degradation were reduced by GSNO treatment and accelerated by L-NAME treatment (p < 0.05). Therefore, it can be speculated that protein S-nitrosylation could affect beef tenderization by regulating the autolysis of µ-calpain and the degradation of myofibrillar proteins.

miRNAs in stem cell-derived extracellular vesicles for acute kidney injury treatment: comprehensive review of preclinical studies.

Stem cell therapy has been applied in many fields. Basic and clinical studies on stem cell therapy for acute kidney injury (AKI) have been conducted. Stem cells have been found to exert renal protection through a variety of mechanisms, such as regulating the immune system and secreting growth factors, cytokines, and extracellular vesicles (EVs). Among them, EVs are considered to be important mediators for stem cell protection because they contain various biological components, including microRNAs (miRNAs). miRNAs are a class of small RNAs that function in posttranscriptional gene regulation. A number of studies have confirmed that miRNAs in stem cell-derived EVs can protect from AKI. miRNAs can enter the injured renal tissue through EVs released from stem cells, thereby exerting anti-inflammatory, anti-apoptotic, anti-fibrotic, and pro-angiogenesis effects on AKI. However, the stem cell sources and AKI models used in these studies have differed. This article will summarize the miRNAs that play a role in kidney protection in stem cell EVs and clarifies the treatment characteristics and mechanisms of different miRNAs. This may provide a reference for clinical practice for acute and chronic kidney diseases.

The emergence of long non-coding RNAs in hepatocellular carcinoma: an update.

Hepatocellular carcinoma (HCC) accounting for roughly 90% of all primary liver neoplasms is the sixth most frequent neoplasm and the second prominent reason of tumor fatality worldwide. As regulators of diverse biological processes, long non-coding RNAs (lncRNAs) are involved in onset and development of neoplasms. With the continuous booming of well-featured lncRNAs in HCC from 2016 to now, we reviewed the newly-presented comprehension about the relationship between lncRNAs and HCC in this study. To be specific, we summarized the overview function and study tools of lncRNAs, elaborated the roles of lncRNAs in HCC, and sketched the molecule mechanisms of lncRNAs in HCC. In addition, the application of lncRNAs serving as biomarkers in early diagnosis and outcome prediction of HCC patients was highlighted.

High TGF-ß1 expression predicts poor disease prognosis in hepatocellular carcinoma patients.

Transforming growth factor beta (TGF-ß) promotes the pathogenesis of hepatocellular carcinoma (HCC). We evaluated the associations between TGF-ß1 expression and clinicopathological parameters in HCC patients from The Cancer Genome Atlas (TCGA), as well as the prognostic power of TGF-ß1 expression. Eligible studies were retrieved from several databases, and effects (hazard ratios (HRs) with 95% confidence intervals (CIs)) for overall survival (OS), disease-free survival (DFS), recurrence-free survival (RFS), metastasis-free survival (MFS), and progression-free survival (PFS) were pooled to assess the prognostic ability of TGF-ß1 expression in HCC patients. Twelve qualified articles and our TCGA data comprising 2,021 HCC patients were incorporated. In the TCGA analysis, HCC patients with higher TGF-ß1 expression presented a shorter OS than those with lower TGF-ß1 expression (HR = 1.42, p < 0.05). In the meta-analysis, univariate analyses showed that HCC patients with higher TGF-ß1 expression had a shorter OS (pooling HR = 1.71, p < 0.01) and DFS/RFS/MFS/PFS (pooling HR = 1.60, p < 0.01) than those with lower TGF-ß1 expression. In conclusion, our results suggested that high TGF-ß1 expression promotes a poor prognosis in HCC patients.

High lncRNA H19 expression as prognostic indicator: data mining in female cancers and polling analysis in non-female cancers.

Upregulation of lncRNA H19 expression is associated with an unfavorable prognosis in some cancers. However, the prognostic value of H19 in female-specific cancers has remained uncharacterized. In this study, the prognostic power of high H19 expression in female cancer patients from the TCGA datasets was analyzed using Kaplan-Meier survival curves and Cox's proportional hazard modeling. In addition, in a meta-analysis of non-female cancer patients from TCGA datasets and 12 independent studies, hazard ratios (HRs) with 95% confidence interval (CI) for overall survival (OS) and disease-free survival (DFS)/relapse-free survival (RFS)/metastasis-free survival (MFS)/progression-free survival (PFS) were pooled to assess the prognostic value of high H19 expression. Kaplan-Meier analysis revealed that patients with uterine corpus cancer and higher H19 expression had a shorter OS (HR=2.710, p<0.05), while females with cervical cancer and increased H19 expression had a shorter RFS (HR=2.261, p<0.05). Multivariate Cox regression analysis showed that high H19 expression could independently predict a poorer prognosis in cervical cancer patients (HR=4.099, p<0.05). In the meta-analysis, patients with high H19 expression showed a poorer outcome in non-female cancer (p<0.05). These results suggest that high lncRNA H19 expression is predictive of an unfavorable prognosis in two female cancers (uterine corpus endometrioid cancer and cervical cancer) as well as in non-female cancer patients.

Prenatal diagnosis for a Chinese family with a de novo DMD gene mutation: A case report.

BACKGROUND: Patients with Duchenne muscular dystrophy (DMD) usually have severe and fatal symptoms. At present, there is no effective treatment for DMD, thus it is very important to avoid the birth of children with DMD by effective prenatal diagnosis. We identified a de novo DMD gene mutation in a Chinese family, and make a prenatal diagnosis. METHODS: First, multiplex ligation-dependent probe amplification (MLPA) was applied to analyze DMD gene exon deletion/duplication in all family members. The coding sequences of 79 exons in DMD gene were analyzed by Sanger sequencing in the patient; and then according to DMD gene exon mutation in the patient, DMD gene sequencing was performed in the family members. On the basis of results above, the pathogenic mutation in DMD gene was identified. RESULTS: MLPA showed no DMD gene exon deletion/duplication in all family members. Sanger sequencing revealed c.2767_2767delT [p.Ser923LeufsX26] mutation in DMD gene of the patient. Heterozygous deletion mutation (T/-) at this locus was observed in the pregnant woman and her mother and younger sister. The analyses of amniotic fluid samples indicated negative Y chromosome sex-determining gene, no DMD gene exon deletion/duplication, no mutations at c.2767 locus, and the inherited maternal X chromosome different from that of the patient. CONCLUSION: The pathogenic mutation in DMD gene, c.2767_2767delT [p.Ser923LeufsX26], identified in this family is a de novo mutation. On the basis of specific conditions, it is necessary to select suitable methods to make prenatal diagnosis more effective, accurate, and economic.

ERCC1 single nucleotide polymorphism C8092A, but not its expression is associated with survival of esophageal squamous cell carcinoma patients from Fujian province, China.

Esophageal carcinoma is one of the world's deadliest cancers. Esophageal squamous cell carcinoma (ESCC) is more frequent than adenocarcenoma (AC) in China. Platinum-based chemotherapy with surgical resection is a common treatment approach for ESCC; however, the treatment response is uncertain. Evidence suggests polymorphisms in genes encoding excision repair cross-complementing group 1 (ERCC1), a protein involved in nuclear excision repair (NER), may help predict response to cisplatin and other platinum-based chemotherapeutics. Multiple ERCC1 single nucleotide polymorphisms (SNPs) have been associated with platinum chemotherapy response. Two common SNPs occur at the C8092A and C118T loci. Our study aimed to determine if 1) an association exists between ERCC1 tumor expression and patient survival, 2) whether adjuvant therapy influence on survival is related to histological ERCC1 presence in tumor cell nuclei, and 3) whether other clinicopathological characteristics in a cohort of patients following surgery for various stages of ESCC are associated with tumor ERCC1 expression. One hundred eight patients were included in the study, and tumor biopsy was collected for genotyping and immunohistochemical analysis of ERCC1. Sixty-seven patients (62%) received no adjuvant therapy, and the rest had either platinum-based chemotherapy (28.5%), radiotherapy (6.5%) or both treatments (2.8%). Log-rank analysis revealed no significant connection between tumor ERCC1 expression (P = 0.12) or adjuvant therapy (P = 0.56) on patient survival. Also, non-parametric Mann-Whitney analysis showed no significant link between tumor size or nodus tumor formation and ERCC1 presence in patients in the study. Interestingly, C8092A SNP showed significant association with patient survival (P = 0.01), with patients homozygous for the mutant allele showing the most significantly reduced survival (P = 0.04) compared to those homozygous for the dominant allele (CC). Our results provide novel insight into the genotypic variation of patients from Quanzhou, Fujian province China.