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Background: Numerous studies have indicated that some Chinese herbal injections (CHIs) might have a beneficial treatment effect when used in combination with chemotherapy. However, the results of these studies have been inconsistent. The aim of this network meta-analysis (NMA) was to evaluate and compare the clinical efficacy and safety of different CHIs combined with gemcitabine plus cisplatin (GP) regimen chemotherapy with that of GP regimen chemotherapy alone in the treatment of patients with advanced non-small cell lung cancer (NSCLC). Materials and Methods: Eight databases were systematically searched to identify randomized clinical trials (RCTs) from the date of inception of the database to August 11, 2021. The primary outcome measures were the objective response rate (ORR) and adverse reactions (including nausea and vomiting, and leukopenia). The secondary outcome measures were median survival time (MST) and quality of life (QOL). The quality of the included studies was assessed using the Cochrane risk of bias tool. Standard pair-wise and Bayesian NMAs were carried out to compare the effectiveness and safety of different CHIs combined with GP regimen chemotherapy using WinBUGS 14 and Stata 15.1 software. Sensitivity analysis and Egger's test were also performed to check robust. Results: A total of 92 eligible RCTs involving 7,728 patients and 10 CHIs were included. The results showed that Kangai injection (KAI), Kanglaite injection (KLT), Aidi injection and Compound Kushen (CKSI) injection displayed obvious advantages in both efficacy and safety. Aidi+GP (79.0%) showed great advantages of ORR, and KAI+GP and KLT+GP had the lowest probability in terms of leukopenia (4.4%) and nausea and vomiting (24.2%). Besides, KLT+GP was shown to positively affect MST. According to the subgroup analyses, CHIs might have a limited effect in reducing adverse reactions, and have a similar effect in squamous cell carcinoma and adenocarcinoma. Conclusions: KAI+GP of adjuvant drugs, Aidi+GP and CKSI+GP of anticancer drugs appeared to be the advantageous treatment options for patients with advanced NSCLC, owing to its superior therapeutic performance and reduced adverse reactions. KLT+GP might prolong survival. Nevertheless, additional results from multicenter trials and high-quality studies will be pivotal in supporting our findings.

Derived from structurally similar precursors, two different azidodiboranes went through distinct aryl migration reactions triggered by different boron-boron separation distances. Biphenylene based diborane with a shorter boron-boron distance underwent heterolateral aryl migration to form a seven-membered azadiborepin, while xanthrene based diborane with a longer boron-boron distance afforded a stable bis-azidoborane scaffold. The pyrolysis of such a bis-azidoborane led to eight-membered oxazadiborocine through homolateral aryl migration and subsequent [3+2] cycloaddition. Density functional theory (DFT) calculations unveiled that the boron-boron separation distances were the intrinsic factors for the distinct migrations.

3,6-dichlorobenzo[b]thiophene-2-carboxylic acid (BT2) is a benzothiophene carboxylate derivative that can suppress the catabolism of branched-chain amino acid (BCAA)-associated mammalian target of rapamycin complex 1 (mTORC1) activation. Previous studies have demonstrated the therapeutic effects of BT2 on arthritis, liver cancer, and kidney injury. However, the effects of BT2 on ulcerative colitis (UC) are unknown.To investigate the anti-UC effects of BT2 and the underlying mechanism.Mouse UC models were created through the administration of 3.5% dextran sodium sulfate (DSS) for 7 d. The mice in the treated groups were administered salazosulfapyridine (300 mg/kg) or BT2 (20 mg/kg) orally from day 1 to day 7. At the end of the study, all of the mice were sacrificed, and colon tissues were removed for hematoxylin and eosin staining, immunoblot analyses, and immunohistochemical assays. Cytokine levels were measured by flow cytometry. The contents of BCAAs including valine, leucine, and isoleucine, in mouse serum were detected by liquid chromatography-tandem mass spectrometry, and the abundance of intestinal flora was analyzed by 16S ribosomal DNA sequencing.Our results revealed that BT2 significantly ameliorated the inflammatory symptoms and pathological damage induced by DSS in mice. BT2 also reduced the production of the proinflammatory cytokines interleukin 6 (IL-6), IL-9, and IL-2 and increased the anti-inflammatory cytokine IL-10 level. In addition, BT2 notably improved BCAA catabolism and suppressed mTORC1 activation and cyclooxygenase-2 expression in the colon tissues of UC mice. Furthermore, high-throughput sequencing revealed that BT2 restored the gut microbial abundance and diversity in mice with colitis. Compared with the DSS group, BT2 treatment increased the ratio ofOur results indicated that BT2 significantly ameliorated DSS-induced UC and that the latent mechanism involved the suppression of BCAA-associated mTORC1 activation and modulation of the intestinal flora.

Background Disorder of lipid metabolism plays an essential role in both initiation and progression of alcoholic fatty liver disease (AFLD), and fatty acid βoxidation is increasingly being considered a crucial factor controlling lipid metabolism. Hif-2α is a member of the Hifs family of nuclear receptors, taking part in regulating hepatic fatty acid β-oxidation. However, its functional role in AFLD and its underlying mechanism remains unclear.Results Hif-2α was upregulated in EtOH-fed mice and EtOH-induced AML-12 cells. Inhibition or silence of Hif-2α led to the enhancement of fatty acid β-oxidation and BNIP3-dependent mitophagy. Further studies have shown that downregulation of Hif-2α was well established to activate the PPARα/PGC-1α signaling pathway concerned in hepatic fatty acid β-oxidation by mediating BNIP3-dependent mitophagy, and ultimately delaying the progression of AFLD. Conclusions Hif-2α induces liver steatosis, which promotes the progression of AFLD. Our results preciously developed a novel Hif-2α-BNIP3-dependent mitophagy regulatory pathway interconnected with EtOH-induced lipid accumulation and might be a potential therapeutic target for prevention and treatment of AFLD.

Purpose Gastric cancer (GC) is a type of malignant cancer with a poor prognosis. The iron’s metabolism plays an important role in the process of GC. The aim of this study was to evaluate the effectiveness of SLC22A17, associated with iron metabolism, in predicting the prognosis of GC patients. Materials and Methods We analyzed genes related to iron metabolism of gastric cancer mRNA-seq data from TCGA database. We identified an iron metabolism-related SLC22A17 as an independent prognostic factor using univariate and multivariate Cox regression analysis. Results Further research showed that SLC22A17 was related with many pathways involved in the process of gastric cancer, and the expression was associated with diverse cancer-infiltrating immune cells. The expression of SLC22A17 was associated with T (Topography). Conclusion We validated that SLC22A17 associated with iron metabolism could serve as a prognostic biomarker for GC patients.

Nitrogen fixation is essential for the maintenance of life and development of society, however, the large bond dissociation energy and nonpolarity of the triple bond constitute a considerable challenge. The transition metals, by virtue of their combination of empty and occupied d orbitals, are prevalent in the nitrogen fixation studies and are continuing to receive a significant focus. The main group metals have always been considered incapable in dinitrogen activation owing to the absence of energetically and symmetrically accessible orbitals. The past decades have witnessed significant breakthroughs in the dinitrogen activation with the main group elements and compounds

The characterization and identification of the dynamics of cluster catalysis are crucial to unraveling the origin of catalytic activity. However, the dynamical catalytic effects during the reaction process remain unclear. Herein, we investigate the dynamic coupling effect of elementary reactions with the structural fluctuations of sub-nanometer Au clusters with different sizes using ab initio molecular dynamics and the free energy calculation method. It was found that the adsorption-induced solid-to-liquid phase transitions of the cluster catalysts give rise to abnormal entropy increase, facilitating the proceeding of reaction, and this phase transition catalysis exists in a range of clusters with different sizes. Moreover, clusters with different sizes show different transition temperatures, resulting in a non-trivial size effect. These results unveil the dynamic effect of catalysts and help understand cluster catalysis to design better catalysts rationally.

Twist is a repressor of E-cadherin transcription that induces epithelial-mesenchymal transition and cancer metastasis. However, the prognostic value of Twist expression in patients with esophageal cancer remains controversial.To investigate the prognostic and clinicopathological value of Twist expression in esophageal cancer.Published literature in databases such as EMBASE, Web of Science, PubMed, China National Knowledge Infrastructure, Wanfang, and VIP databases was searched for eligible articles. Participants with esophageal cancer whose tumor tissues underwent immunohistochemistry to detect the expression of Twist were considered. Our meta-analysis was conducted using Stata version 12.0. The hazard ratio (HR) and relative ratio (RR) with their 95%CI were pooled. Heterogeneity was estimated byEleven articles published between 2009 and 2021 fulfilled the selection criteria. The pooled HR for overall survival was 1.88 (95%CI: 1.32-2.69,High expression of Twist is associated with poor esophageal cancer prognosis. Moreover, Twist overexpression is correlated with T stage, lymph node metastasis, distant metastasis, TNM stage, and clinical stage, which indicates that Twist might accelerate esophageal cancer progression and metastasis.

Purpose Chronic kidney disease (CKD) is a global nephrotic syndrome characterized by chronic inflammation, oxidative stress and fibrosis in the kidney. Isoliquiritigenin (ISL), a flavonoid from licorice, has historically been reported to inhibit innate immune responses to inflammation and fibrosis in vivo. However, the effect of ISL on CKD progression is largely unknown.

Human PRICKLE1 gene has been associated with epilepsy. However, the underlying pathogenetic mechanisms remain elusive. Here we report a

Polycythemia vera (PV) has multiple vascular risk factors and gradual onset and is an important risk factor for stroke. The first manifestation in some patients with PV is thrombotic cerebrovascular events. However, there are few reports on polycythemia vera with multiple cerebral infarctions and cerebral microhemorrhage. The clinical and imaging features of two PV patients with multiple cerebral infarctions complicated by cerebral microhemorrhage were analyzed retrospectively in order to improve the clinical understanding of the disease.

Ammonia-oxidizing microorganisms (AOM) play crucial roles in the degradation of ammonia nitrogen in freshwater lakes. Hence, it is necessary to reveal the spatiotemporal dynamic changes of AOM in freshwater lakes. Here, we conducted a study on the spatial and temporal dynamic changes of AOM in different lake regions under gradient nutrient levels in Lake Taihu, and found that the abundance of AOM had significant spatial changes, while the seasonal changes had relatively little effect on the abundance of AOM. We also found that ammonia-oxidizing archaea (AOA) were adapted to freshwater habitats with low nutrient levels, while ammonia-oxidizing bacteria (AOB) and anaerobic ammonia-oxidizing bacteria (AAOB) had higher abundance in high nutrient level lake regions. Moreover, the amoA gene abundance of AOB was much higher than that of AOA, indicating that AOB was the dominant aerobic ammonia oxidizer in the water of Lake Taihu. In addition, temperature, pH and dissolved oxygen all had a positive effect on AOM, especially AOB; while C- and N-related physicochemical factors had a significant positive effect on AAOB, but exhibited a significant negative correlation with AOA. The community structure of AOM also had obvious spatial changes and Group I.1a, Nitrosomonas and Candidatus Brocadia fulgida were the dominant cluster of AOA, AOB and AAOB, respectively.

Since the bipolar disorder (BD) signals identified by genome-wide association study (GWAS) often reside in the non-coding regions, understanding the biological relevance of these genetic loci has proven to be complicated. Transcriptome-wide association studies (TWAS) providing a powerful approach to identify novel disease risk genes and uncover possible causal genes at loci identified previously by GWAS. However, these methods did not consider the importance of epigenetic regulation in gene expression. Here, we developed a novel epigenetic element-based transcriptome-wide association study (ETWAS) that tested the effects of genetic variants on gene expression levels with the epigenetic features as prior and further mediated the association between predicted expression and BD. We conducted an ETWAS consisting of 20 352 cases and 31 358 controls and identified 44 transcriptome-wide significant hits. We found 14 conditionally independent genes, and 10 genes that did not previously implicate with BD were regarded as novel candidate genes, such as ASB16 in the cerebellar hemisphere (P = 9.29 × 10–8). We demonstrated that several genome-wide significant signals from the BD GWAS driven by genetically regulated expression, and NEK4 explained 90.1% of the GWAS signal. Additionally, ETWAS identified genes could explain heritability beyond that explained by GWAS-associated SNPs (P = 5.60 × 10–66). By querying the SNPs in the final models of identified genes in phenome databases, we identified several phenotypes previously associated with BD, such as schizophrenia and depression. In conclusion, ETWAS is a powerful method, and we identified several novel candidate genes associated with BD.

Ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) play crucial roles in ammonia nitrogen degradation in freshwater lake sediment. However, studies on ammonia-oxidizing microorganisms (AOM) in vertical sediment are still limited, especially with respect to the quantitative analysis of the vertical distribution of active AOM at the RNA level. Herein, by researching the AOM in a 75 cm vertical sediment from Lake Taihu, we found that although the total abundance of AOB throughout the whole vertical sediment surpassed that of AOA, active AOA had a closer correlation with the potential nitrification rate than active AOB. The active transcription abundance of AOM generally decreased with increasing depth, especially for AOA, while that of AOB decreased slightly. Compared to active transcription, the total abundance of AOM varied little. The community structures of AOA and AOB changed significantly with increasing depth, and Group I.1a and Nitrosomonas were the predominant clusters, respectively. Ultimately, our study demonstrated that research methods based on the RNA level can accurately reflect the vertical variation in AOM.

Sulfate and water management can be respectively applied to control Cd accumulation in rice, but the interaction mechanisms remain unclear. Three water management coupled with five sulfate application concentrations were employed to investigate rice Cd uptake. Results showed there was a significant interaction between sulfate application and soil redox state, and the highest sulfate treatments reduced rice grain Cd by 63.2, 53.5, and 59.4% under the flooding, flooding-moist alternate (FM), and moist irrigation (M) conditions, respectively. It could be explained by the reduction in rhizosphere soil available Cd and lower transport coefficient from root to aboveground. The Desulfovibrio was demonstrated to participate in CdS precipitation, and its abundance was promoted by sulfate especially under flooding. Additionaly, sulfate application facilitated Cd bounded to FeMn oxides, as rhizosphere soil pH raising under flooding. Under FM and M treatments, sulfate application reduced the abundance of Fe-reducing bacteria Geobacter, and correspondingly reduced Fe and Cd availability in rhizosphere soil. Summarily, Cd transfer from soil to rice can be reduced by applying sulfate fertilizer; which is favored by higher soil moisture because of the higher abundance of Desulfovibrio and lower abundance of Geobacter.

To determine the association between mammographic density (MD) and the risk of breast cancer (BC) in Chinese women and to investigate the role of fertility risk factors in regulating the relationship between MD and BC. We used Quantra software and the BI-RADS classification to assess MD in 466 patients and 932 controls. Conditional matched logistic multiple regression analysis was used to determine the relationship between MD and BC, and risk was evaluated with the odds ratio (OR) and 95% confidence interval (CI). The ORs for category 4 versus category 2 were 1.95 (95% confidence interval [95% CI] (1.42∼2.66)) and 1.76 (95% CI (1.28∼2.42)) for the BI-RADS and Quantra classifications, respectively. The ORs for category 5 volumetric breast density (VBD) versus category 2 VBD and 5 fibroglandular tissue volume (FGV) versus category 2 FGV were 1.63 (95% CI (1.20∼2.23)) and 1.92 (95% CI (1.40∼2.63)), respectively. Females with category 5 VBD whose age at menarche was ≤13 years had the highest risk of BC (OR = 2.16, 95% CI (1.24∼3.79)), and females with category 5 FGV whose age at menarche was = 15 years had the lowest risk of BC (OR = 1.65, 95% CI (1.05∼2.62)). Females with categories 3–5 VBD and categories 3–5 FGV had reduced risks of BC with increasing number of births. Females with category 5 VBD had an increased risk of BC with increasing age at first childbirth (the OR increased from 1.49 to 1.95). Those with category 5 VBD had a reduced risk of BC with increasing breastfeeding duration (the OR decreased from 2.08 to 1.55). Females with category 5 FGV had a reduced risk of BC with increasing breastfeeding duration (the OR decreased from 4.12 to 1.62). Both the BI-RADS density classification and Quantra measures indicated that MD is positively associated with the risk of BC in Chinese women and that associations between MD and BC risk differ by age at menarche, parity, age at first childbirth and breastfeeding duration.

Gegen Qilian Decoction (GGQLD) is a well-established classic Chinese medicine prescription in treating nonalcoholic steatohepatitis (NASH). However, the molecular mechanism of GGQLD action on NASH is still not clear. This study aimed to assess the anti-NASH effect of GGQLD, and to explore its molecular mechanisms in vivo and in vitro. In HFD-fed rats, GGQLD decreased significantly serum triglyceride (TG), cholesterol (CHO), total bile acid (TBA), low-density lipoprotein (LDL), free fatty acid (FFA) and lipopolysaccharide (LPS) levels, increased levels of differentially expressed proteins (DEPs) Ahcy, Gpx1, Mat1a, GNMT, and reduced the expression of ALDOB. In RAW264.7 macrophages, GGQLD reduced the expression levels of inflammatory factors TNF-α and IL-6 mRNA, and diminished NASH by increasing differentially expressed genes (DEGs) CBS, Mat1a, Hnf4α and Pparα to reduce oxidative stress or lipid metabolism. The results of DEGs verification also showed that GGQLD up-regulated expressions of Hnf4α, Pparα and Cbs genes. In HepG2 cells, GGQLD decreased IL-6 levels and intracellular TG content, and inhibited FFA-induced expression of toll-like receptor 4 (TLR4). In summary, GGQLD abates NASH associated liver injuries via anti-oxidative stress and anti-inflammatory response involved inhibition of TLR4 signal pathways. These findings provide new insights into the anti-NASH therapy by GGQLD.

Purpose. Accumulated evidence suggests that reproductive factors are related to different breast cancer subtypes, but most studies on these relationships are mainly focused on middle-aged and older patients, and it remains unclear how reproductive factors impact different subtypes of breast cancer in young women. Methods. We assessed the relationships between fertility factors and luminal A, luminal B, human epidermal growth factor receptor 2 (HER2)-enriched, and triple-negative breast cancer (TNBC) subtypes in 3792 patients and 4182 controls aged 20–70 years. Data on the reproductive history of the study participants were acquired through face-to-face interviews and questionnaires. We conducted case-control comparisons among tumor subtypes based on estrogen receptor (ER), progesterone receptor (PR), and HER2 statuses using unconditional polychotomous multivariate logistic regression models to compute odds ratios (ORs) and 95% confidence intervals (CIs). Results. Parity was inversely related to both luminal A and luminal B subtypes in young women and older women (all Ptrend<0.05). Later age at first full-term birth was inversely related to the luminal A subtype (Ptrend<0.05) in young women but correlated with an increased risk of the luminal A subtype (Ptrend<0.05) in older women. Parous Chinese women 40 years old or younger who breastfed for 12 months or longer had a lower risk of luminal B and TNBC subtypes than women who never breastfed (OR=0.55, 95% CI 0.36-0.84 and OR=0.52, 95% CI 0.28-0.99, respectively). Conclusions. Our results implied that parity exerted a strong protective effect against luminal A and luminal B subtype breast cancer in young Chinese women, and long-term breastfeeding obviously decreased the risk of luminal B and TNBC subtypes in this population.

Bacterial communities play crucial roles in the biogeochemical cycle of the surface sediments of freshwater lakes, but previous studies on bacterial community changes in this habitat have mostly been based on the total bacterial community (DNA level), while an exploration of the active microbiota at the RNA level has been lacking. Herein, we analysed the bacterial communities in the surface sediments of Lake Taihu at the DNA and RNA levels. Using MiSeq sequencing and real-time quantification, we found that the sequencing and quantitative results obtained at the RNA level compared with the DNA level were more accurate in responding to the spatiotemporal dynamic changes of the bacterial community. Although both sequencing methods indicated that Proteobacteria, Chloroflexi, Acidobacteria, Nitrospirae, Bacteroidetes and Actinobacteria were the dominant phyla, the co-occurrence network at the RNA level could better reflect the close relationship between microorganisms in the surface sediment. Additionally, further analysis showed that Prochlorococcus and Microcystis were the most relevant and dominant genera of Cyanobacteria in the total and active bacterial communities, respectively; our results also demonstrated that the analysis of Cyanobacteria-related groups at the RNA level was more ‘informative’.

The present study shows the basis for the anti-inflammatory effects of pitavastatin in interleukin (IL)-1β-induced human synovial cells. The SW982 cells were pretreated with pitavastatin at different concentrations (5μM and 10μM), followed by IL-1β (10ng/mL) stimulation. The results showed that pitavastatin inhibited the expression of inflammatory mediators IL-6 and IL-8. Furthermore, pitavastatin inhibited the phosphorylation of p38, extracellular signal-related kinase (ERK), c-jun N-terminal kinase (JNK) and protein kinase B (Akt). It also suppressed the degradation of I kappa B alpha and blocked p65 translocation into the nucleus. These findings suggest that the mechanism underlying the inhibitory effects of pitavastatin on IL-1β-induced IL-6 and IL-8 release might be mediated by the suppression of mitogen-activated protein kinase (MAPK), Akt, and nuclear factor-κB (NF-κB) signaling pathways. These results may also indicate that pitavastatin may be potentially utilized as an effective therapeutic agent for the treatment of osteoarthritis.

Ammonium-oxidizing archaea (AOA) and bacteria (AOB) play crucial roles in ammonium oxidation in freshwater lake sediment. However, previous reports on the predominance of AOA and AOB in the surface sediment of Lake Taihu have been based on DNA levels, detecting the total abundance of microbiota (including inactive cells), and have resulted in numerous contradictory conclusions. Existing RNA-level studies detecting active transcription are very limited. The current study, using RNA-based real-time quantification and clone library analysis, demonstrated that the amoA gene abundance of active AOB was higher than that of active AOA, despite conflicting results at the DNA level. Further exploration revealed a significant positive correlation between the potential nitrification rate (PNR) and the abundance of AOA and AOB at the RNA level, with irregular or contradictory correlation found at the DNA level. Ultimately, using quantitative analysis of RNA levels, we show AOB to be the active dominant contributor to ammonium oxidation. Our investigations also indicated that AOB were more diverse in high-ammonium lake regions, with Nitrosomonas being the active and dominating cluster, but that AOA had an advantage in the low-ammonium lake regions.

Purpose: This study aimed to establish and validate an ultrasound radiomics nomogram for the preoperative prediction of central lymph node (LN) metastasis in patients with papillary thyroid carcinoma (PTC). Patients and Methods: The prediction model was developed in 609 patients with clinicopathologically confirmed unifocal PTC who received ultrasonography between Jan 2018 and June 2018. Radiomic features were extracted after the ultrasonography of PTC. Lasso regression model was used for data dimensionality reduction, feature selection, and radiomics signature building. The predicting model was established based on the multivariable logistic regression analysis in which the radiomics signature, ultrasonography-reported LN status, and independent clinicopathologic risk factors were incorporated, and finally a radiomics nomogram was established. The performance of the nomogram was assessed with respect to the discrimination and consistence. An independent validation was performed in 326 consecutive patients from July 2018 to Sep 2018. Results: The radiomics signature consisted of 23 selected features and was significantly associated with LN status in both primary and validation cohorts. The independent predictors in the radiomics nomogram included the radiomics signature, age, TG level, TPOAB level, and ultrasonography-reported LN status. The model showed good discrimination and consistence in both cohorts: C-index of 0.816 (95% CI, 0.808-0.824) in the primary cohort and 0.858 (95% CI, 0.849-0.867) in the validation cohort. The area under receiver operating curve was 0.858. In the validation cohort, the accuracy, sensitivity, specificity and AUC of this model were 0.812, 0.816, 0.810, and 0.858 (95% CI, 0.785-0.930), respectively. Decision curve analysis indicated the radiomics nomogram was clinically useful. Conclusion: This study presents a convenient, clinically useful ultrasound radiomics nomogram that can be used for the pre-operative individualized prediction of central LN metastasis in patients with PTC.

Background: Many research has indicated that some Chinese herb injections (CHIs) might be beneficial in combination with chemotherapy, however, with inconsistent results. Hence, the purpose of this network meta-analysis is to evaluate different CHIs plus cisplatin and gemcitabine (GP) with GP alone in terms of clinical efficacy and safety for treating patients with advanced NSCLC. Methods: A comprehensive systematic search of clinical randomized controlled trials (RCTs) published in the PubMed, Embase, Web of Science (ISI), Cochrane Central Register of Controlled Trials (CENTRAL), China National Knowledge Infrastructure Database (CNKI), Chinese Scientific Journals Full-Text Database (VIP), Wanfang Database and China Biological Medicine Database (CBM) databases will be conducted to identify eligible studies up to the date of May 2020. The primary outcome measures objective response rate and adverse reactions (nausea and vomiting, leukopenia). The secondary outcome measures median survival time (MST), disease control rate, and quality of life. The methodological qualities, including the risk of bias, will be evaluated using the Cochrane risk of bias assessment tool, while confidence in the cumulative evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The network meta-analysis will be performed using WinBUGS 14 and Stata 15.1 software. Results: Based on the current evidence, the potential rank of the efficacy and safety of CHIs plus GP chemotherapy for advanced NSCLC will be assessed, and a prioritization regimen will be summarized. Conclusion: Evidence from this systematic review could be useful for patients, clinical practitioners, and guideline-makers to select an optimum proposal of CHIs plus GP for advanced NSCLC. Ethics and dissemination: It is not necessary for ethical approval because it is based on published studies. The protocol will be disseminated in a peer-reviewed journal or presented at a topic-related conference. PROSPERO registration number: CRD42020167142

Cadmium (Cd) contamination in paddy soils and the related pollution risk of rice grain have received increasing attention. Agronomic measures, such as the application of sulfur and changes in water regimes, were reported to mitigate the accumulation of Cd in rice. However, there is limited information on the combined effects of sulfur application and water regimes. Therefore, a pot experiment was conducted to investigate the effects of two sulfur forms, three water regimes and multiple sulfur application rates on Cd accumulation in rice. The sulfur was applied as SO42− (SVI, replacing the traditional fertilizers by SO42--containing fertilizers), and element S (S0) was applied at 0, 10, 20, 30 and 40 mg S kg−1 soil. The water regimes were continuous flooding (F), flooding-moist alternation (FM), and moist irrigation (M), for a total of 30 treatments. The results indicated that application of SVI exceeding 30 mg S kg−1 significantly reduced the Cd concentrations in brown rice by 31.1–56.3%, and the Cd concentrations decreased with increasing amount of irrigation water. Similar reductions in Cd concentrations in rice shoots and rice straw collected at tillering and maturity stages were observed after application of SVI. However, the effect of S0 application on Cd accumulation in grain was not significant under different water regimes. Furthermore, this study found that application of both SVI and S0 inhibited the transfer of Cd from rice roots to shoots in most cases. These findings indicate that replacing traditional fertilizers with SO42--containing fertilizers, especially combined with increased irrigation, could be a potential approach to mitigate Cd accumulation in rice growing in Cd-contaminated acidic paddy soils.

BACKGROUND Hepatocellular carcinoma (HCC) is one of the most prevalent cancers in the world. Bioinformatics studies have been widely used for screening genes involved in the initiation and progression of HCC. MATERIAL AND METHODS We obtained liver cancer microarray raw data from the GEO database (GSE54238). Next, weighted gene co-expression network analysis (WGCNA) was used to assess the critical modules. Then, we assessed the gene significance by calculating survival, expression level, and receiver operating characteristic (ROC) in the TCGA database. We also validated the expression of selected genes in the Oncomine database and calculated the relationship between 4 hub genes and immune infiltration. Finally, GSEA enrichment analysis was used to explore the potential mechanism. RESULTS We identified the red and blue modules as the critical modules, and found 176 candidate genes by assessing gene significance. GO and KEEG results suggested that the candidate genes are involved in the cell cycle. Four hub genes - SOX4, STK39, TARBP1, and TDRKH - were eventually screened after validating their expression and power in diagnosing HCC in the TCGA database. Immune infiltration analysis and GSEA enrichment analysis showed that these 4 hub genes were correlated with the immune cell populations infiltration and that multiple mechanisms were involved, such as angiogenesis and epithelial-mesenchymal transition. CONCLUSIONS Our findings revealed that these 4 genes can be regarded as potential prognosticators and therapeutic targets for HCC.

Scutellaria-coptis herb couple (SC) is one of the well-known herb couples in many traditional Chinese compound formulas used for the treatment of diabetes mellitus (DM), which has been used to treat DM for thousands of years in China.Few studies have confirmed in detail the anti-diabetic activities of SC in vivo and in vitro. The present investigations aimed to evaluate the anti-diabetic activity of SC in type 2 diabetic KK-Ay mice and in RAW264.7 macrophages to understand its possible mechanism.High-performance liquid chromatography with ultraviolet detection (HPLC-UV) and LC-LTQ-Orbitrap Pro mass spectrometry were used to analyze the active ingredients of SC extracts and control the quality. A type 2 diabetic KK-Ay mice model was established by high-fat diet. Body weight, fasting blood glucose levels, fasting blood insulin levels, glycosylated hemoglobin and glycosylated serum protein were measured. The effects of SC on total cholesterol (TC), high-density lipoprotein (HDL) and triglyceride (TG) levels were examined. The lipopolysaccharide (LPS), interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-α) levels were measured. Gut microbial communities were assayed by polymerase chain reaction (PCR) and PCR-denaturing gradient gel electrophoresis (PCR-DGGE) methods. The expressions of Toll-like receptor 4 (TLR4) and MyD88 protein in the colons were measured by western blot. In RAW264.7 macrophages, IL-6, TNF-α, TLR4 and MyD88 protein levels were measured by enzyme-linked immunosorbent assay (ELISA) kits or western blot, and the mRNA expression of IL-6, TNF-α and TLR4 was examined by the real time PCR.The present results showed that the SC significantly increased blood HDL and significantly reduced fasting blood glucose, fasting blood insulin, glycosylated hemoglobin, glycosylated serum protein, TC, TG, LPS, IL-6 and TNF-α levels (P 0.05 or P 0.01) in type-2 diabetic KK-Ay mice. Furthermore, SC could regulate the structure of intestinal flora. Additionally, the expressions of TLR4 and MyD88 protein in the colons were significantly decreased in the model group (P 0.05 or P 0.01). However, SC had no significant effect on weight gain. In RAW264.7 macrophages, SC containing serum (SC-CS) (5%, 10% and 20%) significantly decreased IL-6, TNF-α, TLR4 and MyD88 protein levels and the mRNA expression of IL-6, TNF-α and TLR4 (P 0.05 or P 0.01).The anti-diabetic effects of SC were attributed to its regulation of intestinal flora and anti-inflammation involving the TLR4 signaling pathway. These findings provide a new insight into the anti-diabetic application for SC in clinical settings and display the potential of SC in the treatment of DM.

Freshwater fungal community composition plays pivotal roles in sustaining the function and health of drinking water reservoir ecosystems. To investigate the vertical evaluative characteristics of an aquatic fungal community under conditions of stable thermal stratification, water samples were collected at 0.5, 10, 25, 40, 60 and 70 m depths of Jinpen Reservoir during thermal stratification. Fungal community composition was determined using a high-throughput DNA sequencing technique and combined with water quality parameters. The results showed that the epilimnion, metalimnion, and hypolimnion water layers were formed in Jinpen Reservoir. The temperature decreased steadily from the surface at 22.33℃ to the bottom with 7.21℃ (

// Yun-Miao Guo 1, 2, * , Ming-Xia Sun 1, 2, * , Jing Li 3, * , Tong-Tong Liu 1, 2 , Hang-Zhen Huang 1, 2 , Jie-Rong Chen 1, 2 , Wen-Sheng Liu 1, 2 , Qi-Sheng Feng 1, 2 , Li-Zhen Chen 1, 2 , Jin-Xin Bei 1, 2 , Yi-Xin Zeng 1, 2, 4, * 1 Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China 2 Department of Experimental Research, Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China 3 Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, P. R. China 4 Peking Union Medical College, Beijing, P. R. China * These authors have contributed equally to this work Correspondence to: Yi-Xin Zeng, e-mail: zengyx@sysucc.org.cn Keywords: nasopharyngeal carcinoma, SNP, CELF2, prognosis Received: March 27, 2015 Accepted: July 30, 2015 Published: August 11, 2015 ABSTRACT Nasopharyngeal carcinoma (NPC) is a malignancy with high metastatic potential and loco-regional recurrence. The overall survival of NPC has been limited from further improvement partly due to the lack of effective biomarker for accurate prognosis prediction and precise treatments. Here, in light of the implication of CELF gene family in cancer prognosis, we selected 112 tagging single nucleotide polymorphisms (SNPs) located in six members of the family and tested their associations with the clinical outcomes in a discovery cohort of 717 NPC patients. Survival analyses under multivariate cox proportional hazards model and Kaplan–Meier curve revealed five promising SNPs, which were further validated in another independent sample of 1,520 cases. Combined analysis revealed that SNP rs3740194 in CELF2 was significantly associated with the decreased risk of death with a Hazard ratio (HR) of 0.69 (95% confidence interval [CI] = 0.58–0.82, codominant model). Moreover, rs3740194 also showed a significant association with superior metastasis-free survival (HR = 0.69, 95% CI = 0.57–0.83, codominant model). Taken together, our findings suggested that genetic variant of rs3740194 in CELF2 gene might be a valuable predictor for NPC prognosis, and potentially useful in the personalized treatment of NPC.

Objective: The objective of this paper is to clarify the demographic, clinical and serologic characteristics of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) overlap syndrome, known as ‘rhupus syndrome’. Methods: Between 1995 and 2012, 51 patients were classified as having rhupus among 3733 consecutive SLE patients. Rhupus was defined as a condition involving an overlap of RA and SLE features meeting the respective criteria of the American College of Rheumatology. The clinical and laboratory parameters of patients with rhupus syndrome were compared with those of 230 RA patients and 120 unselected SLE patients. Results: The age at the onset of rhupus was significantly younger than that of RA ( p