Multidisciplinary Team (MDT) Discussion Improves Overall Survival Outcomes for Metastatic Renal Cell Carcinoma Patients.

Purpose: Multidisciplinary team (MDT) discussion is a widely used model to manage patients diagnosed with cancer. However, there has been no direct evidence to prove its effect on the prognosis of metastatic renal cell carcinoma (mRCC) patients, so this study explored the impact of MDT discussion on mRCC patient survival. Methods: The clinical data of 269 mRCC patients were retrospectively collected from 2012 to 2021. The cases were grouped into the MDT and non-MDT groups, then subgroup analysis was performed according to different histology types, as well as exploring the role of MDT in patients who have undergone multiple-line therapy. Overall survival (OS) and progression free survival (PFS) were set as the study endpoint. Results: Approximately half (48.0%, 129/269) of the patients were in the MDT group, with univariable survival analyses showing these patients had remarkably longer median OS (MDT group: 73.7 months; non-MDT group: 33.2 months, hazard ratio (HR): 0.423 (0.288, 0.622), p<0.001) and longer median PFS (MDT group: 16.9 months, non-MDT group: 12.7 months, HR: 0.722 (0.542, 0.962), p=0.026). Furthermore, MDT management resulted in longer survival for both ccRCC and non-ccRCC subgroups. Patients in the MDT group were more likely to receive multi-line therapy (MDT group: 79/129, 61.2% vs non-MDT group: 56/140, 40.0%, p<0.001), and within this patient group, MDT management still resulted in longer OS (MDT group: 94.0 months; non-MDT group: 43.5 months, p=0.009). Conclusion: MDT is associated with prolonged overall survival in mRCC independent of histology, ensuring that patients receive better management and precise treatment.

Konjac glucomannan/xanthan gum/sodium alginate composite hydrogel simulates fascial tissue by pre-stretching and moisture regulation.

Improving the mechanical strength and creating an anisotropic structure of edible macromolecular hydrogels is crucial to accurately simulate the texture of connective tissues. In this study, konjac glucomannan (KGM), xanthan gum (XG), and sodium alginate (SA) were used to construct hydrogels, and the effects of different pre-stretching degrees and moisture control on the composite gels were investigated. The results of the mechanical property tests and microstructure tests indicate that pre-stretching and moisture control can significantly enhance the strength of the gels and induce anisotropic structures. In addition, the feasibility of the composite gel structure in simulating brisket fascia was investigated, and it was concluded that 1.5 × -DR samples were most suitable for simulating connective tissue. This study provides compelling evidence for the potential of macromolecular hydrogels in simulating connective tissue and provides theoretical guidance for regulating gel texture.

Upregulation of TXNIP contributes to granulosa cell dysfunction in polycystic ovary syndrome via activation of the NLRP3 inflammasome.

Polycystic ovary syndrome (PCOS) is a complex endocrine disease. Thioredoxin-interacting protein (TXNIP) promotes oxidative stress and triggers inflammation. Herein, we investigated the role and potential mechanism of TXNIP in PCOS. In a mouse model of dehydroepiandrosterone (DHEA)-induced PCOS, we found that TXNIP was upregulated in the ovaries, especially in granulosa cells (GCs). TXNIP was also upregulated in testosterone (T)-treated GCs in vitro. Knockdown of TXNIP by lentivirus-constructed shRNA attenuated T-induced GC injury and oxidative stress, as well as inflammation and the NLRP3 inflammasome. The mechanism by which TXNIP promotes inflammation may involve TXNIP dissociation from the TXNIP-TRX complex and binding to NLRP3 to form the inflammasome. Additionally, we verified that knockdown of TXNIP ameliorated ovarian injury and inflammation in mice with DHEA-induced PCOS in vivo. Collectively, we demonstrated that TXNIP is involved in GC inflammation by promoting NLRP3 inflammasome activation in PCOS.

Homologous recombination deficiency (HRD) score in aggressive prostatic adenocarcinoma with or without intraductal carcinoma of the prostate (IDC-P).

BACKGROUND: Intraductal carcinoma of the prostate (IDC-P) is a subtype of prostate cancer featured by poor prognosis. Previous studies suggested IDC-P could have a potentially unstable genome. Homologous recombination deficiency (HRD) score is a result-oriented method to describe the genomic instability status. This study investigates the association of HRD scores with IDC-P and other clinicopathological factors and the prognostic implication of HRD scores in an aggressive prostate cancer cohort. METHODS: This study involved 123 PCa patients, including high-risk localized (M0) and de novo metastatic (M1) diseases. HRD score is calculated based on over 10,000 single-nucleotide polymorphisms distributed across the human genome. We explored the association between HRD scores and clinicopathological characteristics, genomic alterations, and patients' prognoses using rank-sum tests, chi-square tests, Kaplan-Meier curves, and Cox proportional hazards method. RESULTS: The median HRD score of this cohort is 21.0, with 65 (52.8%) patients showing HRD score≥21. Tumors with IDC-P displayed higher HRD scores than adenocarcinoma (P=0.002); other high HRD score-related factors included M1 (P =0.008) and high ISUP grades (4-5) (P=0.001). MYC mutations were associated with high HRD scores (P<0.001) in the total cohort. TP53 mutations (P=0.010) and HRR pathway mutations (P=0.028) corresponded to high HRD scores in IDC-P positive and non-IDC-P patients, respectively, but not vice versa. HRD scores higher than 21 indicated significantly worse survival in the total cohort. CONCLUSIONS: M1, high Gleason score, and IDC-P pathology represent higher HRD scores in PCa. Tumors with IDC-P might have different driven mechanisms for high HRD scores than non-IDC-P. HRD score displayed prognostic value in this aggressive prostate cancer cohort.

The alleles of AGT and HIF1A gene affect the risk of hypertension in plateau residents.

Plateau essential hypertension is a common chronic harmful disease of permanent residents in plateau areas. Studies have shown some single nucleotide polymorphisms (SNPs) associations with hypertension, but few have been verified in plateau area-lived people. In this paper, we examined some hypertension-related gene loci to analyze the relationship between risk SNPs and plateau essential hypertension in residents in Qinghai-Tibet plateau area. We screened hypertension-related SNPs from the literature, Clinvar database, GHR database, GTR database, and GWAS database, and then selected 101 susceptible SNPs for detection. Illumina MiSeq NGS platform was used to perform DNA sequencing on the blood samples from 185 Tibetan dwellings of Qinghai, and bioinformatic tools were used to make genotyping. Genetic models adjusted by gender and age were used to calculate the risk effects of genotypes. Four known SNPs as well as a new locus were found associated with PHE, which were rs2493134 (AGT), rs9349379 (PHACTR1), rs1371182 (CYP2C56P-PRPS1P1), rs567481079 (CYP2C56P-PRPS1P1), and chr14:61734822 (HIF1A). Among them, genotypes of rs2493134, rs9349379, and rs567481079 were risk factors, genotypes of rs1371182 and chr14:61734822 were protective factors. The rs2493134 in AGT was found associated with an increased risk of the plateau essential hypertension by 3.24-, 3.24-, and 2.06-fold in co-dominant, dominant, and Log-additive models, respectively. The rs9349379 in PHACTR1 is associated with a 2.61-fold increased risk of plateau essential hypertension according to the dominant model. This study reveals that the alleles of AGT, HIF1A, and PHACTR1 are closely related to plateau essential hypertension risk in the plateau Tibetan population.

Acidic and alkaline gas sensitive and self-healing chitosan aerogel based on electrostatic interaction.

Gas pollution is a serious problem. More attention has been paid to the detection and monitoring of toxic and harmful gases, and it is urgently needed for a sensor that could simultaneously identify and distinguish between acid and base gases. Based on the electrostatic interaction resulting from amidogen of chitosan (CS) and carboxylic groups of itaconic acid (IA), we successfully prepared a series of biomass aerogels (CS-IA aerogels) that could respond to acidic and alkaline gases with different concentrations. The acidic and alkaline gases could be easily detected and distinguished by changing the content of IA in CS-IA aerogels. Moreover, the electrostatic interactions could also endowed CS-IA aerogels with self-healing ability in the breaks at room temperature. After self-healing, CS-IA aerogels still sensitively answered to acidic and alkaline gases. CS-IA aerogels with sensitivity to acid-base gas and self-healing performance has been suggested to be promising candidates as application of multi-functional aerogels.

Umbilical acupuncture for insomnia: A protocol for systematic review and meta-analysis.

BACKGROUND: Insomnia is characterized by high incidence, easy recurrence, and difficulty in curing. Serious insomnia not only seriously affects the body organ function but also causes great damage psychological.Umbilical acupuncture (UA) has fewer side effects and is increasingly used to treat insomnia. This study aimed to systematically review the effectiveness and safety of UA in the treatment of insomnia. METHODS: Literature on UA for insomnia in PubMed, Excerpt Medica Database, the Cochrane Central Register of Controlled Trials, Web of Science, China National Knowledge Infrastructure Database, China Biomedical Literature Database, Chinese Scientific Journal Database, and Wan Fang Database were searched from the creation of these databases to October 3, 2021. In addition, the reference lists of studies meeting the inclusion criteria will also be searched to achieve a comprehensive retrieval of the maximum. All randomized controlled trials of UA for treating insomnia were included. Two reviewers will conduct literature screening, data extraction, and quality evaluation respectively. The main outcome was the Pittsburgh Sleep Quality Index, and the secondary outcomes included clinical efficacy, and safety. RevMan 5.4.1 software was used for mate analysis. RESULTS: This study aimed to evaluate the current status of UA treatment for insomnia, with the aim of illustrating the effectiveness and safety of UA. CONCLUSION: This study will provides a high-quality evidence to evaluate the effectiveness and safety of UA in treating insomnia. REGISTRATION: PROSPERO CRD42021283036.

MicroRNA-320a inhibits invasion and metastasis in osteosarcoma by targeting cytoplasmic polyadenylation element-binding protein 1.

Osteosarcoma is a primary malignant bone tumor, which affects children, adolescents, and young adults commonly. MicroRNAs (miRNAs) have been proved to be dysregulated in different cancers, including osteosarcoma. Although miR-320a has been implicated in many types of malignancies, little is known about the role of miR-320a in osteosarcoma. In this study, we show that the overexpression of miR-320a or knockdown of cytoplasmic polyadenylation element-binding protein 1 (CPEB1) inhibited osteosarcoma cell migration and invasion. miR-320a downregulates CPEB1 expression by directly targeting the CPEB1 3'-UTR. Furthermore, CPEB1 reintroduction reversed the antiproliferation, antimigration, and antiinvasion roles of miR-320a, indicating that miR-320a might function as a tumor suppressor in osteosarcoma through CPEB1. In conclusion, our study demonstrates that miR-320a plays a critical role in osteosarcoma progression and may provide a potential therapeutic target for osteosarcoma.

MicroRNA-106a suppresses prostate cancer proliferation, migration and invasion by targeting tumor-derived IL-8.

BACKGROUND: Tumor-derived interleukin-8 (IL-8) promotes tumorigenesis and progression of prostate cancer (PCa). MicroRNAs (miRNAs) are noncoding regulatory RNAs and their dysregulation is known to be implicated in carcinogenesis. However, the post-transcriptional mechanism of IL-8 via miRNAs is not fully understood. This study was intended to investigate whether miR-106a could affect the progression of PCa via targeting IL-8 or not. METHODS: Using bioinformatics analysis, we postulated that IL-8 might be post-transcriptionally regulated by miR-106a. This was validated by dual reporter gene assays that miR-106a could bind to the predicted site of IL-8 mRNA. To determine the biological effects of miR-106a on PCa cells (PC-3 and DU145), MTT, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), migration and invasion assays were performed. RESULTS: We found that miR-106a was barely expressed in PCa cells, whereas IL-8 was aberrantly upregulated. Elevated miR-106a could reduce IL-8 expression by directly binding the 3'-UTR of IL-8. Overexpression of miR-106a in PCa cells triggered cell apoptosis and suppressed cell proliferation, migration, and invasion. CONCLUSIONS: This research showed that miR-106a could function as a tumor-suppressor by decreasing IL-8 levels in PCa.

Facile fabrication of wood-inspired aerogel from chitosan for efficient removal of oil from Water.

Aerogels that derived from biomass have long been attractive as absorbents for oil clean-up. However, it remains a significant challenge to prepare fully bio-based oil absorbents that combines fast oil/water separation capacity, adequate mechanical robustness and easy recyclability through green and facile strategy. Inspired by the fascinating structure of wood, here we report a highly porous and anisotropic bio-based aerogel by taking advantage of the directional freezing technology, followed by a freeze-drying and silylation process. Due to the directional growth of ice crystals along the vertical direction, a special spring like morphology was obtained, which is mainly composed of well aligned low-tortuosity channels that seamlessly connected to bottom layer. Superior mechanical properties that allow for high mechanical compressing and fast elastic recovery were consequently acquired. Moreover, the silylated CS aerogel displays a rather high oil absorption capacity of 63 g g-1, together with excellent recyclability via simple hand squeezing. By virtue of such hierarchical morphology, a device that could continuously separate oil from water was successfully designed. Given the natural abundance of raw material as well as the easy processability, this work would lay solid foundation for further fabrication of bio-based oil absorbents toward low-cost, high-performance and large-scale commodities.

The prognosis benefits of adjuvant versus salvage radiotherapy for patients after radical prostatectomy with adverse pathological features: a systematic review and meta-analysis.

BACKGROUND: The appropriate timing of radiotherapy (RT) for patients after radical prostatectomy (RP) with adverse pathological features (APFs) remains controversial. This systematic review was conducted to compare the efficacy of adjuvant radiotherapy (ART) and salvage radiotherapy (SRT). METHODS: PubMed, EMBASE, Web of Science and the Cochrane Library electronic databases were searched to retrieve the required. The hazard ratio (HR) and corresponding 95% confidence interval (CI) of overall survival (OS), biochemical recurrence-free survival (BRFS) and distant metastases-free survival (DMFS) were extracted. The survival benefits of ART with SRT (including early salvage radiotherapy (ESRT)) were analyzed. The process of the meta-analysis was performed with RevMan version 5.3. RESULTS: A total of fifteen retrospective studies were finally included in the final analysis including 5586 patients. The pooled analysis indicated that ART could achieve better control of prostate cancer and improve OS (p = 0.0006), BRFS (p < 0.0001) and DMFS (p < 0.0001), when compared to SRT. The subgroup analysis of the 5-year OS rate demonstrated that the ART group still had survival advantages compared to the SRT group (p = 0.0006). However, ART and SRT were comparable in 10-year OS rate (p = 0.07). ART had advantages over SRT in both 5-year (p = 0.0003) and 10-year BRFS (p = 0.0003). The subgroup analysis with different follow-up starting points from RP or RT was essentially consistent with the above results. The pooled analysis also showed that ART was superior to ESRT on OS (p = 0.008) and DMFS (p = 0.03), and comparable to ESRT on BRFS (p = 0.1). CONCLUSIONS: According to this meta-analysis, ART could be served as a preferential treatment for patients with APFs after RP to improve prognosis. Certainly, high-quality, multicenter randomized controlled trials (RCTs) are expecting to confirm the outcomes of our meta-analysis in the future.

Necrosis of osteosarcoma cells induces the production and release of high-mobility group box 1 protein.

Osteosarcoma is among the commonly observed malignancies worldwide. High-mobility group box 1 protein (HMGB1) is a highly conserved protein and is involved in the progression of various types of human cancer. The aim of the present study was to explore whether the level of HMGB1 was involved in the necrosis of osteosarcoma cells. Doxorubicin (DXR), as an inducer of necrosis, was administered to human osteosarcoma cell lines (MG63, Saos-2 and U2OS), and the results indicated that 0.5 µg/ml DXR significantly induced the necrosis of MG63 cells (P<0.01), while 0.5 and 1.0 µg/ml DXR suppressed the viability of MG63 and U2OS cells (P<0.05), relative to untreated controls. Additionally, treatment with DXR was observed by western blot analysis to markedly increase the expression levels of HMGB1 in MG63 cells, and to significantly increase the levels of secreted HMGB1 in the supernatants of MG63 and U2OS cells (P<0.01). In conclusion, cell necrosis increased the level of HMGB1 in osteosarcoma cells, as well as the level of secreted HMGB1 in cell supernatants. Therefore, HMGB1 may be a potential target in molecular therapy for patients with osteosarcoma.

Phenotypic characterization and genetic dissection of nine agronomic traits in Tokachi nagaha and its derived cultivars in soybean (Glycine max (L.) Merr.).

By using the soybean founder parent Tokachi nagaha and its 137 derived cultivars as materials, a genome-wide association analysis was performed to identify the single nucleotide polymorphisms (SNPs) underlying soybean yield and quality related traits at two planting densities. Results of ANOVA showed that genotype, environment, and genotype by environment interaction effects were all significant for each trait. The Tokachi nagaha-derived soybean population could be divided into two subpopulations based on molecular data, and accessions in each subpopulation were almost all from the same Chinese province. Relatedness was detected between pair-wise accessions within the population. Linkage disequilibrium was obvious and the level of intra-chromosome linkage disequilibrium was about 8370kb. A total of 40 SNPs with significant signal were detected and distributed across 18 chromosomes. Some SNP markers were located in or near regions where QTLs have been previously mapped by linkage analysis. Nineteen SNPs were identified both in low- and high- density planting treatments, indicating those loci were common and sTable Sixteen SNPs were co-associated with two or more different traits, suggesting that some of the QTLs/genes underlying those identified SNPs were likely to be pleiotropic.

Phenotypic Characterization and Genetic Dissection of Growth Period Traits in Soybean (Glycine max) Using Association Mapping.

The growth period traits are important traits that affect soybean yield. The insights into the genetic basis of growth period traits can provide theoretical basis for cultivated area division, rational distribution, and molecular breeding for soybean varieties. In this study, genome-wide association analysis (GWAS) was exploited to detect the quantitative trait loci (QTL) for number of days to flowering (ETF), number of days from flowering to maturity (FTM), and number of days to maturity (ETM) using 4032 single nucleotide polymorphism (SNP) markers with 146 cultivars mainly from Northeast China. Results showed that abundant phenotypic variation was presented in the population, and variation explained by genotype, environment, and genotype by environment interaction were all significant for each trait. The whole accessions could be clearly clustered into two subpopulations based on their genetic relatedness, and accessions in the same group were almost from the same province. GWAS based on the unified mixed model identified 19 significant SNPs distributed on 11 soybean chromosomes, 12 of which can be consistently detected in both planting densities, and 5 of which were pleotropic QTL. Of 19 SNPs, 7 SNPs located in or close to the previously reported QTL or genes controlling growth period traits. The QTL identified with high resolution in this study will enrich our genomic understanding of growth period traits and could then be explored as genetic markers to be used in genomic applications in soybean breeding.

Simultaneous efficient removal of high-strength ammonia nitrogen and chemical oxygen demand from landfill leachate by using an extremely high ammonia nitrogen-resistant strain.

Bioaugmentation is a promising technology for pollutant elimination from stressed environments, and it would provide an efficient way to solve challenges in traditional biotreatment of wastewater with high strength of ammonia nitrogen (NH4(+)-N). A high NH4(+)-N-resistant bacteria strain, identified as Bacillus cereus (Jlu BC), was domesticated and isolated from the bacteria consortium in landfill leachate. Jlu BC could survive in 100 g/L NH4(+)-N environment, which indicated its extremely high NH4(+)-N tolerance than the stains found before. Jlu BC was employed in the bioaugmented system to remove high strength of NH4(+)-N from landfill leachate, and to increase the removal efficiency, response surface methodology (RSM) was used for optimizing bioaugmentation degradation conditions. At the optimum condition (initial pH 7.33, 4.14 days, initial chemical oxygen demand [COD] concentration [18,000 mg/L], 3.5 mL inoculated domesticated bacteria strain, 0.3 mg/mL phosphorus supplement, 30 °C, and 170 rpm), 94.74 ± 3.8% removal rate of NH4(+)-N was obtained, and the experiment data corresponded well with the predicted removal rate of the RSM models (95.50%). Furthermore, COD removal rate of 81.94 ± 1.4% was obtained simultaneously. The results presented are promising, and the screened strain would be of great practical importance in mature landfill leachate and other NH4(+)-N enrichment wastewater pollution control.

Bioaugmentation treatment of mature landfill leachate by new isolated ammonia nitrogen and humic acid resistant microorganism.

The mature landfill leachate, which is characterized by a high concentration of ammonia nitrogen (NH3-N) and humic acid (HA), poses a challenge to biotreatment methods, due to the constituent toxicity and low biodegradable fraction of the organics. In this study, we applied bioaugmentation technology in landfill leachate degradation by introducing a domesticated NH3-N and HA resistant bacteria strain, which was identified as Bacillus cereus (abbreviated as B. cereus Jlu) and Enterococcus casseliflavus (abbreviated as E. casseliflavus Jlu), respectively. The isolated strains exhibited excellent tolerant ability for NH3-N and HA and they could also greatly improved the COD (chemical oxygen demand), NH3-N and HA removal rate, and efficiency of bioaugmentation degradation of landfill leachate. Only 3 days was required for the domesticated bacteria to remove about 70.0% COD, compared with 9 days' degradation for the undomesticated (autochthonous) bacteria to obtain a similar removal rate. An orthogonal array was then used to further improve the COD and NH3-N removal rate. Under the optimum condition, the COD removal rate in leachate by using E. casseliflavus Jlu and B. cereus Jlu increased to 86.0% and 90.0%, respectively after, 2 days of degradation. The simultaneous removal of NH3-N and HA with more than 50% and 40% removal rate in leachate by employing the sole screened strain was first observed.

[Preparation of recombinant human insulin--study of downstream process].

This study was intended to establish a method of preparation of recombinant human insulin, with (His)6-Arg-Arg-human proinsulin (RRhPI) expressed by Escherichia coli. After DEAE-Sepharose Fast Flow ion-exchange chromatography, Sephadex G-25 chromatography and refolding, enzyme cleavage and Superdex 75 size exclusion chromatography,the RRhPI expressed by Escherichia coli in inclusion body form was converted to human insulin. The obtained recombinant human insulin was analyzed by SDS-PAGE, HPLC, amino acid composition analysis and bioidentity test (mouse convulsion test). The results indicate that our obtained preparation is highly purified, active recombinant human insulin.