Pembrolizumab combined with axitinib in the treatment of skin metastasis of renal clear cell carcinoma to nasal ala: A case report.

BACKGROUND: Renal clear cell carcinoma (RCC) is a malignant tumor of the genitourinary system with a predilection for males. The most common metastatic sites are the lung, liver, lymph nodes, contralateral kidney or adrenal gland, however, skin metastasis has only been seen in 1.0%-3.3% of cases. The most common site of skin metastasis is the scalp, and metastasis to the nasal ala region is rare. CASE SUMMARY: A 55-year-old man with clear cell carcinoma of the left kidney was treated with pembrolizumab and axitinib for half a year after surgery and was found to have a red mass on his right nasal ala for 3 mo. The skin lesion of the patient grew rapidly to the size of 2.0 cm × 2.0 cm × 1.2 cm after discontinuation of targeted drug therapy due to the coronavirus disease 2019 epidemic. The patient was finally diagnosed with skin metastasis of RCC in our hospital. The patient refused to undergo surgical resection and the tumor shrank rapidly after resuming target therapy for 2 wk. CONCLUSION: It is rare for an RCC to metastasize to the skin of the nasal ala region. The tumor size change of this patient before and after treatment with targeted drugs shows the effectiveness of combination therapy for skin metastasis.

[Effects of reducing chemical fertilizers combined with organic fertilizers on soil microbial community in litchi orchards]. / å‡æ–½åŒ–è‚¥é æ–½æœ‰æœºè‚¥å¯¹è”æžå›­åœŸå£¤å¾®ç”Ÿç‰©åŒºç³»çš„å½±å“.

Organic fertilizer application can replace a part of chemical fertilizer (CF) to improve the quality and efficiency of litchi production. To further explore the soil microbiological mechanism, with 19-year-old 'Feizixiao' litchi trees as the research objects, we examined the effects of two consecutive years of reduced CF applications (average 21.5% of total nutrients) combined with sheep manure (OF) and bio-organic fertilizers (BIO) on soil microbial diversity, community composition and differential microorganisms. The results showed that reducing the application of chemical fertilizers and combining it with the application of sheep manure and bio-organic fertilizer for two consecutive years could significantly improve yield and quality. The average increase of yield in the two years was 23.1% and 39.0%, respectively. Soil organic matter content and pH increased significantly in response to the combination treatments. Compared to that in the chemical fertilizer treatment, the contents of soil available phosphorus, potassium, calcium, magnesium, iron, manganese, copper, and zinc displayed an increasing trend in the combination treatments. The application of organic fertilizer increased the diversity of bacteria and fungi in rhizosphere soil, but not in non-rhizosphere soil. Both treatments significantly changed soil microbial community structure, increased eutrophic bacterial groups such as Bacteroides, Proteobacteria, and Bacillus phylum, and reduced anatrophic bacterial groups such as Acidobacteria and Chloroflexus. Compared with CF, the relative abundances of MND1 under OF and TK10, Gemmatimonas, Pseudolabrys, Trichoderma and Botryotrichum under BIO were significantly increased, which was positively correlated with yield. In conclusion, reducing CF and applying organic ferti-lizer for two consecutive years could effectively improve soil pH and nutrient availability, increase rhizosphere microbial richness and diversity, change soil microbial community structure, and shape microbial communities being more conducive to yield and quality improvement.

Multiple fluorescence labeling and two dimensional FTIR-13C NMR heterospectral correlation spectroscopy to characterize extracellular polymeric substances in biofilms produced during composting.

Knowledge on the structure and function of extracellular polymeric substances (EPS) in biofilms is essential for understanding biodegradation processes. Herein, a novel method based on multiple fluorescence labeling and two-dimensional (2D) FTIR-(13)C NMR heterospectral correlation spectroscopy was developed to gain insight on the composition, architecture, and function of EPS in biofilms during composting. Compared to other environmental biofilms, biofilms in the thermophilic (>55 °C) and cooling (mature) stage of composting have distinct characteristics. The results of multiple fluorescence labeling demonstrated that biofilms were distributed in clusters during the thermophilic stage (day 14), and dead cells were detected. In the mature stage (day 26), the biofilm formed a continuous layer with a thickness of approximately 20-100 µm around the compost, and recolonization of cells at the surface of the compost was easily observed. Through 2D FTIR-(13)C NMR correlation heterospectral spectroscopy, the following trend in the ease of the degradation of organic compounds was observed: heteropolysaccharides > cellulose > amide I in proteins. And proteins and cellulose showed significantly more degradation than heteropolysaccharides. In summary, the combination of multiple fluorescence labeling and 2D correlation spectroscopy is a promising approach for the characterization of EPS in biofilms.

Prognostic Factors and a Nomogram Predicting Survival in Patients with Breast Ductal Carcinoma in situ with Microinvasion: A Population-Based Study.

PURPOSE: Ductal carcinoma in situ with microinvasion (DCISM) can be challenging to balance the risks of overtreatment versus undertreatment. We aim to identify prognostic factors in patients with DCISM and construct a nomogram to predict breast cancer-specific survival (BCSS). MATERIALS AND METHODS: A retrospective cohort study of women diagnosed with DCISM from 1988 to 2015 who were identified in the Surveillance, Epidemiology and End Results database. Clinical variables and tumor characteristics were evaluated, and Cox proportional-hazards regression was performed. A nomogram was constructed from the multivariate logistic regression to combine all the prognostic factors to predict the prognosis of DCISM patients at 5 years, 10 years, and 15 years. RESULTS: We identified 5438 total eligible breast cancer patients with a median and max survival time of 78 and 227 months, respectively. Here, patients with poorer survival outcomes were those diagnosed between 1988 and 2001, African-American race, under 40 years of age, higher tumor N stage, progesterone receptor-negative tumor, and received no surgery. The nomogram was constructed by the seven variables and passed the calibration and validation steps. The area under the receiver operating characteristic (ROC) curve (AUC) of both the training set and the validating set (5-year AUC: 0.77 and 0.88, 10-year AUC: 0.75 and 0.73, 15-year AUC: 0.72 and 0.65). Receiving chemotherapy was associated with a better BCSS (hazard ratio, HR=0.45, 95% confidence interval, 95% CI = 0.23-0.89), especially in patients with estrogen receptor (ER) negative, progesterone receptor (PR) negative (HR = 0.35, 95% CI = 0.13-0.97) and ER+PR-/ER-PR+ DCISM (HR = 0.07, 95% CI = 0.01-0.59). CONCLUSION: Our current study is the first to construct nomograms of patients with DCISM which could help physicians identify breast cancer patients that more likely to benefit from more intensive treatment and follow-up. Chemotherapy might benefit patients with ER-PR- and ER+PR-/ER-PR+ DCISM.

Hypoxia-inducible factor-1: A potential pharmacological target to manage psoriasis.

Hypoxia-inducible factor-1 (HIF-1) is a heterodimeric transcriptional factor and is composed of HIF-1α and HIF-1ß subunits. An increase in the levels of HIF-1α in the psoriatic lesions and the serum of psoriatic patients has been reported. An increase in the HIF-1α in the epithelial keratinocytes may contribute in promoting angiogenesis and skin inflammation. Accordingly, the drug therapy directed to control HIF-1α levels may effectively manage the disease. An increase in HIF-1α may participate in the pathogenesis of psoriasis in association with IL-6, vascular endothelial growth factor (VEGF), microRNA-150, microRNA-270, reactive oxygen species, bone morphogenetic protein 6 (BMP6), triggering receptor expressed on myeloid cells 1 (TREM-1) and phosphoinositide 3-kinases (PI3K)/Akt pathway. An increase in the levels of IL-6, free radicals, and reduction in miR-150 may increase the expression of HIF-1α, which may act to induce angiogenesis via VEGF-ERK2 signaling pathway. An increase in HIF-1α may attenuate the expression of BMP6 to inhibit the terminal differentiation and increase the proliferation of keratinocytes. Moreover, HIF-1α may increase the expression of miR-210 to decrease the levels of STAT-6 and LYN, which in turn is manifested in the form of excessive activation of immune system. An increase in keratinocyte proliferation, excessive angiogenesis along with abnormal activation of the immune system play a key role in the pathogenesis of psoriasis. The present review discusses the evidence showing the crucial role of HIF-1α in psoriasis along with interrelationship with other mediators/signaling pathways that may contribute to the development of psoriasis.

Childhood atopic dermatitis as a precursor for developing attention deficit/hyperactivity disorder.

Atopic dermatitis (AD) is a skin disease characterized by chronic inflammatory condition that shows hallmark presentations in terms of sleep disturbances, pruritus, and psychological stress, and an association with increased attention deficit/hyperactivity disorder (ADHD) risk. A number of studies have suggested for the co-occurrence of the two diseased conditions. In terms of global prevalence, AD and ADHD almost exhibit a parallel increment according to epidemiological data. In addition, recent reports indicate AD to show a temporal association with later onset of ADHD. Although several studies suggest for the potential link between AD and ADHD, currently there is no definitive answer to this regard. Furthermore, epidemiological evidence of co-occurrence does not ascertain a pathophysiological link between the two conditions. The pathophysiological basis behind the association of AD and ADHD also remain poorly elucidated. The objective of this review is to present an extensive account of AD and associated comorbidities with a special attention toward ADHD as well as to elaborate on the mechanisms underlying their association. The review can provide healthcare providers with the recent updates on AD-ADHD association and help them while dealing with such patients. In general, AD and ADHD show a positive association in majority of the cross-sectional studies. However, large longitudinal studies are required to draw any conclusion on the temporal nature of such association.

Sjogren-Larsson syndrome associated hypermelanosis.

BACKGROUND/OBJECTIVES: Sjogren - Larsson syndrome (SLS) is a rare autosomal recessive disease of the mutation ALDH3A2 that identifies a part of fatty acids for fatty aldehyde dehydrogenase: NAD-oxidoreductase enzyme complex. This study aimed to access variant ALDH3A2 gene coded for FALDH and products regulating pathogenic melanogenesis owing to increased oxidative stress and reactive oxygen species resulting in DNA harm in SLS. By turning them into fatty acids, FALDH avoids the accumulation of toxic fatty aldehydes. The mutation results in the accumulation of aldehyde-modified lipids or fatty alcohols that may interfere with skin and brain function. METHODS: In Nov 2018, we performed a literature search in PubMed for clinical studies, clinical trials, case reports, controlled trials, randomized controlled trials, and systemic reviews. The search terms we used were "SJOGREN-LARSSON SYNDROME" AND "HYPERMELANNOSIS" OR "FALDH" (from 1985). The search resulted in 1,289 articles, out of these 95 articles met our inclusion exclusion criteria. Our inclusion criteria included relevant original articles relevant, critical systemic reviews, and crucial referenced articles, ex-clusion criteria included duplicates and articles not published in English language. RESULTS: Toxicity of long-chain aldehydes to FALDH-deficient cells owing to accumulation under the profound epidermis layer improves oxidative stress in the cell resulting in keratinocyte hyperproliferation. CONCLUSION: While it continues to be determined whether accumulated fatty alcohol and fatty aldehydes obtained from ether glycerolipids and sphingolipids improve the susceptibility of melanocytes and their element accountable for skin hyperpigmentation to biological colour.

Effects of Dietary Fat Profile on Gut Microbiota in Valproate Animal Model of Autism.

Autism spectrum disorder (ASD) is a developmental disability which may cause significant social, communication, and behavioral challenges. Besides certain essential symptoms, a lot of ASD individuals also suffer the comorbidity of gut microbiota dysbiosis, which possibly causes a variety of gastrointestinal (GI) difficulties. Interestingly, evidence has indicated that behavioral output may be modulated through the communication between the central nervous system and gut microbiota via the gut-brain axis. Polyunsaturated fatty acids (PUFAs) and n-3 fatty acids (n-3 PUFA) are structurally and functionally crucial components for the brain, and the state of n-3 PUFAs also affects the gut microbiota. However, how varying intake ratios of n-3/n6 PUFAs affect the gut microbiota composition in ASDs is not well-understood. Pregnant female Wistar rats with intraperitoneal administration of valproate acid (VPA) at embryonic day (E) 12.5 and their male offspring were grouped and fed three diets: a control chow (VPA group), omega-3 deficient (A group), and n-3/n6 (1:5) diet (B group). The diet of pregnant female Wistar rats with intraperitoneal administration of saline and their male offspring was a control chow (normal group). Microbial composition and species abundance were investigated accordingly by the 16S rRNA gene-based metagenomics analysis on the fecal samples. Results showed that fecal microbial abundance was decreased because of VPA administration in the period of pregnancy, and the changing pattern of gut microbiota was similar to that reported in ASD patients. Furthermore, the n-3/n6 (1:5) diet increased the fecal microbial abundance and decreased the elevated Firmicutes. In conclusion, n-3/n6 PUFAs (1:5) diet supplementation may alter gut microbiota composition in VPA-exposed rats. This study put forward a new strategy for the intervention and treatment of autism by n-3/n-6 PUFAs ratio supplementation intakes.

Probiotic Diversity Enhances Rhizosphere Microbiome Function and Plant Disease Suppression.

Bacterial communities associated with plant roots play an important role in the suppression of soil-borne pathogens, and multispecies probiotic consortia may enhance disease suppression efficacy. Here we introduced defined Pseudomonas species consortia into naturally complex microbial communities and measured the importance of Pseudomonas community diversity for their survival and the suppression of the bacterial plant pathogen Ralstonia solanacearum in the tomato rhizosphere microbiome. The survival of introduced Pseudomonas consortia increased with increasing diversity. Further, high Pseudomonas diversity reduced pathogen density in the rhizosphere and decreased the disease incidence due to both intensified resource competition and interference with the pathogen. These results provide novel mechanistic insights into elevated pathogen suppression by diverse probiotic consortia in naturally diverse plant rhizospheres. Ecologically based community assembly rules could thus play a key role in engineering functionally reliable microbiome applications. IMPORTANCE: The increasing demand for food supply requires more-efficient control of plant diseases. The use of probiotics, i.e., naturally occurring bacterial antagonists and competitors that suppress pathogens, has recently reemerged as a promising alternative to agrochemical use. It is, however, still unclear how many and which strains we should choose for constructing effective probiotic consortia. Here we present a general ecological framework for assembling effective probiotic communities based on in vitro characterization of community functioning. Specifically, we show that increasing the diversity of probiotic consortia enhances community survival in the naturally diverse rhizosphere microbiome, leading to increased pathogen suppression via intensified resource competition and interference with the pathogen. We propose that these ecological guidelines can be put to the test in microbiome engineering more widely in the future.

Altering Transplantation Time to Avoid Periods of High Temperature Can Efficiently Reduce Bacterial Wilt Disease Incidence with Tomato.

Tomato bacterial wilt caused by Ralstonia solanacearum bacterium is a severe problem in Southern China, where relatively high environmental temperatures commonly prevails during the crop seasons. Previous research has indicated that bacterial wilt disease incidence generally increases during the warm months of summer leading to reduced tomato yield. Moreover, the efficacy of bio-organic fertilizers (BOFs)-organic compost fortified with pathogen-suppressive bacteria-is often lost during the periods of high environmental temperatures. Here we studied if the disease incidence could be reduced and the BOF performance enhanced by simply preponing and postponing the traditional seedling transplantation times to avoid tomato plant development during periods of high environmental temperature. To this end, a continuous, two-year field experiment was conducted to evaluate the performance of BOF in two traditional (late-spring [LS] and early-autumn [EA]) and two alternative (early-spring [ES] and late-autumn [LA]) crop seasons. We found that changing the transplantation times reduced the mean disease incidence from 33.9% (LS) and 54.7% (EA) to 11.1% (ES) and 7.1% (LA), respectively. Reduction in disease incidence correlated with the reduction in R. Solanacearum pathogen density in the tomato plant rhizosphere and stem base. Applying BOF during alternative transplantation treatments improved biocontrol efficiency from 43.4% (LS) and 3.1% (EA) to 67.4% (ES) and 64.8% (LA). On average, the mean maximum air temperatures were positively correlated with the disease incidence, and negatively correlated with the BOF biocontrol efficacy over the crop seasons. Crucially, even though preponing the transplantation time reduced the tomato yield in general, it was still economically more profitable compared to LS season due to reduced crop losses and relatively higher market prices. Preponing and postponing traditional tomato transplantation times to cooler periods could thus offer simple but effective way to control R. solanacearum disease outbreaks.

Fate of biopolymers during rapeseed meal and wheat bran composting as studied by two-dimensional correlation spectroscopy in combination with multiple fluorescence labeling techniques.

Detailed knowledge of the molecular events during composting is important in improving the efficiency of this process. By combining two-dimensional Fourier transform infrared (FTIR) correlation spectroscopy and multiple fluorescent labeling, it was possible to study the degradation of biopolymers during rapeseed meal and wheat bran composting. Two-dimensional FTIR correlation spectroscopy provided structural information and was used to deconvolute overlapping bands found in the compost FTIR spectra. The degradation of biopolymers in rapeseed meal and wheat bran composts followed the sequence: cellulose, heteropolysaccharides, and proteins. Fluorescent labeling suggested that cellulose formed an intact network-like structure and the other biopolymers were embedded in the core of this structure. The sequence of degradation of biopolymers during composting was related to their distribution patterns.

[Mechanisms for the increased fertilizer nitrogen use efficiency of rice in wheat-rice rotation system under combined application of inorganic and organic fertilizers].

A pot experiment was conducted to study the effects of combined application of organic and inorganic fertilizers on the nitrogen uptake by rice and the nitrogen supply by soil in a wheat-rice rotation system, and approach the mechanisms for the increased fertilizer nitrogen use efficiency of rice under the combined fertilization from the viewpoint of microbiology. Comparing with applying inorganic fertilizers, combined application of organic and inorganic fertilizers decreased the soil microbial biomass carbon and nitrogen and soil mineral nitrogen contents before tillering stage, but increased them significantly from heading to filling stage. Under the combined fertilization, the dynamics of soil nitrogen supply matched best the dynamics of rice nitrogen uptake and utilization, which promoted the nitrogen accumulation in rice plant and the increase of rice yield and biomass, and increased the fertilizer nitrogen use efficiency of rice significantly. Combined application of inorganic and organic fertilizers also promoted the propagation of soil microbes, and consequently, more mineral nitrogen in soil was immobilized by the microbes at rice early growth stage, and the immobilized nitrogen was gradually released at the mid and late growth stages of rice, being able to better satisfy the nitrogen demand of rice in its various growth and development stages.

[Screening, identification, and biocontrol effect of antagonistic bacteria against Phytophthora capsici].

A total of 98 isolates with antagonistic activity against Phytophthora capsici were isolated from the rhizosphere soil of healthy pepper plants in the fields seriously infected by pepper Phytophthora capsicit, and two strains named as HL-3 and LZ-8 were screened, which had the characteristics of wide-spectrum antagonism and good growth under poor soil condition. The HL-3 and LZ-8 were identified as Paenibacillus polymyxa and Bacillus pumilus, respectively, based on their morphological and biochemical characteristics and 16S rDNA sequences. The two strains could inhibit the mycelium growth of P. capsici, and the inhibitory effect of HL-3 and LZ-8 was 72% and 68%, respectively. The two strains also had antifungal activities toward other plant pathogens such as Verticillium dahliae, Fusarium oxysporum f. sp. cucumerinum, F. oxysporum f. sp. vasinfectum, Rhizoctonia solani, Phtophthora parasitica var. nicotiana, and Ralstonia solanacearum. Pot experiment showed that the biocontrol effects of HL-3 and LZ-8 against P. capsici at the seedling stage of pepper were 72% and 83%, respectively, and both of the strains had significant growth-promoting effect on pepper plants.

[Effects of organic-inorganic mixed fertilizers on rice yield and nitrogen use efficiency].

A field experiment was carried to study the effects of organic-inorganic mixed fertilizers on rice yield, nitrogen (N) use efficiency, soil N supply, and soil microbial diversity. Rapeseed cake compost (RCC), pig manure compost (PMC), and Chinese medicine residue compost (MRC) were mixed with chemical N, P and K fertilizers. All the treatments except CK received the same rate of N. The results showed that all N fertilizer application treatments had higher rice yield (7918.8-9449.2 kg x hm(-2)) than the control (6947.9 kg x hm(-2)). Compared with that of chemical fertilizers (CF) treatment (7918.8 kg x hm(-2)), the yield of the three organic-inorganic mixed fertilizers treatments ranged in 8532.0-9449.2 kg x hm(-2), and the increment was 7.7%-19.3%. Compared with treatment CF, the treatments of organic-inorganic mixed fertilizers were significantly higher in N accumulation, N transportation efficiency, N recovery rate, agronomic N use efficiency, and physiological N use efficiency. These mixed fertilizers treatments promoted rice N uptake and improved soil N supply, and thus, increased N use efficiency, compared with treatments CF and CK. Neighbor joining analysis indicated that soil bacterial communities in the five treatments could be classified into three categories, i.e., CF and CK, PMC and MRC, and RCC, implying that the application of exogenous organic materials could affect soil bacterial communities, while applying chemical fertilizers had little effect on them.

[Effects of N fertilization levels on ammonia volatilization from rice shoot at later growth stages].

With simulated pot culture in greenhouse, the ammonia volatilization from rice shoot and its affecting factors after flowering was studied under different N fertilization levels. The results showed that the daily and total amount of volatilized ammonia increased with increasing N application rate, with a certain variance among different N levels observed. At flowering and maturing stages; the ammonia volatilization from rice shoot (y) had significant negative correlations with functional leaf GS activity (x1) and positive correlations with functional leaf apoplastic NH4+ concentration (x2), with y = -0.37846x1 + 0.41821x2 + 0.04925 (R2 = 0.9471, n = 16), and negative correlations with N harvest index (x1) and physiological N use efficiency (x2), following y = -0.02117x1 + 0.75186 (R2 = 0.842, n = 8) and y = -1.10386x2 + 35.52676 (R2 = 0.8489, n = 8), respectively. It was suggested that the increasing ammonia volatilization from rice shoot under high N fertilization level was correlated with the decrease of N use efficiency by rice.

[High effective phosphate-solubilizing bacteria: their isolation and promoting effect on corn seedling growth].

By using modified PVK plate method, 44 strains of phosphate-solubilizing bacteria (PSB) were isolated from the root surface of wild plants growing well in calcareous soil. After 7-day incubation in a liquid medium NBRIP, the total P in the cultures of strains K3 and K9 reached 643.2 microg x ml(-1) and 608.5 microg x ml(-1), and soluble P was 584.8 microg x ml(-1) and 606.4 microg x ml(-1), respectively. About 12.9% of tricalcium phosphate was dissolved, being 9.5 times higher than CK. Pot experiment showed that the plant height, stem diameter, and dry mass of corn seedling were significantly higher in PSB treatments than in CK. Applying PSB agent with manure as a carrier could significantly increase the seedling's dry mass, in comparing with applying PSB agent alone. The strains K3 and K9 were identified as Pseudomonas.