Chinese expert consensus on the diagnosis and treatment of HER2-altered non-small cell lung cancer.

Human epidermal growth factor receptor 2 (HER2) possesses tyrosine kinase activity and participates in cell growth, differentiation and migration, and survival. Its alterations, mainly including mutations, amplifications, and overexpression are associated with poor prognosis and are one of the major drivers in non-small cell lung cancer (NSCLC). Several clinical trials had been investigating on the treatments of HER2-altered NSCLC, including conventional chemotherapy, programmed death 1 (PD-1) inhibitors, tyrosine kinase inhibitors (TKIs) and antibody-drug conjugates (ADCs), however, the results were either disappointing or encouraging, but inconsistent. Trastuzumab deruxtecan (T-DXd) was recently approved by the Food and Drug Administration as the first targeted agent for treating HER2-mutant NSCLC. Effective screening of patients is the key to the clinical application of HER2-targeted agents such as TKIs and ADCs. Various testing methods are nowadays available, including polymerase chain reaction (PCR), next-generation sequencing (NGS), fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), etc. Each method has its pros and cons and should be reasonably assigned to appropriate patients for diagnosis and guiding treatment decisions. To help standardize the clinical workflow, our expert group reached a consensus on the clinical management of HER2-altered NSCLC, focusing on the diagnosis and treatment strategies.

Distribution Characteristics and Controlling Factors of Soil Total Nitrogen: Phosphorus Ratio Across the Northeast Tibetan Plateau Shrublands.

Nitrogen (N) and phosphorus (P) stoichiometry have significant effects on nutrient cycles in terrestrial ecosystems. However, our understanding of the patterns and the driving factors of soil N:P ratios in the Tibetan Plateau shrublands remains limited. Our study aimed to quantify the distribution of soil N:P ratio and its controlling factors based on soil, plant, and climate factors from 59 sites in shrublands across the northeast Tibetan Plateau. The kriging interpolation method was used to quantify the soil N:P distribution. Spatially, the soil N:P ratio was higher in the south than in the north and lower in the west than in the east. The soil N:P ratio in the northeast Tibetan Plateau shrublands was mainly explained by edaphic factors, which also played an important role in regulating the effects of plant and climate factors on soil N:P ratios. Mean annual precipitation, instead of mean annual temperature, significantly controlled the soil N:P ratios, and its effect on the pattern of soil N:P ratios differed between alpine shrublands and desert shrublands. The N:P ratios of different organs in shrublands also played different roles in shaping the soil N:P ratios in alpine and desert shrublands. These results provide support for the hypothesis that edaphic factors were the dominant drivers of spatial variation in soil N:P ratios across the northeast Tibetan Plateau shrublands, and our study contributes to a deeper understanding of biogeochemical cycling at high altitudes.

Non-target metabolomics revealed the differences between Rh. tanguticum plants growing under canopy and open habitats.

BACKGROUND: Rheum tanguticum (Rh. tanguticum) is an important traditional Chinese medicine plant, "Dahuang", which contains productive metabolites and occupies wide habitats on the Qinghai-Tibet plateau. Plants occupying wide habitats usually vary in phenotypes such as in morphology and metabolism, thereby developing into different ecotypes. Under canopy and open habitats are a pair of dissimilar habitats which possess Rh. tanguticum plants. However, few studies have focused on the effect of habitats on Rh. tanguticum growth, particularly combining morphological and metabolic changes. This study focused on Rh. tanguticum plants growing in under canopy and open habitats where morphology and metabolism changes were quantified using non-target metabolism methods. RESULTS: The obtained results indicated that the two dissimilar habitats led to Rh. tanguticum developing into two distinct ecotypes where the morphology and metabolism were simultaneously changed. Under canopy habitats bred morphologically smaller Rh. tanguticum plants which had a higher level of metabolites (22 out of 31) which included five flavonoids, four isoflavonoids, and three anthracenes. On the other hand, the open habitats produced morphologically larger Rh. tanguticum plants having a higher level of metabolites (9 out of 31) including four flavonoids. 6 of the 31 metabolites were predicted to have effect targets, include 4 represent for under canopy habitats and 2 for open habitats. Totally, 208 targets were connected, among which 42 were communal targets for both under canopy and open habitats represent compounds, and 100 and 66 were unique targets for under canopy superior compounds and open habitats superior compounds, respectively. In addition, aloe-emodin, emodin, chrysophanol, physcion, sennoside A and sennoside B were all more accumulated in under canopy habitats, and among which aloe-emodin, emodin, chrysophanol and physcion were significantly higher in under canopy habitats. CONCLUSIONS: This study determined that Rh. tanguticum growing in under canopy and in open habitats developed into two distinct ecotypes with morphological and metabolic differences. Results of network pharmacology study has indicated that "Dahuang" coming from different habitats, such as under canopy and open habitats, are different in effect targets and thus may have different medicinal use. According to target metabolomics, under canopy habitats may grow better "Dahuang".

Examining differences in phylogenetic composition enhances understanding of the phylogenetic structure of the shrub community in the northeastern Qinghai-Tibetan Plateau.

Periodic climatic oscillations and species dispersal during the postglacial period are two important causes of plant assemblage and distribution on the Qinghai-Tibet Plateau (QTP). To improve our understanding of the bio-geological histories of shrub communities on the QTP, we tested two hypotheses. First, the intensity of climatic oscillations played a filtering role during community structuring. Second, species dispersal during the postglacial period contributed to the recovery of species and phylogenetic diversity and the emergence of phylogenetic overdispersion. To test these hypotheses, we investigated and compared the shrub communities in the alpine and desert habitats of the northeastern QTP. Notably, we observed higher levels of species and phylogenetic diversity in the alpine habitat than in the desert habitat, leading to phylogenetic overdispersion in the alpine shrub communities versus phylogenetic clustering in the desert shrub communities. This phylogenetic overdispersion increased with greater climate anomalies. These results suggest that (a) although climate anomalies strongly affect shrub communities, these phenomena do not act as a filter for shrub community structuring, and (b) species dispersal increases phylogenetic diversity and overdispersion in a community. Moreover, our investigation of the phylogenetic community composition revealed a larger number of plant clades in the alpine shrub communities than in the desert shrub communities, which provided insights into plant clade-level differences in the phylogenetic structures of alpine and desert shrub communities in the northeastern QTP.

Nitrogen Fertilizer Levels Affect the Growth and Quality Parameters of Astragalus mongolica.

Owing to overexploitation, wild resources of Astragalus mongolica, a Chinese herbal plant that is widely distributed in the arid and semi-arid areas of Northern China, have gradually become exhausted, and therefore, commercial cultivation is increasingly important to meet the growing demand for astragalus and reduce the pressure on wild populations. Nitrogen level is an important factor that affects the yield and quality of A. mongolica. However, uniform standards for fertilization among production areas have not yet been determined. In this study, the effect of nitrogen fertilizer treatment on the yield and quality of A. mongolica in the Qinghai-Tibet Plateau was explored using a control treatment (no added nitrogen, N0) and five different nutrient levels: 37.5 kg/ha (N1), 75 kg/ha (N2), 112.5 kg/ha (N3), 150 kg/ha (N4), and 187.5 kg/ha (N5). According to grey relational analysis, the optimal nitrogen fertilizer treatment was the N4 level followed by the N5 and N2 levels. Nitrogen fertilizer significantly increased the root biomass, plant height, root length, and root diameter. However, nitrogen fertilization had no significant effect on the content of Astragaloside IV and mullein isoflavone glucoside. The content of ononin and calycosin continually accumulated throughout the growing period. The results showed that the ononin and calycosin content under N4 and N2 is higher than other levels and there is not significantly different between different nitrogen fertilizer levels about them. The content of formononetin decreased gradually with the progression of the growing season. The optimal nitrogen fertilizer treatment for A. mongolica is recommended to be 150 kg/ha and the content of active compounds and yield were observed to reach the maximum in October.

Precipitation and nitrogen addition enhance biomass allocation to aboveground in an alpine steppe.

There are two important allocation hypotheses in plant biomass allocation: allometric and isometric. We tested these two hypotheses in an alpine steppe using plant biomass allocation under nitrogen (N) addition and precipitation (Precip) changes at a community level. An in situ field manipulation experiment was conducted to examine the two hypotheses and the responses of the biomass to N addition (10 g N m-2 y-1) and altered Precip (±50% precipitation) in an alpine steppe on the Qinghai-Tibetan Plateau from 2013 to 2016. We found that the plant community biomass differed in its response to N addition and reduced Precip such that N addition significantly increased aboveground biomass (AGB), while reduced Precip significantly decreased AGB from 2014 to 2016. Moreover, reduced Precip enhanced deep soil belowground biomass (BGB). In the natural alpine steppe, the allocation between AGB and BGB was consistent with the isometric hypotheses. In contrast, N addition or altered Precip enhanced biomass allocation to aboveground, thus leading to allometric growth. More importantly, reduced Precip enhanced biomass allocation into deep soil. Our study provides insight into the responses of alpine steppes to global climate change by linking AGB and BGB allocation.

Effects of different nitrogen fertilizer levels on growth and active compounds of rhubarb from Qinghai plateau.

BACKGROUND: Rheum tanguticum Maxim. ex Balf is one of the plants generically known as rhubarb, a culinary vegetable that has long been used as a herbal remedy both in China and Europe. Increasing demand for rhubarb has triggered the overexploitation of Rh. tanguticum. Cultivation is therefore necessary for quality control and protection of wild resources. Nitrogen fertilizer plays an important role in cultivation. This study aimed to explore how nitrogen fertilizer affects the growth and quality of rhubarb on the Qinghai-Tibetan plateau. RESULTS: Nitrogen fertilizer promoted growth but had no significant influence on the active compounds of Rh. tanguticum. Generally, the N2 (150 kg ha-1 ) and N3 (225 kg ha-1 ) levels showed the most improved growth indexes, with no significant differences between them. The growth index and the amounts of eight of the nine studied active compounds in Rh. tanguticum increased from each year to the next and differed among growth stages. The contents of the active compounds were higher at the green stage and lower at the growth stage, which was opposite to the seasonal trends in root dry matter ratio. Gallic acid levels decreased with the growth of the plant. CONCLUSION: The N2 level (150 kg ha-1 ) was the recommended nitrogen fertilizer level in this study. It was revealed that seasonal changes rather than nitrogen fertilizer influenced active compounds in the root of Rh. tanguticum. © 2018 Society of Chemical Industry.

Differential responses of heterotrophic and autotrophic respiration to nitrogen addition and precipitation changes in a Tibetan alpine steppe.

Soil respiration (Rs) is an important source of atmospheric CO2 flux and is sensitive to changes in soil nutrient and water contents. Despite extensive studies on the effects of enhanced atmospheric nitrogen (N) deposition and changes in precipitation (P) on Rs, few studies have taken into account the effects of interactions between these factors on Rs of alpine grasslands. To address these questions, we investigated the effects of N addition (10 g N m-2 yr-1), changes in precipitation (±50% precipitation), and their interaction on soil respiration and its components, including heterotrophic respiration (Rh) and autotrophic respiration (Ra),in a Tibetan alpine steppe during three consecutive growing seasons. We found that Rs differed in its response to N addition and precipitation regimes. Specifically, decreased precipitation led to a significant reduction in Rs during the last two years, whereas N addition minimally impacted Rs. Another important finding was that soil respiration components differed in their response to N addition and precipitation regimes. Nitrogen addition significantly enhanced Ra, whereas Rh was not altered in response to N addition. By contrast, the precipitation regime led to marked changes in Rh, but exhibited marginally significant effects on Ra. Therefore, our findings highlighted that soil respiration differed in its response to N addition and precipitation regimes mainly due to the different responses of soil respiration components to these factors. Therefore, carbon dynamics should take soil respiration components into account under global change scenarios.

Above- and Belowground Biomass Allocation in Shrub Biomes across the Northeast Tibetan Plateau.

Biomass partitioning has been explored across various biomes. However, the strategies of allocation in plants still remain contentious. This study investigated allocation patterns of above- and belowground biomass at the community level, using biomass survey from the Tibetan Plateau. We explored above- and belowground biomass by conducting three consecutive sampling campaigns across shrub biomes on the northeast Tibetan Plateau during 2011-2013. We then documented the above-ground biomass (AGB), below-ground biomass (BGB) and root: shoot ratio (R/S) and the relationships between R/S and environment factors using data from 201 plots surveyed from 67 sites. We further examined relationships between above-ground and below-ground biomass across various shrub types. Our results indicated that the median values of AGB, BGB, and R/S in Tibetan shrub were 1102.55, 874.91 g m-2, and 0.85, respectively. R/S showed significant trend with mean annual precipitation (MAP), while decreased with mean annual temperature (MAT). Reduced major axis analysis indicated that the slope of the log-log relationship between above- and belowground biomass revealed a significant difference from 1.0 over space, supporting the optimal hypothesis. Interestingly, the slopes of the allometric relationship between log AGB and log BGB differed significantly between alpine and desert shrub. Our findings supported the optimal theory of above- and belowground biomass partitioning in Tibetan shrub, while the isometric hypothesis for alpine shrub at the community level.

Breast cancer in Chinese elderly women: pathological and clinical characteristics and factors influencing treatment patterns.

The aims of this study are to describe tumor characteristics and treatment patterns of elder breast cancer patients and to determine the factors influencing local and systemic treatments. This retrospective cohort included 866 patients (>or=60 years) referred for surgery between January 2002 and December 2006. The patients were divided into four groups according to age. Elderly women had larger tumors at diagnosis with more mucinous carcinomas, more estrogen/progesterone-positive, lower Ki-67 labeling indices and less c-erbB2 positive tumors. Comorbidities were more often recorded for older patients. They were more likely to undergo simple mastectomy or breast-conserving surgery, less likely to receive adjuvant chemotherapy and radiotherapy, compared with their younger counterparts. Multinomial and binary logistic regression showed that age was independently associated with local and systemic treatments. Our data suggest that the tumors of elderly patients are biologically more favorable, and elderly women appear to receive less aggressive treatments.