Two nomograms constructed for predicting the efficacy and prognosis of advanced non­small cell lung cancer patients treated with anti­PD­1 inhibitors based on the absolute counts of lymphocyte subsets.

BACKGROUND: Patients treated with immune checkpoint inhibitors (ICIs) are at risk of considerable adverse events, and the ongoing struggle is to accurately identify the subset of patients who will benefit. Lymphocyte subsets play a pivotal role in the antitumor response, this study attempted to combine the absolute counts of lymphocyte subsets (ACLS) with the clinicopathological parameters to construct nomograms to accurately predict the prognosis of advanced non-small cell lung cancer (aNSCLC) patients treated with anti-PD-1 inhibitors. METHODS: This retrospective study included a training cohort (n = 200) and validation cohort (n = 100) with aNSCLC patients treated with anti-PD-1 inhibitors. Logistic and Cox regression were conducted to identify factors associated with efficacy and progression-free survival (PFS) respectively. Nomograms were built based on independent influencing factors, and assessed by the concordance index (C-index), calibration curve and receiver operating characteristic (ROC) curve. RESULT: In training cohort, lower baseline absolute counts of CD3+ (P < 0.001) and CD4+ (P < 0.001) were associated with for poorer efficacy. Hepatic metastases (P = 0.019) and lower baseline absolute counts of CD3+ (P < 0.001), CD4+ (P < 0.001), CD8+ (P < 0.001), and B cells (P = 0.042) were associated with shorter PFS. Two nomograms to predict efficacy at 6-week after treatment and PFS at 4-, 8- and 12-months were constructed, and validated in validation cohort. The area under the ROC curve (AUC-ROC) of nomogram to predict response was 0.908 in training cohort and 0.984 in validation cohort. The C-index of nomogram to predict PFS was 0.825 in training cohort and 0.832 in validation cohort. AUC-ROC illustrated the nomograms had excellent discriminative ability. Calibration curves showed a superior consistence between the nomogram predicted probability and actual observation. CONCLUSION: We constructed two nomogram based on ACLS to help clinicians screen of patients with possible benefit and make individualized treatment decisions by accurately predicting efficacy and PFS for advanced NSCLC patient treated with anti-PD-1 inhibitors.

Upregulation of MELK promotes chemoresistance and induces macrophage M2 polarization via CSF-1/JAK2/STAT3 pathway in gastric cancer.

BACKGROUND: Gastric cancer (GC) stands out as one of the most prevalent malignancies affecting the digestive system, characterized by a substantial incidence rate and mortality. Maternal embryonic leucine zipper kinase (MELK) has been implicated in the advancement of various cancer types and the modulation of the tumor microenvironment. This study aims to delve into the involvement of MELK in chemoresistance and the tumor microenvironment of GC. METHODS: The MELK expression was detected using quantitative real-time polymerase chain reaction (qRT-PCR), western blotting and immunohistochemistry. Lentiviral transfection was employed to establish stable cell lines with either overexpressed or silenced MELK. The impact of MELK on the chemoresistance of GC cells and the polarization of macrophages was investigated through in vitro and in vivo functional assays. Additionally, the correlation between MELK and the cytokines colony-stimulating factor 1 (CSF-1), as well as stromal macrophages, was analysed. The prognostic significance of MELK, CSF-1, and CD206 expression levels in clinical samples was further investigated. RESULTS: MELK was found to be highly expressed in chemoresistant GC cells and tissues. Furthermore, both in vitro and in vivo assays indicated that MELK overexpression conferred chemoresistance in GC cells. Additionally, MELK overexpression was observed to induce M2 macrophage polarization via the CSF-1/JAK2/STAT3 pathway, thereby contributing to chemoresistance within the tumor microenvironment. The expression of MELK in GC tissues from neoadjuvant chemotherapy patients correlated positively with CSF-1 and CD206. Moreover, patients with higher expression levels of MELK, CSF-1, or CD206 exhibited significantly shorter OS and DFS rates. CONCLUSIONS: Our investigation underscores the critical role of MELK in promoting chemoresistance and inducing M2 macrophage polarization in GC. It proposes novel targets and methods for the treatment of GC, as well as prognostic factors for neoadjuvant chemotherapy.

7,8-dihydroxyflavone displayed antioxidant effect through activating HO-1 expression and inhibiting caspase-3/PARP activation in RAW264.7 cells.

Flavonoids, which contain a benzo-γ-pyrone (C6-C3-C6) skeleton, have been reported to exhibit effective antioxidant ability. This study aimed to compare the antioxidant activities of 7,8-dihydroxyflavone (7,8-DHF) and 7-hydroxyflavone (7-HF) in H2 O2 , lipopolysaccharide (LPS), or tert-butyl hydroperoxide (t-BHP)-induced RAW264.7 cells, respectively. The antioxidant capacities of 7,8-DHF and 7-HF were firstly evaluated by 2,2-azinobis-3-ethyl-benzothiazoline-6-sulphonic acid (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays. Then, reactive oxygen species (ROS), super oxide dismutase (SOD), and malondialdehyde (MDA) productions in H2 O2 , LPS, or t-BHP-induced RAW264.7 cells were tested and compared, respectively. Finally, the antioxidant mechanisms of 7-HF and 7,8-DHF were initially investigated by western blot. Our results showed that 7,8-DHF possessed stronger free-radical scavenging capacity than 7-HF. Both 7,8-DHF and 7-HF suppressed MDA production and ROS accumulation, improved the activity of SOD in H2 O2 , LPS, or t-BHP-induced RAW264.7 cells, respectively. And 7,8-DHF exerted a better antioxidant effect than 7-HF, especially in t-BHP-induced oxidative stress. Mechanically, 7,8-DHF prevented the activation of poly ADP-ribosepolymerase and caspase-3, meanwhile markedly upregulated the expression of HO-1 protein in t-BHP-induced oxidative stress. These results suggested that 7,8-DHF might serve as a potential pharmaceutical drug against oxidative stress injury.

Identification of SPRYD4 as a tumour suppressor predicts prognosis and correlates with immune infiltration in cholangiocarcinoma.

Cholangiocarcinoma (CCA) is an aggressive solid tumour with a 5-year survival rate ranging from 7% to 20%. It is, therefore, urgent to identify novel biomarkers and therapeutic targets to improve the outcomes of patients with CCA. SPRY-domain containing protein 4 (SPRYD4) contains SPRY domains that modulate protein-protein interaction in various biological processes; however, its role in cancer development is insufficiently explored. This study is the first to identify that SPRYD4 is downregulated in CCA tissues using multiple public datasets and a CCA cohort. Furthermore, the low expression of SPRYD4 was significantly associated with unfavourable clinicopathological characteristics and poor prognosis in patients with CCA, indicating that SPRYD4 could be a prognosis indicator of CCA. In vitro experiments revealed that SPRYD4 overexpression inhibited CCA cells proliferation and migration, whereas the proliferative and migratory capacity of CCA cells was enhanced after SPRYD4 deletion. Moreover, flow cytometry showed that SPRYD4 overexpression triggered the S/G2 cell phase arrest and promoted apoptosis in CCA cells. Furthermore, the tumour-inhibitory effect of SPRYD4 was validated in vivo using xenograft mouse models. SPRYD4 also showed a close association with tumour-infiltrating lymphocytes and important immune checkpoints including PD1, PD-L1 and CTLA4 in CCA. In conclusion, this study elucidated the role of SPRYD4 during CCA development and highlighted SPRYD4 as a novel biomarker and tumour suppressor in CCA.

Association between Plasma FGF21 Levels and Body Composition in Patients with Gastric Cancer.

BACKGROUND: Accumulating evidence has suggested that Fibroblast growth factor 21 (FGF21) plays an important role in metabolic diseases. This study aimed to investigate the relationship between plasma FGF21 levels and body composition parameters in gastric cancer (GC) patients. METHODS: This study was cross-sectional based on a prospective cohort of GC patients in a single center. Computer tomography (CT) and bioelectrical impedance analysis (BIA) were used to estimate skeletal muscle and adipose tissue mass. Blood samples were collected and plasma concentrations of FGF21 were measured by ELISA. Spearman's rank correlation test and logistic regression analysis were performed to assess associations between plasma FGF21 levels and these body composition parameters. RESULTS: A total of 66 GC patients were enrolled in this study. Plasma FGF21 levels were significantly higher in women compared with men. The plasma FGF21 levels were positively correlated with fat mass index (FMI), fat mass percentage (FM%), and subcutaneous adipose tissue index (SATI). Furthermore, after adjustment for confounders, the lower plasma FGF21 levels were remain associated with increased odds for low SATI. CONCLUSIONS: Plasma FGF21 levels were positively associated with FMI, FM%, and SATI in GC patients, suggesting a potential mechanistic link between FGF21 and subcutaneous adipose tissue in GC.

Prognostic significance of blood-based PD-L1 analysis in patients with non-small cell lung cancer undergoing immune checkpoint inhibitor therapy: a systematic review and meta-analysis.

BACKGROUND: The main types of PD-L1 in the blood include soluble PD-L1 (sPD-L1), exosomal PD-L1 (exoPD-L1), and PD-L1 in circulating tumor cells (CTCs). However, the predictive and prognostic values of these three indicators in patients with non-small cell lung cancer (NSCLC) undergoing immune checkpoint inhibitor (ICI) therapy are unclear, warranting a systematic meta-analysis. METHODS: A systematic literature search was performed in the PubMed, Cochrane Library, and Embase databases. The pooled hazard ratio (HR) and 95% confidence interval (CI) values were extracted from the included studies to investigate the correlation between the three PD-L1 indicators and overall survival (OS) or progression-free survival (PFS). The Newcastle-Ottawa Scale (NOS) was used to examine the quality of the included studies. Subgroup analyses were employed to investigate the heterogeneity. The publication bias of the included studies was assessed using Begg's and Egger's tests. P < 0.05 was regarded as significantly different. RESULTS: The pooled results revealed that high pre-treatment sPD-L1 levels were significantly associated with inferior OS (HR = 2.32, 95% CI = 1.68-3.18, P < 0.001) and PFS (HR = 2.52, 95% CI = 1.72-3.68, P < 0.001). However, dynamic changes in sPD-L1 after immunotherapy were not statistically significant for OS (HR = 1.46, 95% CI = 0.65-3.26, P > 0.05) or PFS (HR = 1.62, 95% CI = 0.92-2.86, P > 0.05). Meanwhile, the upregulated pre-treatment exoPD-L1 levels were significantly associated with poor PFS (HR = 4.44, 95% CI = 2.87-6.89, P < 0.001), whereas the post-treatment dynamic upregulation of exoPD-L1 was significantly correlated with superior PFS (HR = 0.36, 95% CI = 0.24-0.54, P < 0.001) and OS (HR = 0.20, 95% CI = 0.07-0.53, P < 0.001). For PD-L1 in CTCs, the pooled results indicated that PD-L1 expression in CTCs was not significantly correlated with OS (HR = 0.75, 95% CI = 0.49-1.13, P = 0.170) and PFS (HR = 0.79, 95% CI = 0.59-1.06, P = 0.12). CONCLUSIONS: Blood-based PD-L1 analysis is a potential strategy for predicting treatment efficacy and prognosis in patients with cancer.

Intestinal Nutrition Played a Vital Important Role in an Intestinal Perforation Patient with Chronic Constipation: A Case Report.

Introduction: Nutrition treatment is important in the critically ill patient. Nutritional therapy should be instituted as soon as possible if indicated. Case presentation: A 64-year-old woman with malnutrition and intestinal obstruction with gastrointestinal bleeding came to our emergency room. She had a history of constipation. After CT scan, we found perforations in the digestive tract. Because she could not tolerate surgery and parenteral nutrition (PN), we chose to start enteral nutrition (EN). She recovered after the initiation of EN. Discussion: Chronic constipation may cause intestinal obstruction, which is rare but fatal. Providers should evaluate the nutritional status for the intensive care patient and start PN/EN at once if necessary. EN may help the closure of perforations. Conclusion: EN may play a vital important role even in the patients who have perforations in the digestive tract. Chronic constipation may cause obstruction and perforation, which are rare but fatal.

Antibacterial metabolites from the beetle-associated fungus Penicillium chrysogenum.

The antibacterial secondary metabolites of the fungus Penicillium chrysogenum associated with the beetle Aspongopus chinensis were investigated through chromatographic fractionation methods of ethyl acetate extracts of the fungal cultures. Five compounds were isolated, and their structures were determined as emodin, 4-(methoxymethyl)benzoic acid, isoochracinic acid, secalonic acid D, and dicerandrol A using mass spectroscopy and nuclear magnetic resonance spectroscopic analyses. Emodin exhibited strong antimicrobial activity, especially against Staphylococcus aureus even when growing on cooked pork, with a minimal inhibitory concentration (MIC) of 6.3 µg/mL. Dimeric tetrahydroxanthones, such as secalonic acid D and dicerandrol A, also exhibited potent activity, with MIC values ranging from 9.5 to 28.5 µg/mL. In summary, P. chrysogenum was isolated as a symbiotic fungus of the beetle A. chinensis for the first time and this strain could generate antibacterial secondary metabolites, which could potently inhibit gram-positive bacteria growth in vitro.

Urolithin A suppresses tumor progression and induces autophagy in gastric cancer via the PI3K/Akt/mTOR pathway.

Urolithin A (UA) is a microbial metabolite of natural polyphenols ellagitannins and ellagic acid with well-established antitumor properties against various malignancies. However, the exact role of UA in gastric cancer (GC) progression remains largely unclear. In the present study, we investigated the effects and potential mechanisms of UA in GC in vitro and in vivo. Our results revealed that UA could suppress GC cell proliferation, inhibit migration and invasion, promote apoptosis, and induce autophagy via the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin pathway in vitro. The autophagy inhibitors 3-methyladenine and chloroquine augmented the inhibitory effect of UA on proliferation and promoted apoptosis, implying that UA mediated the cytoprotective role of autophagy. Meanwhile, the in vivo experiments showed that UA effectively suppressed tumor growth, enhanced the therapeutic effects, and alleviated chemotherapy toxicity in xenograft models. Overall, these findings offer novel insights into the role of UA in tumor therapy and suggest that UA may possess potential therapeutic applications for GC.

Reference range of naïve T and T memory lymphocyte subsets in peripheral blood of healthy adult.

Naïve T and T memory cell subsets are closely related to immune response and can provide important information for the diagnosis and treatment of immunological and hematological disorders. Lymphocyte compartment undergoes dramatic changes during adulthood; age-related reference values derived from healthy individuals are crucial. However, extensively detailed reference values of peripheral blood lymphocytes in the whole spectrum of adulthood detected by multi-color flow cytometry on a single platform are rare. Three hundred and nine healthy adult volunteers were recruited from Tianjin in China. The absolute counts and percentages of CD3+CD4+ T cells, CD3+CD8+ T cells, naïve T cells (Tn), T memory stem cells (Tscm), central memory T cells (Tcm), effector memory T cells (Tem), and terminal effector T cells (Tte) were detected by flow cytometry with single platform technologies. Reference range of absolute counts and percentage of T lymphocyte subsets were formulated by different age and gender. The results showed that Tn and Tscm cells, which had stem cell properties, decreased with aging; while, Tcm and Tem increased with aging, which increased from 18 to 64 years old but presented no significant change over the 65 years old. Gender had an influence on the fluctuation of lymphocyte subsets, the absolute count of CD3+CD8+, CD8+Tcm, CD8+Tem in males were higher than those in females. The reference values of percentages and absolute numbers of naïve T and T memory cell subsets can help doctors to understand the immune state of patients and evaluate conditions of prognosis then adjust the treatment for patients. (Chinese Clinic Trial Registry number: ChiCTR-IOR-17014139.).

Crosstalk between tumor-associated macrophages and tumor cells promotes chemoresistance via CXCL5/PI3K/AKT/mTOR pathway in gastric cancer.

BACKGROUND: 5-fluorouracil (5-FU)-based chemotherapy regimen has been widely used for the treatment of gastric cancer, but meanwhile the development of chemotherapeutic resistance remains a major clinical challenge. Tumor microenvironment (TME) frequently correlates with the development of chemoresistance in human cancer. As a major component of TME, the role of tumor-associated macrophages (TAMs) in the chemoresistance of gastric cancer has not been fully elucidated. METHODS: Immunohistochemistry (IHC) was applied to detect the density of TAMs in clinical samples of 103 patients with gastric cancer who had undergone 5-FU-based neoadjuvant chemotherapy. 5-FU-resistant gastric cell lines MKN45-R and HGC27-R were established, macrophages were then separately co-cultured with MKN45-R, HGC27-R cells and their parental cells. The effect of gastric cancer cells on the polarization of macrophages, the biological function of M2-polaried macrophages and the mechanism for promoting 5-FU-resistance were investigated. Then the correlation between the expression of CXC motif chemokine ligand 5 (CXCL5) and the infiltration of hemoglobin scavenger receptor (CD163) positive and mannose receptor (CD206) positive macrophages was analyzed, the prognostic value of CXCL5 expression in clinical samples was further explored. RESULTS: The high infiltration of macrophages marked by CD68 in gastric cancer samples was significantly associated with the resistance of gastric cancer to chemotherapy. Gastric cancer cells could modulate macrophages to M2-like polarization through indirect co-culture, and chemoresistant cells were more efficient in inducing macrophages polarization to M2 phenotype. Co-culturing M2-polarized macrophages in turn enhanced 5-FU-resistance of gastric cancer cells, and it was further verified that CXCL5 derived from M2-polarized macrophages promoted chemoresistance through activing the PI3K/AKT/mTOR pathway. Besides, high level of CXCL5 could recruit monocytes to form more M2-polarized macrophages. Clinically, high expression of CXCL5 in gastric cancer samples was associated with the high infiltration of CD163 positive macrophages and CD206 positive macrophages, and patients with high expression of CXCL5 presented lower overall survival (OS) rates than those with low expression of CXCL5. CONCLUSION: Interaction between TAMs and gastric cancer cells promoted chemoresistance in gastric cancer via CXCL5/PI3K/AKT/mTOR pathway. Thus, targeting TAMs and blocking the cell-cell crosstalk between TAMs and gastric cancer cells may represent prospective therapeutic strategies for patients with gastric cancer.

Divergent Trajectory of Soil Autotrophic and Heterotrophic Respiration upon Permafrost Thaw.

Warming-induced permafrost thaw may stimulate soil respiration (Rs) and thus cause a positive feedback to climate warming. However, due to the limited in situ observations, it remains unclear about how Rs and its autotrophic (Ra) and heterotrophic (Rh) components change upon permafrost thaw. Here we monitored variations in Rs and its components along a permafrost thaw sequence on the Tibetan Plateau, and explored the potential linkage of Rs components (i.e., Ra and Rh) with biotic (e.g., plant functional traits and soil microbial diversity) and abiotic factors (e.g., substrate quality). We found that Ra and Rh exhibited divergent responses to permafrost collapse: Ra increased with the time of thawing, while Rh exhibited a hump-shaped pattern along the thaw sequence. We also observed different drivers of thaw-induced changes in the ratios of Ra:Rs and Rh:Rs. Except for soil water status, plant community structure, diversity, and root properties explained the variation in Ra:Rs ratio, soil substrate quality and microbial diversity were key factors associated with the dynamics of Rh:Rs ratio. Overall, these findings demonstrate divergent patterns and drivers of Rs components as permafrost thaw prolongs, which call for considerations in Earth system models for better forecasting permafrost carbon-climate feedback.

Does postoperative chemotherapy improve overall survival of patients with ypT1-2N0 cancer?

BACKGROUND: Perioperative chemotherapy combined with curative gastrectomy has been increasingly represented the standard therapeutic strategy for resectable gastric cancer (GC). However, it is still unclear whether postoperative chemotherapy has a survival benefit for ypT1-2N0 gastric cancer patients who have undergone preoperative chemotherapy followed curative gastrectomy. METHODS: The data of patients who undergone neoadjuvant chemotherapy followed by gastrectomy and had pathological classification of ypT1-2N0 between March 2016 and December 2020 at Peking Union Medical College Hospital were retrospectively reviewed. Chi-square test was adopted to compare the difference between the patients with postoperative chemotherapy (pCHT) and without postoperative chemotherapy (no pCHT). Survival curves for overall survival (OS) were estimated using the Kaplan-Meier method, and the log-rank test was used to compare survival difference. Univariate and multivariate analyses for prognostic factors were based on the Cox regression. RESULTS: A total of 134 patients met the inclusion criteria and 56 (41.8%) of them have undergone postoperative chemotherapy. There were no statistically significant differences in demographic and clinicopathologic characteristics between pCHT group and no pCHT group (all p > 0.05). Postoperative chemotherapy was not associated with a significant improvement in overall survival (OS) (Hazard ratio [HR] 0.815, 95% confidence interval [CI] 0.403-1.650; p = 0.474). Subgroup analyses demonstrated survival was equivalent between pCHT and no CHT group in ypT1N0 patients (HR 0.832, CI 0.222-3.121; p = 0.786) and ypT2N0 patients (HR 1.284, CI 0.564-2.924; p = 0.551). Multivariable analysis identified that clinical T stage independently influenced prognosis (cT3 vs. cT2: HR 2.875, 95% CI 0.998-8.281, p = 0.050; cT4 vs. cT2: HR 7.382, 95% CI 2.569-21.211, p < 0.001). In clinical T3-4 patients, there was an overall survival benefit for postoperative chemotherapy (HR 0.270, 95% CI 0.114-0.634; p = 0.006). No survival benefit of postoperative chemotherapy was identified in clinical T2 patients (HR 0.689, 95% CI 0.200-2.372; p = 0.579). Furthermore, postoperative chemotherapy was proved to be an independently positive prognostic factor for clinical T3-4 patients (HR 0.132, 95% CI 0.051-0.345; p < 0.001). CONCLUSION: Postoperative chemotherapy might offer survival benefit to patients with ypT1-2N0 gastric cancer whose clinical T stage was T3-4 before preoperative chemotherapy.

Risk factors for inpatient malnutrition and length of stay assessed by 'NutritionDay' in China.

BACKGROUND AND OBJECTIVES: NutritionDay is a yearly global point-prevalence study of malnutrition or nutritional risk in hospitals. We aimed to provide a comprehensive nutritional survey of hospitalized patients and analyze the risk factors of malnutrition and prolonged hospitalization in Chinese inpatients. METHODS AND STUDY DESIGN: The international daylong cross-sectional survey was performed on November 07th, 2019. Ten hospitals were invited to participate in this NutritionDay survey. Nutritional risk was identified by nutritional risk screening 2002, and malnutrition was identified by the ESPEN criteria. We measured the incidence of malnutrition and nutritional risk. And we analysed risk factors for malnutrition and length of stay in Chinese hospitalized patients. RESULTS: 875 hospitalized patients from 6 departments were included in the analysis. The malnutrition rate was 11.6% and the incidence of nutritional risk was 17.8%. It was analyzed that tumor load, end-stage disease, motility, self-rated health, types of oral medicine, and food intake during the past week were independent risk factors for malnutrition or nutritional risk. 56.2% (118/210) of patients at nutritional risk or malnutrition received extra nutritional support, whereas 22.5% (88/391) well-nourished patients did. Moreover, nutrition status, ever stayed in ICU and self-rated health were associated with prolonged length of stay. CONCLUSIONS: In a word, the prevalence of malnutrition or nutritional risk was about 29.4%. Patients with malnutrition or nutritional risk had a higher transfer rate, lower rehabilitation rate and longer hospital stays. The attention to malnutrition patients needs to be further strengthened.

Phosphorus rather than nitrogen regulates ecosystem carbon dynamics after permafrost thaw.

Ecosystem carbon (C) dynamics after permafrost thaw depends on more than just climate change since soil nutrient status may also impact ecosystem C balance. It has been advocated that nitrogen (N) release upon permafrost thaw could promote plant growth and thus offset soil C loss. However, compared with the widely accepted C-N interactions, little is known about the potential role of soil phosphorus (P) availability. We combined 3-year field observations along a thaw sequence (constituted by four thaw stages, i.e., non-collapse and 5, 14, and 22 years since collapse) with an in-situ fertilization experiment (included N and P additions at the level of 10 g N m-2  year-1 and 10 g P m-2  year-1 ) to evaluate ecosystem C-nutrient interactions upon permafrost thaw. We found that changes in soil P availability rather than N availability played an important role in regulating gross primary productivity and net ecosystem productivity along the thaw sequence. The fertilization experiment confirmed that P addition had stronger effects on plant growth than N addition in this permafrost ecosystem. These two lines of evidence highlight the crucial role of soil P availability in altering the trajectory of permafrost C cycle under climate warming.

Above- and below-ground resource acquisition strategies determine plant species responses to nitrogen enrichment.

BACKGROUND AND AIMS: Knowledge of plant resource acquisition strategies is crucial for understanding the mechanisms mediating the responses of ecosystems to external nitrogen (N) input. However, few studies have considered the joint effects of above-ground (light) and below-ground (nutrient) resource acquisition strategies in regulating plant species responses to N enrichment. Here, we quantified the effects of light and non-N nutrient acquisition capacities on species relative abundance in the case of extra N input. METHODS: Based on an N-manipulation experiment in a Tibetan alpine steppe, we determined the responses of species relative abundances and light and nutrient acquisition capacities to N enrichment for two species with different resource acquisition strategies (the taller Stipa purpurea, which is colonized by arbuscular mycorrhizal fungi, and the shorter Carex stenophylloides, which has cluster roots). Structural equation models were developed to explore the relative effects of light and nutrient acquisition on species relative abundance along the N addition gradient. KEY RESULTS: We found that the relative abundance of taller S. purpurea increased with the improved light acquisition along the N addition gradient. In contrast, the shorter C. stenophylloides, with cluster roots, excelled in acquiring phosphorus (P) so as to elevate its leaf P concentration under N enrichment by producing large amounts of carboxylate exudates that mobilized moderately labile and recalcitrant soil P forms. The increased leaf P concentration of C. stenophylloides enhanced its light use efficiency and promoted its relative abundance even in the shade of taller competitors. CONCLUSIONS: Our findings highlight that the combined effects of above-ground (light) and below-ground (nutrient) resources rather than light alone (the prevailing perspective) determine the responses of grassland community structure to N enrichment.

Clinicopathological factors affecting the effect of neoadjuvant chemotherapy in patients with gastric cancer.

BACKGROUND: Neoadjuvant chemotherapy is an important part of the comprehensive treatment of advanced gastric cancer (GC). The effect of neoadjuvant chemotherapy plays a key role in the prognosis of GC patients. Pathological response can represent the effect of neoadjuvant chemotherapy. However, evidence focused on pathological response and associated clinicopathological factors in GC patients is quite little. In this retrospective study, the clinicopathological factors affecting the effect of neoadjuvant chemotherapy in GC patients were investigated, and suggestions were proposed to improve the effect of neoadjuvant chemotherapy on GC. METHODS: Retrospective analysis was performed on GC patients who received radical surgery after neoadjuvant chemotherapy from February 2016 to December 2019 at Peking Union Medical College Hospital. Relevant clinicopathological data was collected to analyze the factors influencing the effect of neoadjuvant chemotherapy. Chi-square test was used for univariate analysis. Logistic regression was used for multivariate analysis. Receiver operating characteristic curve (ROC) was used to determine the cutoff value of variables which significantly influenced the effect of neoadjuvant chemotherapy. RESULTS: A total of 203 GC patients were included in the study. Analyses showed that patients < 60 years old (OR = 1.840 [1.016-3.332], P = 0.044), histological type of poor differentiation or signet-ring cell carcinoma (OR = 2.606 [1.321-5.140], P = 0.006), and weight loss during neoadjuvant chemotherapy (OR = 2.110 [1.161-3.834], P = 0.014) were independent risk factors for neoadjuvant chemotherapy effect. In ROC analysis of weight change and neoadjuvant chemotherapy effect, area under the curve (AUC) was 0.593 (P = 0.024) and cutoff value of weight change was - 2.95%. Chi-square test showed that patients without weight loss during neoadjuvant chemotherapy had a higher rate of oral nutritional supplement (ONS) than patients with weight loss (P = 0.039). CONCLUSIONS: Patients <60 years old, histological type of poor differentiation or signet-ring cell carcinoma, and weight loss during neoadjuvant chemotherapy were independent risk factors for neoadjuvant chemotherapy effect in GC patients. Patients with weight loss > 2.95% during neoadjuvant may have a worse chemotherapy effect. Timely nutritional support such as ONS to maintain patients' body weight is crucial for improving the effect of neoadjuvant chemotherapy.

Low urinary iodine is a protective factor of central lymph node metastasis in papillary thyroid cancer: a cross-sectional study.

BACKGROUND: An abrupt increase of thyroid cancer has been witnessed paralleling the supplemented iodine intake in formerly iodine-deficient countries. And increased iodine intake has been linked to the rising incidence rate of papillary thyroid cancer (PTC). However, the correlation between iodine and clinicopathological features of PTC has not been well-characterized. This study aimed to investigate the associations between iodine intake and the clinicopathological features of PTC patients. METHODS: Three hundred and fifty-nine PTC patients who received surgical treatment in Peking Union Medical College Hospital from May 2015 to November 2020 were retrospectively reviewed. The associations between urinary iodine (UI), urinary iodine/creatinine ratio (UI/U-Cr), and the clinicopathological features of PTC were analyzed. Univariate and multivariate analysis were performed to investigate the relationship between UI level and central lymph node metastasis (CLNM). RESULTS: There were no significant differences in UI in different groups according to the variables studied, except that patients with CLNM had higher UI level than CLNM(-) patients. No associations were found between UI/U-Cr and clinicopathological features except variant subtypes (classic/follicular). After dividing patients into high-iodine group and low-iodine group, more patients were found to have CLNM in the high-iodine group (p = 0.02). In addition, younger age, larger tumor size, and classic variant were positively correlated with CLNM (p < 0.05). Univariate analysis showed that insufficient iodine intake (≤ 99 µg/L) was associated with decreased CLNM risk in PTC. And after defining insufficient iodine intake as ≤ 109 µg/L and above requirements as ≥ 190 µg/L, multivariate analysis showed that lower iodine was associated with CLNM in total population of PTC (OR 0.53, 95% CI 0.31-0.91) and in PTC < 1 cm (papillary thyroid microcarcinoma, PTMC) (OR 0.43, 95% CI 0.21-0.87). CONCLUSIONS: Low iodine was a protective factor for CLNM in papillary thyroid cancer, particularly in those < 1 cm. These results indicated that iodine may not only be an initiator of tumorigenesis, but also a promoter of the development of PTC.

Marked loss of adipose tissue during neoadjuvant therapy as a predictor for poor prognosis in patients with gastric cancer: A retrospective cohort study.

BACKGROUND: The influence of body composition changes during neoadjuvant treatment (NT) on long-term survival in patients with gastric cancer (GC) undergoing radical gastrectomy remains unclear. The present study aimed to explore the association between changes in body composition during NT and survival in patients with GC. METHODS: GC patients treated with NT and radical gastrectomy between 2015 and 2018 were included in this retrospective study. Skeletal muscle mass, visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were measured by computer tomography before and after NT. Body composition changes during NT were compared with Kaplan-Meier curves. Univariate and multivariate regression analyses were applied to determine the predictors of overall survival (OS) and disease-free survival (DFS). RESULTS: In total, 157 GC patients were studied. A marked loss of adipose tissue was associated with poor nutritional status. The median follow-up time for all patients was 25 months. Patients with marked VAT loss (≥ 35.7%) during NT had significantly shorter OS (p = 0.028) and DFS (p = 0.03). Similarly, poorer OS (p = 0.033) and DFS (p = 0.003) were observed in patients with marked SAT loss (≥ 30.1%) during NT. Changes in skeletal muscle mass and body weight during NT were not associated with survival. Marked VAT loss accompanied by marked SAT loss was an independent predictor of OS (hazards ratio = 2.447; p = 0.045) and DFS (hazards ratio = 2.674; p = 0.018). CONCLUSIONS: Patients with locally advanced GC have a worse survival when they experienced marked loss of adipose tissue during NT.

Typical and atypical pelvic MRI characteristics of Mayer-Rokitansky-Küster-Hauser syndrome: a comprehensive analysis of 201 patients.

OBJECTIVES: To comprehensively evaluate the pelvic magnetic resonance imaging (MRI) findings of Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome and summarize the typical and atypical characteristics. METHODS: A retrospective analysis of 201 consecutive MRKH patients was carried out. Pelvic MRI was reviewed by two experienced gynecological radiologists in consensus. Characteristics including the morphology, signal pattern and volumes of the uterine rudiments, location and volume of the ovaries, and the degree of vaginal dysgenesis were evaluated. Other noted abnormalities were also recorded. RESULTS: Morphologically, the majority (95%) of patients displayed bilateral uterine rudiments combined with a fibrous band. The minority of patients showed no (3.5%) or unilateral (1.5%) uterine rudiments. A total of 385 uterine rudiments were detected which showed four types of signal patterns: one-layer differentiation (325, 84.4%), two-layer differentiation (27, 7%), three-layer differentiation without subsequent alteration (23, 6.0%), and three-layer differentiation with hematometra and/or ipsilateral hematosalpinx (10, 2.6%). The median volumes of these four types of uterine rudiments were 2.6 ml (1.69-3.81 ml), 3.19 ml (2.67-4.51 ml), 6.05 ml (3.37-12.44 ml), and 31.97 ml (19.2-38.7 ml), respectively. The mean ovarian volume was 6.49 ± 3.91 ml. Abnormally located ovaries were detected in 63 (31.3%) patients. The distal vagina was discernable in 25.1% of patients. CONCLUSION: MRKH patients typically display bilateral uterine rudiments combined with a fibrous band and normally located ovaries. The uterine rudiments are generally small with only one-layer differentiation, a subset of which might be large and exhibited other atypical presentations, including two- or three-layer differentiation or even hematometra. Abnormally located ovaries are not rare. KEY POINTS: • Morphologically, MRKH patients typically displayed bilateral uterine rudiments combined with a fibrous band. • Typically, the uterine rudiments (84.4%) were small and displayed only one-layer differentiation. • About 15.6% of rudiments showed atypical characteristics including two- or three-layer differentiation, even complicated with hematometra or hematosalpinx.