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Habitat fragmentation is considered a major threat to biodiversity worldwide. Two endangered species, the blood pheasant (Ithaginis cruentus) and the blue eared pheasant (Crossoptilon auritum), co-exist in a fragmented forest in the Qilian Mountains. However, how their habitats react to the fragmenting landscape remains unclear. Therefore, we carried out a field survey in the core habitat of the two species in Qilian Mountains National Park and used the MaxEnt Model to predict their potential distribution and to assess the protection efficiency. Then, we utilized a modified within-patch fragmentation categorizing model to identify how their functional fragmentations differentiated. The results showed that the habitat utilization of the two pheasant species was significantly different, with a potential distribution area of 18,281 km2 for the blood pheasant and 43,223 km2 for the blue eared pheasant. The habitat of the blue eared pheasant is highly fragmented with 27.7% categorized as 'Interior' and 49.3% as 'Edge', while the habitat of the blood pheasant is more severe with 2.1% categorized as 'Interior' and 50.4% as 'Edge'. Analysis shows that large areas of habitat for the two pheasants remain unprotected by the Qilian Mountains National Park. The intense grazing and human infrastructure may have a large effect on the currently highly fragmented landscape. Future measurements are needed to alleviate this conflict. [ABSTRACT FROM AUTHOR]

Among seven species of the order Eulipotyphla (from southern Gansu and northern Sichuan Provinces, Central China) studied cytogenetically, karyotypes of one talpid species, Uropsilus aff. soricipes (2n = 36, NFa = 54), and three soricid species, Chodsigoa hypsibia (2n = 65, NFa = 66), Sorex cansulus (2n = 42, NFa = 64) and Sorex thibetanus (2n = 42, NFa = 60), are described cytogenetically for the first time. All four species are endemic to China with distribution ranges restricted to the Qinghai–Tibet Plateau and adjacent mountain ranges. The Ch. hypsibia karyotype consists of mostly acrocentric autosomes and one metacentric pair of autosomes; besides, a B chromosome was identified. No polymorphism was detected among karyotypes of other species, including shrews Sorex bedfordiae (2n = 26, NFa = 44), Anourosorex squamipes (2n = 48, NFa = 92) and Crocidura suaveolens (2n = 40, NFa = 44). The Chinese shrew mole U. aff. soricipes and three shrew species (S. bedfordiae, Ch. hypsibia and A. squamipes) represent autochthonous fauna of Central/Western China, whereas S. thibetanus, S. cansulus and C. suaveolens belong to phylogenetic groups occurring mostly to the north and west from China; therefore, they should be considered relatively recent colonisers. Thus, considering the relationships of the species within phylogenetic groups, our results on karyotypes are in good agreement with molecular genetic data. [ABSTRACT FROM AUTHOR]

Background and aims: Plant carbon (C), nitrogen (N), phosphorus (P) levels and their stoichiometry and N uptake strategies are important aspects influencing vegetation composition and C dynamics in boreal peatlands. However, C, N and P levels and N sources of different plants remain poorly understood, which prevents a better assessment of plant responses to projected increasing N availability in boreal ecosystems with climate warming and increasing N deposition. Methods: We investigated differences of leaf C, N and P concentrations and C and N isotopes (δ13C and δ15N) between graminoids and shrubs in 18 peatlands in northeastern China. Results: Ericoid mycorrhizal (ERM) and ectomycorrhizal (ECM) shrubs have higher C and P while lower C/N and C/P than nonmycorrhizal (NM) graminoids. Shrubs and graminoids have similar leaf N/P, mainly exhibiting N limitation or N and P co-limitation. ECM shrubs show higher N and lower δ15N than NM graminoids despite having similar rooting depths, indicating higher N availability and more uptake of 15 N-depleted organic N of ECM shrubs. However, deep-rooted ECM shrubs show slightly higher N than shallow-rooted ERM shrubs, and their δ15N differences are insignificant. Shallow-rooted ERM shrubs have higher N and lower δ15N than deep-rooted NM graminoids. Conclusions: Our results imply lower N and P use efficiencies of shrubs than graminoids, and the important role of mycorrhizal association in differentiating N availabilities and sources between shrubs and graminoids. These findings are useful for understanding peatland plant responses to environmental changes. [ABSTRACT FROM AUTHOR]

Background: The psychometric properties of the simplified Chinese version of the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) have not been assessed. Therefore, we aimed to assess its validity, reliability, and responsiveness.Patients and Methods: A Chinese version of the PRO-CTCAE and the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (QLQ-C30) were distributed to 1580 patients from four cancer hospitals in China. Validity assessments included construct validity, measured by Pearson's correlations and confirmatory factor analysis (CFA), and known-groups validity, measured by t-tests. The assessment of reliability included internal consistency, measured by Cronbach's ɑ, and test-retest reliability, measured by the intraclass correlation (ICC). Responsiveness was assessed by standardized response means (SRMs).Results: Data from 1555 patients who completed the instruments were analyzed. The correlations were high between PRO-CTCAE items and parallel QLQ-C30 symptom scales (r > 0.60, p < 0.001), except for fatigue (severity: r = 0.49). Moreover, CFA showed the PRO-CTCAE structure was a good fit with the data (Root Mean Square Error of Approximation = 0.046). Known-groups validity was also confirmed. Cronbach's ɑ of all item clusters were greater than 0.9 and the median test-retest reliability coefficients of the 38 items were 0.85 (range = 0.71-0.91). In addition, the SRMs of PRO-CTCAE items were greater than 0.8, indicating strong responsiveness.Conclusion: The simplified Chinese version of the PRO-CTCAE showed good reliability, validity, and responsiveness. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate the efficacy of induction chemotherapy (IC) in nasopharyngeal carcinoma (NPC) patients with moderate-risk treated with intensity-modulated radiotherapy (IMRT).Methods: We retrospectively assessed 506 patients with T1-2N1M0 or T3-4N0-1M0 NPC (according to the 2010 UICC/AJCC staging system) who received concurrent chemoradiotherapy (CCRT) with or without IC at a single center in China between 2005 and 2010. Survival outcomes were compared between the IC + CCRT and CCRT groups using the Kaplan-Meier method, Log-rank test and a Cox regression model.Results: Among the 506 patients, CCRT alone resulted in equivalent overall survival (86.8% vs 88.5%, p=0.661), progression-free survival (79.6% vs 79.6%, p=0.756), locoregional relapse-free survival (90.2% vs 87.0%, p=0.364) and distant metastasis-free survival (88.0% vs 89.8%, p=0.407) to IC plus CCRT. In multivariate analysis, IC did not lower the risk of death (HR 0.76, 95% CI 0.46-1.25, p=0.278), progression (HR 0.78, 95% CI 0.51-1.19, p=0.244), locoregional relapse (HR 1.06, 95% CI 0.81-1.42, p=0.651) or distant metastasis (HR 0.66, 95% CI 0.38-1.15, p=0.140) in the entire cohort; similar results were obtained in stratified analysis based on N category (N0 vs N1) and EBV DNA (< vs ≥4000 copies/mL).Conclusion: Addition of IC to CCRT does not improve survival outcomes in moderate-risk NPC; the use of IC should be carefully considered in these patients, though additional prospective trials are warranted to confirm the conclusions of this study. [ABSTRACT FROM AUTHOR]

Determining the factors promoting speciation is a major task in ecological and evolutionary research and can be aided by phylogeographic analysis. The Qinling–Daba Mountains (QDM) located in central China form an important geographic barrier between southern subtropical and northern temperate regions, and exhibit complex topography, climatic, and ecological diversity. Surprisingly, few phylogeographic analyses and studies of plant speciation in this region have been conducted. To address this issue, we investigated the genetic divergence and evolutionary histories of three closely related tree peony species (Paeonia qiui, P. jishanensis, and P. rockii) endemic to the QDM. Forty populations of the three tree peony species were genotyped using 22 nuclear simple sequence repeat markers (nSSRs) and three chloroplast DNA sequences to assess genetic structure and phylogenetic relationships, supplemented by morphological characterization and ecological niche modeling (ENM). Morphological and molecular genetic analyses showed the three species to be clearly differentiated from each other. In addition, coalescent analyses using DIYABC conducted on nSSR variation indicated that the species diverged from each other in the late Pleistocene, while ecological niche modeling (ENM) suggested they occupied a larger area during the Last Glacial Maximum (LGM) than at present. The combined genetic evidence from nuclear and chloroplast DNA and the results of ENM indicate that each species persisted through the late Pleistocene in multiple refugia in the Qinling, Daba, and Taihang Mountains with divergence favored by restricted gene flow caused by geographic isolation, ecological divergence, and limited pollen and seed dispersal. Our study contributes to a growing understanding of the origin and population structure of tree peonies and provides insights into the high level of plant endemism present in the Qinling–Daba Mountains of Central China. [ABSTRACT FROM AUTHOR]

Cigarette smoking is associated with the development of esophageal squamous cell carcinoma (ESCC); however, the influence of smoking on survival of patients with ESCC receiving radiotherapy, with or without chemotherapy, has remained elusive. The present study retrospectively analyzed 479 patients with ESCC from southern China who were categorized based on their smoking history (never, previous or current). To consider the cumulative effect of smoking, the number of pack years (PYs) was used as a representative variable. Associations between cigarette smoking and survival were evaluated using the Kaplan-Meier analysis and Cox proportional hazards model. Among the 497 patients, 308 (64.3%) had reported a history of cigarette smoking. The 5-year overall survival for patients void of a smoking history, former smokers and current smokers was 50.9, 27.0 and 34.3%, respectively. The adjusted hazard ratios (HRs) for previous and current smoking vs. no smoking history were 1.57 [95% confidence interval (CI), 1.06–2.32] and 3.01 (95% CI, 1.15–7.86), respectively. Heavy smokers with a high number of PYs had a HR for death of 1.75 (95% CI, 1.28–2.41) compared with light smokers. In the cohort of 407 patients treated with intensity-modulated radiotherapy/three-dimensional conformal radiotherapy, similarly significant results were obtained. In conclusion, cigarette smoking is an independent and poor prognostic factor for patients with ESCC treated with radiotherapy and/or chemotherapy. It is associated with an increased risk of death, and the risk increases with the increase in PYs. This result may help to manage tobacco use among patients with ESCC. The smoking status should be taken into consideration in prospective studies on ESCC. More frequent follow-ups are recommended for those patients with ESCC with a history of smoking. [ABSTRACT FROM AUTHOR]

Aims/Introduction The objective of the present study was to investigate the relationship between plasma interleukin-22 ( IL-22) levels and prediabetes or type 2 diabetes, and search the relevance between plasma concentrations of IL-22 and selected diabetes risk factors in Chinese people. Materials and Methods The Han Chinese origin men and women participants were recruited in our study during a conventional medical checkup. Fasting plasma IL-22 levels were detected by enzyme-linked immunosorbent assay, and their relevance with selected diabetes risk factors was explored. Multiple logistic regression analysis was carried out to assess the odds ratio of impaired fasting glucose ( IFG) and type 2 diabetes according to plasma IL-22 level. Results Compared with normal glucose participants (250 pg/mL [interquartile range 154-901]), the plasma IL-22 levels in IFG participants (185 pg/mL [interquartile range 145-414]) and type 2 diabetes participants (162 pg/mL [interquartile range 128-266]) were significantly lower ( P < 0.05, P < 0.001, respectively). Correlation analysis showed that plasma concentrations of IL-22 were negatively associated with some diabetes risk factors, including body mass index, glucose, systolic blood pressure, diastolic blood pressure and triglyceride. Furthermore, the plasma concentrations of IL-22 showed a highly significant association with IFG and type 2 diabetes. Conclusions In Chinese subjects, the plasma concentration of IL-22 is profoundly associated with susceptibility to IFG and type 2 diabetes, and decreased plasma IL-22 level is a potential trigger of IFG and type 2 diabetes. [ABSTRACT FROM AUTHOR]

The foliar stable N isotope ratio (δN) can provide integrated information on ecosystem N cycling. Here we present the δN of plant and soil in four remote typical tropical rainforests (one primary and three secondary) of southern China. We aimed to examine if (1) foliar δN in the study forests is negative, as observed in other tropical and subtropical sites in eastern Asia; (2) variation in δN among different species is smaller compared to that in many N-limited temperate and boreal ecosystems; and (3) the primary forest is more N rich than the younger secondary forests and therefore is more N enriched. Our results show that foliar δN ranged from −5.1 to 1.3 ‰ for 39 collected plant species with different growth strategies and mycorrhizal types, and that for 35 species it was negative. Soil NO had low δN (−11.4 to −3.2 ‰) and plant NO uptake could not explain the negative foliar δN values (NH was dominant in the soil inorganic-N fraction). We suggest that negative values might be caused by isotope fractionation during soil NH uptake and mycorrhizal N transfer, and by direct uptake of atmospheric NH/NH. The variation in foliar δN among species (by about 6 ‰) was smaller than in many N-limited ecosystems, which is typically about or over 10 ‰. The primary forest had a larger N capital in plants than the secondary forests. Foliar δN and the enrichment factor (foliar δN minus soil δN) were higher in the primary forest than in the secondary forests, albeit differences were small, while there was no consistent pattern in soil δN between primary and secondary forests. [ABSTRACT FROM AUTHOR]

Background: Tree peonies are great ornamental plants associated with a rich ethnobotanical history in Chinese culture and have recently been used as an evolutionary model. The Qinling Mountains represent a significant geographic barrier in Asia, dividing mainland China into northern (temperate) and southern (semi-tropical) regions; however, their flora has not been well analyzed. In this study, the genetic differentiation and genetic structure of Paeonia rockii and the role of the Qinling Mountains as a barrier that has driven intraspecific fragmentation were evaluated using 14 microsatellite markers. Methodology/Principal Findings: Twenty wild populations were sampled from the distributional range of P. rockii. Significant population differentiation was suggested (FST value of 0.302). Moderate genetic diversity at the population level (HS of 0.516) and high population diversity at the species level (HT of 0.749) were detected. Significant excess homozygosity (FIS of 0.076) and recent population bottlenecks were detected in three populations. Bayesian clusters, population genetic trees and principal coordinate analysis all classified the P. rockii populations into three genetic groups and one admixed Wenxian population. An isolation-by-distance model for P. rockii was suggested by Mantel tests (r = 0.6074, P<0.001) and supported by AMOVA (P<0.001), revealing a significant molecular variance among the groups (11.32%) and their populations (21.22%). These data support the five geographic boundaries surrounding the Qinling Mountains and adjacent areas that were detected with Monmonier's maximum-difference algorithm. Conclusions/Significance: Our data suggest that the current genetic structure of P. rockii has resulted from the fragmentation of a formerly continuously distributed large population following the restriction of gene flow between populations of this species by the Qinling Mountains. This study provides a fundamental genetic profile for the conservation and responsible exploitation of the extant germplasm of this species and for improving the genetic basis for breeding its cultivars. [ABSTRACT FROM AUTHOR]

According to the basic principles of contract law, the effectiveness of a lawful and valid contract should be maintained as far as possible. However, during the actual implementation process of a contract having been signed, it's inevitable that any party may breach the contract due to various reasons or there may be unpredictable circumstance. If the above-mentioned breach of contract and unpredictable circumstance has caused serious or fundamental impact on the purpose of the contract, it seems necessary to endow the parties with right for discharge of contract. Yet the issues concerning the theoretical basis for the right for discharge of contract and its legitimacy are the problems to be settled through research on theory of contract law. The author contends that the freedom of contract is the source for the effectiveness of the right for discharge of contract; and the legal right for discharge of contract is a remedy granted to the relevant parties for them to get away with the damaged contractual relationship, arising from the demand for equitability of contract; and in order to safeguard the security of transaction, the construct of the right for discharge of contract is based on principle of good faith. [ABSTRACT FROM AUTHOR]

Three forests with different historical land-use, forest age, and species assemblages in subtropical China were selected to evaluate current soil N status and investigate the responses of soil inorganic N dynamics to monthly ammonium nitrate additions. Results showed that the mature monsoon evergreen broadleaved forest that has been protected for more than 400 years exhibited an advanced soil N status than the pine (Pinus massoniana) and pine-broadleaf mixed forests, both originated from the 1930's clear-cut and pine plantation. Mature forests had greater extractable inorganic N pool, lower N retention capacity, higher inorganic N leaching, and higher soil C/N ratios. Mineral soil extractable NH_4^+-N and NO_3^--N concentrations were significantly increased by experimental N additions on several sampling dates, but repeated ANOVA showed that the effect was not significant over the whole year except NH_4^+-N in the mature forest. In contrast, inorganic N (both NH_4^+-N and NO_3^--N) in soil 20-cm below the surface was significantly elevated by the N additions. From 42% to 74% of N added was retained by the upper 20 cm soils in the pine and mixed forests, while 0%–70% was retained in the mature forest. Our results suggest that land-use history, forest age and species composition were likely to be some of the important factors that determine differing forest N retention responses to elevated N deposition in the study region. [ABSTRACT FROM AUTHOR]

Anti-PD-1 therapy and chemotherapy is a recommended first-line treatment for recurrent or metastatic nasopharyngeal carcinoma, but the role of PD-1 blockade remains unknown in patients with locoregionally advanced nasopharyngeal carcinoma. We assessed the addition of sintilimab, a PD-1 inhibitor, to standard chemoradiotherapy in this patient population. This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was conducted at nine hospitals in China. Adults aged 18–65 years with newly diagnosed high-risk non-metastatic stage III–IVa locoregionally advanced nasopharyngeal carcinoma (excluding T3–4N0 and T3N1) were eligible. Patients were randomly assigned (1:1) using blocks of four to receive gemcitabine and cisplatin induction chemotherapy followed by concurrent cisplatin radiotherapy (standard therapy group) or standard therapy with 200 mg sintilimab intravenously once every 3 weeks for 12 cycles (comprising three induction, three concurrent, and six adjuvant cycles to radiotherapy; sintilimab group). The primary endpoint was event-free survival from randomisation to disease recurrence (locoregional or distant) or death from any cause in the intention-to-treat population. Secondary endpoints included adverse events. This trial is registered with ClinicalTrials.gov (NCT03700476) and is now completed; follow-up is ongoing. Between Dec 21, 2018, and March 31, 2020, 425 patients were enrolled and randomly assigned to the sintilimab (n=210) or standard therapy groups (n=215). At median follow-up of 41·9 months (IQR 38·0–44·8; 389 alive at primary data cutoff [Feb 28, 2023] and 366 [94%] had at least 36 months of follow-up), event-free survival was higher in the sintilimab group compared with the standard therapy group (36-month rates 86% [95% CI 81–90] vs 76% [70–81]; stratified hazard ratio 0·59 [0·38–0·92]; p=0·019). Grade 3–4 adverse events occurred in 155 (74%) in the sintilimab group versus 140 (65%) in the standard therapy group, with the most common being stomatitis (68 [33%] vs 64 [30%]), leukopenia (54 [26%] vs 48 [22%]), and neutropenia (50 [24%] vs 46 [21%]). Two (1%) patients died in the sintilimab group (both considered to be immune-related) and one (<1%) in the standard therapy group. Grade 3–4 immune-related adverse events occurred in 20 (10%) patients in the sintilimab group. Addition of sintilimab to chemoradiotherapy improved event-free survival, albeit with higher but manageable adverse events. Longer follow-up is necessary to determine whether this regimen can be considered as the standard of care for patients with high-risk locoregionally advanced nasopharyngeal carcinoma. National Natural Science Foundation of China, Key-Area Research and Development Program of Guangdong Province, Natural Science Foundation of Guangdong Province, Overseas Expertise Introduction Project for Discipline Innovation, Guangzhou Municipal Health Commission, and Cancer Innovative Research Program of Sun Yat-sen University Cancer Center. For the Chinese translation of the abstract see Supplementary Materials section. [ABSTRACT FROM AUTHOR]

Biological nitrogen fixation plays an important role in nitrogen cycling by transferring atmospheric N2 to plant-available N in the soil. However, the diazotrophic activity and distribution in different types of soils remain to be further explored. In this study, 152 upland soils were sampled to examine the diazotrophic abundance, nitrogenase activity, diversity and community composition by quantitative polymerase chain reaction, acetylene reduction assay and the MiSeq sequencing of nifH genes, respectively. The results showed that diazotrophic abundance and nitrogenase activity varied among the three soil types. The diazotrophic community was mainly dominated by Bradyrhizobium , Azospirillum , Myxobacter , Desulfovibrio and Methylobacterium. The symbiotic diazotroph Bradyrhizobium was widely distributed among soils, while the distribution of free-living diazotrophs showed large variation and was greatly affected by multiple factors. Crop type and soil properties directly affected the diazotrophic ɑ-diversity, while soil properties, climatic factors and spatial distance together influenced the diazotrophic community. Network structures were completely different among all three types of soils, with most complex interactions observed in the Red soil. These findings suggest that diazotrophs have various activities and distributions in the three soil types, which played different roles in nitrogen input in agricultural soil in China, being driven by multiple environmental factors. [ABSTRACT FROM AUTHOR]

Acinetobacter baumannii is an important nosocomial pathogen in hospital-acquired infections, and carbapenem resistance has been increasingly observed worldwide. Oxacillinase production by blaOXA-23 is a predominant and prevalent carbapenem resistance mechanism of A. baumannii, especially in China. Rapid and specific detection of blaOXA-23 may offer valuable insight for administration of directed antimicrobial therapy. In this study, we aimed to develop a loop-mediated isothermal amplification (LAMP)-based method for identifying carbapenem-resistant A. baumannii (CRAB) harboring the blaOXA-23 gene. High-specificity primers for screening blaOXA-23 were designed and synthesized, and the LAMP reactions were performed. Clinical A. baumannii strains isolated from the Former 307th Hospital of People's Liberation Army were used to determine the sensitivity and specificity of this method compared with those of phenotypic antimicrobial susceptibility testing and the traditional PCR method. Multilocus sequence typing (MLST) was performed to investigate the epidemiology of the A. baumannii bacterial population. Compared with antimicrobial susceptibility testing, the sensitivity and specificity of LAMP in detecting blaOXA-23 were 88.4% and 97.7%, respectively. However, the LAMP method is much simpler and less time-consuming (within 60 minutes) than conventional PCR and phenotypic susceptibility testing. The 113 isolates could be clustered into 30 sequence types, and most strains (83/113) belonged to clonal complex (CC) 92, which is also the dominant CC in China. The LAMP-based method detected blaOXA-23 in a simpler manner and could provide rapid results for identifying CRAB. Consequently, blaOXA-23 may serve as a surrogate marker for the presence of CRAB in patients with serious infections in clinical practice. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To evaluate the 7th edition of the International Union against Cancer/American Joint Committee on Cancer (UICC/AJCC) staging system for nasopharyngeal carcinoma (NPC) in patients treated with intensity-modulated radiotherapy. Methods and materials: We performed a retrospective data review from 512 patients with biopsy-proven, nonmetastatic NPC in our cancer center (South China) between January 2003 and December 2006. Results: The local relapse-free survival rates (LRFS) and disease failure-free survival rates (DFS) in the 6th edition system T1 and T2a stages were not significantly different (P =0.629 and P =0.820), while the LRFS and DFS of T1 and T2 using the 7th edition system were significantly different (P =0.019 and P =0.009). The LRFS and DFS between T2 and T3 in the 7th edition systems were lack of significance (P =0.874 and P =0.589). The total difference in distant metastasis-free survival rate and DFS between N0 and N3 was slightly larger using the 7th edition system than the 6th edition. The nodal dimension of a cervical lymph node was not a significant prognostic factor. Conclusions: We observed a better segregation of survival curves by using the 7th edition system. It seems reasonable to downstage T3 as T2 and reject nodal greatest dimension from the N-staging system in the future revised edition. [Copyright &y& Elsevier]

Denitrification and anammox are the main pathways of N loss in wet habitats while their relative contribution to N 2 production and underlying microbial mechanisms across marine-terrestrial ecotone remain unclear. Here we investigated the rates of anammox and denitrification, and the distribution patterns of anammox bacteria and nosZ clade I and II denitrifiers across coastal tidal flat to inland paddy soils. Results showed that denitrification dominated the N 2 production over anammox in all samples, accounting for 87.1%–100% of total N 2 production. Coincident with the rate, the abundance of nosZ clade I and II genes were 1–2 orders of magnitude higher than those of hzsB gene. The community of anammox bacteria was mainly driven by salinity while nosZ clade I and II denitrifiers communities were mainly determined by both salinity and pH. Alphaproteobacteria dominated in the nosZ clade I community in all samples while Betaproteobacteria and Gammaproteobacteria were mainly present in low salinity wetland and paddy soils. The nosZ clade II community was composed of more phyla, in which Bacteoidetes and Chloroflexi were ubiquitous while Gemmatimonadetes was present only in low salinity wetland and paddy soils. These findings have direct implications for explicitly incorporating both nosZ clade I and II into future N loss estimation and N 2 O mitigation in marine-terrestrial ecotone. Unlabelled Image • Denitrification dominantly contributed to N 2 production over anammox. • The nosZ type I and type II gene numerically dominated over the hzsB gene. • nosZ I community was exclusively dominated by α-Proteobacteria in tidal flat. • Gemmatimonadetes -belonging nosZ II denitrifier was sensitive to high salinity. • Both salinity and pH were main factors shaping the nosZ clade I and II community. [ABSTRACT FROM AUTHOR]

• Salivary gland was the most common primary site in HNLELC. • Cervical lymph nodes metastases were common and spread orderly in HNLELC. • EBERs status might be a potential independent prognostic factor for OS in HNLELC. • Surgery and postoperative radiotherapy had better outcomes than surgery alone in HNLELC. We aimed to elucidate the clinical characteristics, prognostic factors and optimal treatment modalities of head and neck lymphoepithelioma-like carcinoma (HNLELC). Consecutive patients newly-diagnosed with non-metastatic HNLELC between December 2001 and March 2021 treated with curative intent were retrospectively reviewed. A total of 288 patients were included, of whom 87 (30.2%) underwent radical surgery alone, 43 (14.9%) underwent definitive radiotherapy with or without concurrent chemotherapy, and 158 (54.9%) underwent surgery followed by postoperative radiotherapy (SRT). Epstein-Barr virus-encoded small RNA (EBER) was positive in 94.8% (239/252) of patients. Cervical node infiltration was seen in 52.8% (152/288) of patients. No significant difference was found in nodal metastasis rate between T1–2 and T3–4 classifications (49.5% vs. 56.5%, p = 0.308). The 3-year overall survival (OS), disease-free survival, locoregional relapse-free survival, and distant metastasis-free survival rates were 89.4%, 78.7%, 89.2%, and 87.7%, respectively. Compared to SRT, surgery alone associated with significant reduced 3-year local (92.8% vs. 96.5%, p = 0.012) and regional relapse-free survival rates (89.3% vs. 96.8%, p = 0.002). Definitive radiotherapy and SRT demonstrated comparable results in all 3-year survival outcomes (all p＞0.05). Multivariate analysis found EBER status was an independent favorable prognostic factor for OS (HR = 0.356, 95% CI: 0.144–0.882, p = 0.026). HNLELC was observed to associate with EBV infection and cervical nodal infiltration. Definitive radiotherapy achieved similar survival outcomes compared to SRT, and may serve as a good substitute for patients unfit or unwilling to undergo surgery. [ABSTRACT FROM AUTHOR]

Aim of the study Previous results from our trial showed that adjuvant cisplatin and fluorouracil chemotherapy did not significantly improve survival after concurrent chemoradiotherapy (CCRT) in locoregionally advanced nasopharyngeal carcinoma (NPC) at 2 years. Here, we present the data of long-term survival and late toxicities to further assess the ultimate therapeutic index of adjuvant chemotherapy (AC). Methods Patients with stage III–IVB (except T3-4N0) NPC were randomly assigned to receive CCRT plus AC or CCRT only at seven institutions in China. Patients in both groups received cisplatin 40 mg/m 2 weekly up to 7 weeks concurrently with radiotherapy. The CCRT plus AC group subsequently received adjuvant cisplatin 80 mg/m 2 and fluorouracil 800 mg/m 2 /d for 120 h every 4 weeks for three cycles. The primary end-point was failure-free survival. Results Two hundred and fifty-one patients were randomised to the CCRT plus AC group and 257 to the CCRT only group. After a median follow-up of 68.4 months, estimated 5-year failure-free survival rate was 75% in the CCRT plus AC group and 71% in the CCRT only group (hazard ratio 0.88, 95% confidence interval 0.64–1.22; p = 0.45). 66 (27%) of 249 patients in the CCRT plus AC group and 53 (21%) of 254 patients in the CCRT only group developed one or more late grade 3–4 toxicities (p = 0.14). Conclusion Adjuvant cisplatin and fluorouracil chemotherapy still failed to demonstrate significant survival benefit after CCRT in locoregionally advanced NPC based on the long-term follow-up data, and addition of adjuvant cisplatin and fluorouracil did not significantly increase late toxicities. Registration number NCT00677118 . [ABSTRACT FROM AUTHOR]

Abstract: Before the design of brucine-containing transdermal formulations, the pharmacodynamics and pharmacokinetics of brucine following transdermal administration should be evaluated. In this study, the effect of addition of ethanol on solubility of bruicne was investigated and 20% ethanol was added into PBS to obtain 10mg/mL brucine solution. Then three transdermal doses (10, 20 and 40mg/kg) were administered to mice to evaluate pharmacological activity. It had been demonstrated that brucine possessed analgesic and anti-inflammatory activity in a dose-dependent manner. Cytotoxicities of brucine against various tumor cells including skin tumor cell were also compared in vitro. Brucine was found to possess antitumor activity in a concentration and time-dependent manner and gastrointestinal tumor cells seemed to be more sensitive to brucine. Then in vitro skin permeation behavior and in vivo pharmacokinetics following transdermal administration were further investigated. The cumulative amounts of brucine across mouse skin in vitro were found to be higher than 90%. The absolute bioavailability of brucine was determined to be 40.83%. And compared with intravenous administration, MRT and T1/2 values were increased about 8~12-fold by transdermal route. Moreover, fluctuations of drug levels were found to be significantly decreased in tissues, especially in brain. Finally, no dermal toxicity of brucine was observed. The results of this study indicated that transdermal administration might be beneficial for the sustained efficacy and reduced toxicity of brucine. [Copyright &y& Elsevier]

Abstract: Aerosol delivery is a route which is advantageous to the therapy of pulmonary diseases, such as lung cancer. The pharmacokinetics and tissue distribution after aerosol delivery of carboxylate form of hydroxycamptothecin (C-HCPT) were investigated. The concentrations of the three different types (lactone, carboxylate and the total of both forms) of HCPT were measured by HPLC analysis. The initial experiment showed no evident difference between lactone and carboxylate in the lungs during the aerosol treatment, compared with the HCPT content in plasma. The AUCinf value of lactone in the lungs was higher than that of carboxylate, which was 138,176.00minngg−1 and 128,460.00minngg−1, respectively. Meanwhile, AUCinf in the plasma during the entire treatment indicated that the lactone content was always at a lower level, and the carboxylate form tended to predominate, as shown by the lactone/carboxylate (L/C) equilibrium. The tissue distribution results showed that the lactone proportion in the liver increased up to the maximum value of 69.69% after aerosol administration, whereas the mean L/C equilibrium index for the liver was 2.07±1.06, and the Cmax and AUC0–∞ values of the total HCPT were highest in the tissues. Based on these results we speculated that the initial wholly carboxylate form of the HCPT atomized liquid did not influence the transformation to lactone form. Moreover, the deposition of the total HCPT and lactone was higher in the lungs and other tissues than in the plasma after the aerosol treatment. This study will be beneficial to the therapy of pulmonary carcinoma. [Copyright &y& Elsevier]

Abstract: Objective: To analyze the safety of combined leflunomide (LEF), methotrexate (MTX), and glucocorticoid (GC) therapy, we investigated the adverse effects of such combination therapy in patients with early active rheumatoid arthritis (RA). Methods: Two hundred sixty-six patients with RA who were receiving LEF and MTX therapy were randomly assigned to 3 groups, as follows: group 1 received no GC, group 2 received 7.5 mg prednisone, and group 3 received 15 mg prednisone. Adverse effects were analyzed using the χ2 test at week 4 or the Fisher exact test at week 12. Results: Patients in group 1 had a higher incidence of skin rash, oral ulcers, leukopenia, and liver damage than did those in groups 2 and 3 (all, P ≤ 0.05). However, the rates of osteoporosis, diabetes, hyperlipidemia, and hypertension in group 3 were statistically higher than in groups 1 and 2 (P ≤ 0.05). Conclusion: In the treatment of RA, the incidence of skin rash, liver dysfunction, and oral ulcers may be decreased with combination therapy using LEF, MTX, and 7.5 mg prednisone, and blood pressure, blood glucose concentration, and bone density are not increased. Most important, 7.5 mg prednisone was synergistic with LEF and MTX, and such combination therapy could be a useful option as initial treatment of early active RA. [Copyright &y& Elsevier]

Summary: Background: The effect of the addition of adjuvant chemotherapy to concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma is unclear. We aimed to assess the contribution of adjuvant chemotherapy to concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone. Methods: We did an open-label phase 3 multicentre randomised controlled trial at seven institutions in China. Randomisation was by a computer-generated random number code. Patients were stratified by treatment centre and randomly assigned in blocks of four. Treatment allocation was not masked. We randomly assigned patients with non-metastatic stage III or IV (except T3–4N0) nasopharyngeal carcinoma to receive concurrent chemoradiotherapy plus adjuvant chemotherapy or concurrent chemoradiotherapy alone. Patients in both groups received 40 mg/m2 cisplatin weekly up to 7 weeks, concurrently with radiotherapy. Radiotherapy was given as 2·0–2·27 Gy per fraction with five daily fractions per week for 6–7 weeks to a total dose of 66 Gy or greater to the primary tumour and 60–66 Gy to the involved neck area. The concurrent chemoradiotherapy plus adjuvant chemotherapy group subsequently received 80 mg/m2 adjuvant cisplatin and 800 mg/m2 per day fluorouracil for 120 h every 4 weeks for three cycles. Our primary endpoint was failure-free survival. We did efficacy analyses in our intention-to-treat population. Our trial is ongoing; in this report we present the 2 year survival results and acute toxic effects. This trial is registered with ClinicalTrials.gov, number NCT00677118. Findings: 251 patients were assigned to the concurrent chemoradiotherapy plus adjuvant chemotherapy group and 257 to the concurrent chemoradiotherapy alone group. After a median follow-up of 37·8 months (range 1·3–61·0), the estimated 2 year failure-free survival rate was 86% (95% CI 81–90) in the concurrent chemoradiotherapy plus adjuvant chemotherapy group and 84% (78–88) in concurrent chemoradiotherapy only group (hazard ratio 0·74, 95% CI 0·49–1·10; p=0·13). Stomatitis was the most commonly reported grade 3 or 4 adverse event during both radiotherapy (76 of 249 patients in the concurrent chemoradiotherapy plus adjuvant chemotherapy group and 82 of 254 in the concurrent chemoradiotherapy alone group) and adjuvant chemotherapy (43 [21%] of 205 patients treated with adjuvant chemotherapy). Interpretation: Adjuvant cisplatin and fluorouracil chemotherapy did not significantly improve failure-free survival after concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma. Longer follow-up is needed to fully assess survival and late toxic effects, but such regimens should not, at present, be used outside well-designed clinical trials. Funding: Sun Yat-sen University Clinical Research 5010 Programme (No 2007037), Science Foundation of Key Hospital Clinical Programme of Ministry of Health PR China (No 2010–178), and Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (2010). [ABSTRACT FROM AUTHOR]

Jiangxi Province is one of the first ecological civilization demonstration provinces in China. Understan-ding the impacts of meteorological conditions on ecosystem regulatory services is beneficial for conducting ecological protection and restoration work. Based on MODIS data, net primary productivity data, and monthly meteorological data from 2000 to 2022, we used models such as water balance equation and soil loss equation to measure the four regulatory service functions of ecosystem in Jiangxi Province, including carbon sequestration, oxygen release, water conservation and soil conservation. We used trend analysis and partial correlation analysis methods to analyze the spatio-temporal patterns and meteorological influencing factors of those four regulation service functions. The results showed that from 2000 to 2022, the annual average values of carbon sequestration and oxygen release in Jiangxi Province were 178.8 and 130.0 g·m -2 , respectively, with annual increases of 0.4 and 0.3 g·m -2 . The spatial distribution of both services was consistent, and the average annual carbon sequestration and oxygen release showed an upward trend in 77.3% regions of Jiangxi Province. The average water conservation and soil retention in Jiangxi Province were 591.8 mm and 723.8 t·hm -2 , respectively, with similar spatial distributions. The annual increases were 5.6 mm and 3.7 t·hm -2 . The soil conservation and water conservation functions of 73.3% and 69.3% regions in Jiangxi Province were steadily improved. Vegetation carbon sequestration and oxygen release was significantly correlated with temperature at monthly scale and seasonal scale. The partial correlation coefficient of those two factors was higher than other factors, which was an important meteorological factor affecting the carbon sequestration and oxygen release function of ecosystem. Precipitation, which was the most important meteorological factor, had a significant positive correlation with water conservation and soil conservation at monthly, seasonal and annual scales. Our results revealed the impacts of climate change on ecosystem regulatory service functions in Jiangxi Province from 2000 to 2022, which could provide scientific and technological support for effectively guaranteeing ecosystem protection and restoration in Jiangxi Province and improving the quality and efficiency of ecological civilization construction.

Background: Gas hydrate-bearing subseafloor sediments harbor a large number of microorganisms. Within these sediments, organic matter and upward-migrating methane are important carbon and energy sources fueling a light-independent biosphere. However, the type of metabolism that dominates the deep subseafloor of the gas hydrate zone is poorly constrained. Here we studied the microbial communities in gas hydrate-rich sediments up to 49 m below the seafloor recovered by drilling in the South China Sea. We focused on distinct geochemical conditions and performed metagenomic and metatranscriptomic analyses to characterize microbial communities and their role in carbon mineralization., Results: Comparative microbial community analysis revealed that samples above and in sulfate-methane interface (SMI) zones were clearly distinguished from those below the SMI. Chloroflexota were most abundant above the SMI, whereas Caldatribacteriota dominated below the SMI. Verrucomicrobiota, Bathyarchaeia, and Hadarchaeota were similarly present in both types of sediment. The genomic inventory and transcriptional activity suggest an important role in the fermentation of macromolecules. In contrast, sulfate reducers and methanogens that catalyze the consumption or production of commonly observed chemical compounds in sediments are rare. Methanotrophs and alkanotrophs that anaerobically grow on alkanes were also identified to be at low abundances. The ANME-1 group actively thrived in or slightly below the current SMI. Members from Heimdallarchaeia were found to encode the potential for anaerobic oxidation of short-chain hydrocarbons., Conclusions: These findings indicate that the fermentation of macromolecules is the predominant energy source for microorganisms in deep subseafloor sediments that are experiencing upward methane fluxes. Video Abstract., (© 2023. The Author(s).)

The development of ecological economy is one of the core elements of the ecological civilization system and an essential means to optimize the social-ecological systems. The key to developing ecological economy lies in preparing the development plan to realize concrete implementation. Given the objective and realistic demand for the development of ecological economy, it is critically needed to propose the approach of eco-economic planning and conduct empirical research. We sorted out the connotation of ecological economy, proposed the general idea of "object identification-resource evaluation-principal construction-target setting-task content-mechanism guarantee", and proposed three work modules, including "preliminary preparation, content design, review & approval", and finally built a technical system for the preparation of provincial-scale ecological economy planning. We outlined the 14th Five-Year Plan for Eco-Economic Development of Liaoning Province, and discussed critical issues such as the connotation definition and index system establishment for eco-economic development plan. This work provides ideas for the scientific and standardized preparation of ecological economy development plan at the provincial level in China.

To explore N 2 O and N 2 emissions from upland soils after nitrogen fertilizer application, a 60-day aerobic incubation experiment (25 ℃,80% water-filled pore space) using the 15 N tracing method was conducted to quantify the N transformation, N 2 O and N 2 emissions from maize soils from four sites (Harbin, Shenyang, Luancheng and Shouguang) and vegetable soils from two sites (Shen-yang and Shouguang), with urea being applied at 167 mg N·kg -1 to simulate the field application rate of 200 kg N·hm -2 . The results showed that for the four sites with maize soils, the cumulative emission of N 2 O was in the order of Shouguang (20 mg N·kg -1 ) > Luancheng (14 mg N·kg -1 ) > Shenyang (5 mg N·kg -1 ) > Harbin (0.5 mg N·kg -1 ) and the cumulative N 2 emission was in the order of Luancheng (176 mg N·kg -1 ) > Shenyang (106 mg N·kg -1 ) > Shouguang (75 mg N·kg -1 ) > Harbin (12 mg N·kg -1 ). For vegetable soils, the cumulative N 2 O emission of Shouguang (21 mg N·kg -1 ) was 10 times of that of Shenyang (2 mg N·kg -1 ), but without differences in cumulative N 2 emissions (28 and 24 mg N·kg -1 , respectively). The N 2 O/(N 2 O+N 2 ) of the six soils ranged from 5% to 40%. The N 2 O/(N 2 O+N 2 ) of the two soils from Shouguang (30%-40%) was significantly higher than other four soils (1%-10%). Soil bulk N pool contributes to 56% of total N 2 O emission and 61% of total N 2 emission, which was higher than the contribution of fertilizer. The cumulative N 2 O emission was positively correlated with soil background pH, which indicated that soil background pH might be an important factor regulating N 2 O and N 2 emission from upland soils. In the alkaline soil regions of North China Plain (such as Luancheng and Shouguang), mea-sures to reduce soil pH might have great impact on reducing N gaseous emission.

As a new strategy capable of uncovering the characteristics of traditional Chinese medicines, the quantitative analysis of multi-components by single-marker(QAMS) has been widely employed for the quality evaluation of Chinese medicinal materials, slices, and extracts. However, its application in the assessment of Chinese patent medicines is yet to be explored. By referring to the determination of three bufogenins in Bufonis Venenum by QAMS described in Chinese Pharmacopoeia(2020 Edition), this paper selected seven representative preparations containing Bufonis Venenum and explored whether the relative correction factors(RCFs) of cinobufagin(CB) to bufalin(BF) and resibufogenin(RB) could be directly used for the quality control of Bufonis Venenum-contained preparations. Based on the qualitative analyses under the same chromatographic conditions as used for toad venom, combing specificity test, five preparations such as Yatong Yili Pills, Houzheng Pills, Xiongdan Jiuxin Pills, Liushen Pills and Niuhuang Xiaoyan Pills, were expected to use validated RCFs for the direct determination of three components. Taking Houzheng Pills as an example, the methodological validation of bufalin, cinobufagin and resibufogenin was carried out, and the recoveries of bufalin, cinobufagin and resibufogenin were 90.64%-106.1%. The obvious difference was not observed between the contents of bufalin and resibufogenin in 24 batches of preparation samples by QAMS and external reference method. In the tested samples, the content of bufalin, cinobufagin and resibufogenin were 1.27-2.61, 2.44-5.66 and 0.988-3.16 mg·g~(-1) in 10 batches of Liushen Pills samples. The contents of bufalin, cinobufagin and resibufogenin were 0.760-1.32, 1.35-2.39 and 0.600-1.55 mg·g~(-1) in 10 batches of Houzheng Pills samples from three manufacturers. The obtained data contribute to improving the quality standard of Bufonis Venenum-contained preparations, and they also provide some ideas for the application of QAMS in the quality evaluation and control of Chinese patent medicines.

Background: The Quaternary had worldwide consequences in forming the contemporary diversity of many populations, species and communities, which is characterized by marked climatic oscillations between glacial and interglacial periods. The origin and evolution of biodiversity in mountainous areas are highly dependent on historical orogenesis and associated climatic changes. The Chinese grouse Tetrastes sewerzowi is a forest-dwelling species endemic to the mountains to the east of the Qinghai-Tibet Plateau, which has been listed as Near Threatened with a decreasing trend by the IUCN because of ongoing deforestation and fragmentation of coniferous forests. It is important to place current population status into a broader ecological and evolutionary context to understand their demographic history., Results: Analyses of the Chinese Grouse genome revealed fluctuations throughout the Pleistocene in effective population size. Populations decreased during early to middle Pleistocene but showed an expansion during late Pleistocene which was then followed by a sharp decline during the last glacial maximum (LGM). Ecological niche modeling indicated that a suitable habitat shift between high altitude regions to low altitude regions was due to a changing climate. This result parallels patterns of population size change in Chinese Grouse estimated from PSMC modelling, which suggested an expansion in population size from the last interglacial period (LIG) and then a peak and a bottleneck occurring at the last glacial maximum (LGM). Furthermore, the present-day distribution of Chinese Grouse is greatly reduced and fragmented. It will likely become even more fragmented in the future since coniferous forest cover is threatened in the region of their distribution and the availability of such habitat restricts their ecological niche., Conclusions: The Chinese Grouse have experienced substantial population size changes from the beginning to the LIG and reached a peak before the LGM. A sharp decrease and bottleneck occurred during the LGM, when the coniferous forests were subjected to extensive loss. The results inferred from the whole genome sequencing and species distribution models both support historical population fluctuations. The distribution of the Chinese Grouse is strongly dependent on the coniferous forest cover. To protect the fragmented coniferous forests is an essential action to protect the Chinese Grouse.

It has been identified that malnutrition can influence the immune system and time of engraftment, and it's also associated with increased incidence of complications, prolonged length of hospital stays, and transplant mortality and morbidity in patients undergoing hematopoietic stem cell transplantation (HSCT), so dynamic nutrition care is highly important. The aim of this study was to better understand the differences between clinical nutrition practices and international recommendations as well as possible barriers to the use of nutrition support in HSCT patients. An evidence-based nutrition support pathway was constructed through a systematic literature review to identify evidence and recommendations relating to the relevant issues. Then, a questionnaire consisting of 28 questions that focused on the 4 topics, namely, assessment and screening for malnutrition, nutrition support interventions, nutrition support in gastrointestinal graft-versus-host disease (GVHD) and neutropenic diet was developed by the study authors and used for data collection. Responses of 18 HSCT centers from 17 provinces were received. General assessment for malnutrition was performed at 72% (13/18) centers. Parenteral nutrition (PN) was given as the first option to HSCT patients in the majority of centers, despite the fact that current guidelines recommend enteral nutrition (EN) over PN. As many as 72% (13/18) of the centers considered a neutropenic diet in the management of HSCT patients, but only one center had a formal neutropenic diet protocol in place for transplant recipients. Criteria for initiating nutrition support in patients with gastrointestinal GVHD were heterogeneous among the centers, and PN was the most widely used technique. The survey results revealed significant heterogeneity with regard to nutrition support practices among the centers, as well as between the practices and the guidelines. Standard nutrition support guidelines or protocols for nutrition support practices were absent in most of the centers.

Infection with SARS-CoV-2, the cause of coronavirus infectious disease-19 (COVID-19), has caused a pandemic with >850,000 cases worldwide and increasing. Several studies report outcomes of COVID-19 in predominately well persons. There are also some data on COVID-19 in persons with predominately solid cancer but controversy whether these persons have the same outcomes. We conducted a cohort study at two centres in Wuhan, China, of 128 hospitalised subjects with haematological cancers, 13 (10%) of whom developed COVID-19. We also studied 226 health care providers, 16 of whom developed COVID-19 and 11 of whom were hospitalised. Co-variates were compared with the 115 subjects with haematological cancers without COVID-19 and with 11 hospitalised health care providers with COVID-19. There were no significant differences in baseline co-variates between subjects with haematological cancers developing or not developing COVID-19. Case rates for COVID-19 in hospitalised subjects with haematological cancers was 10% (95% Confidence Interval [CI], 6, 17%) compared with 7% (4, 12%; P = 0.322) in health care providers. However, the 13 subjects with haematological cancers had more severe COVID-19 and more deaths compared with hospitalised health care providers with COVID-19. Case fatality rates were 62% (32, 85%) and 0 (0, 32%; P = 0.002). Hospitalised persons with haematological cancers have a similar case rate of COVID-19 compared with normal health care providers but have more severe disease and a higher case fatality rate. Because we were unable to identify specific risk factors for COVID-19 in hospitalised persons with haematological cancers, we suggest increased surveillance and possible protective isolation.

Soil is a vital reservoir of antibiotic resistance genes (ARGs), but we still know little about their distribution in cropland soils and the main driving forces. Here we performed an investigation for ARGs patterns in 105 cropland soils (planted with maize, peanut or soybean) along a 2, 200 km transect in China using high-throughput quantitative PCR approaches. Totally, 204 ARGs were detected, with a higher diversity found in central China than that in northeast and south China. The most abundant (top 50%) and highly shared (present in >50% samples) ARGs regarded as core resistome were dominated by multidrug resistance genes such as oprJ, acrA-05 and acrA-04. Regressive analyses revealed that the relative abundance of total ARGs and core resistome both had significant relationships with mobile genetic elements (MGEs). Anthropogenic factors including the consumption of plastic films and soil properties including heavy metals showed good correlations with the diversity of ARGs. Structural equation modelling analysis further explained that anthropogenic factors were the main forces shaping the ARGs patterns. These findings highlight the importance of human activities in shaping soil antibiotic resistome in the croplands, providing potential management strategies to mitigate the dissemination of ARGs to humans via food chain., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Several abundant but yet uncultivated bacterial groups exist in extreme iron- and sulfur-rich environments, and the physiology, biodiversity, and ecological roles of these bacteria remain a mystery. Here we retrieved four metagenome-assembled genomes (MAGs) from an artificial acid mine drainage (AMD) system, and propose they belong to a new deltaproteobacterial order, Candidatus Acidulodesulfobacterales. The distribution pattern of Ca. Acidulodesulfobacterales in AMDs across Southeast China correlated strongly with ferrous iron. Reconstructed metabolic pathways and gene expression profiles showed that they were likely facultatively anaerobic autotrophs capable of nitrogen fixation. In addition to dissimilatory sulfate reduction, encoded by dsrAB, dsrD, dsrL, and dsrEFH genes, these microorganisms might also oxidize sulfide, depending on oxygen concentration and/or oxidation reduction potential. Several genes with homology to those involved in iron metabolism were also identified, suggesting their potential role in iron cycling. In addition, the expression of abundant resistance genes revealed the mechanisms of adaptation and response to the extreme environmental stresses endured by these organisms in the AMD environment. These findings shed light on the distribution, diversity, and potential ecological role of the new order Ca. Acidulodesulfobacterales in nature.

Paeonia ostii is a traditional ornamental and medicinal species that has attracted considerable interest for its high oil value. To facilitate the effective and rational cultivation and application of P. ostii in China, it is necessary to determine its potential spatial habitat distribution and environmental requirements. Using high-resolution environmental data for current and future climate scenarios, the potential suitable area and climatic requirements of P. ostii were modelled. Among the 11 environmental variables investigated, growing degree days, precipitation of the wettest month, mean temperature of the coldest quarter, global UV-B radiation, annual precipitation, and soil pH played major roles in determining the suitability of a habitat for the cultivation of P. ostii. Under the current environmental conditions in China, a total area of 20.31 × 10 5  km 2 is suitable for growing P. ostii, accounting for 21.16% of the country's total land area. Under the two future climate scenario/year combinations (i.e., representative concentration pathways [RCPs], RCP2.6 and RCP8.5 in 2050), this species would increase its suitable area at high latitudes while decrease at low latitudes. These results present valuable information and a theoretical reference point for identifying the suitable cultivation areas of P. ostii.

Objective: The aim of this study was to perform molecular characterization for and determine the antimicrobial susceptibility profiles of Clostridium difficile collected from hospitals during a 4-year period (2009-2013) in China., Methods: Strains of toxigenic C. difficile were isolated from patients with diarrhoea, and this was followed by typing using multilocus sequence typing (MLST) and testing for susceptibility to 10 antimicrobials by using the E-test. The mechanisms of resistance to moxifloxacin, erythromycin, clindamycin and tetracycline were investigated by PCR., Results: A total of 405 non-duplicate toxigenic C. difficile isolates were identified, while 31 sequence types (STs) were identified. A predominant type, ST-54, accounted for 20.2 % of the STs, followed by ST-35 (16.3 %) and ST-37 (13.6 %). We found that 6.2 % of the isolates were binary toxin genes-positive, and 83.7 % of these belonged to ST-5. All of the isolates demonstrated 100 % susceptibility to first-line Clostridium difficile infection (CDI) therapies (i.e. metronidazole and vancomycin), while the resistance rates varied for the other antibiotics tested. Two hundred and ninety three (72.3 %) isolates were susceptible to moxifloxacin. All 112 moxifloxacin-resistant isolates had mutations resulting in an amino acid substitution in gryA and/or gyrB. The ermB gene was detected in 86.7 % (241/278) of the erythromycin- and clindamycin-resistant isolates, while the tetM gene was present in 97.1 % (85/87) of the tetracycline-resistant isolates., Conclusion: MLST typing revealed a wide variety of STs causing CDI, while ST-54 was the most common ST. All of the isolates were susceptible to metronidazole and vancomycin, while the resistance rates varied for the other antibiotics tested. There were no changes in the trends for the STs and antibiotic susceptibility profiles over 4 years.

Objectives: We aimed to validate and compare the 7th and 8th edition of AJCC staging systems for non-metastatic nasopharyngeal carcinoma, and proposed staging systems from Hong Kong, Guangzhou, and Guangxi., Materials and Methods: We retrospectively included 899 patients treated between November 5, 2002 and May 27, 2010. Separation and discrimination of each staging system in overall survival were primarily compared., Results: Compared with the 7th AJCC, the 8th AJCC and all proposed staging systems well separated across T-classification. T-classification from Guangzhou seemed to perform best in discrimination (C-index 0.6454), followed by the 8th AJCC (0.6451), the 7th AJCC (0.6386), Hong Kong (0.6376) and Guangxi (0.5889). For N-classification, no staging systems improved the weakness of the 7th AJCC in separating N2 and N1, except that suggestion from Guangzhou showed higher potential (P=0.096). Besides, N-classification from Guangzhou had a C-index of 0.6444, larger than that of the 8th AJCC (0.6235), the 7th AJCC (0.6179), Hong Kong (0.6175) and Guangxi (0.6175). Accordingly, stage group of staging system from Guangzhou showed higher discrimination (C-index 0.6839), compared with the 8th AJCC (0.6791), the 7th AJCC (0.6766), Hong Kong (0.6765) and Guangxi (0.6688), despite that stage I and II remained inseparable (P=0.322)., Conclusions: The 8th AJCC staging system appeared to be better than the 7th AJCC. But the proposed staging system from Guangzhou was more likely to improve the separation and discrimination abilities., (Copyright © 2017. Published by Elsevier Ltd.)

Paeonia ostii, a member of tree peony, is an emerging oil crop with important medical and oil uses and widely cultivated in China. Dissolving the genetic diversity and domestication history of this species is important for further genetic improvements and deployments. We firstly selected 29 simple sequence repeats (SSRs) via transcriptome mining, segregation analyses and polymorphism characterizations; then, 901 individuals from the range-wide samples were genotyped using well-characterized SSR markers. We observed moderate genetic diversity among individuals, and Shaanxi Province was identified as the center of genetic diversity for our cultivated plants. Five well-separated gene pools were detected by STRUCTURE analyses, and the results suggested that multiple independent domestication origins occurred in Shaanxi Province and Tongling City (Anhui Province). Taken together, the genetic evidence and the historical records suggest multiple long-distance introductions after the plant was domesticated in Shandong, Henan and Hunan provinces. The present study provides the first genetic evaluation of the domestication history of P. ostii, and our results provide an important reference for further genetic improvements and deployments of this important crop.

Background: It has been proposed that the energy-sensing enzyme AMP-activated protein kinase (AMPK) is a key agent in the pathophysiology of type 2 diabetes mellitus (T2DM). The gene encoding protein kinase AMP-activated catalytic subunit alpha 2 (PRKAA2) is located at one of the Asian T2DM loci (1p32). Therefore, the aim of the present study was to test for the association of common variants in PRKAA2 with T2DM in the Han Chinese population., Methods: We genotyped 221 T2DM patients and 111 controls to assess possible associations of two tagging single nucleotide polymorphisms (tSNPs) in the PRKAA2 gene with T2DM., Results: The clinical characteristics of T2DM cases compared with controls differed significantly. No significant association was observed with the rs2143754 polymorphism whereas the rs2746342 polymorphism exhibited a highly significant association with T2DM. Fasting plasma glucose (FPG) of subjects carrying the G/G genotype of the rs2746342 polymorphism was higher than that of subjects carrying the T allele (P = 0.0049). These associations were magnified in the presence of the G/G genotype of the rs2143754 polymorphism., Conclusions: The rs2746342 polymorphism is significantly associated with susceptibility to T2DM and seems to interact with the rs2143754 polymorphism in the modulation of FPG in the Han Chinese population., (© 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Infection with Clostridium difficile has been shown to have particularly poor outcomes for pregnant women, including an increased risk of death. The purpose of this study was to investigate the prevalence, genotypic distribution, and characterization of C. difficile strains isolated from pregnant women without diarrhea in China. As part of this study, 3.7% (37 out of 1009) of samples acquired from pregnant females tested positive for C. difficile. Of these positive samples, 27.0% (10) were toxigenic isolates containing both toxin A and toxin B genes (A+B+), 13.5% (5) of the variant strains contained the toxin B gene (A-B+) only, while the rest were non-toxigenic isolates (59.5%, 22 isolates). Among the non-pregnant women without diarrhea tested, 1.4% (9 of 651) contained toxigenic isolates (all of which were A+B+). Sixteen different sequence types (STs) were isolated during the course of this study. ST-37 (ribotype 017) and ST-54 (ribotype 012) were the most frequent toxigenic types observed in pregnant women. All strains showed susceptibility to the antibiotics metronidazole and vancomycin. The resistance rates of toxigenic C. difficile strains isolated from pregnant females to clindamycin, erythromycin, moxifloxacin, levofloxacin, and rifampicin were 20%, 46.7%, 13.6%, 46.7% and 13.3%, respectively. There was no significant difference between resistance rates of toxigenic and non-toxigenic strains with respect to their susceptibility to these antibiotics. However, when compared with the same data from non-pregnant women, toxigenic strains from pregnant women showed lower resistance rates to clindamycin (P < 0.05)., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The purpose of this study was to investigate the risk factors for central and lateral neck lymph node metastases in papillary thyroid carcinoma (PTC) and multifocal papillary thyroid carcinoma (MPTC), particularly when associated with Hashimoto thyroiditis (HT).A retrospective analysis of 763 consecutive patients who underwent total thyroidectomy with bilateral central neck dissection in the First Affiliated Hospital, College of Medicine, Zhejiang University between October 2011 and October 2014 was conducted. All patients had formal histological diagnoses of HT. Multivariable logistic regression analysis was performed to identify risk factors of neck lymph node metastases.Our study identified 277 PTC patients with HT and showed comparatively low rates of central lymph node metastases (CLNM) compared with the PTC patients without HT (37.2% versus 54.7%, P < 0.001). There were no statistically significant differences in lateral lymph node metastases (LLNM) (P = 0.656). Neck lymph node metastases were histologically proven in 127 (45.8%) patients with PTC with HT, including 103 CLNM and 24 LLNM. There were no significant differences in LLNM between the MPTC-associated HT and classic MPTC cases; however, a significantly reduced risk of CLNM was observed in the MPTC-associated HT compared with the MPTC cases (35.7% versus 72.4%, respectively, P < 0.001). In the multivariate analysis, HT was identified as an independent alleviating factor for CLNM in all PTC patients (odds ratio, 0.369; 95% confidence interval (CI), 0.261 to 0.521; P < 0.001) and in MPTC patients (odds ratio, 0.227; 95% CI, 0.126-0.406; P < 0.001). A cut-off of thyroid peroxidase antibody >140 IU/mL was established as the most sensitive and specific level for the prediction of MPTC based on receiver operating characteristic curve analyses. Thyroid peroxidase antibody, age, tumor size, and multifocality exhibited the ability to predict CLNM in PTC with HT patients with an area under the curve of 81.1% based on a multivariate model.Hashimoto thyroiditis was associated with increased prevalences of multifocality and capsular invasion. In contrast, HT was associated with a reduced risk of CLNM in PTC and MPTC patients, which indicated a potential protective effect. We found that the prognostic prediction model was applicable for predicting multifocality and CLNM in PTC patients with HT.

The effect of pretreatment body mass index on survival of nasopharyngeal carcinoma remains contradictory.All patients (N = 1778) underwent intensity-modulated radiotherapy with or without chemotherapy. Body mass index was categorized as underweight (<18.5 kg/m2), normal weight (18.5-22.9 kg/m2), overweight (22.9-27.5 kg/m2), and obesity (≥27.5 kg/m2). Propensity score matching method was used to identify patients with balanced characteristics and treatment regimen. Disease-specific survival (DSS), overall survival (OS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival were estimated by Kaplan-Meier method and Cox regression.Following propensity matching, 115 (underweight vs normal), 399 (overweight vs normal), and 93 (obese vs normal) pairs of patients were selected, respectively. In univariate analysis, underweight patients had inferior DSS/OS (P = 0.042) and DMFS (P = 0.025) while both overweight and obese patients showed similar survival across all the endpoints (P ≥ 0.098) to those with normal weight. In multivariate analysis, underweight remained predictive of poor DSS/OS (P = 0.044) and DMFS (P = 0.040), whereas overweight (P ≥ 0.124) or obesity (P ≥ 0.179) was not associated with any type of survival.Underweight increased the risk of death and distant metastasis, whereas overweight or obese did not affect the survival of nasopharyngeal carcinoma. This provides support for early nutritional intervention during the long waiting time before treatment.

Background: Due to its high prevalence and associated sight-threatening pathologies, myopia has emerged as a major health issue in East Asia. The purpose was to test the impact on myopia development of a school-based intervention program aimed at increasing the time student spent outdoors., Methods: A total of 3051 students of two primary (grades 1-5, aged 6-11) and two junior high schools (grades 7-8, aged 12-14) in both urban and rural Northeast China were enrolled. The intervention group (n = 1735) unlike the control group (n = 1316) was allowed two additional 20-min recess programs outside the classroom. A detailed questionnaire was administered to parents and children. Uncorrected visual acuity (UCVA) was measured using an E Standard Logarithm Vision Acuity Chart (GB11533-2011) at baseline, 6-month and 1-year intervals. A random subsample (n = 391) participated in the clinic visits and underwent cycloplegia at the beginning and after 1 year., Results: The mean UCVA for the entire intervention group was significantly better than the entire control group after 1 year (P < 0.001). In the subgroup study, new onset of myopia and changes in refractive error towards myopia were direction during the study period was significantly lower in the intervention group than in the control group (3.70 % vs. 8.50 %, P = 0.048; -0.10 ± 0.65 D/year vs. -0.27 ± 0.52 D/year, P = 0.005). Changes in axial length and IOP were also significantly lower following the intervention group (0.16 ± 0.30 mm/year vs. 0.21 ± 0.21 mm/year, P = 0.034; -0.05 ± 2.78 mmHg/year vs. 0.67 ± 2.21 mmHg/year, P = 0.006)., Conclusions: Increasing outdoor activities prevented myopia onset and development, as well as axial growth and elevated IOP in children., Trial Registration: Current controlled trials NCT02271373.

Background: Esophageal squamous cell carcinoma (ESCC) is very common in China and is also one of the most common cancers worldwide. The purpose of this study was to examine the associations between genetic variants of various cancer-related genes and the risk of ESCC., Methods: In this study, we first examined the association between 18 potentially disruptive genetic variants of 17 genes, including alcohol dehydrogenase 4 (ADH4) and checkpoint kinase 2 (CHEK2), and ESCC risk in a Hangzhou population of 617 patients matched with 534 controls. Among the 18 single nucleotide polymorphisms (SNPs), two were validated in a Jinan population of 540 patients matched with 550 controls., Results: Sixteen SNPs in 15 genes, including CHEK2, did not have significantly different allele frequency distributions between ESCC patients and control subjects. A significantly increased risk of developing ESCC was revealed in subjects with the AA genotype of rs3805322 (ADH4) compared with those with the AG or GG genotype by unconditional univariate logistic regression analysis. Using a dominant model, the CC genotype of rs4822983 (CHEK2) had a marginally significant protective effect compared to the CT and TT genotypes. The association of ESCC risk with these two SNPs (rs3805322 and rs4822983) was further validated in a Jinan case-control set. Individuals with the ADH4 rs3805322 AA or AG genotype had ORs of 1.10 (95% CI = 0.81-1.49, P < 0.001) or 1.86 (95% CI = 1.33-2.59, P = 0.559), respectively, for developing ESCC compared with individuals with the GG genotype. CHEK2 rs4822983 CC carriers showed a marginally significantly decreased ESCC risk compared with those carrying the CT and TT genotypes in the validation set (95% CI = 0.61-1.01, P = 0.064). However, no evidence of interaction existed between the two SNPs and smoking or drinking in the Jinan case-control set., Conclusions: In conclusion, this current study provides substantial evidence that genetic polymorphisms of rs3805322 in the ADH4 gene may be associated with an increased risk of developing ESCC in two Chinese Han populations. Future studies to address the biological function of this polymorphism in the development of ESCC are warranted.

This retrospective analysis was set to understand the epidemiological status of the critically ill obstetric patients in Dongguan city, Guangdong, China. Understanding the risk factors for the death cases can provide scientific evidences for future preventive strategies to decrease the maternal mortality rate. This retrospective included the statistical data and clinical data on the cases of critically ill and dead obstetric patients admitted to Dongguan People's Hospital and Dongguan Maternal & Child Health Hospital from September 1st, 2009 to August 31st, 2013. Data included numbers of the critically ill maternal and obstetric women, common obstetric and maternal comorbidities and complications in the critically ill patients, the basic characteristics of maternal and obstetric deaths, records of regular prenatal examinations, the time intervals between onset of acute symptoms and ICU admission, blood purification, and the acute physiology and chronic health evaluation II (APACHE II) score. During the 5-year period, there were increasing trend of critically ill pregnant and obstetric patients, and the prevalence rate of critically ill obstetric patients was 8.99-9.28 %. The most common obstetric causes of admission were massive postpartum hemorrhage (63.54 %), followed by pregnancy-associated hypertension (15.85 %) and placenta previa (8.92 %). The most common non-obstetric causes of admission were acute heart failure (1.98 %). In the observed period, 20 critically ill obstetric patients died in these two hospitals (mortality rate 0.24 %, 20/8,129). The mean age of dead women was (30.3 ± 6.6) years old and mean gestational age was (30.1 ± 9.3) weeks. 75 % of the patient had more than two pregnancies. Over 90 % of the patients received education below junior high school level. 85 % of the patients were non-Dongguan natives and regular prenatal care rate was only 15 % on dead cases. The most common causes of death were pregnancy-associated hypertension, acute heart failure, and massive postpartum hemorrhage. The dead patients experienced longer interval between onset of acute symptoms and ICU admission (media = 62.5 h), higher APACHE II score (25.4 ± 5.4), and lower blood purification treatment rate (10 %). The incidence of critically ill pregnant and obstetric patients is high in Dongguan city. The group of dead obstetric patients, the majority of which were non-Dongguan natives, usually experienced above-average pregnancies, lower educational level, lower regular prenatal care rate, and longer interval between onset of acute symptoms and ICU admission. Critically ill obstetric patients may benefit from publicized informed relevant education, government-supported health care, preventative interventions of critical obstetric and medical complications, timely ICU admission after onset of acute symptoms, and the enhanced support of organ functions within the ICU.

Objective: To study the epidemiological patterns of hepatitis A, and immunity of entire population in Shijiazhuang prefecture, Hebei province, a former hyper-endemic area in north China., Methods: Cross-sectional, seroprevalence surveys with two-stage cluster sampling were conducted among population older than 2-year between 1992 and 2011. During the 2011 serological survey, blood samples from infants <18 months without hepatitis A immunization history were also collected to determine maternal anti-HAV antibody. Serum samples were tested for anti-HAV antibody by domestic reagent or Abbott reagent. Viral hepatitis incidence rates and gross domestic product data were derived from local governmental statistics., Results: Concomitant with the reduction of reported hepatitis A cases between 1992 and 1996 was a significant decline of HAV infections. The average prevalence decreased from 93.6% to 41.9%, and the average age at new infection was postponed from infancy to adolescence. This was attributed to improved socio-economic conditions. With intensive vaccination, a return of new seroconversion rate and seroprevalence was observed. A well fitted exponential regression equation (R(2)=0.96, p<0.0001) modeled that the maternal antibody would wane to <20 mIU/mL at 13 months., Conclusion: Benefiting from the booming economy, rapid improvement in sanitation, safe water supply, and implementation of hepatitis A vaccines, the epidemiological pattern of hepatitis A moved from high to intermediate endemicity in Shijiazhuang. Policy makers should be aware of the waning of immunity in entire population, and adapt immunization strategy timely, to ensure a lifelong protection against hepatitis A virus., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

An understanding of plant domestication history provides insights into general mechanisms of plant adaptation and diversification and can guide breeding programmes that aim to improve cultivated species. Cultivated tree peonies (genus Paeonia L.) are among the most popular ornamental plants in the world; yet, the history of their domestication is still unresolved. Here, we explored whether the domestication in China of historically cultivated peonies, that is, the common and flare cultivated tree peonies, was a single event or whether independent domestications occurred. We used 14 nuclear microsatellite markers and a comprehensive set of 553 tree peonies collected across China, including common tree peonies, flare tree peonies and the wild species or subspecies that are potential contributors to the cultivated tree peonies, that is, Paeonia rockii ssp. rockii, P. rockii ssp. atava, P. jishanensis and P. decomposita. Assignment methods, a principal component analysis and approximate Bayesian computations provided clear evidence for independent domestications of these common tree and flare tree peonies from two distinct and allopatric wild species, P. jishanensis and P. rockii ssp. atava, respectively. This study provides the first example of independent domestications of cultivated trees from distinct species and locations. This work also yields crucial insight into the history of domestication of one of the most popular woody ornamental plants. The cultivated peonies represent an interesting case of parallel and convergent evolution. The information obtained in this study will be valuable both for improving current tree peony breeding strategies and for understanding the mechanisms of domestication, diversification and adaptation in plants., (© 2013 John Wiley & Sons Ltd.)

We examined the variation in sexual ornamentation of male Chinese grouse (Tetrastes sewerzowi) in the Gansu Province, China, seeking to identify factors involved in whether ornament size and brightness are honest signals of male quality. Compared to unmated males, mated males had significantly larger and redder combs and, although they did not have significantly larger territories, they defended them more vigorously. Mated males had significantly higher blood carotenoid and testosterone levels, significantly better body condition, and significantly lower parasite loads than unmated males. Our findings are thus consistent with the hypothesis that comb size and color are honest signals of better male quality in the grouse, mediated through lower parasite loads and/or higher testosterone levels.

Background: Cigarette smoking is associated with the etiology of nasopharyngeal carcinoma; however, the influence of smoking on survival in patients with established nasopharyngeal carcinoma remains unknown., Methods: We retrospectively analyzed 1,849 patients with nasopharyngeal carcinoma who were categorized as never, former, and current smokers. Cumulative effect of smoking was defined in terms of pack-years. Associations between cigarette exposure and survival were estimated by Cox proportional hazards model., Results: The risks of death, progression, locoregional relapse, and distant metastasis were significantly higher for former and current smokers (all P ≤ 0.002) than never smokers. Heavy smokers with high pack-years had HRs for death of 3.31 [95% confidence interval (CI), 2.58-4.26; P < 0.001], for progression of 2.53 (95% CI, 2.03-3.16; P < 0.001), and for distant metastasis of 2.65 (95% CI, 1.89-3.70; P < 0.001). Specifically, in the cohort of 495 patients treated with intensity-modulated radiotherapy/three-dimensional conformal radiotherapy, we obtained similarly significant results. All of the survival outcomes remained significant in multivariate analyses., Conclusions: Pretreatment cigarette smoking is an independent, poor prognostic factor for patients with nasopharyngeal carcinoma, which is associated with increased risk of death, progression, locoregional relapse, and distant metastasis, with the risk increasing with pack-years., Impact: It is clear that cigarette smoking not only promotes carcinogenesis in the normal nasopharyngeal epithelium, but also affects the survival of patients with nasopharyngeal carcinoma., (©2013 AACR.)