Concurrent chemoradiotherapy followed by adjuvant cisplatin-gemcitabine versus cisplatin-fluorouracil chemotherapy for N2-3 nasopharyngeal carcinoma: a multicentre, open-label, randomised, controlled, phase 3 trial.

BACKGROUND: Patients with N2-3 nasopharyngeal carcinoma have a high risk of treatment being unsuccessful despite the current practice of using a concurrent adjuvant cisplatin-fluorouracil regimen. We aimed to compare the efficacy and safety of concurrent adjuvant cisplatin-gemcitabine with cisplatin-fluorouracil in N2-3 nasopharyngeal carcinoma. METHODS: We conducted an open-label, randomised, controlled, phase 3 trial at four cancer centres in China. Eligible patients were aged 18-65 years with untreated, non-keratinising, stage T1-4 N2-3 M0 nasopharyngeal carcinoma, an Eastern Cooperative Oncology Group performance status score of 0-1, and adequate bone marrow, liver, and renal function. Eligible patients were randomly assigned (1:1) to receive concurrent cisplatin (100 mg/m2 intravenously) on days 1, 22, and 43 of intensity-modulated radiotherapy followed by either gemcitabine (1 g/m2 intravenously on days 1 and 8) and cisplatin (80 mg/m2 intravenously for 4 h on day 1) once every 3 weeks or fluorouracil (4 g/m2 in continuous intravenous infusion for 96 h) and cisplatin (80 mg/m2 intravenously for 4 h on day 1) once every 4 weeks, for three cycles. Randomisation was done using a computer-generated random number code with a block size of six, stratified by treatment centre and nodal category. The primary endpoint was 3-year progression-free survival in the intention-to-treat population (ie, all patients randomly assigned to treatment). Safety was assessed in all participants who received at least one dose of chemoradiotherapy. This study was registered at ClinicalTrials.gov, NCT03321539, and patients are currently under follow-up. FINDINGS: From Oct 30, 2017, to July 9, 2020, 240 patients (median age 44 years [IQR 36-52]; 175 [73%] male and 65 [27%] female) were randomly assigned to the cisplatin-fluorouracil group (n=120) or cisplatin-gemcitabine group (n=120). As of data cutoff (Dec 25, 2022), median follow-up was 40 months (IQR 32-48). 3-year progression-free survival was 83·9% (95% CI 75·9-89·4; 19 disease progressions and 11 deaths) in the cisplatin-gemcitabine group and 71·5% (62·5-78·7; 34 disease progressions and seven deaths) in the cisplatin-fluorouracil group (stratified hazard ratio 0·54 [95% CI 0·32-0·93]; log rank p=0·023). The most common grade 3 or worse adverse events that occurred during treatment were leukopenia (61 [52%] of 117 in the cisplatin-gemcitabine group vs 34 [29%] of 116 in the cisplatin-fluorouracil group; p=0·00039), neutropenia (37 [32%] vs 19 [16%]; p=0·010), and mucositis (27 [23%] vs 32 [28%]; p=0·43). The most common grade 3 or worse late adverse event (occurring from 3 months after completion of radiotherapy) was auditory or hearing loss (six [5%] vs ten [9%]). One (1%) patient in the cisplatin-gemcitabine group died due to treatment-related complications (septic shock caused by neutropenic infection). No patients in the cisplatin-fluorouracil group had treatment-related deaths. INTERPRETATION: Our findings suggest that concurrent adjuvant cisplatin-gemcitabine could be used as an adjuvant therapy in the treatment of patients with N2-3 nasopharyngeal carcinoma, although long-term follow-up is required to confirm the optimal therapeutic ratio. FUNDING: National Key Research and Development Program of China, National Natural Science Foundation of China, Guangdong Major Project of Basic and Applied Basic Research, Sci-Tech Project Foundation of Guangzhou City, Sun Yat-sen University Clinical Research 5010 Program, Innovative Research Team of High-level Local Universities in Shanghai, Natural Science Foundation of Guangdong Province for Distinguished Young Scholar, Natural Science Foundation of Guangdong Province, Postdoctoral Innovative Talent Support Program, Pearl River S&T Nova Program of Guangzhou, Planned Science and Technology Project of Guangdong Province, Key Youth Teacher Cultivating Program of Sun Yat-sen University, the Rural Science and Technology Commissioner Program of Guangdong Province, and Fundamental Research Funds for the Central Universities.

Clinical characteristics and prognostic factors affecting survival after radical radiotherapy for early and late post-treatment metastatic nasopharyngeal carcinoma.

OBJECTIVE: We compared the clinical characteristics and survival outcomes after radical radiotherapy between nasopharyngeal carcinoma (NPC) with early and late metastases based on a relatively large cohort, which provides valuable data for the planning of clinical surveillance strategies. METHODS: This was a single-center retrospective analysis of 10,566 patients who received radical radiotherapy in China from January 2000 to December 2016. Overall survival was the primary endpoint. Kaplan-Meier survival analysis and log-rank tests were applied to investigate the association between early or late metastasis and the endpoints. The prognostic value of clinicopathological features was identified using univariate and multivariate Cox proportional hazards models. RESULTS: The cutoff value for time to metastasis was based on ROC analysis. A total of 559 (5.3%) patients developed distant metastases, 297 (53.1%) of which developed early metastatic disease, with the rest (46.9%) developing late metastatic disease. The K-M analysis showed that the patients with late metastatic foci had significantly better post-metastatic OS (P = 0.0056). Multivariate analysis indicated that age, liver metastasis, the number of metastatic foci and time to metastasis (P = 0.013) are independent prognostic factors for OS. After analyzing the impact of different treatment methods, we found that local treatment was an independent protective factor for LM, while local treatment was not associated with a survival benefit for EM disease. CONCLUSIONS: The time to metastasis after radical radiotherapy affected the prognosis of NPC patients and local treatment was an independent protective factor that could improve the survival of late metastatic NPC patients.

Apolipoprotein E*Ɛ2 carriers exhibit high aspirin-treated platelet reactivity and low cardiovascular risk during long-term aspirin treatment.

OBJECTIVE: Apolipoprotein E (APOE) loci, including rs429358 (Ɛ4) and rs7412 (Ɛ2), are involved in cardiovascular (CV) health. However, their effect on the CV-protective effect of aspirin remains unknown. METHODS: A total of 515 aspirin-treated individuals with existing CV diseases were recruited, and their APOE genotypes, platelet functions and other routine laboratory parameters were assessed when they enrolled. The first major CV events (myocardial infarction, stroke, revascularisation and CV death) and all CV events (major CV events plus unstable angina and transient ischaemic attack) during a mean 5.2-year follow-up period were recorded. RESULTS: After adjusting for age, gender, BMI, lifestyle, lipid profiles and other CV drugs and comorbidities, Ɛ2 carriers were found to exhibit ~80% lower risk of major CV and 60% lower risk of all CV (HR = 0.186, CI: 0.048-0.715, P = 0.014; HR = 0.435, CI: 0.234-0.812, P = 0.009, respectively) than Ɛ2 noncarriers. Furthermore, high incidence of high platelet reactivity assessed by arachidonic acid-induced light transmission aggregometry (23.4 vs. 13.7%, P = 0.038), triglyceride and haemoglobin and low low-density lipoprotein were observed. Ɛ4 carriers had slightly increased cholesterol and hypercholesterolemia incidence relative to Ɛ4 noncarriers. CONCLUSIONS: Our results demonstrated that APOE*Ɛ2 carriers can derive additional CV benefit from long-term aspirin treatment. Moreover, it was observed that APOE2 interacts with cyclooxygenase-1 (COX-1) and upregulates its activity. The CV-protective effect of aspirin in Ɛ2 carriers is likely attributed to APOE2 upregulating vascular COX-1-mediated CV protective pathway, together with aspirin partially inhibiting platelet COX-1-mediated platelet aggregation.

Subdivision of de-novo metastatic nasopharyngeal carcinoma based on tumor burden and pretreatment EBV DNA for therapeutic guidance of locoregional radiotherapy.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a malignancy predominantly associated with infection by the Epstein-Barr virus (EBV). Approximately 12,900 new cases of NPC occur each year, with more than 70% of cases occurring in the east and southeast Asia. NPC is different from ordinary head and neck squamous cell carcinoma due to its particular biological properties and it is highly sensitive to radiotherapy. With the development of RT technology, the 3-year local control rate and survival rates of non-metastatic NPC reached 80-90% in the intensity-modulated RT (IMRT) era. However, whether distant metastatic NPC (de novo mNPC, dmNPC) should receive locoregional RT (LRRT) needs to be clarified. RESULTS: Multivariate analysis identified three independent prognostic factors: Epstein-Barr virus (EBV) DNA, number of metastatic lesions, and number of metastatic organs. Through these factors, all patients were successfully divided into 3 subgroups: low-risk (single metastatic organ, EBV DNA ≤ 25,000 copies/ml, and ≤ 5 metastatic lesions), intermediate-risk (single metastatic organ, EBV DNA > 25,000 copies/ml, and ≤ 5 metastatic lesions), and high-risk (multiple metastatic organs or > 5 metastatic lesions or both). By comparing LRRT and non-LRRT groups, statistical differences were found in OS in the low-risk and intermediate-risk subgroups (p = 0.039 and p = 0.010, respectively) but no significant difference was found in OS in the high-risk subgroup (p = 0.076). Further multivariate analysis of different risk stratifications revealed that LRRT can improve OS of low- and intermediate-risk subgroups. CONCLUSIONS: The risk stratification of dmNPC may be used as a new prognostic factor to help clinicians organize individualized LRRT treatment to improve the survival outcomes of dmNPC patients.

[Detection of Carbon Dioxide Concentration in Soil Profile Based on Nondispersive Infrared Spectroscopy Technique].

In order to explore the variation of CO2 concentration and soil respiration in soil profile, the nondispersive infrared (NDIR) spectroscopy technique was applied to continually estimate the soil CO2 concentration in different soil layers (the humus horizon, A-, B-, C-horizon) in situ. The main instrument used in this experiment was silicon-based nondispersive infrared sensor, which could work in severe environment. We collected the Measurement value by NDIR spectroscopy technique throughout 2013. The values of soil carbon flux in different soil layers were calculated based on the model of gradient method and calibrated by measuring with an automated soil CO2 efflux system (LI-8100). The results showed that: a vertical gradient for the carbon dioxide concentration in soil profile was found, and the concentration was highest in the deepest soil horizon. Moreover, A linear correlation between the soil CO2 effluxes was calculated based on model and measurement, and the model prediction correlation coefficient was 0.9069, 0.7185, 0.8382, and 0.9030 in the H-, A-, B-, and C-horizon, respectively. The roots of mean square error (RMSE) were 0.2067, 0.1041, 0.0156, and 0.0096 in the H-, A-, B-, and C-horizon, respectively. These results suggest that the gradient method based on the NDIR spectroscopy technique can be successfully used to measure soil CO2 efflux in different soil layers, which reveal that diffusion and convection transport CO2 between the soil layers. It is a promising sensor for detecting CO2 concentration in soil profile, providing the basic data for calculating the global carbon in soil profile.

[Clinical observation of minimally invasive extraction of lower third molar by retaining the buccal bone plate].

PURPOSE: To explore the effect of extracting the completely impacted teeth by minimally invasive surgery with preserving the buccal bone plate. METHODS: Eighty-six cases were selected and randomly divided into 2 groups. In the experimental group, a fenestration was made with a ball drill to expose the buccal and lingual margin of crown, and the buccal bone plate was preserved. T-shaped crown cuttings were performed, minimally invasive extraction was conducted.In the control group, the distal and buccal bone plates were removed with a ball drill, the distal and buccal crowns were exposed, and T-shaped crown was cut. The other procedures were the same. The degree of swelling, restricted mouth opening and VAS pain score after operation were observed, the levels of C-reactive protein and anti-hemolytic streptoglobulin were detected by laboratory tests, and the periodontal probing depth(PD), bleeding index (BI), and clinical attachment loss(CAL) of the adjacent second molar were examined 1 month after surgery. SPSS 25.0 software package was used for data analysis. RESULTS: The swelling degree of the two groups was significantly relieved in the experimental group than in the control group (P＜0.05), and there was no significant difference in the degree of mouth opening limitation and pain (P＞0.05). The level of C-reactive protein in the control group was significantly higher than that in the observation group (P＜0.05). There was no significantly difference in the level of anti-hemolytic streptococcus between the 2 groups (P＞0.05). One month after operation, the PD and CAL in the control group were significantly higher than those in the experimental group(P＜0.05). There was no significant difference between the 2 groups in BI(P＞0.05). CONCLUSIONS: The patients who preserve the buccal bone plate by minimally invasive extraction of impacted mandibular teeth have less reaction and better wound healing.

[Ecological Environment Assessment and Driving Mechanism Analysis of Nagqu and Amdo Sections of Qinghai-Xizang Highway Based on Improved Remote Sensing Ecological Index].

The ecological environment along the Qinghai-Xizang highway is an important part of the construction of the ecological civilization in the Xizang region, and current research generally suffers from difficulties in data acquisition, low timeliness, and failure to consider the unique "alpine saline" environmental conditions in the study area due to the unique geographical environment of the Qinghai-Xizang plateau. Based on the GEE platform and the unique geographical environment of the study area, the remote sensing ecological index (RSEI) was improved, and a new saline remote sensing ecological index (SRSEI) applicable to the alpine saline region was constructed by using principal component analysis as an ecological environment quality evaluation index. The spatial distribution pattern and temporal variation trend of ecological environment quality along the Qinghai-Xizang Highway Nagqu-Amdo section were analyzed at multiple spatial and temporal scales using the ArcGIS 10.3 platform and geographic probes, and the driving mechanisms of eight control factors, including natural and human-made, on the spatial and temporal changes in SRSEI were investigated. The results showed that:① compared with RSEI, SRSEI was more sensitive to vegetation and had a stronger discriminatory ability in areas with sparse vegetation and severe salinization, which is suitable for ecological quality evaluation in alpine saline areas. ② The spatial scale of ecological environment quality in the study area had obvious geographical differentiation, and the areas with poor ecological quality were mainly concentrated in the northern Amdo County, whereas the areas with excellent and good quality grades were mainly distributed in the central-western and southeastern Nagqu areas. On the temporal scale, the ecological environment of the study area as a whole showed an improvement trend over 32 years, and the vegetation cover in the central-western and southeastern areas increased significantly, which had a strong improvement effect on the ecological environment. The improvement area was 1 425.98 km2, accounting for 99.82%. The mean value of SRSEI was 0.49, with an overall fluctuating upward trend and an average increase of 0.015 7 a-1. ③ The land use pattern was the most driving influence factor in the change of ecological environment quality in the study area, with an average q value of 0.157 6 over multiple years, and the influence of environmental factors was low. The multi-factor interaction results showed that the ecological environment in the study area was the result of multiple factors acting together, all factors had synergistic enhancement under the interaction, the influence of human factors was gradually increasing, and the interaction of the net primary productivity (NPP) of vegetation and land use pattern was the main interactive control factor of ecological environment quality in the study area. This study can provide a theoretical basis for ecological environmental protection and sustainable development along the Nagqu to Amdo section.

[Seasonal variation of water utilization sources and responses to precipitation in the dominant species of broad-leaved and needle-leaved mixed forests in Mount Lushan, China]. / 庐山针阔混交林优势种水分利用来源季节变化及对降水的响应.

Elucidating the seasonal patterns of water sources for dominant species in the sub-tropical humid mountainous forest, analyzing the eco-hydrological complementarity and competition mechanisms among coexisting species, investigating the responses of plant water utilization to precipitation, could provide a theoretical basis for vegetation restoration and management. Based on the stable hydrogen and oxygen isotope technique, we analyzed the δ2H and δ18O characteristics of precipitation, xylem water from Pinus massoniana and Quercus variabilis, and soil water from 0-100 cm depth in Mount Lushan, China. The MixSIAR model, Levins index, and PS index were used to calculate the relative contribution rate of each water source, the hydrological niche breadth, and niche overlap of P. massoniana and Q. variabilis. The results showed that, in the wet season (March to July), P. massoniana primarily utilized soil water from the 0-20 cm and 20-40 cm depths, while Q. variabilis primarily utilized that from the 20-40 cm and 40-60 cm depths. During the dry season (August to September), P. massoniana and Q. variabilis utilized 40-60 cm and 60-80 cm of soil water, respectively, resulting in an increase in the depth of water absorption. In the early growing season (March to April) and the late growing season (September), there was a high hydrological niche overlap between P. massoniana and Q. variabilis, resulting in intensitive water competition. In the middle of the growing season (May to August), the water source was adequately allocated, and the hydrolo-gical niche was segregated to meet the high transpiration demand. Q. variabilis primarily utilized soil water from a depth of 60-80 cm and 60-80 cm before a precipitation event, and from a depth of 0-20 cm and 20-40 cm after the event. In contrast, P. massoniana primarily utilized soil water from a depth of 0-20 cm and 20-40 cm both before and after a precipitation event. In conclusion, water utilization patterns of P. massoniana and Q. variabilis exhibited a seasonal trend, with shallow water uptake during the rainy season and deep water uptake during the dry season. These species are capable of efficiently allocating water resources during the peak growth season, and their root systems actively respond to change in soil moisture level. They have strong adaptability to extreme precipitation events and exhibit remarkable water conservation capabilities.

Effect of electric field on the partitioning behavior of solutes in entropic interaction chromatography.

In this study, a novel column design with a round cross-section was proposed to be suitable for a transverse electric field (EF). Additionally, two beads for entropic interaction chromatography (EIC) were prepared by grafting glycidyl methacrylate onto Toyopearl HW-65F (T65F) beads. Solute partitioning was then investigated to elucidate the role of graft polymerization with and without an EF. In a T65F column, solute partitioning was attributed to the distinct pore structure in the beads and was governed by pore flow. Under EF, partition coefficients (Kp) for solutes decreased with increasing EF strength. In the two EIC columns, a decrease of Kp was also observed without an EF while the fractionation windows were extended. It was more pronounced in the EIC column with a high grafting density (T65F-H). This was explained by the decrease in the effective pore size of solutes caused by the steric hindrance of polymer chains. Under an EF, the solutes showed different partitioning behaviours in the T65F-H column. With increasing EF strength, Kp for vitamin B12 and myoglobin was decreased. In contrast, Kp for large solutes increased as a result of concentration polarization on the bead surface. Both behaviors were related to the modulation of graft polymerization to residual charge on the matrix and the pore size of the solutes.

Camrelizumab combined with apatinib in patients with first-line platinum-resistant or PD-1 inhibitor resistant recurrent/metastatic nasopharyngeal carcinoma: a single-arm, phase 2 trial.

Immunotherapy combined with antiangiogenic targeted therapy has improved the treatment of certain solid tumors, but effective regimens remain elusive for refractory recurrent/metastatic nasopharyngeal carcinoma (RM-NPC). We conducted a phase 2 trial to evaluate the safety and activity of camrelizumab plus apatinib in platinum-resistant (cohort 1, NCT04547088) and PD-1 inhibitor resistant NPC (cohort 2, NCT04548271). Here we report on the primary outcome of objective response rate (ORR) and secondary endpoints of safety, duration of response, disease control rate, progression-free survival, and overall survival. The primary endpoint of ORR was met for cohort 1 (65%, 95% CI, 49.6-80.4, n = 40) and cohort 2 (34.3%; 95% CI, 17.0-51.8, n = 32). Grade ≥ 3 treatment-related adverse events (TRAE) were reported in 47 (65.3%) of 72 patients. Results of our predefined exploratory investigation of predictive biomarkers show: B cell markers are the most differentially expressed genes in the tumors of responders versus non-responders in cohort 1 and that tertiary lymphoid structure is associated with higher ORR; Angiogenesis gene expression signatures are strongly associated with ORR in cohort 2. Camrelizumab plus apatinib combination effectiveness is associated with high expression of PD-L1, VEGF Receptor 2 and B-cell-related genes signatures. Camrelizumab plus apatinib shows promising efficacy with a measurable safety profile in RM-NPC patients.

Reduced-dose radiotherapy for Epstein-Barr virus DNA selected staged III nasopharyngeal carcinoma: A single-arm, phase 2 trial.

BACKGROUND: Radiotherapy-related toxicities of nasopharyngeal carcinoma (NPC) caused by a standard dose of 70 Gy remain a critical issue. Therefore, we assessed whether a radiotherapy dose of 60 Gy was non-inferior to the standard dose in patients with low-risk stage III NPC with a favourable response to induction chemotherapy (IC). PATIENTS AND METHODS: We did a single-arm, single-centre, phase II clinical trial in China. Patients with low-risk (Epstein-Barr virus [EBV] DNA level <4000 copies/ml) stage III NPC were treated with two cycles IC. Patients with complete/partial response and undetectable EBV DNA level were assigned 60 Gy intensity-modulated radiotherapy concurrently with three cycles of cisplatin. The primary end-point was 2-year progression-free survival (PFS). This trial is registered with ClinicalTrials.gov, number NCT03668730. RESULTS: One patient quit because of withdrawal of informed consent after IC. In total, 215 patients completed two cycles of IC, after which 116 (54.0%) and 99 (46.0%) patients were assigned 60 and 70 Gy radiotherapy, respectively. For 215 patients, the 2-year PFS was 90.7% (95% CI, 86.8%-94.6%) with a median follow-up of 43.9 months (interquartile range [IQR], 39.8-46.2). For patients treated with 60 Gy radiotherapy, the 2-year PFS rate was 94.8% (95%CI 90.7%-98.9%) with a median follow-up of 43.9 months (IQR 40.2-46.2). The most common late toxicity was grade 1-2 dry mouth (incidence rate: 54.3%). No grade 3+ long-term adverse event was observed, and most quality-of-life items, domains, and symptom scores returned to baseline by 6 months. CONCLUSION: Reduced-dose radiation (60 Gy) is associated with favourable survival outcomes and limited treatment-related toxicities in patients with low-risk stage III NPC sensitive to IC.

Identifying distinct risks of treatment failure in nasopharyngeal carcinoma: Study based on the dynamic changes in peripheral blood lymphocytes, monocytes, N classification, and plasma Epstein-Barr virus DNA.

BACKGROUND: To evaluate the prognostic value of the dynamic change in absolute lymphocyte counts (ALCs) and absolute monocyte counts (AMCs) and identify patients with N stage and plasma Epstein-Barr virus (EBV) DNA levels in nasopharyngeal carcinoma (NPC) who are at risk of treatment failure. METHODS: A total of 1124 eligible patients with Stage II-IVb NPC treated with concurrent chemoradiotherapy (CCRT) were enrolled. Percentage changes in the ALC (ΔALC%) and AMC (ΔAMC%) were calculated. RESULTS: Patients with high ΔALC% were correlated with poorer 5-year overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS) rates than those with low ΔALC%. Likewise, high ΔAMC% was significantly associated with worse outcome than low ΔAMC% (OS, p = 0.001; PFS, p = 0.001; DMFS, p = 0.034). Multivariate analyses revealed that ΔALC% (p = 0.046), ΔAMC% (p = 0.019), and EBV DNA level (p < 0.001) were independent prognostic factors for OS. With respect to PFS, ΔALC% (p = 0.036), ΔAMC% (p = 0.011), N classification (p = 0.016), and EBV DNA level (p < 0.001) were also independent prognosticators. Based on the aforementioned independent risk factors (ΔALC% ≥ 83.33%, ΔAMC% ≥ 40.00%, Stage N2-3, EBV DNA ≥ 4000 copies/ml), patients were divided into three different risk groups (low-risk group [with <1 risk factor], intermediate risk group [with 1-3 risk factors], and high-risk group [with 4 risk factors]) that correlated with disparate risks of death (p < 0.001), disease progression (p < 0.001), and distant metastasis (p < 0.001). CONCLUSIONS: High ΔALC% and ΔAMC% were correlated with poor prognosis in patients with NPC. Risk stratification based on ΔALC%, ΔAMC%, N classification, and plasma EBV DNA levels could provide potential utility for risk-adapted therapeutic strategies for NPC.

Deintensified Chemoradiotherapy for Pretreatment Epstein-Barr Virus DNA-Selected Low-Risk Locoregionally Advanced Nasopharyngeal Carcinoma: A Phase II Randomized Noninferiority Trial.

PURPOSE: Cumulative doses of 200 mg/m2 for concurrent cisplatin (DDP) were indicated by retrospective studies as sufficient in conferring survival benefit for locoregionally advanced nasopharyngeal carcinoma (LA-NPC). We performed an open-label, phase II, randomized, controlled trial to test the noninferiority of a two-cycle 100 mg/m2 concurrent DDP regimen over three-cycle in patients with low-risk LA-NPC with pretreatment Epstein-Barr virus DNA levels < 4,000 copies/mL. PATIENTS AND METHODS: Eligible patients were randomly assigned 1:1 to receive two cycles or three cycles concurrent DDP-based chemoradiotherapy. The primary end point was 3-year progression-free survival (PFS). The secondary end points included overall survival, distant metastasis-free survival, locoregional relapse-free survival, etc. RESULTS: Between September 2016 and October 2018, 332 patients were enrolled, with 166 in each arm. After a median follow-up of 37.7 months, the estimated 3-year PFS rates were 88.0% in the two-cycle group and 90.4% in the three-cycle group, with a difference of 2.4% (95% CI, -4.3 to 9.1, Pnoninferiority = .014). No differences were observed between groups in terms of PFS, overall survival, and the cumulative incidences of locoregional relapse and distant metastasis. Patients in the three-cycle group developed significantly more grade 3-4 mucositis (41 [24.8%] v 25 [15.1%]), hyponatremia (26 [15.8%] v 14 [8.4%]), and dermatitis (9 [5.5%] v 2 [1.2%]). The overall all-grade and grade 3-4 toxicity burdens were heavier in three-cycle group (T-scores, 12.33 v 10.57, P < .001 for all grades; 1.76 v 1.44, P = .05 for grade 3-4). Patients in the three-cycle group also showed more all-grade hearing impairment, dry mouth and skin fibrosis, and impaired long-term quality of life. CONCLUSION: Intensity-modulated radiotherapy plus two cycles of concurrent 100 mg/m2 DDP could be an alternative treatment option for patients with low-risk LA-NPC.

[Quantitative separation of evapotranspiration components of Platycladus orientalis ecosystem based on multiple isotope models]. / åŸºäºŽå¤šç§åŒä½ç´ æ¨¡åž‹çš„ä¾§æŸæž—ç”Ÿæ€ç³»ç»Ÿè’¸æ•£ç»„åˆ†å®šé‡æ‹†åˆ†.

To fully understand the changes in the evapotranspiration components in forest ecosystem and their contribution to evapotranspiration at daily scale, we used the hypothesis theory of isotopic steady state and non-steady state combined with the water isotope analyzer system to quantitatively split and compare the evapotranspiration components of Platycladus orientalis ecosystem during the growing season. Results showed that the 18O of water from different sources during the four mea-surement days (August 5, 8, 10, 11, 2016) all showed surface soil water and oxygen isotope composition (δS) > branch water and oxygen isotope composition (δX) > atmospheric water vapor oxygen isotopes composition (δV), with obvious differences due to the isotope fractionation. Oxygen isotopes composition of soil evaporated water vapor (δE) was between -26.89‰ï½ž-59.68‰ at the daily scale, showing a pattern of first rising and then decreasing. The oxygen isotopic composition of evapotranspiration water vapor in forest ecosystem (δET) was between -15.99‰ï½ž-10.04‰. The oxygen isotopic composition of transpired water vapor under steady state(δT-ISS) was between -12.10‰ï½ž-9.51‰. The oxygen isotopic composition of transpired water vapor under non-steady state (δT-NSS) was between -13.02‰ï½ž-7.23‰. δET and δT-NSS had the same changing trend throughout the day at the daily scale, while the trend of δET, δT-ISS and δT-NSS was approximately the same during 11:00-17:00. In general, the contribution rate of plant transpiration to total evapotranspiration showed that FT-ISS was between 79.1%-98.7%, and FT-NSS was between 88.7%-93.7%. Our results suggested that water consumption through soil evaporation was far less than that of vegetation transpiration in the study area, and that vegetation transpiration dominated forest evapotranspiration.

[Erosion process of loess slope and influencing factors in the loess hilly-gully region, China]. / é»„åœŸä¸˜é™µæ²Ÿå£‘åŒºé»„åœŸå¡é¢ä¾µèš€è¿‡ç¨‹åŠå ¶å½±å“å› ç´ .

Rainfall intensity, slope length, and slope gradient are the important factors affecting runoff and sediment yield. In order to quantitatively analyze the effects of rainfall intensity, slope length, and slope gradient on the erosion process of Ansai loess slope in loess hilly and gully region, we analyzed the variation of runoff and sediment yield on Ansai loess with two slope lengths (5, 10 m), three slopes (5°, 10°, 15°) and two rainfall intensities (60, 90 mm·h-1) in an indoor simulated rainfall experiment. The results showed that the initial runoff generation time decreased with the increases of slope length, though the overall change was not significant. The initial runoff generation time decreased with the increases of rainfall intensity. Compared with the intensity of 60 mm·h-1, the initial runoff generation time decreased by 5.7-18 min under the intensity of 90 mm·h-1. Among them, the runoff initiation time on the slope of 10° was the fastest. With the duration of rainfall, runoff yield rate increased rapidly at first, and then gradually fluctuated around a certain value. The sediment yield rate increased rapidly in a short period of time at the initial stage of runoff generation, and then decreased after reaching the maximum, and being gradua-lly stable. The rates of runoff and sediment yield increased with the increases of slope length and rainfall intensity, but the law of change with slope was not obvious. With the increases of rainfall intensity, slope length and gradient, the total sediment yield increased accordingly. Under the rainfall intensity of 90 mm·h-1, the slope surface with the length of 10 m and slope of 15° generated rill, leading to the highest total erosion amount (11885.66 g). Under the rainfall intensity of 60 mm·h-1, the erosion amount per unit area decreased with the increases of slope length, and there was a critical erosion slope length in 5-10 m slope section. Slope length, slope and rainfall intensity all played a promoting role in runoff process. Rainfall intensity, slope length, and their interaction contributed more to runoff yield rate and total erosion amount. Rainfall intensity contributed the most to runoff yield rate, with a contribution rate of 49.8%. The contribution rate of slope length to the total erosion was the largest, which reached 37.8%.

[Long-term water use characteristics and patterns of typical tree species in seasonal drought regions]. / å­£èŠ‚æ€§å¹²æ—±åœ°åŒºå ¸åž‹æ ‘ç§é•¿æœŸæ°´åˆ†åˆ©ç”¨ç‰¹å¾ä¸Žæ¨¡å¼.

In the areas with seasonal drought, water is the key factor affecting plant growth and development. Based on long-term continuous observation data, it is of great significance to explore plant water use patterns for vegetation construction in areas with seasonal drought. Taking Platycladus orientalis in Beijing mountainous area as the research object, stable hydrogen and oxygen isotope technique was applied to measure the isotopic composition of water from the soil, plant branches, and precipitation from 2012 to 2017. The relative contribution of soil water from different soil layers to P. orientalis was quantified by the MixSIAR model. The results showed that soil water in the deep layer (40-100 cm) was more stable than that in the shallow layer (0-40 cm). The variation of soil water content and water isotope values in the shallow layer were more obvious due to the effects of evaporation and precipitation. P. orientalis mainly absorbed stable deep soil water, with a relative contribution rate of 55.7%. In the dry season, with the decreases of soil water content, the absorption depth of plants to soil water gradually shifted to the shallow layer. Under conditions of moist, natural condition, mild drought and moderate drought, the relative contribution rates of deep soil water were 59.8%, 57.9%, 54.6%, 52.7%, respectively. To maintain higher transpiration in the wet season, P. orientalis relied more on deep soil water under mild and moderate drought conditions than in the dry season. Under the conditions of moist, natural condition, mild drought and moderate drought, the relative contribution rates of deep soil water were 58.9%, 57.6%, 56.4%, and 57.1%, respectively. The adaptive characteristic of P. orientalis, which adjusts the depth of root water absorption according to soil moisture condition, is of great significance for tree species selection in ecological afforestation and long-term management planning in areas with seasonal drought.

Effects of thinning intensity on the understory water-holding capacity of Pinus sylvestris var. mongolica plantation in the Bashang area of north China.

The complex terrain and poor climatic conditions in Bashang area of Hebei Province result in water and soil loss and geological disasters, which pose a serious threat to ecological safety in North China. In order to improve local environmental quality, barren-resistant and fast-growing tree species such as Pinus sylvestris var. mongolica and Larix gmelinii are planted with large areas. However, unreasonable plantation density will lead to inefficient utilization of rainfall and intensify the conflict between forest and water. In this study, we analyzed the effects of five thinning intensities (0, 20%, 40%, 60%, 80%) of P. sylvestris var. mongolica plantation on herbs, litter, soil and overall water-holding capacity, with the aim to provide scientific basis for management of P. sylvestris var. mongolica. The results showed that water-holding rate of herb varied from 47.7% to 90.7%, and that the water-holding capacity of herb decreased with increasing thinning intensity. When the thinning intensity was less than 40%, water-holding capacity decreased slowly, and then decreased rapidly. With the increase of thinning intensity, natural water-holding rate and maximum water-holding rate of undecomposed layer and semi-decomposed layer decreased gradually, with the effective water-holding rate being 60%>40%>20%>80%>0, and the water-holding capacity of semi-decomposed layer being better than that of undecomposed layer. The water-holding capacity of soil decreased gradually with the increases of thinning intensity. Thinning intensity less than 40% promoted water holding capacity. Under different thinning intensities, the total water-holding rate of understory was 8.3%-14.3%, with an order of 20%>0>40%>60%>80%. In view of understory all layers and overall changes, the thinning intensity at 20% in the study area could effectively improve the understory water-holding capacity and achieve better ecological benefits.

[Characteristics and processes of reverse sap flow of Platycladus orientalis based on stable isotope technique and heat ratio method].

Plants could maintain growth by foliar water uptake and reverse sap flow under certain conditions, particularly in regions with seasonal drought. This physiological activity is often overlooked, however, leaving a gap in quantitatively understanding the processes and mechanisms underlying water utilization of forest vegetation under drought stress. In this study, with both field comparison experiments and pot experiments, we used heat ratio method with stable isotope technique to monitor a typical plantation tree species, Platycladus orientalis, in the Beijing mountainous area. We aimed to analyze the patterns and the influencing factors of the reverse sap flow occurrence in P. orientalis, to quantify the amount and the replenishment rate of reverse sap flow, and to examine the characteristics and processes of reverse sap flow at different parts of plants. In the field comparison experiment, reverse sap flow was detected at the breast height of stem and in the root in the controlled plot (drought plot) after rainfall. The reverse sap flow of root system was detected later than that in the stem. By contrast, no reverse sap flow was observed in the natural plot. In the pot experiments, the recharge rate of all the groups reached the peak value two hours after the rainfall treatment. Except for the groups of severe and moderate drought, recovery of δD to the original level was observed eight hours after rainfall, and the reverse sap flow on plants generally lasted no more than 24 h. The amount of foliar water uptake and the reverse sap flow to the branches and rhizosphere soil had a negative relationship with the initial soil moisture. The maximum recharge rates for leaves, branches, and rhizosphere soil were (9.5±0.1)%, (5.9±0.3)% and (5.7%±0.6)%, respectively. Different rates and timing of the reverse sap flow were observed at different parts of P. orientalis. Under complex and variable conditions of water supply, it is of great significance to examine the process and mechanism of reverse water movement of plants to better understand its survival and competitive strategies.

[Assessing water sources for Populus simonii with different degrees of degradation based on stable isotopes].

Water availability is the key factor limiting plant growth in arid regions. Populus simonii is a typical shelterbelt tree species in Zhangbei County, Hebei Province, with an important role in constructing ecological barrier. With stable isotope technique, graphical method, and multiple linear mixing model, we analyzed water sources and water use strategies of P. simonii in different growth periods with four different degrees of degradation (non-degraded, slightly degraded, modera-tely degraded and severely degraded) in Zhangbei County. Results would help improve our understanding on the cause and mechanism of the large-scale degradation of P. simonii in this area. The results showed that water sources of P. simonii in the early growth stage (May-June) from all four degradation degrees were relatively simple. P. simonii mainly used soil water in 0-40 cm, with the utilization rates being 34.2%, 50.1%, 41.6%, and 55.7% for the four degradation degrees, respectively. At the middle growth stage (July-August), non-degraded P. simonii utilized soil water from layers of 200-280 cm and 280-400 cm, with utilization rates of 20.2% and 30.9%, respectively. Soil water at 200-280 cm and 280-400 cm layers was utilized by slightly degraded poplar, with the contribution rates of each layer being 33.2% and 27.9%, respectively. Moderately degraded P. simonii utilized soil water from the depths of 0-40 cm and 40-120 cm, with the rates of 30% and 26.9%, respectively. Water utilization rate of severely degraded P. simonii to 0-40 cm depth was 55.4%. At the late growth stage (September-October), water sources of non-degraded P. simonii transferred to the upper-middle soil layers, with the utilization rate of 0-40 cm, 40-80 cm, and 80-120 cm being 23.3%, 17.2%, and 16.5%, respectively. The utilization rate of the slightly degraded P. simonii was 35.7% at 0-40 cm and 20.6% at 80-200 cm. The moderately and severely degraded P. simonii mainly utilized soil water at 0-40 cm layer, with the contribution rates of soil water being 43.7% and 51.8%, respectively. With the exacerbation of degradation, the main water source of P. simonii gradually transferred from deep to surface soil water.

[Simulation of δ18O in Platycladus orientalis leaf water with different kinetic fractionation coefficients].

Clarifying 18O isotope composition of leaf water (δL,b) would provide theoretical refe-rence for the study of leaf physiology and forest hydrology. We continuously monitored the concentration of atmospheric water vapor (Wa) and 18O isotope composition of atmospheric water vapor (δv) at the canopy of Platycladus lateralis plantation in the mountain area of Beijing. We analyzed the effects of kinetic fractionation coefficients Δk1(32%) and Δk2(28%) on the prediction of δL,b by combining the measured leaf water 18O isotope (δx) and δL,b of P. lateralis. The results showed that the diurnal variation of Wa was irregular. Atmospheric relative humidity (RH) showed a "V" shape of diurnal variation, and stomatal conductance (gs) increased first and then decreased at the diurnal scale. Wa, RH, and gs showed a significant negative correlation with δL,b when isotopes approached a steady-state equilibrium around noon. The kinetic fractionation coefficient Δk1 and Δk2 were applied to the Craig-Gordon model to predict δL,b under the isotopic quasi-steady-state condition. The results showed that the predicted values of Δk2 approached the observed values of δL,b. This result indicated that the application of Δk2 to the model was more consistent with the change of water isotope concentration in the leaves of P. lateralis in the mountain area of Beijing. These results would improve our understanding of water isotope enrichment model and evapotranspiration resolution model in leaves.