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The North China Plain (NCP) has been suffering from groundwater storage (GWS) depletion and land subsidence for a long period. This paper collects data on GWS changes and land subsidence from in situ groundwater-level measurements, literature, and satellite observations to provide an overview of the evolution of the aquifer system during 1971–2015 with a focus on the sub-regional variations. It is found that the GWS showed a prolonged declining rate of −17.8 ± 0.1 mm/yr during 1971–2015, with a negative correlation to groundwater abstraction before year ~2000 and a positive correlation after ~2000. Statistical correlations between subsidence rate and the GWS anomaly (GWSA), groundwater abstraction, and annual precipitation show that the land subsidence in three sub-regions (Beijing, Tianjin, and Hebei) represents different temporal variations due to varying driver factors. Continuous drought caused intensive GWS depletion (−76.1 ± 6.5 mm/yr) and land subsidence in Beijing during 1999–2012. Negative correlations between total groundwater abstraction and land subsidence exhibited after the 1980s indicate that it may be questionable to infer subsidence from regional abstraction data. Instead, the GWSA generally provides a reliable correlation with subsidence. This study highlights the spatio-temporal variabilities of GWS depletion and land subsidence in the NCP under natural and anthropogenic impacts, and the importance of GWS changes for understanding land subsidence development.

The full pore size distribution represents the integrated characteristics of micro‐nano pore‐throat systems in tight reservoirs. And it involves experiments of different scales to fully analyze the microscope properties. In this paper, we established a new approach for full pore size characterization through conducting the high‐pressure mercury intrusion (HPMI) experiments and low‐temperature nitrogen gas adsorption (LTN2GA) experiments. Meanwhile, we studied the petrology feature of the tight sandstones through X‐ray diffraction (X‐rD) and TESCAN Integrated Mineral Analyzer (TIMA). Then, we investigated the HPMI capillary pressure curves and pore size distribution characteristics, as well as the adsorption‐desorption isotherms features and BET‐specific surface area. Finally, the BJH, non‐local density functional theory (NLDFT) and the quenched solid density functional theory (QSDFT) are contrasted for analyzing the adsorption and pore size distribution characteristics. The HPMI method characterizes the macropores distribution accurately, and the micro/mesopores take up of 14.47% of the total pore spaces. The physisorption isotherms take on the combining shape of type II and IV(a), and the hysteresis loops are like type H3 combined with H4. The BET‐specific surface area is inversely proportional to permeability, and the constant of adsorption heat shows consistence with the analysis results of mineral content. QSDFT can characterize the pore size distribution of micro/mesopores more accurately than the BJH, HPMI, and NLDFT method. By combining the pores narrower than 34 nm calculated from QSDFT method and pores larger than 34 nm calculated from HPMI data with mercury intrusion pressure lower than 42.65 MPa, the full pore size distribution features of tight sandstones are accurately characterized. The micro/mesopores from the new combination method are 3.72% more than that calculated from the HPMI data, and it is of great significance for the accurate pore distribution evaluation and development of tight reservoirs. We performed low‐temperature nitrogen gas adsorption (LTN2GA), high‐pressure mercury intrusion (HPMI), and X‐ray diffraction (X‐rD) experiments on different ultra‐low permeability/tight sandstones to accurately characterize the full pore size distribution of this kind of reservoir rocks. By combining the micropore and mesopore distribution calculated by QSDFT with the mesopore and macropore distribution calculated by HPMI, the accurate characterization of full pore size distribution for the ultra‐low permeability/ tight sandstones is achieved.

The geomorphology of river basin is complex, and its soil sedimentary characteristics are poorly defined. To study the spatial variability of soil structure in different sedimentary environments at the basin scale, 356 sets of soil samples were collected from five typical sedimentary environments in the Yellow River Basin and the Haihe River Basin, including the upper and lower reaches of the rivers, mountain-front plains, central alluvial plains and eastern coastal plains. The particle size distribution (PSD) of the soil samples was obtained using a laser particle size analyzer, and the fractal dimension (D) of the soil structure was derived by applying fractal theory. The PSD, D and the correlation between them were analyzed by  the Pearson correlation method for typical sedimentary environments in two basins. The results show that: (1) The main soil types in the typical geological environments in the basin are sand, loamy sand, sandy loam, silty loam, and silty soil. The soil particle size in the upper and lower reaches of the rivers was higher than that in the plain areas. (2) In the plane, The D value descended in different regions in the following order: the mountain-front plain > the eastern coastal plain > the upper Yellow River > the central alluvial plain > the lower Yellow River. In the vertical direction for both rivers, the D value showed a decreasing trend with increasing burial depth. (3) The model results showed a cubic polynomial correlation between D values and PSD, which was closely related to the non-uniformity of particle size during sorting and deposition. The soil PSD and fractal characteristics are effective tools for the quantitative evaluation of soil structure in various sedimentary environments in the basin.

Therapeutic options for advanced neuroendocrine tumours (NETs) are limited. We investigated the efficacy and safety of surufatinib (HMPL-012, sulfatinib) in patients with extrapancreatic NETs. SANET-ep was a randomised, double-blind, placebo-controlled, phase 3 trial undertaken at 24 hospitals across China. Patients (aged 18 years or older) with unresectable or metastatic, well differentiated, extrapancreatic NETs, with an Eastern Cooperative Oncology Group performance status of 0 or 1, and progression on no more than two types of previous systemic regimens were enrolled. Patients were centrally randomly assigned (2:1) using stratified block randomisation (block size 3) via an interactive web response system to receive oral surufatinib at 300 mg per day or matching placebo. Randomisation was stratified by tumour origin, pathological grade, and previous treatment. Patients, investigators, research staff and the sponsor study team were masked to treatment allocation. Crossover to the surufatinib group was allowed for patients in the placebo group at disease progression. The primary endpoint was investigator-assessed progression-free survival, which was analysed in the intention-to-treat population. A preplanned interim analysis was done at 70% of predicted progression-free survival events. This study was registered with ClinicalTrials.gov, NCT02588170. Follow-up is ongoing. Between Dec 9, 2015, and March 31, 2019, 198 patients were randomly assigned to surufatinib (n=129) or placebo (n=69). Median follow-up was 13·8 months (95% CI 11·1–16·7) in the surufatinib group and 16·6 months (9·2–not calculable) in the placebo group. Investigator-assessed median progression-free survival was 9·2 months (95% CI 7·4–11·1) in the surufatinib group versus 3·8 months (3·7–5·7) in the placebo group (hazard ratio 0·33; 95% CI 0·22–0·50; p<0·0001). As the trial met the predefined criteria for early discontinuation of the study at the interim analysis, the study was terminated early, as recommended by the independent data monitoring committee. The most common treatment-related adverse events of grade 3 or worse were hypertension (47 [36%] of 129 patients in the surufatinib group vs nine [13%] of 68 patients in the placebo group) and proteinuria (25 [19%] vs zero). Treatment-related serious adverse events were reported in 32 (25%) of 129 patients in the surufatinib group and nine (13%) of 68 patients in the placebo group. Treatment-related deaths occurred in three patients in the surufatinib group (disseminated intravascular coagulation and hepatic encephalopathy, liver injury, and death with unknown reason) and one patient in the placebo group (cachexia and respiratory failure). Progression-free survival was significantly longer in patients given surufatinib compared with patients given placebo, and surufatinib has a favourable benefit-to-risk profile in patients with progressive, advanced, well differentiated extrapancreatic NETs. Our results suggest that surufatinib might be a new treatment option for this population. Hutchison MediPharma.

Patients with advanced or metastatic oesophageal squamous cell carcinoma have poor prognosis and few treatment options after first-line therapy. We aimed to assess efficacy and safety of the anti-PD-1 antibody camrelizumab versus investigator's choice of chemotherapy in previously treated patients. ESCORT is a randomised, open-label, phase 3 study of patients aged 18 to 75 years with a histological or cytological diagnosis of advanced or metastatic oesophageal squamous cell carcinoma done at 43 hospitals in China. Eligible patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and had progressed on, or were intolerant to, first-line standard therapy. Patients were randomly assigned (1:1) to camrelizumab (200 mg every 2 weeks) or chemotherapy with docetaxel (75 mg/m2 every 3 weeks) or irinotecan (180 mg/m2 every 2 weeks), all given intravenously. Central randomisation was done using the Randomization and Trial Supply Management system with block size randomly generated as four or six and stratified by disease and ECOG performance status. The primary endpoint was overall survival, assessed in randomised patients who had received at least one dose of treatment. Safety was assessed in all treated patients. The trial is registered with ClinicalTrials.gov, NCT03099382, and is closed to new participants. From May 10, 2017, to July 24, 2018, 457 (75%) of 607 screened patients were randomly assigned to treatment, of whom 228 received camrelizumab treatment and 220 received chemotherapy. As of data cutoff on May 6, 2019, with a median follow-up time of 8·3 months (IQR 4·1–12·8) in the camrelizumab group and 6·2 months (3·6–10·1) in the chemotherapy group, median overall survival was 8·3 months (95% CI 6·8–9·7) in the camrelizumab group and 6·2 months (5·7–6·9) in the chemotherapy group (hazard ratio 0·71 [95% CI 0·57–0·87]; two-sided p=0·0010). The most common treatment-related adverse events of grade 3 or worse were anaemia (camrelizumab vs chemotherapy: six [3%] vs 11 [5%]), abnormal hepatic function (four [2%] vs one [<1%]), and diarrhoea (three [1%] vs nine [4%]). Serious treatment-related adverse events occurred in 37 (16%) of 228 patients in the camrelizumab group, and in 32 (15%) of 220 patients in the chemotherapy group. Ten treatment-related deaths occurred, seven (3%) in the camrelizumab group (three deaths from unknown causes, one enterocolitis, one hepatic function abnormal, one pneumonitis, and one myocarditis) and three (1%) in the chemotherapy group (two deaths from unknown causes, and one gastrointestinal haemorrhage). Second-line camrelizumab significantly improved overall survival in patients with advanced or metastatic oesophageal squamous cell carcinoma compared with chemotherapy, with a manageable safety profile. It might represent a potential option of standard second-line treatment for patients with oesophageal squamous cell carcinoma in China. Jiangsu Hengrui Medicine.

Surufatinib showed superior efficacy in extrapancreatic neuroendocrine tumours (NETs) in the phase 3 SANET-ep study. In SANET-p, we aimed to assess the efficacy and safety of surufatinib in patients with advanced pancreatic NETs. SANET-p was a multicentre, randomised, double-blind, placebo-controlled, phase 3 study, done in 21 hospitals across China. Eligible patients were adults (aged 18 years or older) with progressive, advanced, well differentiated pancreatic NETs, Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and progression on up to two kinds of previous systemic regimens for advanced disease. Patients were randomly assigned (2:1) via an interactive web response system to receive 300 mg of surufatinib or placebo, taken orally once per day in consecutive 4-week treatment cycles until disease progression, intolerable toxicity, withdrawal of consent, poor compliance, use of other antitumour medication, pregnancy, loss to follow-up, or if the investigator deemed discontinuation in the patient's best interest. Randomisation was done centrally using stratified block randomisation (block size three), stratified by pathological grade, previous systemic antitumour treatment, and ECOG performance status score. Patients, investigators, research staff, and the sponsor study team were masked to treatment allocation. Crossover to surufatinib was permitted for patients in the placebo group with disease progression. The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population, which included all patients in randomisation. A pre-planned interim analysis was done at 70% of the predicted progression-free survival events. This study is registered at ClinicalTrials.gov, NCT02589821. Between Feb 18, 2016, and Nov 11, 2019, of 264 patients who were screened, 172 (65%) patients were randomly assigned to receive surufatinib (n=113) or placebo (n=59). The median follow-up was 19·3 months (95% CI 9·3–19·4) in the surufatinib group and 11·1 months (5·7–35·9) in the placebo group. The median investigator-assessed progression-free survival was 10·9 months (7·5–13·8) for surufatinib versus 3·7 months (2·8–5·6) for placebo (hazard ratio 0·49, 95% CI 0·32–0·76; p=0·0011). The trial met the early stopping criteria at the interim analysis and was terminated on recommendation from the independent data monitoring committee. The most common grade 3 or worse treatment-related adverse events were hypertension (43 [38%] of 113 with surufatinib vs four [7%] of 59 with placebo), proteinuria (11 [10%] vs one [2%]), and hypertriglyceridaemia (eight [7%] vs none). Treatment-related serious adverse events were reported in 25 (22%) patients in the surufatinib group and four (7%) patients in the placebo group. There were three on-treatment deaths in the surufatinib group, including two deaths due to adverse events (gastrointestinal haemorrhage [possibly treatment-related] and cerebral haemorrhage [unlikely to be treatment-related]), and one death attributed to disease progression. One on-treatment death in the placebo group was attributed to disease progression. Surufatinib significantly improves progression-free survival and has an acceptable safety profile in patients with progressive, advanced pancreatic NETs, and could be a potential treatment option in this patient population. Hutchison MediPharma.

Salt precipitation near injection wells critically influences both the efficiency and integrity of CO2 geological storage in saline aquifers, especially under high‐salinity conditions. To clarify the dominant mechanisms of supercritical CO2 (ScCO2)‐induced salt crystallization and inform mitigation strategies, we conducted static high‐temperature, high‐pressure soaking experiments. Results demonstrate a coupled mechanism whereby ScCO2‐induced interfacial dehydration and acid‐driven water–rock interactions jointly alter pore structures and surface wettability. A CO2–brine–rock tri‐phase reaction system was established using nuclear magnetic resonance (NMR), low‐temperature nitrogen adsorption, SEM/EDS, XRD, ion chromatography, and contact angle measurements. These analyses revealed a cascade of physicochemical processes, including mineral dissolution, ion accumulation, crystal nucleation, pore blockage, and wettability shift. Compared to N2 controls, supercritical CO2 (ScCO2) significantly accelerates salt crystallization, forming NaCl, KCl, CaSO4, and MgCO3 phases. These precipitates reduce total pore volume by 15%–20% and cause a leftward NMR T2 shift, indicating 30% macropore signal attenuation. Mesopore fraction increases from 47% to 60%, while micropore content decreases to 34%. Surface wettability shifts from hydrophilic (41.6°) to hydrophobic (58.0°). Based on these findings, we propose a multi‐dimensional mitigation framework encompassing aqueous‐phase regulation, injection protocol optimization, pore structure preconditioning, and real‐time in situ monitoring. These insights support improved injection stability, long‐term CO2 storage security, and risk control in saline reservoirs.

This work establishes an analytical model for determining the critical velocity for proppant flowback, and evaluates how proppant flowback affects fracture conductivity for tight reservoirs. The multiphase effects are considered for determining the critical velocity for proppant flowback before and after fracture closure, respectively. The model’s performance is demonstrated by comparing the results against previous models. A finite-element model is built to simulate the proppant flowback process for a hydraulic-fractured well completed in the Ordos Basin. The change in fracture conductivity caused by proppant flowback for several scenarios with varying saturation and net pressure in fractures is further quantitatively assessed. Our results highlight the importance of multiphase effects in determining the critical velocity for proppant flowback at relatively low water saturation in fractures. The critical velocity generally increases with increasing water saturation in fractures and net pressure in fractures. At a flowback velocity higher than the critical value, the loss in fracture conductivity becomes relatively more pronounced at a lower water saturation in fractures and a lower net pressure in fractures. The findings of this work are expected to provide insights into the mechanisms of proppant flowback and flowback drawdown management for field operations in tight reservoirs.

With the improvement of natural gas network interconnection, the network topology becomes increasingly complex. The significance of analyzing topology is gradually becoming prominent, and a systematic analysis method is required. This paper selects two typical natural gas pipeline networks: one in Europe, and the other in North China. Based on complex network theory and the nature of natural gas pipelines, topological models for the two typical networks were established and the evaluation indexes were developed based on four factors: network type, overall topological structure characteristics, path-related topological structure characteristics, and topological structure robustness. Using these indexes, the topological structure of the two typical networks is compared and analyzed quantitatively. The comparison shows that the European network topology has more redundancy, higher transmission efficiency, and greater robustness. The topology analysis method proposed in this paper is practical and suitable for the preliminary analysis of natural gas pipeline networks. The conclusions achieved by this method can assist operators in gaining an intuitive understanding of the overall characteristics, robustness, and key features of pipeline network topology, which is useful in the implementation of hierarchical prevention and control. It also serves as a solid theoretical foundation and guidance for network expansion, interconnection construction, and precise hydraulic simulation calculation in the next stage.

We developed a novel preparative method for nanoparticle albumin-bound (nab) paclitaxel with high drug loading, which was based on improved paclitaxel solubility in polyethylene glycol (PEG) and self-assembly of paclitaxel in PEG with albumin powders into nanoparticles. That is, paclitaxel and PEG were firstly dissolved in ethanol, which was subsequently evaporated under vacuum. The obtained liquid was then mixed with human serum albumin powders. Thereafter, the mixtures were added into phosphate-buffered saline and nab paclitaxel suspensions emerged after ultrasound. Nab paclitaxel was finally acquired after dialysis and freeze drying. The drug loading of about 15% (W/V) were realized in self-made nab paclitaxel, which was increased by approximately 50% compared to 10% (W/V) in Abraxane. Now this new preparative method has been authorized to obtain patent from China and Japan. The similar characteristics of self-made nab paclitaxel compared to Abraxane were observed in morphology, encapsulation efficiency, in vitro release, X-ray diffraction analysis, differential scanning calorimetry analysis, and circular dichroism spectra analysis. Consistent concentration-time curves in rats, biodistributions in mice, anti-tumor activities in mice, and histological transmutation in mice were also found between Abraxane and self-made nanoparticles. In a word, our novel preparative method for nab paclitaxel can significantly improve drug loading, obviously decrease product cost, and is considered to have potent practical value.