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Abstract Background The combination of anti‐PD‐1 antibody serplulimab and chemotherapy is considered standard first‐line therapy for advanced esophageal squamous cell carcinoma (ESCC), but few later‐line treatments are available. Here we evaluated the therapeutic efficacy of the recombinant, humanized anti‐EGFR antibody HLX07 when used alone or together with serplulimab and chemotherapy against advanced ESCC. Methods This open‐label, non‐randomized, two‐cohort, phase 2 trial involved patients 18‐75 years old with histologically or cytologically confirmed locally advanced, unresectable, or metastatic ESCC, and an Eastern Cooperative Oncology Group performance status of 0‐1. Patients who had failed first‐line immuno‐chemotherapy or at least two lines of other systemic therapy received HLX07 monotherapy intravenously at a dose of 1,000 mg once every 2 weeks (Q2W). Patients with no prior systemic therapy received HLX07 (1,000 mg, day 1) and serplulimab (200 mg, day 1) intravenously Q2W for up to 2 years, concurrently with cisplatin (50 mg/m2, day 1) for up to 8 cycles and 5‐fluorouracil (1,200 mg/m2, days 1‐2) for up to 12 cycles intravenously Q2W. The primary endpoints were progression‐free survival (PFS) and objective response rate (ORR). Results Overall, 50 patients were enrolled. In the HLX07 monotherapy group, ORR was 15.0% (3/20), and the median PFS was 1.5 months (95% confidence interval [CI], 1.3 to 3.7). The median duration of response was not reached, and the rate of patients showing an objective response lasting at least 6 months was 66.7% (95% CI, 5.4 to 94.5). Two (10.0%, 2/20) patients experienced grade 3‐4 treatment‐related adverse events (TRAEs), including hypomagnesemia, hypocalcemia, and fatigue. No patient experienced grade 5 TRAEs. In the HLX07 combination group, the ORR was 60.0% (18/30), and the median PFS was 7.8 months (95% CI, 3.3 to 9.1). Fourteen (46.7%, 14/30) patients experienced grade 3‐4 TRAEs, and one (3.3%, 1/30) patient died due to serplulimab‐related pneumonitis. Conclusions HLX07 monotherapy and its combination with serplulimab and chemotherapy showed manageable toxicity and promising antitumor activity in patients with recurrent or metastatic ESCC. Randomized controlled trials are warranted to further establish the safety and efficacy of HLX07 against ESCC. Trial registration This trial was registered at Clinicaltrials.gov (NCT05221658).

Abstract Objective To explore the efficacy of serplulimab plus chemotherapy in esophageal squamous cell carcinoma (ESCC) patients with liver metastases. Methods A post hoc exploratory analysis of ASTRUM‐007 study was performed, focusing on the association between the liver metastases status and the clinical outcomes. A systematic literature search of electronic databases was conducted to identify eligible randomized controlled trials for the meta‐analysis. Study‐level pooled analyses of hazard ratios (HRs) for PFS according to liver metastases were performed. Results The post hoc analysis of ASTRUM‐007 showed that although patients with liver metastases had a worse prognosis comparing with the non‐liver metastases patients in both treatment arms (serplulimab plus chemotherapy arm: median PFS, 5.7 vs. 6.6 months, HR 1.57 [95% CI, 1.15–2.13]; median OS, 13.7 vs. 15.3 months, HR 1.48 [95% CI, 1.09–1.98]; placebo plus chemotherapy arm: median PFS, 4.3 vs. 5.5 months, HR 1.58 [95% CI, 1.01–2.39]; median OS, 10.3 vs. 11.2 months, HR 1.32 [95% CI, 0.84–2.00]), OS and PFS benefits derived from serplulimab plus chemotherapy versus placebo plus chemotherapy in this study were observed in both patients with liver metastases (HR of PFS: 0.60; 95% CI, 0.37–0.97; HR of OS: 0.68; 95% CI, 0.43–1.11) and the non‐liver metastases patients (HR of PFS: 0.62; 95% CI, 0.49–0.80; HR of OS: 0.69; 95% CI, 0.55–0.87) with similar magnitude. Three randomized controlled trials were included in the meta‐analysis. Pooled HRs demonstrated that the addition of anti‐PD‐1 antibodies significantly improved PFS compared to chemotherapy alone regardless of liver metastases status. Conclusions This study reveals that the presence of liver metastases is a poor prognostic factor but does not affect the improvements in both PFS and OS brought by adding PD‐1 blockade to chemotherapy in ESCC patients. Predictive biomarkers for survival in these patients warrant further investigation.

Accurate identification and understanding of various metallic minerals are crucial for deciphering geological formations, structures, and ages. Giving their pivotal role as essential natural resources, a microscopic exploration of metallic minerals becomes imperative. Traditional analytical methods, while helpful, exhibit certain limitations. However, terahertz time-domain spectroscopy, distinguished by its high signal-to-noise ratio, expansive frequency band, and low incident wave energy, is a promising complement to conventional techniques in characterizing metallic minerals. This study employs terahertz time-domain spectroscopy to examine samples of Stibnite, Sphalerite, Galena, and Pyrite originating from diverse geological conditions. The vibrations of molecules within these metallic minerals induce discernible changes in the terahertz spectra. Our findings untiate the extensive potential of terahertz time-domain spectroscopy in the characterization of metallic minerals, affirming its considerable practical value in mineral resource exploration.

Although the Ordovician petroleum exploration in the Sichuan Basin has been developed slowly for a long time, deepening the research of reservoir characteristics and genesis is still a robust way to accelerate it. This paper characterizes the Ordovician reservoirs in the central part of Sichuan Basin and analyzes their genesis based on cores, thin sections, well logs and drilling data. The results show the reservoirs concentrated in the Lower Ordovician Tongzi Formation, which consist mainly of sandy oolitic dolostones, bioclastic dolostones, fine crystalline dolostones, sandy dolomitized conglomerates, sandy dolostones and dolomite sandstone. The porosity types include interparticle pore, intraparticle pore, moldic pore, fracture and vug. Throats are mostly necked and flaky. The Tongzi Formation reservoirs mainly experienced three types of diageneses, including compaction, cementation and dissolution. The reservoir development was controlled by multiple factors of deposition, diagenesis and tectonics; the shoal facies is the basis, the penecontemporaneous dissolution and dolomitization are the main driving force, and the burial dissolution is the aid. The study can provide reference for deepening the Ordovician petroleum exploration and development in the Sichuan Basin.

To efficiently address the challenge of thermoelastic coupling in functionally graded materials, we propose an approach that combines the radial integral boundary element method (RIBEM) with proper orthogonal decomposition (POD). This integration establishes a swift reduced-order model to transform the high-dimensional system of equations into a more manageable, low-dimensional counterpart. The implementation of this reduced-order model offers the potential for rapid numerical simulations of functionally graded materials (FGMs) under thermal shock loading. Initially, the RIBEM is utilized to resolve the thermal coupling issue within the FGMs. From these solutions, a snapshot matrix is constructed, capturing the solved temperature and displacement fields. Subsequently, the POD modes are established and a POD reduced-order model is constructed for the boundary element format of the thermally coupled problem. Finally, a system of low-order discrete differential equations is solved. Numerical experiments demonstrate that the results obtained from the reduced-order model closely align with those of the full-order model, even when considering variations in structural parameters or impact loads. Thus, the introduction of the reduced-order model not only guarantees solution accuracy but also significantly enhances computational efficiency.