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Approximately one-third of patients with HER2-positive breast cancer experienced recurrence within 10 years after receiving 1 year of adjuvant trastuzumab. The ExteNET study showed that 1 year of extended adjuvant neratinib after trastuzumab-based adjuvant therapy could reduce invasive disease-free survival (iDFS) events compared with placebo. This study investigated the efficacy and safety of pyrotinib, an irreversible pan-HER receptor tyrosine kinase inhibitor, after trastuzumab-based adjuvant therapy in patients with high-risk, HER2-positive early or locally advanced breast cancer. This multicenter phase II trial was conducted at 23 centers in China. After enrollment, patients received 1 year of extended adjuvant pyrotinib (400 mg/day), which should be initiated within 6 months after the completion of 1-year adjuvant therapy (trastuzumab alone or plus pertuzumab). The primary endpoint was 2-year iDFS rate. Between January 2019 and February 2022, 141 eligible women were enrolled and treated. As of October 10, 2022, the median follow-up was 24 (interquartile range, 18.0-34.0) months. The 2-year iDFS rate was 94.59% (95% confidence interval [CI]: 88.97-97.38) in all patients, 94.90% (95% CI: 86.97-98.06) in patients who completed 1-year treatment, 90.32% (95% CI: 72.93-96.77) in patients who completed only 6-month treatment, 96.74% (95% CI: 87.57-99.18) in the hormone receptor (HR)-positive subgroup, 92.77% (95% CI: 83.48-96.93) in the HR-negative subgroup, 96.88% (95% CI: 79.82-99.55) in the lymph node-negative subgroup, 93.85% (95% CI: 86.81-97.20) in the lymph node-positive subgroup, 97.30% (95% CI: 82.32-99.61) in patients with adjuvant trastuzumab plus pertuzumab, and 93.48% (95% CI: 86.06-97.02) in patients with adjuvant trastuzumab. The most common adverse events were diarrhea (79.4%), fatigue (36.9%), lymphocyte count decreased (36.9%), nausea (33.3%), and hand-foot syndrome (33.3%). Extended adjuvant pyrotinib administrated after trastuzumab-based adjuvant therapy showed promising efficacy in patients with high-risk HER2-positive breast cancer. The follow-up is ongoing to determine the long-term benefit. No external funding was received for this work. ClinicalTrials.gov: NCT05880927.

Background: Few studies have explored the expression profile of RPL3 in breast cancer (BRCA). Our research provided an in-depth analysis of RPL3 expression patterns in BRCA, highlighting its significance for therapy prediction and prognosis. Methods: RPL3 was notably elevated in malignant cells, and its expression level was closely associated with tumor size and overall survival outcomes. Our study also identified RPL3-related terms and pathways and revealed a strong correlation between RPL3 expression and breast carcinoma immunity, demonstrating inconsistent expression levels in various immune cell lines. In addition, we examined the relationship between RPL3 expression and tumor mutational burden (TMB) in BRCA. To assess the clinical implications of BRCA chemotherapy, we investigated the correlation between RPL3 expression levels and drug sensitivity. Results: Our findings suggest that RPL3 plays a critical role in the BRCA process and is associated with immune infiltration, indicating its potential as a novel immunotherapy target in BRCA treatment. Conclusions: In summary, our research underscores the importance of RPL3 expression levels in tumorigenesis and its potential for guiding BRCA immunotherapy.

The sentinel lymph node (SLN) is defined as the first draining node from the primary lesion, and it has proven to be a good indicator of the metastatic status of regional lymph nodes in solid tumors. The aim of this study was to evaluate the clinical application of SLN biopsy (SLNB) in papillary thyroid carcinoma (PTC) with occult lymph nodes. From April 2006 to October 2012, 212 consecutive PTC patients were treated with SLNB using carbon nanoparticle suspension (CNS). Then, the stained nodes defined as SLN were collected, and prophylactic central compartment neck dissection (CCND) followed by total thyroidectomy or subtotal thyroidectomy were performed. All the samples were sent for pathological examination. There were 78 (36.8%) SLN metastasis (SLNM)-positive cases and 134 (63.2%) SLNM-negative cases. The sensitivity, specificity, positive and negative predictive values, and false-positive and false-negative rates of SLNB were 78.8%, 100%, 100%, 84.3%, 0%, and 21.2%, respectively. The PTC patients with SLNM were more likely to be male (48.2% vs. 32.7%, p = 0.039) and exhibited multifocality (52.6% vs. 33.3%, p = 0.025) and extrathyroidal extension (56.7% vs. 33.5%, p = 0.015). A greater incidence of non-SLN metastases in the central compartment was found in patients with SLNM (41/78, 52.6%) than in those without SLNM (21/134, 15.7%; p < 0.05). However, the SLNM-negative PTC patients with non-SLN metastases were more likely to be male (37.9% vs. 9.5%, p < 0.05). The application of SLNB using CNS is technically feasible, safe, and useful, especially for male patients with co-existing multifocality and extrathyroidal extension. However, the sensitivity of SLNB must be improved and its false-negative rate reduced before it can be a routine procedure and replace prophylactic CCND. More attention should be paid to PTC patients (especially males) without SLNM for signs of non-SLN metastases.

Thyroid implantation after endoscopic thyroidectomy were rarely reported. In this case, we report a patient with benign thyroid tissue implantation after endoscopic thyroidectomy.

FP3 is an engineered protein which contains the extracellular domain 2 of vascular endothelial growth factor (VEGF) receptor 1 (Flt-1) and the extracellular domain 3 and 4 of VEGF receptor 2 (Flk-1, KDR) fused to the Fc portion of human immunoglobulin G1. Previous studies have demonstrated its antiangiogenic effects in vitro and in vivo, and its antitumor activity in vivo. Cetuximab is a monoclonal antibody against epidermal growth factor (EGF) receptor. Combined inhibition of VEGF and EGF signaling may act additively or synergistically. In this study, patient-derived tumor tissue (PDTT) xenograft models of primary colon carcinoma and lymphatic and hepatic metastases were established for assessment of the antitumor activity of FP3 in combination with cetuximab. Xenografts were treated with FP3 and cetuximab, alone or in combination. After tumor growth was confirmed, volume and microvessel density in tumors were evaluated. Levels of VEGF, EGFR and PCNA in the tumor were examined by immunohistochemical staining, and levels of related cell signaling pathway proteins were examined by western blotting. FP3 in combination with cetuximab showed significant antitumor activity in three xenograft models (primary colon carcinoma, lymphatic metastasis and hepatic metastasis). The microvessel density in tumor tissues treated with FP3 in combination with cetuximab was lower compared to that of the control. Antitumor activity of FP3 in combination with cetuximab was significantly higher than that of each agent alone in two xenograft models (colon carcinoma lymphatic metastasis and hepatic metastasis). This study indicated that addition of FP3 to cetuximab significantly improved tumor growth inhibition in the PDTT xenograft models of colon carcinoma lymphatic and hepatic metastases. Combination anti-VEGF (FP3) and anti-EGFR (cetuximab) therapies may represent a novel therapeutic strategy for the management of metastatic colon carcinoma.

Results of a systematic paleomagnetic study are reported based on Late Carboniferous to Early Permian sedimentary rocks on the north slope of the Tanggula Mountains, in the northern Qiangtang terrane （NQT）, Tibet, China. Data revealed that magnetic minerals in limestone samples from the Zarigen Formation （CP^z）are primarily composed of magnetite, while those in sandstone samples from the Nuoribagaribao Formation （Pnr） are dominated by hematite alone, or hematite and magnetite in combination. Progressive thermal, or alternating field, demagnetization allowed us to isolate a stable high temperature component （HTC） in 127 specimens from 16 sites which successfully passed the conglomerate test, consistent with primary remnance. The tilt-corrected mean direction for Late Carboniferous to Early Permian rocks in the northern Qiangtang terrane is D°=30.2°, Is=-40.9°, ks=269.0, a95=2.3°, N=16, which yields a corresponding paleomagnetic pole at 25.7°N, 241.5°E （alp/rim=2.8°/1.7°）, and a paleolatitude of 23.4°S. Our results, together with previously reported paleomagnetic data, indicate that： （1） the NQT in Tibet, China, was located at a low latitude in the southern hemisphere, and may have belonged to the northern margin of Gondwana during the Late Carboniferous to Early Permian; （2） the Paleo-Tethys Ocean was large during the Late Carboniferous to Early Permian, and （3） the NQT subsequently moved rapidly northwards, perhaps related to the fact that the Paleo-Tethys Ocean was rapidly contracting from the Late Permian to Late Triassic while the Bangong Lake-Nujiang Ocean, the northern branch of the Neo-Tethys Ocean, expanded rapidly during this time.

Results of a systematic paleomagnetic study are reported based on Late Carboniferous to Early Permian sedimentary rocks on the north slope of the Tanggula Mountains,in the northern Qiangtang terrane（NQT）,Tibet,China.Data revealed that magnetic minerals in limestone samples from the Zarigen Formation（CP^z）are primarily composed of magnetite,while those in sandstone samples from the Nuoribagaribao Formation（Pnr）are dominated by hematite alone,or hematite and magnetite in combination.Progressive thermal,or alternating field,demagnetization allowed us to isolate a stable high temperature component（HTC）in 127 specimens from 16 sites which successfully passed the conglomerate test,consistent with primary remnance.The tilt-corrected mean direction for Late Carboniferous to Early Permian rocks in the northern Qiangtang terrane is Ds=30.2°,Is=-40.9°,ks=269.0,a95=2.3°,N=16,which yields a corresponding paleomagnetic pole at 25.7°N,241.5°E（dp/dm=2.8°/1.7°）,and a paleolatitude of 23.4°S.Our results,together with previously reported paleomagnetic data,indicate that:（1）the NQT in Tibet,China,was located at a low latitude in the southern hemisphere,and may have belonged to the northern margin of Gondwana during the Late Carboniferous to Early Permian;（2）the Paleo-Tethys Ocean was large during the Late Carboniferous to Early Permian,and（3）the NQT subsequently moved rapidly northwards,perhaps related to the fact that the Paleo-Tethys Ocean was rapidly contracting from the Late Permian to Late Triassic while the Bangong Lake-Nujiang Ocean,the northern branch of the Neo-Tethys Ocean,expanded rapidly during this time.

Arctic extreme precipitation (EP) broadly impacts permafrost degradation, glacier and snow cover changes, and ice sheet mass balance as well as ecosystems. However, investigation of EP spatiotemporal variations over the Arctic remains challenging, and their primary drivers are still poorly understood. Performance estimation of three state-of-the-art reanalysis products (Climate Forecast System Reanalysis (CFSR), European Centre for Medium-Range Weather Forecasts Reanalysis version 5 (ERA-5), and Modern-Era Retrospective analysis for Research and Applications, version 2 (MERRA-2)) against gauge-based precipitation observations reveals that MERRA-2 outperforms other reanalysis for Arctic EP changes. Based on MERRA-2 data, both annual EP amount and occurrence days averaged over the Arctic show statistically significant positive trends during 1980–2022 (3.37 ± 1.03 mm dec−1 and 0.42 ± 0.17 d dec−1, respectively), with the most pronounced increase in the autumn. Spatial heterogeneity in annual and seasonal EP trends is found across the Arctic, with the largest positive annual trends of 30 mm dec−1 over the Bering Sea and the Denmark Strait. The significant EP increase is closely associated with intensified atmospheric rivers (ARs) and widespread decline in sea ice concentration (SIC). Specially, SIC and ARs are responsible for 12% and 50% of Arctic EP inter-annual variance, respectively, while ARs directly contribute 28.3% of the total annual EP amounts. These findings explain the mechanistic controls on Arctic EP, providing critical insights for projecting polar weather and climate extremes and their impacts on the Arctic environment.

The effects of variations in the heat treatment process of milk on its quality and flavor are inevitable. This study investigated the effect of direct steam injection and instantaneous ultra-high-temperature (DSI-IUHT, 143 °C, 1–2 s) sterilization on the physicochemical properties, whey protein denaturation (WPD) rate, and volatile compounds (VCs) of milk. The experiment compared raw milk as a control with high-temperature short-time (HTST, 75 °C 15 s and 85 °C 15 s) pasteurization and indirect ultra-high-temperature (IND-UHT, 143 °C, 3–4 s) sterilization. The results showed no significant differences (p > 0.05) in physical stability between milk samples with different heat treatments. The DSI-IUHT and IND-UHT milks presented smaller particle sizes (p < 0.05) and more concentrated distributions than the HTST milk. The apparent viscosity of the DSI-IUHT milk was significantly higher than the other samples (p < 0.05) and is consistent with the microrheological results. The WPD of DSI-IUHT milk was 27.52% lower than that of IND-UHT milk. Solid-phase microextraction (SPME) and solvent-assisted flavor evaporation (SAFE) were combined with the WPD rates to analyze the VCs, which were positively correlated with ketones, acids, and esters and negatively associated with alcohols, heterocycles, sulfur, and aldehydes. The DSI-IUHT samples exhibited a higher similarity to raw and HTST milk than the IND-UHT samples. In summary, DSI-IUHT was more successful in preserving the milk’s quality due to its milder sterilization conditions compared to IND-UHT. This study provides excellent reference data for the application of DSI-IUHT treatment in milk processing.