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Abstract Background Heat and drought stresses usually occur together in nature, and both are expected to increase in frequency and intensity as a result of climate change. The synergistic impacts of these compound climate extremes on potatoes are far from the effects of individual stresses. However, the dynamics of the effects of combined heat and drought stresses on potato physiology and biochemistry have yet to be thoroughly assessed. To elucidate this point, we set up a pot experiment using ‘Atlantic’ potato seedlings as test material. A total of six treatments were set up: CK (normal growth conditions: 21 ℃, 0 PEG), A1B1 (31 ℃, 20% PEG), A1B2 (31 ℃, 10% PEG), A1B3 (31 ℃, 0 PEG), A2B1 (21 ℃, 20% PEG), and A2B2 (21 ℃, 10% PEG), and 15 physiological indices were determined with the stress time of 0, 6, 12 and 18 days. Results After 18 days of stress, the phenotype of potato seedlings was significantly different. Compared with CK, the thickness of potato leaves and palisade tissue increased under heat and drought stress, and the combined stress reduced the photosynthetic efficiency of potato leaves. In all treatments except CK, the chlorophyll content decreased significantly, the antioxidant enzyme activity increased first and then decreased, and the relative conductivity and malondialdehyde content increased significantly. The heat and combined treatment made the content of the osmotic regulator first increase and then decrease, while the treatment of 21 ℃ had no significant change. According to the correlation, principal component and interaction analysis, both heat and drought treatment had significant effects on each index, and the longer the stress time, the greater the effect, and the effect of combined stress was greater than that of single stress. However, after 6 days of stress, the activity of antioxidant enzymes and the content of transparent regulatory substances increased. Conclusions In conclusion, potato can cope with heat, drought and combined stress by adjusting leaf tissue structure, antioxidant enzyme activity and osmotic regulatory substances in a short time. Graphical Abstract

Abstract Background Potato (Solanum tuberosum L.) production is seriously threatened by the oomycete Phytophthora infestans (P. infestans). However, it remains unclear how the two potato cultivars, Q9 (moderately resistant) and Atl (susceptible), initiate distinct defense responses after inoculation with P. infestans. To uncover the underlying process, we investigated the dynamic gene expression profiles and the functions of the differentially expressed genes (DEGs). Results The results showed that the numbers of up-regulated DEGs were 1345, 1063 and 1694 in Q9 and 272, 603 and 2554 in Atl at 1 day post inoculation (dpi), 3 dpi and 5 dpi, respectively. Meanwhile, the down-regulated DEGs were 1557, 1417 and 389 in Q9 and 114, 364 and 2528 in Atl simultaneously. KEGG enrichment analysis revealed that plant-pathogen interaction, phenylpropanoid biosynthesis and MAPK signaling pathway were significantly enriched in Q9 at the later stage. Furthermore, DEGs associated with plant-pathogen interaction and phenylpropanoid biosynthesis showed higher expression levels in Q9 compared to Atl, especially at the later stage. The expressions of eight DEGs were validated by quantitative real-time PCR (qRT-PCR), which further verified the accuracy of the transcriptomics analysis. In addition, DEGs that were exclusively up-regulated and down-regulated in Q9 were analyzed, which may contribute to the resistance of Q9. Transient expression analysis revealed that four DEGs, including StHP1, StMYB2, StHSP3 and StNAC5, exhibited increased tolerance to P. infestans, indicating a positive role in enhancing the resistance of Q9. Conclusion Therefore, the DEGs associated with plant-pathogen interaction, phenylpropanoid biosynthesis and MAPK signaling pathway were involved in regulating late blight, and the expression level of the related genes significantly increased in Q9. In addition, StHP1, StHSP3 and the transcription factors, including StMYB2 and StNAC5, played positive roles in improving the resistance of potato Q9 to P. infestans. These findings provide useful information for further understanding the molecular mechanism of potato resistance to late blight. Furthermore, our study identified novel resistance genes that can be used in resistance breeding and functional research. Graphical abstract

Abstract Background GAox is a key enzyme involved in GA biosynthesis pathway and plays an important role in regulating various processes in plant life cycle. However, it has not been systematic, studies have been conducted in potato, which is the world's fourth largest food crop. Methods In this work, we systematically identified GAox gene family (StGAox) in potato by analyzing the potato genome sequence using a set of bioinformatics approaches, and analyze their physical, chemical properties, distribution on chromosomes, gene structure, conserved motifs, gene duplication events and expression patterns were analyzed. Results The results showed that a total of 33 GAox proteins were identified and unevenly distributed on 10 chromosomes. Based on their protein structure and phylogenetic characteristics, these 33 StGAoxes were divided into 5 distinct subclasses. Collinearity analysis revealed that there were 5 pairs of duplicated genes in the StGAox gene family, and all of which evolved under purifying selection. Analysis of RNA-seq data of double haploid (DM) potatoes under different tissues, abiotic stresses and hormone treatments showed that PG0002068, PG0024249 and PG0027963 were higher expressed in leaves, PG009427, PG0026762, PG0009021 and PG0021095 were higher expressed in tubers, PG2003479, PG0024249, PG0005698, and PG0009021were higher expressed in shoots than those of other tissues. In addition, the expression of PG0002068, PG2003479, PG0032156, PG0024249, and PG0021292 were up-regulated under mannitol and drought stress. Conclusions Comparative genome-wide analysis of StGAox genes and their expression analyses revealed that members of this family may be involved in tissue-specific developmental and abiotic stress responses. Graphical Abstract

Abstract Background Cyclin‐dependent kinase (CDK) 4/6 inhibitor plus endocrine therapy (ET) become standard‐of‐care for patients with hormone receptor‐positive, human epidermal growth factor receptor‐2 negative (HR+/HER2−) metastatic breast cancer (MBC). However, the optimal therapeutic paradigm after progression on CDK4/6 inhibitor remains unclear. This study aimed to evaluate the efficacy and safety of abemaciclib with switching ET versus chemotherapy after progression on prior palbociclib‐based ET in Chinese patients with HR+/HER2− MBC. Methods From 414 consecutive patients with HR+/HER2− MBC who had been treated with palbociclib plus ET from September 2018 to May 2022 in Peking University Cancer Hospital, we identified 80 patients who received abemaciclib plus switching ET or chemotherapy after progression on palbociclib, matched for age, original stage at diagnosis, disease‐free interval, and tumor burden at 1:1 ratio. The primary endpoint was progression‐free survival (PFS) compared using the Kaplan–Meier method. A Cox proportional hazard model was performed to identify clinical factors associated with PFS in the abemaciclib group. Results The median PFS was 6.0 months (95% confidence interval [CI]: 3.94–8.06) in abemaciclib group and 4.0 months (95% CI, 2.52–5.49) in chemotherapy group (p = 0.667). And, there was no difference in median PFS between the sequential and nonsequential arm (6.0 vs. 6.0 months) in the abemaciclib group though fewer lines of prior systemic therapy and longer PFS from prior palbociclib in the sequential arm. However, patients with prior palbociclib as the first‐line therapy had a significantly longer median PFS versus prior palbociclib as ≥2nd‐line therapy (11.0 vs. 5.0 months, p = 0.043). Based on multivariable analysis, ER+/PR+ was an independent factor associated with longer PFS. There was no significant difference in overall survival between the abemaciclib and chemotherapy groups (p = 0.069). Conclusion Our findings indicate that abemaciclib plus switching ET might be one of feasible treatment options for Chinese patients with HR+/HER2− MBC after progression on prior palbociclib‐based therapy in addition to chemotherapy.

Abstract Background Continuous cropping can reduce soil quality and affect rhizosphere metabolism, ultimately reducing crop yield. Crop rotation can mitigate the damage caused by continuous cropping, but different crop rotation patterns respond differently to soil quality and rhizosphere metabolism. We investigated the effects of different cropping patterns on soil physicochemical properties, enzyme activities, microbial quantity, and rhizosphere metabolism of continuous potato cropping based on a long-term field study from 2018 to 2022. The experiment was set up with the following three treatments: potato (Solanum tuberosum L.)-potato-potato-potato-potato (CK), potato-potato-potato-pea (Pisum arvense L.)-potato (T1), and potato-potato-potato-faba bean (Vicia faba L.)-potato (T2). Results The results showed that pea-potato rotation (T1) and faba bean-potato rotation (T2) significantly improved soil physicochemical properties and microbial quantity, enhanced enzyme activity, and increased yield by 21.19% and 28.38%, respectively, compared with the continuous potato crop. Non-targeted metabolomics analysis showed that the differential metabolites of pea-potato and faba bean-potato rotation were mainly nucleotides, organic acids and derivatives, and flavonoids compared to continuous potato cropping. These differential metabolites are mainly enriched in the ABC transporter, purine metabolism, pyrimidine metabolism, and phenylalanine metabolism pathways. Combined analyses showed that legume-potato rotations improved soil physicochemical properties, enzyme activities, and microbial quantity of continuous potato cropping, ultimately increasing tuber yields. In addition, correlation analyses showed that differential metabolites significantly enriched in purine and phenylalanine metabolism (l-Tyrosine, Trans-Cinnamic acid, Guanine, and Adenine) were also strongly associated with these measurements. Conclusions Therefore, we conclude that legume-potato rotations modulate the abundance and function of rhizosphere metabolites and significantly alter the low molecular metabolite profile of the soil under continuous potato conditions. Some of these important metabolites may play a part in the cycling of nutrients in the soil, making its physicochemical properties and microbial quantity better, raising the activity of soil enzymes, and ultimately increasing the yield of potato tubers. The above results indicate that legume-potato rotation has a positive effect on continuous potato soils. It lays a solid foundation for revealing the complex molecular network and metabolic pathways of microbial communities in soil after legume crop rotation. Graphical Abstract

Abstract Background The effect of the combination of an anti-angiogenic agent with a poly (ADP-ribose) polymerase (PARP) inhibitor in cancer treatment is unclear. We assessed the oral combination of fuzuloparib, a PARP inhibitor, and apatinib, a VEGFR2 inhibitor for treating advanced ovarian cancer (OC) or triple-negative breast cancer (TNBC). Methods This dose-escalation and pharmacokinetics-expansion phase 1 trial was conducted in China. We used a standard 3 + 3 dose-escalation design, with 7 dose levels tested. Patients received fuzuloparib orally twice daily, and apatinib orally once daily. The study objectives were to determine the safety profile, recommended phase 2 dose (RP2D), pharmacokinetics, preliminary efficacy, and efficacy in relation to germline BRCA mutation (gBRCA mut). Results Fifty-two pre-treated patients were enrolled (30 OC/22 TNBC). 5 (9.6%) patients had complete response, 14 (26.9%) had partial response, and 15 (28.8%) had stable disease. Objective response rate (ORR) and disease control rate were 36.5% (95% CI 23.6–51.0) and 65.4% (95% CI 50.9–78.0), respectively. At the highest dose level of fuzuloparib 100 mg plus apatinib 500 mg, the ORR was 50.0% (4/8; 95% CI 15.7–84.3); this dose was determined to be the RP2D. Patients with gBRCA mut had higher ORR and longer median progression-free survival (PFS) than those with gBRCA wt, both in OC (ORR, 62.5% [5/8] vs 40.9% [9/22]; PFS, 9.4 vs 6.7 months) and TNBC (ORR, 66.7% [2/3] vs 15.8% [3/19]; PFS, 5.6 vs 2.8 months). Two dose-limiting toxicities occurred: grade 4 febrile neutropenia (fuzuloparib 100 mg plus apatinib 250 mg) and thrombocytopenia (fuzuloparib 100 mg plus apatinib 375 mg). Maximum tolerated dose was not reached. The most common treatment-related grade ≥ 3 toxicities in all patients were hypertension (19.2%), anaemia (13.5%), and decreased platelet count (5.8%). Exposure of apatinib increased proportionally with increasing dose ranging from 250 to 500 mg, when combined with fuzuloparib 100 mg. Conclusions Fuzuloparib plus apatinib had acceptable safety in patients with advanced OC or TNBC. Fuzuloparib 100 mg bid plus apatinib 500 mg qd was established as the RP2D. With the promising clinical activity observed, this combination is warranted to be further explored as a potential alternative to chemotherapy. Trial registration ClinicalTrials.gov, NCT03075462 (Mar. 9, 2017).

Summary: Background: Although the antibody–drug conjugates (ADCs) have significantly improved the survival outcomes of patients with human epidermal receptor 2 (HER2)-expressing gastric or gastroesophageal junction (G/GEJ) cancer, the efficacy of ADC used as a single agent is limited. Therefore, it is necessary to investigate effective and safe combination regimens. Preclinical data indicated a synergetic antitumour effect of RC48 and programmed cell death protein 1 (PD-1) inhibitors. We aimed to evaluate the safety and efficacy of RC48 plus toripalimab in patients with HER2-expressing G/GEJ cancer and other solid tumours. Methods: This was a open-label, multicentre, phase 1 trial performed at three hospitals in China. Eligible patients had advanced G/GEJ cancer or other solid tumours with HER2 IHC≥1 or ISH positivity and were refractory to at least one line of treatment, or standard treatment was intolerable or unavailable for these patients. This study followed a “3 + 3” design with predefined RC48 dosages of 2.0 mg/kg and 2.5 mg/kg plus toripalimab 3 mg/kg, once every 2 weeks (q2w). The primary objectives were to evaluate the safety and determine the recommended phase II dose (RP2D), and the secondary objectives included assessing the pharmacokinetics (PK) and preliminary efficacy. This study was registered with ClinicalTrials.gov, NCT04280341. Findings: Between July 13, 2020 and August 30, 2022, 56 patients, including 30 patients with G/GEJ cancer and 26 patients with other solid tumours, were enrolled and received RC48 plus toripalimab (n = 7 for RC48 2.0 mg/kg, toripalimab 3 mg/kg, q2w; n = 49 for RC48 2.5 mg/kg, toripalimab 3 mg/kg, q2w). No dose-limiting toxic effects occurred. The RP2D was declared as RC48 2.5 mg/kg plus toripalimab 3 mg/kg, q2w. The most common grade 3 adverse events were a decreased neutrophil count (n = 13), and a decreased white blood cell count (n = 7). The efficacy assessment was completed for 52 patients. Among patients with G/GEJ cancer (n = 30), the confirmed objective response rate (ORR) was 43% (12/28, 95% CI 25, 63), median progression-free survival (PFS) was 6.2 months (95% CI 4.0, 6.9), median overall survival (OS) was 16.8 months (95% CI 7.2, NE). The ORR of patients with G/GEJ cancer receiving RP2D (n = 24) reached 50% (11/22, 95% CI 28, 72), with median PFS of 5.1 months (95% CI 1.4, 7.3) and median OS of 14.0 months (95% CI 6.3, NE). Among patients with G/GEJ cancer who received RP2D, a clinical benefit was observed in both HER2-positive and low HER2 expressing populations, with an ORR of 56% (5/9, 95% CI 21, 86) vs. 46% (6/13, 95% CI 19, 75), median PFS of 7.8 months (95% CI 0.9, NE) vs. 5.1 months (95% CI 1.2, 6.9), median OS of NE months (95% CI 4.3, NE) vs. 14.0 months (95% CI 5.1, NE), respectively. Antitumour activity was also observed for other solid tumours, including breast cancer (5/13) and endometrial carcinoma (1/1). Interpretation: Our findings suggested that RC48 plus toripalimab had a manageable safety profile and showed encouraging efficacy in pretreated patients with HER2-positive and low HER2-expressing G/GEJ cancer. The findings of our phase 1 clinical trial support further investigation of HER2-targeted ADC plus immunotherapy in HER2-expressing G/GEJ cancer and pancancer treatment in the future. Funding: Beijing Municipal Medical Research Institutes, Beijing Medical Research Institute (Z200015).

Abstract Background Potato (Solanum tuberosum L.) continuous cropping causes the decrease of tuber yield, deterioration of quality and soil degradation in the semi-arid area. These negative effects can generally be mitigated by legume rotation and mulching. However, little is known about how can mulching and legume rotation alleviate the above damage through altering soil environment. Methods A field experiment was conducted to investigate changes in soil properties and microbial community in response to legume rotation and mulching under six planting patterns: potato continuous cropping without film mulching (PC), potato continuous cropping with film mulching (PCF), potato–broad bean rotation without film mulching (R1), potato–broad bean rotation with film mulching (R1F), potato–pea rotation without film mulching (R2) and potato–pea rotation with film mulching (R2F). Results Compared with the PC, the R1F and R2F had significantly enhanced the contents of alkaline nitrogen (AN), available phosphorus (AP), available potassium (AK), total carbon (TC) and total nitrogen (TN), but reduced soil pH and electrical conductivity (EC). The Shannon index of fungi in R1F and R2 was significantly higher than other treatments. The dominant bacterial and fungal phyla of each treatment was Proteobacteria and Ascomycota. R1, R1F, R2 and R2F enhanced the relative abundance of metabolic fungi and altered key differential microbial species. Soil EC, AN and AK were major factors influencing the soil bacterial and fungal communities. Conclusion Overall, the study demonstrated that potato-broad bean/pea rotation with mulching can be adopted as the preferred cropping systems to alleviate potato continuous cropping obstacles through enhancing soil fertility and regulating soil microbial communities in the semi-arid of Loess Plateau, China. Graphical Abstract

Highlights 1. Glutathione affected the synthesis of phenylpropanoid in the potato. 2. Glutathione affected the levels of plant hormone and the expression of related genes in potato. 3. Glutathione enhanced the tolerance of potato to cadmium stress. 4. Some genes play an important role in potato response to cadmium stress.

Abstract Background The potato (Solanum tuberosum L.) is an important food crop in the alkaline soil area of northwest China. It is abundant in ascorbic acid (vitamin C), which facilitates iron absorption in the body. The large consumption of potato makes it a good food source of iron absorption for human body. However, iron deficiency in alkaline soil regions reduced chlorophyll synthesis in the leaves, resulting in lower photosynthesis and less sugar supply to the plant's healthy organs, significantly restricted crop development and yield, and inflicted major economic losses. Methods In this study, a 2-year (2020–2021) field trial was designed. Under foliar application of five different iron fertilizers: ferric sulfate [(Fe2(SO4)3], T1; ferrous sulfate (FeSO4·7H2O), T2; citric acid/ferric sulfate (CA/Fe2(SO4)3), T3; citric acid/ferrous sulfate (CA/FeSO4·7H2O), T4; ethylenediamine tetra acetic acid (EDTA-Fe·Na), T5, changes in potato plant photosynthesis were compared to no iron fertilization, CK conditions. The effects of various iron fertilizers on the yield, quality, and iron content of potato tubers, their correlations to chlorophyll levels, and the characteristics of photosynthetic fluorescence were studied. Results The results indicated that spraying iron fertilizers increased the yield, quality and Fe content of the tubers, which might be due to the improvement of the plants’ photosynthetic pigment content, gas exchange parameters and chlorophyll fluorescence. In two consecutive years of cultivation, we found that potato tuber yield and Fe content increased in potatoes treated with five iron fertilizer sprays. Among them, tuber yield increased most significantly by T5 and T3 treatments compared to CK, while Fe content was significantly higher by the T5 treatment than by CK and other treatments. Tuber yield was increased by 33.28% and 18.85% in 2020 and 50.74% and 54.48% in 2021 by T5 and T3 treatments, respectively, compared to CK. Fe content was increased by 112.64% and 54.98% in 2020 and 2021 by T5 treatment, respectively, compared to CK. Conclusions EDTA-Fe·Na and CA/Fe2(SO4)3 excelled over the other iron fertilizers. The findings of this study are instructive for developing cost-effective iron fertilizer management systems to maximize the impact of iron biofortification on human health. Graphical Abstract

This study aimed to examine the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) and other clinicopathological features in HER2+ MBC patients who received first-line anti-HER2 therapy. A total of 129 patients were assigned to NLR-low and NLR-high groups based on a cutoff value of 3.0 at baseline. Peripheral blood lymphocyte subsets and gene mutations in circulating tumor DNA were analyzed by flow cytometry and Next-generation sequencing, respectively. Survival was evaluated by the Kaplan–Meier method and Cox regression analysis. Of the 129 patients, 77 and 52 were assigned to the NLR-low (≤3) and NLR-high (>3) groups, respectively. Compared with NLR-high patients, the NLR-low patients had significantly longer median progression-free survival (PFS) (11.7 vs. 7.7 months) (p = 0.001, HR = 2.703 95% CI 1.543–4.736 and overall survival (OS) (37.4 vs. 28.7 months) (p = 0.044, HR = 2.254 95% CI 1.024–4.924). Furthermore, this association was independent of metastatic sites or estrogen receptor status. Peripheral blood CD3+ (p = 0.034) and CD4+ (p = 0.010) T cell numbers were significantly higher in the NLR-low group than the NLR-high group. The mutational profile of MBC was generally similar between the two groups. Baseline NLR was a prognostic factor of PFS and OS for patients with HER2+ MBC in the first-line setting. These results may facilitate the selection of patients who will benefit most from anti-HER2 treatment.

ObjectivesThis study evaluated the efficacy and safety of apatinib (an oral small-molecule tyrosine kinase inhibitor targeting VEGFR-2) 250 mg combined with chemotherapy in patients with pretreated metastatic breast cancer in a real-world setting.Patients and methodsA database of patients with advanced breast cancer who received apatinib between December 2016 and December 2019 in our institution was reviewed, and patients who received apatinib combined with chemotherapy were included. Progression-free survival (PFS), overall survival (OS), the objective response rate (ORR), the disease control rate (DCR), and treatment-related toxicity were analyzed.ResultsIn total, 52 evaluated patients with metastatic breast cancer previously exposed to anthracyclines or taxanes who received apatinib 250 mg combined with chemotherapy were enrolled in this study. Median PFS and OS were 4.8 (95% confidence interval [CI] = 3.2–6.4) and 15.4 months (95% CI = 9.2–21.6), respectively. The ORR and DCR were 25% and 86.5%, respectively. Median PFS for the previous line of treatment was 2.1 months (95% CI = 0.65–3.6), which was significantly shorter than that for the apatinib–chemotherapy combination (p < 0.001). No significant difference was identified in the ORR and PFS among the subgroups(subtypes, target lesion, combined regimens and treatment lines). The common toxicities related to apatinib were hypertension, hand-foot syndrome, proteinuria, and fatigue events.ConclusionApatinib 250 mg combined with chemotherapy provided favorable efficacy in patients with pretreated metastatic breast cancer regardless of molecular types and treatment lines. The toxicities of the regimen were well tolerated and manageable. This regimen could be a potential treatment option in patients with refractory pretreated metastatic breast cancers.

Abstract Background The growth of potato (Solanum tuberosum L.) is severely affected by the complex and variable soil environment, and film mulching has been widely used for potato growth in semiarid areas of western China. However, there are few studies on the effects of film mulching on soil quality and tuber yield in potato fields. Methods The effects of four mulching patterns (flat plot without film mulching, FP; flat plot with film mulching, FPM; ridge planting with half mulch, RPHM; ridge planting with full mulch, RPFM) on soil chemical and biological properties and potato tuber yield were investigated during two growing seasons (2018 and 2019) in the field. Results The results showed that compared with FP, the mulching treatments significantly increased the tuber yield of potato, with an increase of 3.7–20.77% and 7.89–26.35% in 2018 and 2019, respectively, and the yield of RPFM was higher than that of other treatments. In both growing seasons, RPFM significantly increased the contents of alkali-hydrolyzed N and available P, and the activities of soil urease, catalase, alkaline phosphatase, and sucrase. Bacterial and actinomycete counts were significantly higher in RPFM than those in the other treatments. Furthermore, RPFM significantly increased large potatoes and decreased small potatoes. Pearson’s correlation analysis revealed that soil alkaline dissolved nitrogen and actinomycete populations were the main factors affecting potato yield formation. Conclusions These results indicate that RPFM can improve the soil environment and further increase potato tuber yield, which is a viable option for potato production in semiarid areas. Graphical Abstract

Ocean waves are crucial for driving various oceanic processes. In this study, the spatial and temporal distribution of significant wave height (SWH) in the North Pacific (NP) is analyzed using the 42-year ERA5 reanalysis dataset from European Centre for Medium-Range Weather Forecasts (ECMWF). The presence of an ENSO signal is confirmed in wave fields of the North Pacific. Furthermore, the spatial distributions of swells and wind waves are analyzed using the Empirical Orthogonal Function (EOF) method, revealing that waves can transport large-scale signals from the NP to lower latitudes through swells. In addition, our research reveals a relationship between ENSO and Stokes drift in the NP. Stokes drift contributes positively to the maintenance of stable sea surface temperatures (SSTs) by transporting more (less) water towards the equatorial Pacific during El Niño (La Niña year) years. It is further noted that during strong ENSO events, the strength of the Stokes drift anomaly intensifies accordingly, which implies a strong link between wave-induced transport and ENSO.

The investigation of the propagation of swells throughout the ocean has long been a subject of significant interest in physical oceanography. This paper investigates the interannual variability of the Pacific swell pools and examines the factors contributing to their formation using the European Centre for Medium-Range Weather Forecasts (ECMWF) ERA5 re-analysis dataset. Our results show that the interaction between swell propagation and wind fields influences the formation and development of Pacific swell pools. The eastern and southern Pacific swell pools are mainly caused by the northward propagation of swells from the South Pacific; the western and northern swell pools are primarily influenced by the southward propagation of swells from the North Pacific; and the central part of the swell pools is the result of the combined impact of both swell propagation from the north and south Pacific. The size of the swell pools in the Pacific Ocean is at its maximum in the northern hemisphere during the winter (December, January, and February) and at its minimum during the summer (June, July, and August). Due to the impact of the low-pressure systems, the swell pools in the winter hemisphere are relatively small, while the swell pools in the summer hemisphere are significantly larger. There is a relationship between the swell pools and ENSO events. When an El Niño event (La Niña event) occurs, the swells propagating to the low latitudes of the Pacific Ocean from high latitudes will strengthen (weaken), resulting in an increase (decrease) in the size of the swell pools. Analyzing the spatial and temporal distribution of the swell pools is important for understanding the large-scale effect of waves.

Abstract Bilateral breast cancer (BBC) is an uncommon subset of breast cancer (BC), and it may present as synchronous bilateral breast cancer (sBBC) or metachronous bilateral breast cancer (mBBC). Through this study, we aimed to evaluate the proportion of BBC in BC and compare the clinicopathological characteristics, treatment, and outcomes of sBBC and mBBC at an academic cancer center in China. Patients with BC consecutively treated between 2006 and 2016 were retrospectively reviewed. Patients with BBC were included. In total, 3924 patients with BC were analyzed and 127 patients with BBC (28 sBBC, 99 mBBC) with a median follow‐up of 98 months were identified. The proportion of BBC was 3.2% (0.7%, sBBC; 2.5%, mBBC). The median age at the first diagnosis of mBBC was significantly younger than that at the first diagnosis of sBBC (p = 0.027). Patients diagnosed as having sBBC were more likely to have a positive family history (p = 0.047). The first tumors of mBBC were detected at a significantly earlier tumor stage compared with those of sBBC (p = 0.028). The concordance rates of histopathologic type in the first and second tumors were 60.7% and 58.0% in sBBC and mBBC, respectively. sBBC had a significantly poorer disease‐free survival than mBBC did (p = 0.001). BBC is a rare disease affecting the Chinese population. sBBC is associated with a greater prevalence of a family history of breast cancer and poorer prognosis, compared with mBBC.

BackgroundGenetic testing for breast cancer (BC) patients may shift the paradigm towards more personalized management and treatment strategies. While gene alterations may be ethnic-specific in breast cancer, our understanding of genetic epidemiology of BC remains mainly driven by data from Caucasian populations and further limited to selected handful of genes.MethodsWe collected whole blood samples from 356 BC patients at metastatic first line BC and primary stage IV disease at Beijing Cancer Hospital between Jan. 2013 to Dec. 2019. A comprehensive 600-gene cancer panel was used to detect germline variants in the covered genes with a median 300x sequencing depth. Variants were classified into pathogenic, likely pathogenic, variant of uncertain significance, likely benign and benign groups according to the ACMG/AMP Standards and Guidelines. Pathogenic and likely pathogenic variants were considered as deleterious mutations.ResultsThe median age of 356 BC patients was 49 years (range, 21-87 years) at the first diagnosis of BC. Deleterious germline mutations across 48 cancer-related genes were identified in 21.6% (77/356) of the patients. The most prevalent mutations were BRCA1/2 mutations (7.0%), followed by ATM and RAD50 mutations (1.4% each). In addition, patients with family history were more likely to carry BRCA1 mutations (P=0.04). Moreover, patients with triple-negative breast cancer (TNBC) were more likely to harbor BRCA1 mutations than those with HR+ or HER2+ breast cancer (P=0.006). While there was no significant survival difference observed in BRCA1/2 carriers relative to non-carriers, patients with DNA damage repair (DDR) gene mutations (mostly frequently BRCA, ATM, RAD50) had worse disease-free survival (P=0.02).ConclusionsThe most prevalent germline mutations in a large cohort of Chinese patients with advanced BC were BRCA1/2 mutations, followed by ATM and RAD50 mutations. In total, approximately 16.0% (57/356) of patients carry deleterious mutations in DDR pathway. Patients with breast or ovarian cancer family history were more likely to carry BRCA1/2 mutations, and ones with DDR mutations had worse survival. These findings suggest that DDR mutations are prevalent in Chinese BC patients who may potentially benefit from treatment with Poly (ADP-ribose) polymerase inhibitors.

Background. Due to extended life expectancy and recent improvements in surgical techniques, limb salvage has replaced amputation as the gold standard and is now performed in 90–95% of upper extremity malignancies. However, many of these salvage procedures are associated with significant postsurgical complications. In particular, the clavicula pro humero (CPH) procedure is associated with high rates of nonunion. We present our experience with upper extremity salvage using the free vascularized fibular flap (VFF) after failure or nonunion of the original CPH procedure in the pediatric population. Methods. Five patients under the age of 18 diagnosed with upper extremity sarcoma who underwent tumor resection with immediate CPH reconstruction complicated with nonunion, and subsequent revision with free VFF were included. Data on patient demographics, oncologic characteristics, surgical procedures, intraoperative details, postoperative complications, and time to graft union were recorded. Results. Five patients (average age = 8.4 years; range = 5–10 years at surgery date) underwent secondary limb salvage procedure with free VFF reconstruction following failed CPH reconstruction for proximal humeral osteosarcoma (n = 4) or Ewing sarcoma (n = 1). The mean follow-up was 3.7 years. Complications occurred in five patients (100%), with three patients requiring reoperation (60%). Four patients achieved graft union (average union time = 3.7 months) and successful limb reconstruction. Four patients were alive with no local recurrence of the disease. One patient did not achieve union and was lost to follow-up. Conclusion. Primary bone tumors in the pediatric population require wide surgical resection, and reconstruction often has high complication rates that can warrant further procedures. A free VFF is a viable option for upper extremity salvage after previously failed reconstructions because it provides vascularized tissue to a scarred tissue bed and allows for the replacement or augmentation of large bony defects.

Purpose: This study aims to evaluate the efficacy and safety of trastuzumab biosimilar (HLX02) in combination with pertuzumab and chemotherapy in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) after progression of trastuzumab. Materials and Methods: In this prospective, single-arm, phase II study, patients with HER2-positive MBC after progression of trastuzumab received pertuzuamb, HLX02, and chemotherapy in Beijing Cancer Hospital from March 2020 to December 2022. The primary endpoint was progression-free survival (PFS), and secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. The study was registered with ClinicalTrials.gov (NCT05188495). Results: A total of 45 patients were included in this study. Twelve patients (26.7%) were treated in second-line and 33 patients (73.3%) were in third-line and later setting. Eighty percent and 15.5% patients had previously received pyrotinib/lapatinib and T-DM1, respectively. With a median follow-up of 24.4 months (range, 1.2 to 43.9 months), the median PFS was 7.6 months (95% confidence interval, 4.3 to 10.9), OS was not reached, the ORR was 31.1%, and DCR was 91.1%. The treatment was well tolerated. Conclusion The combination of trastuzumab biosimilar HLX02, pertuzumab, and chemotherapy exhibited promising efficacy and a favorable safety profile as second- and beyond-line treatment in HER2-positive MBC. [ABSTRACT FROM AUTHOR]

Chronic wounds are a common and difficult problem in clinics. It is of great significance to develop effective and economical methods to treat chronic wounds. The present study aimed to investigate the effects of liposomal gel loaded with Pro-xylane intermediate on chronic wounds. Rat models of chronic wounds were created and verified. The pro-xylane intermediate (C-β-D-xylopyranoside-n-propan-2-one, PXYI) were encapsulated with liposomes and the liposomes containing PXYI were mixed with Pluronic F-127 gel to obtain PXYI liposomal gel (PXYI-LG). PXYI-LG has been applied to the rat's chronic wounds. The therapeutic effects were evaluated by wound healing rate and wound healing time. Additionally, Alamar Blue was used to detect the effect of PXYI on the proliferation of human skin fibroblasts (HF) and human immortalized epidermal cells (HaCaT). It was not found that PXYI alone could promote the proliferation of HF and HaCaT. From the 12th to the 32nd day, the wound healing rate of PXYI-LG group were significantly higher than that of the normal saline (NS) group (P<0.05). The number of days when the wound healing rate reached 90% was significantly shorter in the PXYI-LG group (21.8±1.8) than in the NS group (28.4±1.6) (P< 0.01). In summary, the results demonstrate that the PXYI-LG can promote chronic wound healing. [ABSTRACT FROM AUTHOR]