Neoadjuvant pertuzumab plus trastuzumab in combination with chemotherapy for human epidermal growth factor receptor 2 positive breast cancer: a real-world retrospective single-institutional study in China.

INTRODUCTION: Real-world studies on neoadjuvant dual anti-HER2 therapy combined with chemotherapy for breast cancer (BC) are scarce in China. This study aimed to evaluate the efficacy and safety of neoadjuvant dual anti-HER2 therapy combined with chemotherapy in a real-world setting. Moreover, differences in estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and proliferation cell nuclear antigen (Ki-67) expression pre- and post-neoadjuvant therapy were analyzed. METHODS: Clinical and pathological data of patients with HER2-positive BC who received neoadjuvant dual anti-HER2 therapy combined with chemotherapy at Liaoning Cancer Hospital & Institute, China, between September 2021 and September 2023, were retrospectively reviewed. RESULTS: Among 179 included patients, a pathologic complete response (pCR) was achieved in 109 patients (60.9%). The univariate analysis results indicated that the hormone receptor (HR) status (P = 0.013), HER2 status (P = 0.003), and cycles of targeted treatment (P = 0.035) were significantly correlated with pCR. Subsequent multivariable analysis showed that HR negative and HER2 status 3 + were independent predictive factors of pCR. Anemia was the most common adverse event (62.0%), and the most common grade 3-4 adverse event was neutropenia (6.1%). The differences in HER2 (34.5%) and Ki-67 (92.7%) expression between core needle biopsy and the residual tumor after neoadjuvant therapy were statistically significant, whereas the differences were insignificant in terms of ER or PR status. CONCLUSIONS: The combination of neoadjuvant trastuzumab and pertuzumab with chemotherapy showed good efficiency, and the toxic side effects were tolerable in patients with BC. In cases where pCR was not achieved after neoadjuvant therapy, downregulation of HER2 and Ki-67 expressions was observed.

Improving Photocatalytic Activity for Formaldehyde Degradation by Encapsulating C60 Fullerenes into Graphite-like C3N4 through the Enhancement of Built-in Electric Fields.

The photocatalytic degradation of formaldehyde by graphite-like C3N4 is one of the most attractive and environmentally friendly strategies to address the significant threat to human health posed by indoor air pollutants. Despite its potential, this degradation process still faces issues with suboptimal efficiency, which may be attributed to the rapid recombination of photogenerated excitons and the broad band gap. As a proof of concept, a series of graphite-like C3N4@C60 composites combining graphite-like C3N4 and C60 was developed via an in situ generation strategy. The obtained graphite-like C3N4@C60 composites exhibited a remarkable increase in the photocatalytic degradation efficiency of formaldehyde, of up to 99%, under visible light irradiation, outperforming pure graphite-like C3N4 and C60. This may be due to the composites' enhanced built-in electric field. Additionally, the proposed composites maintained a formaldehyde removal efficiency of 84% even after six cycles, highlighting their potential for indoor air purification and paving the way for the development of efficient photocatalysts.

Ultrasound-guided percutaneous injection of Pseudomonas aeruginosa-mannose sensitive hemagglutinin for treatment of chyle fistula following neck dissection: Two case reports.

RATIONALE: Chyle fistula is a rare but troublesome complication of neck dissection. Topical application of Pseudomonas aeruginosa-mannose sensitive hemagglutinin (PA-MSHA) injection has been reported as a novel, viable, and effective approach in the treatment of chyle fistula following neck dissection. However, there have been no reports regarding the treatment of chyle fistula using ultrasound (US)-guided percutaneous injection of PA-MSHA. PATIENT CONCERNS: We describe 2 patients with thyroid cancer who developed chyle fistula following neck dissection, which remained unresolved despite the use of conservative treatment. DIAGNOSES: Both the patients were diagnosed with chyle fistula by laboratory testing, which showed that drainage fluid triglyceride concentration was >100 mg/dL. INTERVENTIONS: When conservative treatment failed, a 2 mL undiluted PA-MSHA preparation was percutaneously injected at the effusion site of the left supraclavicular area under US guidance with aseptic technique. Concomitantly, the drainage tube was clamped for at least 30 minutes. OUTCOMES: Chyle fistula in both patients were successfully resolved with this technique within 2 or 4 days, without notable side effects. LESSONS: US-guided percutaneous injection of PA-MSHA is a simple and effective method to treat chyle fistula following neck dissection, which may serve as a useful addition to the medical treatment for cervical chyle fistula.

miR-146b-5p Plays a Critical Role in the Regulation of Autophagy in ∆per Brucella melitensis-Infected RAW264.7 Cells.

Brucella-caused brucellosis is one of the most widespread worldwide zoonoses. Lipopolysaccharide (LPS) of Brucella, which functions as pathogen-associated molecular patterns (PAMPs), is an important virulence factor that elicits protective antibodies. Per of B. melitensis is involved in the biosynthesis of the O-side chain of LPS. Autophagy is a crucial element of the innate immune response against intracellular pathogens including Brucella. In this study, we observed that autophagy was inhibited in RAW264.7 cells infected with Brucella melitensis ∆per. And, a high-throughput array-based screen and qRT-PCR validation were performed to identify the differentially expressed miRNAs in RAW264.7 cells infected with B. melitensis M5-90 ∆per. The results suggested that mmu-miR-146a-5p, mmu-miR-155-5p, mmu-miR-146b-5p, and mmu-miR-3473a were upregulated and mmu-miR-30c-5p was downregulated. During B. melitensis M5-90 ∆per infection, the increased expression of miR-146b-5p inhibited the autophagy activation in RAW264.7 cells. Using a bioinformatics approach, Tbc1d14 was predicted to be a potential target of miR-146b-5p. The results of a luciferase reporter assay indicated that miR-146b-5p directly targeted the 3'-UTR of Tbc1d14, and the interaction between miR-146b-5p and the 3'-UTR of Tbc1d14 was sequence-specific. High-throughput RNA-Seq-based screening was performed to identify differentially expressed genes in Tbc1d14-expressing RAW264.7 cells, and these were validated by qRT-PCR. Among the differentially expressed genes, four autophagy associated genes, IFNγ-inducible p47 GTPase 1 (IIGP1), nuclear receptor binding protein 2 (Nrbp2), transformation related protein 53 inducible nuclear protein 1 (Trp53inp1), and immunity-related GTPase family M member 1 (Irgm1), were obtained. Our findings provide important insights into the functional mechanism of LPS of B. melitensis.

Upregulation of Immune Process-Associated Genes in RAW264.7 Macrophage Cells in Response to Burkholderia pseudomallei Infection.

Melioidosis is a severe and fatal tropical zoonosis, which is triggered by Burkholderia pseudomallei. To better understand the host's response to infection of B. pseudomallei, an RNA-Seq technology was used to confirm differentially expressed genes (DEGs) in RAW264.7 cells infected with B. pseudomallei. In total, 4668 DEGs were identified across three time points (4, 8, and 11 hours after infection). Short Time-Series Expression Miner (STEM) analysis revealed the temporal gene expression profiles and identified seven significant patterns in a total of 26 profiles. Kyoto Encyclopedia of Genes and Genomes (KEGG) was utilized to confirm significantly enriched immune process-associated pathways, and 10 DEGs, including Ccl9, Ifnb1, Tnfα, Ptgs2, Tnfaip3, Zbp1, Ccl5, Ifi202b, Nfkbia, and Nfkbie, were mapped to eight immune process-associated pathways. Subsequent quantitative real-time PCR assays confirmed that the 10 DEGs were all upregulated during infection. Overall, the results showed that B. pseudomallei infection can initiate a time-series upregulation of immune process-associated DEGs in RAW264.7 macrophage cells. The discovery of this article helps us better understand the biological function of the immune process-associated genes during B. pseudomallei infection and may aid in the development of prophylaxis and treatment protocols for melioidosis.

Alterations of microRNAs and their predicted targeting mRNAs expression in RAW264.7 macrophages infected with Omp25 mutant Brucella melitensis.

Brucellosis is a worldwide zoonosis caused by Brucella species and represents a serious threat to both human and animal health. Omp25 is an important immunogenic and protective antigen in Brucella species; however, the functional mechanism of Omp25 in macrophages has not yet been elucidated. Here, we constructed a Brucella melitensis omp25 deletion mutant (M5-90-Δ omp25) and performed microRNA (miRNA) profiling of infected RAW264.7 cells. Eight differentially expressed miRNAs ( mmu-miR-146a-5p, mmu-miR-155-5p, mmu-miR-3473a, mmu-miR-149-3p, mmu-miR-671-5p, mmu-miR-1224-5p, mmu-miR-1895, and mmu-miR-5126) were identified, with quantitative real-time PCR (qRT-PCR) analysis confirming the up-regulation of mmu-miR-146-a-5p and mmu-miR-155-5p and down-regulation of mmu-miR-149-3p and mmu-miR-5126. mRNA profiling of B. melitensis M5-90-Δo mp25-infected RAW264.7 cells identified 967 differentially expressed genes (DEGs) (fold change ≥ 2). Among these, we focused on genes that were predicted by TargetScan, miRanda, and PicTar to be the potential targets of the differentially expressed miRNAs. The results suggested that 17 separate genes are potentially targeted by mmu-miR-149-3p, with one of these genes, Tbr1, also targeted by mmu-miR-5126. qRT-PCR analysis confirmed the up-regulation of nine of the predicted target genes. Our findings provide important information about the functional molecules in host cells, including miRNA and their target genes, affected by Omp25 from Brucella. This information is particularly valuable for the prophylaxis and treatment of brucellosis.

CD14 gene silencing alters the microRNA expression profile of RAW264.7 cells stimulated by Brucella melitensis infection.

Innate recognition of Brucella spp. is a key step in the activation of inflammation. CD14 binds PAMPs and is involved in LPS-induced pro-inflammatory cytokine release. Previously we showed that knock down of CD14 in RAW264.7 macrophages disrupted Brucella-host interactions. However, its effect on the macrophage microRNA (miRNA) expression profile, especially after stimulation by Brucella infection, is still unclear. To identify miRNAs involved in the macrophage response to Brucella infection, we performed miRNA expression profiling of CD14 knock-down RAW264.7 (224.3) macrophages infected with Brucella melitensis, and demonstrated, for the first time, that CD14 knock down significantly up-regulated the expression of mmu-miR-199a-3p and mmu-miR-183-5p in these conditions. These miRNAs have a well-characterized association with the target genes involved in immune response, inflammatory response, innate immune response, apoptosis processes, anti-apoptosis, cytokine production and cytokine-mediated signaling pathways. Among the 104 inflammation-related candidate target genes of mmu-miR-199a-3p and mmu-miR-183-5p in the 224.3+ B. melitensis group cells, the expression of the Cbl-b, a potential target of mmu-miR-199a-3p, was confirmed to be down-regulated using qRT-PCR and Western blot analysis. Our findings suggest that CD14 functions in the Brucella-host interaction may be through altered miRNA expression, and regulation of Cbl-b proteins.

Transcriptome Analysis of HepG2 Cells Expressing ORF3 from Swine Hepatitis E Virus to Determine the Effects of ORF3 on Host Cells.

Hepatitis E virus- (HEV-) mediated hepatitis has become a global public health problem. An important regulatory protein of HEV, ORF3, influences multiple signal pathways in host cells. In this study, to investigate the function of ORF3 from the swine form of HEV (SHEV), high-throughput RNA-Seq-based screening was performed to identify the differentially expressed genes in ORF3-expressing HepG2 cells. The results were validated with quantitative real-time PCR and gene ontology was employed to assign differentially expressed genes to functional categories. The results indicated that, in the established ORF3-expressing HepG2 cells, the mRNA levels of CLDN6, YLPM1, APOC3, NLRP1, SCARA3, FGA, FGG, FGB, and FREM1 were upregulated, whereas the mRNA levels of SLC2A3, DKK1, BPIFB2, and PTGR1 were downregulated. The deregulated expression of CLDN6 and FREM1 might contribute to changes in integral membrane protein and basement membrane protein expression, expression changes for NLRP1 might affect the apoptosis of HepG2 cells, and the altered expression of APOC3, SCARA3, and DKK1 may affect lipid metabolism in HepG2 cells. In conclusion, ORF3 plays a functional role in virus-cell interactions by affecting the expression of integral membrane protein and basement membrane proteins and by altering the process of apoptosis and lipid metabolism in host cells. These findings provide important insight into the pathogenic mechanism of HEV.

Characterizing air temperature changes in the Tarim Basin over 1960-2012.

There has been evidence of warming rate varying largely over space and between seasons. However, little has been done to evaluate the spatial and temporal variability of air temperature in the Tarim Basin, northwest China. In this study, we collected daily air temperature from 19 meteorological stations for the period of 1960-2012, and analyzed annual mean temperature (AMT), the annual minimum (T min) and maximum temperature (Tmax), and mean temperatures of all twelve months and four seasons and their anomalies. Trend analyses, standard deviation of the detrended anomaly (SDDA) and correlations were carried out to characterize the spatial and temporal variability of various mean air temperatures. Our data showed that increasing trend was much greater in the T min (0.55°C/10a) than in the AMT (0.25°C/10a) and Tmax (0.12°C/10a), and the fluctuation followed the same order. There were large spatial variations in the increasing trends of both AMT (from -0.09 to 0.43 °C/10a) and T min (from 0.15 to 1.12°C/10a). Correlation analyses indicated that AMT had a significantly linear relationship with T min and the mean temperatures of four seasons. There were also pronounced changes in the monthly air temperature from November to March at decadal time scale. The seasonality (i.e., summer and winter difference) of air temperature was stronger during the period of 1960-1979 than over the recent three decades. Our preliminary analyses indicated that local environmental conditions (such as elevation) might be partly responsible for the spatial variability, and large scale climate phenomena might have influences on the temporal variability of air temperature in the Tarim Basin. In particular, there was a significant correlation between index of El Niño-Southern Oscillation (ENSO) and air temperature of May (P = 0.004), and between the index of Pacific Decadal Oscillation (PDO) and air temperature of July (P = 0.026) over the interannual to decadal time scales.

[Effects of drip irrigation under mulching on cotton root and shoot biomass and yield].

By using bidirectional sampling method with soil drill, the effects of different amounts of drip irrigation (2618, 2947, 3600 and 4265 m3 x hm(-2)) under mulching on the root distribution, aboveground growth, and yield of cotton was studied in field. The results indicated that irrigation amount affected the root and shoot growth significantly. In all irrigation treatments, cotton root was mainly distributed in mulched area, occupying 60.65%-73.45% of total root biomass, while only 39.35%-26.55% was distributed in bare area. Water stress increased rooting depth, root biomass, and the extent of lateral rooting. Significant differences were observed in the biological characteristics and the biomass accumulation and allocation of cotton plant among different irrigation treatments. Over-irrigation (4265 m3 x hm(-2)) increased plant height, width of inverse fourth leaf, and amounts of branch and bud, and thus, accelerated biomass accumulation rate. Over-irrigation also increased the root/shoot ratio and the proportion of biomass allocated to vegetative organs, but increased the fruit abscission rate and therefore reduced the economic yield. It was suggested that both excessive soil moisture content and water stress could affect the biomass accumulation and allocation in different cotton organs and at various life stages. Under the conditions of our experiment, 3600 m3 x hm(-2) was the optimal irrigation amount.