Hepatocyte-derived Igκ promotes HCC progression by stabilizing electron transfer flavoprotein subunit α to facilitate fatty acid ß-oxidation.

BACKGROUND: Lipid metabolism dysregulation is a key characteristic of hepatocellular carcinoma (HCC) onset and progression. Elevated expression of immunoglobulin (Ig), especially the Igκ free light chain with a unique Vκ4-1/Jκ3 rearrangement in cancer cells, is linked to increased malignancy and has been implicated in colon cancer tumorigenesis. However, the role of Igκ in HCC carcinogenesis remains unclear. The aim of this study was to elucidate the pivotal roles of hepatocyte-derived Igκ in HCC development. METHODS: The rearrangement sequence and expression level of hepatocyte-derived Igκ in HCC cells were determined via RT-PCR, Sanger sequencing, immunohistochemistry, and western blot analysis. The function of Igκ in HCC tumorigenesis was assessed by silencing Igκ using siRNA or gRNA in various HCC cell lines. To assess the role of Igκ in HCC pathogenesis in vivo, a mouse model with hepatocyte-specific Igκ knockout and diethylnitrosamine (DEN) and carbon tetrachloride (CCL4)-induced HCC was utilized. The molecular mechanism by which Igκ affects HCC tumorigenesis was investigated through multiomics analyses, quantitative real-time PCR, immunoprecipitation, mass spectrometry, immunofluorescence, and metabolite detection. RESULTS: We confirmed that Igκ, especially Vκ4-1/Jκ3-Igκ, is highly expressed in human HCC cells. Igκ depletion inhibited HCC cell proliferation and migration in vitro, and hepatocyte-specific Igκ deficiency ameliorated HCC progression in mice with DEN and CCL4-induced HCC in vivo. Mechanistically, Vκ4-1/Jκ3-Igκ interacts with electron transfer flavoprotein subunit α (ETFA), delaying its protein degradation. Loss of Igκ led to a decrease in the expression of mitochondrial respiratory chain complexes III and IV, resulting in aberrant fatty acid ß-oxidation (FAO) and lipid accumulation, which in turn inhibited HCC cell proliferation and migration. CONCLUSION: Our findings indicate that the Igκ/ETFA axis deregulates fatty acid ß-oxidation, contributing to HCC progression, which suggests that targeting fatty acid metabolism may be an effective HCC treatment strategy. The results of this study suggest that hepatocyte-derived Vκ4-1/Jκ3-Igκ may serve as a promising therapeutic target for HCC.

[Characteristics, Sources Analysis, and Environmental Impacts of VOCs Based on Photochemical Loss in Summer in Zhengzhou].

To clarify the pollution characteristics and sources of atmospheric VOCs in Zhengzhou City in the summer, multi-site offline sampling and laboratory analyses of atmospheric VOCs in Zhengzhou were carried out in August 2022. The observed and initial VOC volume fraction levels, OFP, SOAFP, and sources were compared. During the study period, the average values of three-site observation and initial φ（VOCs） during the study period were （31.83 ±13.51）×10-9 and （35.92 ±15.30）×10-9,respectively. Olefins （52.5 %） and aromatic hydrocarbons （29.7 %） were the components with a higher photochemical loss rate, and the spatial variations of the observed TVOCs concentration at each site were： Zhengzhou University （ZZU） > Gangli Reservoir （GLR） > Jingkaiqu （JKQ）, and the concentrations of alkanes and OVOCs at each site were higher. Olefins and aromatic hydrocarbons were the components that contributed greatly to the formation of O3 and SOA. Motor vehicle sources, solvent-use sources, and industrial sources were the main contributing sources of atmospheric VOCs in Zhengzhou. Compared with the source analysis results based on the initial concentration, the contribution rates of motor vehicle sources, industrial sources, and solvent use sources were relatively high, and the contribution rates of combustion sources, plant sources, and oil and gas volatilization sources were relatively low.

A Comparative Analysis of the Immunoglobulin Repertoire in Leukemia Cells and B Cells in Chinese Acute Myeloid Leukemia by High-Throughput Sequencing.

It is common knowledge that immunoglobulin (Ig) is produced by B lymphocytes and mainly functions as an antibody. However, it has been shown recently that myeloblasts from acute myeloid leukemia (AML) could also express Ig and that AML-Ig played a role in leukemogenesis and AML progression. The difference between Ig from myeloblasts and B cells has not been explored. Studying the characteristics of the Ig repertoire in myeloblasts and B cells will be helpful to understand the function and significance of AML-Ig. We performed 5' RACE-related PCR coupled with PacBio sequencing to analyze the Ig repertoire in myeloblasts and B cells from Chinese AML patients. Myeloblasts expressed all five classes of IgH, especially Igγ, with a high expression frequency. Compared with B-Ig in the same patient, AML-Ig showed different biased V(D)J usages and mutation patterns. In addition, the CDR3 length distribution of AML-Ig was significantly different from those of B-Ig. More importantly, mutations of AML-IgH, especially Igµ, Igα, and Igδ, were different from that of B-IgH in each AML patient, and the mutations frequently occurred at the sites of post-translational modification. AML-Ig has distinct characteristics of variable regions and mutations, which may have implications for disease monitoring and personalized therapy.

The Structure Characteristics and Function of Non B Cell-Derived Immunoglobulin.

According to classical immunology theory, immunoglobulin (Ig) is exclusively produced by differentiated B lymphocytes, which exhibit a typical tetrapeptide chain structure and are predominantly present on the surface of B cells and in bodily fluids. B-Ig is one of the critical effector molecules for humoral immune responses specifically recognising antigens and eliminating them. However, mounting evidence has demonstrated that Ig is widely expressed in non B lineage cells, especially malignant ones (referred to as non B-Ig). Interestingly, non B-Ig mainly resides in the cytoplasm and secretion, but to some extent on the cell surface. Furthermore non B-Ig not only displays a tetrapeptide chain structure but also shows free heavy chains and free light chains (FLCs). Additionally, Ig derived from non B cancer cell typically displays unique glycosylation modifications. Functionally, non B-Ig demonstrated diversity and versatility, showing antibody activity and cellular biological activity, such as promoting cell proliferation and survival, and it is implicated in cancer progression and some immune-related diseases, such as renal diseases.

[A multicenter study of neonatal stroke in Shenzhen, China]. / 深圳市新生儿脑卒中多中心现况调查.

OBJECTIVES: To investigate the incidence rate, clinical characteristics, and prognosis of neonatal stroke in Shenzhen, China. METHODS: Led by Shenzhen Children's Hospital, the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022. The incidence, clinical characteristics, treatment, and prognosis of neonatal stroke in Shenzhen were analyzed. RESULTS: The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137, 1/6 060, and 1/7 704, respectively. Ischemic stroke accounted for 75% (27/36); boys accounted for 64% (23/36). Among the 36 neonates, 31 (86%) had disease onset within 3 days after birth, and 19 (53%) had convulsion as the initial presentation. Cerebral MRI showed that 22 neonates (61%) had left cerebral infarction and 13 (36%) had basal ganglia infarction. Magnetic resonance angiography was performed for 12 neonates, among whom 9 (75%) had involvement of the middle cerebral artery. Electroencephalography was performed for 29 neonates, with sharp waves in 21 neonates (72%) and seizures in 10 neonates (34%). Symptomatic/supportive treatment varied across different hospitals. Neonatal Behavioral Neurological Assessment was performed for 12 neonates (33%, 12/36), with a mean score of (32±4) points. The prognosis of 27 neonates was followed up to around 12 months of age, with 44% (12/27) of the neonates having a good prognosis. CONCLUSIONS: Ischemic stroke is the main type of neonatal stroke, often with convulsions as the initial presentation, involvement of the middle cerebral artery, sharp waves on electroencephalography, and a relatively low neurodevelopment score. Symptomatic/supportive treatment is the main treatment method, and some neonates tend to have a poor prognosis.

Regulation of Photophysical Behaviors in Hyperbranched Aggregation-Induced Emission Polymers for Reactive Oxygen Species Scavenging.

Developing nonconjugated materials with large Stokes shifts is highly desired. In this work, three kinds of hyperbranched aggregation-induced emission (AIE) polymers with tunable n/π electronic effects were synthesized. HBPSi-CBD contains alkenyl groups in the backbone and possesses a promoted n-π* transition and red-shifted emission wavelength with a large Stokes shift of 186 nm. Experiments and theoretical simulations confirmed that the planar π electrons in the backbone are responsible for the red-shifted emission due to the strong through-space n···π interactions and restricted backbone motions. Additionally, the designed HBPSi-CBD could be utilized as an ROS scavenger after coupling with l-methionine. The HBPSi-Met exhibits remarkable ROS scavenging properties with a scavenging capacity of 77%. This work not only gains further insight into the structure-property relationship of nonconjugated hyperbranched AIE polymers but also provides a promising ROS-scavenging biomaterial for the treatment of ROS-related diseases.

Recent advances in cellulosic materials for aqueous zinc-ion batteries: An overview.

Aqueous zinc-ion batteries (AZIBs), with the merits of high safety, environmental friendliness, abundant resources, and competitive energy density are recognized as a promising secondary battery technology and are anticipated to be a great alternative to organic lithium-ion batteries (LIBs). However, the commercial application of AZIBs is severely hindered by intractable issues, including high desolvation barrier, sluggish ion transport kinetics, growth of zinc dendrite, and side reactions. Nowadays, cellulosic materials are frequently employed in the fabrication of advanced AZIBs, because of the intrinsically excellent hydrophilicity, strong mechanical strength, sufficient active groups, and unexhaustible production. In this paper, we start from reviewing the success and dilemma of organic LIBs, followed by introducing the next-generation power source of AZIBs. After summarizing the features of cellulose with great potential in advanced AZIBs, we comprehensively and logically analyze the applications and superiorities of cellulosic materials in AZIBs electrodes, separators, electrolytes, and binders with an in-depth perspective. Finally, a clear outlook is delivered for future development of cellulose in AZIBs. Hopefully, this review can offer a smooth avenue for future direction of AZIBs by means of cellulosic material design and structure optimization.

The whole-cell proteome shows the characteristics of macrolides-resistant Bordetella pertussis in China linked to the biofilm formation.

The macrolides-resistant Bordetella pertussis (MR-Bp) isolates in China evolved from the ptxP1/fhaB3 allele and rapidly became predominant, suggestive of an adaptive transmission ability. This was different from the global prevalent ptxP3 strains, in which MR-Bp was rarely reported. The study aimed to determine the underlying mechanism responsible for fitness and resistance in these two strains. We identify proteomic differences between ptxP1/fhaB3 and ptxP3/fhaB1 strains using tandem mass tag (TMT)-based proteomics. We then performed in-depth bioinformatic analysis to determine differentially expressed genes (DEGs), followed by gene ontology (GO), and protein-protein interaction (PPI) network analysis. Further parallel reaction monitoring (PRM) analysis confirmed the expression of four target proteins. Finally, the crystal violet method was used to determine biofilm-forming ability. The results showed that the main significantly different proteins between the two represent isolates were related to biofilm formation. Furthermore, we have confirmed that ptxP1/fhaB3 showed hyperbiofilm formation in comparison with ptxP3/fhaB1. It is suggested that the resistance and adaptability of ptxP1/fhaB3 strains may be related to the formation of biofilm through proteomics. In a word, we determined the significantly different proteins between the ptxP1/fhaB3 and ptxP3/fhaB1 strains through whole-cell proteome, which were related to biofilm formation.

CCDC134 facilitates T cell activation through the regulation of early T cell receptor signaling.

Modulation of surface T cell antigen receptor (TCR) expression is crucial for proper T cell development and maintenance of mature T cell function at steady state and upon stimulation. We previously determined that CCDC134 (coiled-coil domain containing 134), a cytokine-like molecule that served as a potential member of the γc cytokine family, contributes to antitumor responses by augmenting CD8+ T cell-mediated immunity. Here we show that T cell-specific deletion of Ccdc134 decreased peripheral mature CD4+ and CD8+ T cells, which resulted in impaired T cell homeostasis. Moreover, Ccdc134-deficient T cells exhibited an attenuated response to TCR stimulation in vitro, showing lower activation and proliferative capacity. This was further reflected in vivo, rendering mice refractory to T cell-mediated inflammatory and antitumor responses. More importantly, CCDC134 is associated with TCR signaling components, including CD3ϵ, and attenuated TCR signaling in Ccdc134-deficient T cells via altered CD3ϵ ubiquitination and degradation. Taken together, these findings suggest a role for CCDC134 as a positive regulator of TCR-proximal signaling and provide insight into the cell-intrinsic functional consequences of Ccdc134 deficiency in the attenuation of T cell-mediated inflammatory and antitumor responses.

Disparities in COVID-19 clinical studies from high-income and low-and middle-income countries.

OBJECTIVES: To examine the disparities between COVID-19 studies conducted in high-income countries (HICs) and low-and middle-income countries (LMICs). METHODS: We used the International Clinical Trials Registry Platform to identify COVID-19-related studies registered from December 31, 2019 to December 31, 2021. The World Bank definition was used to classify countries as high-, upper-middle-, lower-middle-, and low-income. The last three were considered to be LMICs. We examined the disparities in response speed, classification of medicines and vaccines, and registration and results reporting compliance between COVID-19 studies conducted in HICs and LMICs. RESULTS: We included 12,396 COVID-19 studies, with 6631 (53.5%) from HICs. HIC-registered studies reached a peak of 1039 in April 2020, whereas LMICs had only 440 studies. Of the 6969 interventional trials, those from HICs showed higher registration compliance (2199, 62.3% vs 1979, 57.6%, P <0.001) and results reporting compliance (hazard ratio 0.39, 95% confidence interval 0.28-0.55, P < 0.001) than LMICs. HICs also conducted significantly more small-molecule drug (956, 57.5% vs 868, 41.2%, P <0.001) and messenger RNA vaccine trials (135, 32.9% vs 19, 4.8%, P <0.001) than LMICs. CONCLUSION: HICs conducted COVID-19 trials with faster response speed and higher registration and publication compliance and produced more innovative pharmaceutical and vaccine products to combat COVID-19 than LMICs.

Enhanced osmotic energy conversion through bacterial cellulose based double-network hydrogel with 3D interconnected nanochannels.

Hydrogel with 3D networks have shown great potential for ion transportation and energy conversion. However, the micron size pores of hydrogel greatly limit the ion selectivity and energy conversion performance. Here, we report a bacterial cellulose (BC) derived hydrogel membrane with double-network (DN) and tailored ion transport channels by rationally filling acrylic acid (AAc)-co-acrylamide (AAm)-co-methyl methacrylate (MMA) polymers into BC hydrogel micropores. Fabricated AAM/BC DN hydrogel membrane displays a unique hierarchical interconnected porous structure and 3D cation transport channels. From the results, the maximum power density reached up to 7.63 W·m-2 at 50-fold salinity gradient under alkaline conditions (pH 11). Interestingly, the power density of 45.5 W·m-2 was achieved through acid-base neutralization reaction. Furthermore, hydrogel successfully obtained a power density of 28.4 W·m-2 from a mixed system of paper black liquor wastewater/seawater. The results of this investigation suggested the enormous potential of BC-based nanofluidic membrane in sustainable osmotic energy conversion.

[Variation Characteristics and Source Apportionment of Atmospheric VOCs at Multi-sites in Zhengzhou].

From July 2020 to June 2021, monthly offline sampling of atmospheric VOCs was carried out and analyzed at three urban sites and one suburban site in Zhengzhou. Then, the volume fraction levels, composition characteristics, reactivity, and source apportionment of atmospheric VOCs were discussed. The results showed that the volume fraction of atmospheric VOCs in Zhengzhou was (37.50±14.30)×10-9 during the sampling period, and the proportion of components was represented by alkanes (33%)>OVOCs (24%)>halogenated hydrocarbons (23%)>aromatic hydrocarbons (8%)>alkenes (7%)>alkynes (4%)>sulfides (1%). The seasonal variation characteristics were winter>autumn>summer>spring, and the monthly average value of VOCs had the highest value in January and the lowest value in May; the spatial variation characteristics were Zhengzhou University (ZD)>Jiancezhan (JCZ)>Jingkaiqu (JKQ)>Gangli Reservoir (GLR). The average·OH loss rate (L·OH) was 4.24 s-1, and the average ozone formation potential (OFP) was 172.27 µg·m-3; the top ten species of L·OH and OFP at each site and in each season were dominated by alkenes, OVOCs, and aromatic hydrocarbons. The results of positive matrix factorization (PMF) showed that the main sources of VOCs were vehicle emissions (28%), solvent utilization (24%), industrial emissions (24%), and oil and gas volatilization (19%) and plant emissions (5%).

Efficacy and safety of pyrotinib-containing regimen in the patients with HER2-positive metastatic breast cancer: A multicenter real-world study.

BACKGROUND: Pyrotinib, a novel irreversible epidermal growth factor receptor 2 (EGFR)/HER2 dual tyrosine kinase inhibitor, has shown promising antitumor efficacy with tolerable toxicity in HER2-positive metastatic breast cancer (MBC) in several clinical trials. However, the clinical trials do not usually well reflect the patients in real clinical settings. Despite several small-sample studies in real world, the data on pyrotinib as first-line and third-or-later-line treatment and the efficacy comparison of pyrotinib combined with different regimens are still lacking. Therefore, this study aimed to investigate the efficacy and safety of pyrotinib for the HER2-positive MBC in real world to replenish more comprehensive data. METHODS: A total of 172 HER2-positive MBC patients treated with pyrotinib-based therapy were recruited from multiple centers in nonclinical trial settings from September 2017 to June 2020. RESULTS: The median progression-free survival (mPFS) of 172 patients was 8.83 months. The patients, receiving first-line pyrotinib treatment, had the longest mPFS (20.93 months) compared with those receiving second-line (8.67 months, p = 0.0339) and third-or-later-line (7.13 months, p = 0.0075) treatments, respectively. Prior treatment with lapatinib (p = 0.012) and site of metastasis (visceral vs. nonvisceral) (p = 0.033) were the independent prognostic factors for PFS. The prior treatment with lapatinib compared with lapatinib-native treatment (5.96 vs. 10.97 months, p = 0.0036) and those with visceral metastasis compared with nonvisceral metastasis (8.40 vs. 23.70 months, p = 0.0138) had worse mPFS. Among 146 patients evaluated for efficacy, 2.1%, 58.9%, and 32.9% showed complete response, partial response, and stable disease, respectively. Adverse events occurred in 92.4% of the patients with 33.3% Grade 3 and higher adverse events and diarrhea (57.0%), anemia (44.8%), and leukopenia (40.7%) as the most frequent ones. CONCLUSIONS: Pyrotinib-containing regimen could effectively treat HER2-positive MBC with acceptable toxicity, including the patients who progressed after lapatinib treatment and with brain metastasis.

Evaluation of a Functional Single Nucleotide Polymorphism of the SARS-CoV-2 Receptor ACE2 That Is Potentially Involved in Long COVID.

Since the occurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019, SARS-CoV-2 has led to a global coronavirus disease 2019 (COVID-19) pandemic. A better understanding of the SARS-CoV-2 receptor ACE2 at the genetic level would help combat COVID-19, particularly for long COVID. We performed a genetic analysis of ACE2 and searched for its common potential single nucleotide polymorphisms (SNPs) with minor allele frequency >0.05 in both European and Chinese populations that would contribute to ACE2 gene expression variation. We thought that the variation of the ACE2 expression would be an important biological feature that would strongly affect COVID-19 symptoms, such as "brain fog", which is highlighted by the fact that ACE2 acts as a major cellular receptor for SARS-CoV-2 attachment and is highly expressed in brain tissues. Based on the human GTEx gene expression database, we found rs2106809 exhibited a significant correlation with the ACE2 expression among multiple brain and artery tissues. This expression correlation was replicated in an independent European brain eQTL database, Braineac. rs2106809*G also displays significantly higher frequency in Asian populations than in Europeans and displays a protective effect (p = 0.047) against COVID-19 hospitalization when comparing hospitalized COVID-19 cases with non-hospitalized COVID-19 or SARS-CoV-2 test-negative samples with European ancestry from the UK Biobank. Furthermore, we experimentally demonstrated that rs2106809*G could upregulate the transcriptional activity of ACE2. Therefore, integrative analysis and functional experiment strongly support that ACE2 SNP rs2106809 is a functional brain eQTL and its potential involvement in long COVID, which warrants further investigation.

[Trend Changes in Ozone Pollution and Sensitivity Analysis of Ozone in Henan Province].

Based on air quality station data and satellite remote sensing data, the interannual variation characteristics and seasonal variation trends of near-surface ozone (O3) in Henan province were studied, and the variation in O3 sensitivity was analyzed. The results showed that the O3 concentration near the surface of Henan province increased first and then decreased from 2015 to 2020. The highest O3 concentration was found in 2018, and the annual mean of the maximum daily 8 h moving mean (MDA8) of O3 was 110.70 µg·m-3. The difference in MDA8 values among different stations gradually decreased. From 2015 to 2020, the average monthly MDA8 in Henan province showed an upward trend, with a growth rate of 2.46 µg·(m3·a)-1. According to the MK trend test, except for in Luohe, Nanyang, and Pingdingshan, the rising trend in other cities was significant (P<0.05). The concentration of MDA8 in the four seasons also showed an increasing trend during the 6 years as follows:autumn (19.31%)>winter (17.09%)>spring (16.82%)>summer (7.24%). From 2015 to 2019, the high value of tropospheric NO2 was concentrated in the northwest of Henan province, and the concentration showed a decreasing trend with a decreasing rate of 0.34×1015 molecules·(cm2·a)-1, whereas the tropospheric HCHO showed a slow rising trend with an annual growth rate of 0.19×1015 molecules·(cm2·a)-1, with a higher concentration in the northern urban area. The O3 sensitivity control area from 2015 to 2019 showed that most of the eastern part of Henan province belonged to the VOCs limited category.

Potential Predictive and Prognostic Value of Biomarkers Related to Immune Checkpoint Inhibitor Therapy of Triple-Negative Breast Cancer.

As an aggressive subtype of breast cancer, triple-negative breast cancer (TNBC) is associated with poor prognosis and lack of effective therapy, except chemotherapy. In recent years, immunotherapy based on immune checkpoint (IC) inhibition has emerged as a promising therapeutic strategy in TNBC. TNBC has more tumor-infiltrating lymphocytes (TILs) and higher rate of mutation and programmed cell death ligand-1 (PD-L1) expression than other subtypes of breast cancer have. However, previous studies have shown that monotherapy has little efficacy and only some TNBC patients can benefit from immunotherapy. Therefore, it is important to identify biomarkers that can predict the efficacy of IC inhibitors (ICIs) in TNBC. Recently, various biomarkers have been extensively explored, such as PD-L1, TILs and tumor mutational burden (TMB). Clinical trials have shown that PD-L1-positive patients with advanced TNBC benefit from ICIs plus chemotherapy. However, in patients with early TNBC receiving neoadjuvant therapy, PD-L1 cannot predict the efficacy of ICIs. These inconsistent conclusions suggest that PD-L1 is the best to date but an imperfect predictive biomarker for efficacy of ICIs. Other studies have shown that advanced TNBC patients with TMB ≥10 mutations/Mb can achieve clinical benefits from pembrolizumab. TILs also have potential predictive value in TNBC. Here, we select some biomarkers related to ICIs and discuss their potential predictive and prognostic value in TNBC. We hope these biomarkers could help to identify suitable patients and realize precision immunotherapy.

[Characteristics and Source Apportionment of Vehicular VOCs Emissions in a Tunnel Study].

To explore the emission characteristics of volatile organic compounds (VOCs) from vehicular exhaust sources and evaporative sources with ethanol gasoline (E10) as the main fuel, VOCs sampling campaigns were carried out in the north third ring tunnel of Zhengzhou city for two consecutive weeks in December 2019. In addition, the characteristics of traffic flow and environmental information were also monitored in the tunnel. Firstly, 106 VOCs were quantified using gas chromatography/mass spectrometry (GC/MS), and then source apportionment of VOCs in the tunnel was carried out using a positive matrix factorization (PMF5.0)-chemical mass balance (CMB8.2) composite model. Finally, the ozone formation potential (OFP) and secondary organic aerosol formation potential (SOAFP) of vehicle exhaust sources and evaporative sources were analyzed using the maximum incremental reactivity (MIR) and fractional aerosol coefficient (FAC). The results showed that ρ(VOCs) in the tunnel was (2794.5±147.4) µg·m-3 during the experiment, among which halogenated hydrocarbons[(32.4±2.0)%] accounted for the highest proportion, followed by aromatic hydrocarbons[(27.5±0.6)%] and alkanes[(23.3±0.8)%]. Source apportionment of vehicular VOCs showed that exhaust emissions (62.5%)>evaporative emissions (37.5%), whereas the contribution of OFP was that exhaust emissions (71.9%)>evaporative emissions (28.1%), and the contribution of SOAFP was that exhaust emissions (75.8%)>evaporative emissions (24.2%). The dominant components of OFP in evaporative sources were m,p-diethylbenzene, isoprene, and trans-2-pentene, whereas m,p-diethylbenzene, m,p-xylene, and 1,2,3-trimethylbenzene were the dominant components of SOAFP. The major components of OFP in exhaust sources were m,p-xylene, 1,2,4-trimethylbenzene, and 1,3,5-trimethylbenzene, whereas m,p-xylene, m,p-diethylbenzene, and 1,3,5-trimethylbenzene were the dominant components of SOAFP. In regions where ethanol gasoline is used, special attention should be paid not only to the exhaust emissions control but also to strengthening the emissions reduction of VOCs from vehicle evaporative sources, especially the high active components such as aromatic hydrocarbons and alkenes.

Durable Effect of Pyrotinib and Metronomic Vinorelbine in HER2-Positive Breast Cancer With Leptomeningeal Disease: A Case Report and Literature Review.

Leptomeningeal metastases (LM) are rare and catastrophic for metastatic breast cancer (MBC). The prognosis of HER2-positive breast cancer (BC) with LM is extremely poor. There is no high-quality evidence of treatment regimens in HER2-positive BC with LM yet. Here, we present a case of LM in a 50-year-old woman with HER2-positive BC. Immunohistochemistry revealed invasive ductal carcinoma, estrogen receptor negative, progesterone receptor negative, HER2 3+, P53 positive 80%, and Ki-67 positive 35%. Reported for the first time, the patient was given pyrotinib-targeted therapy (400 mg, oral, every day), metronomic vinorelbine (40 mg, oral, three times a week), and intrathecal methotrexate (10 mg, infrequent and irregular use due to poor compliance) synchronously. The patient received and benefited from the treatment regimen for 16 months. And the quality of life, as self-reported, improved significantly. We also comprehensively summarized all the case reports, observational studies, and clinical trials related to HER2-positive BC with LM in the PubMed database and ClinicalTrials.gov. Intrathecal chemotherapy (methotrexate, cytarabine, thiotepa), intrathecal trastuzumab, whole-brain radiotherapy, and systemic therapy are commonly used treatment options according to a review of the literature and research. Pembrolizumab and trastuzumab deruxtecan (DS-8201) as novel drugs are promising in LM. Furthermore, trastuzumab emtansine (T-DM1) and tyrosine kinase inhibitors (TKIs) such as tucatinib and neratinib have exhibited good efficacy in HER2-positive BC with central nervous system (CNS) metastases and deserve further exploration. In our report, combining pyrotinib-targeted therapy with metronomic chemotherapy is a potential regimen, which has presented satisfactory therapeutic efficacy and also warrants additional investigation in HER2-positive BC with LM.

Survival analysis and nomogram for early-stage occult breast cancer with positive lymph nodes based on the SEER database.

Background: Occult breast cancer (OBC) is a rare type of breast cancer, which accounts for 0.3-1.0% of all breast cancers. However, the treatment of OBC remains controversial, especially the local treatment. We aimed to analyze the impact of different treatment and N stage on survival in early-stage OBC patients, and construct a nomogram to predict the prognosis. Methods: The data of patients with early-stage breast cancer were obtained from 17 registries in the Surveillance, Epidemiology, and End Results (SEER) database. Patient characteristics and breast cancer-specific survival (BCSS) were compared among the groups. Cox proportional risk models were used for both the univariate and multivariate analyses. Variables with a P value <0.07 in the univariate analysis were included in the multivariate analysis. The independent prognostic factors were included in the nomogram and validated internally. Results: A total of 492 early-stage OBC patients were randomized at a 7:3 ratio into the training cohort (n=348) and the testing cohort (n=144). N2+ stage patients had a worse prognosis than N1 stage patients (P=0.0051). Triple-negative breast cancer (TNBC) patients had the worst prognosis. Early-stage OBC patients benefited from surgery (P=0.0093) and radiotherapy (P=0.0102), but not chemotherapy (P=0.4030). An analysis of OBC patients with different N stages showed that in terms of treatment, N1 stage patients benefited from surgery (P=0.023), but did not benefit significantly from radiotherapy (P=0.0793), whereas N2+ stage patients benefited from radiotherapy (P=0.0098), but the benefit from surgery was not significant (P=0.1005). In the multivariate analysis, N stage, surgery, and radiotherapy remained statistically significant. Based on the results of the multivariate analysis, we constructed a nomogram for estimating the 3- and 5-year BCSS of OBC patients. The concordance index and the calibration plots show that our nomogram had sufficient accuracy and good coordination. Conclusions: N stage, surgery, and radiotherapy were identified as independent prognostic factors for OBC. We successfully constructed a nomogram using these independent risk factors and demonstrated that it could help predict the 3- and 5-year BCSS of OBC patients. Further data analyses need to be conducted to revise the treatment of early-stage OBC.

[Atmospheric NH3 Emission Inventory and Analysis of the Driving Force in Zhengzhou City].

In this study, a 2017-based emission inventory of ammonia(NH3) was established for Zhengzhou by using the emission factor method. The 1 km×1 km gridded emission inventory was mapped using GIS technology. The NH3 emissions between 2007 and 2017 and driving force between 1989 and 2017 were also analyzed. Results showed that the total 2017-based NH3 emission in Zhengzhou was 18143.3 t, and the average emission intensity reached 2.4 t·km-2. The top emission source was from agriculture, accounting for 63.4% of the total emission, followed by fugacity(11.3%). The main contribution sources of livestock were egg poultry, pigs, and cattle. Dengfeng, Xingyang, and Xinmi had the highest emissions, accounting for 19.3%, 16.5%, and 15.6% of the total emission, respectively. The NH3 emission was higher in the southern and central western regions of Zhengzhou and lower in the northeastern region. The NH3 emission in Zhengzhou showed a downward trend from 2007 to 2017. The NH3 emissions from 1987 to 2017 were similar to the environmental Kuznets Curve, i.e., the emissions increased first and then decreased with the increase of per capita gross domestic product(GDP) and urbanization rate.