PD-1-induced encephalopathy: a report of 2 cases on neurological toxicities with immune checkpoint inhibitors.

Background: Immune-related adverse effects (irAEs) often occur during immune checkpoint inhibitor (ICI) therapy. In the nervous system, the incidence of irAEs ranges from 0.1-12%, with 80% occurring within the first 4 months of ICI application. For complications of the nervous system, adequate diagnosis is made by signs, symptoms, imaging and cerebrospinal fluid. If severe irAEs occur, ICIs should be discontinued and patients should be treated with high-dose glucocorticoids, immunoglobulins, or immunosorbent therapy with systemic support. Patients who develop severe neurologic irAEs have a poorer prognosis. Case Description: In this article, we report 2 cases of encephalopathy induced by anti-programmed cell death protein 1 (PD-1) monoclonal antibodies at the initial diagnoses. Our findings may help clinicians to differentiate between encephalopathy caused by immunotherapy and other neurological disorders. Case 1 was a 24-year-old male patient who had undergone PD-1 immunotherapy to treat olfactory neuroblastoma. After the 6th course of therapy, he began to develop persistent epilepsy, which decreased significantly after high doses of glucocorticoid and immunosorbent therapy were administered. Based on his medical history and laboratory examination results, PD-1-induced encephalopathy was the most likely diagnosis. Case 2 was a 67-year-old female patient who had been treated with PD-1/programmed death ligand-1 therapy for lung adenocarcinoma. She began to have headaches after 1 cycle of treatment, and her cognitive function gradually decreased with the continuation of immunotherapy. Conclusions: These case reports show the difficulty in distinguishing PD-1-induced encephalopathy from other neurological disorders, especially paraneoplastic neurological syndromes. If not treated properly, patients' lives may be endangered. Thus, early identification and early treatment are very important.

Identification and molecular mechanism of novel bifunctional peptides from Duroc × (Landrace × Yorkshire) pig dry-cured ham: A peptidomics and in silico analysis.

Duroc × (Landrace × Yorkshire) pigs are popular in the Chinese market because of their rapid growth, leanness, and economic value. Despite their widespread use in dry-cured ham processing, there is a lack of research on the bioactive peptides of Duroc × (Landrace × Yorkshire) pig ham (DLYH). This study aimed to investigate the presence of peptides with antioxidant and α-glucosidase inhibitory activities in DLYH using peptidomics and in silico analysis. A total of 453 peptides were identified from DLYH, originating mainly from myosin, actin, and the EF-hand domain-containing protein. Notably, two peptides, YDEAGPSIVH (YH10) and FAGDDAPRAVF (FF11), emerged as novel bioactive peptides with antioxidant and α-glucosidase inhibitory activities. Among these peptides, YH10 exhibited a high DPPH radical scavenging activity (IC50 = 1.93 mM), ABTS radical scavenging activity (IC50 = 0.10 mM), α-glucosidase inhibitory activity (IC50 = 2.13 mM), and good gastrointestinal tolerance. Molecular docking analysis showed that YH10 was bound to the ABTS and DPPH radicals and the active site of α-glucosidase (3A4A) primarily through hydrogen bonding and hydrophobic interactions. Furthermore, molecular dynamics (MD) simulation indicated that the YH10-3A4A complexes maintained stable and compact conformations. In conclusion, our findings indicated that peptide YH10 derived from DLYH possesses bifunctional properties of α-glucosidase inhibition and antioxidant activity, which could be beneficial for maintaining ham quality and promoting human health.

Scd-1 deficiency promotes the differentiation of CD8+ T effector.

The impact of various fatty acid types on adaptive immunity remains uncertain, and their roles remain unelucidated. Stearoyl-CoA desaturase (Scd) is a Δ-9 desaturase, which is a key rate-limiting enzyme for the conversion of saturated fatty acids (SFA) to monounsaturated fatty acids (MUFA) in the fatty acid de novo synthesis. Scd-1 converts stearic acid (SA) and palmitic acid (PA) to oleic acid (OA) and palmitoleic acid (PO), respectively. In this study, through a series of experiments, we showed that Scd-1 and its resulting compound, OA, have a substantial impact on the transformation of CD8+ naïve T cells into effector T cells. Inactivation of Scd-1 triggers the specialization of CD8+ T cells into the Teff subset, enhancing the effector function and mitochondrial metabolism of Teff cells, and OA can partially counteract this. A deeper understanding of lipid metabolism in immune cells and its impact on cell function can lead to new therapeutic approaches for controlling the immune response and improving prognosis.

Spatiotemporal variations in soil pollution by polycyclic aromatic hydrocarbons over a 20-year economic boom in different districts of a heavy industrial city in North China.

Urbanization-related human activities, such as population aggregation, rapid industrial expansion, and intensified traffic, are key factors that impact local polycyclic aromatic hydrocarbon emissions and their associated health risks. Consequently, regions with varying degrees of urbanization within a megacity may exhibit diverse spatiotemporal patterns in the presence and distribution of soil polycyclic aromatic hydrocarbons, resulting in different levels of ecological risks for local inhabitants following the same period of development. In this study, we measured the concentrations of 16 polycyclic aromatic hydrocarbons in soil samples collected from industrial district and rural district in Tianjin (China) in 2018, and compared with polycyclic aromatic hydrocarbon data in 2001 from a previous study to characterize these regional variations in occurrence, source, and human risk of polycyclic aromatic hydrocarbons induced by urbanization with time and space. The results indicate the 20-year rapid urbanization and industrialization has differentially affected the composition, distribution and sources of polycyclic aromatic hydrocarbons in soils from different economic functional zones in Tianjin. Additionally, its impact on health risks in rural district appeared to be more significant than that in industrial district.

Construction and application of a nursing human resource allocation model based on the case mix index.

BACKGROUND: The case mix index (CMI) may reflect the severity of disease and the difficulty of care objectively, and is expected to be an ideal indicator for assessing the nursing workload. The purpose of this study was to explore the quantitative relationship between daily nursing worktime (DNW) and CMI to provide a method for the rational allocation of nursing human resources. METHODS: Two hundred and seventy-one inpatients and 36 nurses of the department of hepatobiliary surgery were prospectively included consecutively from August to September 2022. The DNW of each patient were accurately measured, and the CMI data of each patient were extracted. Among 10 curve estimations, the optimal quantitative model was selected for constructing the nursing human resource allocation model. Finally, the applicability of the allocation model was preliminarily assessed by analyzing the relationship between the relative gap in nursing human resources and patient satisfaction, as well as the incidence of adverse events in 17 clinical departments. RESULTS: The median (P25, P75) CMI of the 271 inpatients was 2.62 (0.92, 4.07), which varied by disease type (F = 3028.456, P < 0.001), but not by patient gender (F = 0.481, P = 0.488), age (F = 2.922, P = 0.089), or level of care (F = 0.096, P = 0.757). The median (P25, P75) direct and indirect DNW were 76.07 (57.98, 98.85) min and 43.42 (39.42, 46.72) min, respectively. Among the 10 bivariate models, the quadratic model established the optimal quantitative relationship between CMI and DNW; DNW = 92.3 + 4.8*CMI + 2.4*CMI2 (R2 = 0.627, F = 225.1, p < 0.001). The relative gap between theoretical and actual nurse staffing in the 17 clinical departments were linearly associated with both patient satisfaction (r = 0.653, P = 0.006) and incidence of adverse events (r = - 0.567, P = 0.021). However, after adjusting for other factors, it was partially correlated only with patient satisfaction (rpartial = 0.636, P = 0.026). CONCLUSION: The DNW derived from CMI can be used to allocate nursing human resources in a rational and convenient way, improving patient satisfaction while ensuring quality and safety.

Multivariate analysis of medical adhesive-related skin injury at the site of peripherally inserted central catheter insertion in cancer patients: A prospective cohort study.

OBJECTIVE: At the site of peripherally inserted central catheter (PICC) catheterization in tumor patients, medical adhesive-related skin injury (MARSI) was reported related to patient age, infusion of certain chemotherapeutic agents, and tumor type, but did not review its relation to the use of clear patches and the puncture site of PICC. This study aims to analyze the risk factors for MARSI in more detail to provide supported data for reducing MARSI. METHOD: Total 382 cancer patients receiving catheterization via PICC were involved in this study from March 1, 2021, to September 28, 2021. According to MARSI occurrence or not, they were assigned into MARSI or non-MARSI group. Univariate and multivariate logistic regressions were used to analyze the risks of MARSI occurrence at PICC insertion site. RESULTS: 15% (60 of 382 cases) resulted in MARSI, out of which 8.1% (31/382) was categorized as contact dermatitis, and 7.1% (27/382) as mechanical injuries. The univariate analysis showed that there were significant differences in six aspects of the study, including BMI, MARSI history, dressing types, treatment by paclitaxel or 5-FU versus oxaliplatin, dressing frequency, and catheterization at biceps brachii medial (p < 0.05). Via multivariate logistic regression analysis, it was discovered that except for previously reported risk factors, dressing change frequency (OR (95% CI) = 7.49 (2.36-23.80), p = 0.001), catheterization at biceps brachii medial (OR (95% CI) = 4.07 (1.82-9.10), p = 0.001), and breast cancer (OR (95% CI) = 3.27 (1.05-10.15), p = 0.041), there were significant risk factors for MARSI occurrence in tumor patients with PICC catheterization. CONCLUSION: Our study revealed a high incidence of MARSI at the PICC insertion site of cancer patients, presenting with contact dermatitis and mechanical injury. Independent risk factors were previous history of MARSI, a diagnosis of breast cancer, frequent dressing replacement, use of paclitaxel or 5-FU, and PICC catheterization at biceps brachii medial.

Efficacy and safety of osimertinib for leptomeningeal metastases from EGFR-mutant non-small cell lung cancer: a pooled analysis.

BACKGROUND: The aim of this study was to evaluate the efficacy and safety of osimertinib for the treatment of leptomeningeal metastases (LM) from epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). METHODS: We conducted a systematic review and meta-analysis to aggregate the clinical outcomes of patients with LM from EGFR-mutant NSCLC treated with osimertinib. A comprehensive literature search for published and unpublished studies was implemented in April 2021 of PubMed, EMBASE, the Cochrane Library, and several international conference databases, in accordance with the PRISMA guidelines. Meta-analysis of proportions was conducted to calculate the pooled rate of overall response rate (ORR), disease control rate (DCR), one-year overall survival (OS), and adverse events (AEs). RESULTS: A total of eleven studies (five prospective and six retrospective) including 353 patients were included. The majority of patients (346/353, 98.0%) received osimertinib as ≥ 2nd-line treatment for LM, either at a dosage of 80 mg (161/353, 45.6%) or 160 mg (191/353, 54.1%). The pooled rates of ORR and DCR were 42% (95% CI 24% to 59%) and 93% (95% CI 88% to 97%), respectively. The pooled one-year OS rate was 59% (95% CI 53% to 65%) in 233 patients from five studies. The highest incidence of AEs of all grades was rash (53%), followed by diarrhea (45%), paronychia (35%), decreased appetite (35%), and dry skin (27%), based on data from four studies. CONCLUSIONS: Our study highlighted and confirmed the meaningful efficacy and a manageable safety profile of osimertinib for the treatment of LM from EGFR-mutant advanced NSCLC.

Efficacy and safety of combined immunotherapy and stereotactic radiosurgery in NSCLCBM patients and a novel prognostic nomogram: A real-world study.

Objective: To explore the effectiveness of combined immunotherapy (IT) and stereotactic radiosurgery (SRS) and address the gap between evidence-based clinical practice and academic knowledge of optimal timing of IT relative to SRS. In addition, to meet the unmet need for an up-to-date prognostic assessment model in the era of IT. Methods: The data of 86 non-small cell lung cancer brain metastasis (NSCLCBM) patients treated with SRS to 268 brain metastases (BMs) were retrospectively extracted from our hospital database. The Kaplan-Meier analysis was employed for overall survival (OS) and a log-rank test for comparison between groups. Cox proportional hazards regression models were used to identify the significant prognostic factors. The prognostic nomogram was established utilizing the rms package of R software. Results: IT was found to be associated with improved OS (from BM diagnosis: HR 0.363, 95% CI 0.199 - 0.661, P < 0.001; from SRS: HR 0.472, 95% CI 0.260 - 0.857, P = 0.014). Individuals who received IT in combination with SRS had better OS than those who didn't (from the day of BM diagnosis: 16.8 vs. 8.4 months, P = 0.006; from the day of SRS: 12 vs. 7 months, P = 0.037). Peri-SRS timing of IT administration was a significant prognostic factor for OS (from BM diagnosis: HR 0.132, 95% CI 0.034 - 0.517, P = 0.004; from SRS: HR 0.14, 95% CI 0.044 - 0.450, P = 0.001). Initiating IT after SRS led to superior OS than concurrent or before (from BM diagnosis: 26.5 vs. 14.1 vs. 7.1 months; from SRS: 21.4 vs. 9.9 vs. 4.1 months, respectively). Additionally, we build a nomogram incorporating IT, cumulative intracranial tumor volume (CITV), and recursive partitioning analysis (RPA), demonstrating a remarkable prognosis prediction performance for SRS-treated NSCLCBM patients. Conclusion: Peri-SRS IT is a promising approach in treating NSCLCBM, as improved OS was observed without significantly increasing adverse events. Receipt of IT post-SRS was associated with superior OS than those who received IT concurrently or before. Incorporating IT and CITV into the RPA index could augment its prognosis assessment value for SRS-treated NSCLCBM patients, predominantly in the wild-type.

The immune-metabolic crosstalk between CD3+C1q+TAM and CD8+T cells associated with relapse-free survival in HCC.

Introduction: Although multiple targeted treatments have appeared, hepatocellular carcinoma (HCC) is still one of the most common causes of cancer-related deaths. The immunosuppressive tumor microenvironment (TME) is a critical factor in the oncogenesis and progression of HCC. The emerging scRNA-seq makes it possible to explore the TME at a high resolution. This study was designed to reveal the immune-metabolic crosstalk between immune cells in HCC and provide novel strategies to regulate immunosuppressive TME. Method: In this study, we performed scRNA-seq on paired tumor and peri-tumor tissues of HCC. The composition and differentiation trajectory of the immune populations in TME were portrayed. Cellphone DB was utilized to calculate interactions between the identified clusters. Besides, flow cytometry, RT-PCR and seahorse experiments were implemented to explore potential metabolic and epigenetic mechanisms of the inter-cellular interaction. Result: A total of 19 immune cell clusters were identified and 7 were found closely related to HCC prognosis. Besides, differentiation trajectories of T cells were also presented. Moreover, a new population, CD3+C1q+ tumor-associated macrophages (TAM) were identified and found significantly interacted with CD8+ CCL4+T cells. Compared to the peri-tumor tissue, their interaction was attenuated in tumor. Additionally, the dynamic presence of this newly found cluster was also verified in the peripheral blood of patients with sepsis. Furthermore, we found that CD3+C1q+TAM affected T cell immunity through C1q signaling-induced metabolic and epigenetic reprogramming, thereby potentially affecting tumor prognosis. Conclusion: Our study revealed the interaction between CD3+C1q+TAM and CD8+ CCL4+T cells and may provide implications for tackling the immunosuppressive TME in HCC.

Exploring the Relationship between Ecosystem Services under Different Socio-Economic Driving Degrees.

The large-scale transformation of natural ecosystems to socio-economic development land types under human activities was a primary reason for the decline of regional ecosystem services. It is a key issue for regional ecosystem planning and management to reveal the relationship between ecosystem services of different land use types under different socio-economic driving degrees. However, the current related research was not in-depth. Based on the land use data of Wuhan City in 1980, 1990, 2000, 2010, and 2020, this study classified land use into three categories according to the different degrees of human activities on natural ecosystem development: the land use of a natural ecosystem (LUNE), the land use of a productive ecosystem (LUPE), and the land use of a socio-economic system (LUSE). The InVEST model was used to simulate five ecosystem services (grain yield, water yield, carbon storage, habitat quality, and water purification), and the spatio-temporal distribution and functional transformation of the three land use types were analyzed. Results showed that with the intensified urban expansion in Wuhan, the LUSE types increased to 2.7 times that of the original. However, the natural land types basically maintained a stable area, coupling with the large-scale transformation between the LUPE and LUSE types. Land use change resulted in significant spatial changes of five ecosystem services, especially carbon storage and habitat quality. The correlation analysis indicated that the five kinds of ecosystem services mainly showed a synergistic relationship, meanwhile the LUSE type denoted the most significant correlation with ecosystem services among these three category types. This study indicated that besides the protection of natural ecosystems, the LUSE type would become the key land use type in the planning and management of improving regional ecological function.

Antidiabetic drug metformin suppresses tumorigenesis through inhibition of mevalonate pathway enzyme HMGCS1.

Metformin, an antidiabetic drug, shows some potent antitumor effects. However, the molecular mechanism of metformin in tumor suppression has not been clarified. Here, we provided evidence using in vitro and in vivo data that metformin inhibited mevalonate pathway by downregulation of 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1), a key enzyme in this pathway. Our results further demonstrated that metformin downregulated HMGCS1 expression through inhibition of transcription factor nuclear factor E2-related factor 2. In addition, we determined that HMGCS1 was highly expressed in human liver and lung cancer tissues and associated with lower survival rates. In summary, our study indicated that metformin suppresses tumorigenesis through inhibition of the nuclear factor E2-related factor 2-HMGCS1 axis, which might be a potential target in cancer prevention and treatment.

Computed Tomography Comparative Analysis of Nontuberculous Mycobacterial Lung Disease in the Elderly and Secondary Pulmonary Tuberculosis.

OBJECTIVES: The study aimed to explore the key points of computed tomography (CT) differential diagnosis of nontuberculous mycobacteria (NTM) and secondary pulmonary tuberculosis in elderly patients. METHODS: We retrospectively analyzed 45 patients with NTM pulmonary disease and 65 patients with secondary pulmonary tuberculosis. All patients were older than 60 years. The diseases were confirmed by laboratory examination. The general data and CT images of the 2 groups were compared and analyzed using χ 2 tests, single-factor analysis, and multivariate logistic regression analysis. RESULTS: Single-factor analysis showed significant differences between the 2 groups in 9 factors: bronchiectasis of the left upper lobe lingual segment, bronchiectasis of the right middle lobe, small nodules, large nodules, thin-walled cavities, thick-walled cavities, nonsubpleural hollows, strip opacity, and mediastinal lymph node enlargement ( P < 0.05). Multivariate logistic regression analysis showed that thin-walled cavities, bronchiectasis of the right middle lobe, small nodules, and large nodules were important factors in the differential diagnosis of the two groups. CONCLUSIONS: Nontuberculous mycobacteria show certain characteristics on CT, which are helpful for differential diagnosis when coupled with clinical and sputum smear examinations.

Case Report: Identification of a Novel GNAS Mutation and 1p/22q Co-Deletion in a Patient With Multiple Recurrent Meningiomas Sensitive to Sunitinib.

BACKGROUND: Although surgical resection can cure the majority of meningiomas, there are still approximately 20% of patients suffering from an aggressive course with recurrence or progression. In this study, we reported a novel GNAS mutation and 1p/22q co-deletion responding to sunitinib in a patient with multiple recurrent meningiomas. CASE PRESENTATION: A 53-year-old woman with meningioma was hospitalized due to postoperative tumor progression for 3 weeks. WHO grade I meningioma was pathologically diagnosed after the first three surgeries, but the second recurrence occurred approximately 3 years following the third surgery. Next-generation sequencing was performed on the first two recurrent samples. GNAS mutations and 1p/22q co-deletion were both identified, and amplification at 17q and chromosome 19 was also found in the second recurrent sample, based on which WHO grade II/III meningioma was diagnosed. The lesion in the left cerebellopontine angle area enlarged after use of radiotherapy combined with temozolomide chemotherapy for 2 months. When sunitinib was added, the residual lesions began to lessen and continuously reduced. CONCLUSION: This typical case suggested that timely molecular diagnosis for refractory meningiomas contributed to guiding the molecular classification and clinicians to make more reasonable individualized therapeutic regimens, consequently benefiting the patients. This case report also highlighted the potential role of sunitinib in the treatment of refractory meningiomas.

Methods for Optimizing Student Pharmacist Learning of Clinical Note Writing.

Objective. To investigate the effectiveness of using problem-solving and worked examples in teaching clinical note writing to Doctor of Pharmacy students.Methods. First year student pharmacists who were recruited to participate in the study first studied a worked example on generating a clinical note from a written patient case. Participants were then randomized either to study another worked example or to practice writing a clinical note from a written patient case. Embedded in each condition was problem variability (ie, participants encountered either a similar disease state as that in the initial worked example or a different disease state). The primary outcome was the combined performance on writing two clinical notes. Secondary outcomes included quiz performance on knowledge of the components of a clinical note and ability to transfer writing skills to a novel disease state.Results. Seventy-nine students completed the study. Participants who studied a worked example followed by problem-solving (WE-PS) practice performed better than participants who studied two worked examples (WE-WE) on clinical note writing. However, there was no difference in their respective knowledge as determined by quiz performance.Conclusion. Both worked examples and problem-solving facilitated students' learning of the basic knowledge of clinical note writing. However, only problem-solving improved student pharmacists' ability to apply that knowledge. While there were significant improvements in student pharmacists' knowledge of the basics of clinical note writing, it is unclear how worked examples or problem-solving influence the clinical decision-making skills needed to write a clinical note.

Stereotactic radiosurgery for treatment of large cerebellum metastases from lung cancer.

BACKGROUND: Stereotactic radiosurgery (SRS) is an important treatment option. This report evaluated the efficacy and safety of SRS in patients with large cerebellum metastases from lung cancer. METHODS: Between September 2016 and January 2020, a total of 44 patients with large cerebellum metastases >2 cm from lung cancer were evaluated. A median dose of 20 Gy (range, 8-24 Gy) was delivered in 1 to 3 fractions for SRS treatment. The survival rate was analyzed with SPSS software 21.0 and compared by log-rank test using the Kaplan-Meier method. RESULTS: The median overall survival (OS) and neurological progression-free survival (PFS) were 10.5 months (range, 1-32 months) and 9.0 months (range, 1-32 months), respectively. The median diameter and volume of the metastases were 3.5 cm (range, 2.1-5.7 cm) and 12.5 cc (range, 1.8-39.7 cc), respectively. The median volume of peritumoral edema was 36.3 cc (range, 3.7-100.3 cc). The median ratio of tumor volume to cerebellum volume was 8.7% (range, 1.3-27.0%). The median ratio of peritumoral edema volume to cerebellum volume was 25.0% (range, 2.5-68.6%). Neurological symptoms were present in 97.7% (43/44) of patients. After SRS treatment, symptoms improved in 83.7% (36/44) patients, stabilized in 11.6% (5/44) patients, whilst two patients experienced symptomatic progression. Of the latter, one patient accepted emergency surgery and the other accepted palliative care. CONCLUSIONS: Large cerebellum metastases are amongst the most severe forms of brain tumors. Increased tumor volume and peritumoral edema volume correlate with the most severe symptoms. SRS may be an effective alternative treatment for large cerebellum metastases from lung cancer and may preserve neurological function.

Contamination and human health risks of polycyclic aromatic hydrocarbons in surface soils from Tianjin coastal new region, China.

Polycyclic aromatic hydrocarbons (PAHs) in urban soils are of increasing concern because of their potential toxicity and persistence. However, there is limited information about PAHs in Tianjin coastal new region, although it is an important economic and industrial center in Northern China. Here we determined the concentrations of PAHs in 210 surface soil samples collected from this region according to administrative divisions covering Han'gu district, Tanggu district, and Dagang district, to evaluate their contamination and potential cancer risks. The concentrations of 16 PAHs ranged from 58.2 to 9160 ng g-1, and the highest concentration was found in Han'gu district. According to the incremental lifetime cancer risk (ILCR) model, the soils from Han'gu district and Dagang district posed a moderate carcinogenic risk to residents, and dermal contact was the main exposure pathway. Besides, ILCRs for children through ingestion were comparable to those for adults but apparently higher than adolescents, while ILCRs of dermal contact for adults were higher than children and adolescents. Comparisons between the layout of industrial zones and the distributions of PAHs as well as ILCRs indicate that PAHs accumulating in soils and then incurring risk areas is partly controlled by the economic and industrial structure.

Application of controlled release urea improved grain yield and nitrogen use efficiency: A meta-analysis.

The application of controlled release urea (CRU) has been proposed as a crucial method to reduce the adverse environmental effects induced by conventional urea (CU). Yet, a systematic and quantitative analysis on how CRU affects staple crop production including wheat (Triticum aestivum L.), maize (Zea mays L.), and rice (Oryza sativa L.) is lacking. Here, a meta-analysis was conducted to determine how CRU influences soil chemical properties, total nitrogen (TN) uptake, grain yield, and nitrogen use efficiency (NUE) of staple crop in China. The results indicated that CRU application significantly increased soil organic carbon (SOC), TN, and available nitrogen (AN) by 5.93%, 3.89% and 13.98% respectively overall, while soil pH showed no significant changes. Compared to the application of CU, applying CRU significantly increased grain yield by 7.23%, which was mainly owing to the higher TN uptake (9.13%) across all the studies. In addition, the application of CRU significantly increased NUE, nitrogen agronomy efficiency (NAE), utilization rate of nitrogen fertilizer (NUR), and nitrogen physiological efficiency (NPE) by an average of 23.4%, 34.65%, 25.83% and 15.8% respectively which could be attributed to the slow nitrogen (N) release characteristics of CRU. The positive effect of CRU on grain yield and NUE of staple crop was greatest when the content of SOC and TN were extremely low, indicating that it was most effective to improve grain production of infertile soil by applying CRU. The finding of this study indicated that the application of CRU should be promoted for grain production, especially for infertile soil.

Analysis of single-cell RNAseq identifies transitional states of T cells associated with hepatocellular carcinoma.

BACKGROUND: Exhausted T cells and regulatory T cells (Tregs) comprise diverse subsets of tumor immunosuppressive microenvironment that play key roles in tumor progress. Understanding subset diversity in T cells is a critical question for developing cancer immunotherapy. METHODS: A total of 235 specimens from surgical resections of hepatocellular carcinoma (HCC) patients were examined for infiltration of exhausted T cell (Tex) in tumor and adjacent tissue. We conducted deep single-cell targeted immune profiling on CD3+ cells collected from tumor tissues, adjacent normal tissues (ANTs) and peripheral blood of HCC patients. Total 10 cell clusters were identified with distinct distributions and characteristics. RESULTS: We observed transitional differentiation of exhausted CD8+ T cells and Tregs increasingly enriched in tumor tissue. The accumulation and location of Tex were related to the differences in the long-term clinical outcome of HCC. Furthermore, data of single-cell RNA-seq showed that (1) cells transforming from effector CD8+ T cells to exhausted CD8+ T cells simultaneously expressed upregulated effector molecules and inhibitory receptors, (2) indicated alteration of gene expression related to stress response and cell cycle at early exhaustion stage, and (3) immunosuppressive Treg had profound activation in comparison to resting Tregs. CONCLUSIONS: T cell exhaustion is a progressive process, and the gene-expression profiling displayed T cell exhaustion and anergy are different. Accordingly, it is possible that functional exhaustion is caused by the combination effects of passive defects and overactivation in stress response. The results help to understand the dynamic framework of T cells function in cancer which is important for designing rational cancer immunotherapies.

Inhibitory effect of Siwei Xiaoliuyin on glioma angiogenesis in nude mice.

OBJECTIVE: Application of Siwei Xiaoliuyin in glioma mice. Explore the effect of Siwei Xiaoliuyin on angiogenesis of nude mice glioma and its mechanism. METHODS: Establish human glioma cell line U87 tumor model. Mice were randomized to the saline group, the conventional dose of Siwei Xiaoliuyin, high dose group of Siwei Xiaoliuyin, TMZ group, combination therapy group, record the tumor volume. Using the method of Weidner counted the microvessel density. ELISA enzyme-linked adsorption method to detect the content of nude mice serum VEGF and ES. The difference was statistically significant (P<0.05). RESULTS: The tumor volume and MVD of conventional dose group, large dose group, Siwei Xiaoliuyin combined temozolomide group was smaller than the blank group，the difference was statistically significant (P<0.05). VEGF levels in three groups of nude mice were lower than the blank group and ES content is higher than blank group, the difference was statistically significant (P<0.05). CONCLUSION: Siwei Xiaoliuyin can inhibit glioma angiogenesis. Its mechanism of glioma angiogenesis inhibition may be through regulation VEGF and down-regulation of endostatin expression of vascular endothelial growth factor achieved. Down-regulation of endostatin expression of vascular endothelial growth factor achieved.