Acetate enables metabolic fitness and cognitive performance during sleep disruption.

Sleep is essential for overall health, and its disruption is linked to increased risks of metabolic, cognitive, and cardiovascular dysfunctions; however, the molecular mechanisms remain poorly understood. This study investigated how sleep disturbances contribute to metabolic imbalance and cognition impairment using a chronic sleep fragmentation (SF) mouse model. SF mice exhibited impaired cognition, glucose metabolism, and insulin sensitivity compared with controls. We identified increased acetate levels in hypothalamic astrocytes as a defensive response in SF mice. Through acetate infusion or astrocyte-specific Acss1 deletion to elevate acetate levels, we observed mitigated metabolic and cognitive impairments in SF mice. Mechanistically, acetate binds and activates pyruvate carboxylase, thereby restoring glycolysis and the tricarboxylic acid cycle. Among individuals most commonly affected by SF, patients with obstructive sleep apnea exhibited elevated acetate levels when coupled with type 2 diabetes. Our study uncovers the protective effect of acetate against sleep-induced metabolic and cognitive impairments.

Enhanced nitrous oxide emission factors due to climate change increase the mitigation challenge in the agricultural sector.

Effective nitrogen fertilizer management is crucial for reducing nitrous oxide (N2O) emissions while ensuring food security within planetary boundaries. However, climate change might also interact with management practices to alter N2O emission and emission factors (EFs), adding further uncertainties to estimating mitigation potentials. Here, we developed a new hybrid modeling framework that integrates a machine learning model with an ensemble of eight process-based models to project EFs under different climate and nitrogen policy scenarios. Our findings reveal that EFs are dynamically modulated by environmental changes, including climate, soil properties, and nitrogen management practices. Under low-ambition nitrogen regulation policies, EF would increase from 1.18%-1.22% in 2010 to 1.27%-1.34% by 2050, representing a relative increase of 4.4%-11.4% and exceeding the IPCC tier-1 EF of 1%. This trend is particularly pronounced in tropical and subtropical regions with high nitrogen inputs, where EFs could increase by 0.14%-0.35% (relative increase of 11.9%-17%). In contrast, high-ambition policies have the potential to mitigate the increases in EF caused by climate change, possibly leading to slight decreases in EFs. Furthermore, our results demonstrate that global EFs are expected to continue rising due to warming and regional drying-wetting cycles, even in the absence of changes in nitrogen management practices. This asymmetrical influence of nitrogen fertilizers on EFs, driven by climate change, underscores the urgent need for immediate N2O emission reductions and further assessments of mitigation potentials. This hybrid modeling framework offers a computationally efficient approach to projecting future N2O emissions across various climate, soil, and nitrogen management scenarios, facilitating socio-economic assessments and policy-making efforts.

Calix[2]azolium[2]benzimidazolone hosts for selective binding of neutral substrates in water.

The separation and purification of chemical raw materials, particularly neutral compounds with similar physical and chemical properties, represents an ongoing challenge. In this study, we introduce a class of water-soluble macrocycle compound, calix[2]azolium[2]benzimidazolone (H), comprising two azolium and two benzimidazolone subunits. The heterocycle subunits form a hydrophobic binding pocket that enables H1 to encapsulate a series of neutral guests in water with 1:1 or 2:1 stoichiometry, including aldehydes, ketones, and nitrile compounds. The host-guest complexation in the solid state was further confirmed through X-ray crystallography. Remarkably, H1 was shown to be a nonporous adaptive crystal material to separate valeraldehyde from the mixture of valeraldehyde/2-methylbutanal/pentanol with high selectivity and recyclability in the solid states. This work not only demonstrates that azolium-based macrocycles are promising candidates for the encapsulation of organic molecules but also shows the potential application in separation science.

Plasma aldosterone concentrations elevation in hypertensive patients: the dual impact on hyperuricemia and gout.

Background: Prior research has highlighted the association between uric acid (UA) and the activation of the renin-angiotensin-aldosterone system (RAAS). However, the specific relationship between aldosterone, the RAAS's end product, and UA-related diseases remains poorly understood. This study aims to clarify the impact of aldosterone on the development and progression of hyperuricemia and gout in hypertensive patients. Methods: Our study involved 34534 hypertensive participants, assessing plasma aldosterone concentration (PAC)'s role in UA-related diseases, mainly hyperuricemia and gout. We applied multiple logistic regression to investigate the impact of PAC and used restricted cubic splines (RCS) for examining the dose-response relationship between PAC and these diseases. To gain deeper insights, we conducted threshold analyses, further clarifying the nature of this relationship. Finally, we undertook subgroup analyses to evaluate PAC's effects across diverse conditions and among different subgroups. Results: Multivariate logistic regression analysis revealed a significant correlation between the occurrence of hyperuricemia and gout and the elevation of PAC levels. Compared to the first quartile (Q1) group, groups Q2, Q3, and Q4 all exhibited a significantly increased risk of occurrence. Moreover, the conducted RCS analysis demonstrated a significant nonlinear dose-response relationship, especially when PAC was greater than 14 ng/dL, with a further increased risk of hyperuricemia and gout. Finally, comprehensive subgroup analyses consistently reinforced these findings. Conclusion: This study demonstrates a close association between elevated PAC levels and the development of UA-related diseases, namely hyperuricemia and gout, in hypertensive patients. Further prospective studies are warranted to confirm and validate this relationship.

Corticothalamic input derived from corticospinal neurons contributes to chronic neuropathic pain after spinal cord injury.

Neuropathic pain is a significant and persistent issue for individuals with spinal cord injuries (SCI), severely impacting their quality of life. While changes at the peripheral and spinal levels are known to contribute to SCI-related pain, whether and how supraspinal centers contribute to post SCI chronic neuropathic pain is poorly understood. Here, we first validated delayed development of chronic neuropathic pain in mice with moderate contusion SCI. To identify supraspinal regions involved in the pathology of neuropathic pain after SCI, we next performed an activity dependent genetic screening and identified multiple cortical and subcortical regions that were activated by innocuous tactile stimuli at a late stage following contusion SCI. Notably, chemogenetic inactivation of pain trapped neurons in the lateral thalamus alleviated neuropathic pain and reduced tactile stimuli evoked cortical overactivation. Retrograde tracing showed that contusion SCI led to enhanced corticothalamic axonal sprouting and over-activation of corticospinal neurons. Mechanistically, ablation or silencing of corticospinal neurons prevented the establishment or maintenance of chronic neuropathic pain following contusion SCI. These results highlighted a corticospinal-lateral thalamic feed-forward loop whose activation is required for the development and maintenance of chronic neuropathic pain after SCI. Our data thus shed lights into the central mechanisms underlying chronic neuropathic pain associated with SCI and the development of novel therapeutic avenues to treat refractory pain caused by traumatic brain or spinal cord injuries.

Enhanced recovery after surgery-based nursing in older patients with postoperative intestinal obstruction after gastric cancer surgery: A retrospective study.

BACKGROUND: Gastric cancer-related morbidity and mortality rates are high in China. Patients who have undergone gastric cancer surgery should receive six cycles of chemotherapy according to their condition. During this period, intestinal obstruction is likely to occur. Electrolyte balance disorders, peritonitis, intestinal necrosis, and even hypovolemic shock and septic shock can seriously affect the physical and mental recovery of patients and threaten their health and quality of life (QoL). AIM: To quantitatively explore the effects of enhanced recovery after surgery (ERAS)-based nursing on anxiety, depression, and QoL of elderly patients with postoperative intestinal obstruction after gastric cancer. METHODS: The clinical data of 129 older patients with intestinal obstruction after gastric cancer surgery who were treated and cared for in our hospital between January 2019 and December 2021 were examined retrospectively. Nine patients dropped out because of transfer, relocation, or death. According to the order of admissions, the patients were categorized into either a comparison group or an observation group according to the random number table, with 60 cases in each group. RESULTS: After nursing care, the observation group required significantly less time to eat for the first time, recover bowel sounds, pass gas, and defecate than the comparison group (P < 0.05). No significant difference was noted in nutrition-related indicators between the two groups before care. Before care, the Symptom Check List-90 scores between the two groups were comparable, whereas anxiety, depression, paranoia, fear, hostility, obsession, somatization, interpersonal sensitivity, and psychotic scores were significantly lower in the observation group after care (P < 0.05). The QoL scores between the two groups before care did not differ significantly. After care, the physical, social, physiological, and emotional function scores; mental health score; vitality score; and general health score were significantly higher in the observation group, whereas the somatic pain score was significantly lower in the observation group (P < 0.05). CONCLUSION: ERAS-based nursing combined with conventional nursing interventions can effectively improve patient's QoL, negative emotions, and nutritional status; accelerate the time to first ventilation; and promote intestinal function recovery in elderly patients with postoperative intestinal obstruction after gastric cancer surgery.

Association between preterm delivery and the risk of maternal renal disease: A systematic review and meta­analysis.

The present systematic review and meta-analysis aimed to generate high-quality evidence on the association between preterm delivery (PTD) and subsequent risk of renal disease in the mother. A literature search was conducted on PubMed, Embase, CENTRAL and Scopus until the 15th of May 2023 for studies reporting an adjusted association between PTD and the risk of maternal renal disease. A total of seven studies were eligible. The pooled analysis found that women with PTD had a statistically significant increased risk of chronic kidney disease in the long term [hazard ratio (HR): 1.82 95% confidence interval (CI): 1.38, 2.40; I2=85%]. Similarly, the meta-analysis also found a statistically significant increased risk of end-stage renal disease (ESRD) amongst women with PTD as compared with those without PTD (HR: 2.22 95% CI: 1.95, 2.53; I2=0%). Overall, the pooled analysis showed a significantly higher incidence of renal disorders with PTD (HR: 1.98; 95% CI: 1.57, 2.50; I2=88%). The results were unchanged on sensitivity analysis. Women with PTD could be at increased risk of future chronic kidney disease and ESRD. The small number of studies and retrospective nature of data are important limitations. Further studies are needed to supplement the available evidence.

Nickel-Catalyzed α-selective Hydroalkylation of Vinylarenes.

C(sp3) centers adjacent to (hetero)aryl groups are widely present in physiologically active molecules. Metal-hydride-catalyzed hydroalkylation of alkenes represents an efficient means of forging C(sp3)-C(sp3) bonds, boasting advantages as a wide source of substrates, mild reaction conditions, and facile selectivity manipulation. Nevertheless, the hydroalkylation of vinylarenes encounters constraints in terms of substrate scope, necessitating the employment of activated alkyl halides or alkenes containing chelating groups, remains a challenge. In this context, we report a general nickel-hydride-catalyzed hydroalkylation protocol for vinylarenes. Remarkably, this system enables α-selective hydroalkylation of both aryl and heteroaryl alkenes under an extra ligand-free condition, demonstrating excellent coupling efficiency and selectivity. Furthermore, through the incorporation of chiral bisoxazoline ligands, we have achieved regio- and enantioselective hydroalkylation of vinylpyrroles, thereby facilitating the synthesis of α-branched alkylated pyrrole derivatives.

Integrated multi-omics analysis reveals molecular changes associated with chronic lipid accumulation following contusive spinal cord injury.

Functional and pathological recovery after spinal cord injury (SCI) is often incomplete due to the limited regenerative capacity of the central nervous system (CNS), which is further impaired by several mechanisms that sustain tissue damage. Among these, the chronic activation of immune cells can cause a persistent state of local CNS inflammation and damage. However, the mechanisms that sustain this persistent maladaptive immune response in SCI have not been fully clarified yet. In this study, we integrated histological analyses with proteomic, lipidomic, transcriptomic, and epitranscriptomic approaches to study the pathological and molecular alterations that develop in a mouse model of cervical spinal cord hemicontusion. We found significant pathological alterations of the lesion rim with myelin damage and axonal loss that persisted throughout the late chronic phase of SCI. This was coupled by a progressive lipid accumulation in myeloid cells, including resident microglia and infiltrating monocyte-derived macrophages. At tissue level, we found significant changes of proteins indicative of glycolytic, tricarboxylic acid cycle (TCA), and fatty acid metabolic pathways with an accumulation of triacylglycerides with C16:0 fatty acyl chains in chronic SCI. Following transcriptomic, proteomic, and epitranscriptomic studies identified an increase of cholesterol and m6A methylation in lipid-droplet-accumulating myeloid cells as a core feature of chronic SCI. By characterizing the multiple metabolic pathways altered in SCI, our work highlights a key role of lipid metabolism in the chronic response of the immune and central nervous system to damage.

Progress and prospects of biomarker-based targeted therapy and immune checkpoint inhibitors in advanced gastric cancer.

Gastric cancer and gastroesophageal junction cancer represent the leading cause of tumor-related death worldwide. Although advances in immunotherapy and molecular targeted therapy have expanded treatment options, they have not significantly altered the prognosis for patients with unresectable or metastatic gastric cancer. A minority of patients, particularly those with PD-L1-positive, HER-2-positive, or MSI-high tumors, may benefit more from immune checkpoint inhibitors and/or HER-2-directed therapies in advanced stages. However, for those lacking specific targets and unique molecular features, conventional chemotherapy remains the only recommended effective and durable regimen. In this review, we summarize the roles of various signaling pathways and further investigate the available targets. Then, the current results of phase II/III clinical trials in advanced gastric cancer, along with the superiorities and limitations of the existing biomarkers, are specifically discussed. Finally, we will offer our insights in precision treatment pattern when encountering the substantial challenges.

Disseminated Hypertrophic Discoid Lupus Erythematosus in a Patient with Vitiligo: A Case Report and Literature Review.

Vitiligo has been reported to occur in association with lupus erythematosus (LE) and other autoimmune diseases. However, it remains unclear whether this association occurs because of shared immunopathogenesis. We hereby describe a case of discoid lupus erythematosus (DLE) in a 51-year-old man with a 3 years history of skin lesions on his face, arms, and the V zone of the neck, and with the coexistence of vitiligo for 12 years, who developed from DLE to hypertrophic discoid lupus erythematosus (HDLE) after 10 months. We reviewed the previously reported cases to summarize the clinical characteristics of these patients and hope it may provide a reference for dermatologists.

TRIM65 deficiency alleviates renal fibrosis through NUDT21-mediated alternative polyadenylation.

Chronic kidney disease (CKD) is a major global health concern and the third leading cause of premature death. Renal fibrosis is the primary process driving the progression of CKD, but the mechanisms behind it are not fully understood, making treatment options limited. Here, we find that the E3 ligase TRIM65 is a positive regulator of renal fibrosis. Deletion of TRIM65 results in a reduction of pathological lesions and renal fibrosis in mouse models of kidney fibrosis induced by unilateral ureteral obstruction (UUO)- and folic acid. Through screening with a yeast-hybrid system, we identify a new interactor of TRIM65, the mammalian cleavage factor I subunit CFIm25 (NUDT21), which plays a crucial role in fibrosis through alternative polyadenylation (APA). TRIM65 interacts with NUDT21 to induce K48-linked polyubiquitination of lysine 56 and proteasomal degradation, leading to the inhibition of TGF-ß1-mediated SMAD and ERK1/2 signaling pathways. The degradation of NUDT21 subsequently altered the length and sequence content of the 3'UTR (3'UTR-APA) of several pro-fibrotic genes including Col1a1, Fn-1, Tgfbr1, Wnt5a, and Fzd2. Furthermore, reducing NUDT21 expression via hydrodynamic renal pelvis injection of adeno-associated virus 9 (AAV9) exacerbated UUO-induced renal fibrosis in the normal mouse kidneys and blocked the protective effect of TRIM65 deletion. These findings suggest that TRIM65 promotes renal fibrosis by regulating NUDT21-mediated APA and highlight TRIM65 as a potential target for reducing renal fibrosis in CKD patients.

Evolutionary and immune-activating character analyses of NLR genes in algae suggest the ancient origin of plant intracellular immune receptors.

Nucleotide-binding leucine-rich repeat (NLR) proteins are crucial intracellular immune receptors in plants, responsible for detecting invading pathogens and initiating defense responses. While previous studies on the evolution and function of NLR genes were mainly limited to land plants, the evolutionary trajectory and immune-activating character of NLR genes in algae remain less explored. In this study, genome-wide NLR gene analysis was conducted on 44 chlorophyte species across seven classes and seven charophyte species across five classes. A few but variable number of NLR genes, ranging from one to 20, were identified in five chlorophytes and three charophytes, whereas no NLR gene was identified from the remaining algal genomes. Compared with land plants, algal genomes possess fewer or usually no NLR genes, implying that the expansion of NLR genes in land plants can be attributed to their adaptation to the more complex terrestrial pathogen environments. Through phylogenetic analysis, domain composition analysis, and conserved motifs profiling of the NBS domain, we detected shared and lineage-specific features between NLR genes in algae and land plants, supporting the common origin and continuous evolution of green plant NLR genes. Immune-activation assays revealed that both TNL and RNL proteins from green algae can elicit hypersensitive responses in Nicotiana benthamiana, indicating the molecular basis for immune activation has emerged in the early evolutionary stage of different types of NLR proteins. In summary, the results from this study suggest that NLR proteins may have taken a role as intracellular immune receptors in the common ancestor of green plants.

J-Shaped Relationship Between Weight-Adjusted-Waist Index and Cardiovascular Disease Risk in Hypertensive Patients with Obstructive Sleep Apnea: A Cohort Study.

Background: A newly introduced obesity-related index, the weight-adjusted-waist index (WWI), emerges as a promising predictor of cardiovascular disease (CVD). Given the known synergistic effects of hypertension and obstructive sleep apnea (OSA) on cardiovascular risk, we aimed to explore the relationship between the WWI and CVD risk specifically within this high-risk cohort. Methods: A total of 2265 participants with hypertension and OSA were included in the study. Multivariate Cox regression analysis was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD events. The restricted cubic spline (RCS) was used to further evaluate the nonlinear dose-response relationship. Results: During a median follow-up period of 6.8 years, 324 participants experienced a CVD event. Multivariate Cox regression analysis revealed that compared to the reference group, the HRs for the second, third, and fourth groups were 1.12 (95% CI, 0.79-1.59), 1.35 (95% CI, 0.96-1.89), and 1.58 (95% CI, 1.13-2.22), respectively. Moreover, RCS analysis illustrated a clear J-shaped relationship between the WWI and CVD risk, particularly notable when WWI exceeded 11.5 cm/√kg, signifying a significant increase in CVD risk. Conclusion: There was a J-shaped relationship between WWI and CVD in hypertensive patients with OSA, especially when the WWI was greater than 11.5 cm/√kg, the risk of CVD was significantly increased.

Global net climate effects of anthropogenic reactive nitrogen.

Anthropogenic activities have substantially enhanced the loadings of reactive nitrogen (Nr) in the Earth system since pre-industrial times1,2, contributing to widespread eutrophication and air pollution3-6. Increased Nr can also influence global climate through a variety of effects on atmospheric and land processes but the cumulative net climate effect is yet to be unravelled. Here we show that anthropogenic Nr causes a net negative direct radiative forcing of -0.34 [-0.20, -0.50] W m-2 in the year 2019 relative to the year 1850. This net cooling effect is the result of increased aerosol loading, reduced methane lifetime and increased terrestrial carbon sequestration associated with increases in anthropogenic Nr, which are not offset by the warming effects of enhanced atmospheric nitrous oxide and ozone. Future predictions using three representative scenarios show that this cooling effect may be weakened primarily as a result of reduced aerosol loading and increased lifetime of methane, whereas in particular N2O-induced warming will probably continue to increase under all scenarios. Our results indicate that future reductions in anthropogenic Nr to achieve environmental protection goals need to be accompanied by enhanced efforts to reduce anthropogenic greenhouse gas emissions to achieve climate change mitigation in line with the Paris Agreement.

Compact bone mesenchymal stem cells-derived paracrine mediators for cell-free therapy in sepsis.

Sepsis, a life-threatening condition resulting in multiple organ dysfunction, is characterized by a dysregulated immune response to infection. Current treatment options are limited, leading to unsatisfactory outcomes for septic patients. Here, we present a series of studies utilizing compact bone mesenchymal stem cells (CB-MSCs) and their derived paracrine mediators, especially exosome (CB-MSCs-Exo), to treat mice with cecal ligation and puncture-induced sepsis. Our results demonstrate that CB-MSCs treatment significantly improves the survival rate of septic mice by mitigating excessive inflammatory response and attenuating sepsis-induced organ injuries. Furthermore, CB-MSCs-conditioned medium, CB-MSCs secretome (CB-MSCs-Sec), and CB-MSCs-Exo exhibit potent anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated murine macrophage (RAW264.7). Intriguingly, intravenous administration of CB-MSCs-Exo confers superior protection against inflammation and organ damage in septic mice compared to CB-MSCs in certain aspects. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS) shotgun proteomic analysis, we identify a range of characterized proteins derived from the paracrine activity of CB-MSCs, involved in critical biological processes such as immunomodulation and apoptosis. Our findings highlight that the paracrine products of CB-MSCs could serve as a promising cell-free therapeutic agent for sepsis.

Cu-Co bimetallic organic framework as effective adsorbents for enhanced adsorptive removal of tetracycline antibiotics.

In this study, the removal effect of a new MOF-on MOF adsorbent based on Cu-Co bimetallic organic frameworks on tetracycline antibiotics (TCs) in water system was studied. The adsorbent (Cu-MOF@Co-MOF) were synthesized by solvothermal and self-assembly method at different concentrations of Co2+/Cu2+. The characterization results of SEM, XRD, XPS, FTIR and BET indicated that the MOF-on MOF structure of Cu-MOF@Co-MOF exhibited the best recombination and physicochemical properties when the molar ratio of Co2+: Cu2+ is 5:1. In addition, the Cu-MOF@Co-MOF have a high specific surface area and bimetallic clusters, which can achieve multi-target synergistic adsorption of TCs. Based on above advantages, Cu-MOF@Co-MOF provided a strong affinity and could efficiently adsorb more than 80% of pollutants in just 5 to 15 min using only 10 mg of the adsorbent. The adsorption capacity of tetracycline and doxycycline was 434.78 and 476.19 mg/g, respectively, showing satisfactory adsorption performance. The fitting results of the experimental data were more consistent with the Langmuir isotherm model and pseudo-second-order kinetic model, indicating that the adsorption process of TC and DOX occurred at the homogeneous adsorption site and was mainly controlled by chemisorption. Thermodynamic experiments showed that Cu-MOF@Co-MOF was thermodynamically advantageous for the removal of TCs, and the whole process was spontaneous. The excellent adsorption capacity and rapid adsorption kinetics indicate the prepared MOF-on MOF adsorbent can adsorb TCs economically and quickly, and have satisfactory application prospects for removing TCs in practical environments. The results of the study pave a new way for preparing novel MOFs-based water treatment materials with great potential for efficient removal.

Co-mutation of OsLPR1/3/4/5 provides a promising strategy to minimize Cd contamination in rice grains.

Minimizing cadmium (Cd) contamination in rice grains is crucial for ensuring food security and promoting sustainable agriculture. Utilizing genetic modification to generate rice varieties with low Cd accumulation is a promising strategy due to its cost-effectiveness and operational simplicity. Our study demonstrated that the CRISPR-Cas9-mediated quadruple mutation of the multicopper oxidase genes OsLPR1/3/4/5 in the japonica rice cultivar Tongjing 981 had little effect on yields. However, a notable increase was observed in the cell wall functional groups that bind with Cd. As a result, the quadruple mutation of OsLPR1/3/4/5 enhanced Cd sequestration within the cell wall while reducing Cd concentrations in both xylem and phloem sap, thereby inhibiting Cd transport from roots to shoots. Consequently, Cd concentrations in brown rice and husk in oslpr1/3/4/5 quadruple mutants (qm) decreased by 52% and 55%, respectively, compared to the wild-type. These findings illustrate that the quadruple mutation of OsLPR1/3/4/5 is an effective method for minimizing Cd contamination in rice grains without compromising yields. Therefore, the quadruple mutation of OsLPR1/3/4/5 via biotechnological pathways may represent a valuable strategy for the generation of new rice varieties with low Cd accumulation.

SPOP expression is associated with tumor-infiltrating lymphocytes in pancreatic cancer.

BACKGROUND: Speckle Type POZ Protein (SPOP), despite its tumor type-dependent role in tumorigenesis, primarily as a tumor suppressor gene is associated with a variety of different cancers. However, its function in pancreatic cancer remains uncertain. METHODS: SPOP expression and the association between its expression and patient prognosis and immune function were evaluated using The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), The Tumor Immune Estimation Resource 2.0 (TIMER2.0) database, cBioportal, and various bioinformatic databases. Enrichment analysis of SPOP and the association between SPOP expression with clinical stage and grade were analyzed using the R software package. Then immunohistochemistry (IHC) was used to estimate the correlation between SPOP and tumor-infiltrating lymphocytes (TILs) in patients with pancreatic cancer. RESULTS: As part of our study, we assessed that SPOP was anomalously expressed in kinds of cancers, associated with clinical stage and outcomes. Meanwhile, SPOP also played a crucial role in the tumor microenvironment (TME). The expression level of SPOP was significantly correlated to tumor-infiltrating immune cells (TICs) in pancreatic cancer. CONCLUSIONS: Our study uncovered the potential corrections in SPOP with TICs, suggesting that SPOP may act as a biomarker for immunotherapy in pancreatic cancer.

Development and Implementation of a Dynamically Updated Big Data Intelligence Platform Using Electronic Medical Records for Secondary Hypertension.

Background: The accurate identification and diagnosis of secondary hypertension is critical,especially while cardiovascular heart disease continues to be the leading cause of death. To develop a big data intelligence platform for secondary hypertension using electronic medical records to contribute to future basic and clinical research. Methods: Using hospital data, the platform, named Hypertension DATAbase at Urumchi (UHDATA), included patients diagnosed with hypertension at the People's Hospital of Xinjiang Uygur Autonomous Region since December 2004. The electronic data acquisition system, the database synchronization technology, and data warehouse technology (extract-transform-load, ETL) for the scientific research big data platform were used to synchronize and extract the data from each business system in the hospital. Standard data elements were established for the platform, including demographic and medical information. To facilitate the research, the database was also linked to the sample database system, which includes blood samples, urine specimens, and tissue specimens. Results: From December 17, 2004, to August 31, 2022, a total of 295,297 hypertensive patients were added to the platform, with 53.76% being males, with a mean age of 59 years, and 14% with secondary hypertension. However, 75,802 patients visited the Hypertension Center at our hospital, with 43% (32,595 patients) being successfully diagnosed with secondary hypertension. The database contains 1458 elements, with an average fill rate of 90%. The database can continuously include the data for new hypertensive patients and add new data for existing hypertensive patients, including post-discharge follow-up information, and the database updates every 2 weeks. Presently, some studies that are based on the platform have been published. Conclusions: Using computer information technology, we developed and implemented a big database of dynamically updating electronic medical records for patients with hypertension, which is helpful in promoting future research on secondary hypertension.