Challenges in treating coexisting scrotal apocrine carcinoma and gastric cancer: insights from an elderly patient: a case report and literature review.

BACKGROUND: Apocrine carcinoma associated with Paget's disease is a rare malignancy that typically manifests in elderly individuals, predominantly affecting the geriatric population. It commonly arises in regions rich in apocrine glands and often exhibits an insidious onset, potentially requiring several years to be diagnosed. CASE PRESENTATION: An 80-year-old male was simultaneously diagnosed with scrotal apocrine carcinoma (showing Paget changes) and early-stage gastric cancer. Whole-genome exome sequencing confirmed these as independent malignancies with minimal genetic overlap, indicating that they were two primary tumors. The patient initially underwent successful surgery but experienced recurrence and metastasis. Treatment with capecitabine and paclitaxel showed promising responses, highlighting similarities between breast and apocrine carcinomas. Challenges were noted in the use of genetic testing and drug susceptibility assessments for treatment guidance. Notably, HER-2 expression in metastatic lesions, a trait of apocrine carcinoma, has remained unexplored due to negative HER-2 FISH results and a lack of available targeted therapies in China. CONCLUSION: Elderly patients often exhibit a lesser degree of aggressiveness toward treatment following a diagnosis of malignant tumors. It is imperative to carefully consider how to strike a balance between effective treatment and maintaining a satisfactory quality of life for these patients. This case underscores the complexity of treating coexisting rare cancers in older adults and emphasizes the need for personalized treatments and continued innovation in cancer therapy. The insights gained offer significant value in understanding and managing such rare cancer cases.

Amentoflavone maintaining extracellular matrix homeostasis and inhibiting subchondral bone loss in osteoarthritis by inhibiting ERK, JNK and NF-κB signaling pathways.

Amentoflavone (AF), a plant biflavone isolated from Selaginella sinensis ethanol extract, is characterized by anti-inflammatory and anti-oxidant properties. According to previous studies, inflammation and oxidative stress are closely related to the pathophysiology of osteoarthritis (OA). However, the effects and mechanisms of AF on OA have not been elucidated.To investigate the inhibitory effects and its molecular mechanism of AF on extracellular matrix (ECM) degradation stimulated by IL-1ß as well as subchondral bone loss induced by RANKL in mice chondrocytes. Quantitative PCR was used to detect the mRNA expression of genes related to inflammation, ECM, and osteoclast differentiation. Protein expression level of iNOS, COX-2, MMP13, ADAMTS5, COL2A1, SOX9, NFATc1, c-fos, JNK, ERK, P65, IκBα was measured by western blotting. The levels of TNF-α and IL-6 in the supernatants were measured by ELISA. The amount of ECM in chondrocytes was measured using toluidine blue staining. The levels of Aggrecan and Col2a1 in chondrocytes were measured using immunofluorescence. Tartrate-resistant acid phosphatase (TRAP) staining, F-actin staining and immunofluorescence were used to detect the effect of AF on osteoclast differentiation and bone resorption. The effect of AF on destabilization of the medial meniscus (DMM)-induced OA mice can be detected in hematoxylin-eosin (H&E) staining, Safranin O green staining and immunohistochemistry.AF might drastically attenuated IL-1ß-stimulated inflammation and reduction of ECM formation by blocking ERK and NF-κB signaling pathways in chondrocytes. Meanwhile, AF suppressed the formation of osteoclasts and the resorption of bone function induced by RANKL. In vivo, AF played a protective role by stabilizing cartilage ECM and inhibiting subchondral bone loss in destabilization of the medial meniscus (DMM)-induced OA mice, further proving its protective effect in the development of OA. Our study show that AF alleviated OA by suppressing ERK, JNK and NF-κB signaling pathways in OA models in vitro and DMM-induced OA mice, suggesting that AF might be a potential therapeutic agent in the treatment of OA.

Cynarin inhibits microglia-induced pyroptosis and neuroinflammation via Nrf2/ROS/NLRP3 axis after spinal cord injury.

BACKGROUND: Spinal cord injury (SCI) elicits excess neuroinflammation and resident microglial pyroptosis, leading further terrible neurological collapse and locomotor dysfunction. However, the current clinical therapy is useless and a feasible treatment is urgent to be explored. Cynarin is a natural component in artichoke playing anti-inflammatory and anti-aging roles in hepatoprotection and cardioprotection, but it is unclear that the pharmacologic action and underlying mechanism of Cynarin in neuropathy. METHODS: Using the SCI mouse model and the BV2 cell line, we here investigated whether Cynarin reduces neuroinflammation and pyroptosis to promote neurological recovery after SCI. RESULTS: Our results showed that treatment with Cynarin reduces the level of neuroinflammation and microglial pyroptosis. Moreover, the mice treated with Cynarin exhibited lower level of reactive oxygen species (ROS) and cell death, less damage of neurohistology and better locomotor improvement of hindlimbs than the untreated mice and the nuclear factor erythroid 2-related factor 2 (Nrf2)-inhibited mice. Mechanically, Cynarin inhibited the assembly of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome by Nrf2-dependent expression to attenuate microglial pyroptosis and neuroinflammation. CONCLUSIONS: To sum up, the current study suggested that administration of Cynarin is a promising compound for anti-neuroinflammation and anti-pyroptosis after SCI. It may be an efficient Nrf2 activator and a NLRP3 inhibitor for microglia in neuropathies.

Post-Transition State Bifurcation Controls Torsional Selectivity in Radical Addition of Allenes.

Post-transition state bifurcation (PTSB) has received wide attention in the field of reaction mechanism research due to its role in producing nonstatistical reaction selectivity, which cannot be solely explained by transition state theory. Particularly, even subtle molecular motions such as bond torsion can precipitate PTSB, thereby significantly complicating the quantitative understanding of dynamic selectivity. In this work, we found that the radical addition of allenes is an elementary transformation that generally exhibits PTSB stereoselectivity, where a single radical addition transition state can lead to both Z- and E-allylic radicals via the post-transition state allylic single bond torsion. Interestingly, dynamic Z/E-selectivity favors the Z-allylic radicals, which contrasts the thermodynamic preference. Based on the dynamics study of twenty-five radical additions of mono-substituted allenes with diverse electronic and steric effects, we have identified that this dynamic stereoselectivity is synergistically controlled by the transition state structure and the differential trends within specific dimensions of the bifurcating reaction coordinates, which also holds true for di-substituted allene substrates. This study refines the mechanism of radical addition of allenes and underscores the importance of the differential trend of the reaction coordinates in controlling dynamic selectivity, offering a deeper insight into PTSB selectivity factors.

Paper-Recorded ECG Digitization Method with Automatic Reference Voltage Selection for Telemonitoring and Diagnosis.

In electrocardiograms (ECGs), multiple forms of encryption and preservation formats create difficulties for data sharing and retrospective disease analysis. Additionally, photography and storage using mobile devices are convenient, but the images acquired contain different noise interferences. To address this problem, a suite of novel methodologies was proposed for converting paper-recorded ECGs into digital data. Firstly, this study ingeniously removed gridlines by utilizing the Hue Saturation Value (HSV) spatial properties of ECGs. Moreover, this study introduced an innovative adaptive local thresholding method with high robustness for foreground-background separation. Subsequently, an algorithm for the automatic recognition of calibration square waves was proposed to ensure consistency in amplitude, rather than solely in shape, for digital signals. The original signal reconstruction algorithm was validated with the MIT-BIH and PTB databases by comparing the difference between the reconstructed and the original signals. Moreover, the mean of the Pearson correlation coefficient was 0.97 and 0.98, respectively, while the mean absolute errors were 0.324 and 0.241, respectively. The method proposed in this study converts paper-recorded ECGs into a digital format, enabling direct analysis using software. Automated techniques for acquiring and restoring ECG reference voltages enhance the reconstruction accuracy. This innovative approach facilitates data storage, medical communication, and remote ECG analysis, and minimizes errors in remote diagnosis.

Clinical efficacy of Xuebijing injection for the treatment of sepsis: A retrospective cohort study.

OBJECTIVE: The objective of this study was to investigate the clinical efficacy and safety of treating sepsis patients with Xuebijing injection (XBJI). METHODS: We conducted a retrospective analysis of 418 patients who experienced severe infections and were treated with XBJI from June 2018 to June 2021. Propensity score matching was used to match the patient cases. The study population included 209 pairs of cases (418 individuals), and the analysis included data from before and after a 14-day course of treatment with carbapenem alone, or carbapenem with XBJI. RESULTS: There were no significant differences in the 14-day mortality or length of hospital stay (P > 0.05) between the two groups. The combined treatment group had more patients with C-reactive protein that returned to normal levels (compared to baseline) than the non-combined treatment group (14.4% vs 8.1%; odds ratio [OR]: 0.528; 95% confidence interval [CI]: 0.282-0.991; P = 0.026). Similarly, the combined treatment group had higher procalcitonin attainment rate (55.0% vs 39.7%; OR: 0.513; 95% CI: 0.346-0.759; P = 0.001) than the non-combined treatment group. Further, more patients in the combined treatment group achieved normal creatinine levels than in the non-combined treatment group (64.1% vs 54.1%; OR: 0.659; 95% CI: 0.445-0.975; P = 0.037). CONCLUSION: The combination of XBJI with carbapenem did not reduce the 14-day mortality rate of patients with severe infection, but it was able to reduce the level of inflammatory factors in patients with sepsis, and had a protective effect on liver and kidney function. Please cite this article as: Gong ZT, Yang HX, Zhu BB, Liu HH, Siri GL. Clinical efficacy of Xuebijing injection for the treatment of sepsis: A retrospective cohort study. J Integr Med. 2024; Epub ahead of print.

Short-term outcomes of totally robotic versus robotic-assisted distal gastrectomy for gastric cancer: a single-center retrospective study.

BACKGROUND: Totally robotic distal gastrectomy (TRDG) is being used more and more in gastric cancer (GC) patients. The study aims to evaluate the short-term efficacy of TRDG and robotic-assisted distal gastrectomy (RADG) in the treatment of GC. METHODS: We retrospectively collected the clinical data of patients who underwent TRDG or RADG, of which 60 patients were included in the study: 30 cases of totally robotic and 30 cases of robotic-assisted. The short-term efficacy of the two groups was compared. RESULTS: There was no significant difference in the clinicopathological data between the two groups. Compared to RADG, TRDG had less intraoperative blood loss(P = 0.019), less postoperative abdominal drainage(P = 0.031), shorter time of exhaust( P = 0.001) and liquid diet(P = 0.001), shorter length of incision(P<0.01), shorter postoperative hospital stays(P = 0.033), lower postoperative C-reactive protein(CRP)(P = 0.024) and lower postoperative Visual Analogue Scale(VAS) scores(P = 0.048). However, no significant statistical differences were found in terms of total operation time(P = 0.108), number of lymph nodes retrieved(P = 0.307), time for anastomosis(P = 0.450), proximal resection margin(P = 0.210), distal resection margin(P = 0.202), postoperative complication(P = 0.506), total hospital cost(P = 0.286) and postoperative white blood cell(WBC)(P = 0.113). CONCLUSIONS: In terms of security and technology, TRDG could serve as a better treatment method for GC.

Exploring Prostate Cancer Incidence Trends and Age Change in Cancer Registration Areas of Jiangsu Province, China, 2009 to 2019.

(1) Background: Over the past few decades, Jiangsu Province, China, has witnessed a remarkable surge in the incidence of prostate cancer (PCa), accompanied by notable demographic shifts; (2) Methods: PCa data for Jiangsu Province from 2009 to 2019 were obtained from the Jiangsu Cancer Registry. We calculated crude and age-specific incidence rates (ASIRs), average age at onset, and age-specific composition ratios. Standardization was performed based on the Segi's world population. Birth cohorts (1929-2019) were analyzed to assess PCa incidence by birth year. Trend analysis was conducted using the Joinpoint Regression Model, and average annual percent changes (AAPCs) with corresponding 95% confidence interval (CI) were computed. A linear regression model was used to analyze the relationship between the average age at diagnosis and calendar years; (3) Results: The ASIRs of PCa in Jiangsu Province increased significantly, with an AAPC of 11.25% (95%CI: 10.09%, 12.42%) from 2009 to 2019. This increase was observed across all age groups, particularly among those aged 0-59 years. Birth cohort analysis revealed a rising trend with earlier birth years showing higher incidence, notably in the 1959 cohort. In rural areas, the age-standardized average age at onset of PCa decreased from 75.45 years in 2009 to 73.39 years in 2019, and the peak age group shifted from 75-79 years in 2009 to 70-74 years in 2019; (4) Conclusions: The rising incidence of PCa in Jiangsu Province, along with an increased proportion of cases in younger age groups, highlights the need for targeted interventions.

Primary signet-ring cell carcinoma of the urinary bladder ‒ A rare bladder tumor.

AIM: Primary Signet Ring Cell Carcinoma (SRCC) of the bladder accounts for only 1%‒4% of all bladder malignancies. To date, few studies have been conducted to investigate the characteristics of SRCC. This study aimed to investigate the clinical features and treatments of SRCC and explore the independent risk factors of survival in SRCC patients. PATIENTS AND METHODS: A retrospective study was conducted on 32 eligible patients. The survival rate was calculated with the Kaplan-Meier method, and the COX proportional hazards model was used to investigate the independent risk factors of prognosis. RESULTS: In the present study, the 1-year and 2-year survival rates of SRCC patients were 53.1% and 9.4%, respectively. The TNM stage, tumor differentiation, and metastasis after treatment were risk factors for the prognosis of SRCC patients (p < 0.05), while surgical treatment, chemotherapy, and positive GATA3 expression were protective for prognosis (p < 0.05). Multivariate analysis showed that GATA3 was an independent protective factor for prognosis (p < 0.05), and T-stage was an independent risk factor (p < 0.05). CONCLUSIONS: Primary SRCC of the bladder is highly malignant and has a poor prognosis. Its clinical and imaging findings are usually non-specific. Early radical cystectomy and postoperative adjuvant systemic chemotherapy are helpful to improve the survival rate. T-stage is an independent risk factor for survival, and positive GATA3 expression is protective for primary SRCC of the bladder.

Early-onset scoliosis in children aged 4-7 years in Nanjing, China: A cross-sectional study.

Background: This study aimed to investigate the potential variance in the prevalence of early-onset scoliosis among children aged 4-7 years and analyze the influencing factors. The goal was to establish a crucial reference point for monitoring and evaluating spinal curvature development in preschoolers, ultimately to reduce the occurrence of adverse health outcomes. Methods: Children aged 4-7 years within the main urban area of Nanjing were selected using a stratified random sampling method. A team of four senior therapists conducted screenings for spinal curvature among children using visual inspection, the Adams forward bending test, and an electronic scoliometer to measure the angle of trunk rotation (ATR) and identify children displaying signs of scoliosis. Children with suspected scoliosis in the initial screening underwent X-ray Cobb angle assessment for confirmation. The prevalence of early-onset scoliosis was then determined from the screening results. R version 4.2.0 software was used to analyze the factors associated with scoliosis among children using partial least squares structural equation modeling. Results: A total of 2281 children were included in this study, consisting of 1211 boys and 1070 girls, with a mean age of 5.44 ± 0.81 years (ranging from 4 to 7 years). Among them, 7.58% exhibited positive signs of scoliosis, 5.87% had early-onset scoliosis, and the positive predictive value was 77.5%. Significant differences in ATR were observed among children in different age groups (Kruskal-Wallis = 15, p = 0.0104) and by sex (t = 3.17, p = 0.00153). Significant variations in ATR were noted in children with scoliosis (t = -22.7, p < 0.001), with a cutoff at ATR = 4.5°, and auxiliary values of 0.947 and 0.990. Children diagnosed with early-onset scoliosis generally exhibited lower body mass index values, with a statistically significant difference (t = 2.99, p = 0.003). Conclusions: Using visual inspection, the Adams test, and an electronic scoliometer to measure the ATR, the present triad method is more sensitive for early scoliosis screening in children with abnormal posture aged 4-7 years. A full spine X-ray is advised in children with an ATR over 4.5° and poor posture.

An unusual winter bloom of dinoflagellates with notable damage to kelp cultivation around Shandong peninsula, China.

In the coastal waters around Shandong peninsula, an unprecedented winter bloom of dinoflagellates Gonyaulax polygramma and Akashiwo sanguinea occurred in 2021 from late November to early December. The bloom affected a wide area of coastal waters extending from west to east along the northern Shandong peninsula and had a devastating blow to the kelp cultivation industry. Based on the remote-sensing data, the initiation of the bloom was traced back to the region adjacent to the mouth of the Yellow River in Laizhou Bay, where enhanced freshwater discharge from the Yellow River was recorded from September to November. It's proposed that the increased precipitation in the Yellow River basin associated with northward extension of the precipitation band in China could be an important reason for this winter bloom. This unusual winter bloom around Shandong peninsula highlights the potential risks of harmful algal blooms and their impacts on coastal ecosystems under the background of climate change.

Identifying neuroimaging biomarkers in major depressive disorder using machine learning algorithms and functional near-infrared spectroscopy (fNIRS) during verbal fluency task.

One of the most prevalent psychiatric disorders is major depressive disorder (MDD), which increases the probability of suicidal ideation or untimely demise. Abnormal frontal hemodynamic changes detected by functional near-infrared spectroscopy (fNIRS) during verbal fluency task (VFT) have the potential to be used as an objective indicator for assessing clinical symptoms. However, comprehensive quantitative and objective assessment instruments for individuals who exhibit symptoms suggestive of depression remain undeveloped. Drawing from a total of 467 samples in a large-scale dataset comprising 289 MDD patients and 178 healthy controls, fNIRS measurements were obtained throughout the VFT. To identify unique MDD biomarkers, this research introduced a data representation approach for extracting spatiotemporal features from fNIRS signals, which were subsequently utilized as potential predictors. Machine learning classifiers (e.g., Gradient Boosted Decision Trees (GBDT) and Multilayer Perceptron) were implemented to assess the ability to predict selected features. The mean and standard deviation of the cross-validation indicated that the GBDT model, when combined with the 180-feature pattern, distinguishes patients with MDD from healthy controls in the most effective manner. The accuracy of correct classification for the test set was 0.829 ± 0.053, with an AUC of 0.895 (95 % CI: 0.864-0.925) and a sensitivity of 0.914 ± 0.051. Channels that made the most important contribution to the identification of MDD were identified using Shapley Additive Explanations method, located in the frontopolar area and the dorsolateral prefrontal cortex, as well as pars triangularis Broca's area. Assessment of abnormal prefrontal activity during the VFT in MDD serves as an objectively measurable biomarker that could be utilized to evaluate cognitive deficits and facilitate early screening for MDD. The model suggested in this research could be applied to large-scale case-control fNIRS datasets to detect unique characteristics of MDD and offer clinicians an objective biomarker-based analytical instrument to assist in the evaluation of suspicious cases.

COVID-19-Related Post-Traumatic Stress Disorders Relation With Social Media Addiction Among University Students: Mediating Role of Fear of Missing Out.

OBJECTIVE: Traumatic experiences and stressful life events have crippling outcomes on individuals' psychiatric disorders and are also frequently comorbid with addictive behaviors. This study aims to propose a mediation model to examine the association between coronavirus disease-2019 (COVID-19)-related post-traumatic stress disorder (PTSD) and social media addiction (SMA) among university students, and the mediating role of fear of missing out (FoMO). METHODS: A cross-sectional study with 856 university students (mean age 19.2 years; 67.9% female) was conducted in China. The COVID-19-related PTSD scale, the FoMO scale, and the Bergen Social Media Addiction Scale were used, in addition to an online questionnaire addressing participants' sociodemographic information. Descriptive statistics and correlations were conducted with SPSS 21.0. The Structural Equation Model (SEM) with AMOS 21.0 was performed to assess the hypothesized mediation mode. The bootstrap with the 95% confidence interval (CI) was computed to test the significance of the mediating effect. RESULTS: SEM demonstrated that COVID-19-related PTSD symptoms significantly and negatively influenced SMA (ß=0.247, p<0.001), FoMO significantly and positively affected university students' SMA (ß=0.341, p<0.001), and FoMO partially mediated the association between COVID-19-related PTSD symptoms and SMA. The mediation effect of FoMO was 0.176, with bootstrapping 95% CI=0.123, 0.235. CONCLUSION: The main effects of COVID-19-related PTSD symptoms and FoMO on SMA among university students were identified, providing intervention strategies for mental health professionals on how to reduce the risk of SMA when confronting future traumatic events and public health crises.

Advances in macrophage metabolic reprogramming in myocardial ischemia-reperfusion.

Acute myocardial infarction (AMI) is the leading cause of death worldwide, and reperfusion therapy is a critical therapeutic approach to reduce myocardial ischemic injury and minimize infarct size. However, ischemia/reperfusion (I/R) itself also causes myocardial injury, and inflammation is an essential mechanism by which it leads to myocardial injury, with macrophages as crucial immune cells in this process. Macrophages are innate immune cells that maintain tissue homeostasis, host defence during pathogen infection, and repair during tissue injury. During the acute phase of I/R, M1-type macrophages generate a pro-inflammatory milieu, clear necrotic myocardial tissue, and further recruit mononuclear (CCR2+) macrophages. Over time, the reparative (M2 type) macrophages gradually became dominant. In recent years, metabolic studies have shown a clear correlation between the metabolic profile of macrophages and their phenotype and function. M1-type macrophages are mainly characterized by glycolytic energy supply, and their tricarboxylic acid (TCA) cycle and mitochondrial oxidative phosphorylation (OXPHOS) processes are impaired. In contrast, M2 macrophages rely primarily on OXPHOS for energy. Changing the metabolic profile of macrophages can alter the macrophage phenotype. Altered energy pathways are also present in macrophages during I/R, and intervention in this process contributes to earlier and greater M2 macrophage infiltration, which may be a potential target for the treatment of myocardial I/R injury. Therefore, this paper mainly reviews the characteristics of macrophage energy metabolism alteration and phenotypic transition during I/R and its mechanism of mediating myocardial injury to provide a basis for further research in this field.

Biofluorescence imaging-guided spatial metabolic tracing: In vivo tracking of metabolic activity in circulating tumor cell-mediated multi-organ metastases.

Circulating tumor cells (CTC) are considered metastatic precursors that are shed from the primary or metastatic deposits and navigate the bloodstream before undergoing extravasation to establish distant metastases. Metabolic reprogramming appears to be a hallmark of metastatic progression, yet current methods for evaluating metabolic heterogeneity within organ-specific metastases in vivo are limited. To overcome this challenge, we present Biofluorescence Imaging-Guided Spatial Metabolic Tracing (BIGSMT), a novel approach integrating in vivo biofluorescence imaging, stable isotope tracing, stain-free laser capture microdissection, and liquid chromatography-mass spectrometry. This innovative technology obviates the need for staining or intricate sample preparation, mitigating metabolite loss, and substantially enhances detection sensitivity and accuracy through chemical derivatization of polar metabolites in central carbon pathways. Application of BIGSMT to a preclinical CTC-mediated metastasis mouse model revealed significant heterogeneity in the in vivo carbon flux from glucose into glycolysis and the tricarboxylic acid (TCA) cycle across distinct metastatic sites. Our analysis indicates that carbon predominantly enters the TCA cycle through the enzymatic reaction catalyzed by pyruvate dehydrogenase. Thus, our spatially resolved BIGSMT technology provides fresh insights into the metabolic heterogeneity and evolution during melanoma CTC-mediated metastatic progression and points to novel therapeutic opportunities.

Association between blood pressure multi-trajectory and cardiovascular disease among a Chinese elderly medical examination population.

Objective: This study aimed to characterize multivariate trajectories of blood pressure [systolic blood pressure (SBP) and diastolic blood pressure (DBP)] jointly and examine their impact on incident cardiovascular disease (CVD) among a Chinese elderly medical examination population. Methods: A total of 13,504 individuals without CVD during 2018-2020 were included from the Chinese geriatric physical examination cohort study. The group-based trajectory model was used to construct multi-trajectories of systolic blood pressure and diastolic blood pressure. The primary outcome was the incidence of the first CVD events, consisting of stroke and coronary heart diseases, in 2021. The Cox proportional hazards model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between BP multi-trajectories and incident CVD events. Results: We identified four blood pressure (BP) subclasses, summarized by their SBP and DBP levels from low to high as class 1 (7.16%), class 2 (55.17%), class 3 (32.26%), and class 4 (5.41%). In 2021, we documented 890 incident CVD events. Compared with participants in class 1, adjusted HRs were 1.56 (95% CI: 1.12-2.19) for class 2, 1.75 (95% CI: 1.24-2.47) for class 3, and 1.88 (95% CI: 1.24-2.85) for class 4 after adjustment for demographics, health behaviors, and metabolic index. Individuals aged 65 years and above with higher levels of BP trajectories had higher risks of CVD events in China. Conclusions: Individuals with higher levels of both SBP and DBP trajectories over time were associated with an increased risk of incident CVD in the Chinese elderly population.

Analysis of the efficacy of angiojet percutaneous mechanical thrombectomy combined with catheter-directed thrombolysis versus catheter-directed thrombolysis alone in the treatment of subacute iliofemoral deep venous thrombosis in elderly patients.

PURPOSE: To analysis the clinical efficacy of Angiojet percutaneous mechanical thrombectomy (PMT) combined with Catheter-Directed Thrombolysis (CDT) compared to CDT in treatment of subacute iliofemoral deep venous thrombosis (IFDVT) in elderly patients. METHODS: A retrospective analysis of the clinical data of 117 elderly patients hospitalized for subacute IFDVT was conducted. The patients'basic perioperative data and 2-years follow-up data were compared. RESULTS: Group A (PMT + CDT) had a more patients reaching Grade III thrombus clearance, and a lower thrombolysis time, dosage of thrombolytic drugs, hospital stay, and bleeding incidence compared to Group B (CDT). There was a statistically significant difference in the occurrence rate of severe PTS within 2 years (p < 0.05). CONCLUSION: In treating elderly patients with subacute IFDVT, PMT + CDT effectively reduces the thrombus burden and the dosage of thrombolytic drugs, shortens the hospital stay, and importantly, reduces the occurrence rate of severe PTS within 2 years.

CDCA7 is an evolutionarily conserved hemimethylated DNA sensor in eukaryotes.

Mutations of the SNF2 family ATPase HELLS and its activator CDCA7 cause immunodeficiency, centromeric instability, and facial anomalies syndrome, characterized by DNA hypomethylation at heterochromatin. It remains unclear why CDCA7-HELLS is the sole nucleosome remodeling complex whose deficiency abrogates the maintenance of DNA methylation. We here identify the unique zinc-finger domain of CDCA7 as an evolutionarily conserved hemimethylation-sensing zinc finger (HMZF) domain. Cryo-electron microscopy structural analysis of the CDCA7-nucleosome complex reveals that the HMZF domain can recognize hemimethylated CpG in the outward-facing DNA major groove within the nucleosome core particle, whereas UHRF1, the critical activator of the maintenance methyltransferase DNMT1, cannot. CDCA7 recruits HELLS to hemimethylated chromatin and facilitates UHRF1-mediated H3 ubiquitylation associated with replication-uncoupled maintenance DNA methylation. We propose that the CDCA7-HELLS nucleosome remodeling complex assists the maintenance of DNA methylation on chromatin by sensing hemimethylated CpG that is otherwise inaccessible to UHRF1 and DNMT1.

Numerical simulation of CO2-ECBM for deep coal reservoir with strong stress sensitivity.

CH4 production rate of coalbed methane (CBM) well decreases rapidly during primary recovery in the deeply buried coal seam, resulting in a lot of CH4 residues. CO2 pour into deep coal seam with high stress sensitivity is available for enhancing CH4 recovery by improving permeability for reservoir fracture and displacing CH4 adsorbed in matrix. A coupled adsorp-hydro-thermo-mechanical (AHTM) model for deep methane development is established by considering the coupling relationships of non-isothermal and non-constant pressure competitive adsorption between CO2 and CH4, multi-phase flow, unsteady diffusion, heat transmission and in-situ stress variety. The model is verified by historical production and then used for CO2 enhanced CBM (CO2-ECBM) of deep coal reservoir in a sedimentary basin in Northwest China. The simulation results show that: (1) For primary recovery, permeability in coal reservoir drops rapidly with the development of CBM, which seriously restricts the production of CH4. The permeability of the reservoir decreases from 7.89 × 10-16 m2 to less than 1.50 × 10-16 m2, CH4 production rate in CBM well reduces to below 2000 m3/d, and the average total CH4 content of coal reservoir is reduced by 5.49 m3/t with the decrease of only 1.12 m3/t of average adsorbed CH4 in a production duration of 2000 d (2) With 10 MPa CO2 continuous injection into coal seam after 700d of primary, the permeability for reservoir and CH4 production rate increase while the total CH4 content and adsorption CH4 content in reservoir decrease compared with the primary recovery. (3) CO2 pouring into coal reservoir increases the CH4 production time and rate, which improves CH4 recovery of coal reservoir. And it increases by 23.36 %, 23.07 % and 22.46 % with shut-in thresholds of CH4 production rate of 1000 m3/d, 800 m3/d and 600 m3/d, respectively. The investigation is of great significance for the development of deep coalbed methane.

Characterization of the novel broad-spectrum lytic phage Phage_Pae01 and its antibiofilm efficacy against Pseudomonas aeruginosa.

Introduction: Pseudomonas aeruginosa is present throughout nature and is a common opportunistic pathogen in the human body. Carbapenem antibiotics are typically utilized as a last resort in the clinical treatment of multidrug-resistant infections caused by P. aeruginosa. The increase in carbapenem-resistant P. aeruginosa poses an immense challenge for the treatment of these infections. Bacteriophages have the potential to be used as antimicrobial agents for treating antibiotic-resistant bacteria. Methods and Results: In this study, a new virulent P. aeruginosa phage, Phage_Pae01, was isolated from hospital sewage and shown to have broad-spectrum antibacterial activity against clinical P. aeruginosa isolates (83.6%). These clinical strains included multidrug-resistant P. aeruginosa and carbapenem-resistant P. aeruginosa. Transmission electron microscopy revealed that the phage possessed an icosahedral head of approximately 80 nm and a long tail about 110 m, indicating that it belongs to the Myoviridae family of the order Caudovirales. Biological characteristic analysis revealed that Phage_Pae01 could maintain stable activity in the temperature range of 4~ 60°C and pH range of 4 ~ 10. According to the in vitro lysis kinetics of the phage, Phage_Pae01 demonstrated strong antibacterial activity. The optimal multiplicity of infection was 0.01. The genome of Phage_Pae01 has a total length of 93,182 bp and contains 176 open reading frames (ORFs). The phage genome does not contain genes related to virulence or antibiotic resistance. In addition, Phage_Pae01 effectively prevented the formation of biofilms and eliminated established biofilms. When Phage_Pae01 was combined with gentamicin, it significantly disrupted established P. aeruginosa biofilms. Conclusion: We identified a novel P. aeruginosa phage and demonstrated its effective antimicrobial properties against P. aeruginosa in both the floating and biofilm states. These findings offer a promising approach for the treatment of drug-resistant bacterial infections in clinical settings.