Biodegradable Microembolics with Nanografted Polyanions Enable High-Efficiency Drug Loading and Sustained Deep-Tumor Drug Penetration for Locoregional Chemoembolization Treatment.

Transarterial chemoembolization (TACE), the mainstay treatment of unresectable primary liver cancer that primarily employs nondegradable drug-loaded embolic agents to achieve synergistic vascular embolization and locoregional chemotherapy effects, suffers from an inferior drug burst behavior lacking long-term drug release controllability that severely limits the TACE efficacy. Here we developed gelatin-based drug-eluting microembolics grafted with nanosized poly(acrylic acid) serving as a biodegradable ion-exchange platform that leverages a counterion condensation effect to achieve high-efficiency electrostatic drug loading with electropositive drugs such as doxorubicin (i.e., drug loading capacity >34 mg/mL, encapsulation efficiency >98%, and loading time <10 min) and an enzymatic surface-erosion degradation pattern (∼2 months) to offer sustained locoregional pharmacokinetics with long-lasting deep-tumor retention capability for TACE treatment. The microembolics demonstrated facile microcatheter deliverability in a healthy porcine liver embolization model, superior tumor-killing capacity in a rabbit VX2 liver cancer embolization model, and stabilized extravascular drug penetration depth (>3 mm for 3 months) in a rabbit ear embolization model. Importantly, the microembolics finally exhibited vessel remodeling-induced permanent embolization with minimal inflammation responses after complete degradation. Such a biodegradable ion-exchange drug carrier provides an effective and versatile strategy for enhancing long-term therapeutic responses of various local chemotherapy treatments.

Home Blood Pressure Telemonitoring and Nurse Case Management in Black and Hispanic Patients With Stroke: A Randomized Clinical Trial.

Importance: Black and Hispanic patients have high rates of recurrent stroke and uncontrolled hypertension in the US. The effectiveness of home blood pressure telemonitoring (HBPTM) and telephonic nurse case management (NCM) among low-income Black and Hispanic patients with stroke is unknown. Objective: To determine whether NCM plus HBPTM results in greater systolic blood pressure (SBP) reduction at 12 months and lower rate of stroke recurrence at 24 months than HBPTM alone among Black and Hispanic stroke survivors with uncontrolled hypertension. Design, Setting, and Participants: Practice-based, multicenter, randomized clinical trial in 8 stroke centers and ambulatory practices in New York City. Black and Hispanic study participants were enrolled between April 18, 2014, and December 19, 2017, with a final follow-up visit on December 31, 2019. Interventions: Participants were randomly assigned to receive either HBPTM alone (12 home BP measurements/week for 12 months, with results transmitted to a clinician; n = 226) or NCM plus HBPTM (20 counseling calls over 12 months; n = 224). Main Outcomes and Measures: Primary outcomes were change in SBP at 12 months and rate of recurrent stroke at 24 months. Final statistical analyses were completed March 14, 2024. Results: Among 450 participants who were enrolled and randomized (mean [SD] age, 61.7 [11.0] years; 51% were Black [n = 231]; 44% were women [n = 200]; 31% had ≥3 comorbid conditions [n = 137]; 72% had household income <$25 000/y [n = 234/324]), 358 (80%) completed the trial. Those in the NCM plus HBPTM group had a significantly greater SBP reduction than those in the HBPTM alone group at 12 months (-15.1 mm Hg [95% CI, -17.2 to -13.0] vs -5.8 mm Hg [95% CI, -7.9 to -3.7], respectively; P < .001). The between-group difference in SBP reduction at 12 months, adjusted for primary care physician clustering, was -8.1 mm Hg (95% CI, -11.2 to -5.0; P < .001) at 12 months. The rate of recurrent stroke was similar between both groups at 24 months (4.0% in the NCM plus HBPTM group vs 4.0% in the HBPTM alone group, P > .99). Conclusions and Relevance: Among predominantly low-income Black and Hispanic stroke survivors with uncontrolled hypertension, addition of NCM to HBPTM led to greater SBP reduction than HBPTM alone. Additional studies are needed to understand the long-term clinical outcomes, cost-effectiveness, and generalizability of NCM-enhanced telehealth programs among low-income Black and Hispanic stroke survivors with significant comorbidity. Trial Registration: Clinical Trials.gov Identifier: NCT02011685.

[Neuroimaging-based study of scalp acupuncture targets for common psychiatric diseases (Part 2)].

In this study, based on the neuroimaging literature Meta analysis retrieved from Neurosynth platform, the scalp stimulation targets for common psychiatric diseases are developed, which provided the stimulation target protocols of scalp acupuncture for attention deficit hyperactivity disorder, autism spectrum disorder, obsessive-compulsive disorder and schizophrenia. The paper introduces the functions of the brain areas that are involved in each target and closely related to the diseases, and lists the therapeutic methods of common acupuncture/scalp acupuncture and common neuromodulation methods for each disease so as to provide the references for clinical practice. Based on the study results above, the paper further summarizes the overlapped stimulation targets undergoing the intervention with scalp acupuncture for common psychiatric diseases, and the potential relationship between these stimulation targets and treatments with acupuncture and moxibustion.

PDE1B, a potential biomarker associated with tumor microenvironment and clinical prognostic significance in osteosarcoma.

PDE1B had been found to be involved in various diseases, including tumors and non-tumors. However, little was known about the definite role of PDE1B in osteosarcoma. Therefore, we mined public data on osteosarcoma to reveal the prognostic values and immunological roles of the PDE1B gene. Three osteosarcoma-related datasets from online websites were utilized for further data analysis. R 4.3.2 software was utilized to conduct difference analysis, prognostic analysis, gene set enrichment analysis (GSEA), nomogram construction, and immunological evaluations, respectively. Experimental verification of the PDE1B gene in osteosarcoma was conducted by qRT-PCR and western blot, based on the manufacturer's instructions. The PDE1B gene was discovered to be lowly expressed in osteosarcoma, and its low expression was associated with poor OS (all P < 0.05). Experimental verifications by qRT-PCR and western blot results remained consistent (all P < 0.05). Univariate and multivariate Cox regression analyses indicated that the PDE1B gene had independent abilities in predicting OS in the TARGET osteosarcoma dataset (both P < 0.05). GSEA revealed that PDE1B was markedly linked to the calcium, cell cycle, chemokine, JAK STAT, and VEGF pathways. Moreover, PDE1B was found to be markedly associated with immunity (all P < 0.05), and the TIDE algorithm further shed light on that patients with high-PDE1B expression would have a better immune response to immunotherapies than those with low-PDE1B expression, suggesting that the PDE1B gene could prevent immune escape from osteosarcoma. The PDE1B gene was found to be a tumor suppressor gene in osteosarcoma, and its high expression was related to a better OS prognosis, suppressing immune escape from osteosarcoma.

Scalp acupuncture targets for neurological disorders：evidence from neuroimaging studies (part 1). / åŸºäºŽç¥žç»å½±åƒå­¦çš„å¸¸è§ç¥žç»ç³»ç»Ÿç–¾ç— å¤´é’ˆåˆºæ¿€é¶ç‚¹ç ”ç©¶ï¼ˆä¸Šï¼‰.

OBJECTIVES: Scalp acupuncture is a unique acupuncture method developed based on brain functional and pathophysiological knowledge. In past decades, there has been significant development in the understanding of the brain pathology of many neurological disorders through cutting-edge brain imaging techniques. Yet, these findings have not been incorporated into scalp acupuncture. In the present paper, we aimed to initiate an attempt to develop/identify scalp acupuncture targets based on neuroimaging findings. METHODS: Based on the meta-analysis of neuroimaging studies in the Neurosynth database platform (http：//neurosynth.org/), the brain clusters related to neurological disorders were automatically identified according to the search terms "Parkinson's disease"(PD), "chronic pain"(CP), "aphasia"(APH), "dyslexia"(DYS), "mild cognitive impairment", "Alzheimer's disease" and "dementia". Subsequently, the discovered brain region clusters projected onto the brain surface and scalp surface were listed, and the peak points of the clusters projected to the scalp surface were proposed as the potential stimulation targets for the corresponding diseases. Further, by combining the traditional scalp acupoints (including the scalp acupuncture lines) with 10-20 EEG system sites, we made localization suggestions for scalp stimulation targets and made acupuncture operation suggestions by combining with the shape of the brain region clusters. The literature search was conducted on July 30, 2022. RESULTS: The localization and manipulation suggestions of neuroimage-based scalp acupuncture targets were introduced in two parts. This part (part 1) includes PD, CP, APH, and DYS. Here are 3 target examples of each of these 4 diseases simply introduced due to word limitation. 1) PD. Based on the 175 articles retrieved from Neurosynth, we identified 7 potential scalp acupuncture targets for PD, the locations of the acupuncture stimulation and the recommended acupuncture needle operation (RANO) as well as the corresponding brain regions (CBRs) respectively are as below. PD1：about 0.5 cun (1 cun≈33.3 mm) superior-posterior to the left Xuanlu (GB5)；puncturing subcutaneously and forward-upward；the left premotor area, subfrontal cortex of the island, inferior frontal gyrus and middle frontal gyrus. PD2：about 1 cun lateral-inferior to the left Chengling (GB18)；puncturing subcutaneously and backward-upward；the inferior parietal lobule and postcentral gyrus. PD3：about 0.5 cun lateral-anterior to the left GB18；puncturing subcutaneously and inward-backward；left anterior central gyrus and posterior central gyrus. 2) CP. Based on the retrieved 92 articles, we identified 8 potential scalp acupuncture targets, the location of the acupuncture stimulation and the RANO, and CBRs respectively are as below. CP1：about 1 cun anterior-inferior to the left Xuanli (GB8)；puncturing subcutaneously and backward-inwards；the left inferior frontal gyrus orbitalis and pars triangularis. CP2：about 0.5 cun posterior-superior to the left GB5；puncturing subcutaneously and forward-upward；the left anterior central gyrus and premotor area. CP3：about 0.5 cun posterior-superior to the left GB8；puncturing subcutaneously and forward；left inferior central area/central sulci operculum (second somatosensory area). 3) APH. Based on the retrieved 82 papers, we identified 7 potential scalp acupuncture targets for APH, their locations, RANO, and CBRs respectively are as below. APH1：close to the left GB5；puncturing subcutaneously and forward-downward；left subfrontal gyrus operculi/triangularis. APH2：about 0.5 cun posterior to the left Hanyan (GB4)；puncturing subcutaneously and backward-upward；the left anterior central gyrus and posterior central gyrus. APH3：about 0.5 cun anterior-inferior to the left Qubin (GB7)；puncturing subcutaneously and backward-downward；left medial/superior temporal gyrus. 4) DYS. Based on the retrieved 76 researches, we identified 8 potential scalp acupuncture targets for DYS, their locations, RANO and CBRs respectively are as below. DYS1：about 1 cun anterior-inferior to the left GB5；puncturing subcutaneously and forward-upward；the pars triangularis of the left inferior frontal gyrus. DYS2：about 0.5 cun posterior-superior to the left GB5；puncturing subcutaneously and forward-downward；the left subfrontal gyrus operculum, pars triangularis and anterior central gyrus. DYS3：the midpoint between the left GB5 and GB18；puncturing subcutaneously and forward；the left anterior central gyrus and posterior central gyrus. CONCLUSIONS: We identified scalp acupuncture targets for several common neurological disorders based on neuroimaging evidence for clinical application and research. The proposed targets may also be used for treating these disorders using brain stimulation methods.

[Neuroimaging-based study of scalp acupuncture targets for common psychiatric diseases].

Scalp acupuncture is a unique acupuncture method, developed based on the cerebral cortex localization. Neuroimaging technology enables the combination of contemporary brain science findings with the studies of scalp stimulation sites. In this study, based on the neuroimaging literature retrieved from Neurosynth platform, the scalp stimulation targets of common psychiatric diseases are developed, which provides the stimulation target protocol of scalp acupuncture for anxiety, bipolar disorder, major depressive disorder and post-traumatic stress disorder. The paper introduces the functions of the brain areas that are involved in each target and closely related to the diseases, and lists the therapeutic methods of common acupuncture and scalp acupuncture for each disease so as to provide the references for clinical practice. These targets can be used not only for the stimulation of scalp acupuncture, but also for the different neuromodulation techniques to treat related diseases.

Estimated Prevalence of Resident-to-Resident Aggression in Assisted Living.

Importance: Resident-to-resident aggression in assisted living facilities can result in physical and psychological harm, but its prevalence is unknown. Objective: To estimate the prevalence of resident-to-resident aggression, including physical, verbal, and sexual, among residents in assisted living facilities. Design, Setting, and Participants: This study used cross-sectional, observational data from a clinical trial, in which residents of assisted living facilities were monitored for events over a 1-month period. All residents of 14 large facilities randomly selected from 2 geographic locations (N = 1067), except those receiving hospice care (n = 11), were invited to participate; 93 died or moved prior to enrollment. There were 33 family and resident refusals; 930 residents were enrolled. Data were collected between May 30, 2018, and August 11, 2022. Main Outcomes and Measures: The data are from a clinical trial testing the effectiveness of an intervention to reduce resident-to-resident aggression. In addition, the study was designed to assess prevalence using the Time 1 (baseline) data, using a probability sample of facilities to allow for this analysis. Resident-to-resident aggression was identified using a mixed-method, case-finding strategy involving 6 sources: (1) cognitively capable resident reports regarding 22 possible events, (2) direct care staff report, (3) staff member reports collected from event-reporting forms, (4) research assistant observation of events in real time, (5) facility accident or incident reports, and (6) resident records. Results: The prevalence of resident-to-resident aggression among the 930 participants (mean [SD] age, 88.0 [7.2] years; 738 women [79.4%]) during the past month was estimated to be 15.2% (141 of 930 residents; 95% CI, 12.1%-18.8%). The most common forms of aggression included verbal (11.2% [104 of 930 residents; 95% CI, 8.8%-14.2%]), physical (41 of 930 residents; 4.4% [95% CI, 3.1%-6.3%]), sexual (0.8% [7 of 930 residents; 95% CI, 0.4%-1.6%]), and other (70 of 930 residents; 7.5% [95% CI, 5.5%-10.2%]). These categories are not mutually exclusive as residents could be involved with more than 1 type of aggressive behavior. Conclusions and Relevance: In this cross-sectional, observational prevalence study, resident-to-resident aggression in assisted living facilities was highly prevalent. Verbal aggression was the most common form, and physical aggression also occurred frequently. The effects of resident-to-resident aggression can be both morbid and mortal; therefore, intervention research is needed to prevent it and to treat it when it occurs.

Chrysin mitigated neuropathic pain and peripheral sensitization in knee osteoarthritis rats by repressing the RAGE/PI3K/AKT pathway regulated by HMGB1.

BACKGROUND: Knee osteoarthritis (KOA) is a chronic progressive osteoarthropathy. Chrysin's anti-KOA action has been demonstrated, however more research is needed to understand how chrysin contributes to KOA. METHODS: LPS/ATP-induced macrophages transfected with or without HMGB1 overexpression underwent 5 µg/mL chrysin. The cell viability and macrophage pyroptosis were examined by cell counting kit-8 and flow cytometer. In vivo experiments, rats were injected with 1 mg monosodium iodoacetate by the infrapatellar ligament of the bilateral knee joint to induce KOA. The histological damage was analyzed by Safranin O/Fast Green staining and hematoxylin and eosin staining. The PWT, PWL and inflammatory factors were analyzed via Von-Frey filaments, thermal radiometer and ELISA. Immunofluorescence assay examined the expressions of CGRP and iNOS. The levels of HMGB1/RAGE-, NLRP3-, PI3K/AKT- and neuronal ion channel-related markers were examined by qPCR and western blot. RESULTS: Chrysin alleviated macrophage pyroptosis by inhibiting HMGB1 and the repression of chrysin on HMGB1/RAGE pathway and ion channel activation was reversed by overexpressed HMGB1. HMGB1 facilitated neuronal ion channel activation through the RAGE/PI3K/AKT pathway. Chrysin could improve the pathological injury of knee joints in KOA rats. Chrysin suppressed the HMGB1-regulated RAGE/PI3K/AKT pathway, hence reducing KOA damage and peripheral sensitization. CONCLUSION: Chrysin mitigated neuropathic pain and peripheral sensitization in KOA rats by repressing the RAGE/PI3K/AKT pathway modulated by HMGB1.

Single-incision plus one-port laparoscopy surgery versus conventional multi-port laparoscopy surgery for colorectal cancer: a systematic review and meta-analysis.

OBJECTIVE: The efficacy of single-incision plus one-port laparoscopic surgery (SILS + 1) versus conventional laparoscopic surgery (CLS) for colorectal cancer treatment remains unclear. This study compares the short-term and long-term outcomes of SILS + 1 and CLS using a high-quality systematic review and meta-analysis. METHOD: Literature search followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, drawing from PubMed, Embase, Web of Science, and the Cochrane Library until December 10, 2023. Statistical analysis was conducted using RevMan and Stata. RESULT: The review and meta-analysis included seven studies with 1740 colorectal cancer patients. Compared to CLS, SILS + 1 showed significant improvements in operation time (WMD = - 18.33, P < 0.00001), blood loss (WMD = - 21.31, P < 0.00001), incision length (WMD = - 2.07, P < 0.00001), time to first defecation (WMD = - 14.91, P = 0.009), time to oral intake (WMD = - 11.46, P = 0.04), and time to ambulation (WMD = - 11.52, P = 0.01). There were no significant differences in lymph node harvest, resection margins, complications, anastomotic leakage, hospital stay, disease-free survival, overall survival, and postoperative recurrence. CONCLUSIONS: Compared to CLS, SILS + 1 demonstrates superiority in shortening the surgical incision and promoting postoperative recovery. SILS + 1 can provide a safe and feasible alternative to CLS.

Optimization of chaotic light output in semiconductor laser systems based on multi-objective optimization algorithm.

Aiming at the weak performance of chaotic light output in semiconductor laser systems, the study designed a power control algorithm for semiconductor laser drive systems based on linear self-disturbance rejection control. Then the optimization parameters and scope were determined, and multi-objective optimization and direction preference algorithms were introduced. A chaotic optical performance optimization model based on improved multi-objective genetic algorithm was constructed using adaptive functions as evaluation indicators. These results confirmed that the larger the bandwidth of the controller, the faster the response speed of the resonant converter, but the stability was poor. When the input voltage underwent a sudden change, the current ripple coefficient of the PID algorithm was 0.55%. The linear active disturbance rejection control algorithm could ensure that the voltage and current maintained at the set values, and the output current of the algorithm was more stable when the load underwent sudden changes. The directional preference algorithm could further provide more valuable solutions on the basis of adaptive genetic algorithms. When the peak value of the autocorrelation function was equal to 0.2, the delay characteristics of chaotic light were effectively suppressed, having strong signal bandwidth and complexity. In summary, the constructed model has good application effects in optimizing chaotic optical performance and has certain positive significance for communication security.

Hybrid Fabrication of Cold Metal Transfer Additive Manufacturing and Laser Metal Deposition for Ti6Al4V: The Microstructure and Dynamic/Static Mechanical Properties.

The titanium alloy components utilized in the aviation field are typically large in size and possess complex structures. By utilizing multiple additive manufacturing processes, the precision and efficiency requirements of production can be met. We investigated the hybrid additive manufacturing of Ti-6Al-4V using a combination of cold metal transfer additive manufacturing (CMTAM) and laser metal deposition (LMD), as well as the feasibility of using the CMT-LMD hybrid additive manufacturing process for fabricating Ti-6Al-4V components. Microstructural examinations, tensile testing coupled with digital image correlation and dynamic compressive experiments (by the split Hopkinson pressure bar (SHPB) system) were employed to assess the parts. The results indicate that the interface of the LMD and CMTAM zone formed a compact metallurgical bonding. In the CMTAM and LMD zone, the prior-ß grains exhibit epitaxial growth, forming columnar prior-ß grains. Due to laser remelting, the CMT-LMD hybrid additive zone experiences grain refinement, resulting in equiaxed prior-ß grains at the interface with an average grain size smaller than that of the CMTAM and LMD regions. The microstructures reveal significant differences in grain orientation and morphology among the zones, with distinct textures forming in each zone. In the CMT-LMD hybrid zone, due to interfacial strengthening, strain concentration occurs in the arc additive zone during tensile testing, leading to fracture on the CMTAM zone. Under high-strain-rate dynamic impact conditions, the LMD region exhibits ductile fracture, while the CMTAM zone demonstrates brittle fracture. The hybrid zone combines ductile and brittle fracture modes, and the CMT-LMD hybrid material exhibits superior dynamic impact performance compared to the single deposition zone.

Community Health workers United to Reduce Colorectal cancer and cardiovascular disease among people at Higher risk (CHURCH): study protocol for a randomized controlled trial.

BACKGROUND: Colorectal cancer (CRC) is the second most lethal cancer in the United States (U.S.) with the highest incidence and mortality rates among African Americans (AAs) compared to other racial groups. Despite these disparities, AAs are the least likely to undergo CRC screening, have precancerous colorectal polyps removed, and have CRC detected at stages early enough for curative excision. In addition, compelling evidence links inflammatory dietary patterns to increased CRC and cardiovascular disease risk. Studies show that AA churches can successfully engage in health promotion activities including those related to cancer control. The current study seeks to leverage church-placed Community Health Workers (CHWs) to increase CRC screening and reduce CRC risk. DESIGN AND METHODS: We aim to (1) increase guideline concordant CRC screening uptake using church-placed CHWs trained in screening with a validated instrument, Brief Intervention using Motivational Interviewing, and Referral to Treatment (SBIRT); and (2) reduce dietary risk factors (inflammatory dietary patterns) linked to CRC. The latter will be addressed by culturally adapting an existing, web-based lifestyle program called Alive!. Using a Hybrid Type 1 Implementation-Effectiveness cluster randomized design, we will randomize 22 AA churches into either the dual intervention arm (CHW-led SBIRT intervention plus Alive!) or a usual care arm comprised of CRC prevention educational pamphlets and a list of CRC screening sites. We will recruit 440 subjects and evaluate the effects of both arms on screening uptake (colonoscopy, fecal DNA) (primary outcome) and dietary inflammation score (secondary outcome) at 6-month follow-up, and Life Simple7 (LS7)-a cardiovascular disease (CVD) risk score-at 6 months and 1 year (secondary outcome). Finally, guided by a racism-conscious adaptation of the Consolidated Framework for Implementation Research (CFIR), we will conduct a mixed-methods process evaluation with key stakeholders to understand multi-level influences on CRC screening and CVD risk behaviors. DISCUSSION: Church-placed CHWs are trusted influential connectors between communities and health systems. Studies have shown that these CHWs can successfully implement health prevention protocols in churches, including those related to cancer control, making them potentially important community mediators of CRC screening uptake and CRC/CVD risk reduction. TRIAL REGISTRATION: NCT05174286; clinicaltrials.gov; August 31st, 2023.

Community Health workers United to Reduce Colorectal cancer and cardiovascular disease among people at Higher risk (CHURCH): study protocol for a randomized controlled trial.

Background: Colorectal cancer (CRC) is the second most lethal cancer in the United States (U.S.) with the highest incidence and mortality rates among African Americans (AAs) compared to other racial groups. Despite these disparities, AAs are the least likely to undergo CRC screening, have precancerous colorectal polys removed, and have CRC detected at stages early enough for curative excision. In addition, compelling evidence links inflammatory dietary patterns to increased CRC and cardiovascular disease risk. Studies show that AA churches can successfully engage in health promotion activities including those related to cancer control. The current study seeks to leverage church-placed Community Health Workers (CHWs) to increase CRC screening and reduce CRC risk. Design and Methods: We aim to (1) increase guideline concordant CRC screening uptake using church-placed CHWs trained in screening with a validated instrument, Brief Intervention using Motivational Interviewing, and Referral to Treatment (SBIRT); and (2) reduce dietary risk factors (inflammatory dietary patterns) linked to CRC. The latter will be addressed by culturally adapting an existing, web-based lifestyle program called Alive!. Using a Hybrid Type 1 Implementation-Effectiveness cluster randomized design, we will randomize 22 AA churches into either the dual intervention arm (CHW-led SBIRT intervention plus Alive!) or a usual care arm comprised of CRC prevention educational pamphlets and a list of CRC screening sites. We will recruit 440 subjects and evaluate the effects of both arms on screening uptake (colonoscopy, fecal DNA) (primary outcome) and dietary inflammation score (secondary outcome) at 6-months follow up, and Life Simple7 (LS7) - a cardiovascular disease (CVD) risk score - at 6 months and 1-year (secondary outcome). Finally, guided by a racism-conscious adaptation of the Consolidated Framework for Implementation Research (CFIR), we will conduct a mixed-methods process evaluation with key stakeholders to understand multi-level influences on CRC screening and CVD risk behaviors. Discussion: Church-placed CHWs are trusted influential connectors between communities and health systems. Studies have shown that these CHWs can successfully implement health prevention protocols in churches, including those related to cancer control, making them potentially important community mediators of CRC screening uptake and CRC/CVD risk reduction. Trial registration: NCT05174286.

Physical activity may a probably protective factor for postoperative delirium: the PNDABLE study.

Objective: This study aims to explore the relationship between physical activity (PA) and postoperative delirium (POD). Methods: We selected 400 patients from the Perioperative Neurocognitive Disorder and Biomarkers Lifestyle (PNDABLE) database, and the patients in the PNDABLE database were sampled and tested Alzheimer's biomarkers. The diagnosis of POD was made using the Confusion Assessment Scale (CAM) and the severity was assessed using Memorial Delirium Assessment Scale (MDAS). Mini-Mental State Examination (MMSE) scale was used to detect the mental state of the patients. Enzyme-linked immunosorbent assay (ELISA) was used to detect the level of preoperative cerebrospinal fluid (CSF) biomarkers, such as amyloid ß plaque 42 (Aß42), total tau protein (T-tau), and phosphorylated tau protein (P-tau). Logistic regression, sensitivity analysis, and post hoc analysis were used to explore the relationship between risk and protective factors on POD. We used the mediating effect to explore whether PA mediates the occurrence of POD through CSF biomarkers. Results: The incidence of POD was 17.5%. According to our research, the consequence prompted that PA might be the protective factor for POD [odds ratio (OR): 0.336, 95% confidence interval (95 CI) 0.206-0.548, P < 0.001]. The result of logistic regression revealed that CSF biomarker Aß42 (OR: 0.997, 95 CI 0.996-0.999, P < 0.001) might be a protective factor against POD, and the T-tau (OR: 1.006, 95 CI 1.003-1.009, P = 0.001) and P-tau (OR: 1.039, 95 CI 1.018-1.059, P < 0.001) might risk factors for POD. Sensitivity analysis confirmed the correlation between PA and CSF biomarkers in the patients with POD. Mediation effect analysis showed that PA may reduce the occurrence of POD partly through CSF biomarkers, such as Aß42 (proportion: 11%, P < 0.05), T-tau (proportion: 13%, P < 0.05), and P-tau (proportion: 12%, P < 0.05). Conclusion: Physical activity is probably a protective factor for POD and may exert a mediating effect through CSF biomarkers.

Metagenomic analysis of individual mosquito viromes reveals the geographical patterns and drivers of viral diversity.

Mosquito transmitted viruses are responsible for an increasing burden of human disease. Despite this, little is known about the diversity and ecology of viruses within individual mosquito hosts. Here, using a meta-transcriptomic approach, we determined the viromes of 2,438 individual mosquitoes (81 species), spanning ~4,000 km along latitudes and longitudes in China. From these data we identified 393 viral species associated with mosquitoes, including 7 (putative) species of arthropod-borne viruses (that is, arboviruses). We identified potential mosquito species and geographic hotspots of viral diversity and arbovirus occurrence, and demonstrated that the composition of individual mosquito viromes was strongly associated with host phylogeny. Our data revealed a large number of viruses shared among mosquito species or genera, enhancing our understanding of the host specificity of insect-associated viruses. We also detected multiple virus species that were widespread throughout the country, perhaps reflecting long-distance mosquito dispersal. Together, these results greatly expand the known mosquito virome, linked viral diversity at the scale of individual insects to that at a country-wide scale, and offered unique insights into the biogeography and diversity of viruses in insect vectors.

Development of Zn2+-controlled expression system for lactic acid bacteria and its application in engineered probiotics.

Lactococcus lactis and Streptococcus thermophilus are considered as ideal chassis of engineered probiotics, while food-grade genetic tools are limited in those strains. Here, a Zn2+-controlled gene expression (ZICE) system was identified in the genome of S. thermophilus CGMCC7.179, including a transcriptional regulator sczAst and a promoter region of cation transporter czcD (PczcDst). Specific binding of the SczAst to the palindromic sequences in PczcDst was demonstrated by EMSA analysis, suggesting the regulation role of SczAst on PczcDst. To evaluate their possibility to control gene expression in vivo, the sczAst-PczcDst was employed to drive the expression of green fluorescence protein (GFP) gene in L. lactis NZ9000 and S. thermophilus CGMCC7.179, respectively. Both of the transformants could express GFP under Zn2+ induction, while no fluorescence without Zn2+ addition. For optimal conditions, Zn2+ was used at a final concentration of 0.8 mM in L. lactis and 0.16 mM in S. thermophilus at OD600 close to 0.4, and omitting yeast extract powder in the medium unexpectedly improved GFP expression level by 2.2-fold. With the help of the ZICE system, engineered L. lactis and S. thermophilus strains were constructed to secret cytokine interleukin-10 (IL-10) with immunogenicity, and the IL-10 content in the supernatant of the engineered L. lactis was 59.37 % of that under the nisin controlled expression system. This study provided a tightly controlled expression system by the food-grade inducer Zn2+, having potential in development of engineered probiotics.

Prediction of initial objective response to drug-eluting beads transcatheter arterial chemoembolization for hepatocellular carcinoma using CT radiomics-based machine learning model.

Objective: A prognostic model utilizing CT radiomics, radiological, and clinical features was developed and validated in this study to predict an objective response to initial transcatheter arterial chemoembolization with drug-eluting beads (DEB-TACE) for hepatocellular carcinoma (HCC). Methods: Between January 2017 and December 2022, the baseline clinical characteristics and preoperative and postoperative follow-up imaging data of 108 HCC patients who underwent the first time treatment of DEB-TACE were analyzed retrospectively. The training group (n = 86) and the validation group (n = 22) were randomly assigned in an 8:2 ratio. By logistic regression in machine learning, radiomics, and clinical-radiological models were constructed separately. Finally, the integrated model construction involved the integration of both radiomics and clinical-radiological signatures. The study compared the integrated model with radiomics and clinical-radiological models using calibration curves, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA). Results: The objective response rate observed in a group of 108 HCC patients who received initial DEB-TACE treatment was found to be 51.9%. Among the three models, the integrated model exhibited superior predictive accuracy in both the training and validation groups. The training group resulted in an area under the curve (AUC) of 0.860, along with sensitivity and specificity values of 0.650 and 0.913, respectively. Based on the findings from the validation group, the AUC was estimated to be 0.927. Additionally, it was found that values of sensitivity and specificity were 0.875 and 0.833, respectively. In the validation group, the AUC of the integrated model showed a significant improvement when contrasted to the clinical-radiological model (p = 0.042). Nevertheless, no significant distinction was observed in the AUC when comparing the integrated model with the radiomics model (p = 0.734). The DCA suggested that the integrated model demonstrates advantageous clinical utility. Conclusion: The integrated model, which combines the CT radiomics signature and the clinical-radiological signature, exhibited higher predictive efficacy than either the radiomics or clinical-radiological models alone. This suggests that during the prediction of the objective responsiveness of HCC patients to the first DEB-TACE treatment, the integrated model yields superior outcomes.

Heme-Inducing Endothelial Pyroptosis Plays a Key Role in Radiofrequency Ablation of Hepatic Hemangioma Leading to Systemic Inflammatory Response Syndrome.

Purpose: Systemic inflammatory response syndrome (SIRS) is a common complication of radiofrequency ablation (RFA) for hepatic hemangiomas. RFA can cause hemolytic reactions during hepatic hemangioma ablation. However, the mechanisms underlying RFA-induced SIRS remain unclear. Methods: We established an orthotopic liver hemangioma model and performed radiofrequency ablation. The levels of interleukin (IL)-1ß and IL-18 and the production of ROS were measured. The wet-to-dry lung ratio, inflammation score, and in vivo endothelial cell permeability were examined. GSDMD-/- mice were used to investigate the effect of heme-inducing SIRS. RNA sequencing (RNA-seq) was performed to identify the main pathways underlying heme-induced SIRS. Western blotting and immunoprecipitation were used to determine the changes and interactions of associated proteins. Results: The levels of heme, IL-1ß, and IL-18 were significantly increased after RFA. The wet-to-dry lung ratio increased in hepatic hemangiomas after RFA, indicating that SIRS occurred. Heme induced increased levels of IL-1ß and IL-18, cell death, wet-to-dry lung radio, and inflammation score in vitro and in vivo, indicating that heme induced SIRS and pyroptosis. Furthermore, GSDMD participates in heme-induced SIRS in mice, and GSDMD deletion in mice reverses the effect of heme. Heme regulates NLRP3 activation through the NOX4/ROS/TXNIP-TRX pathway, and an N-acetyl-L-cysteine (NAC) or NOX4 inhibitor (GLX351322) reverses heme-induced SIRS. Conclusion: Our findings suggest that heme induces endothelial cell pyroptosis and SIRS in mice and decreasing heme levels and ROS scavengers may prevent SIRS in hepatic hemangioma after RFA.