An Estimation of the Prevalence of Smoking and e-Cigarette Use among U.S. Adults If Menthol Cigarettes and Flavored Cigars Are Banned.

INTRODUCTION: People's reaction to the FDA's ban on flavored cigarettes and cigars may be modified by a concurrent ban on flavored e-cigarettes. We aim to estimate the prevalence of smoking and e-cigarette use among U.S. adults under various ban scenarios. METHODS: We collected the reactions of people who used cigarettes, cigars, and e-cigarettes reactions to three hypothetical ban scenarios, (1) restricting menthol cigarettes and flavored cigars only, or (2) further restricting e-cigarettes with any flavors except menthol or tobacco, or (3) further restricting e-cigarettes with all flavors. The above data were analyzed to identify determinants of reactions and to estimate and calibrate the probabilities of quitting and switching to non-flavored cigarettes and cigars. Afterward, the probabilities were applied to 2018-2019 TUS-CPS respondents to estimate the prevalence of smoking and e-cigarette use. RESULTS: Compared with the baseline, the prevalence of smoking decreased from 12.6% to 10.5%, and e-cigarette use increased from 2.6% to 3.8% in Scenario No.1. In Scenario No.2 and No.3, the prevalence of smoking was 10.5% and 10.7%, and the prevalence of e-cigarette use were 3.1% and 2.4%, respectively. For black people, the prevalence of smoking decreased from 14.2% in baseline to 8.1%-8.8% in three scenarios. CONCLUSIONS: The result indicated that for a ban on menthol cigarettes and flavored cigars, a concurrent ban on flavored e-cigarettes with an exemption of menthol flavor could be more effective in encouraging people to quit smoking. Black people may see a disproportionate benefit from all ban scenarios compared with other race/ethics groups.

What is already known on this topic: ban menthol in cigarettes and flavored cigars increases quitting among people who currently smoke.What this study adds: For a ban on menthol cigarettes and flavored cigars, a concurrent ban on flavored e-cigarettes could be complementary if menthol flavor was exempted.How this study might affect research, practice or policy: For flavor bans, inventions to mitigate the increasing use of e-cigarettes and alternative tobacco products are needed, also the interventions should be tailored to various population segments.

Risk Factors of New Symptomatic Fractures after Vertebroplasty: A Retrospective Cohort Study of 268 Patients with Painful Osteoporotic Vertebral Compression Fracture.

OBJECTIV: To evaluate the risk factors of new osteoporotic vertebral compression fractures (OVCFs) after percutaneous vertebroplasty (PVP). METHODS: From January 2016 to November 2019, patients suffering from OVCFs were retrospectively reviewed. The independent influence factors for new OVCFs after PVP were assessed, from following variables: age, sex, BMI, BMD, history of alcoholism, smoking, hypertension, diabetes, glucocorticoid use, and prior vertebral fractures, the number of initial fractures, mean cement volume, method of puncture, D-type of cement leakage and regular anti-osteoporosis treatment. RESULTS: A total of 268 patients with 347 levels met the inclusion criteria and were finally included in this study. 49 levels of new OVCFs among 33 patients (12.31%) were observed during the follow-up period. It indicated that female (Adjusted OR: 6.812, 95%CI: [1.096, 42.337], P = 0.040), lower BMD (Adjusted OR: 0.477, 95%CI: [0.300, 0.759], P = 0.002), prior vertebral fractures (Adjusted OR: 16.145, 95%CI: [5.319, 49.005], P = 0.000), and regular anti-osteoporosis treatment (Adjusted OR: 0.258, 95%CI: [0.086, 0.774], P = 0.016) were independent influence factors for new OVCF. The cut-off value of BMD to reach new OVCF was -3.350, with a sensitivity of 0.660 and a specificity of 0.848. CONCLUSION: Female, lower BMD (T- score of lumbar), prior vertebral fractures and regular anti-osteoporosis treatment were independent influencing factors. BMD (T- score of lumbar) lower than -3.350 would increase risk for new OVCF, and none osteoporotic treatment has detrimental effect on new onset fractures following PVP.

Machine learning techniques for prediction in pregnancy complicated by autoimmune rheumatic diseases: Applications and challenges.

Autoimmune rheumatic diseases are chronic conditions affecting multiple systems and often occurring in young women of childbearing age. The diseases and the physiological characteristics of pregnancy significantly impact maternal-fetal health and pregnancy outcomes. Currently, the integration of big data with healthcare has led to the increasing popularity of using machine learning (ML) to mine clinical data for studying pregnancy complications. In this review, we introduce the basics of ML and the recent advances and trends of ML in different prediction applications for common pregnancy complications by autoimmune rheumatic diseases. Finally, the challenges and future for enhancing the accuracy, reliability, and clinical applicability of ML in prediction have been discussed. This review will provide insights into the utilization of ML in identifying and assisting clinical decision-making for pregnancy complications, while also establishing a foundation for exploring comprehensive management strategies for pregnancy and enhancing maternal and child health.

A Prospective Multicenter Study on the Additive Value of Contrast-Enhanced Ultrasound for Biopsy Decision of Ultrasound BI-RADS 4 Breast Lesions.

OBJECTIVE: The main aim of this study was to determine whether the use of contrast-enhanced ultrasound (CEUS) could improve the categorization of suspicious breast lesions based on the Breast Imaging Reporting and Data System (BI-RADS), thereby reducing the number of benign breast lesions referred for biopsy. METHODS: This prospective study, conducted between January 2017 and December 2018, enrolled consenting patients from eight teaching hospitals in China, who had been diagnosed with solid breast lesions classified as BI-RADS 4 using conventional ultrasound. CEUS was performed within 1 wk of diagnosis for reclassification of breast lesions. Histopathological results obtained from core needle biopsies or surgical excision samples served as the reference standard. The simulated biopsy rate and cancer-to-biopsy yield were used to compare the accuracy of CEUS and conventional ultrasound (US). RESULTS: Among the 1490 lesions diagnosed as BI-RADS 4 with conventional ultrasound, 486 malignant and 1004 benign lesions were confirmed based on histology. Following CEUS, 2, 395, and 211 lesions were reclassified as CEUS-based BI-RADS 2, 3, and 5, respectively, while 882 (59%) remained as BI-RADS 4. The actual cancer-to-biopsy yield based on US was 32.6%, which increased to 43.4% when CEUS-based BI-RADS 4A was used as the cut-off point to recommend biopsy. The simulated biopsy rate decreased to 73.4%. Overall, in this preselected BI-RADS 4 population, only 2.5% (12/486) of malignant lesions would have been miscategorized as BI-RADS 3 using CEUS-based reclassification. The diagnostic accuracy, sensitivity, and specificity of contrast-enhanced ultrasound reclassification were 57.65%, 97.53%, and 38.35%, respectively. CONCLUSION: Our collective findings indicate that CEUS is a valuable tool in further triage of BI-RADS category 4 lesions and facilitates a reduction in the number of biopsies while increasing the cancer-to-biopsy yield.

Integrated framework to assess soil potentially toxic element contamination through 3D pollution analysis in a typical mining city.

Soil potentially toxic elements (PTEs) pollution of contaminated sites has become a global environmental issue. However, given that previous studies mostly focused on pollution assessment in surface soils, the current status and environmental risks of potentially toxic elements in deeper soils remain unclear. The present study aims to cognize distribution characteristics and spatial autocorrelation, pollution levels, and risk assessment in a stereoscopic environment for soil PTEs through 3D visualization techniques. Pollution levels were assessed in an integrated manner by combining the geoaccumulation index (Igeo), the integrated influence index of soil quality (IICQs), and potential ecological hazard index. Results showed that soil environment at the site was seriously threatened by PTEs, and Cu and Cd were ubiquitous and the predominant pollutants in the study area. The stratigraphic models and pollution plume simulation revealed that pollutants show a decreasing trend with the deepening of the soil layer. The ranking of contamination soil volume is as follows: Cu > Cd > Zn > As > Pb > Cr > Ni. According to the IICQs evaluation, this region was subject to multiple PTE contamination, with more than 60% of the area becoming seriously and highly polluted. In addition, the ecological hazard model revealed the existence of substantial ecological hazards in the soils of the site. The integrated potential ecological risk index (RI) indicated that 45.7%, 10.13%, and 4.15% of the stereoscopic areas were in considerable, high, and very high risks, respectively. The findings could be used as a theoretical reference for applying multiple methods to integrate evaluation through 3D visualization analysis in the assessment and remediation of PTE-contaminated soils.

IAIH-PG consensus for histological criteria of AIH: Multicentre validation with focus on chronic liver diseases in China.

BACKGROUND AND AIMS: The International AIH Pathology Group (IAIH-PG) put forward the new histological criteria of autoimmune hepatitis (AIH) in 2022, which have not undergone adequate verification. In this study, we verified the applicability of the new histological criteria in the population of Chinese patients with chronic liver disease, comparing it with the simplified criteria. METHODS: The gold standard for diagnosis in all patients was based on histological findings, combined with clinical manifestations and laboratory tests and determined after a follow-up period of at least 3 years. A total of 640 patients with various chronic liver diseases from multiple centres underwent scoring using the new histological criteria and the simplified criteria, comparing their diagnostic performance. RESULTS: In this study, the new histological criteria showed a sensitivity of 73.6% and 100% for likely and possible AIH, with specificities of 100% and 69.0% respectively. The coincidence rates of possible AIH for the new histological criteria, simplified histological criteria and simplified score were 81.7%, 72.8% and 69.7% respectively. For likely AIH, the rates were 89.2%, 75.9% and 65.6% respectively. Based on the new histological criteria, all patients with AIH were correctly diagnosed. Specifically, 73.6% were diagnosed with likely AIH and 26.4% were possible AIH. Additionally, the simplified histological criteria achieved a diagnosis rate of 98.6% for AIH, while the simplified score could only diagnose 53.8% of AIH. CONCLUSIONS: Compared with the simplified score and simplified histological criteria, the sensitivity and specificity of the new histological criteria for AIH were significantly improved. The results indicate that the new histological criteria exhibit high sensitivity and specificity for diagnosing AIH in China.

Flexible and Free-Standing Metal-Organic Framework Nanowire Paper.

Beyond traditional paper, multifunctional nanopaper has received much attention in recent years. Currently, many nanomaterials have been successfully used as building units of nanopaper. However, it remains a great challenge to prepare flexible and freestanding metal-organic framework (MOF) nanopaper owing to the low aspect ratio and brittleness of MOF nanocrystals. Herein, this work develops a flexible and free-standing MOF nanopaper with MOF nanowires as building units. The manganese-based MOF (Mn-MOF) nanowires with lengths up to 100 µm are synthesized by a facile solvothermal method. Through a paper-making technique, the Mn-MOF nanowires interweave with each other to form a three-dimensional architecture, thus creating a flexible and free-standing Mn-MOF nanowire paper. Furthermore, the surface properties can be engineered to obtain high hydrophobicity by modifying polydimethylsiloxane (PDMS) on the surfaces of the Mn-MOF nanowire paper. The water contact angle reaches 130°. As a proof of concept, this work presents two potential applications of the Mn-MOF/PDMS nanowire paper: (i) The as-prepared Mn-MOF/PDMS nanowire paper is compatible with a commercial printer. The as-printed colorful patterns are of high quality, and (ii) benefiting from the highly hydrophobic surfaces, the Mn-MOF/PDMS nanowire paper is able to efficiently separate oil from water.

Effect of umbilical cord blood-mononuclear cells on knee osteoarthritis in rabbits.

BACKGROUND: To investigate the effect and underlying mechanism of umbilical cord blood-mononuclear cells (UCB-MNCs) in treating knee osteoarthritis (KOA) in rabbits. METHODS: A rabbit KOA model was prepared by anterior cruciate ligament transection (ACLT). Fifty New Zealand white rabbits were randomly divided into the control group, model group, sodium hyaluronate (SH) group, platelet-rich plasma (PRP) group and UCB-MNC group. Knee injections were performed once a week for five consecutive weeks. The gross view of the knee joint, morphology of knee cartilage and structural changes in the knee joint were observed on CT scans, and graded by the Lequesne MG behavioral score and the Mankin score. TNF-α and IL-1ß levels in the synovial fluid of the knee were measured by the enzyme-linked immunosorbent assay (ELISA). Expression levels of MMP-13 and COL-II in the knee cartilage were detected by Western blotting and qRT-PCR. RESULTS: The Lequesne MG behavioral score and the Mankin score were significantly higher in the model group than those in the control group (P < 0.05). Rabbits in the SH, PRP and UCB-MNC groups had sequentially lower scores than those in the model group. Imaging features of KOA were more pronounced in the model group than in the remaining groups. CB-MNC significantly relieved KOA, compared to SH and PRP. Significantly higher levels of TNF-α and IL-1ß in the synovial fluid of the knee, and up-regulated MMP-13 and down-regulated COL-II in the knee cartilage were detected in the model group than in the control group. These changes were significantly reversed by the treatment with SH, PRP and UCB-MNCs, especially UCB-MNCs. CONCLUSION: Injections of UCB-MNCs into knees protect the articular cartilage and hinder the progression of KOA in rabbits by improving the local microenvironment at knee joints.

Targeting ARNT attenuates chemoresistance through destabilizing p38α-MAPK signaling in glioblastoma.

Glioblastoma (GBM) is the most aggressive and lethal brain tumor in adults. This study aimed to investigate the functional significance of aryl hydrocarbon receptor nuclear translocator (ARNT) in the pathogenesis of GBM. Analysis of public datasets revealed ARNT is upregulated in GBM tissues compared to lower grade gliomas or normal brain tissues. Higher ARNT expression correlated with the mesenchymal subtype and poorer survival in GBM patients. Silencing ARNT using lentiviral shRNAs attenuated the proliferative, invasive, and stem-like capabilities of GBM cell lines, while ARNT overexpression enhanced these malignant phenotypes. Single-cell RNA sequencing uncovered that ARNT is highly expressed in a stem-like subpopulation and is involved in regulating glycolysis, hypoxia response, and stress pathways. Mechanistic studies found ARNT activates p38 mitogen-activated protein kinase (MAPK) signaling to promote chemoresistance in GBM cells. Disrupting the ARNT/p38α protein interaction via the ARNT PAS-A domain restored temozolomide sensitivity. Overall, this study demonstrates ARNT functions as an oncogenic driver in GBM pathogenesis and represents a promising therapeutic target.

Reproducibility and reliability of pancreatic pharmacokinetic parameters derived from dynamic contrast-enhanced magnetic resonance imaging.

BACKGROUND: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with an extended Tofts linear (ETL) model for tissue and tumor evaluation has been established, but its effectiveness in evaluating the pancreas remains uncertain. PURPOSE: To understand the pharmacokinetics of normal pancreas and serve as a reference for future studies of pancreatic diseases. MATERIAL AND METHODS: Pancreatic pharmacokinetic parameters of 54 volunteers were calculated using DCE-MRI with the ETL model. First, intra- and inter-observer reliability was assessed through the use of the intra-class correlation coefficient (ICC) and coefficient of variation (CoV). Second, a subgroup analysis of the pancreatic DCE-MRI pharmacokinetic parameters was carried out by dividing the 54 individuals into three groups based on the pancreatic region, three groups based on age, and two groups based on sex. RESULTS: There was excellent agreement and low variability of intra- and inter-observer to pancreatic DCE-MRI pharmacokinetic parameters. The intra- and inter-observer ICCs of Ktrans, kep, ve, and vp were 0.971, 0.952, 0.959, 0.944 and 0.947, 0.911, 0.978, 0.917, respectively. The intra- and inter-observer CoVs of Ktrans, kep, ve, vp were 9.98%, 5.99%, 6.47%, 4.76% and 10.15%, 5.22%, 6.28%, 5.40%, respectively. Only the pancreatic ve of the older group was higher than that of the young and middle-aged groups (P = 0.042, 0.001), and the vp of the pancreatic head was higher than that of the pancreatic body and tail (P = 0.014, 0.043). CONCLUSION: The application of DCE-MRI with an ETL model provides a reliable, robust, and reproducible means of non-invasively quantifying pancreatic pharmacokinetic parameters.

Ewing sarcoma of the pancreas: a pediatric case report and narrative literature review.

Ewing's Sarcoma (ES) is an rare, small round-cell sarcoma that predominantly occurs in children and young adults, with both skeletal and extraskeletal manifestations. However, pancreatic ES, due to its rarity, is infrequently featured in scholarly literature, with only a scant 43 reported instances. Our study describes a case of pancreatic ES in an 8-year-old boy who was found to have an abdominal mass. Following an exhaustive examination, the boy was diagnosed with a neoplasm in the pancreatic head and underwent a complex surgical procedure encompassing pancreatoduodenectomy and partial transverse colectomy. Immunohistochemical assays confirmed the neoplastic cells' positivity for Cluster of Differentiation 99(CD99), Vimentin, and NK2 Homeobox 2(NKX2.2), while genomic testing identified an EWSR1-FLI1(Ewing Sarcoma Breakpoint Region 1-Friend Leukemia Integration 1) gene fusion. This led to a conclusive diagnosis of pancreatic Ewing's Sarcoma. The patient underwent seven cycles of adjuvant chemotherapy, alternating between VDC (Vincristine, Doxorubicin, Cyclophosphamide) and IE (Ifosfamide, Etoposide) tri-weekly, but did not undergo radiotherapy. At present, the patient remains neoplasm-free. Through our case analysis and comprehensive review of the existing literature, we aim to underscore th rarity of pancreatic Ewing's sarcoma and to highlight the efficacy of our individualized therapeutic approach.

Commissioning of a novel PET-Linac for biology-guided radiotherapy (BgRT).

BACKGROUND: Biology-guided radiotherapy (BgRT) is a novel radiotherapy delivery technique that utilizes the tumor itself to guide dynamic delivery of treatment dose to the tumor. The RefleXion X1 system is the first radiotherapy system developed to deliver SCINTIX® BgRT. The X1 is characterized by its split arc design, employing two 90-degree positron emission tomography (PET) arcs to guide therapeutic radiation beams in real time, currently cleared by FDA to treat bone and lung tumors. PURPOSE: This study aims to comprehensively evaluate the capabilities of the SCINTIX radiotherapy delivery system by evaluating its sensitivity to changes in PET contrast, its adaptability in the context of patient motion, and its performance across a spectrum of prescription doses. METHODS: A series of experimental scenarios, both static and dynamic, were designed to assess the SCINTIX BgRT system's performance, including an end-to-end test. These experiments involved a range of factors, including changes in PET contrast, motion, and prescription doses. Measurements were performed using a custom-made ArcCHECK insert which included a 2.2 cm spherical target and a c-shape structure that can be filled with a PET tracer with varying concentrations. Sinusoidal and cosine4 motion patterns, simulating patient breathing, was used to test the SCINTIX system's ability to deliver BgRT during motion-induced challenges. Each experiment was evaluated against specific metrics, including Activity Concentration (AC), Normalized Target Signal (NTS), and Biology Tracking Zone (BTZ) bounded dose-volume histogram (bDVH) pass rates. The accuracy of the delivered BgRT doses on ArcCHECK and EBT-XD film were evaluated using gamma 3%/2 mm and 3%/3 mm analysis. RESULTS: In static scenarios, the X1 system consistently demonstrated precision and robustness in SCINTIX dose delivery. The end-to-end delivery to the spherical target yielded good results, with AC and NTS values surpassing the critical thresholds of 5 kBq/mL and 2, respectively. Furthermore, bDVH analysis consistently confirmed 100% pass rates. These results were reaffirmed in scenarios involving changes in PET contrast, emphasizing the system's ability to adapt to varying PET avidities. Gamma analysis with 3%/2 mm (10% dose threshold) criteria consistently achieved pass rates > 91.5% for the static tests. In dynamic SCINTIX delivery scenarios, the X1 system exhibited adaptability under conditions of motion. Sinusoidal and cosine4 motion patterns resulted in 3%/3 mm gamma pass rates > 87%. Moreover, the comparison with gated stereotactic body radiotherapy (SBRT) delivery on a conventional c-arm Linac resulted in 93.9% gamma pass rates and used as comparison to evaluate the interplay effect. The 1 cm step shift tests showed low overall gamma pass rates of 60.3% in ArcCHECK measurements, while the doses in the PTV agreed with the plan with 99.9% for 3%/3 mm measured with film. CONCLUSIONS: The comprehensive evaluation of the X1 radiotherapy delivery system for SCINTIX BgRT demonstrated good agreement for the static tests. The system consistently achieved critical metrics and delivered the BgRT doses per plan. The motion tests demonstrated its ability to co-localize the dose where the PET signal is and deliver acceptable BgRT dose distributions.

Feasibility of Using Intraoperative Neurophysiological Monitoring for Detecting Bone Layer of Cervical Spine Surgery.

STUDY DESIGN: Intraoperative neurophysiological monitoring (IONM) as a guide to bone layer estimation was examined during posterior cervical spine lamina grinding. OBJECTIVE: To explore the feasibility of IONM to estimate bone layer thickness. SUMMARY OF BACKGROUND DATA: Cervical laminoplasty is a classic operation for cervical spondylosis. To increase safety and accuracy, surgery-assistant robots are currently being studied. It combines the advantages of various program awareness methods to form a feasible security strategy. In the field of spinal surgery, robots have been successfully used to help place pedicle screws. IONM is used to monitor intraoperative nerve conditions in spinal surgery. This study was designed to explore the feasibility of adding IONM to robot safety strategies. METHODS: Chinese miniature pig model was used. Electrodes were placed on the lamina, and the minimum stimulation threshold of DNEP for each lamina was measured (Intact lamina, IL). The laminae were ground to measure the DNEP threshold after incomplete grinding (Inner cortical bone preserved, ICP) and complete grinding (Inner cortical bone grinded, ICG). Subsequently, the lateral cervical mass screw canal drilling was performed, and the t-EMG threshold of the intact and perforated screw canals was measured and compared. RESULT: The threshold was significantly lower than that of the recommended threshold of DENP via percutaneous cervical laminae measurement. The DNEP threshold decreases with the process of laminae grinding. The DNEP threshold of the IL group was significantly higher than ICP and ICG group, while there was no significant difference between the ICP group and the ICG group. There was no significant relationship between the integrity of the cervical spine lateral mass screw path and t-EMG threshold. CONCLUSIONS: It is feasible to use DENP threshold to estimate lamina thickness. Cervical lateral mass screw canals by t-EMG showed no help to evaluate the integrity.

CYP1A2 Polymorphism and Drug Co-administration Affect the Blood Levels and Adverse Effects of Pirfenidone.

BACKGROUND: Mutations in metabolic enzymes and co-administration of drugs may affect the blood concentration of pirfenidone effective in pulmonary fibrosis. To provide a basis for the precise clinical use of pirfenidone, the authors analyzed the correlation between steady-state pirfenidone trough concentration and adverse drug reactions (ADRs) and examined the impact of CYP1A2*1C (rs2069514) and *1F (rs762551) variants and co-administration on pirfenidone blood concentrations and ADRs. METHODS: Forty-four patients were enrolled. The blood concentration of pirfenidone was determined using high-performance liquid chromatography. CYP1A2*1C and *1F genotypes were determined using direct SNP sequencing. Additional information related to drug associations was collected to screen factors affecting drug metabolism. RESULTS: The highest predictive value of ADRs was observed when the steady-state trough concentration of pirfenidone was 3.18 mcg·mL-1 and the area under the receiver operating characteristic curve was 0.701 (P = 0.024). The pirfenidone concentration-to-dose ratio (C/D) in CYP1A2*1F homozygous AA mutants was lower than that in C carriers (CC+AC) (1.28 ± 0.85 vs. 2.03 ± 1.28 mcg·mL-1; P = 0.036). Adverse drug reaction (ADR) incidence in the homozygous AA mutant group (28.0%) was significantly lower than that in the C carriers (CC+AC) (63.2%; P = 0.020), and ADR incidence in the A carriers (AC+AA) was considerably lower than that in the CC group (85.7%; P = 0.039). The C/D value of the combined lansoprazole/rabeprazole group was lower than that of the noncombination group (P < 0.05). CONCLUSIONS: The ADR incidence was positively correlated with pirfenidone blood concentration. The CYP1A2 (rs762551) AA genotype is associated with lower pirfenidone concentrations and fewer ADRs. Lansoprazole/rabeprazole co-administration reduced pirfenidone concentrations. Randomized controlled trials should further explore personalized dosing of pirfenidone and combination therapies.

The potential association between metabolic disorders and pulmonary tuberculosis: a Mendelian randomization study.

BACKGROUND: Metabolic disorders (MetDs) have been demonstrated to be closely linked to numerous diseases. However, the precise association between MetDs and pulmonary tuberculosis (PTB) remains poorly understood. METHOD: Summary statistics for exposure and outcomes from genome-wide association studies (GWASs) for exposures and outcomes were obtained from the BioBank Japan Project (BBJ) Gene-exposure dataset. The 14 clinical factors were categorized into three groups: metabolic laboratory markers, blood pressure, and the MetS diagnostic factors. The causal relationship between metabolic factors and PTB were analyzed using two-sample Mendelian Randomization (MR). Additionally, the direct effects on the risk of PTB were investigated through multivariable MR. The primary method employed was the inverse variance-weighted (IVW) model. The sensitivity of this MR analysis was evaluated using MR-Egger regression and the MR-PRESSO global test. RESULTS: According to the two-sample MR, HDL-C, HbA1c, TP, and DM were positively correlated with the incidence of active TB. According to the multivariable MR, HDL-C (IVW: OR 2.798, 95% CI 1.484-5.274, P = 0.001), LDL (IVW: OR 4.027, 95% CI 1.140-14.219, P = 0.03) and TG (IVW: OR 2.548, 95% CI 1.269-5.115, P = 0.009) were positively correlated with the occurrence of PTB. TC (OR 0.131, 95% CI 0.028-0.607, P = 0.009) was negatively correlated with the occurrence of PTB. We selected BMI, DM, HDL-C, SBP, and TG as the diagnostic factors for metabolic syndrome. DM (IVW, OR 1.219, 95% CI 1.040-1.429 P = 0.014) and HDL-C (IVW, OR 1.380, 95% CI 1.035-1.841, P = 0.028) were directly correlated with the occurrence of PTB. CONCLUSIONS: This MR study demonstrated that metabolic disorders, mainly hyperglycemia, and dyslipidemia, are associated with the incidence of active pulmonary tuberculosis.

Targeted delivery strategies: The interactions and applications of nanoparticles in liver diseases.

In recent years, nanoparticles have been broadly utilized in various drugs delivery formulations. Nanodelivery systems have shown promise in solving problems associated with the distribution of hydrophobic drugs and have promoted the accumulation of nanomedicines in the circulation or in organs. However, the injection dose of nanoparticles (NPs) is much greater than that needed by diseased tissues or organs. In other words, most of the NPs are localized off-target and do not reach the desired tissue or organs. With the rapid development of biodegradable and biosafety nanomaterials, the nanovectors represent assurance of safety. However, the off-target effects also induce concerns about the application of NPs, especially in the delivery of gene editing tools. Therefore, a complete understanding of the biological responses to NPs in the body will clearly guide the design of targeted delivery of NPs. The different properties of various nanodelivery systems may induce diverse interactions between carriers and organs. In this review, we describe the relationship between the liver, the most influenced organ of systemic administration of NPs, and targeted delivery nanoplatforms. Various transport vehicles have adopted multiple delivery strategies for the targeted delivery to the cells in the homeostasis liver and in diseased liver. Additionally, nanodelivery systems provide a novel strategy for treating incurable diseases. The appearance of a targeted delivery has profoundly improved the application of NPs to liver diseases.

Naodesheng Pills Ameliorate Cerebral Ischemia Reperfusion-Induced Ferroptosis via Inhibition of the ERK1/2 Signaling Pathway.

Background: Ferroptosis plays a crucial role in the occurrence and development of cerebral ischemia-reperfusion (I/R) injury and is regulated by mitogen-activated protein kinase 1/2 (ERK1/2). In China, Naodesheng Pills (NDSP) are prescribed to prevent and treat cerebrosclerosis and stroke. However, the protective effects and mechanism of action of NDSP against cerebral I/R-induced ferroptosis remain unclear. We investigated whether NDSP exerts its protective effects against I/R injury by regulating ferroptosis and aimed to elucidate the underlying mechanisms. Methods: The efficacy of NDSP was evaluated using a Sprague-Dawley rat model of middle cerebral artery occlusion and an in vitro oxygen-glucose deprivation/reoxygenation (OGD/R) model. Brain injury was assessed using 2,3,5-triphenyltetrazolium chloride (TTC), hematoxylin and eosin staining, Nissl staining, and neurological scoring. Western blotting was performed to determine the expression levels of glutathione peroxidase 4 (GPX4), divalent metal-ion transporter-1 (DMT1), solute carrier family 7 member 11 (SLC7A11), and transferrin receptor 1 (TFR1). Iron levels, oxidative stress, and mitochondrial morphology were also evaluated. Network pharmacology was used to assess the associated mechanisms. Results: NDSP (1.08 g/kg) significantly improved cerebral infarct area, cerebral water content, neurological scores, and cerebral tissue damage. Furthermore, NDSP inhibited I/R- and OGD/R-induced ferroptosis, as evidenced by the increased protein expression of GPX4 and SLC7A11, suppression of TFR1 and DMT1, and an overall reduction in oxidative stress and Fe2+ levels. The protective effects of NDSP in vitro were abolished by the GPX4 inhibitor RSL3. Network pharmacology analysis revealed that ERK1/2 was the core target gene and that NDSP reduced the amount of phosphorylated ERK1/2. Conclusion: NDSP exerts its protective effects against I/R by inhibiting cerebral I/R-induced ferroptosis, and this mechanism is associated with the regulation of ferroptosis via the ERK1/2 signaling pathway.

Non-O1, Non-O139 Vibrio cholerae Bacteremia in an Autoimmune Pancreatitis Patient.

Over 200 different serogroups of Vibrio cholerae based on O-polysaccharide specificity have been described worldwide, including the two most important serogroups, O1 and O139. Non-O1/non-O139 V. cholerae serogroups generally do not produce the cholera-causing toxin but do sporadically cause gastroenteritis and extra-intestinal infections. Recently, however, bloodstream infections caused by non-O1/non-O139 V. cholerae are being increasingly reported, and these infections are associated with high mortality in immunocompromised hosts. We describe a case of non-O1/non-O139 V. cholerae bacteremia in a patient with autoimmune pancreatitis and stenosis of the intra- and extrahepatic bile ducts. The clinical manifestations of bacteremia were fever and mild digestive symptoms. The blood cultures showed V. cholerae, which was identified as a non-O1, non-O139 serogroup by slide agglutination tests and PCR. The bloodstream infection of the patient was likely caused by the consumption of contaminated seafood at a banquet. The patient recovered after the administration of a third-generation cephalosporin. Non-O1/non-O139 V. cholerae infection presents with or without gastrointestinal manifestations; close attention should be paid to the possibility of disseminated non-O1/non-O139 V. cholerae infection in high-risk patients.

A Pillar/Perfusion Plate Enhances Cell Growth, Reproducibility, Throughput, and User Friendliness in Dynamic 3D Cell Culture.

Static three-dimensional (3D) cell culture has been demonstrated in ultralow attachment well plates, hanging droplet plates, and microtiter well plates with hydrogels or magnetic nanoparticles. Although it is simple, reproducible, and relatively inexpensive, thus potentially used for high-throughput screening, statically cultured 3D cells often suffer from a necrotic core due to limited nutrient and oxygen diffusion and waste removal and have a limited in vivo-like tissue structure. Here, we overcome these challenges by developing a pillar/perfusion plate platform and demonstrating high-throughput, dynamic 3D cell culture. Cell spheroids were loaded on the pillar plate with hydrogel by simple sandwiching and encapsulation and cultured dynamically in the perfusion plate on a digital rocker. Unlike traditional microfluidic devices, fast flow velocity was maintained within perfusion wells and the pillar plate was separated from the perfusion plate for cell-based assays. It was compatible with common lab equipment and allowed cell culture, testing, staining, and imaging in situ. The pillar/perfusion plate enhanced cell growth by rapid diffusion, reproducibility, assay throughput, and user friendliness in a dynamic 3D cell culture.