Activating UCHL1 through the CRISPR activation system promotes cartilage differentiation mediated by HIF-1α/SOX9.

Developing strategies to enhance cartilage differentiation in mesenchymal stem cells and preserve the extracellular matrix is crucial for successful cartilage tissue reconstruction. Hypoxia-inducible factor-1α (HIF-1α) plays a pivotal role in maintaining the extracellular matrix and chondrocyte phenotype, thus serving as a key regulator in chondral tissue engineering strategies. Recent studies have shown that Ubiquitin C-terminal hydrolase L1 (UCHL1) is involved in the deubiquitylation of HIF-1α. However, the regulatory role of UCHL1 in chondrogenic differentiation has not been investigated. In the present study, we initially validated the promotive effect of UCHL1 expression on chondrogenesis in adipose-derived stem cells (ADSCs). Subsequently, a hybrid baculovirus system was designed and employed to utilize three CRISPR activation (CRISPRa) systems, employing dead Cas9 (dCas9) from three distinct bacterial sources to target UCHL1. Then UCHL1 and HIF-1α inhibitor and siRNA targeting SRY-box transcription factor 9 (SOX9) were used to block UCHL1, HIF-1α and SOX9, respectively. Cartilage differentiation and chondrogenesis were measured by qRT-PCR, immunofluorescence and histological staining. We observed that the CRISPRa system derived from Staphylococcus aureus exhibited superior efficiency in activating UCHL1 compared to the commonly used the CRISPRa system derived from Streptococcus pyogenes. Furthermore, the duration of activation was extended by utilizing the Cre/loxP-based hybrid baculovirus. Moreover, our findings show that UCHL1 enhances SOX9 expression by regulating the stability and localization of HIF-1α, which promotes cartilage production in ADSCs. These findings suggest that activating UCHL1 using the CRISPRa system holds significant potential for applications in cartilage regeneration.

Simultaneous imaging and element differentiation by energy-resolved x-ray absorption ghost imaging.

Based on the x-ray absorption edges of different elements, we simultaneously image and distinguish the composition of three differently shaped components of an object by using energy-resolved x-ray absorption ghost imaging (GI). The initial x-ray beam is spatially modulated by a series of Hadamard matrix masks, and the object is composed of three pieces of Mo, Ag, and Sn foil in the shape of a triangle, square, and circle, respectively. The transmitted x-ray intensity is measured by an energy-resolved single-pixel detector with a spectral resolution better than 0.8 keV. Through correlation of the transmission spectra with the corresponding Hadamard patterns, the spectral image of the sample is reconstructed, with a spatial resolution of 108 µm. Our experiment demonstrates a practical application of spectral ghost imaging, which has important potential for the noninvasive analysis of material composition and distribution in biology, medical science, and many other fields.

Cross-waveband optical computing imaging.

A novel, to the best of our knowledge, cross-spectral optical computing imaging experiment has been achieved through a single exposure of a charge-coupled device. The experimental setup integrates single-pixel imaging (SPI) with ghost imaging (GI) through a photoelectric conversion circuit and a synchronous modulation system. The experimental process involves modulation in one wavelength band (in SPI) and demodulation using the GI algorithm in another. Significantly, our approach utilizes optical computing demodulation, a departure from the conventional electronic demodulation in GI (SPI), which involves the convolution between the bucket optical signals and the modulated patterns on the digital micromirror device. A proof-of-concept cross-band imaging experiment from near-infrared to visible light has been carried out. The results highlight the system's ability to capture images at up to 20 frames per second using near-infrared illumination, which are then reconstructed in the visible light spectrum. This success not only validates the feasibility of our approach but also expands the potential applications in the SPI or GI fields, particularly in scenarios where two-dimensional detector arrays are either unavailable or prohibitively expensive in certain electromagnetic spectra such as x-ray and terahertz.

Mendelian randomization study on causal association of TEF and circadian rhythm with pulmonary arterial hypertension.

BACKGROUND: Previous research has revealed the potential impact of circadian rhythms on pulmonary diseases; however, the connection between circadian rhythm-associated Thyrotroph Embryonic Factor (TEF) and Pulmonary Arterial Hypertension (PAH) remains unclear. We aim to assess the genetic causal relationship between TEF and PAH by utilizing two sets of genetic instrumental variables (IV) and publicly available Pulmonary Arterial Hypertension Genome-Wide Association Studies (GWAS). METHODS: Total of 23 independent TEF genetic IVs from recent MR reports and PAH GWAS including 162,962 European individuals were used to perform this two-sample MR study. Gain- and loss-of-function experiments were used to demonstrate the role of TEF in PAH. RESULTS: Our analysis revealed that as TEF levels increased genetically, there was a corresponding increase in the risk of PAH, as evidenced by IVW (OR = 1.233, 95% CI: 1.054-1.441; P = 0.00871) and weighted median (OR = 1.292, 95% CI for OR: 1.064-1.568; P = 0.00964) methods. Additionally, the up-regulation of TEF expression was associated with a significantly higher likelihood of abnormal circadian rhythm (IVW: P = 0.0024733, ß = 0.05239). However, we did not observe a significant positive correlation between circadian rhythm and PAH (IVW: P = 0.3454942, ß = 1.4980398). In addition, our in vitro experiments demonstrated that TEF is significantly overexpressed in pulmonary artery smooth muscle cells (PASMCs). And overexpression of TEF promotes PASMC viability and migratory capacity, as well as upregulates the levels of inflammatory cytokines. CONCLUSION: Our analysis suggests a causal relationship between genetically increased TEF levels and an elevated risk of both PAH and abnormal circadian rhythm. Consequently, higher TEF levels may represent a risk factor for individuals with PAH.

Identifying Veterans with a Higher Risk of Social Needs Using Cluster Analysis.

IMPORTANCE: Many social need screening to advance population health and reduce health disparities, but barriers to screening remain. Improved knowledge of patient populations at risk for social needs based on administrative data could facilitate more targeted practices, and by extension, feasible social need screening and referral efforts. OBJECTIVE: To illustrate the use of cluster analysis to identify patient population segments at risk for social needs. DESIGN: We used clustering analysis to identify population segments among Veterans (N=2010) who participated in a survey assessing nine social needs (food, housing, utility, financial, employment, social disconnection, legal, transportation, and neighborhood safety). Clusters were based on eight variables (age, race, gender, comorbidity, region, no-show rate, rurality, and VA priority group). We used weighted logistic regression to assess association of clusters with the risk of experiencing social needs. PARTICIPANTS: National random sample of Veterans with and at risk for cardiovascular disease who responded to a mail survey (N=2010). MAIN OUTCOMES AND MEASURES: Self-reported social needs defined as the risk of endorsing (1) each individual social need, (2) one or more needs, and (3) a higher total count of needs. KEY RESULTS: From the clustering analysis process with sensitivity analysis, we identified a consistent population segment of Veterans. From regression modeling, we found that this cluster, with lower average age and higher proportions of women and racial minorities, was at higher risk of experiencing ≥ 1 unmet need (OR 1.74, CI 1.17-2.56). This cluster was also at a higher risk for several individual needs, especially utility needs (OR 3.78, CI 2.11-6.78). CONCLUSIONS: The identification of characteristics associated with increased unmet social needs may provide opportunities for targeted screenings. As this cluster was also younger and had fewer comorbidities, they may be less likely to be identified as experiencing need through interactions with healthcare providers.

Transcatheter Closure of Atrial Septal Defects with Absent Aortic Rim and the Predictors of Right Atrial Reverse Remodeling: 5 Years Experience in China.

INTRODUCTION: Atrial septal defect (ASD) is one of the most common congenital heart malformations. Although not recommended, a significant proportion of patients with aortic root defects receive ASD closure, some of whom have improved right ventricular function. The study aimed to investigate the safety of interventional therapy in ASD patients with complete aortic rim deficiency and explore the predictors of right atrial (RA) non-reverse remodeling. METHODS: 1,011 patients with ASD who underwent transcatheter closure in the Department of Cardiology, Zhongshan Hospital, affiliated to Fudan University from June 2017 to June 2023 were enrolled in the study. They were divided into a complete aortic rim deficiency group and without absent aortic rim group. Furthermore, patients who had an enlarged RA in the absent aortic rim group were divided into two subgroups according to whether their RA remodeling was reversed post-procedure. Multivariate logistic regression was used to determine the predictors of RA reverse remodeling. RESULTS: During the 1-year follow-up, no major operative complications occurred in all patients with the absence of an aortic rim and a normal edge. After the operation, the right heart remodeling was significantly reversed, multivariate logistic regression analysis was performed, and it was found that no coronary heart disease before an operation, lower plasma creatinine level, and larger RA and RV dimensions were the predictive factors for the reverse of RA remodeling after treatment. CONCLUSION: Transcatheter closure of ASD with complete aortic rim deficiency is safe and feasible. For patients without coronary heart disease, the lower the creatinine value and the lower the tricuspid regurgitation before an operation, the more improvement of RA remodeling after the operation.

Left atrial appendage closure in a patient previously implanted with an interatrial shunt device: a case report.

Patients with previous interatrial shunt device (IASD) implantation may face greater challenges during future left atrial interventional procedures. Herein, we report the first case of left atrial appendage closure (LAAC) in a patient with previous IASD implantation. The patient successfully underwent LAAC using the LAmbre device without complications.

Serum VEGF, P-Selectin, HDL-C, Platelet Index, and Coagulation Function Index in Deep Vein Thrombosis after Traumatic Fracture.

BACKGROUND: The goal was to investigate the relationship between serum vascular endothelial growth factor (VEGF), P-selectin, high-density lipoprotein cholesterol (HDL-C), platelet parameters, and coagulation function indexes and postoperative deep vein thrombosis (DVT) in patients with traumatic fracture. METHODS: A total of 150 patients with traumatic fractures after DVT were selected as the DVT group, and 150 patients with traumatic fractures without DVT during the same period were selected as the non-DVT group. Serum VEGF, P-selectin, HDL-C, platelet parameters including platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), plateletcrit (PCT), platelet large cell ratio (P-LCR), and plasma coagulation function indexes including thrombin time (TT), prothrombin time (PT), activated partial thrombin time (APTT), fibrinogen (FIB), and D-dimer (D-D) were measured. Pearson's correlation was performed to analyze the correlation between serum VEGF, P-selectin, and coagulation function indexes, and binary logistic regression was used to analyze the risk factors of DVT. RESULTS: Serum VEGF and P-selectin in the DVT group were higher while HDL-C was lower than those in the non-DVT group (p < 0.05). Serum VEGF and P-selectin were negatively correlated with plasma D-D and FIB (p < 0.05), and serum HDL-C was negatively correlated (p < 0.05). Compared with the non-DVT group, MPV, PDW, and P-LCR in the DVT group were decreased (p < 0.05). Multivariate logistic regression analysis showed that P-LCR was a risk factor for postoperative DVT in patients with traumatic fractures (p < 0.05). CONCLUSIONS: Serum VEGF and P-selectin are higher and HDL-C is lower in patients with DVT after postoperative traumatic fracture than in patients without DVT. Combined detection of serum VEGF, P-selectin, HDL-C, and coagulation function indexes may help to reduce the risk of DVT. Platelet parameters (MPV, PDW, P-LCR) have certain reference values for the clinical diagnosis and disease evaluation of DVT.

A thermoresponsive nanocomposite integrates NIR-II-absorbing small molecule with lonidamine for pyroptosis-promoted synergistic immunotherapy.

Photothermal immunotherapy is regarded as the ideal cancer therapeutic modality to against malignant solid tumors; however, its therapeutic benefits are often modest and require improvement. In this study, a thermoresponsive nanoparticle (BTN@LND) composed of a photothermal agent (PTA) and pyroptosis inducer (lonidamine) were developed to enhance immunotherapy applications. Specifically, our "two-step" donor engineering strategy produced the strong NIR-II-absorbing organic small-molecule PTA (BTN) that exhibited high NIR-II photothermal performance (ε1064 = 1.51 × 104 M-1 cm-1, η = 75.8%), and this facilitates the diagnosis and treatment of deep tumor tissue. Moreover, the fabricated thermally responsive lipid nanoplatform based on BTN efficiently delivered lonidamine to the tumor site and achieved spatiotemporal release triggered by the NIR-II photothermal effect. In vitro and in vivo experiments demonstrated that the NIR-II photothermal therapy (PTT)-mediated on-demand release of cargo effectively faciliated tumor cell pyroptosis, thereby intensifying the immunogenic cell death (ICD) process to promote antitumor immunotherapy. As a result, this intelligent component bearing photothermal and chemotherapy can maximally suppress the growth of tumors, thus providing a promising approach for pyroptosis/NIR-II PTT synergistic therapy against tumors.

Rivaroxaban and Aspirin in Drug-Coated Balloon Angioplasty for Femoropopliteal In-Stent Restenosis: A Retrospective Cohort Study.

BACKGROUND: After drug-coated balloon (DCB) treatment of the femoropopliteal artery in-stent restenosis (ISR), a certain proportion of patients also experience target lesion restenosis. The purpose of this study was to explore the efficacy and safety of rivaroxaban combined with aspirin in the treatment of ISR after DCB intervention. METHODS: Patients who underwent DCB treatment for ISR after femoropopliteal artery intervention at our center from March 2017 to February 2022 were included consecutively. According to the drug treatment after DCB intervention of ISR, the patients were divided into rivaroxaban and aspirin group (RA Group) and dual antiplatelet therapy (DAPT) group. The outcomes of 2 groups during the 12-month follow-up after DCB intervention were compared. RESULTS: A total of 92 patients were included in final analysis, with 43 in RA group and 49 in DAPT group. During 12-month follow-up, a total of 15 cases of recurrent ISR were detected, and the recurrence rate of ISR and clinically driven target lesion revascularization in the RA group were lower than those in the DAPT group (P < 0.05). The vascular patency rate in the RA group was higher than that in the DAPT group at 6 and 12 months of follow-up (P < 0.05). During the follow-up, there were no adverse events such as death, myocardial infarction, stroke, amputation, or major bleeding, and only a total of 5 cases of minor bleeding occurred. CONCLUSIONS: Compared with the standard DAPT regimen, rivaroxaban combined with aspirin can safely improve the follow-up outcome after DCB for femoropopliteal ISR.

Association between total body muscle-fat ratio and risk of thyroid disorders: a cross-sectional study.

BACKGROUND: Thyroid disorders(TD) poses a significant health threat to Americans due to its high incidence rate. Obesity, a common factor linked to thyroid disorders, has garnered increasing attention. While Body mass index (BMI) is a widely used obesity index, it fails to account for the distribution of muscle and fat in the body. Recently, tMFR has emerged as a crucial obesity index in clinical research, warranting further investigation into its association with TD. OBJECTIVE: Exploring the association between tMFR and thyroid disorders. METHOD: A comprehensive survey and data analysis were conducted using the NHANES database to investigate the relationship between tMFR and the risk of TD. This study utilized multiple logistic regression, smooth curve fitting, and subgroup analysis across four periods from 2011 to 2018. RESULT: A total of 11,912 subjects were included in the study, showing a prevalence of 7.14% for TD. The research indicated that tMFR had an inverse correlation with the risk of TD in a comprehensive model (OR = 0.90, 95% CI 0.82 to 1.00). When tMFR was divided into quartiles (Q1-Q4), individuals in the highest quartile had a 28% lower risk of TD than those in Q1 (OR = 0.72, 95% CI 0.57 to 0.91). Analysis using smoothed curve fitting demonstrated a nonlinear relationship between tMFR and TD risk, with the inflection point for tMFR saturation effect identified as 1.5. Subgroup analysis further confirmed the strong association between tMFR and TD risk. Receiver operating characteristic (ROC) curve analysis indicated that tMFR exhibited superior predictive ability for TD relative to BMI. CONCLUSION: The study found a negative association between tMFR and the risk of TD; however, additional prospective studies are required to validate these findings.

Rural Veterans' Experiences with Social Risk Factors: Impacts, Challenges, and Care System Recommendations.

BACKGROUND: Social risk factors, such as food insecurity and financial needs, are associated with increased risk of cardiovascular diseases, health conditions that are highly prevalent in rural populations. A better understanding of rural Veterans' experiences with social risk factors can inform expansion of Veterans Health Administration (VHA) efforts to address social needs. OBJECTIVE: To examine social risk and need from rural Veterans' lived experiences and develop recommendations for VHA to address social needs. DESIGN: We conducted semi-structured interviews with participants purposively sampled for racial diversity. The interview guide was informed by Andersen's Behavioral Model of Health Services Use and the Outcomes from Addressing Social Determinants of Health in Systems framework. PARTICIPANTS: Rural Veterans with or at risk of cardiovascular disease who participated in a parent survey and agreed to be recontacted. APPROACH: Interviews were recorded and transcribed. We analyzed transcripts using directed qualitative content analysis to identify themes. KEY RESULTS: Interviews (n = 29) took place from March to June 2022. We identified four themes: (1) Social needs can impact access to healthcare, (2) Structural factors can make it difficult to get help for social needs, (3) Some Veterans are reluctant to seek help, and (4) Veterans recommended enhancing resource dissemination and navigation support. CONCLUSIONS: VHA interventions should include active dissemination of information on social needs resources and navigation support to help Veterans access resources. Community-based organizations (e.g., Veteran Service Organizations) could be key partners in the design and implementation of future social need interventions.

Relationship Between Unmet Social Needs and Care Access in a Veteran Cohort.

BACKGROUND: The association between unmet social needs (e.g., food insecurity) and adverse health outcomes is well-established, especially for patients with and at risk for cardiovascular disease (CVD). This has motivated healthcare systems to focus on unmet social needs. Yet, little is known about the mechanisms by which unmet social needs impact health, which limits healthcare-based intervention design and evaluation. One conceptual framework posits that unmet social needs may impact health by limiting care access, but this remains understudied. OBJECTIVE: Examine the relationship between unmet social needs and care access. DESIGN: Cross-sectional study design using survey data on unmet needs merged with administrative data from the Veterans Health Administration (VA) Corporate Data Warehouse (September 2019-March 2021) and multivariable models to predict care access outcomes. Pooled and separate rural and urban logistic regression models were utilized with adjustments from sociodemographics, region, and comorbidity. SUBJECTS: A national stratified random sample of VA-enrolled Veterans with and at risk for CVD who responded to the survey. MAIN MEASURES: No-show appointments were defined dichotomously as patients with one or more missed outpatient visits. Medication non-adherence was measured as proportion of days covered and defined dichotomously as adherence less than 80%. KEY RESULTS: Greater burden of unmet social needs was associated with significantly higher odds of no-show appointments (OR = 3.27, 95% CI = 2.43, 4.39) and medication non-adherence (OR = 1.59, 95% CI = 1.19, 2.13), with similar associations observed for rural and urban Veterans. Social disconnection and legal needs were especially strong predictors of care access measures. CONCLUSIONS: Findings suggest that unmet social needs may adversely impact care access. Findings also point to specific unmet social needs that may be especially impactful and thus might be prioritized for interventions, in particular social disconnection and legal needs.

Identification of recurrent variants implicated in disease in bicuspid aortic valve patients through whole-exome sequencing.

Bicuspid aortic valve (BAV) is the most common congenital heart defect in human beings, with an estimated prevalence in the general population of between 0.5 and 2%. Moreover, BAV is the most common cause of aortic stenosis in the pediatric population. Patients with BAV may have no symptoms for life, and some of them may progress to aortic stenosis. Genetic factors increase the susceptibility and development of BAV. However, the pathogenesis and BAV are still unclear, and more genetic variants are still needed for elucidating the molecular mechanism and stratification of patients. The present study carried out screening of variants implicated in disease in BAV patients. The whole-exome sequencing (WES) was performed in 20 BAV patients and identified 40 different heterozygous missense mutations in 36 genes (MIB2, FAAH, S100A1, RGS16, MAP3K19, NEB, TTN, TNS1, CAND2, CCK, KALRN, ATP10D, SLIT3, ROS1, FABP7, NUP205, IL11RA, NPR2, COL5A1, CUBN, JMJD1C, ANXA7, TRIM8, LGR4, TPCN2, APOA5, GPR84, LRP1, NCOR2, AKAP11, ESRRB, NGB, AKAP13, WWOX, KCNJ12, ARHGEF1). The mutations in these genes were identified as recurrent variants implicated in disease by in silico prediction tool analysis. Nine genes (MIB2, S100A1, TTN, CCK, NUP205, LGR4, NCOR2, ESRRB, and WWOX) among the 36 genes were identified as variants implicated in disease via unanimous agreement of in silico prediction tool analysis and sequenced in an independent cohort of 137 BAV patients to validate the results of WES. BAV patients carrying these variants demonstrated reduced left ventricular ejection fractions (LVEF) (63.8 ± 7.5% vs. 58.4 ± 5.2%, P < 0.001) and larger calcification volume [(1129.3 ± 154) mm3 vs. (1261.8 ± 123) mm3, P < 0.001]. The variants in TTN, NUP205 and NCOR2 genes are significantly associated with reduced LVEF, and the variants in S100A1, LGR4, ESRRB, and WWOX genes are significantly associated with larger calcification volume. We identified a panel of recurrent variants implicated in disease in genes related to the pathogenesis of BAV. Our data speculate that these variants are promising markers for risk stratification of BAV patients with increased susceptibility to aortic stenosis.

Novel arm-width-expandable transcatheter edge-to-edge repair system: Preclinical experiment and first-in-human study.

BACKGROUND: The ValveClasp system is a novel transcatheter edge-to-edge repair (TEER) device with an arm-width-expandable clip that allows treatment of patients with only one clip more frequently. OBJECTIVES: This study aimed to evaluate the feasibility and safety of a novel TEER device in porcine models and patients. METHODS: Fourteen young adult pigs were enrolled. A clip with an expanded arm was implanted under epicardial echocardiography and fluoroscopy guidance. Five patients with at least moderate-to-severe mitral regurgitation underwent TEER using the ValveClasp system to test the safety and effectiveness of the device. RESULTS: The device success rate was 100% (14/14) in the animal experiments, and all clips were deployed at the A2P2 segments, forming a double-orifice mitral valve. Gross observations on day 180 showed a wide and continuous tissue bridge between the leaflets. The acute procedural success rate was 100% (5/5). Only one clip was required in all patients, and all achieved effective postoperative endpoints (grade ≤2+). During 30-day follow-up, no adverse events occurred. All patients' vena Contracta width (from 8.04 0.71 mm to 3.84 ± 1.18 mm, p = 0.012), mitral regurgitation area (from 12.75 ± 3.13 cm2 to 3.50 ± 1.66 cm2 , p = 0.008), and left ventricular end diastolic diameter (from 52.00 ± 2.92 mm to 46.00 ± 3.08 mm, p = 0.040) were considerably decreased, without obvious mitral stenosis. CONCLUSIONS: The novel arm-width-expandable ValveClasp device is safe for TEER for treating severe mitral regurgitation.

Glycemic Variability and Prognosis of Patients with Intracerebral Hemorrhage: A Meta-Analysis.

Glycemic disorder may affect the outcomes of patients with intracerebral hemorrhage (ICH). However, the association between glycemic variability (GV) and prognosis in these patients remains to be determined. We performed a meta-analysis to compressive the influence of GV on functional outcome and mortality in patients with ICH. Observational studies comparing the risks of poor functional outcome (defined as modified Rankin Scale>2) and all-cause mortality between ICH patients with higher versus lower acute GV were retrieved by systematic search of Medline, Web of Science, Embase, CNKI, and Wanfang databases. A random-effect model was used to pool the data after incorporating the between-study heterogeneity. Sensitivity analyses were performed to evaluate the stability of the findings. Eight cohort studies involving 3400 patients with ICH were included in the meta-analysis. The follow-up duration was within 3 months after admission. All of the included studies used standard deviation of blood glucose (SDBG) as the indicator of acute GV. Pooled results showed that ICH patients with higher SDBG were associated with a higher risk of poor functional outcome as compared to those with lower SDBG [risk ratio (RR): 1.84, 95% confidence interval (CI): 1.41 to 2.42, p<0.001, I2=0%]. In addition, patients with higher category of SDBG were also associated with a higher mortality risk (RR: 2.39, 95% CI: 1.79 to 3.19, p<0.001, I2=0%). In conclusion, high acute GV may be a predictor of poor functional outcome and mortality of patients with ICH.

Correlation between Serum MMP-2/-16 Levels and Inflammation in Patients with Deep Vein Thrombosis.

BACKGROUND: The aim of the study was to clarify the correlation between serum MMP-2/-16 and inflammation in patients with deep venous thrombosis (DVT). METHODS: Sixty DVT patients and 60 healthy people who underwent health examinations were collected. Serum MMP-2/-16, IL-6/-8, and TNF-α were determined by ELISA. MMP-2/-16 protein levels were detected by western blot, and IL-6/-8 and TNF-α by RT-qPCR. Correlation analysis was performed on MMP-2/-16xdd, IL-6/-8, and TNF-α in DVT patients. RESULTS: MMP-2/-16, IL-6/-8, and TNF-α in DVT patients after treatment were lower than before treatment. Serum IL-6/-8 and TNF-α levels in DVT patients were both positively correlated with MMP-2/-16 levels. CONCLUSIONS: MMP-2/-16 and inflammatory factors are related to DVT development, and IL-6/-8 and TNF-α are positively correlated with MMP-2/-16.

Quasi-dendritic sulfonate-based organic small molecule for high-quality NIR-II bone-targeted imaging.

The visualization of bone imaging in vivo is of great significance for the understanding of some bone-related diseases or physiological processes. Herein, a bone-targeted NIR-II small molecule (TTQF-SO3), which was modified with multiple sulfonate groups, was successfully fabricated for the second near-infrared (NIR-II) bone imaging. In vitro studies revealed that TTQF-SO3 showed high affinity for hydroxyapatite and excellent macrophage accumulation ability. In in vivo assays, TTQF-SO3 displayed high bone uptake ability and high NIR-II bone imaging quality, demonstrating the specific bone-targeting ability of the sulfonate-containing probe. In addition, the noninvasive NIR-II imaging detection in bone calcium loss was successfully verified in osteoporosis mice models. Moreover, the negative charge characteristic of TTQF-SO3 showed efficient lymphoid enrichment in living mice by intravenous injection. Overall, these warrant that our TTQF-SO3 is an optimal bone-targeted diagnostic agent for high-quality NIR-II imaging, highlighting its potential promise for clinical translation.

Near infrared II excitation nanoplatform for photothermal/chemodynamic/antibiotic synergistic therapy combating bacterial biofilm infections.

Drug-resistant bacterial biofilm infections (BBIs) are refractory to elimination. Near-infrared-II photothermal therapy (NIR-II PTT) and chemodynamic therapy (CDT) are emerging antibiofilm approaches because of the heavy damage they inflict upon bacterial membrane structures and minimal drug-resistance. Hence, synergistic NIR-II PTT and CDT hold great promise for enhancing the therapeutic efficacy of BBIs. Herein, we propose a biofilm microenvironment (BME)-responsive nanoplatform, BTFB@Fe@Van, for use in the synergistic NIR-II PTT/CDT/antibiotic treatment of BBIs. BTFB@Fe@Van was prepared through the self-assembly of phenylboronic acid (PBA)-modified small-molecule BTFB, vancomycin, and the CDT catalyst Fe2+ ions in DSPE-PEG2000. Vancomycin was conjugated with BTFB through a pH-sensitive PBA-diol interaction, while the Fe2+ ions were bonded to the sulfur and nitrogen atoms of BTFB. The PBA-diol bonds decomposed in the acidic BME, simultaneously freeing the vancomycin and Fe2+ irons. Subsequently, the catalytic product hydroxyl radical was generated by the Fe2+ ions in the oxidative BME overexpressed with H2O2. Moreover, under 1064 nm laser, BTFB@Fe@Van exhibited outstanding hyperthermia and accelerated the release rate of vancomycin and the efficacy of CDT. Furthermore, the BTFB@Fe@Van nanoplatform enabled the precise NIR-II imaging of the infected sites. Both in-vitro and in-vivo experiments demonstrated that BTFB@Fe@Van possesses a synergistic NIR-II PTT/CDT/antibiotic mechanism against BBIs.

Meta-analysis of the Efficacy of Huoxue Huayu Method Combined With Conventional Western Medicine in the Treatment of Hydrocephalus After Cerebral Hemorrhage.

Context: Hydrocephalus refers to excessive secretion of cerebrospinal fluid, its insufficient absorption, or its blocked circulation and frequently occurs after a cerebral hemorrhage. The mortality and disability rates for cerebral hemorrhage are high. Objective: The study intended to evaluate the clinical efficacy of integrated traditional Chinese and Western medicine in the treatment of hydrocephalus after a cerebral hemorrhage, using systematic screening and analysis of published literature. Design: The research team performed a meta-analysis by searching databases-PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang database, and Chinese Biomedical Literature-and collected Chinese and English publications from the establishment of each database until December 2022 discussing studies that used a TCM treatment that promoted blood circulation and removed blood stasis, combined with conventional western medicine, for hydrocephalus after cerebral hemorrhage. The keywords were promoting blood circulation and removing blood stasis, cerebral hemorrhage, and hydrocephalus. The team performed the meta-analysis using RevMan 5.3. Results: The research team found five relevant studies, all of which were randomized controlled trials. The clinical efficacy TCM combined with conventional Western medicine was significantly better than that of other treatments [MD = 1.77, 95% CI (0.23, 3.31), Z = 12.18, P < .001]. The NIHSS score after the integrated treatments also improved significantly more than those of other treatments [MD = -2.54, 95% CI (-4.07, -1.01), Z = 5.16, P < .00001]. Conclusions: Activating blood circulation and removing blood stasis using TCM, combined with conventional Western medicine, can achieve ideal therapeutic effects for patients with hydrocephalus after a cerebral hemorrhage, which can have a positive influence on clinical efficacy and reduce the NIHSS score, and the combined treatments have a clinical value.