The efficacy and safety of ZR2 versus R-CHOP-like for elderly patients with newly diagnosed diffuse large B cell lymphoma: a single-center prospective study in China.

Bruton's tyrosine kinase inhibitors have been demonstrated preliminary efficacy in diffuse large B-cell lymphoma (DLBCL). To compare the safety and efficacy of zanubrutinib plus rituximab and lenalidomide (ZR2) and R-CHOP-like for elderly patients with newly diagnosed DLBCL, we conducted this single-center prospective study. Patients were treated with 6 cycles of ZR2 or R-CHOP-like regimen for the first-line treatment. The primary endpoint was complete response ratio (CRR). The secondary outcome measures were progression-free survival (PFS), overall survival (OS), and adverse events. Between June 15, 2020, and March 11, 2023, 30 patients with ZR2 and 60 patients with R-CHOP-like were enrolled. There were no significant differences observed in CRR (P = 0.878), PFS (P = 0.555) and OS (P = 0.769) between ZR2 and R-CHOP-like group. While, patients in ZR2 group had the following features: significantly older (P = 0.002), more unfit (P < 0.001) and higher prognosis risk scores (P = 0.025). The incidence of grade ≥ 3 anemia (P = 0.008) and pneumonia (P = 0.001) was significantly lower in ZR2 group. Patients with germinal center B-cell-like subtype (GCB), large masses or TP53 mutations had a satisfactory remission rate in ZR2 group (57.1%, 77.8% and 60.0%, respectively). ZR2 and R-CHOP-like regimen had similar efficacy and survival. While, the safety profile for ZR2 was superior. GCB subtype, large masses and TP53 mutations may benefit from ZR2 regimen as well. Patients with EBV-positive and CARD11 mutations may need additional treatment rather than ZR2. Patients with gastrointestinal DLBCL have to be monitored closely by abdominal enhanced CT every cycle. Overall, ZR2 chemo-free regimen might be more appropriate for elderly DLBCL patients.

Usefulness of magnetic resonance imaging characteristics in discriminating H3 K27M-mutant gliomas from wildtype gliomas in spinal cord.

AIM: The aim of this study was to determine the usefulness of magnetic resonance imaging (MRI) characteristics in discriminating H3 K27M-mutant gliomas from wildtype gliomas in the spinal cord. MATERIALS AND METHODS: Fifty-eight patients with spinal cord gliomas were enrolled in this study. The H3 K27 gene status was identified by Sanger sequencing or immunohistochemistry test of resection tumor specimens. The MR imaging characteristics were evaluated and compared between H3 K27M-mutant and wildtype gliomas using the χ2 test and the Mann-Whitney U test. RESULTS: Of 58 recruited patients, 23 (39.7%) were diagnosed with H3 K27M-mutant glioma. The H3 K27M-mutant gliomas were found to more likely occur in men compared with wildtype gliomas (87.0% vs. 42.9%, p = 0.001). On T2-weighted MR images, the signal-to-noise ratio (SNR) of H3 K27M-mutant gliomas was significantly lower than that of wildtype gliomas (103.9 ± 72.0 vs. 168.9 ± 86.8, p < 0.001). Of 35 wildtype tumors, 60% showed well-defined margin but this feature was not found in all mutant tumors (p < 0.001). The SNR of tumors on contrast-enhanced T1-weighted images of the H3 K27M-mutant gliomas was significantly lower than that of wildtype gliomas (187.7 ± 160.4 vs. 295.1 ± 207.8, p = 0.006). Receiver operating-characteristic analysis revealed that area under curve (AUC) of combination of 1/SNR on T2-weighted images, 1/SNR on contrast-enhanced T1-weighted images, ill-defined margin, and sex reached 0.937 (95% CI, 0.873-1.000) in discriminating H3 K27M-mutant gliomas. CONCLUSIONS: The MR imaging characteristics are valuable in discriminating H3 K27M-mutant from wildtype gliomas in the spinal cord and the combination of these imaging features with sex had a high strength in this discrimination.

Quantifying COVID-19 importation risk in a dynamic network of domestic cities and international countries.

Since its outbreak in December 2019, the novel coronavirus 2019 (COVID-19) has spread to 191 countries and caused millions of deaths. Many countries have experienced multiple epidemic waves and faced containment pressures from both domestic and international transmission. In this study, we conduct a multiscale geographic analysis of the spread of COVID-19 in a policy-influenced dynamic network to quantify COVID-19 importation risk under different policy scenarios using evidence from China. Our spatial dynamic panel data (SDPD) model explicitly distinguishes the effects of travel flows from the effects of transmissibility within cities, across cities, and across national borders. We find that within-city transmission was the dominant transmission mechanism in China at the beginning of the outbreak and that all domestic transmission mechanisms were muted or significantly weakened before importation posed a threat. We identify effective containment policies by matching the change points of domestic and importation transmissibility parameters to the timing of various interventions. Our simulations suggest that importation risk is limited when domestic transmission is under control, but that cumulative cases would have been almost 13 times higher if domestic transmissibility had resurged to its precontainment level after importation and 32 times higher if domestic transmissibility had remained at its precontainment level since the outbreak. Our findings provide practical insights into infectious disease containment and call for collaborative and coordinated global suppression efforts.

Association between symptomatic intracranial atherosclerotic disease and the integrity of the circle of Willis.

The relationship between the severity of intracranial atherosclerotic disease and the circle of Willis integrity is unclear. In this brief report, we investigate the associations between symptomatic intracranial atherosclerotic disease and the integrity of the circle of Willis. Patients with symptomatic intracranial atherosclerosis were enrolled and underwent intracranial artery magnetic resonance vessel wall imaging and time-of-flight angiography. The presence or absence of an intracranial atherosclerotic plaque and its maximum wall thickness and stenosis were evaluated. The presence or absence of the A1 segment of the bilateral anterior cerebral arteries (from the internal carotid artery to the anterior communicating artery segment is called anterior cerebral artery A1 segment), and anterior communicating artery, the P1 segment of the bilateral posterior cerebral arteries (The P1 segment of the posterior cerebral artery is a horizontally outward segment), and bilateral posterior communicating arteries were determined. The associations of the intracranial plaque features with the integrity of the circle of Willis were analyzed. Of the 110 recruited subjects (57.2 ± 11.1 years; 65% males), 51 had intracranial plaques, and 44 had stenosis. In patients with bilateral A1 and P1 segments (n = 85), intracranial stenosis was more severe in patients with an anterior communicating artery than those without an anterior communicating artery (19.7% ± 21.7% vs. 1.4% ± 3.3%, p = 0.046). In patients with bilateral A1 and P1 segments and an anterior communicating artery (n = 79), intracranial stenosis was more severe in patients with posterior communicating arteries than those without posterior communicating arteries (27.9% ± 23.7% vs. 13.5% ± 17.9%, p = 0.007). The odds ratio of intracranial stenosis was 1.214 (95% confidence interval (CI), 1.054-1.398; p = 0.007) in discriminating for the presence of posterior communicating arteries in patients with bilateral A1 and P1 segments and an anterior communicating artery after adjusting for confounding factors. The severity of intracranial atherosclerosis was independently associated with the presence of posterior communicating arteries in patients with a complete anterior part of the circle of Willis.

Pushing or clicking the grocery cart? Health and economic concerns during the COVID-19 pandemic.

Online Grocery Shopping (OGS) has grown dramatically during the COVID-19 pandemic. It is unknown, however, how consumers weighed pandemic situational factors versus household production considerations of timesaving and cost. We collect and analyze survey data from a nationally representative sample to examine how consumers with different health and socio-demographic profiles consider these factors for OGS choices and how their choices changed in the first seven months of the pandemic. We find that consumers with moderate-to-high income, white, having insurance, and not in the labor force value the timesaving and convenience of OGS more than pandemic situational factors. Still, some consumers with health risks choose to shop in person because of the cost of OGS. Lung disease, diabetes, mental health conditions, age, income, and college degree explain the dynamics of OGS choice as the pandemic evolved. Our findings shed light on the development of technology-assisted adaptation to future public health emergencies.

An investigation of the antidepressant-like effect of Jiaotaiwan in rats by nontargeted metabolomics based on ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry.

Depression is a mental disorder characterized by persistent unhappiness, lack of interest, with cognitive and sleep disorders. Jiaotaiwan is a traditional Chinese medicine for the treatment of insomnia and depressive-like symptoms. In this study, the major chemical components in Jiaotaiwan were qualitatively analyzed using ultra high performance liquid chromatography quadrupole time-of-flight mass spectrometry, and a model of depression in rats was subsequently established with chronic unpredictable mild stress followed by Jiaotaiwan intervention. Next, the metabolic profile of rat serum samples was analyzed using nontargeted metabolomics, wherein changes in the metabolites in serum samples before and after Jiaotaiwan administration were measured by multiple statistical approaches. Principal component analysis and partial least squares discriminant analysis indicated that the Jiaotaiwan treatment improved the metabolic phenotype depression. Moreover, the heatmap analysis identified the most important ten biomarkers involved in depression. According to the pathway analysis, the therapeutic effect of Jiaotaiwan on depression may involve the regulation of amino acid metabolism, glycerophospholipid metabolism, and energy metabolism. These findings help us understand the pathogenesis of depression in-depth, and discover targets for clinical diagnosis and treatment. And it also lays a foundation for the use of Jiaotaiwan as an antidepressant agent.

Low-/high-density lipoprotein cholesterol ratio and carotid plaques in patients with coronary heart disease: a Chinese cohort study.

BACKGROUND: Evidence on the relationship between the low-/high-density lipoprotein cholesterol ratio (LDL-C/HDL-C) and carotid plaques remains limited. This study aimed to examine the association between LDL-C/HDL-C and carotid plaques in participants with coronary heart disease (CHD) and to further explore the extent to which a healthy lifestyle reduces the risk of LDL-C/HDL-C-related carotid plaques. METHODS: This large-scale and multi-centre retrospective study included 9426 CHD patients (aged 35-75 years) between January 1, 2014 and September 30, 2020. The LDL-C/HDL-C values were converted to the following tertiles: lowest (< 2.15), middle (2.15-3), and highest (> 3). Healthy lifestyle-related factors referred to whether or not the participant was a non-smoker and non-drinker. Participants were divided into an unfavourable group (those who did not adhere to healthy lifestyle factors), intermediate (only one unhealthy factor), and favourable (neither of the two unhealthy factors). Logistic regression was used for statistical analyses. RESULTS: Of the 9426 participants, 6989 (74.15%) CHD patients had carotid plaques. After adjustment for confounders, each unit increase in the LDL-C/HDL-C was significantly associated with carotid plaques (OR: 1.61; 95%CI: 1.43-1.84; P <  0.001). Multivariate logistic regression revealed that carotid plaques risk for the highest tertile (> 3) was 1.18 times that of the lowest quartile (< 2.15). Compared with an unfavourable lifestyle, an intermediate or a favourable lifestyle was associated with a significant 30% (OR: 0.70; 95%CI: 0.64-0.78; P <  0.001) or 67% (OR: 0.33; 95%CI: 0.29-0.37; P <  0.001) reduction in carotid plaques risk, respectively, among CHD patients with high LDL-C/HDL-C. There were significantly additive and multiplicative interactions between lifestyle and LDL-C/HDL-C with regards to carotid plaques. CONCLUSION: A high LDL-C/HDL-C is associated with a risk of carotid plaques developing in CHD patients. Adhering to a healthy lifestyle has additive beneficial effects on reducing the risk of carotid plaques, especially in relation to the highest LDL-C/HDL-C.

Assessment of pulmonary toxicity of potential antioxidant drug PEGylated nanoceria after intratracheal instillation in rats.

Cerium oxide (CeO2 ) nanoparticles have unique redox properties and exert excellent antioxidant effects in the biological environment. In recent years, many researchers have focused on the CeO2 nanoparticles as an effective antioxidant drug in the prevention and treatment of various diseases. However, the toxicity of CeO2 nanoparticles in vivo remains controversial and still needs intensive research. Therefore, the objective of this study is to investigate the pulmonary and systemic toxicity in rats after 14 days of exposure to the PEGylated CeO2 nanoparticles (abbreviated as CNPs; exposure dose of 2, 10, or 20 mg/kg) through a single intratracheal instillation (IT). We assessed the indicators of lung injury and the pathological damage degree of lung tissue. The bronchoalveolar lavage fluid (BALF) analysis and lung histopathology revealed the occurrence of slight pulmonary inflammation in the 20-mg/kg experimental group rats. However, the inflammation factors in the lung tissue of every group rats did not significantly increase, and the levels of superoxide dismutase (SOD) and glutathione (GSH) in lung tissue homogenate rose considerably in the experimental groups. Collectively, these results indicated that pulmonary exposure by the high dose of CNPs could induce mild pulmonary inflammation but did not cause severe systemic toxicity. Moreover, we speculate that the mechanism of pulmonary toxicity of CNPs in rats was due to the autophagic death of healthy lung epithelial cells mediated by endoplasmic reticulum stress. Our results implicate that CNPs can be safely used as an antioxidant drug for the oxidative stress pulmonary diseases.

Irregularity of Carotid Plaque Surface Predicts Subsequent Vascular Event: A MRI Study.

BACKGROUND: The relationship between plaque compositions and irregular plaque surface and its predictive value for vascular events (VEs) are unknown. PURPOSE: To investigate the relationship between irregular carotid plaque surface and plaque compositional features and its predictive values for future VEs utilizing magnetic resonance (MR) vessel wall imaging. STUDY TYPE: Prospective study. POPULATION: In total, 140 patients with cerebrovascular symptoms were recruited. FIELD STRENGTH/SEQUENCE: 3T, black blood T1 -weighted, black blood T2 -weighted, 3D time-of-flight, magnetization-prepared rapid acquisition gradient echo (MP-RAGE), and 3D motion sensitized driven equilibrium rapid gradient echo (MERGE). ASSESSMENT: The carotid artery stenosis and maximum wall thickness (Max WT) were measured. The presence/absence of irregular carotid plaque surface, calcification, lipid-rich necrotic core (LRNC), intraplaque hemorrhage (IPH), and fibrous cap rupture was determined. After baseline examination, all patients were followed-up for at least 1 year to record the VEs. STATISTICAL TESTS: Independent t-test, Mann-Whitney U-test, Chi-square, logistic regression, and Cox regression were used. RESULTS: In total, 82 (58.6%) had irregular plaque surfaces. The carotid Max WT, stenosis, and the presence of surface calcification, LRNC and IPH were significantly associated with irregular plaque surface (all P < 0.05). After adjusted for baseline confounding factors, these associations remained statistically significant (all P < 0.05). During the median follow-up time of 12.1 months, 37 (26.4%) patients had VEs. Univariable Cox regression analysis showed that the irregular carotid plaque surface was significantly associated with subsequent VEs (hazard ratio [HR], 11.02; 95% confidence interval [CI], 2.65-45.85; P = 0.001). After adjusted for baseline and follow-up confounding factors, this association remained statistically significant (HR, 13.03; 95% CI, 1.71-99.42, P = 0.013). After further adjusted for intracranial stenosis, this association also remained statistically significant (HR, 12.57; 95% CI, 1.63-96.83, P = 0.015). DATA CONCLUSION: The morphology of carotid atherosclerotic plaque surface determined by MR vessel wall imaging, particularly irregular plaque surface, is an independent predictor for subsequent vascular events. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage: 5 J. Magn. Reson. Imaging 2020;52:185-194.

Co-existing cerebrovascular atherosclerosis predicts subsequent vascular event: a multi-contrast cardiovascular magnetic resonance imaging study.

BACKGROUND: It is still unknown that whether co-existing intracranial stenosis and extracranial carotid vulnerable plaques have higher predictive value for subsequent vascular events. This study aimed to determine the relationship between co-existing extracranial carotid vulnerable plaques and intracranial stenosis and subsequent vascular events utilizing cardiovascular magnetic resonance (CMR) vessel wall imaging. METHODS: Patients who had recent cerebrovascular symptoms in anterior circulation (< 2 weeks) were consecutively enrolled and underwent multi-contrast CMR vessel wall imaging for extracranial carotid arteries and 3D time-of flight CMR angiography for intracranial arteries at baseline. After baseline examination, all patients were followed-up for at least 1 year to determined recurrence of vascular events. The co-existing cerebrovascular atherosclerosis was defined as presence of both intracranial artery stenosis and at least one the following measures of extracranial artery atherosclerosis: plaque, calcification, lipid-rich necrotic core (LRNC), or intraplaque hemorrhage. Univariate and multivariate Cox regressions were used to calculate the hazard ratio (HR) and corresponding 95% confidence interval (CI) of co-existing plaques in predicting subsequent vascular events. RESULTS: In total, 150 patients (mean age: 61.8 ± 11.9 years; 109 males) were recruited. During the median follow-up time of 12.1 months, 41 (27.3%) patients experienced vascular events. Co-existing intracranial artery stenosis and extracranial carotid plaque (HR, 3.57; 95% CI, 1.63-7.82; P = 0.001) and co-existing intracranial artery stenosis and extracranial carotid LRNC (HR, 4.47; 95% CI, 2.15-9.27; P < 0.001) were significantly associated with subsequent vascular events, respectively. After adjusted for confounding factors and carotid stenosis, these associations remained statistically significant (HR, 5.12; 95% CI, 1.36-19.24; P = 0.016 and HR, 8.12; 95% CI, 2.41-27.31; P = 0.001, respectively). CONCLUSIONS: The co-existing cerebrovascular atherosclerotic diseases, particularly co-existing carotid lipid-rich necrotic core and intracranial stenosis, are independent predictors for subsequent vascular events.

Incremental value of plaque enhancement in predicting stroke recurrence in symptomatic intracranial atherosclerosis.

PURPOSE: To investigate the association between plaque enhancement and stroke recurrence in subjects with intracranial atherosclerosis. METHODS: Ischemic stroke patients with symptomatic intracranial atherosclerosis were prospectively included and followed in a comprehensive stroke center. Pre- and post-contrast vessel wall images were used to evaluate plaque enhancement. Other established suggestive imaging markers were also acquired simultaneously. Univariate- and multivariate-adjusted Cox proportional hazard regression models were used to determine the association between plaque enhancement and stroke recurrence. Finally, receiver operating characteristic (ROC) curves were used to demonstrate the predictive value of different imaging markers. RESULTS: Of the 60 subjects included, 12 (20.0%) patients presented with ipsilateral stroke recurrence during the median 12-month follow-up. Cox proportional hazard regression models indicated that plaque enhancement was an independent risk factor associated with stroke recurrence after adjusted covariates, with a hazard ratio (HR) of 14.24 and 95% confidence interval (95% CI) (1.21, 168.11), p = 0.04. In addition, border zone infarction was also statistically significant in predicting stroke recurrence in multi-variable regression (HR = 3.80; 95% CI = 1.04, 13.80; p = 0.04). Collateral status was in marginal significance (HR = 0.25; 95% CI = 0.06, 1.08; p = 0.06). ROC analysis indicated that the area under the curve and 95% CI to identify stroke recurrence are 0.67 (0.51, 0.82) for plaque enhancement and 0.71 (0.54, 0.88) for infarction pattern and collateral status and may increase to 0.82 (0.70, 0.93) by combining the three markers above. CONCLUSION: Plaque enhancement is independently associated with stroke recurrence in subjects with intracranial atherosclerosis and has added value to hemodynamic indicators in predicting stroke recurrence.

Utilization of carbon sources in the rice rhizosphere and nonrhizosphere soils with different long-term fertilization management.

Carbon (C) plays an important role in the interaction between plant and rhizosphere microbial communities, but there is still limited information about how C source utilization soil microbial structure responds to soil fertility changes under the double-cropping rice (Oryza sativa L.) system in Southern China paddy fields. Therefore, the effects of long-term (33 years) fertilizer regimes on the characteristics of C utilization in both rhizosphere and nonrhizosphere soils under double-cropping rice fields in Southern China were investigated by using the metagenome sequencing technology. The experiment began in 1986, and included five fertilizer treatments: without fertilizer input (CK), chemical fertilizer alone (MF), rice straw residue and chemical fertilizer (RF), 30% organic matter, and 70% chemical fertilizer (LOM), and 60% organic matter and 40% chemical fertilizer (HOM). The results showed that the relative abundance of Gemmatimonadetes and Planctomycetia in both the rhizosphere and nonrhizosphere soils was increased by application of rice straw residue and organic manure, whereas the relative abundance of Gammaproteobacteria and Nitrospira was promoted by application of inorganic fertilizers. The largest group of clusters of orthologous groups of proteins categories was "amino acid transport and metabolism" with 16.46% unigenes, followed by "general function prediction only" (12.23%). Regarding the gene ontology categories, biological process were the largest category (174 949, 46.40%), followed by cellular component (126 766, 33.62%), and molecular function (110 353, 29.26%). The principal coordinate analysis indicated that different parts of the root zone were the most important factors affecting the variation of C source utilization bacteria community, and the different fertilizer treatments were the second important factor affecting the variation of C source utilization bacteria community. As a result, the application of fertilization practices had significant effects on the abundance and community composition of C source utilization microbes in paddy soils. The results showed that the combined application of rice straw residue or organic manure with chemical fertilizer practices significantly increases the C source utilization of soil microorganisms in double-cropping rice fields.

Genetic and environmental influences on household financial distress.

Heterogeneity of household financial outcomes emerges from various individual and environmental factors, including personality, cognitive ability, and socioeconomic status (SES), among others. Using a genetically informative data set, we decompose the variation in financial management behavior into genetic, shared environmental and non-shared environmental factors. We find that about half of the variation in financial distress is genetically influenced, and personality and cognitive ability are associated with financial distress through genetic and within-family pathways. Moreover, genetic influences of financial distress are highest at the extremes of SES, which in part can be explained by neuroticism and cognitive ability being more important predictors of financial distress at low and high levels of SES, respectively.

Co-existing intracranial and extracranial carotid artery atherosclerotic plaques and recurrent stroke risk: a three-dimensional multicontrast cardiovascular magnetic resonance study.

BACKGROUND: As a systemic disease, atherosclerosis commonly affects intracranial and extracranial carotid arteries simultaneously which is defined as co-existing plaques. Previous studies demonstrated that co-existing atherosclerotic diseases are significantly associated with ischemic cerebrovascular events. The aim of this study was to investigate the characteristics of co-existing intracranial and extracranial carotid atherosclerotic plaques and their relationships with recurrent stroke by using 3D multi-contrast magnetic resonance (MR) vessel wall imaging. METHODS: Patients with recent cerebrovascular symptoms in anterior circulation and at least one carotid plaque were recruited. All patients underwent cardiovascular magnetic resonance (CMR) for brain and intracranial and extracranial arteries. Presence/absence of atherosclerotic plaque at each arterial segment was identified. The maximum wall thickness (Max WT), length, stenosis of each plaque was measured. The presence/absence of calcification, lipid-rich necrotic core (LRNC), and intraplaque hemorrhage (IPH) was assessed. Cerebral old and acute infarcts in anterior circulation were evaluated. RESULTS: Fifty-eight patients (mean age: 58.0 ± 8.5 years old, 34 males) were recruited. Of the 58 patients, co-existing intracranial and extracranial carotid artery plaques were found in 45 patients (77.6%), of which 7 (15.6%) had first time acute stroke and 26 (57.8%) had recurrent stroke. For these 33 patients with stroke, the number of intracranial plaques (OR = 11.26; 95% CI, 1.27-100; p = 0.030) and co-existing intracranial and extracranial carotid artery plaques (OR = 2.42; 95% CI, 1.04-5.64; p = 0.040) was significantly associated with recurrent stroke. After adjusting for traditional risk factors, the number of co-existing plaques was still significantly correlated with recurrent stroke (OR = 3.31; 95% CI, 1.09-10.08; p = 0.035). No correlations were found between recurrent stroke and Max WT, length, stenosis, and compositions of plaques. CONCLUSIONS: Co-existing intracranial and extracranial carotid artery plaques are prevalent in symptomatic patients and the number of co-existing plaques is independently associated with the risk of recurrent stroke.

Opportunities and challenges for anti-CD47 antibodies in hematological malignancies.

CD47 is a cell-surface ligand that is overexpressed in various malignancies and that binds to SIRPα on macrophages to promote tumor cell evasion of phagocytosis. Blocking the CD47-SIRPα axis can increase the phagocytosis of macrophages to exert antitumor effects. CD47-based immunotherapy is a current research focus. The combination of anti-CD47 antibodies with other drugs has shown encouraging response rates in patients with hematological tumors, but side effects also occur. Bispecific antibodies and SIRPα/Fc fusion proteins appear to balance the efficacy and safety of treatment. We review the latest clinical research advances and discuss the opportunities and challenges associated with CD47-based immunotherapy for hematological malignancies.

Wirelessly Actuated Microfluidic Pump and Valve for Controlled Liquid Delivery in Dental Implants.

Enabling minimally invasive and precise control of liquid release in dental implants is crucial for therapeutic functions such as delivering antibiotics to prevent biofilm formation, infusing stem cells to promote osseointegration, and administering other biomedicines. However, achieving controllable liquid cargo release in dental implants remains challenging due to the lack of wireless and miniaturized fluidic control mechanisms. Here wireless miniature pumps and valves that allow remote activation of liquid cargo delivery in dental implants, actuated and controlled by external magnetic fields (<65 mT), are reported. A magnet-screw mechanism in a fluidic channel to function as a piston pump, alongside a flexible magnetic valve designed to open and close the fluidic channel, is proposed. The mechanisms are showcased by storing and releasing of liquid up to 52 µL in a dental implant. The liquid cargos are delivered directly to the implant-bone interface, a region traditionally difficult to access. On-demand liquid delivery is further showed by a metal implant inside both dental phantoms and porcine jawbones. The mechanisms are promising for controllable liquid release after implant placement with minimal invasion, paving the way for implantable devices that enable long-term and targeted delivery of therapeutic agents in various bioengineering applications.

Anterior approach versus posterior approach for the treatment of multilevel cervical spondylotic myelopathy: a systemic review and meta-analysis.

PURPOSE: To compare the clinical outcomes, complications, and surgical trauma between anterior and posterior approaches for the treatment of multilevel cervical spondylotic myelopathy. STUDY DESIGN: Systematic review and meta-analysis. METHODS: We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials databases for randomized controlled trials or non-randomized controlled trials that compared anterior and posterior surgical approaches for the treatment of multilevel cervical spondylotic myelopathy. Exclusion criteria were non-controlled studies, combined anterior and posterior surgery, follow-up <1 year, cervical kyphosis >15°, and cervical myelopathy caused by ossification of the posterior longitudinal ligament. The main end points included: recovery rate; Japanese Orthopedic Association (JOA) score; reoperation rate; complication rate; blood loss; and operation time. Subgroup analysis was conducted according to the mean number of surgical segments. RESULT: A total of eight studies were included in the meta-analysis; none of which were randomized controlled trials. All of the selected studies were of high quality as indicated by the Newcastle-Ottawa scale. In five studies involving 351 patients, the preoperative JOA score was similar between the anterior and posterior groups [P > 0.05, WMD: -0.00 (-0.56, 0.56)]. In four studies involving 268 patients, the postoperative JOA score was higher in the anterior group compared with the posterior group [P < 0.05, WMD: 0.79 (0.16, 1.42)]. For recovery rate, there was significant heterogeneity among the four studies involving 304 patients, hence, only descriptive analysis was performed. In seven studies involving 447 patients, the postoperative complication rate was significant higher in the anterior group compared with the posterior group [P < 0.05, odds ratio: 2.60 (1.63, 4.15)]. Of the 245 patients in the 8 studies who received anterior surgery, 21 (8.57%) received reoperation. Of the 285 patients who received posterior surgery, only 1 (0.3%) received reoperation. The reoperation rate was significantly higher in the anterior group compared with the posterior group (P < 0.001). In the 3 studies involving 236 patients compared subtotal corpectomy and laminoplasty/laminectomy, blood loss and operation time were significantly higher in the anterior subtotal corpectomy group compared with the posterior laminoplasty/laminectomy group [P < 0.05, WMD: 150.10 (63.53, 236.66) and P < 0.05, WMD: 59.17 (45.69, 72.66)]. CONCLUSION: The anterior approach was associated with better postoperative neural function than the posterior approach in the treatment of multilevel cervical spondylotic myelopathy. There was no apparent difference in the neural function recovery rate. The complication and reoperation rates were significantly higher in the anterior group compared with the posterior group. The surgical trauma associated with corpectomy was significantly higher than that associated with laminoplasty/laminectomy.

Wireless Millimeter-Size Soft Climbing Robots with Omnidirectional Steerability on Tissue Surfaces.

Wirelessly actuated miniature soft robots actuated by magnetic fields that can overcome gravity by climbing soft and wet tissues are promising for accessing challenging enclosed and confined spaces with minimal invasion for targeted medical operation. However, existing designs lack the directional steerability to traverse complex terrains and perform agile medical operations. Here we propose a rod-shaped millimeter-size climbing robot that can be omnidirectionally steered with a steering angle up to 360 degrees during climbing beyond existing soft miniature robots. The design innovation includes the rod-shaped robot body, its special magnetization profile, and the spherical robot footpads, allowing directional bending of the body under external magnetic fields and out-of-plane motion of the body for delivery of medical patches. With further integrated bio-adhesives and microstructures on the footpads, we experimentally demonstrated inverted climbing of the robot on porcine gastrointestinal (GI) tract tissues and deployment of a medical patch for targeted drug delivery.

Aspects of a Suspended Bioprinting System Affect Cell Viability and Support Bath Properties.

Suspended hydrogel printing is a growing method for fabricating bioprinted hydrogel constructs, largely due to how it enables nonviscous hydrogel inks to be used in extrusion printing. In this work, a previously developed poly(N-isopropylacrylamide)-based thermogelling suspended bioprinting system was examined in the context of chondrocyte-laden printing. Material factors such as ink concentration and cell concentration were found to have a significant effect on printed chondrocyte viability. In addition, the heated poloxamer support bath was able to maintain chondrocyte viability for up to 6 h of residence within the bath. The relationship between the ink and support bath was also assessed by measuring the rheological properties of the bath before and after printing. Bath storage modulus and yield stress decreased during printing as nozzle size was reduced, indicating the likelihood that dilution occurs over time through osmotic exchange with the ink. Altogether this work demonstrates the promise for printing high-resolution cell-encapsulating tissue engineering constructs, while also elucidating complex relationships between the ink and bath, which must be taken into consideration when designing suspended printing systems.

Association of Serum γ-Glutamyltransferase With C-Reactive Protein Levels in Patients With Coronary Heart Disease.

Serum γ-glutamyltransferase (GGT) levels have been shown to be associated with C-reactive protein (CRP) levels. Nevertheless, studies on this relationship in coronary heart disease (CHD) populations are limited. This study retrospectively assessed 17 523 patients with CHD undergoing GGT and CRP testing. They were divided into 3 groups according to GGT tertiles. The critical points for high CRP levels was 10.0 mg/L, which corresponded to the 75th percentile. Logistic regression analysis was used to analyze the association between GGT and CRP levels in CHD patients. The baseline analysis showed significant differences in related parameters among patients with CHD. Compared with GGT tertile 1 (T1), the odds ratio (OR) of T3 for GGT in CHD patients was 2.15 (95% confidence interval [CI]: 1.96-2.36). The association between GGT and CRP was higher in males (OR: 2.23; 95% CI: 1.98-2.52) than in females (OR: 2.18; 95% CI: 1.89-2.51). This study showed an association between serum GGT and CRP levels in patients with CHD. GGT may be an inflammatory marker and an additional measure for assessing cardiovascular risk.