[Application of intra-articular graft length measurement in total anterior cruciate ligament reconstruction].

OBJECTIVE: To investigate the clinical efficacy of arthroscopic measurement of intra-articular graft length in the application of total internal reconstruction of the anterior cruciate ligament(ACL). METHODS: The 60 patients with ACL injury treated between January 2020 and January 2022 were retrospectively analyzed. There were 37 males and 23 females, aged from 22 to 44 years. According to the different surgical methods, they were divided into two groups:conventional surgery group (conventional group) and pull-line measurement group (measurement group), with 30 cases in each group. In the conventional group, there were 20 males and 10 females, with an average age of (30.00±3.95) years old;the body mass index (BMI) was (22.58±1.41) kg·m-2;there were 9 cases on the left side and 21 cases on the right side;the time from injury to operation was (3. 00±1.35) days. In the measurement group, there were 17 males and 13 females, with an average of(32.00±4.29) years;BMI was (23.29±1.39) kg·m-2;there were 12 cases on the left side and 18 cases on the right side;the time from injury to operation was (3.00±1.27) days. The clinical data of the patients before surgery, 6 months after surgery and 12 months after surgery were collected and recorded. The clinical efficacy of the two methods was compared in terms of postoperative VAS, KOOS, Lysholm score, IKDC score, knee stability (Lachman test, anterior drawer test and axial shift test), the degree of widening of bone tunnel diameter measured by CT at different stages of the postoperative period and MRI scoring system. RESULTS: At 12 months after surgery, the VAS of the measurement group was lower than that of the conventional group(P<0.001). At 12 months after surgery, KOOS scores in the measurement group were higher than those in the conventional group, and there were statistically significant differences in all scores except symptom scores (P<0.05). Six months after operation, Lysholm total score and IKDC total score in the measurement group were higher than those in the conventional group, and the difference was statistically significant (P<0.05). At 12 months after surgery, knee stability tests were performed, and the differences between the Lachman test, anterior drawer test and axial shift test measurement group and the conventional group were not statistically significant (P>0.05). However, overall knee instability analysis showed that the knee stability of the measurement group was better than that of the control group, and the difference between the groups was statistically significant (P=0.038). The imaging assessment of patients in both groups at 6 months after surgery showed that the widening of tendon tunnel diameter in both femur and tibia was reduced in the measurement group compared with the conventional group after surgery, and the difference was statistically significant(P<0.05);MRI scores were higher in all patients in the measurement group those in the conventional group, at 6 months and 12 months agter surgery(P<0.05). CONCLUSION: Arthroscopic measurement of intra-articular cavity graft length in total internal technique for ACL reconstruction, high tendon utilization, good stability, the knee joint function has recovered satisfactorily within one year, and the therapeutic effect is affirmed.

Establishment and Validation of a Risk Prediction Model for Non-Invasive Ventilation Failure After Birth in Premature Infants with Gestational Age < 32 Weeks.

OBJECTIVES: This study was performed to construct and validate a risk prediction model for non-invasive ventilation (NIV) failure after birth in premature infants with gestational age < 32 weeks. METHODS: The data were derived from the multicenter retrospective study program - Jiangsu Provincial Neonatal Respiratory Failure Collaboration Network from Jan 2019 to Dec 2021. The subjects finally included were preterm infants using NIV after birth with gestational age less than 32 weeks and admission age within 72 h. After screening by inclusion and exclusion criteria, 1436 babies were subsequently recruited in the study, including 1235 infants in the successful NIV group and 201 infants in the failed NIV group. RESULTS: (1) Gestational age, 5 min Apgar, Max FiO2 during NIV, and FiO2 fluctuation value during NIV were selected by univariate and multivariate analysis. (2) The area under the curve of the prediction model was 0.807 (95% CI: 0.767-0.847) in the training set and 0.825 (95% CI: 0.766-0.883) in the test set. The calibration curve showed good agreement between the predicted probability and the actual observed probability (Mean absolute error = 0.008 for the training set; Mean absolute error = 0.012 for the test set). Decision curve analysis showed good clinical validity of the risk model in the training and test cohorts. CONCLUSION: This model performed well on dimensions of discrimination, calibration, and clinical validity. This model can serve as a useful tool for neonatologists to predict whether premature infants will experience NIV failure after birth.

Intraoperative cytokine adsorption in cardiothoracic transplant patients: an Australian propensity-score matched pilot study.

BACKGROUND: It is unclear if immunomodulation via cytokine adsorption (CA) to reduce perioperative inflammatory cascade in cardiothoracic transplants is associated with better outcomes. OBJECTIVE: This pilot study aims to assess the clinical outcomes of intraoperative CA in heart/lung transplantation. METHODS: From July to October 2020, intraoperative CA was instituted in 11 patients who underwent heart/lung transplantation. One-to-one propensity score matching without replacement was conducted with historical patients who did not receive CA at the time of surgery. Primary end-points evaluated were vasopressor/ inotropic demands, blood loss and mortality. Secondary end-points measured were operative morbidities. RESULTS: After matching, there were 2 (18.2%) ventricular assist device explant with heart transplantation, 2 (18.2%) heart transplantation and 7 (63.6%) lung transplantation in each group. Mean age in both groups were 53.3 years and 54.9 years respectively. The duration of noradrenaline requirement in the CA group was shorter (median, 1627 versus 3144 min, P = 0.5) and postoperative dopamine demand was significantly higher (median peak dose, 5.0 versus 0 µg/kg/min, P = 1.0; median duration of use, 7729 versus 0 min, P = 0.01). Non-red blood cell transfusion rate was two times higher in CA patients (90.9% versus 45.4%, P = 0.06). Early mortality was higher in the control group (18.2% versus 9.1%, P = 1.0). No differences were observed in the incidences of operative morbidities. CONCLUSION: Intraoperative CA in heart and lung transplantation in our institution was not associated with significant improvement in clinical outcomes, including vasopressor/inotropic demand. Larger studies are required to evaluate the transfusion requirements and mortality risks with CA use in this patient population.

The effect of developmental care on the length of hospital stay and family centered care practice for very low birth weight infants in neonatal intensive care units: A cluster randomized controlled trial.

BACKGROUND: Despite previous studies suggesting that developmental care can provide benign stimulation to promote neural development of newborns, more evidence is needed regarding the other clinical benefits of developmental care. OBJECTIVE: To evaluate the effect of implementing developmental care on the length of hospital stay, the improvement of care practice in neonatal intensive care units, as well as the short-term outcome of very low birth weight infants. DESIGN: Cluster-randomized controlled trial. SETTING(S) AND PARTICIPANTS: From March 1, 2021 to March 1, 2022, 1400 very low birth weight infants were recruited from 14 tertiary neonatal intensive care units in China. METHODS: We assigned 14 neonatal intensive care units to either developmental care or standard care. The length of hospital stay of the infants was the primary outcome analyzed at the individual level. Secondary outcomes were family centered care practice including parental involvement, the skin to skin care, exclusive breast milk, oral immune therapy and breastfeeding. The environmental management (noise and light) and the short-term outcomes were also evaluated. RESULTS: The length of hospital stay for the developmental care group was 65 % as long as that for the control group (HR: 0.65, 95 % CI, 0.451-0936, p = 0.021). After controlling the covariables, the adjusted HR = 0.755 (95 % CI, 0.515 to 1.107, p = 0.150). When compared to the control group, the developmental care group had greater access to SSC, with 22 infants (3.8 %) in the developmental care group compared to 13 infants (1.7 %) in the standard care group (p = 0.013). A greater proportion of infants in the developmental care group were fed at the breast, than those in the standard care group (136 [23.6 %] vs 9 [1.1 %]; p = 0.029). Compared to the control group, exclusively breast milk was significantly more favorable in the developmental care group (435 [75.6 %] vs 114 [15.0 %]; p = 0.001). The difference remained significant even after adjusting for covariates. However, the rate of oral immune therapy and parental involvement was similar in the two groups. The average noise and light levels in the developmental care group were significantly lower than those in the standard care group. After adjusting for confounders, the difference remained significant. There were no significant differences among groups in the mortality and major morbidity. CONCLUSIONS: Developmental care might have developed an accumulated effect over time on the length of hospital stay among very low birth weight infants. The implementation of developmental care can greatly improve family centered care practices and the neonatal intensive care unit environment. REGISTRATION: ClinicalTrials.govNCT05166720. Registration date: 1 March, 2021.

Preparation and characterization of a polyurethane-based sponge wound dressing with a superhydrophobic layer and an antimicrobial adherent hydrogel layer.

Bacterial infection poses a significant impediment in wound healing, necessitating the development of dressings with intrinsic antimicrobial properties. In this study, a multilayered wound dressing (STPU@MTAI2/AM1) was reported, comprising a surface-superhydrophobic treated polyurethane (STPU) sponge scaffold coupled with an antimicrobial hydrogel. A superhydrophobic protective outer layer was established on the hydrophilic PU sponge through the application of fluorinated zinc oxide nanoparticles (F-ZnO NPs), thereby resistance to environmental contamination and bacterial invasion. The adhesive and antimicrobial inner layer was an attached hydrogel (MTAI2/AM1) synthesized through the copolymerization of N-[2-(methacryloyloxy)ethyl]-N, N, N-trimethylammonium iodide and acrylamide, exhibits potent adherence to dermal surfaces and broad-spectrum antimicrobial actions against resilient bacterial strains and biofilm formation. STPU@MTAI2/AM1 maintained breathability and flexibility, ensuring comfort and conformity to the wound site. Biocompatibility of the multilayered dressing was demonstrated through hemocompatibility and cytocompatibility studies. The multilayered wound dressing has demonstrated the ability to promote wound healing when addressing MRSA-infected wounds. The hydrogel layer demonstrates no secondary damage when peeled off compared to commercial polyurethane sponge dressing. The STPU@MTAI2/AM1-treated wounds were nearly completely healed by day 14, with an average wound area of 12.2 ± 4.3 %, significantly lower than other groups. Furthermore, the expression of CD31 was significantly higher in the STPU@MTAI2/AM1 group compared to other groups, promoting angiogenesis in the wound and thereby contributing to wound healing. Therefore, the prepared multilayered wound dressing presents a promising therapeutic candidate for the management of infected wounds. STATEMENT OF SIGNIFICANCE: Healing of chronic wounds requires avoidance of biofouling and bacterial infection. However developing a wound dressing which is both anti-biofouling and antimicrobial is a challenge. A multilayered wound dressing with multifunction was developed. Its outer layer was designed to be superhydrophobic and thus anti-biofouling, and its inner layer was broad-spectrum antimicrobial and could inhibit biofilm formation. The multilayered wound dressing with adhesive property could easily be removed from the wound surface preventing the cause of secondary damage. The multilayered wound dressing has demonstrated good abilities to promote MRSA-infected wound healing and presents a viable treatment for MRSA-infected wound.

Efficacy and safety of PD-1/PD-L1 inhibitor-based immune combination therapy versus sorafenib in the treatment of advanced hepatocellular carcinoma: a meta-analysis.

Objective: To systematically evaluate the safety and efficacy of PD-1/PD-L1 inhibitor-based immunotherapy (hereafter referred to as "combination immunotherapy") compared with that of sorafenib in the treatment of hepatocellular carcinoma (HCC). Methods: Databases such as PubMed, Embase, and the Cochrane Library were searched from the date of their establishment to September 2023 to identify randomized controlled trials (RCTs) of combination immunotherapy versus sorafenib for the treatment of advanced HCC. Two reviewers independently evaluated the quality of the included studies, extracted the data, and cross-checked the information. The meta-analysis was performed using RevMan 5.3 software. Results: A total of 5 RCTs were included. The results of the meta-analysis showed the following: (1) Effectiveness. Compared to sorafenib, combination immunotherapy significantly improved overall survival (OS, HR = 0.69, 95% CI: 0.58 ~ 0.82, p < 0.01) and progression-free survival (PFS, HR = 0.62, 95% CI: 0.50 ~ 0.78, p < 0.001) in patients with advanced HCC. (2) Safety. Both groups had comparatively high incidences of adverse events (AEs), but the difference in any treatment-related adverse events was not significant between the two arms (OR = 0.98, 95% CI: 0.95 ~ 1.02, p = 0.34). The difference in the incidence of grade 1-2 adverse reactions was statistically significant (OR = 0.66, 95% CI = 0.49-0.90, p = 0.001). There were no differences in grade 3/4 TRAEs or grade 5 TRAEs (OR = 1.46, 95% CI = 0.78 ~ 2.71, p = 0.24; OR = 1.08, 95% CI = 0.73 ~ 1.58, p = 0.71). Conclusion: Combined immunotherapy can significantly prolong the OS and PFS of patients with advanced HCC without increasing the incidence of adverse effects in terms of safety, but the incidence of AEs in different systems is different.

Revealing the spatiotemporal brain dynamics of covert speech compared with overt speech: A simultaneous EEG-fMRI study.

Covert speech (CS) refers to speaking internally to oneself without producing any sound or movement. CS is involved in multiple cognitive functions and disorders. Reconstructing CS content by brain-computer interface (BCI) is also an emerging technique. However, it is still controversial whether CS is a truncated neural process of overt speech (OS) or involves independent patterns. Here, we performed a word-speaking experiment with simultaneous EEG-fMRI. It involved 32 participants, who generated words both overtly and covertly. By integrating spatial constraints from fMRI into EEG source localization, we precisely estimated the spatiotemporal dynamics of neural activity. During CS, EEG source activity was localized in three regions: the left precentral gyrus, the left supplementary motor area, and the left putamen. Although OS involved more brain regions with stronger activations, CS was characterized by an earlier event-locked activation in the left putamen (peak at 262 ms versus 1170 ms). The left putamen was also identified as the only hub node within the functional connectivity (FC) networks of both OS and CS, while showing weaker FC strength towards speech-related regions in the dominant hemisphere during CS. Path analysis revealed significant multivariate associations, indicating an indirect association between the earlier activation in the left putamen and CS, which was mediated by reduced FC towards speech-related regions. These findings revealed the specific spatiotemporal dynamics of CS, offering insights into CS mechanisms that are potentially relevant for future treatment of self-regulation deficits, speech disorders, and development of BCI speech applications.

Shell Modulation of Hollow Metal Sulfide Nanocomposite for Stable Potassium Storage at Room and High Temperature.

The large size of K-ion makes the pursuit of stable high-capacity anodes for K-ion batteries (KIBs) a formidable challenge, particularly for high temperature KIBs as the electrode instability becomes more aggravated with temperature climbing. Herein, we demonstrate that a hollow ZnS@C nanocomposite (h-ZnS@C) with a precise shell modulation can resist electrode disintegration to enable stable high-capacity potassium storage at room and high temperature. Based on a model electrode, we identify an interesting structure-function correlation of the h-ZnS@C: with an increase in the shell thickness, the cyclability increases while the rate and capacity decrease, shedding light on the design of high-performance h-ZnS@C anodes via engineering the shell thickness. Typically, the h-ZnS@C anode with a shell thickness of 60 nm can deliver an impressive comprehensive performance at room temperature; the h-ZnS@C with shell thickness increasing to 75 nm can achieve an extraordinary stability (88.6 % capacity retention over 450 cycles) with a high capacity (450 mAh g-1) and a superb rate even at an extreme temperature of 60 °C, which is much superior than those reported anodes. This contribution envisions new perspectives on rational design of functional metal sulfides composite toward high-performance KIBs with insights into the significant structure-function correlation.

A therapeutic strategy of parthenolide in improving imiquimod-induced psoriasis-like skin inflammation targeting IL-36/NETs through skin transdermal therapeutic system.

BACKGROUND: Psoriasis is an inflammatory skin disease that occurs repeatedly over time. The natural product of sesquiterpene lactones, Parthenolide (Par), is isolated from Tanacetum parthenium L. (feverfew) which has significant effects on anti-inflammatory. The therapeutic effect of the medication itself is crucial, but different routes of administration of the same drug can also produce different effects. PURPOSE: The aim of our research sought to investigate the ameliorating effects of Par in psoriasis-like skin inflammation and its related mechanism of action. RESULTS: In the IMQ-induced model, intragastric administration of Par reduced the Psoriasis Area and Severity Index (PASI) score, improved skin erythema, scaling, and other symptoms. And Par decreased the expression of Ki67, keratin14, keratin16 and keratin17, and increased the expression of keratin1. Par could reduce IL-36 protein expressions, meanwhile the expression of Il1b, Cxcl1 and Cxcl2 mRNA were also decreased. Par regulated the expression levels of F4/80, MPO and NE. However, skin transdermal administration of Par was more effective. Similarly, Par attenuated IL-36γ, IL-1ß and caspase-1 activated by Poly(I:C) in in vitro and ex vivo. In addition, Par also reduced NE, PR3, and Cathepsin G levels in explant skin tissues. CONCLUSION: Par ameliorated psoriasis-like skin inflammation in both in vivo and in vitro, especially after treatment with transdermal drug delivery, possibly by inhibiting neutrophil extracellular traps and thus by interfering IL-36 signaling pathway. It indicated that Par provides a new research strategy for the treatment of psoriasis-like skin inflammation and is expected to be a promising drug.

Recycling drinking water treatment sludge in construction and building materials: A review.

Drinking water treatment sludge (DWTS) is a by-product of water treatment, and it is difficult to recycle to high value and poses potential environmental risks. Recycling DWTS into cement-based materials is an effective measure to achieve its high-volume utilization and reduce its environmental load. DWTS is rich in silica-alumina phases and has potential pozzolanic activity after drying, grinding and calcination, giving it similar properties to traditional supplementary cementitious materials. Adjusting the sludge production process and coagulant type will change its physical and chemical properties. Adding a small amount of DWTS can generate additional hydration products and refine the pore structure of the cement sample, thus improving the mechanical properties and durability of the sample. However, adding high-volume DWTS to concrete causes microstructural deterioration, but it is feasible to use high-volume DWTS to produce artificial aggregates, lightweight concrete, and sintered bricks. Meanwhile, calcined DWTS has similar compositions to clay, which makes it a potential raw material for cement clinker production. Cement-based materials can effectively solidify heavy metal ions in DWTS, and alkali-activated binders, magnesium-based cement, and carbon curing technology can further reduce the risk of heavy metal leaching. This review provides support for the high-value utilization of DWTS in cement-based materials and the reduction of its potential environmental risks.

Upcycling textile sludge into magnesium oxychloride cement: Physical properties, microstructure, and leaching behavior.

Textile sludge is a by-product produced during the wastewater treatment process in the textile printing and dyeing industry. Textile sludge is rich in heavy metal elements, which makes it a potential risk to the surrounding environment. This study designs a magnesium oxychloride cement (MOC) components to solidify harmful substances in textile sludge and studies the influence of textile sludge ash (TSA) on the mechanical properties and microstructure of MOC samples. The results indicated that adding 5 %-20 % TSA is beneficial for increasing the compressive strength of air-cured MOC paste and improving its water resistance. Meanwhile, the MOC sample shows volume expansion in 168 h, which is related to the further hydration of residual MgO. Incorporating 10 %-20 % TSA substantially increased the volume expansion ratio of the mixture compared to plain MOC sample. In addition, the porosity of TSA-modified MOC after water curing did not change significantly compared to the sample before water curing, while the pore structure of plain MOC after water curing significantly coarsened. This is mainly because TSA reacts with MOC and generates Mg-Al-Cl-Si-H and Mg-Cl-Si-H gels, consequently improving the water stability of MOC sample. At the nanoscale, the 3/5-phase crystal and unreacted MgO content in the 15 % TSA-modified MOC sample is relatively reduced by 7.79 % and 25 %, respectively, compared to the plain sample, but the 13 % gel phase is detected. In addition, the MOC component can effectively solidify heavy metal elements in textile sludge. For the leachate of 20 % TSA-modified MOC paste, the Ni element is not detected, and its solidifying effect on heavy elements such as Zn and Mn exceeded 99 %.

Product innovation design process combined Kano and TRIZ with AD: Case study.

In the era of rapid product iteration, companies need simple and effective methods to guide the entire process of product innovation design and enhance their product innovation capabilities. Most research focused on improving one or several steps in the product design process. Although some scholars have proposed methods that guided the entire process, they combined more than three different theories, which increased the difficulty of theoretical learning and the complexity of practical implementation. This paper proposed a product innovation design process composed of three theoretical methods: Kano, Axiomatic Design (AD), and Theory of the Solution of Inventive Problems (TRIZ). This new process guided the entire product design process with fewer theoretical methods, reducing the difficulty of learning and implementation. The paper demonstrated the effectiveness of this method through the design practice of a portable two-wheeled self-balancing vehicle. Additionally, the discussion section explored the method's potential from the design management perspective.

Network pharmacology-based investigation and experimental validation of the therapeutic potential and molecular mechanism of Danshen Chuanxiongqin injection in acute pancreatitis.

BACKGROUND: Danshen Chuanxiong Injection (DCI) has demonstrated significant clinical efficacy in the treatment of acute pancreatitis (AP); however, the precise molecular mechanisms underlying its therapeutic effects remain incompletely understood. OBJECTIVE: In this study, we employed network pharmacology analysis to comprehensively investigate the active components, potential targets, and signaling pathways involved in DCI-mediated treatment of AP. METHODS: We utilized the mouse pancreatic acinar cell line 266-6 to establish an cholecystokinin (CCK)-induced AP cell injury model and evaluated cell viability using the Cell counting kit-8 assay. Western blotting and quantitative PCR were employed to determine the expression levels of key target proteins and genes. RESULTS: Network pharmacology analysis identified a total of 144 active components and 430 potential targets within DCI. By integrating data from public databases, we identified 762 AP-related genes. Among these, we identified 93 potential targets that may be involved in the therapeutic effects of DCI for AP. These targets were significantly enriched in biological processes such as oxidative stress, regulation of cytokine production, leukocyte migration, and the TNF signaling pathway. Molecular docking studies revealed a high binding affinity between the active components and the key targets AKT1 and NFKBA, indicative of potential interaction. Additionally, CCK-induced acinar cell injury led to upregulation of AKT1, NFKBA, and P53 proteins, as well as TNF, IL6, and MMP9 genes. Conversely, treatment with DCI dose-dependently attenuated CCK-induced acinar cell injury and restored the expression levels of the aforementioned proteins and genes. CONCLUSION: Overall, this study provides a comprehensive understanding of the molecular mechanisms underlying the therapeutic effects of DCI in the treatment of AP. Our findings confirm the protective effect of DCI against CCK-induced acinar cell injury and its regulation of key targets.

Catheter ablation of atrial fibrillation in patients with left bundle branch block.

BACKGROUND: Left bundle branch block (LBBB) and atrial fibrillation (AF) are commonly coexisting conditions. The impact of LBBB on catheter ablation of AF has not been well determined. This study aims to explore the long-term outcomes of patients with AF and LBBB after catheter ablation. METHODS: Forty-two patients with LBBB of 11,752 patients who underwent catheter ablation of AF from 2011 to 2020 were enrolled as LBBB group. After propensity score matching in a 1:4 ratio, 168 AF patients without LBBB were enrolled as non-LBBB group. Late recurrence and a composite endpoint of stroke, all-cause mortality, and cardiovascular hospitalization were compared between the two groups. RESULTS: Late recurrence rate was significantly higher in the LBBB group than that in the non-LBBB group (54.8% vs. 31.5%, p = .034). Multivariate analysis showed that LBBB was an independent risk factor for late recurrence after catheter ablation of AF (hazard ratio [HR] 2.19, 95% confidence interval [CI] 1.09-4.40, p = .031). LBBB group was also associated with a significantly higher incidence of the composite endpoint (21.4% vs. 6.5%, HR 3.98, 95% CI 1.64-9.64, p = .002). CONCLUSIONS: LBBB was associated with a higher risk for late recurrence and a higher incidence of composite endpoint in the patients underwent catheter ablation.

Sternal sparing aortic valve replacement via right anterior minithoracotomy: An early experience.

Purpose: This study aims to evaluate the perioperative outcomes of aortic valve replacement (AVR) via right anterior minithoracotomy (RAT) during the learning curve. Methods: It was a retrospective, observational, cohort study of patients who underwent RAT AVR from June 2015 to April 2022. Primary outcomes measured were 30-day morbidity and mortality. Results: A total of 107 consecutive patients underwent elective RAT AVR. Our patients were mostly male (78.5%), elderly (mean 68.7 years), and obese (34.6%). A majority of the patients (93.5%) were of low operative risk. Median cross-clamp and bypass times were 95 and 123 minutes respectively. There was a statistically significant correlation between increase in number of cases and decrease in operative time. All patients had no paravalvular leak at discharge. There were no operative cardiovascular mortality or major morbidity including stroke, myocardial infarction, renal failure requiring dialysis, or vascular complication. No patient required intraoperative conversion to full sternotomy for completion of AVR. Conclusion: Our study demonstrated that RAT AVR can be safely introduced. The learning curve required in performing RAT AVR can be safely negotiated through training, previous experience in minimally invasive surgery, careful patient selection including use of preoperative computed tomography of the aorta, and introduction of sutureless/rapid deployment valves.

Heating tumors with tumor cell-derived nanoparticles to enhance chemoimmunotherapy for colorectal cancer.

Aim: To investigate the mechanism of doxorubicin (DOX)-induced immunogenic cell death (ICD) and to improve immunotherapy efficacy. Materials & methods: In this study, hybrid vesicles containing DOX (HV-DOX) were prepared by thin-film hydration with extrusion, and the formulated nanoparticles were characterized physically. Furthermore, in vitro experiments and animal models were used to investigate the efficacy and new mechanisms of chemotherapy combined with immunotherapy. Results: DOX improved tumor immunogenicity by alkalinizing lysosomes, inhibiting tumor cell autophagy and inducing ICD. HVs could activate dendritic cell maturation, synergistically enhancing chemotherapeutic immunity. Conclusion: The mechanism of DOX-induced ICD was explored, and antitumor immunity was synergistically activated by HV-DOX to improve chemotherapeutic drug loading and provide relevant antigenic information.

Blocking brown adipocyte ß3-adrenoceptor attenuates blood-spinal cord barrier impairment and chronic postsurgical pain in a rat model of preoperative stress.

Preoperative stress has been recognized as an independent risk factor for chronic postsurgical pain (CPSP). However, the underlying mechanisms of CPSP influenced by preoperative stress remain elusive. Previous studies indicated that excessive stress could induce disruption of the blood-spinal cord barrier (BSCB). We wondered whether and how BSCB involves in CPSP by using a single prolonged stress (SPS) combining plantar incision model in male rats to mimic preoperative stress-related postsurgical pain. Here, we observed that preoperative SPS-exposed rats exhibited relentless incisional pain, which was accompanied by impairment of BSCB and persistent elevation of serum IL-6. Intraperitoneal injections of Tocilizumab (an IL-6 receptor monoclonal antibody) not only mitigated BSCB breakdown but also alleviated pain behaviors. In addition, intervening ß3-adrenoceptor (ADRB3) signaling in brown adipocytes by SR59230a (a specific ADRB3 antagonist) treatment or removal of brown adipose tissues could effectively decrease serum IL-6 levels, ameliorate BSCB disruption, and alleviate incisional pain. Further results displayed that SI-exposed rats also showed markedly spinal microglia activation. And exogenous His-tagged IL-6 could pass through the disrupted BSCB, which might contribute to microglia activation. Injection of SR59230a or ablation of brown adipose tissues could effectively reduce the activation of spinal microglia. Thus, our findings suggest that serum IL-6 induced by brown adipocyte ADRB3 signaling contributed to BSCB disruption and spinal microglia activation, which might be involved in preoperative stress mediated CPSP. This work indicates a promising treatment strategy for preoperative stress induced CPSP by blocking ADRB3.

Unraveling the molecular freezing behavior of water on a calcium silicate hydrate matrix.

The hydration process of cement-based materials primarily results in the formation of calcium silicate hydrate (CSH), which is crucial in deciding how long concrete will last. This study utilizes molecular dynamics simulation technology to explore the freezing behavior of pure water solutions within various calcium silicate hydrate (CSH) matrices. The investigated matrices encompass four different Ca/Si ratios. According to the simulation, as ice crystals develop close to the surface of CSH, the CSH matrix strengthens its hydrogen and ionic interactions with water molecules, which effectively prevents water molecules from crystallizing and nucleating. Consequently, these molecules compose an unfrozen water film structure that bridges between ice crystals and the CSH matrix. The research also reveals an intriguing relationship between silica chain behavior on the Ca/Si ratio and the CSH surface. Surface flaws arise as a result of the silica chains of CSH breaking into shorter segments as the Ca/Si ratio increases. These surface defects manifest as grooves on the matrix's surface, effectively capturing and retaining specific water molecules. The CSH matrix's hydrogen bonds with water molecules are weakened as a result of this process, facilitating their participation in the crystallization process, and leading to a thinner unfrozen water film thickness with an increased Ca/Si ratio. This study contributes to a greater knowledge of the performance and dependability of cement-based products by offering molecular-level insights into the freezing actions of liquids in gel pores.

Furosemide Responsiveness Predicts Acute Kidney Injury Progression After Cardiac Surgery.

BACKGROUND: As patients with acute kidney injury (AKI) progress to a higher stage, the risk for poor outcomes dramatically rises. Early identification of patients at high risk for AKI progression remains a major challenge. This study aimed to evaluate the value of furosemide responsiveness (FR) for predicting AKI progression in patients with initial mild and moderate AKI after cardiac surgery. METHODS: We performed 2 separate exploratory analyses. The Zhongshan cohort was a single-center, prospective, observational cohort, whereas the Beth Israel Deaconess Medical Center cohort was a single-center, retrospective cohort. We calculated 2 FR parameters for each patient, namely the FR index and modified FR index, defined as 2-hour urine output divided by furosemide dose (FR index, mL/mg/2 h) and by furosemide dose and body weight (modified FR index, mL/[mg·kg]/2 h), respectively. The primary outcome was AKI progression within 7 days. RESULTS: AKI progression occurred in 80 (16.0%) and 359 (11.3%) patients in the Zhongshan and Beth Israel Deaconess Medical Center cohorts, respectively. All FR parameters (considered continuously or in quartiles) were inversely associated with risk of AKI progression in both cohorts (all adjusted P < .01). The addition of FR parameters significantly improved prediction for AKI progression based on baseline clinical models involving C-index, net reclassification improvement, and integrated discrimination improvement index in both cohorts (all P < .01). CONCLUSIONS: FR parameters were inversely associated with risk of AKI progression in patients with mild and moderate AKI after cardiac surgery. The addition of FR parameters significantly improved prediction for AKI progression based on baseline clinical models.