Pediatric Sedation Assessment and Management System (PSAMS) for Pediatric Sedation in China: Development and Implementation Report.

Background: Recently, the growing demand for pediatric sedation services outside the operating room has imposed a heavy burden on pediatric centers in China. There is an urgent need to develop a novel system for improved sedation services. Objective: This study aimed to develop and implement a computerized system, the Pediatric Sedation Assessment and Management System (PSAMS), to streamline pediatric sedation services at a major children's hospital in Southwest China. Methods: PSAMS was designed to reflect the actual workflow of pediatric sedation. It consists of 3 main components: server-hosted software; client applications on tablets and computers; and specialized devices like gun-type scanners, desktop label printers, and pulse oximeters. With the participation of a multidisciplinary team, PSAMS was developed and refined during its application in the sedation process. This study analyzed data from the first 2 years after the system's deployment. Unlabelled: From January 2020 to December 2021, a total of 127,325 sedations were performed on 85,281 patients using the PSAMS database. Besides basic variables imported from Hospital Information Systems (HIS), the PSAMS database currently contains 33 additional variables that capture comprehensive information from presedation assessment to postprocedural recovery. The recorded data from PSAMS indicates a one-time sedation success rate of 97.1% (50,752/52,282) in 2020 and 97.5% (73,184/75,043) in 2021. The observed adverse events rate was 3.5% (95% CI 3.4%-3.7%) in 2020 and 2.8% (95% CI 2.7%-2.9%) in 2021. Conclusions: PSAMS streamlined the entire sedation workflow, reduced the burden of data collection, and laid a foundation for future cooperation of multiple pediatric health care centers.

Combined effects of sleep timing and nighttime sleep duration on non-alcoholic fatty liver disease.

BACKGROUND: While short sleep duration is linked to higher risk of non-alcoholic fatty liver disease (NAFLD), the combined effects of sleep timing and sleep duration on NAFLD are less explored. METHODS: In this cross-sectional study of 39,471 participants from Beijing-Tianjin-Hebei region of China, self-reported sleep information and ultrasonography-diagnosed NAFLD were obtained from Jan 2018 to Jan 2020. Sleep timing was categorized based on sleep midpoint: early-type (before 2:00 AM), intermediate-type (2:00-2:30 AM), and late-type (after 2:30 AM). We used multivariable logistic regression to explore the relationship between sleep timing, duration, and NAFLD. We analyzed sleep midpoint and duration categorically and continuously, and conducted stratification analyses by age, sex, body mass index, hypertension, diabetes, and dyslipidemia. RESULTS: Intermediate-type (OR: 1.15, 95% confidence interval: 1.05-1.26) and late-type sleep timing (OR: 1.08, 1.00-1.16) were associated with higher NAFLD risk compared to early-type. Additionally, longer sleep duration was linked to lower risk (OR: 0.92, 0.90-0.95 per hour increase). Notably, intermediate to late-type sleepers with normal sleep duration (7 to <8 h) exhibited a 20% higher NAFLD risk compared to early-type sleepers with the same duration (OR: 1.20, 1.04-1.39). The increased NAFLD risk associated with intermediate to late sleep timing was particularly evident in men, hypertension, and prediabetes or diabetes participants. CONCLUSIONS: Intermediate to late sleep timing, even with normal sleep duration, is associated with increased NAFLD risk. These findings underscore the importance of considering both sleep timing and sleep duration for NAFLD prevention, especially in men and individuals with cardiometabolic conditions.

Isolation, Purification of Phenolic Glycoside 1 from Moringa oleifera Seeds and Formulation of Its Liposome Delivery System.

In this study, N, N '-bis {4- [(α-L- rhamnosyloxy) benzyl]} thiourea (PG-1), a phenolic glycoside compound was purified from Moringa seed. The PG-1 has attracted extensive attention due to its anti-cancer, antioxidant, anti-inflammatory and hypoglycemic properties. However, some of its physicochemical properties such as oral bioavailability has not been studied. Herein, a highly purified PG-1 was extracted and incorporated in multiple layered liposomes (PG-1-L) to avoid its burst release and enhance oral bioavailability. After appropriate characterization, it was discovered that the obtained PG-1-L was stable, homogeneous and well dispersed with the average particle size being 89.26 ± 0.23 nm. Importantly, the in vitro release and in vivo oral bioavailability of PG-1-L were significantly improved compared with PG-1. In addition, MTT results showed that compared with the free PG-1, PG-1-L displayed obvious inhibitory effect on the HepG2 cells, while the inhibitory effect on healthy non-malignant 3T6 and LO-2 cells was not significant, indicating that PG-1-L had high safety. In conclusion, PG-1-L can be used as a promising delivery system and an ideal novel approach to improve the oral bioavailability and anticancer activity of PG-1.

Plant-derived exosomes extracted from Lycium barbarum L. loaded with isoliquiritigenin to promote spinal cord injury repair based on 3D printed bionic scaffold.

Plant-derived exosomes (PEs) possess an array of therapeutic properties, including antitumor, antiviral, and anti-inflammatory capabilities. They are also implicated in defensive responses to pathogenic attacks. Spinal cord injuries (SCIs) regeneration represents a global medical challenge, with appropriate research concentration on three pivotal domains: neural regeneration promotion, inflammation inhibition, and innovation and application of regenerative scaffolds. Unfortunately, the utilization of PE in SCI therapy remains unexplored. Herein, we isolated PE from the traditional Chinese medicinal herb, Lycium barbarum L. and discovered their inflammatory inhibition and neuronal differentiation promotion capabilities. Compared with exosomes derived from ectomesenchymal stem cells (EMSCs), PE demonstrated a substantial enhancement in neural differentiation. We encapsulated isoliquiritigenin (ISL)-loaded plant-derived exosomes (ISL@PE) from L. barbarum L. within a 3D-printed bionic scaffold. The intricate construct modulated the inflammatory response following SCI, facilitating the restoration of damaged axons and culminating in ameliorated neurological function. This pioneering investigation proposes a novel potential route for insoluble drug delivery via plant exosomes, as well as SCI repair. The institutional animal care and use committee number is UJS-IACUC-2020121602.

Copper homeostasis and cuproptosis in radiation-induced injury.

Radiation therapy for cancer treatment brings about a series of radiation injuries to normal tissues. In recent years, the discovery of copper-regulated cell death, cuproptosis, a novel form of programmed cell death, has attracted widespread attention and exploration in various biological functions and pathological mechanisms of copper metabolism and cuproptosis. Understanding its role in the process of radiation injury may open up new avenues and directions for exploration in radiation biology and radiation oncology, thereby improving tumor response and mitigating adverse reactions to radiotherapy. This review provides an overview of copper metabolism, the characteristics of cuproptosis, and their potential regulatory mechanisms in radiation injury.

Validating the performance of organ dysfunction scores in children with infection: A cohort study.

PURPOSE: We aimed to validate the performance of six available scoring models for predicting hospital mortality in children with suspected or confirmed infections. METHODS: This single-center retrospective cohort study included pediatric patients admitted to the PICU for infection. The primary outcome was hospital mortality. The six scores included the age-adapted pSOFA score, SIRS score, PELOD2 score, Sepsis-2 score, qSOFA score, and PMODS. RESULTS: Of the 5,356 children admitted to the PICU, 9.1% (488) died, and 25.1% (1,342) had basic disease with a mortality rate of 12.7% (171); 65.3% (3,499) of the patients were younger than 2 years, and 59.4% (3,183) were male. The discrimination abilities of the pSOFA and PELOD2 scores were superior to those of the other models. The calibration curves of the pSOFA and PELOD2 scores were consistent between the predictions and observations. Elevated lactate levels were a risk factor for mortality. CONCLUSION: The pSOFA and PELOD2 scores had superior predictive performance for mortality. Given the relative unavailability of items and clinical operability, the pSOFA score should be recommended as an optimal tool for acute organ dysfunction in pediatric sepsis patients. Elevated lactate levels are related to a greater risk of death from infection in children in the PICU.

Engineered Cellular Vesicles Displaying Glycosylated Nanobodies for Cancer Immunotherapy.

Immune checkpoint blockade targeting the CD47/SIRPα axis represents an alluring avenue for cancer immunotherapy. However, the compromised efficacy and safety concerns in vivo of conventional anti-CD47 antibodies impede their wide clinical applications. Here we introduced a single type of high-mannose glycans into the nanobodies against CD47 (HM-nCD47) and subsequently displayed HM-nCD47 on cellular vesicles (CVs) for enhanced cancer immunotherapy. In this platform, the CVs significantly improved the circulation time of HM-nCD47-CVs, the nCD47 enabled the blockade of the CD47/SIRPα axis, and the HM enhanced recognition of mannose-binding lectin, all synergistically activating the macrophage-mediated antitumor immunity. In both subcutaneous and metastatic murine tumor models, the HM-nCD47-CVs possessed significantly extended half-lives and increased accumulation at the tumor site, resulting in a remarkable macrophage-dependent inhibition of tumor growth, a transcriptomic remodeling of the immune response, and an increase in survival time. By integrating the chemical biology toolbox with cell membrane nanotechnology, the HM-nCD47-CVs represent a new immunotherapeutic platform for cancer and other diseases.

How does ferrocene correlate with ferroptosis? Multiple approaches to explore ferrocene-appended GPX4 inhibitors as anticancer agents.

Ferroptosis has emerged as a form of programmed cell death and exhibits remarkable promise for anticancer therapy. However, it is challenging to discover ferroptosis inducers with new chemotypes and high ferroptosis-inducing potency. Herein, we report a new series of ferrocenyl-appended GPX4 inhibitors rationally designed in a "one stone kills two birds" strategy. Ferroptosis selectivity assays, GPX4 inhibitory activity and CETSA experiments validated the inhibition of novel compounds on GPX4. In particular, the ROS-related bioactivity assays highlighted the ROS-inducing ability of 17 at the molecular level and their ferroptosis enhancement at the cellular level. These data confirmed the dual role of ferrocene as both the bioisostere motif maintaining the inhibition capacity of certain molecules with GPX4 and also as the ROS producer to enhance the vulnerability to ferroptosis of cancer cells, thereby attenuating tumor growth in vivo. This proof-of-concept study of ferrocenyl-appended ferroptosis inducers via rational design may not only advance the development of ferroptosis-based anticancer treatment, but also illuminate the multiple roles of the ferrocenyl component, thus opening the way to novel bioorganometallics for potential disease therapies.

The effects of delayed appropriate antimicrobial therapy on children with Staphylococcus aureus blood infection.

Early appropriate antimicrobial therapy plays a critical role for patients with Staphylococcus aureus bloodstream infection (SAB). We aim to determine the optimal time-window for appropriate antimicrobial therapy and evaluate the effects of delayed therapy on adverse clinical outcomes (in-hospital mortality, sepsis, and septic shock) in children with SAB by propensity score matching (PSM) analysis. Receiver-operating characteristic was used to determine the cut-off point of the time to appropriate therapy (TTAT), the patients were divided into timely and delayed appropriate antimicrobial therapy (delayed therapy) groups accordingly. The PSM was used to balance the characteristics between the two groups, controlling the effects of potential confounders. Kaplan-Meier methods and Cox proportional hazards regression were applied to the matched groups to analyze the association between delayed therapy and clinical outcomes. Inverse probability of treatment weighting and propensity score covariate adjustment were also performed to investigate the sensitivity of the results under different propensity score-based approaches. In total, 247 patients were included in this study. The optimal cut-off point of TTAT was identified as 6.4 h, with 85.0% sensitivity and 69.2% specificity (AUC 0.803, 95% confidence interval 0.702-0.904). Eighty-seven (35.22%) of the 247 patients who received delayed therapy (TTAT ≥ 6.4 h) had higher in-hospital mortality (19.54% vs 1.88%, p < 0.001), higher incidences of sepsis (44.83% vs 15.00%, p < 0.001) and septic shock (32.18% vs 6.25%, p < 0.001) when compared to timely therapy (TTAT < 6.4 h) patients. After PSM analysis, a total of 134 episodes (67 in each of the two matched groups) were further analyzed. No statistically significant difference was observed in in-hospital mortality between delayed and timely -therapy groups (log-rank test, P = 0.157). Patients with delayed therapy had a higher incidence of sepsis or septic shock than those with timely therapy (log-rank test, P = 0.009; P = 0.018, respectively). Compared to the timely-therapy group, the hazard ratio and 95% confidence interval in delayed-therapy group were 2.512 (1.227-5.144, P = 0.012) for sepsis, 3.109 (1.166-8.290, P = 0.023) for septic shock.    Conclusion: Appropriate therapy delayed 6.4 h may increase the incidence of sepsis and septic shock, with similar in-hospital mortality in patients with SAB. What is Known: • Staphylococcus aureus (S. aureus) is a major cause of bloodstream infections in children. Undoubtedly, early antimicrobial application plays a critical role in the treatment of children with Staphylococcus aureus bloodstream infections (SAB). • However, rapid, and aggressive administration of antimicrobials may lead to the overuse of these drugs and the emergence of multidrug-resistant microorganisms. Therefore, it is crucial to determine the optimal time-window for appropriate antimicrobial administration in children with SAB. Unfortunately, the optimal time-window for appropriate antimicrobial administration in children with SAB remains unclear. What is New: • Determining the optimal time-window for appropriate antimicrobial administration in patients with matched data variables is particularly important. The Propensity score matching (PSM) analysis effectively controls for confounding factors to a considerable extent when assessing the impact of treatment, thereby approximating the effects observed in randomized controlled trials. • To our knowledge, this is the first study using PSM method to assess the effects of delayed appropriate antimicrobial therapy on adverse outcomes in children with SAB. In low-risk populations with SAB, a delay of 6.4 h in appropriate therapy might increase the occurrence rate for sepsis and septic shock; however, no correlation has been found between this delay and an increased risk for hospital mortality.

An exploration of clinical features and factors associated with pain frequency and pain intensity in children with growing pains: a cross-sectional study from Chongqing, China.

Instruction: Growing pains are the most common cause of musculoskeletal pain in children, affecting both children's and caregivers' well-being. The lack of definitive diagnostic criteria complicates diagnosis and treatment. Objectives: This study aims to outline the clinical features and identify factors associated with the frequency and intensity of growing pains in children in Chongqing, China. Methods: A cross-sectional study was conducted in a children's hospital using its Internet hospital follow-up platform. Children initially diagnosed with growing pains between July and September 2022 were enrolled. Sociodemographics, pain locations, duration, frequency, intensity, and potentially related factors were collected. Results: Eight hundred sixty-three children were enrolled (average age: 8.19 ± 3.24 years; 455 boys [52.72%]). Pain frequency was reported as quarterly (62.11%), monthly (24.80%), biweekly (1.74%), weekly (10.08%), and daily (1.27%). The prevalence of mild, moderate, and severe pain was 26.65%, 55.74%, and 17.61%, respectively. The knee was the most common pain location (63.85%), mostly encountered between 4 pm and 5 pm (20.51%). Multivariate analysis revealed that pain frequency negatively correlated with vitamin supplementation during pregnancy, positively correlated with underweight, bad temper, increased exercise, and cold lower extremities. Pain intensity positively correlated with irritability, increased exercise, and pain sensitivity but negatively correlated with age and vitamin supplementation during lactation. Conclusion: Growing pains typically occur on a quarterly basis, predominantly affecting the knees during 4 pm to 5 pm. Factors in sociodemographics, maternal aspect, temperament, and exercise levels can influence pain frequency and intensity. Clinicians should consider these aspects when developing comprehensive strategies for pain management.

Progress of reprogramming astrocytes into neuron.

As the main players in the central nervous system (CNS), neurons dominate most life activities. However, after accidental trauma or neurodegenerative diseases, neurons are unable to regenerate themselves. The loss of this important role can seriously affect the quality of life of patients, ranging from movement disorders to disability and even death. There is no suitable treatment to prevent or reverse this process. Therefore, the regeneration of neurons after loss has been a major clinical problem and the key to treatment. Replacing the lost neurons by transdifferentiation of other cells is the only viable approach. Although much progress has been made in stem cell therapy, ethical issues, immune rejection, and limited cell sources still hinder its clinical application. In recent years, somatic cell reprogramming technology has brought a new dawn. Among them, astrocytes, as endogenously abundant cells homologous to neurons, have good potential and application value for reprogramming into neurons, having been reprogrammed into neurons in vitro and in vivo in a variety of ways.

Nasal mucosa-derived mesenchymal stem cells prolonged the survival of septic rats by protecting macrophages from pyroptosis.

Sepsis is characterized by an exacerbated inflammatory response, driven by the overproduction of cytokines, a phenomenon known as a cytokine storm. This condition is further compounded by the extensive infiltration of M1 macrophages and the pyroptosis of these cells, leading to immune paralysis. To counteract this, we sought to transition M1 macrophages into the M2 phenotype and safeguard them from pyroptosis. For this purpose, we employed ectodermal mesenchymal stem cells (EMSCs) sourced from the nasal mucosa to examine their impact on both macrophages and septic animal models. The co-culture protocol involving LPS-stimulated rat bone marrow macrophages and EMSCs was employed to examine the paracrine influence of EMSCs on macrophages. The intravenous administration of EMSCs was utilized to observe the enhancement in the survival rate of septic rat models and the protection of associated organs. The findings indicated that EMSCs facilitated M2 polarization of macrophages, which were stimulated by LPS, and significantly diminished levels of pro-inflammatory cytokines and NLRP3. Furthermore, EMSCs notably restored the mitochondrial membrane potential (MMP) of macrophages through paracrine action, eliminated excess reactive oxygen species (ROS), and inhibited macrophage pyroptosis. Additionally, the systemic integration of EMSCs substantially reduced injuries to multiple organs and preserved the fundamental functions of the heart, liver, and kidney in CLP rats, thereby extending their survival.

Platelet Membrane-Coated Curcumin-PLGA Nanoparticles Promote Astrocyte-Neuron Transdifferentiation for Intracerebral Hemorrhage Treatment.

Intracerebral hemorrhage (ICH) is a hemorrhagic disease with high mortality and disability rates. Curcumin is a promising drug for ICH treatment due to its multiple biological activities, but its application is limited by its poor watersolubility and instability. Herein, platelet membrane-coated curcumin polylactic-co-glycolic acid (PLGA) nanoparticles (PCNPs) are prepared to achieve significantly improved solubility, stability, and sustained release of curcumin. Fourier transform infrared spectra and X-ray diffraction assays indicate good encapsulation of curcumin within nanoparticles. Moreover, it is revealed for the first time that curcumin-loaded nanoparticles can not only suppress hemin-induced astrocyte proliferation but also induce astrocytes into neuron-like cells in vitro. PCNPs are used to treat rat ICH by tail vein injection, using in situ administration as control. The results show that PCNPs are more effective than curcumin-PLGA nanoparticles in concentrating on hemorrhagic lesions, inhibiting inflammation, suppressing astrogliosis, promoting neurogenesis, and improving motor functions. The treatment efficacy of intravenously administered PCNPs is comparable to that of in situ administration, indicating a good targeting effect of PCNPs on the hemorrhage site. This study provides a potent treatment for hemorrhagic injuries and a promising solution for efficient delivery of water-insoluble drugs using composite materials of macromolecules and cell membranes.

Targeting senescent HDF with the USP7 inhibitor P5091 to enhance DFU wound healing through the p53 pathway.

OBJECTIVE: The objective of this study was to examine the potential of USP7 as a target for senolytic therapy and to investigate the molecular mechanism by which its inhibitor selectively induced apoptosis in senescent HDF and enhanced DFU wound healing. METHODS: Clinical samples of DFU were collected to detect the expression of USP7 and aging-related proteins using immunohistochemistry and Western blot. In addition, ß-galactosidase staining, qPCR, flow cytometry, ROS and MMP kits, and Western blot were used to analyze the biological functions of P5091 on senescence, cycle, and apoptosis. RNAseq was employed to further analyze the molecular mechanism of P5091. Finally, the DFU rat model was established to evaluate the effect of P5091 on wound healing. RESULTS: The expression of USP7 and p21 were increased in DFU clinical samples. After treatment with d-glucose (30 mM, 7 days), ß-galactosidase staining was deepened, proliferation rate decreased. USP7 inhibitors (P5091) could reduce the release of SASP factors, activate the production of ROS, and reduce MMP. In addition, it induced apoptosis and selectively clears senescent cells through the p53 signaling pathway. Finally, P5091 can improve diabetic wound healing in rats. CONCLUSION: This study clarified the molecular mechanism of USP7 inhibitor (P5091) selectively inducing apoptosis of high glucose senescent HDF cells. This provides a new senolytics target and experimental basis for promoting DFU wound healing.

The CT Classification of Multilevel Cervical Ossification of the Posterior Longitudinal Ligament to Guide Hybrid Anterior Controllable Antedisplacement and Fusion vs. Posterior Laminoplasty.

OBJECTIVE: For precise and minimally invasive treatment of ossification of the posterior longitudinal ligament of the cervical spine, the lifting segment is minimized, anterior controllable antedisplacement and fusion (ACAF) was refined and improved. In addition, the development of appropriate surgical procedures for the ossification of each segment was rarely reported. Therefore, this study aimed to compare the efficacy and safety of hybrid anterior controlled antedisplacement fusion (Hybrid ACAF) with laminoplasty for multilevel ossification of the posterior longitudinal ligament (OPLL). METHODS: Between May 2018 and May 2021, 70 patients with multilevel OPLL were divided into a hybrid ACAF group and a laminoplasty group according to surgical methods. All patients were followed up for at least 1 year. Japanese Orthopaedic Association (JOA) score and recovery rate (JOARR), (VAS, NDI) score and C2-C7 Cobb angle, the sagittal vertical axis of the neck (SVA), and complications (cerebrospinal fluid leakage, C5 paralysis, etc.) were compared between the two groups by t test or non-parametric test. RESULTS: The operation time of hybrid ACAF was longer. C5 paralysis and axial pain were more common in the laminoplasty group, while dysphagia and hoarseness were more common in the hybrid ACAF group. At the last follow-up, the hybrid ACAF group had better recovery and maintenance of cervical lordosis and sagittal plane balance and a higher JOA score and recovery rate than the laminoplasty group. CONCLUSIONS: Hybrid ACAF can reduce the number of vertebral bodies and expand the decompression range, which is safe, effective, and tailored to local conditions. Compared with laminoplasty, hybrid ACAF is a precise alternative for patients with OPLL.

Screening and optimization of shark nanobodies against SARS-CoV-2 spike RBD.

SARS-CoV-2 continues to threaten human health, antibody therapy is one way to control the infection. Because new SARS-CoV-2 mutations are constantly emerging, there is an urgent need to develop broadly neutralizing antibodies to block the viral entry into host cells. VNAR from sharks is the smallest natural antigen binding domain, with the advantages of small size, flexible paratopes, good stability, and low manufacturing cost. Here, we used recombinant SARS-CoV-2 Spike-RBD to immunize sharks and constructed a VNAR phage display library. VNAR R1C2, selected from the library, efficiently binds to the RBD domain and blocks the infection of ACE2-positive cells by pseudovirus. Next, homologous bivalent VNARs were constructed through the tandem fusion of two R1C2 units, which enhanced both the affinity and neutralizing activity of R1C2. R1C2 was predicted to bind to a relatively conserved region within the RBD. By introducing mutations at four key binding sites within the CDR3 and HV2 regions of R1C2, the affinity and neutralizing activity of R1C2 were significantly improved. Furthermore, R1C2 also exhibits an effective capacity of binding to the Omicron variants (BA.2 and XBB.1). Together, these results suggest that R1C2 could serve as a valuable candidate for preventing and treating SARS-CoV-2 infections.

The exploration of surgery and survival prediction in patients with peritoneal metastasis from gastric adenocarcinoma based on the SEER database.

Background: As one of the most common diseases in terms of cancer-related mortality worldwide, gastric adenocarcinoma (GA) frequently develops peritoneal metastases (PMs) in advanced stages. Systemic therapy or optimal supportive care are recommended for advanced GA; however, patients frequently develop drug resistance. Surgical resection is not recommended for stage IV patients, and there have been some controversies regarding the role of it in GA patients with PMs. The aim of the study was to preliminarily evaluate the possible effect of surgical treatments on patients with only PMs from GA. Methods: Data were collected from the Surveillance, Epidemiology and End Results (SEER) database (year 2000-2022). A propensity score matching (PSM) was performed to reduce the influence of selection bias and confounding variables on comparisons. Then Cox proportional hazard regression, Kaplan-Meier analysis, and log-rank test were performed to assess the efficacy of surgical treatment in patients with PMs from GA. Results: A total of 399 patients diagnosed with PMs from GA were enrolled for our analysis, of which, 180 (45.1%) patients did not receive surgery and 219 (54.9%) patients received surgery. Multivariate Cox regression analysis before PSM indicated higher rates of overall survival (OS) outcome for patients who had received surgery [hazard ratio (HR) =0.4342, 95% confidence interval (CI): 0.3283-0.5742, P<0.001]. After PSM, a total of 172 patients were enrolled, with 86 in each group. Multivariate Cox analysis showed that surgery was the independent factor reflecting patients' survival (HR =0.4382, 95% CI: 0.3037-0.6324, P<0.001). Subgroup survival analysis revealed that surgery may bring advantages to patients with grades I-IV, stages T1-T4, stage N0, and tumor size less than 71 mm (P<0.05). We also found that the OS of chemotherapy patients who had undergone surgery was better than that of chemotherapy patients who had not undergone surgery (P<0.01). Conclusions: Based on the SEER database, surgery has better OS for patients only with PMs from GA. Patients without lymph node metastasis and those who received chemotherapy before may benefit from surgery. These specific groups of patients may have surgery as an option to improve the prognosis.

A Novel "De-tension"-guided Anterior Decompression Strategy-Thoracic Anterior Controllable Antedisplacement Fusion (TACAF) for Multilevel Ossification of Posterior Longitudinal Ligament in Thoracic Spine: A Retrospective Study with at Least 2-Year Follow-Up.

OBJECTIVE: To propose a novel surgical strategy-thoracic anterior controllable antedisplacement fusion (TACAF) to treat multilevel thoracic ossification of the posterior longitudinal ligament (mT-OPLL), and investigate its safety and efficacy. METHODS: Between January 2019 and December 2021, a total of 49 patients with thoracic myelopathy due to mT-OPLL surgically treated with TACAF were retrospectively reviewed. Patients' demographic data, radiologic parameters, and surgery-related complications, modified Japanese Orthopedic Association (mJOA) and visual analog scale (VAS) scores, thoracic kyphosis (TK), kyphosis angle in fusion area (FSK), thoracic curvature, spinal cord curvature, and curvature of curved rod in surgical region, diameter, and area of the spinal cord at the most compressed level were included. RESULTS: All patients acquired satisfactory recovery of neurologic function and overall complication rate was low at the final follow up. The mean mJOA of the laminectomy+TACAF and Full Lamina Preservation +TACAF groups, respectively, was 3.74 ± 2.05, 3.67 ± 1.95 before surgery, and 9.97 ± 0.83, 9.80 ± 0.68 at the final followed up, with the recovery rate of 84.26% ± 14.20%, 82.79% ± 10.35%, as to VAS Scores. The mean FSK was 34.50 ± 4.46,35.33 ± 3.44 before surgery, and was restored to 20.97 ± 5.70, 22.93 ± 6.34 at the final followed up respectively, as to mean TK (P < 0.05). Spinal cord curvature was improved from 34.12 ± 3.59, 33.93 ± 3.45 before surgery to 19.47 ± 3.53, 18.80 ± 3.17 at the final follow-up respectively, as to thoracic curvature (P < 0.05). In addition, the area and diameter of the spinal cord was also significantly improved at the final follow up (all P < 0.05). The curvature of the thoracic pulp and thoracic vertebra is closely related to the curvature of the rod. There was no statistically significant difference in the incidence of the pelvis and the slope value of the sacrum. CONCLUSIONS: This strategy provides a novel solution for the treatment of mT-OPLL with favorable recovery of neurological function, the tension of spinal cord, and fewer complications.

FraHMT: A Fragment-Oriented Heterogeneous Graph Molecular Generation Model for Target Proteins.

The molecular generation task stands as a pivotal step in the domains of computational chemistry and drug discovery, aiming to computationally generate molecular structures for specific properties. In contrast to previous models that focused primarily on SMILES strings or molecular graphs, our model placed a special emphasis on the substructure information on molecules, enabling the model to learn richer chemical rules and structure features from fragments and chemical reaction information on molecules. To accomplish this, we fragmented the molecules to construct heterogeneous graph representations based on atom and fragment information. Then our model mapped the heterogeneous graph data into a latent vector space by using an encoder and employed a self-regressive generative model as a decoder for molecular generation. Additionally, we performed transfer learning on the model using a small set of ligand molecules known to be active against the target protein to generate molecules that bind better to the target protein. Experimental results demonstrate that our model is highly competitive with state-of-the-art models. It can generate valid and diverse molecules with favorable physicochemical properties and drug-likeness. Importantly, they produce novel molecules with high docking scores against the target proteins.