A new genetic diagnosis strategy for paroxysmal kinesigenic dyskinesia: Targeted high-throughput detection of PRRT2 gene c.649 locus.

BACKGROUND: Paroxysmal kinesigenic dyskinesia (PKD) is the most prevalent kind type of paroxysmal Dyskinesia, characterized by recurrent and transient episodes of involuntary movements. Most PKD cases were attributed to the proline-rich transmembrane protein 2 (PRRT2) gene, in which the c.649 region is a hotspot for known mutations. Even though some patients with PKD have been genetically diagnosed using whole-exome sequencing (WES) and Sanger sequencing, there are still cases of missed diagnoses due to the limitations of sequencing technology and analytic methods on throughput. METHODS: Patients meeting the diagnosis criteria of PKD with negative results of PRRT2-Sanger sequencing and WES were included in this study. Mutation screening and targeted high-throughput sequencing were performed to analyze and verify the sequencing results of the potential mutations. RESULTS: Six patients with PKD with high mutation ratios of c.649dupC were screened using our targeted high-throughput sequencing from 26 PKD patients with negative results of PRRT2-Sanger sequencing and WES (frequency = 23.1%), which compensated for the comparatively shallow sequencing depth and statistical flaws in this region. Compared with the local normal population and other patients with PKD, the mutation ratios of c.649dupC of these six patients with PKD were much higher and also had truncated protein structures and differentially altered mRNA expression. CONCLUSION: Based on the above studies, we emphasize the routine targeted high-throughput sequencing of the c.649 site in the PRRT2 gene in so-called genetic-testing-negative patients with PKD, and manually calculate the deletion and duplication mutations depth and ratios to lower the rate of clinical misdiagnosis.

The Causal Effect of Gut Microbiota and Plasma Metabolome on Lung Cancer and the Heterogeneity across Subtypes: A Mendelian Randomization Study.

The causal effect and pathways of gut microbiota and plasma metabolome on lung cancer have been important topics for personalized medicine; however, the heterogeneity of lung cancer subtypes has not gained enough attention in previous studies. This study sought to employ a Mendelian randomization analysis to screen the specific gut microbiota and plasma metabolome, which may have a causal effect on lung cancer. We further extended our analysis to estimate the effects of these exposures on various pathological subtypes of lung cancer. Furthermore, a mediation analysis was performed to identify the potential pathway underlying the influence of microbiota and metabolites. Our study identified 13 taxa and 15 metabolites with a causal association with the overall risk of lung cancer. Furthermore, we found 8 taxa and 14 plasma metabolites with a causal effect on lung adenocarcinoma, 4 taxa and 10 metabolites with a causal effect on squamous cell lung carcinoma, and 7 taxa and 16 metabolites with a causal effect on SCLC. We also identified seven mediation pathways that could potentially elucidate the influence of these microbiota and metabolites on overall lung cancer or special subtypes. Our study highlighted the heterogeneity of the gut microbiome and plasma metabolome in a lung cancer subtype and elucidated the potential underlying mechanisms. This could pave the way for more personalized lung cancer prevention and treatment.

Efficacy of chidamide maintenance therapy versus autologous stem cell transplantation versus observation as a post-remission choice in the survival of adult patients with peripheral T-cell lymphoma: Post hoc analysis of a prospective, multicenter, phase 2 study in China.

In this prospective, multicenter, Phase 2 clinical trial (NCT02987244), patients with peripheral T-cell lymphomas (PTCLs) who had responded to first-line chemotherapy with cyclophosphamide, doxorubicin or epirubicin, vincristine or vindesine, etoposide, and prednisone (Chi-CHOEP) were treated by autologous stem cell transplantation (ASCT) or with chidamide maintenance or observation. A total of 85 patients received one of the following interventions: ASCT (n = 15), chidamide maintenance (n = 44), and observation (n = 26). estimated 3 PFS and OS rates were 85.6%, 80.8%, and 49.4% (P = 0.001). The two-year OS rates were 85.6%, 80.8%, and 69.0% (P = 0.075).The ASCT and chidamide maintenance groups had significantly better progression-free survival (PFS) than the observation group (P = 0.001, and P = 0.01, respectively). The overall survival (OS) differed significantly between the chidamide maintenance group and the observation group ( P = 0.041). The multivariate and propensity score matching analyses for PFS revealed better outcomes in the subjects in the chidamide maintenance than observation groups (P = 0.02). The ASCT and chidamide maintenance groups had significant survival advantages over the observation group. In the post-remission stage of the untreated PTCL patients, single-agent chidamide maintenance demonstrated superior PFS and better OS than observation. Our findings highlight the potential benefit of chidamide in this patient subset, warranting further investigation through larger prospective trials. Clinical trial registration: clinicaltrial.gov, NCT02987244. Registered 8 December 2016, http://www.clinicaltrials.gov/ct2/show/NCT02987244 .

Efficacy and safety of video double-lumen tube intubation in lateral position in patients undergoing thoracic surgery: a randomized controlled trial.

BACKGROUND: Video double-lumen tube (VDLT) intubation in lateral position is a potential alternative to intubation in supine position in patients undergoing thoracic surgery. This non-inferiority trial assessed the efficacy and safety of VDLT intubation in lateral position. METHODS: Patients (18-70 yr) undergoing right thoracoscopic lung surgery were randomized to either the left lateral position group (group L) or the supine position group (group S). The VDLT was placed under video larygoscopy. The primary endpoint was the intubation time. Secondary endpoints included VDLT displacement rate, intubation failure rate, the satisfaction of surgeon and nurse, and intubation-related adverse events. RESULTS: The analysis covered 80 patients. The total intubation time was 52.0 [20.4]s in group L and 34.3 [13.2]s in group S, with a mean difference of 17.6 s [95% confidence interval (CI): 9.9 s to 25.3 s; P = 0.050], failing to demonstrate non-inferiority with a non-inferiority margin of 10 s. Group L, compared with group S, had significantly lower VDLT displacement rate (P = 0.017) and higher nurse satisfaction (P = 0.026). No intubation failure occurred in any group. Intubation complications (P = 0.802) and surgeon satisfaction (P = 0.415) were comparable between two groups. CONCLUSIONS: The lateral VDLT intubation took longer time than in the supine position, and non-inferiority was not achieved. The incidence of displacement as the secondary endpoint was lower in the L group, possibly due to changing body positions beforehand. The indication of lateral VDLT intubation should be based on a balance between the safety of airway management and the lower incidence of displacement. TRIAL REGISTRATION: The study was registered at Chictr.org.cn with the number ChiCTR2200064831 on 19/10/2022.

Continuous renal Surface Cooling Technique (CSCT) in robotic assisted kidney transplantation: technique and outcomes from a high-volume center, a prospective cohort study.

BACKGROUND: Robot-assisted kidney transplantation (RAKT) surgery is an advanced minimally invasive technique, albeit with extended surgical and kidney ischemia time. To safeguard kidney function, we have devised a continuous surface cooling method (CSCT) for intraoperative kidney cooling. MATERIALS AND METHODS: Patients receiving RAKT were divided into CSCT group and conventional group. The CSCT is a custom-designed apparatus composed of a single-layer plastic bag, featuring an inflow and an outflow that create a closed circuit for the continuous flow of cooling saline. The conventional group utilized ice slush for kidney graft cooling (Vattikuti Urology Institute-Medanta Technique, VUIMT). Patients who underwent open renal transplantation during the same period were also included in the study. All patients were subject to a minimum 2-month follow-up. And 1:3 propensity score matching was used to minimize selection bias. RESULTS: A total of 144 patients underwent CSCT, 47 underwent VUIMT, and 196 underwent open surgery were included in the study, while after matching, 129, 43, 129 patients were included in the three groups, respectively. The median follow-up time was 19 months. None of the patients experienced delayed graft function, patient mortality, or graft loss. After introducing the kidney into the abdominal cavity for 20 minutes, the surface temperature of the kidney in the CSCT group was notably lower compared to the VUIMT group (15.42±0.88 vs. 21.74±2.53°C, P=0.001). This temperature disparity became more pronounced at 65 minutes (19.74±1.61 vs. 29.82±1.63°C, P<0.001). At both 3 and 7 days post-transplantation, creatinine levels in the VUIMT group were significantly higher than those in the CSCT and open surgery groups (at 3 d, 244.13±45.61 vs. 182.51±55.47 in CSCT group, P<0.001, or vs. 182.77±61.32 in the open surgery group, P<0.001; at 7 d, 162.42±54.86 vs. 143.11±44.32 in the CSCT group, P<0.001, or vs. 135.23±45.27 in the open surgery group, P<0.001). No differences were observed in blood creatinine, estimated glomerular filtration rate, and perioperative complications between the CSCT and open surgery groups. CONCLUSION: The CSCT presents a significant advantage over the traditional VUIMT method in terms of kidney cooling and early postoperative kidney function preservation. Additional research is required to ascertain whether the CSCT can enhance the long-term prognosis of kidney transplant recipients.

Genomic characterization and related functional genes of γ- poly glutamic acid producing Bacillus subtilis.

γ- poly glutamic acid (γ-PGA), a high molecular weight polymer, is synthesized by microorganisms and secreted into the extracellular space. Due to its excellent performance, γ-PGA has been widely used in various fields, including food, biomedical and environmental fields. In this study, we screened natto samples for two strains of Bacillus subtilis N3378-2at and N3378-3At that produce γ-PGA. We then identified the γ-PGA synthetase gene cluster (PgsB, PgsC, PgsA, YwtC and PgdS), glutamate racemase RacE, phage-derived γ-PGA hydrolase (PghB and PghC) and exo-γ-glutamyl peptidase (GGT) from the genome of these strains. Based on these γ-PGA-related protein sequences from isolated Bacillus subtilis and 181 B. subtilis obtained from GenBank, we carried out genotyping analysis and classified them into types 1-5. Since we found B. amyloliquefaciens LL3 can produce γ-PGA, we obtained the B. velezensis and B. amyloliquefaciens strains from GenBank and classified them into types 6 and 7 based on LL3. Finally, we constructed evolutionary trees for these protein sequences. This study analyzed the distribution of γ-PGA-related protein sequences in the genomes of B. subtilis, B. velezensis and B. amyloliquefaciens strains, then the evolutionary diversity of these protein sequences was analyzed, which provided novel information for the development and utilization of γ-PGA-producing strains.

Transcriptomic analysis of differentially alternative splicing patterns in mice with inflammatory and neuropathic pain.

Although the molecular mechanisms of chronic pain have been extensively studied, a global picture of alternatively spliced genes and events in the peripheral and central nervous systems of chronic pain is poorly understood. The current study analyzed the changing pattern of alternative splicing (AS) in mouse brain, dorsal root ganglion, and spinal cord tissue under inflammatory and neuropathic pain. In total, we identified 6495 differentially alternatively spliced (DAS) genes. The molecular functions of shared DAS genes between these two models are mainly enriched in calcium signaling pathways, synapse organization, axon regeneration, and neurodegeneration disease. Additionally, we identified 509 DAS in differentially expressed genes (DEGs) shared by these two models, accounting for a small proportion of total DEGs. Our findings supported the hypothesis that the AS has an independent regulation pattern different from transcriptional regulation. Taken together, these findings indicate that AS is one of the important molecular mechanisms of chronic pain in mammals. This study presents a global description of AS profile changes in the full path of neuropathic and inflammatory pain models, providing new insights into the underlying mechanisms of chronic pain and guiding genomic clinical diagnosis methods and rational medication.

Spatiotemporal characteristics of tissue derived small extracellular vesicles is associated with tumor relapse and anti-PD-1 response.

Small extracellular vesicles (sEVs) residing at tumor tissues are valuable specimens for biopsy. Tumor heterogeneity is common across all cancer types, but the heterogeneity of tumor tissue-derived sEVs (Ti-sEVs) is undefined. This study aims to discover the spatial distributions of Ti-sEVs in oral squamous cell carcinoma (OSCC) tissues and explore how these vesicle distributions affect the patients' prognosis. Multi-regional sampling enabled us to uncover that Ti-sEVs' accumulation at peritumoral sites correlates with a higher disease-free survival rate, and conversely, sparse peritumoral Ti-sEVs tend to forecast a higher risk of relapse. Of those relapsed patients, Ti-sEVs strongly bind to extracellular matrix and subsequently degrade it for allowing themselves enter the bloodstream rather than staying in situ. In advanced OSCC patients, the quantity and spatial distribution of Ti-sEVs prior to anti-PD-1 treatment, as well as the temporal variance of Ti-sEVs before and after immunotherapy, strongly map the clinical response and can help to distinguish the patients with shrinking tumors from those with growing tumors. Our work elucidates the correlation of spatiotemporal features of Ti-sEVs with patients' therapeutic outcomes and exhibit the potential for using Ti-sEVs as a predictor to forecast prognosis and screen the responders to anti-PD-1 therapy.

Mas receptor activation facilitates innate hematoma resolution and neurological recovery after hemorrhagic stroke in mice.

BACKGROUND: Intracerebral hemorrhage (ICH) is a devastating neurological disease causing severe sensorimotor dysfunction and cognitive decline, yet there is no effective treatment strategy to alleviate outcomes of these patients. The Mas axis-mediated neuroprotection is involved in the pathology of various neurological diseases, however, the role of the Mas receptor in the setting of ICH remains to be elucidated. METHODS: C57BL/6 mice were used to establish the ICH model by injection of collagenase into mice striatum. The Mas receptor agonist AVE0991 was administered intranasally (0.9 mg/kg) after ICH. Using a combination of behavioral tests, Western blots, immunofluorescence staining, hematoma volume, brain edema, quantitative-PCR, TUNEL staining, Fluoro-Jade C staining, Nissl staining, and pharmacological methods, we examined the impact of intranasal application of AVE0991 on hematoma absorption and neurological outcomes following ICH and investigated the underlying mechanism. RESULTS: Mas receptor was found to be significantly expressed in activated microglia/macrophages, and the peak expression of Mas receptor in microglia/macrophages was observed at approximately 3-5 days, followed by a subsequent decline. Activation of Mas by AVE0991 post-treatment promoted hematoma absorption, reduced brain edema, and improved both short- and long-term neurological functions in ICH mice. Moreover, AVE0991 treatment effectively attenuated neuronal apoptosis, inhibited neutrophil infiltration, and reduced the release of inflammatory cytokines in perihematomal areas after ICH. Mechanistically, AVE0991 post-treatment significantly promoted the transformation of microglia/macrophages towards an anti-inflammatory, phagocytic, and reparative phenotype, and this functional phenotypic transition of microglia/macrophages by Mas activation was abolished by both Mas inhibitor A779 and Nrf2 inhibitor ML385. Furthermore, hematoma clearance and neuroprotective effects of AVE0991 treatment were reversed after microglia depletion in ICH. CONCLUSIONS: Mas activation can promote hematoma absorption, ameliorate neurological deficits, alleviate neuron apoptosis, reduced neuroinflammation, and regulate the function and phenotype of microglia/macrophages via Akt/Nrf2 signaling pathway after ICH. Thus, intranasal application of Mas agonist ACE0991 may provide promising strategy for clinical treatment of ICH patients.

Tumour organoids and assembloids: Patient-derived cancer avatars for immunotherapy.

BACKGROUND: Organoid technology is an emerging and rapidly growing field that shows promise in studying organ development and screening therapeutic regimens. Although organoids have been proposed for a decade, concerns exist, including batch-to-batch variations, lack of the native microenvironment and clinical applicability. MAIN BODY: The concept of organoids has derived patient-derived tumour organoids (PDTOs) for personalized drug screening and new drug discovery, mitigating the risks of medication misuse. The greater the similarity between the PDTOs and the primary tumours, the more influential the model will be. Recently, 'tumour assembloids' inspired by cell-coculture technology have attracted attention to complement the current PDTO technology. High-quality PDTOs must reassemble critical components, including multiple cell types, tumour matrix, paracrine factors, angiogenesis and microorganisms. This review begins with a brief overview of the history of organoids and PDTOs, followed by the current approaches for generating PDTOs and tumour assembloids. Personalized drug screening has been practised; however, it remains unclear whether PDTOs can predict immunotherapies, including immune drugs (e.g. immune checkpoint inhibitors) and immune cells (e.g. tumour-infiltrating lymphocyte, T cell receptor-engineered T cell and chimeric antigen receptor-T cell). PDTOs, as cancer avatars of the patients, can be expanded and stored to form a biobank. CONCLUSION: Fundamental research and clinical trials are ongoing, and the intention is to use these models to replace animals. Pre-clinical immunotherapy screening using PDTOs will be beneficial to cancer patients. KEY POINTS: The current PDTO models have not yet constructed key cellular and non-cellular components. PDTOs should be expandable and editable. PDTOs are promising preclinical models for immunotherapy unless mature PDTOs can be established. PDTO biobanks with consensual standards are urgently needed.

Asymmetric XMoGeY2 (X = S, Se, Te; Y = N, P, As) monolayers as potential flexible materials for nano piezoelectric devices and nanomedical sensors.

Highly efficient nano piezoelectric devices and nanomedical sensors are in great demand for high-performance piezoelectric materials. In this work, we propose new asymmetric XMoGeY2 (X = S, Se, Te; Y = N, P, As) monolayers with excellent piezoelectric properties, dynamic stability and flexible elastic properties. The piezoelectric coefficients (d11) of XMoGeY2 monolayers range from 2.92 to 8.19 pm V-1. Among them, TeMoGeAs2 exhibits the highest piezoelectric coefficient (d11 = 8.19 pm V-1), which is 2.2 times higher than that of common 2D piezoelectric materials such as 2H-MoS2 (d11 = 3.73 pm V-1). Furthermore, all XMoGeY2 monolayers demonstrate flexible elastic properties ranging from 96.23 to 253.70 N m-1. Notably, TeMoGeAs2 has a Young's modulus of 96.23 N m-1, which is only one-third of that of graphene (336 N m-1). The significant piezoelectric coefficients of XMoGeY2 monolayers can be attributed to their asymmetric structures and flexible elastic properties. This study provides valuable insights into the potential applications of XMoGeY2 monolayers in nano piezoelectric devices and nanomedical sensors.

The regulatory role of autophagy between TAMs and tumor cells.

Cancer has become a global public health problem and its harmful effects have received widespread attention. Conventional treatments such as surgical resection, radiotherapy and other techniques are applicable to clinical practice, but new drugs are constantly being developed and other therapeutic approaches, such as immunotherapy are being applied. In addition to studying the effects on individual tumor cells, it is important to explore the role of tumor microenvironment on tumor cell development since tumor cells do not exist alone but in the tumor microenvironment. In the tumor microenvironment, tumor cells are interconnected with other stromal cells and influence each other, among which tumor-associated macrophages (TAMs) are the most numerous immune cells. At the same time, it was found that cancer cells have different levels of autophagy from normal cells. In cancer therapy, the occurrence of autophagy plays an important role in promoting tumor cell death or inhibiting tumor cell death, and is closely related to the environment. Therefore, elucidating the regulatory role of autophagy between TAMs and tumor cells may be an important breakthrough, providing new perspectives for further research on antitumor immune mechanisms and improving the efficacy of cancer immunotherapy.

Quercetin Enhances 5-fluorouracil Sensitivity by Regulating the Autophagic Flux and Inducing Drp-1 Mediated Mitochondrial Fragmentation in Colorectal Cancer Cells.

BACKGROUND: While chemotherapy treatment demonstrates its initial effectiveness in eliminating the majority of the tumor cell population, nevertheless, most patients relapse and eventually succumb to the disease upon its recurrence. One promising approach is to explore novel, effective chemotherapeutic adjuvants to enhance the sensitivity of cancer cells to conventional chemotherapeutic agents. In the present study, we explored the effect of quercetin on the sensitivity of colorectal cancer (CRC) cells to conventional chemotherapeutic agent 5-fluorouracil (5-FU) and the molecular mechanisms. METHODS: MTT assay, colony formation assay and Hoechst staining were performed to investigate the growth inhibition effect of quercetin alone or combined with 5-FU. The expression levels of apoptosis- and autophagy-related proteins were assessed by western blotting. Intracellular ROS was detected using DCFH-DA. The change in the mitochondrial membrane potential was measured by a JC-1 probe. The effect of quercetin on mitochondrial morphology was examined using a mitochondrial-specific fluorescence probe, Mito-Tracker red. RESULTS: The results demonstrated quercetin-induced apoptosis and autophagy, as well as imbalanced ROS, decreased mitochondrial membrane potential, and Drp-1-mediated mitochondrial fission in CRC cells. Autophagy blockage with autophagy inhibitor chloroquine (CQ) enhanced quercetininduced cytotoxicity, indicating that quercetin-induced cytoprotective autophagy. Meanwhile, quercetin enhanced the sensitivity of CRC cells to 5- FU via the induction of mitochondrial fragmentation, which could be further enhanced when the quercetin-induced protective autophagy was blocked by CQ. CONCLUSION: Our findings suggested that quercetin could induce protective autophagy and Drp-1-mediated mitochondrial fragmentation and enhance the sensitivity of CRC cells to conventional agent 5-FU, which not only suggests that quercetin may act as a chemotherapeutic adjuvant but also implies that the regulation of autophagic flux may be a potential therapeutic strategy for colorectal cancer.

Early ontogenesis from embryo to juvenile in Senegalese sole Solea senegalensis under laboratory conditions.

Senegalese sole, Solea senegalensis, is a flatfish of high commercial value in the world. It has been identified as an interesting and promising species for marine commercial aquaculture diversification in Europe for at least four decades and was introduced to China in 2003. Early ontogenesis from embryo to juvenile stages in S. senegalensis was analysed under controlled laboratory conditions to provide morphological information for aquaculture. From 0 to 59 days post hatching (dph), 10-20 larvae were sampled and measured each day (0-17 dph) or every 2-6 days (17-59 dph). Morphological characteristics from the egg to the juvenile stage were described. The eggs were separate and spherical with multiple oil globules. After 3 dph, the yolk sac was completely absorbed, mouth and anus were open, a swim bladder appeared, and larvae began feeding on rotifers (Brachionus plicatilis). The larvae began metamorphosis as the notochord flexed upward and the left eye migrated upward after 10 dph. The left eye migrated to the dorsal midline at 15 dph. At 19 dph, the left eye was translocated to the right-ocular side, and the juveniles adopted a benthic lifestyle. The swim bladder degenerated, and the juveniles completed metamorphosis at 23 dph. The growth patterns of some parameters (TL, SL, BH, BW) during larval and juvenile development stages were identified. The inflection points, which are slopes of growth changes, were calculated in growth curves. Three inflection points occurring in the growth curves of larvae and juveniles were found to be associated with metamorphosis, weaning, and transitions in feeding habits. The basic information of embryo development and ontogenesis in this study represents a valuable contribution to the S. senegalensis industry, especially in artificial breeding and rearing techniques.

[Effectiveness of unilateral biportal endoscopy combined with percutaneous pedicle screw fixation in treatment of lumbar burst fractures with neurological symptoms].

Objective: To evaluate the effectiveness of spinal canal decompression assisted by unilateral biportal endoscopy (UBE) and percutaneous uniplanar pedicle screw internal fixation in the treatment of lumbar burst fractures with neurological symptoms. Methods: Between June 2021 and December 2022, 10 patients with single level lumbar burst fracture with neurological symptoms were treated with spinal canal decompression assisted by UBE and percutaneous uniplanar pedicle screw internal fixation. There were 7 males and 3 females with an average age of 43.1 years (range, 21-57 years). The injured vertebrae located at L 1 in 2 cases, L 2 in 4 cases, L 3 in 3 cases, and L 4 in 1 case. There were 7 cases of AO type A3 fractures and 3 cases of AO type A4 fractures. The total operation time, the time of operation under endoscopy, and complications were recorded. Pre- and post-operative visual analogue scale (VAS) score and American Spinal Injury Association (ASIA) scale (grading A-E corresponding to assigning 1-5 points for statistical analysis) were used to evaluate effectiveness. X-ray film and CT were performed to observe the fracture healing, and the ratio of anterior vertebral body height, Cobb angle, and rate of spinal canal invasion were measured to evaluate the reduction of fracture. Results: All operations was successfully completed, and the spinal canal decompression and the bone fragment in spinal canal reduction completed under the endoscopy. Total operation time was 119 minutes on average (range, 95-150 minutes), and the time of operation under endoscopy was 46 minutes on average (range, 35-55 minutes). There was no complication such as dural sac, nerve root, or blood vessel injury during operation. All incisions healed by first intention. All patients were followed up 18.7 months on average (range, 10-28 months). The VAS score after operation significantly decreased when compared with that before operation ( P<0.05), and further improved at last follow-up ( P<0.05). The ASIA scale after operation significantly improved when compared with that before operation ( P<0.05), and there was no significant difference ( P>0.05) in the ASIA scale between at 1 week after operation and at last follow-up. The imaging examination showed that the screw position was good and the articular process joint was preserved. During follow-up, there was no loosening, fracture, or fixation failure of the internal fixation. The ratio of anterior vertebral body height and Cobb angle significantly improved, the rate of spinal canal invasion significantly decreased after operation ( P<0.05), and without significant loss of correction during the follow-up ( P>0.05). Conclusion: Spinal canal decompression assisted by UBE and percutaneous uniplanar pedicle screw fixation is a feasible minimally invasive treatment for lumbar burst fractures with neurological symptoms, which can effectively restore the vertebral body sequence, as well as relieve the compression of spinal canal, and improve the neurological function.

Six unprecedented 2-(2-phenethyl)chromone dimers from agarwood of Aquilaria filaria.

Six new dimeric 2-(2-phenylethyl)chromones (1-6) were successfully isolated from the ethanol extract of agarwood of Aquilaria filaria from Philippines under HPLC-MS guidance. Compounds 1-6 are all dimers formed by linking 5,6,7,8-tetrahydro-2-(2-phenylethyl)chromone and flindersia 2-(2-phenylethyl)chromone via a single ether bond, and the linkage site (C5-O-C8'') of compound 2 is extremely rare. A variety of spectroscopic methods were used to ascertain their structures, including extensive 1D and 2D NMR spectroscopic analysis, HRESIMS, and comparison with literature. The in vitro tyrosinase inhibitory and anti-inflammatory activities of each isolate were assessed. Among these compounds, compound 2 had a tyrosinase inhibition effect with an IC50 value of 27.71 ± 2.60 µM, and compound 4 exhibited moderate inhibition of nitric oxide production in lipopolysaccharide-stimulated RAW264.7 cells with an IC50 value of 35.40 ± 1.04 µM.

Layered assembly of PEGylated graphene oxide and Mg-Al layered double hydroxide nanosheets with superior adsorption capacity and selective isolation of hemoglobin.

This study developed a novel organic-inorganic hybrid composite, shortly as GO-PEG-LDHs, by self-assembly of exfoliated Mg-Al layer double hydroxide (LDHs) on the polyethylene glycol (PEG) grafted graphene oxide (GO) to achieve the selective adsorption of hemoglobin (Hb). The prepared GO-PEG-LDHs has a hierarchical structure with a homogeneous loading of exfoliated LDHs nano-sheets on its surface. The adsorption test reveals that GO-PEG-LDHs exhibits an adsorption efficiency of 95.03% for Hb and 3.45% for bovine serum albumin (BSA). The adsorption of Hb follows the Langmuir model, with an ultrahigh adsorption capacity of 55248.6 mg/g, which is higher than any previously reported materials. Meanwhile, the adsorbed Hb can be efficiently recovered through elution with a 50 mM Tris-HCl buffer, with an elution efficiency of 80.77%. Circular dichroism (CD) spectra indicate no conformational change for Hb during the process of adsorption/desorption. Furthermore, the composite demonstrates the ability to selectively isolate Hb in the presence of interfering protein BSA, indicating its potential for practical applications.

3-methyl-1H-indol-1-yl dimethylcarbamodithioate attenuates periodontitis through targeting MAPK signaling pathway-regulated mitochondrial function.

Periodontitis, the second most common oral disease, is primarily initiated by inflammatory responses and osteoclast differentiation, in which the MAPK signaling pathway and mitochondrial function play important roles. 3-methyl-1H-indol-1-yl dimethylcarbamodithioate (3o), a hybrid of indole and dithiocarbamate, was first synthesized by our group. It has shown anti-inflammatory activity against lipopolysaccharide-induced acute lung injury. However, it is not known if 3o can exert effects in periodontitis. In vitro study: LPS-induced macrophage inflammation initiation and a receptor activator of nuclear factor κB ligand-stimulated osteoclast differentiation model were established. Cell viability, inflammatory cytokines, osteoclast differentiation, the MAPK signaling pathway, and mitochondrial function before and after treatment with 3o were investigated. In vivo study: Alveolar bone resorption, inflammatory cytokine expression, osteoclast differentiation, and the underlying mechanisms were assessed in mice with periodontitis. Inflammatory cytokine expression and osteoclast differentiation appeared downregulated after 3o treatment. 3o inhibited the MAPK signaling pathway and restored mitochondrial function, including mitochondrial reactive oxygen species, mitochondrial membrane potential, and ATP production. Meanwhile, 3o reduced inflammation activation and bone resorption in mice with periodontitis, reflected by the decreased expression of inflammatory cytokines and osteoclasts, implying that 3o inhibited the MAPK signaling pathway and the mitochondrial oxidative DNA damage marker 8-OHdG. These results highlight the protective role of 3o in periodontitis in mice and reveal an important strategy for preventing periodontitis.

The Impact of Ultrasound-Guided Combined with Water and Air Mixed Injection Method for Nasal Intestinal Tube Placement on Gastrointestinal Burden in Patients with Severe Acute Pancreatitis.

Objective: This study aims to investigate the impact of ultrasound-guided combined with water and air mixed injection method for nasal intestinal tube placement on gastrointestinal burden in patients with severe acute pancreatitis. Methods: A cohort of 116 patients with severe acute pancreatitis admitted to the hospital from August 2021 to July 2023 were included. They were randomly divided into the control group (58 cases, nasal intestinal tube placement using ultrasound-guided combined water injection) and the observation group (58 cases, nasal intestinal tube placement using ultrasound-guided combined with water and air mixed injection). The incubation time, volume of water injected during the incubation, nasal intestinal tube visualization rate, and success rate of one-time incubation were recorded for both groups. Gastrointestinal mucosal barrier function, Nutritional index level including intestinal fatty acid-binding protein (I-FABP), D-lactate and nutritional index levels including hemoglobin (Hb), serum albumin (ALB), retinol-binding protein (RBP) were compared between the two groups before tube placement and at 7 days after incubation. Complications in both groups were also recorded. Results: The incubation time in the observation group was shorter, and the volume of water injected during the incubation was lower than in the control group. The nasal intestinal tube visualization rate and success rate of one-time incubation were higher in the observation group (P < .05). At 7 days after incubation, the levels of I-FABP and D-lactate were lower in the observation group than in the control group (P < .05). At 7 days after incubation, The levels of I-FABP and D-lactate in the observation group were lower than those in the control group, Hb and RBP levels were higher in the observation group than in the control group (P < .05), while there was no significant difference in ALB levels between the two groups (P > .05). The incidence of complications was lower in the observation group than in the control group (P < .05). Conclusion: Ultrasound-guided combined with water and air mixed injection method for nasal intestinal tube placement in patients with severe acute pancreatitis can shorten the incubation time, reduce the volume of water injected during the incubation, improve the nasal intestinal tube visualization rate and success rate of one-time incubation, enhance gastrointestinal mucosal barrier function and nutritional index in patients, and reduce the incidence of complications.