Bioscience trends最新文献

This study aimed to investigate the causal role of diabetes mellitus (DM), glycemic traits, and sodium-glucose cotransporter 2 (SGLT2) inhibition in pulmonary arterial hypertension (PAH). Utilizing a two-sample two-step Mendelian randomization (MR) approach, we determined the causal influence of DM and glycemic traits (including insulin resistance, glycated hemoglobin, and fasting insulin and glucose) on the risk of PAH. Moreover, we examined the causal effects of SGLT2 inhibition on the risk of PAH. Genetic proxies for SGLT2 inhibition were identified as variants in the SLC5A2 gene that were associated with both levels of gene expression and hemoglobin A1c. Results showed that genetically inferred DM demonstrated a causal correlation with an increased risk of PAH, exhibiting an odds ratio (OR) of 1.432, with a 95% confidence interval (CI) of 1.040-1.973, and a p-value of 0.028. The multivariate MR analysis revealed comparable outcomes after potential confounders (OR = 1.469, 95%CI = 1.021-2.115, p = 0.038). Moreover, genetically predicted SGLT2 inhibition was causally linked to a reduced risk of PAH (OR = 1.681*10^-7, 95%CI = 7.059*10^-12-0.004, p = 0.002). Therefore, our study identified the suggestively causal effect of DM on the risk of PAH, and SGLT2 inhibition may be a potential therapeutic target in patients with PAH.

Relatively little is known about education placements for children with autism spectrum disorder (ASD) in China. While disparities in ASD diagnoses and services for the population broadly are often documented, the presence and determinants of differences in the educational placement of ASD children are less studied and understood. By identifying who is likely to be in segregated settings, we can discern how to best support them and facilitate a possible transition to a less restrictive setting. This study describes four placements (regular schools, special schools, institutions, homes) and their influencing factors retrospectively in a large sample (n = 2,190) of Chinese primary school-aged children (6-12 years old). We divided ASD into severe and mild to moderate categories for analysis. Children with ASD were more likely to study in a regular school (48.60%), while 13.88% were in a special school. Children with severe ASD were placed in less regular settings than children with mild to moderate ASD. However, families with higher socioeconomic status (SES) were more likely to place their children in regular schools than lower SES families if their children experienced mild to moderate symptoms. Children with severe ASD were more likely to be placed in expensive institutions for families with higher SES than those with lower SES. SES disparities in educational placement existed and had two manifestations. It is important to characterize educational placements of students with ASD to determine the extent to which they are placed in general education settings, which are often the preferred placement.

Diagnosis-related groups (DRG) based hospital payment systems are gradually becoming the main mechanism for reimbursement of acute inpatient care. We reviewed the existing literature to ascertain the global use of DRG-based hospital payment systems, compared the similarities and differences of original DRG versions in ten countries, and used ischemic stroke as an example to ascertain the design and implementation strategies for various DRG systems. The current challenges with and direction for the development of DRG-based hospital payment systems are also analyzed. We found that the DRG systems vary greatly in countries in terms of their purpose, grouping, coding, and payment mechanisms although based on the same classification concept and that they have tended to develop differently in countries with different income classifications. In high-income countries, DRG-based hospital payment systems have gradually begun to weaken as a mainstream payment method, while in middle-income countries DRG-based hospital payment systems have attracted increasing attention and increased use. The example of ischemic stroke provides suggestions for mutual promotion of DRG-based hospital payment systems and disease management. How to determine the level of DRG payment incentives and improve system flexibility, balance payment goals and disease management goals, and integrate development with other payment methods are areas for future research on DRG-based hospital payment systems.

The main technological difficulties of developing an intracellular (transmembrane) transport system for protein drugs lie in two points: i) overcoming the barriers in the cellular membrane, and ii) loading enough protein drugs, and particularly high-dose proteins, into particles. To address these two technological problems, we recently developed a novel cholesterol tag (C-Tag)-based transmembrane transport system. This pilot study found that the C-Tag dramatically improved the cellular uptake of Fab (902-fold, vs. Fab alone) into living cells, indicating that it successfully achieved transmembrane transport. Moreover, C-Tag-mediated membrane transport was verified using micron-scale large unilamellar vesicles (LUVs, approximately 1.5 μm)-based particles. The C-Tagged Fab was able to permeate the liposomal bilayer and it greatly enhanced (a 10.1-fold increase vs. Fab alone) internalization of proteins into the LUV-based particles, indicating that the C-Tag loaded enough proteins into particles for use of high-dose proteins. Accordingly, we established a novel C-Tag-based transport system that has overcome the known technological difficulties of protein transmembrane delivery, and this might be a useful technology for drug development in the future.

This study aimed to explore the patterns of postoperative recurrence in patients with pT2-3N0M0 esophageal squamous cell carcinoma (ESCC) and to identify the risk factors for the recurrence. Patients with pT2-3N0M0 ESCC who were treated at our hospital from January 2010 to August 2019 were divided into three categories: those with anastomotic recurrence, those with lymph node recurrence, and those with hematogenous metastasis. The sites of initial recurrence and metastasis were counted and potential risk factors were analyzed using univariate and multivariate Cox proportional hazard regression. Four hundred and eighty-five patients with pT2-3N0M0 ESCC were ultimately included, 176 (36.29%) of whom experienced tumor recurrence or metastasis. Cox multivariate analysis revealed that the postoperative T-stage, procedure, tumor location, and degree of differentiation were independent risk factors for postoperative recurrence (P < 0.05). The median time of recurrence was 38 months, and the most common site of recurrence was the lymph nodes in 126 patients (71.59%), followed by hematogenous metastasis in 73 patients (41.47%), and anastomotic recurrence in 21 patients (11.93%). 119 patients (67.61%) experienced recurrence within 36 months, with a probability of recurrence of 84.09% within 5 years, and recurrence remained relatively unchanged after 5 years. The proportion of postoperative lymph node recurrence and hematogenous metastasis in patients with pT3N0M0 ESCC was significantly higher than that in patients with pT2N0M0 ESCC (P < 0.05). At higher tumor locations in the body, the proportion of lymph node recurrence increased (P < 0.05). In conclusion, postoperative T-stage, procedure, tumor location, and degree of differentiation were independent risk factors for postoperative recurrence in pT2-3N0M0 ESCC, with regional lymph node recurrence being the most common pattern, emphasizing the importance of regional lymph nodes in this context.

As SARS-CoV-2 transitions from a pandemic to an endemic presence, a significant rise in respiratory diseases such as influenza and Mycoplasma pneumonia is challenging healthcare systems weakened by the impact of COVID-19. This commentary examines the global resurgence of respiratory pathogens, heightened by the post-pandemic "immunity debt", through an analysis of WHO surveillance data and national health reports. Findings reveal a substantial increase in respiratory illnesses, notably among children, compounded by a shortage of pediatricians and growing antimicrobial resistance. This underscores the need to improve hospital preparedness, optimize clinical responses, and enhance public health strategies to effectively navigate the impending peak of concurrent respiratory infections.

To analyze the feasibility and clinical effect of novel intraoperative navigation of real-time virtual sonography (RVS) combined with indocyanine green (ICG) fluorescent imaging technology in anatomical liver resection (ALR) for hepatocellular carcinoma. The clinical data of 41 patients who underwent ALR using RVS intraoperative navigation combined with ICG fluorescent imaging technology in the Department of Hepatobiliary Surgery of Peking University International Hospital from January 2020 to May 2022 were retrospectively analyzed. RVS was applied to guide the surgical plane through fusing real-time intraoperative ultrasound images with corresponding preoperative CT or MRI images. Operation methods, operation time, intraoperative blood loss, operative margin, hospital stay and postoperative complications were analyzed. The 1-year overall survival rate and tumor-free survival rate of patients were followed up by outpatient review or telephone calls. ALR surgery was performed on each of 41 patients. There were no deaths during perioperative period and postoperative complications occurred in 7 cases (17.1%). The postoperative pathological examinations demonstrated all cases of hepatocellular carcinoma and negative operative margins. The 41 patients were followed up for 12 to 20 months, with a median follow-up time of 14 months. The overall survival rate 1 year after surgery was 100.0% (41/41), 3 patients (7.3%) experienced tumor recurrence, and the tumor-free survival rate of 1 year after surgery was 92.7% (38/41). In conclusion, novel intraoperative navigation of RVS combined with ICG fluorescent imaging technology is safe and feasible in anatomical segmental hepatectomy of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is associated with a highly heterogeneous immune environment that produces an immune response to various locoregional treatments (LRTs), which in turn affects the effectiveness of immunotherapy. Although LRTs still dominate HCC therapies, 50-60% of patients will ultimately be treated with systemic therapies and might receive those treatments for the rest of their life. TACE, SIRT, and thermal ablation can dramatically increase the immunosuppressive state of HCC, a condition that can be addressed by combination with immunotherapy to restore the activity of lymphocytes and the secretion of cellular immune factors. Immune treatment with locoregional and systemic treatments has dramatically changed the management of HCC. In this review, we examine the research on the changes in the immune microenvironment after locoregional or systemic treatment. We also summarize the regulation of various immune cells and immune factors in the tumor microenvironment and discuss the different infiltration degrees of immune cells and factors on the prognosis of HCC to better compare the efficacy between different treatment methods from the perspective of the tumor microenvironment. This information can be used to help develop treatment options for the upcoming new era of HCC treatment in the future.

Hepatoblastoma (HB) remains the most common paediatric liver tumour and survival in children with hepatoblastoma has improved considerably since the advent of sequential surgical regimens of chemotherapy based on platinum-based chemotherapeutic agents in the 1980s. With the advent of modern diagnostic imaging and pathology techniques, new preoperative chemotherapy regimens and the maturation of surgical techniques, new diagnostic and treatment options for patients with hepatoblastoma have emerged and international collaborations are investigating the latest diagnostic approaches, chemotherapy drug combinations and surgical strategies. Diagnosis of hepatoblastoma relies on imaging studies (such as ultrasound, computed tomography, and magnetic resonance imaging), alpha-fetoprotein (AFP) levels, and histological confirmation through biopsy. The standard treatment approach involves a multimodal strategy with neoadjuvant chemotherapy followed by surgical resection. In cases where complete resection is not feasible or tumors exhibit invasive characteristics, liver transplantation is considered. The management of metastatic and recurrent hepatoblastoma poses significant challenges, and ongoing research focuses on developing targeted therapies and exploring the potential of immunotherapy. Further studies are necessary to gain a better understanding of the etiology of hepatoblastoma, develop prevention strategies, and personalize treatment approaches. We aim to review the current status of diagnosis and treatment of hepatoblastoma.

The bacterial flagellar motor is a molecular nanomachine, the assembly and regulation of which requires many accessory proteins. Their identity, structure and function are often discovered through characterisation of mutants with impaired motility. Here, we demonstrate the functional association of the Helicobacter pylori peptidoglycan-associated lipoprotein (HpPal) with the flagellar motor by analysing the motility phenotype of the ∆pal mutant, and present the results of the preliminary X-ray crystallographic analysis of its globular C-terminal domain HpPal-C. Purified HpPal-C behaved as a dimer in solution. Crystals of HpPal-C were grown by the hanging drop vapour diffusion method using medium molecular weight polyethylene glycol (PEG) Smear as the precipitating agent. The crystals belong to the primitive orthorhombic space group P1 with unit cell parameters a = 50.7, b = 63.0, c = 75.1 Å. X-ray diffraction data were collected to 1.8 Å resolution on the Australian Synchrotron beamline MX2. Calculation of the Matthews coefficient (V_M=2.24 ų/Da) and molecular replacement showed that the asymmetric unit contains two protein subunits. This study is an important step towards elucidation of the non-canonical role of H. pylori Pal in the regulation, or function of, the flagellar motor.