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Background: Intervertebral disc degeneration (IDD) was the most common cause of low back pain. Platelet rich plasma (PRP) has the potential to repair IDD, however, there is still no conclusion on whether Leukocyte-poor platelet rich plasma (Lp-PRP) or Leukocyte-rich platelet rich plasma (Lr-PRP) is better for the treatment of IDD., Methods: First, we conducted an in vitro study to compare the effects of autologous Lp-PRP and Lr-PRP on human degenerated nucleus pulposus (NP) cells. Then we verified the in vivo effects of autologous Lp-PRP and Lr-PRP in treating disc degeneration through a rabbit IDD model., Results: The in vitro study showed both autologous Lp-PRP and Lr-PRP can promote the cell proliferation, the synthesis of COL II and Aggrecan of human degenerated NP cells, while Lp-PRP are better than Lr-PRP (P<0.05). In addition, only Lp-PRP can inhibit the apoptosis of human degenerated NP cells (P<0.05), whereas Lr-PRP activates the catabolism on the contrary (P<0.05). Further, the in vivo study through the rabbit IDD model verified that autologous Lp-PRP has better effects than autologous Lr-PRP in repairing IDD according to X-ray, MRI, histological, and immunohistochemical assessment (P<0.05, respectively). And the caspase-3 IHC results also showed that only autologous Lp-PRP treatment could inhibit apoptosis of NP cells in the rabbit IDD model (P<0.05)., Conclusion: Combining in vivo and in vitro studies, the present study confirmed that autologous Lp-PRP has a better effect than autologous Lr-PRP in repairing IDD, which may be due to the inflammatory factors (TNFα, IL-1β, etc.) in Lr-PRP antagonizing part of the repair effects and promoting the catabolism additionally. Therefore, our findings suggest that Lp-PRP may provide better results than Lr-PRP for treating IDD. Further randomized clinical trials will provide evidence to guide practice., (© 2024. The Author(s).)

Background: Manual placement of cervical pedicle screws is risky, and robot-assisted placement of atlantoaxial pedicle screws has not been reported., Case Report: We describe a 74-year-old female patient with atlantoaxial fracture and dislocation combined with spinal cord injury caused by a car accident. The left lower limb muscle strength was grade 0, the right upper limb muscle strength was grade 1, and the right lower limb muscle strength was grade 2. Loss of sensation below the clavicle level, decreased superficial sensation in the extremities, loss of deep sensation in the left lower extremity, and incontinence were observed. We successfully placed atlas pedicle screws with the assistance of the Mazor X robot. One week after the operation, radiological imaging revealed that the reduction effect was good, the placement of the pedicle screws was satisfactory, the left upper limb and left lower limb muscle strength was level 2, the right upper limb and the muscle strength of the right lower limb were grade 3, and the sensory function was partially restored. No complications related to screw placement were found at the 3-month postoperative follow-up., Conclusions: Mazor X robot-assisted descending pedicle screw fixation of the atlas is feasible and safe., (© 2024. The Author(s).)

Objective: This study employs integrated bioinformatics analysis and in vitro cellular experiments to elucidate the role of Synaptotagmin-12 (SYT12) in the progression of gastric cancer., Methods: We utilized databases and platforms such as Xiantao Academic Tools, UALCAN, Kaplan-Meier plotter analysis, and The Cancer Genome Atlas (TCGA) to extract datasets on SYT12 in gastric cancer. We analyzed the relationship between SYT12 expression and the clinicopathological features, prognosis, diagnosis, and immune infiltration of stomach adenocarcinoma (STAD) patients. Verification was conducted using samples from 31 gastric cancer patients. Additionally, in vitro cellular experiments were performed to determine the role and potential mechanisms of SYT12 in the malignant behavior of gastric cancer cells., Results: Comprehensive bioinformatics analysis indicated that SYT12 is highly expressed in most cancers and is associated with promoter DeoxyriboNucleic Acid (DNA) methylation levels. SYT12 expression correlated with clinicopathological features, immune cell infiltration, immune checkpoint gene expression, and poor prognosis in STAD patients. In vitro experiments suggest that SYT12 may promote the proliferation and migration of gastric cancer cells by inducing epithelial-mesenchymal transition (EMT)., Conclusions: This study highlights the significant role of SYT12 in gastric cancer, suggesting its potential as a new target for early diagnosis, treatment, immunological, and prognostic evaluation in gastric cancer, offering new insights for precision medicine in this disease., (© 2024. The Author(s).)

Background: Pancreatic cancer is a malignant tumor of the digestive tract with a high mortality rate. Erianin has antitumor activity, but the regulatory targets and mechanism of action in pancreatic cancer are unclear. The objective of this study was to evaluate the anti-pancreatic cancer activity of Erianin and explore its underlying mechanisms., Methods: A network pharmacology approach was used to investigate the mechanism of action of Erianin in pancreatic cancer cells. Cell proliferation was analyzed using CCK8, colony-formation, and EdU proliferation assays. Cell migration was evaluated through wound healing and transwell assays, as well as determination of the protein expression levels of EMT markers and β-catenin. Apoptosis and the cell cycle were measured using flow cytometry and JC-1 staining, respectively. The protein expression levels of p-Rb, CyclinB1, P21, Cleaved-PARP, and Cleaved-Caspase3 were assessed using western blotting. RNA sequencing (RNA-seq) and bioinformatics analyses were performed to elucidate the mechanism underlying the action of Erianin in pancreatic cancer. Western blotting was used to examine the expression levels of key proteins in the AKT, JNK, and p38 MAPK signaling pathways. Molecular docking and CETSA were used to test hypotheses. The tumor-suppressive ability of Erianin in vivo was assessed using a tumor-bearing assay in nude mice., Results: Network pharmacology revealed that Erianin inhibited pancreatic cancer through multiple pathways. Erianin significantly inhibited pancreatic cancer cell proliferation and migration while promoting intracellular ROS and inducing apoptosis. Mechanistically, Erianin inhibited pancreatic cancer cell proliferation by regulating the AKT/FOXO1 and ASK1/JNK/p38 MAPK signaling pathways. In vivo experiments showed that Erianin inhibited subcutaneous tumor growth and promoted tumor tissue apoptosis in nude mice., Conclusions: The component-target-pathway network revealed that Erianin exerted anti-cancer effects through multiple components, targets, and pathways. Erianin inhibited the proliferation and migration of pancreatic cancer cells and induced apoptosis through the AKT/FOXO1 and ASK1/JNK/p38 MAPK signaling pathways. These results indicate that Erianin is a promising agent for pancreatic cancer treatment., (© 2024. The Author(s).)

Background: Hepatitis B remains a significant global health concern with widespread communicability. Nevertheless, data on its burden and trends in children and adolescents were limited. We aim to evaluate the global, regional, and national trends of total burden related to hepatitis B in children and adolescents aged 0-19 years from 1990 to 2021., Methods: The age-standardized incidence, prevalence, mortality, and disability-adjusted life years (DALYs) were calculated by the Global Burden of Disease (GBD) study from 1990 to 2021. These indicators were stratified by sex, age, socio-demographic index (SDI), and disease stage. We calculated the correlation between them and SDI. The temporal trends were examined using the annual average percentage change (AAPC) and joinpoint regression., Results: The global age-standardized incidence of hepatitis B in children and adolescents decreased from 1385.20 per 100,000 population in 1990 to 418.68 per 100,000 population in 2021, with an AAPC of -3.76%. Similarly, age-standardized DALYs decreased from 70.78 per 100,000 population to 36.31 per 100,000 population, with an AAPC of -2.13%. The age-standardized prevalence (AAPC - 3.53%) and mortality (AAPC - 2.09%) of hepatitis B also decreased significantly. From 1990 to 2021, the age-standardized incidence and prevalence among males exhibited a higher trend compared to females, although both declined over time. These two indicators also decreased across all age subgroups, with consistently higher rates observed in the 15-19 age group compared to other age groups. The burden of hepatitis B demonstrated a notable reduction in countries with high-middle SDI, while it was highest in countries with low SDI. In 2021, Central sub-Saharan Africa and West sub-Saharan Africa reported the highest age-standardized incidence. For age-standardized DALYs, South Asia was the only region to experience an increase (AAPC 1.09%), while East Asia showed the largest decline (AAPC - 7.58%). Alcohol and drug use remained important risk factors for DALYs among people aged 15-19 years. Furthermore, the impact of drug use on disease burden was increasing, particularly in high-SDI countries., Conclusions: The global burden and trends of hepatitis B decreased significantly in children and adolescents, exhibiting regional and national variations. Management of alcohol and drug use remains a major challenge for people aged 15-19 years., (© 2024. The Author(s).)

Antibacterial bone cements (ABCs), such as antibiotic-loaded bone cements (ALBCs), have been widely utilized in clinical treatments. Currently, bone cements loaded with vancomycin, gentamicin, tobramycin, or clindamycin are approved by the US Food and Drug Administration. However, traditional ALBCs exhibit drawbacks like burst release and bacterial resistance. Therefore, there is a demand for the development of antibacterial bone cements containing novel agents to address these defects. In this review, we provide an overview and prospect of the new antibacterial agents that can be used or have the potential to be applied in bone cement, including metallic antibacterial agents, pH-switchable antibacterial agents, cationic polymers, N-halamines, non-leaching acrylic monomers, antimicrobial peptides and enzymes. Additionally, we have conducted a preliminary assessment of the feasibility of bone cement containing N-halamine, which has demonstrated good antibacterial activities. The conclusion of this review is that the research and utilization of bone cement containing novel antibacterial agents contribute to addressing the limitations of ALBCs. Therefore, it is necessary to continue expanding the research and use of bone cement incorporating novel antibacterial agents. This review offers a novel perspectives for designing ABCs and treating bone infections., (© 2024. The Author(s).)

Background: Spontaneous intracerebral hemorrhage (SICH) is a severe stroke with high mortality and disability rates. Endoscopic surgery is an increasingly widely used minimally invasive method for the treatment of SICH. However, the impact of fever on patient outcomes remains unclear., Methods: We retrospectively included patients aged 18 years or older with supratentorial SICH confirmed by CT, who underwent endoscopic hematoma evacuation within 48 h of symptom onset. The primary outcome was the modified Rankin Scale (mRS) score at 3 months. Secondary outcomes included hospital and neurosurgical intensive care unit (NSICU) stays, and perioperative complications. We analyzed the association between postoperative fever (highest temperature within 24 h after surgery) and these outcomes using multivariate analysis, generalized additive models, and segmented regression analysis., Results: Of the 56 patients, 38 had favorable outcomes (mRS ≤ 3) and 18 had unfavorable outcomes (mRS > 3) at 3 months. A threshold effect at 38.2 °C was observed between postoperative body temperature and clinical outcomes. The mean age was 56 years (SD = 9) for the > 38.2 °C group and 58 years (SD = 8) for the ≤ 38.2 °C group, with a similar proportion of male patients (63% vs. 69%, P = 0.635). Patients with postoperative fever had larger hematoma volumes (65 vs. 56 mL; P = 0.008). Other characteristics were similar between the groups. Postoperative fever (> 38.2 °C) was independently associated with a 4.99-fold increased risk of unfavorable outcomes (95% CI = [1.13 to 25.90]; P = 0.040), which remained significant after excluding patients with postoperative complications (adjusted RR = 16.03, 95% CI = [1.69 to 417.24]; P = 0.033). The association was consistent across subgroups with different Glasgow Coma Scale scores, hematoma volumes, and intraventricular extension. Postoperative fever was also associated with longer NSICU stays (3.1 vs. 2.3 days; P = 0.023), longer hospital stays (17.2 vs. 13.6 days; P = 0.010), more residual hematoma, and greater edema volume. Different antipyretic therapies did not affect outcomes., Conclusions: This study identifies a temperature threshold (38.2 °C) associated with poor outcomes in SICH patients undergoing endoscopic surgery. Further research is needed to mitigate postoperative fever and improve patient outcomes., (© 2024. The Author(s).)

Background: The blunt snout bream (Megalobrama amblycephala) is an important economic freshwater fish in China with tender flesh and high nutritional value. With the cultivation of superior new varieties and the expansion of breeding scale, it becomes imperative to employ sex-control technology to cultivate monosexual populations of M. amblycephala, thereby preventing the deterioration of desirable traits. The development of specific markers capable of accurately identifying the sex of M. amblycephala would facilitate the determination of the genetic sex of the breeding population before gonad maturation, thereby expediting the processes of sex-controlled breeding of M. amblycephala., Results: A whole-genome re-sequencing was performed for 116 females and 141 males M. amblycephala collected from nine populations. Seven candidate male-specific sequences were identified through comparative analysis of male and female genomes, which were further compared with the sequencing data of 257 individuals, and finally three male-specific sequences were generated. These three sequences were further validated by PCR amplification in 32 males and 32 females to confirm their potential as male-specific molecular markers for M. amblycephala. One of these markers showed potential applicability in M. pellegrini as well, enabling males to be identified using this specific molecular marker., Conclusions: The study provides a high-efficiency and cost-effective approach for the genetic sex identification in two species of Megalobrama. The developed markers in this study have great potential in facilitating sex-controlled breeding of M. amblycephala and M. pellegrini, while also contributing valuable insights into the underlying mechanisms of fish sex determination., (© 2024. The Author(s).)

Background: Cereal diseases caused by insect-transmitted viruses are challenging to forecast and control because of their intermittent outbreak patterns, which are usually attributed to increased population densities of vector insects due to cereal crop rotations and indiscriminate use of pesticides, and lack of resistance in commercial varieties. Root microbiomes are known to significantly affect plant health, but there are significant knowledge gaps concerning epidemics of cereal virus diseases at the microbiome-wide scale under a variety of environmental and biological factors., Results: Here, we characterize the diversity and composition of rice (Oryza sativa) root-associated bacterial communities after infection by an insect-transmitted reovirus, rice black-streaked dwarf virus (RBSDV, genus Fijivirus, family Spinareoviridae), by sequencing the bacterial 16S rRNA gene amplified fragments from 1240 samples collected at a consecutive 3-year field experiment. The disease incidences gradually decreased from 2017 to 2019 in both Langfang (LF) and Kaifeng (KF). BRSDV infection significantly impacted the bacterial community in the rice rhizosphere, but this effect was highly susceptible to both the rice-intrinsic and external conditions. A greater correlation between the bacterial community in the rice rhizosphere and those in the root endosphere was found after virus infection, implying a potential relationship between the rice-intrinsic conditions and the rhizosphere bacterial community. The discrepant metabolites in rhizosphere soil were strongly and significantly correlated with the variation of rhizosphere bacterial communities. Glycerophosphates, amino acids, steroid esters, and triterpenoids were the metabolites most closely associated with the bacterial communities, and they mainly linked to the taxa of Proteobacteria, especially Rhodocyclaceae, Burkholderiaceae, and Xanthomonadales. In addition, the greenhouse pot experiments demonstrated that bulk soil microbiota significantly influenced the rhizosphere and endosphere communities and also regulated the RBSDV-mediated variation of rhizosphere bacterial communities., Conclusions: Overall, this study reveals unprecedented spatiotemporal dynamics in rhizosphere bacterial communities triggered by RBSDV infection with potential implications for disease intermittent outbreaks. The finding has promising implications for future studies exploring virus-mediated plant-microbiome interactions. Video Abstract., (© 2024. The Author(s).)

Background: This study aimed to evaluate whether social, familial and personal factors can predict incident and prevalent depressive symptoms in Chinese adults aged ≥ 45 years using data from the China Health and Retirement Longitudinal Study (CHARLS)., Methods: Study subjects without depressive symptoms from CHARLS at baseline were enrolled. Depressive symptoms were defined by the 10-item Center for Epidemiologic Studies Depression Scale. Statistical adjustment, subgroup exploration and unmeasured confounding assessment were undertaken to derive reliable estimates., Results: 1681 (27.04%) of 6215 subjects who had no depressive symptoms in 2011, suffered one or more depressive symptoms in 2018. Multivariate analyses showed that number of grandchildren (odds ratio [95% confidence interval]: 1.06 [1.02, 1.10]), social activity score (0.95 [0.91, 0.98]), instrumental activities of daily living (IADL) (1.35 [1.11, 1.65]) and number of comorbidities (1.16 [1.10, 1.22]) were independently and significantly associated with the presence of incident depressive symptoms. Further categorization revealed significance for social activity score (odds ratio [95% confidence interval]: 0.78 [0.69, 0.89] and 0.71 [0.53, 0.95] for 1-5 and > 5 vs. 0), IADL (1.35 [1.11, 1.65] for yes vs. no) and number of comorbidities (1.38 [1.20, 1.58], 1.44 [1.16, 1.81] and 2.42 [1.54, 3.80] for 1-2, 3-4 and > 4 vs. 0) associated with incident depressive symptoms. Restricting analysis to wave IV data in 2018 observed significant association of number of grandchildren, social activity score, IADL and number of comorbidities with prevalent depressive symptoms., Conclusions: The present study findings support the marked contribution of social activity score, IADL and number of comorbidities to incident and prevalent depressive symptoms in Chinese middle-aged and older adults., (© 2024. The Author(s).)

By inhibiting acetylcholinesterase (AChE) activity, organophosphate compounds (OPs) can quickly cause severe injury to the nervous system and death, making it extremely difficult to rescue victims after OP exposure. However, it is quite challenging to construct scavengers that neutralize and eliminate these harmful chemical agents promptly in the blood circulation system. Herein, we report an enzyme-armed biomimetic nanoparticle that enables a 'targeted binding and catalytic degradation' action mechanism designed for highly efficient in vivo detoxification (denoted as 'Nanocleaner'). Specifically, the resulting Nanocleaner is fabricated with polymeric cores camouflaged with a modified red blood cell membrane (RBC membrane) that is inserted with the organophosphorus hydrolase (OPH) enzyme. In such a subtle construct, Nanocleaner inherits abundant acetylcholinesterase (AChE) on the surface of the RBC membrane, which can specifically lure and neutralize OPs through biological binding. The OPH enzyme on the membrane surface breaks down toxicants catalytically. The in vitro protective effects of Nanocleaner against methyl paraoxon (MPO)-induced inhibition of AChE activity were validated using both preincubation and competitive regimens. Furthermore, we selected the PC12 neuroendocrine cell line as an experimental model and confirmed the cytoprotective effects of Nanocleaner against MPO. In mice challenged with a lethal dose of MPO, Nanocleaner significantly reduces clinical signs of intoxication, rescues AChE activity and promotes the survival rate of mice challenged with lethal MPO. Overall, these results suggest considerable promise of enzyme-armed Nanocleaner for the highly efficient removal of OPs for clinical treatment., (© 2024. The Author(s).)

Background: The Persian walnut (Juglans regia), an economically vital species within the Juglandaceae family, has seen its mitochondrial genome sequenced and assembled in the current study using advanced Illumina and Nanopore sequencing technology., Results: The 1,007,576 bp mitogenome of J. regia consisted of three circular chromosomes with a 44.52% GC content encoding 39 PCGs, 47 tRNA, and five rRNA genes. Extensive repetitive sequences, including 320 SSRs, 512 interspersed, and 83 tandem repeats, were identified, contributing to genomic complexity. The protein-coding sequences (PCGs) favored A/T-ending codons, and the codon usage bias was primarily shaped by selective pressure. Intracellular gene transfer occurred among the mitogenome, chloroplast, and nuclear genomes. Comparative genomic analysis unveiled abundant structure and sequence variation among J. regia and related species. The results of selective pressure analysis indicated that most PCGs underwent purifying selection, whereas the atp4 and ccmB genes had experienced positive selection between many species pairs. In addition, the phylogenetic examination, grounded in mitochondrial genome data, precisely delineated the evolutionary and taxonomic relationships of J. regia and its relatives. We identified a total of 539 RNA editing sites, among which 288 were corroborated by transcriptome sequencing data. Furthermore, expression profiling under temperature stress highlighted the complex regulation pattern of 28 differently expressed PCGs, wherein NADH dehydrogenase and ATP synthase genes might be critical in the mitochondria response to cold stress., Conclusions: Our results provided valuable molecular resources for understanding the genetic characteristics of J. regia and offered novel perspectives for population genetics and evolutionary studies in Juglans and related woody species., (© 2024. The Author(s).)

Background: Given the established link between obesity and hyperuricemia (HUA), the research want to investigate the relationship between different obesity indices and HUA, and further analyze which obesity index can better predict HUA., Methods: The data were obtained from a longitudinal study involving middle-aged and elderly populations in Dalian, China. The research encompassed individuals who exhibited typical uric acid levels initially and tracked their progress over a three-year period. 8 obesity indices were evaluated retrospectively. Subgroup analyses were conducted to identify susceptible populations. Restricted cubic splines (RCS) were utilized to model the dose-response relationships between obesity indices and HUA. Receiver operating characteristic (ROC) curves were applied to visualize and compare the predictive value of both traditional and new obesity indices for HUA., Results: Among 4,112 individuals with normal baseline uric acid levels, 950 developed HUA. Significant associations with HUA were observed for body mass index (BMI), waist circumference (WC), body roundness index (BRI), cardiometabolic index (CMI), visceral adiposity index (VAI), Chinese visceral adiposity index (CVAI), lipid accumulation product (LAP), and abdominal volume index (AVI). Subgroup analysis indicated that all obesity indices proved more effective in assessing the onset of HUA in women without Metabolic Syndrome (MetS). Further analysis using RCS revealed non-linear dose-response relationships between LAP, CMI, VAI, and HUA in males, with similar non-linear relationships observed for all indices in females. The results from the ROC curves indicate that LAP may serve as a better predictor of HUA in males, and CVAI may serve as a better predictor in females., Conclusion: HUA is closely associated with obesity indices. Among females, CVAI emerges as the preferred predictive index for HUA. In males, LAP emerges as the preferred predictive index for HUA., (© 2024. The Author(s).)

Background: In recent times, a number of new indices for measuring visceral obesity have been developed. This research sought to investigate the relationship between four visceral obesity indices and prediabetes and diabetes., Methods: Conducted in 2011 as a cross-sectional analysis in Dalian, China, this study utilized logistic regression models to explore the relationships between four visceral obesity indices and prediabetes and diabetes. It also assessed the dose-response relationships using restricted cubic splines (RCS), performed subgroup analyses, and conducted interaction tests. The predictive values of four visceral obesity indices were evaluated using receiver operating characteristic (ROC) curves., Results: The study enrolled 10,090 participants, with prediabetes and diabetes prevalence at 80.53%. Multifactorial logistic regression revealed positive relationships between the four visceral obesity indices and prediabetes and diabetes. The results of the RCS analysis revealed a linear relationship between the body roundness index (BRI), cardiometabolic index (CMI) and prediabetes and diabetes. Conversely, a non-linear relationship was observed between Chinese visceral adiposity index (CVAI), lipid accumulation product (LAP) and prediabetes and diabetes. Subgroup analyses demonstrated stronger relationships of CMI, CVAI, and LAP with prediabetes and diabetes among females. ROC curves suggested that LAP could be an effective predictor of these conditions., Conclusion: This research confirmed that four visceral obesity indices are linked with a higher risk of prediabetes and diabetes in middle-aged and elderly individuals in Dalian. Importantly, LAP could be an effective predictor of prediabetes and diabetes. Effective weight management significantly reduces the risk of both prediabetes and diabetes., (© 2024. The Author(s).)

Objective: To explore the high-risk factors affecting the prognosis of pT 1 - 2 N 1 M 0 patients after mastectomy, establish a nomogram prediction model, and screen the radiotherapy benefit population., Method: The clinical data of 936 patients with pT 1 - 2 N 1 M 0 who underwent mastectomy in the fourth hospital of Hebei Medical University from 2010 to 2016 were retrospectively analyzed. There were 583 patients received postmastectomy radiotherapy(PMRT), and 325 patients without PMRT. Group imbalances were mitigated using the propensity score matching (PSM) method, and the log-rank test was employed to compare overall survival (OS) and disease-free survival (DFS) between the cohorts. The efficacy of PMRT across various risk groups was evaluated using a nomogram model., Result: The median follow-up period was 98 months, Patients who received PMRT demonstrated significantly improved 5-year and 8-year OS and DFS compared to those who did not (P < 0.001). Multivariate analysis revealed that age, primary tumor site, positive lymph node, stage, and Ki-67 level independently influenced OS, while age, primary tumor site, and stage independently affected DFS. PMRT drastically enhanced OS in the high-risk group (P = 0.001), but did not confer benefits in the low-risk and intermediate risk groups (P = 0.057, P = 0.099). PMRT led to a significant improvement in disease-free survival (DFS) among patients in the intermediate and high-risk groups (P = 0.036, P = 0.001), whereas the low-risk group did not experience a significant benefit (P = 0.475)., Conclusion: Age ≤ 40 years, tumor located in the inner quadrant or central area, T 2 stage, 2-3 lymph nodes metastasis, and Ki67 > 30% were the high-risk factors affecting the prognosis of this cohort of patients. In OS nomogram, patients with a risk score of 149 or higher who received PMRT exhibited improved OS. Similarly, in DFS nomogram, patients with a risk score of 123 or higher who received PMRT demonstrated enhanced DFS., (© 2024. The Author(s).)

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and debilitating respiratory disease with a median survival of less than 5 years. In recent years, glutamine has been reported to be involved in the regulation of collagen deposition and cell proliferation in fibroblasts, thereby influencing the progression of IPF. However, the relationships between glutamine and the incidence, progression, and treatment response of IPF remain unclear. Our study aimed to investigate the relationship between circulating glutamine levels and IPF, as well as its potential as a therapeutic target., Methods: We performed a comprehensive Mendelian Randomization (MR) analysis using the most recent genome-wide association study summary-level data. A total of 32 single nucleotide polymorphisms significantly correlated to glutamine levels were identified as instrumental variables. Eight MR analysis methods, including inverse variance weighted, MR-Egger, weighted median, weighted mode, constrained maximum likelihood, contamination mixture, robust adjusted profile score, and debiased inverse-variance weighted method, were used to assess the relationship between glutamine levels with IPF., Results: The inverse variance weighted analysis revealed a significant inverse correlation between glutamine levels and IPF risk (Odds Ratio = 0.750; 95% Confidence Interval : 0.592-0.951; P = 0.017). Sensitivity analyses, including MR-Egger regression and MR-PRESSO global test, confirmed the robustness of our findings, with no evidence of horizontal pleiotropy or heterogeneity., Conclusion: Our study provides novel evidence for a causal relationship between lower circulating glutamine levels and increased risk of IPF. This finding may contribute to the early identification of high-risk individuals for IPF, disease monitoring, and development of targeted therapeutic strategies., (© 2024. The Author(s).)

Breast cancer therapy has significantly advanced by targeting the programmed cell death-ligand 1/programmed cell death-1 (PD-L1/PD-1) pathway. BMS-202 (a smallmolecule PD-L1 inhibitor) induces PD-L1 dimerization to block PD-1/PD-L1 interactions, allowing the T-cell-mediated immune response to kill tumor cells. However, immunotherapy alone has limited effects. Clinically approved photodynamic therapy (PDT) activates immunity and selectively targets malignant cells. However, PDT aggravates hypoxia, which may compromise its therapeutic efficacy and promote tumor metastasis. We designed a tumor-specific delivery nanoplatform of liposomes that encapsulate the hypoxia-sensitive antitumor drug tirapazamine (TPZ) and the small-molecule immunosuppressant BMS. New indocyanine green (IR820)-loaded polyethylenimine-folic acid (PEI-FA) was complexed with TPZ and BMS-loaded liposomes via electrostatic interactions to form lipid nanocomposites. This nanoplatform can be triggered by near-infrared irradiation to induce PDT, resulting in a hypoxic tumor environment and activation of the prodrug TPZ to achieve efficient chemotherapy. The in vitro and in vivo studies demonstrated excellent combined PDT, chemotherapy, and immunotherapy effects on the regression of distant tumors and lung metastases, providing a reference method for the preparation of targeted agents for treating breast cancer., (© 2024. The Author(s).)

Background: Lanping black-boned sheep (LPB) represent a distinctive mammalian species characterized by hyperpigmentation, resulting in black bone and muscle features, in contrast to their conventional counterparts exhibiting red muscle and white bone. The genetic basis underlying LPB hyperpigmentation has remained enigmatic., Methods: In this study, we conducted whole-genome sequencing of 100 LPB and 50 Lanping normal sheep (LPN), and integrated this data with 421 sequenced datasets from wild and domestic sheep, shedding light on the genetic backdrop and genomic variations associated with LPB. Furthermore, we performed comparative RNA-Seq analysis using liver sample to pinpoint genes implicated in the pigmentation process. We generated a comprehensive dataset comprising 97,944,357 SNPs from 571 sheep, facilitating an in-depth exploration of genetic factors., Results: Population genetic structure analysis revealed that the LPB breed traces its origin back to LPN, having evolved into a distinct breed. The integration of positively selected genes with differentially expressed genes identified two candidates, ERBB4 and ROR1, potentially linked to LPB hyperpigmentation. Comparative analysis of ERBB4 and ROR1 mRNA relative expression levels in liver, spleen, and kidney tissues of LPB, in comparison to Diqing sheep, revealed significant upregulation, except for ERBB4 in the liver. Gene expression heatmaps further underscored marked allelic frequency disparities in different populations., Conclusion: Our findings establish the evolutionary lineage of the LPB breed from LPN and underscore the involvement of ERBB4 and ROR1 genes in melanin synthesis. These results enhance our comprehension of the molecular basis of hyperpigmentation and contribute to a more comprehensive depiction of sheep diversity., (© 2024. The Author(s).)

Background and Objective: Community-acquired pneumonia (CAP) is a common respiratory disease that frequently requires hospitalisation, and is a significant cause of death worldwide. This study aimed to evaluate the usefulness of alpha-1-antichymotrypsin (AACT) as a diagnostic and prognostic biomarker of CAP., Methods: We conducted a multicentre prospective cohort study in patients hospitalised with CAP. Plasma AACT levels were measured using a quantitative enzyme-linked immunosorbent assay. Receiver-operating characteristic (ROC) curves and Cox proportional hazards regression were used to assess the association between plasma AACT levels and CAP diagnosis and prognosis., Results: A total of 274 patients with CAP were enrolled in the study. AACT levels were elevated in patients with CAP, especially those with severe CAP and non-survivors. The area under the curve (AUC) of AACT and CRP for diagnosing CAP was 0.755 and 0.843. Cox regression showed that CURB-65 and AACT levels were independent predictors of 30-day mortality. ROC curves showed that plasma AACT levels had the highest accuracy for predicting acute respiratory distress syndrome (ARDS), with an AUC of 0.862. Combining AACT with Pneumonia Severity Index and CURB-65 significantly improved their predictive accuracy for predicting 30-day mortality., Conclusion: Plasma AACT levels are elevated in patients with CAP, but plasma AACT level is inferior to the C-reactive protein level for diagnosing CAP. The AACT level can reliably predict the occurrence of ARDS and 30-day mortality in patients with CAP., (© 2024. The Author(s).)

Context: Polycystic ovary syndrome (PCOS), a common endocrine disorder in women of reproductive age, is closely associated with chronic low-grade inflammation and metabolic disturbances. In PCOS mice, dietary inulin has been demonstrated to regulate intestinal flora and inflammation. However, the efficacy of dietary inulin in clinical PCOS remains unclear., Objective: The intestinal flora and related metabolic indexes of obese patients with polycystic ovary syndrome (PCOS) after 3 months of inulin treatment were analyzed., Setting and Design: To analyze the intestinal flora and related metabolic indexes in healthy controls and obese patients with polycystic ovary syndrome after 3 months of inulin treatment., Results: The results showed that dietary inulin improved sex hormone disorders, reduced BMI and WHR levels in obese women with PCOS. In addition, the inulin intervention reduced plasma TNF-α, IL-1β, IL-6, and MCP-1levels. Inulin intervention increased the abundance of Actinobacteria, Fusobacteria, Lachnospira, and Bifidobacterium, as well as decreased the ratio of F/B and the abundance of proteobacteria, Sutterella, and Enterobacter. Correlation analyses showed a strong relationship among plasma inflammatory factors, sex steroid hormones, and the intestinal flora of patients., Conclusions: Dietary inulin may improve obese PCOS women disease through the gut flora-inflammation-steroid hormone pathway., The Clinical Trial Registration Number: ChiCTR-IOR-17012281., (© 2024. The Author(s).)

Goatpoxvirus (GTPV), sheeppoxvius (SPPV), and the Lumpy skin disease virus (LSDV) is a Capripoxvirus belonging to the family poxviridae. They can cause significant economic losses in countries where this disease are endemic. However, effective and convenient diagnostic tools against sera antibody are not readily available until now. Toward this goal, a polyclonal antibody competitive enzyme-linked immunosorbent assay (c-ELISA) of detecting serogroup-specific antibody is established based on major LSDV antigen A33. Serum samples (n = 605) were collected to optimize the c-ELISA from different areas. The cut-off value for the c-ELISA was estimate using percent inhibition (PI) values. The diagnostic performance of test including sensitivity (sn) and specificity (sp) were obtained by receiver operator characteristic (ROC) analysis. Among these analysis, > 57.61% PI value was accepted as cut-off of the c-ELISA, the diagnostic sn an diagnostic sp were reached to 96.4% and 98.5%, at > 95% confidence interval. These results show that the developed competitive ELISA is sensitive, specific, and reliable, which make it appropriate for serological investigation., (© 2024. The Author(s).)

N6-methyladenosine (m 6 A) is dynamically regulated by methyltransferases (termed "writers") and demethylases (referred to as "erasers"), facilitating a reversible modulation. Changes in m 6 A levels significantly influence cellular functions, such as RNA export from the nucleus, mRNA metabolism, protein synthesis, and RNA splicing. They are intricately associated with a spectrum of pathologies. Moreover, dysregulation of m 6 A modulation has emerged as a promising therapeutic target across many diseases. m 6 A plays a pivotal role in controlling vital downstream molecules and critical biological pathways, contributing to the pathogenesis and evolution of numerous conditions. This review provides an overview of m 6 A demethylases, explicitly detailing the structural and functional characteristics of FTO and ALKBH5. Additionally, we explore their distinct involvement in various diseases, examine factors regulating their expression, and discuss the progress in inhibitor development., (© 2024. The Author(s).)

Background: Grafting with dwarf rootstock is an efficient method to control plant height in fruit production. However, the molecular mechanism remains unclear. Our previous study showed that plants with Prunus mume (mume) rootstock exhibited a considerable reduction in plant height, internode length, and number of nodes compared with Prunus persica (peach) rootstock. The present study aimed to investigate the mechanism behind the regulation of plant height by mume rootstocks through transcriptomic and metabolomic analyses with two grafting combinations, 'Longyan/Mume' and 'Longyan/Peach'., Results: There was a significant decrease in brassinolide levels in plants that were grafted onto mume rootstocks. Plant hormone signal transduction and brassinolide production metabolism gene expression also changed significantly. Flavonoid levels, amino acid and fatty acid metabolites, and energy metabolism in dwarf plants decreased. There was a notable upregulation of PmLBD3 gene expression in plant specimens that were subjected to grafting onto mume rootstocks. Auxin signalling cues promoted PmARF3 transcription, which directly controlled this upregulation. Through its binding to PmBAS1 and PmSAUR36a gene promoters, PmLBD3 promoted endogenous brassinolide inactivation and inhibited cell proliferation., Conclusions: Auxin signalling and brassinolide levels are linked by PmLBD3. Our findings showed that PmLBD3 is a key transcription factor that regulates the balance of hormones through the auxin and brassinolide signalling pathways and causes dwarf plants in stone fruits., (© 2024. The Author(s).)

Background: Recent years have seen the emergence of numerous novel indicators for visceral obesity. This study investigates the potential correlation between the Chinese visceral adiposity index (CVAI) and hyperuricemia (HUA)., Methods: This research, derived from a 2011 cross-sectional analysis in Dalian, China, employed restricted cubic spline (RCS) plots to identify inflection points. Subsequently, one-way and multifactorial logistic regression models were utilized, with HUA as the outcome variable. Additionally, subgroup analyses and interaction tests were conducted. Eventually, receiver operating characteristic (ROC) curves were calculated to assess the effectiveness of CVAI and other body composition indices in predicting HUA., Results: The study included 10,061 individuals, with a HUA prevalence of 14.25%. Significant relationships with HUA were observed for CVAI. RCS analysis revealed a J-shaped relationship between CVAI and HUA. Compared to those in the low CVAI category, HUA was notably associated with individuals in the high CVAI category in multifactorial logistic regression (OR = 2.661, 95% CI: 2.323, 3.047). Subgroup analyses demonstrated stronger relationships in women, participants without hypertension, and participants without diabetes. Additional modeling via ROC curves suggested that the CVAI may offer effective predictive value for HUA., Conclusion: This study confirmed that an elevated CVAI elevates the risk of HUA in middle-aged and elderly populations in the Dalian community. The findings advance obesity prevention strategies that mitigate HUA risk and support healthcare initiatives for China's aging population., (© 2024. The Author(s).)

Background: Cardiac autonomic neuropathy (CAN) in diabetes mellitus (DM) is independently associated with cardiovascular (CV) events and CV death. Diagnosis of this complication of DM is time-consuming and not routinely performed in the clinical practice, in contrast to fundus retinal imaging which is accessible and routinely performed. Whether artificial intelligence (AI) utilizing retinal images collected through diabetic eye screening can provide an efficient diagnostic method for CAN is unknown., Methods: This was a single center, observational study in a cohort of patients with DM as a part of the Cardiovascular Disease in Patients with Diabetes: The Silesia Diabetes-Heart Project (NCT05626413). To diagnose CAN, we used standard CV autonomic reflex tests. In this analysis we implemented AI-based deep learning techniques with non-mydriatic 5-field color fundus imaging to identify patients with CAN. Two experiments have been developed utilizing Multiple Instance Learning and primarily ResNet 18 as the backbone network. Models underwent training and validation prior to testing on an unseen image set., Results: In an analysis of 2275 retinal images from 229 patients, the ResNet 18 backbone model demonstrated robust diagnostic capabilities in the binary classification of CAN, correctly identifying 93% of CAN cases and 89% of non-CAN cases within the test set. The model achieved an area under the receiver operating characteristic curve (AUCROC) of 0.87 (95% CI 0.74-0.97). For distinguishing between definite or severe stages of CAN (dsCAN), the ResNet 18 model accurately classified 78% of dsCAN cases and 93% of cases without dsCAN, with an AUCROC of 0.94 (95% CI 0.86-1.00). An alternate backbone model, ResWide 50, showed enhanced sensitivity at 89% for dsCAN, but with a marginally lower AUCROC of 0.91 (95% CI 0.73-1.00)., Conclusions: AI-based algorithms utilising retinal images can differentiate with high accuracy patients with CAN. AI analysis of fundus images to detect CAN may be implemented in routine clinical practice to identify patients at the highest CV risk., Trial Registration: This is a part of the Silesia Diabetes-Heart Project (Clinical-Trials.gov Identifier: NCT05626413)., (© 2024. The Author(s).)

Background: Obesity has been linked to arterial stiffness, while no consensus was reached on the association. We aimed to clarify the association of general and central obesity with arterial stiffness by combining observational studies and Mendelian randomization (MR) study., Methods: Two cross-sectional studies were performed in UK Biobank and Fuqing Cohort, respectively. Two-sample MR study was conducted using summary data of GWASs from GIANT consortium and UK Biobank. General obesity and central obesity were measured using body mass index (BMI) and waist circumference (WC), respectively. Arterial stiffness was measured by arterial stiffness index (ASI) in UK Biobank or branchial-ankle pulse wave velocity (baPWV) in Fuqing Cohort., Results: Two observational studies found a consistent positive association of BMI and WC with arterial stiffness when adjusting for age, sex, education, smoking, alcohol drinking, physical activity, and LDL cholesterol. However, when additionally adjusting for metabolic traits (i.e., systolic blood pressure, diastolic blood pressure, blood glucose, triglycerides, high-density lipoprotein cholesterol, and WC or BMI), the association with BMI changed to be inverse. As compared to the lowest quintile group, the adjusted ORs across groups of second to fifth quintile were 0.93, 0.90, 0.83, and 0.72 in UK Biobank and 0.88, 0.65, 0.63, and 0.50 in Fuqing Cohort. In contrast, the positive relationship with WC remained stable with the adjusted ORs of 1.23, 1.46, 1.60, and 1.56 in UK Biobank and 1.35, 1.44, 1.77, and 1.64 in Fuqing Cohort. MR analyses provided supportive evidence of the negative association with BMI (OR = 0.97, 95%CI = 0.94-1.00) and the positive association with WC (OR = 1.14, 95%CI = 1.08-1.20)., Conclusions: Observational and genetic analyses provide concordant results that central obesity is independently related to arterial stiffness, while the role of general obesity depends on metabolic status., (© 2024. The Author(s).)

Objective: Laparoscopic choledochectomy and hepatojejunostomy have been reported in children since 1995, but this procedure is technically demanding. Robotic surgical systems can simplify complex minimally invasive procedures. Currently, few reports have been made on neonates. We present the experience of 6 cases of neonatal CC(choledochal cysts)., Study Design: Between January 2022 and December 2023, 6 neonates underwent robotic resection of choledochal cyst and hepaticojejunostomy using the Da Vinci surgical system at Children's Hospital, Zhejiang University School of Medicine, a high-volume hepatobiliary disease center. demographic data of the patients and surgical outcomes were collected and analyzed., Results: All 6 patients were successfully treated by robotic cystectomy and hepaticojejunostomy. The mean age was 17.3 days (range 4-25) and the mean weight was 3.6 kg (range 2.55-4.4). 5 cysts were type Ia and 1 was type Iva. The mean diameter of the cysts was 3.8 cm (range 1.25-5). The mean time to establish feeding was 4.83 days (range 4-6), and patients were discharged after a median time of 16.83 days (range 7-42) without postoperative complications., Conclusions: This procedure is safe and effective for neonates. The authors found that the use of robot-assisted surgery has ergonomic advantages in this delicate, minimally invasive procedure., (© 2024. The Author(s).)

Background: Patients with lung adenocarcinoma (LUAD) have a low response rate to immune checkpoint blockade. It is highly important to explore the tumor immune escape mechanism of LUAD patients and expand the population of patients who may benefit from immunotherapy., Methods: Based on 954 bulk RNA-seq data of LUAD patients and 15 single-cell RNA-seq data, the relationships between tumor immune dysfunction and exclusion (TIDE) scores and survival prognosis in each patient were calculated and evaluated, and the immune escape mechanism affecting the independent prognosis of LUAD patients was identified. Functional enrichment analysis explored the antitumour immune response and biological behavior of tumor cells among different LUAD groups. Single-cell annotation and pseudotemporal analysis were used to explore the target molecules and immune escape mechanisms of LUAD., Results: Myeloid-derived suppressor cells (MDSCs) and IRF8 were identified as risk and protective factors for the independent prognosis of LUAD patients, respectively. In the tumor microenvironment of patients with high infiltration of MDSCs, the antitumor immune response is significantly suppressed, while tumor cell division, proliferation, and distant metastasis are significantly enhanced. Single-cell RNA-seq analysis revealed that IRF8 is an important regulator of MDSC differentiation in LUAD myeloid cells. In addition, IRF8 may regulate the differentiation of MDSCs through the IL6-JAK-STAT3 signalling pathway., Conclusions: IRF8 deficiency impairs the normal development of LUAD myeloid cells and induces their differentiation into MDSCs, thereby accelerating the immune escape of LUAD cells. IRF8-targeted activation to inhibit the formation of MDSCs may be a new target for immunotherapy in LUAD., (© 2024. The Author(s).)

In this article, we read with great attention the correspondence by Bullement et al., regarding our published study on cost-effectiveness of first-line immunotherapy combinations with or without chemotherapy for advanced non-small cell lung cancer. We referred to a few the most important comments from Bullement et al. in our opinion, including proportional hazard (PH) assumption, accelerated failure time (AFT) model, and health utility, and made some explanations., (© 2024. The Author(s).)

Background: Many effective therapies for psoriasis are being applied in clinical practice in recent years, however, some patients still can't achieve satisfied effect even with biologics. Therefore, it is crucial to identify factors associated with the treatment efficacy among psoriasis patients. This study aims to explore factors influencing the treatment efficacy of psoriasis patients based on decision tree model and logistic regression., Methods: We implemented an observational study and recruited 512 psoriasis patients in Shanghai Skin Diseases Hospital from 2021 to 2022. We used face-to-face questionnaire interview and physical examination to collect data. Influencing factors of treatment efficacy were analyzed by using logistic regression, and decision tree model based on the CART algorithm. The receiver operator curve (ROC) was plotted for model evaluation and the statistical significance was set at P < 0.05., Results: The 512 patients were predominately males (72.1%), with a median age of 47.5 years. In this study, 245 patients achieved ≥ 75% improvement in psoriasis area and severity index (PASI) score in week 8 and was identified as treatment success (47.9%). Logistic regression analysis showed that patients with senior high school and above, without psoriasis family history, without tobacco smoking and alcohol drinking had higher percentage of treatment success in patients with psoriasis. The final decision tree model contained four layers with a total of seventeen nodes. Nine classification rules were extracted and five factors associated with treatment efficacy were screened, which indicated tobacco smoking was the most critical variable for treatment efficacy prediction. Model evaluation by ROC showed that the area under curve (AUC) was 0.79 (95%CI: 0.75 ~ 0.83) both for logistic regression model (0.80 sensitivity and 0.69 specificity) and decision tree model (0.77 sensitivity and 0.73 specificity)., Conclusion: Psoriasis patients with higher education, without tobacco smoking, alcohol drinking and psoriasis family history had better treatment efficacy. Decision tree model had similar predicting effect with the logistic regression model, but with higher feasibility due to the nature of simple, intuitive, and easy to understand., (© 2024. The Author(s).)

The advent of PD1/PD-L1 inhibitors has significantly transformed the therapeutic landscape for clear cell renal cell carcinoma (ccRCC). This review provides an in-depth analysis of the biological functions and regulatory mechanisms of PD1 and PD-L1 in ccRCC, emphasizing their role in tumor immune evasion. We comprehensively evaluate the clinical efficacy and safety profiles of PD1/PD-L1 inhibitors, such as Nivolumab and Pembrolizumab, through a critical examination of recent clinical trial data. Furthermore, we discuss the challenges posed by resistance mechanisms to these therapies and potential strategies to overcome them. We also explores the synergistic potential of combination therapies, integrating PD1/PD-L1 inhibitors with other immunotherapies, targeted therapies, and conventional modalities such as chemotherapy and radiotherapy. In addition, we examine emerging predictive biomarkers for response to PD1/PD-L1 blockade and biomarkers indicative of resistance, providing a foundation for personalized therapeutic approaches. Finally, we outline future research directions, highlighting the need for novel therapeutic strategies, deeper mechanistic insights, and the development of individualized treatment regimens. Our work summarizes the latest knowledge and progress in this field, aiming to provide a valuable reference for improving clinical efficacy and guiding future research on the application of PD1/PD-L1 inhibitors in ccRCC., (© 2024. The Author(s).)

Background: Biotransformation of CO 2 into high-value-added carbon-based products is a promising process for reducing greenhouse gas emissions. To realize the green transformation of CO 2 , we use fatty acids as carbon source to drive CO 2 fixation to produce succinate through a portion of the 3-hydroxypropionate (3HP) cycle in Cupriavidus necator H16., Results: This work can achieve the production of a single succinate molecule from one acetyl-CoA molecule and two CO 2 molecules. It was verified using an isotope labeling experiment utilizing NaH 13 CO 3 . This implies that 50% of the carbon atoms present in succinate are derived from CO 2 , resulting in a twofold increase in efficiency compared to prior methods of succinate biosynthesis that relied on the carboxylation of phosphoenolpyruvate or pyruvate. Meanwhile, using fatty acid as a carbon source has a higher theoretical yield than other feedstocks and also avoids carbon loss during acetyl-CoA and succinate production. To further optimize succinate production, different approaches including the optimization of ATP and NADPH supply, optimization of metabolic burden, and optimization of carbon sources were used. The resulting strain was capable of producing succinate to a level of 3.6 g/L, an increase of 159% from the starting strain., Conclusions: This investigation established a new method for the production of succinate by the implementation of two CO 2 fixation reactions and demonstrated the feasibility of ATP, NADPH, and metabolic burden regulation strategies in biological carbon fixation., (© 2024. The Author(s).)

Background: The efficacy and reliability of erector spinae plane block (ESPB) in posterior open lumbar spine surgery has been demonstrated; however, few randomized controlled trials of lumbar ESPB (L-ESPB) in lumbar unilateral bi-portal endoscopic (UBE) surgery have been reported., Methods: A total of 120 patients, aged 18 to 65 (who underwent elective lumbar UBE surgery under general anesthesia and exhibited an American Society of Anesthesiologists physical status of I to III) were randomly assigned in a 1:1 ratio to the ESPB group and the Control group. Ultrasound(US)-guided unilateral single-shot 0.25% ropivacaine L-ESPB was performed in the ESPB group, but not in the control group. Postoperative analgesic strategy for all patients: patient controlled intravenous analgesia (PCIA, diluted and dosed with fentanyl alone) was initiated immediately after surgery combined with oral compound codeine phosphate and ibuprofen sustained release tablets (1 tablet containing ibuprofen 200 mg and codeine 13 mg, 1 tablet/q12h) commenced 6 h postoperatively. We collected and compared patient-centred correlates intraoperatively and 48 h postoperatively. The primary outcomes were intraoperative and postoperative opioid consumption and postoperative quality of recovery-15 (QoR-15) scores., Results: Compared to the control group (n = 56), the ESPB group (n = 58) significantly reduced intraoperative remifentanil consumption (estimated median difference - 280 mcg, 95% confidence interval [CI] - 360 to - 200, p < 0.001, power = 100%); significantly reduced fentanyl consumption at 24 h postoperatively (estimated median difference - 80mcg, 95%[CI] - 128 to - 32, p = 0.001, power = 90%); and significantly enhanced the QoR-15 score at 24 h postoperatively (estimated median difference 11, 95%[CI] 8 to 14, p < 0.001, power = 100%). Compared to the control group, the ESPB group enhanced the resting numeric rating scale (NRS) score up to 8 h postoperatively, and the active movement NRS score up to 4 h postoperatively. The incidence of postoperative nausea and vomiting (PONV) (p = 0.015, power = 70%), abdominal distension (p = 0.024, power = 64%), and muscular calf vein thrombosis (MCVT) (p = 0.033, power = 58%) was lower in the ESPB group than in the control group. Moreover, the occurrence of L-ESPB related adverse reactions was not found herein., Conclusion: US-guided L-ESPB reduces intraoperative and 24 h postoperative opioid consumption and improves patients' QoR-15 scores at 24 h postoperatively. L-ESPB can be safely and effectively utilized in lumbar UBE surgery., Trial Registration: Chinese Clinical Trial Registry, ChiCTR2200061908 , date of registration: 10/07/2022. Registry URL., (© 2024. The Author(s).)

Background: Colorectal cancer (CRC) is a serious global health burden because of its high morbidity and mortality rates. Hypoxia and massive lactate production are hallmarks of the CRC microenvironment. However, the effects of hypoxia and lactate metabolism on CRC have not been fully elucidated. This study aimed to develop a novel molecular subtyping based on hypoxia-related genes (HRGs) and lactate metabolism-related genes (LMRGs) and construct a signature to predict the prognosis of patients with CRC and treatment efficacy., Methods: Bulk and single-cell RNA-sequencing and clinical data of CRC were downloaded from the TCGA and GEO databases. HRGs and LMRGs were obtained from the Molecular Signatures Database. The R software package DESeq2 was used to perform differential expression analysis. Molecular subtyping was performed using unsupervised clustering. A predictive signature was developed using univariate Cox regression, random forest model, LASSO, and multivariate Cox regression analyses. Finally, the sensitivity of tumor cells to chemotherapeutic agents before and after hypoxia was verified using in vitro experiments., Results: We classified 575 patients with CRC into three molecular subtypes and were able to distinguish their prognoses clearly. The C1 subtype, which exhibits high levels of hypoxia, has a low proportion of CD8 + T cells and a high proportion of macrophages. The expression of immune checkpoint genes is generally elevated in C1 patients with severe immune dysfunction. Subsequently, we constructed a predictive model, the HLM score, which effectively predicts the prognosis of patients with CRC and the efficacy of immunotherapy. The HLM score was validated in GSE39582, GSE106584, GSE17536, and IMvigor210 datasets. Patients with high HLM scores exhibit high infiltration of CD8 + exhausted T cells (Tex), especially terminal Tex, and oxidative phosphorylation (OXPHOS)-Tex in the immune microenvironment. Finally, in vitro experiments confirmed that CRC cell lines were less sensitive to 5-fluorouracil, oxaliplatin, and irinotecan under hypoxic conditions., Conclusion: We constructed novel hypoxia- and lactate metabolism-related molecular subtypes and revealed their immunological and genetic characteristics. We also developed an HLM scoring system that could be used to predict the prognosis and efficacy of immunotherapy in patients with CRC., (© 2024. The Author(s).)

The Wnt/β-catenin signaling pathway plays a crucial role in various physiological processes, encompassing development, tissue homeostasis, and cell proliferation. Under normal physiological conditions, the Wnt/β-catenin signaling pathway is meticulously regulated. However, aberrant activation of this pathway and downstream target genes can occur due to mutations in key components of the Wnt/β-catenin pathway, epigenetic modifications, and crosstalk with other signaling pathways. Consequently, these dysregulations contribute significantly to tumor initiation and progression. Therapies targeting the Wnt/β-catenin signaling transduction have exhibited promising prospects and potential for tumor treatment. An increasing number of medications targeting this pathway are continuously being developed and validated. This comprehensive review aims to summarize the latest advances in our understanding of the role played by the Wnt/β-catenin signaling pathway in carcinogenesis and targeted therapy, providing valuable insights into acknowledging current opportunities and challenges associated with targeting this signaling pathway in cancer research and treatment., (© 2024. The Author(s).)

Background: Robot-assisted total knee arthroplasty (TKA) has been shown to facilitate high-precision bone resection, which is an important goal in TKA. The aim of this cadaveric study was to analyze the accuracy of the target angle and bone resection thickness of a recently introduced robotic TKA system., Methods: This study used 4 frozen cadaveric specimens (8 knees), 2 different implant designs, navigation, and a robotic system. The 4 surgeons who participated in this study were trained and familiar with the basic principles and operating procedures of this system. The angle of the bone cuts performed using the robotic system was compared with the target angles from the intraoperative plan. For each bone cut, the resection thickness was recorded and compared with the planned resection thickness., Results: The mean angular difference for all specimens was less than 1°, and the standard deviation was less than 2°. The mean difference between the planned and measured angles was close to 0 and not significantly different from 0 except for the difference in the frontal tibial component angle, which was 0.88°. The mean difference in the hip-knee-ankle axis angle was - 0.21°± 1.06°. The mean bone resection difference for all specimens was less than 1 mm, and the standard deviation was less than 0.5 mm., Conclusions: The results of the cadaveric experimental study showed that the new TKA system can realize highly accurate bone cuts and achieve planned angles and resection thicknesses. Despite the limitations of small sample sizes and large differences between cadaveric and clinical patients, the accuracy of cadaveric experiments provides strong support for subsequent clinical trials., (© 2024. The Author(s).)

Background: Resistance to immune checkpoint inhibitors (ICIs) represents a major unmet medical need in non-small cell lung cancer (NSCLC) patients. Vascular endothelial growth factor (VEGF) inhibition may reverse a suppressive microenvironment and recover sensitivity to subsequent ICIs., Methods: This phase Ib/IIa, single-arm study, comprised dose-finding (Part A) and expansion (Part B) cohorts. Patients with ICIs-refractory NSCLC were enrolled to receive anlotinib (a multi-target tyrosine kinase inhibitor) orally (from days 1 to 14 in a 21-day cycle) and nivolumab (360 mg every 3 weeks, intravenously) on a 21-day treatment cycle. The first 21-day treatment cycle was a safety observation period (phase Ib) followed by a phase II expansion cohort. The primary objectives were recommended phase 2 dose (RP2D, part A), safety (part B), and objective response rate (ORR, part B), respectively., Results: Between November 2020 and March 2022, 34 patients were screened, and 21 eligible patients were enrolled (6 patients in Part A). The RP2D of anlotinib is 12 mg/day orally (14 days on and 7 days off) and nivolumab (360 mg every 3 weeks). Adverse events (AEs) of any cause and treatment-related AEs (TRAEs) were reported in all treated patients. Two patients (9.5%) experienced grade 3 TRAE. No grade 4 or higher AEs were observed. Serious AEs were reported in 4 patients. Six patients experienced anlotinib interruption and 4 patients experienced nivolumab interruption due to TRAEs. ORR and disease control rate (DCR) was 19.0% and 76.2%, respectively. Median PFS and OS were 7.4 months (95% CI, 4.3-NE) and 15.2 months (95% CI, 12.1-NE), respectively., Conclusion: Our study suggests that anlotinib combined with nivolumab shows manageable safety and promising efficacy signals. Further studies are warranted., Trial Registration: NCT04507906 August 11, 2020., (© 2024. The Author(s).)

Objective: To investigate the efficacy of 125 I seed brachytherapy for non-central pelvic recurrence of cervical cancer after external beam radiotherapy, and to analyze the clinical influential factors., Methods: Between June 2015 and April 2022, 32 patients with 41 lesions were treated with 125 I seed brachytherapy. The seeds were implanted under the guidance of CT and/or 3D-printed template images at a median dose of 100 Gy (range, 80-120 Gy), and the local control rate (LCR) and survival rates were calculated. We used multivariate logistic regression to identify prognosis predictors, and receiver operating characteristic (ROC) curve analysis to determine the optimal cut-off values., Results: The median follow-up was 48.52 months (range, 4-86 months), and the 6-, 12-, and 24-month LCR was 88.0%, 63.2%, and 42.1%, respectively. The 1- and 2-year survival rates were 36% and 33%, respectively, and the median survival time was 13.26 months. No significant adverse events occurred. Multivariate regression analysis showed that tumor diameter, tumor stage, and LCR were independent factors influencing survival. ROC curve analysis showed that the area under the curve for tumor diameter and D90 were 0.765 and 0.542, respectively, with cut-off values of 5.3 cm and 108.5 Gy., Conclusions: The present findings indicate that 125 I seed brachytherapy is feasible for treating non-central pelvic recurrence of cervical cancer after external beam radiotherapy. Further, tumor diameter < 5.3 cm and immediate postoperative D90 > 108.5 Gy were associated with better efficacy., (© 2024. The Author(s).)

Background: China experienced an overwhelming COVID-19 pandemic from middle December 2022 to middle January 2023 after lifting the zero-COVID-19 policy on December 7, 2022. However, the infection rate was less studied. We aimed to investigate the SARS-CoV-2 infection rate in children shortly after discontinuation of the zero-COVID-19 policy., Methods: From February 20 to April 10, 2023, we included 393 children aged 8 months to less than 3 years who did not receive COVID-19 vaccination and 114 children aged 3 to 6 years who received inactivated COVID-19 vaccines based on the convenience sampling in this cross-sectional study. IgG and IgM antibodies against nucleocapsid (N) and subunit 1 of spike (S1) of SARS-CoV-2 (anti-N/S1) were measured with commercial kits (Shenzhen YHLO Biotech, China)., Results: Of the 393 unvaccinated children (1.5 ± 0.6 years; 52.2% boys), 369 (93.9%) were anti-N/S1 IgG positive. Of the 114 vaccinated children (5.3 ± 0.9 years; 48.2% boys), 112 (98.2%) were anti-N/S1 IgG positive. None of the unvaccinated or vaccinated children was anti-N/S1 IgM positive. The median IgG antibody titers in vaccinated children (344.91 AU/mL) were significantly higher than that in unvaccinated children (42.80 AU/mL) (P < 0.0001). The positive rates and titers of anti-N/S1 IgG had no significant difference between boys and girls respectively., Conclusion: Vast majority of children were infected with SARS-CoV-2 shortly after ending zero-COVID-19 policy in China. Whether these unvaccinated infected children should receive COVID-19 vaccine merits further investigation., (© 2024. The Author(s).)

Background: Many randomized controlled trials (RCTs) and network meta-analyses have demonstrated that the progression-free survival (PFS) and overall survival (OS) of advanced non-small cell lung cancer (NSCLC) patients can be improved through combination immunotherapy or monotherapies. However, time-dependent analysis of the treatment effect is currently lacking. Thus, we aimed to evaluate the efficacy of first-line immunotherapy, and establish a hazard ratio function to reflect the time-varying progression or mortality risk of patients with NSCLC., Methods: Seventeen clinical trials were selected based on search strategy. Baseline characteristics, including the age, sex, smoking status, geographical region, and Eastern Cooperative Oncology Group (ECOG) performance status of patients, were balanced, resulting in ten immunotherapies from nine appropriate clinical trials to conduct treatment effect comparison., Results: We found that nivolumab plus ipilimumab (nivo + ipi) improved the PFS and OS over time. The hazard ratio of nivo + ipi, relative to that of pembrolizumab, decreased from 1.11 to 0.36 for PFS, and from 0.93 to 0.49 for OS over a 10-year period. In terms of the response to immunotherapy in patients with different PD-L1 expression levels, patients with PD-L1 > = 50% experienced lower rates of progression and a reduced mortality risk over time. The hazard ratio of patients with PD-L1 > = 50% relative to all of the patients decreased from 0.73 to 0.69 for PFS, and from 0.78 to 0.67 for OS., Conclusions: Based on the fact that time-dependent progression and mortality risk existed during the treatment duration, physicians should select a suitable treatment regimen for patients based on the hazard ratio., (© 2024. The Author(s).)

Background: We aimed to establish a novel method for automatically constructing three-dimensional (3D) median sagittal plane (MSP) for mandibular deviation patients, which can increase the efficiency of aesthetic evaluating treatment progress. We developed a Euclidean weighted Procrustes analysis (EWPA) algorithm for extracting 3D facial MSP based on the Euclidean distance matrix analysis, automatically assigning weight to facial anatomical landmarks., Methods: Forty patients with mandibular deviation were recruited, and the Procrustes analysis (PA) algorithm based on the original mirror alignment and EWPA algorithm developed in this study were used to construct the MSP of each facial model of the patient as experimental groups 1 and 2, respectively. The expert-defined regional iterative closest point algorithm was used to construct the MSP as the reference group. The angle errors of the two experimental groups were compared to those of the reference group to evaluate their clinical suitability., Results: The angle errors of the MSP constructed by the two EWPA and PA algorithms for the 40 patients were 1.39 ± 0.85°, 1.39 ± 0.78°, and 1.91 ± 0.80°, respectively. The two EWPA algorithms performed best in patients with moderate facial asymmetry, and in patients with severe facial asymmetry, the angle error was below 2°, which was a significant improvement over the PA algorithm., Conclusions: The clinical application of the EWPA algorithm based on 3D facial morphological analysis for constructing a 3D facial MSP for patients with mandibular deviated facial asymmetry deformity showed a significant improvement over the conventional PA algorithm and achieved the effect of a dental clinical expert-level diagnostic strategy., (© 2024. The Author(s).)

Background: Rice (Oryza sativa L.) is one of the most important food crops in the world and the application of nitrogen fertilizer is an effective means of ensuring stable and high rice yields. However, excessive application of nitrogen fertilizer not only causes a decline in the quality of rice, but also leads to a series of environmental costs. Nitrogen reutilization is closely related to leaf senescence, and nitrogen deficiency will lead to early functional leaf senescence, whereas moderate nitrogen application will help to delay leaf senescence and promote the production of photosynthetic assimilation products in leaves to achieve yield increase. Therefore, it is important to explore the mechanism by which nitrogen affects rice senescence, to search for genes that are tolerant to low nitrogen, and to delay the premature senescence of rice functional leaves., Results: The present study was investigated the transcriptional changes in flag leaves between full heading and mature grain stages of rice (O. sativa) sp. japonica 'NanGeng 5718' under varying nitrogen (N) application: 0 kg/ha (no nitrogen; 0N), 240 kg/ha (moderate nitrogen; MN), and 300 kg/ha (high nitrogen; HN). Compared to MN condition, a total of 10427 and 8177 differentially expressed genes (DEGs) were detected in 0N and HN, respectively. We selected DEGs with opposite expression trends under 0N and HN conditions for GO and KEGG analyses to reveal the molecular mechanisms of nitrogen response involving DEGs. We confirmed that different N applications caused reprogramming of plant hormone signal transduction, glycolysis/gluconeogenesis, ascorbate and aldarate metabolism and photosynthesis pathways in regulating leaf senescence. Most DEGs of the jasmonic acid, ethylene, abscisic acid and salicylic acid metabolic pathways were up-regulated under 0N condition, whereas DEGs related to cytokinin and ascorbate metabolic pathways were induced in HN. Major transcription factors include ERF, WRKY, NAC and bZIP TF families have similar expression patterns which were induced under N starvation condition., Conclusion: Our results revealed that different nitrogen levels regulate rice leaf senescence mainly by affecting hormone levels and ascorbic acid biosynthesis. Jasmonic acid, ethylene, abscisic acid and salicylic acid promote early leaf senescence under low nitrogen condition, ethylene and ascorbate delay senescence under high nitrogen condition. In addition, ERF, WRKY, NAC and bZIP TF families promote early leaf senescence. The relevant genes can be used as candidate genes for the regulation of senescence. The results will provide gene reference for further genomic studies and new insights into the gene functions, pathways and transcription factors of N level regulates leaf senescence in rice, thereby improving NUE and reducing the adverse effects of over-application of N., (© 2024. The Author(s).)

Background: Epigenetic modifications of histones play important roles in the response of eukaryotic organisms to environmental stress. However, many histone acetyltransferases (HATs), which are responsible for histone acetylation, and their roles in mediating the tick response to cold stress have yet to be identified. In the present study, HATs were molecularly characterized and their associations with the cold response of the tick Haemaphysalis longicornis explored., Methods: HATs were characterized by using polymerase chain reaction (PCR) based on published genome sequences, followed by multiple bioinformatic analyses. The differential expression of genes in H. longicornis under different cold treatment conditions was evaluated using reverse transcription quantitative PCR (RT-qPCR). RNA interference was used to explore the association of HATs with the cold response of H. longicornis., Results: Two HAT genes were identified in H. longicornis (Hl), a GCN5-related N-acetyltransferase (henceforth HlGNAT) and a type B histone acetyltransferase (henceforth HlHAT-B), which are respectively 960 base pairs (bp) and 1239 bp in length. Bioinformatics analysis revealed that HlGNAT and HlHAT-B are unstable hydrophilic proteins characterized by the presence of the acetyltransferase 16 domain and Hat1&#95;N domain, respectively. RT-qPCR revealed that the expression of HlGNAT and HlHAT-B decreased after 3 days of cold treatment, but gradually increased with a longer period of cold treatment. The mortality rate following knockdown of HlGNAT or HlHAT-B by RNA interference, which was confirmed by RT-qPCR, significantly increased (P < 0.05) when H. longicornis was treated at the lowest lethal temperature (- 14 °C) for 2 h., Conclusions: The findings demonstrate that HATs may play a crucial role in the cold response of H. longicornis. Thus further research is warranted to explore the mechanisms underlying the epigenetic regulation of the cold response in ticks., (© 2024. The Author(s).)

Background: One goal of Anterior Cervical Discectomy and Fusion (ACDF) is to restore the loss of intervertebral disc height (IDH) results from the degenerative process. However, the effects of IDH on postoperative dysphagia after ACDF remain unclear., Methods: Based on the results of a one-year telephone follow-up, A total of 217 consecutive patients after single-level ACDF were enrolled. They were divided into dysphagia and non-dysphagia groups. The age, BMI, operation time and blood loss of all patients were collected from the medical record system and compared between patients with and without dysphagia. Radiologically, IDH, spinous process distance (SP) of the operated segment, and C2-7 angle (C2-7 A) were measured preoperatively and postoperatively. The relationship between changes in these radiological parameters and the development of dysphagia was analyzed., Results: Sixty-three (29%) cases exhibited postoperative dysphagia. The mean changes in IDH, SP, and C2-7 A were 2.84 mm, -1.54 mm, and 4.82 degrees, respectively. Changes in IDH (P = 0.001) and changes in C2-7 A (P = 0.000) showed significant differences between dysphagia and non-dysphagia patients. Increased IDH and increased C2-7 A (P = 0.037 and 0.003, respectively) significantly and independently influenced the incidence of postoperative dysphagia. When the change in IDH was ≥ 3 mm, the chance of developing postoperative dysphagia for this patient was significantly greater. No significant relationship was observed between the change in spinous process distance (SP) and the incidence of dysphagia. The age, BMI, operation time and blood loss did not significantly influence the incidence of postoperative dysphagia., Conclusion: The change in IDH could be regarded as a predictive factor for postoperative dysphagia after single-level ACDF., (© 2024. The Author(s).)

Purpose: The debate surrounding factors influencing postoperative flatus and defecation in patients undergoing colorectal resection prompted this study. Our objective was to identify independent risk factors and develop prediction models for postoperative bowel function in patients undergoing colorectal surgeries., Methods: A retrospective analysis of medical records was conducted for patients who undergoing colorectal surgeries at Peking University People's Hospital from January 2015 to October 2021. Machine learning algorithms were employed to identify risk factors and construct prediction models for the time of the first postoperative flatus and defecation. The prediction models were evaluated using sensitivity, specificity, the Youden index, and the area under the receiver operating characteristic curve (AUC) through logistic regression, random forest, Naïve Bayes, and extreme gradient boosting algorithms., Results: The study included 1358 patients for postoperative flatus timing analysis and 1430 patients for postoperative defecation timing analysis between January 2015 and December 2020 as part of the training phase. Additionally, a validation set comprised 200 patients who undergoing colorectal surgeries from January to October 2021. The logistic regression prediction model exhibited the highest AUC (0.78) for predicting the timing of the first postoperative flatus. Identified independent risk factors influencing the time of first postoperative flatus were Age (p < 0.01), oral laxatives for bowel preparation (p = 0.01), probiotics (p = 0.02), oral antibiotics for bowel preparation (p = 0.02), duration of operation (p = 0.02), postoperative fortified antibiotics (p = 0.02), and time of first postoperative feeding (p < 0.01). Furthermore, logistic regression achieved an AUC of 0.72 for predicting the time of first postoperative defecation, with age (p < 0.01), oral antibiotics for bowel preparation (p = 0.01), probiotics (p = 0.01), and time of first postoperative feeding (p < 0.01) identified as independent risk factors., Conclusions: The study suggests that he use of probiotics and early recovery of diet may enhance the recovery of bowel function in patients undergoing colorectal surgeries. Among the various analytical methods used, logistic regression emerged as the most effective approach for predicting the timing of the first postoperative flatus and defecation in this patient population., (© 2024. The Author(s).)

Background: Despite the existence of available therapeutic interventions for HIV-1, this virus remains a significant global threat, leading to substantial morbidity and mortality. Within HIV-1-infected cells, the accessory viral protein r (Vpr) exerts control over diverse biological processes, including cell cycle progression, DNA repair, and apoptosis. The regulation of gene expression through DNA methylation plays a crucial role in physiological processes, exerting its influence without altering the underlying DNA sequence. However, a thorough examination of the impact of Vpr on DNA methylation in human CD4 + T cells has not been conducted., Methods: In this study, we employed base-resolution whole-genome bisulfite sequencing (WGBS), real-time quantitative RCR and western blot to explore the effect of Vpr on DNA methylation of host cells under HIV-1 infection., Results: We observed that HIV-1 infection leads to elevated levels of global DNA methylation in primary CD4 + T cells. Specifically, Vpr induces significant modifications in DNA methylation patterns, particularly affecting regions within promoters and gene bodies. These alterations notably influence genes related to immune-related pathways and olfactory receptor activity. Moreover, Vpr demonstrates a distinct ability to diminish the levels of methylation in histone genes., Conclusions: These findings emphasize the significant involvement of Vpr in regulating transcription through the modulation of DNA methylation patterns. Together, the results of this investigation will considerably enhance our understanding of the influence of HIV-1 Vpr on the DNA methylation of host cells, offer potential avenues for the development of more effective treatments., (© 2024. The Author(s).)

Background: Lenvatinib is widely used in treatment of unresectable hepatocellular carcinoma (uHCC), but the benefit of its combination with immunotherapy needs to be verified. This study evaluated the efficacy and safety of tislelizumab plus lenvatinib in systemic treatment-naïve patients with uHCC., Methods: In this multicenter, single-arm, phase 2 study, systemic treatment-naïve patients with uHCC received tislelizumab 200 mg every three weeks plus lenvatinib (bodyweight ≥ 60 kg: 12 mg; < 60 kg: 8 mg; once daily). Dose-limiting toxicities (DLTs) were evaluated in safety run-in phase to determine whether to enter the expansion phase. The primary endpoint was objective response rate (ORR) assessed by independent review committee (IRC) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1). Based on Simon's two-stage design, > 6 responders were needed in stage 1 (n = 30) to continue the study, and ≥ 18 responders were needed by the end of stage 2 (n = 60) to demonstrate statistical superiority to a historical control of lenvatinib monotherapy., Results: Sixty-four patients were enrolled. No DLTs were reported. The study achieved statistical superiority (p = 0.0003) with 23 responders assessed by IRC per RECIST v1.1 in the first 60 patients of the efficacy evaluable analysis set (n = 62). After a median follow-up of 15.7 months, confirmed ORR and disease control rate were 38.7% (24/62, 95% confidence interval [CI], 26.6-51.9) and 90.3% (56/62, 95% CI, 80.1-96.4), respectively. Median progression-free survival was 8.2 months (95% CI, 6.8-not evaluable). Overall survival rate at 12 months was 88.6% (95% CI, 77.7-94.4). Grade ≥ 3 treatment-related adverse events occurred in 18 (28.1%) patients., Conclusions: Tislelizumab plus lenvatinib demonstrated promising antitumor activity with favourable tolerability as first-line therapy for patients with uHCC., Trial Registration: ClinicalTrials.gov (NCT04401800)., (© 2024. The Author(s).)

Background: The gastric conduit is the most commonly used replacement organ for reconstruction after minimally invasive McKeown esophagectomy. Although the optimal route of gastric conduit remains controversial, the posterior mediastinal route is physiologically preferable but is not without disadvantages. Here, we report the safety and efficacy of a method of gastric conduit reconstruction via the anterior of the pulmonary hilum route., Methods: We have used the anterior of the pulmonary hilum route since 2021. This procedure involves pulling the gastric conduit up through a substernal tunnel between the right thoracic cavity and the abdominal cavity and passing it into the neck via the anterior of the pulmonary hilum route. In this retrospective study, we compared the clinical outcomes between 20 patients who underwent this procedure and 20 patients who underwent the posterior mediastinal route from 2021 to 2022., Results: No mortality was reported in either group. No significant differences were observed between the two groups in duration of surgery, blood loss, incidence of postoperative complications, and postoperative hospital stay. As a result of the anterior of the pulmonary hilum route, the primary tumor bed and lymph node drainage area were effectively bypassed, which facilitates postoperative adjuvant radiotherapy or chemoradiotherapy. The distance of the gastric conduit accompanying the airway was significantly shorter in the anterior of the pulmonary hilum route group., Conclusions: Our method is considered to be a safe and useful technique for the reconstruction of gastric conduit., (© 2024. The Author(s).)

Background: Laryngeal squamous cell carcinoma (LSCC) is one of the most common malignant tumors of the head and neck. Vasculogenic mimicry (VM) is crucial for tumor growth and metastasis and refers to the formation of fluid channels by invasive tumor cells rather than endothelial cells. However, the regulatory mechanisms underlying VM during the malignant progression of LSCC remain largely unknown., Methods: Gene expression and clinical data for LSCC were obtained from the TCGA and Gene GEO (GSE27020) databases. A risk prediction model associated with VM was established using LASSO and Cox regression analyses. Based on their risk scores, patients with LSCC were categorized into high- and low-risk groups. The disparities in immune infiltration, tumor mutational burden (TMB), and functional enrichment between these two groups were examined. The core genes in LSCC were identified using the machine learning (SVM-RFE) and WGCNA algorithms. Subsequently, the involvement of bone morphogenetic protein 2 (BMP2) in VM and metastasis was investigated both in vitro and in vivo. To elucidate the downstream signaling pathways regulated by BMP2, western blotting was performed. Additionally, ChIP experiments were employed to identify the key transcription factors responsible for modulating the expression of BMP2., Results: We established a new precise prognostic model for LSCC related to VM based on three genes: BMP2, EPO, and AGPS. The ROC curves from both TCGA and GSE27020 validation cohorts demonstrated precision survival prediction capabilities, with the nomogram showing some net clinical benefit. Multiple algorithm analyses indicated BMP2 as a potential core gene. Further experiments suggested that BMP2 promotes VM and metastasis in LSCC. The malignant progression of LSCC is promoted by BMP2 via the activation of the PI3K-AKT signaling pathway, with the high expression of BMP2 in LSCC resulting from its transcriptional activation by runt-related transcription factor 1 (RUNX1)., Conclusion: BMP2 predicts poor prognosis in LSCC, promotes LSCC VM and metastasis through the PI3K-AKT signaling pathway, and is transcriptionally regulated by RUNX1. BMP2 may be a novel, precise, diagnostic, and therapeutic biomarker of LSCC., (© 2024. The Author(s).)

Background: Cancer-associated fibroblasts (CAFs) drive cancer progression and treatment failure on one hand, while their tumor-restraining functions are also observed on the other. Recent single cell RNA sequencing (scRNA-seq) analyses demonstrates heterogeneity of CAFs and defines molecular subtypes of CAFs, which help explain their different functions. However, it remains unclear whether these CAF subtypes have the same or different biological/clinical implications in prostate cancer (PCa) or other malignancies., Methods: PCa cells were incubated with supernatant from normal fibroblasts and CAFs to assess their effects on cell behaviors. Sequencing, genomic, and clinical data were collected from TCGA, MSKCC, CPGEA and GEO databases. CAF molecular subtypes and total CAF scores were constructed and grouped into low and high groups based on CAF-specific gene expression. Progression free interval (PFI), clinicopathological features, telomere length, immune cell infiltration, drug treatment and somatic mutations were compared among CAF molecular subtypes and low/high score groups., Results: The PCa CAF-derived supernatant promoted PCa cell proliferation and invasion. Based on differentially expressed genes identified by scRNA-seq analyses, we classified CAFs into 6 molecular subtypes in PCa tumors, and each subtype was then categorized into score-high and low groups according to the subtype-specific gene expression level. Such score models in 6 CAF subtypes all predicted PFI. Telomeres were significantly shorter in high-score tumors. The total CAF score from 6 CAF subtypes was also associated with PFI in PCa patients inversely, which was consistent with results from cellular experiments. Immunosuppressive microenvironment occurred more frequently in tumors with a high CAF score, which was characterized by increased CTLA4 expression and indicated better responses to CTLA4 inhibitors. Moreover, this model can also serve as a useful PFI predictor in pan-cancers., Conclusion: By combining scRNA-seq and bulk RNA-seq data analyses, we develop a CAF subtype score system as a prognostic factor for PCa and other cancer types. This model system also helps distinguish different immune-suppressive mechanisms in PCa, suggesting its implications in predicting response to immunotherapy. Thus, the present findings should contribute to personalized PCa intervention., (© 2024. The Author(s).)