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Purpose: The study's objective was to assess the effect of the screw insertion depth into fractured vertebrae in treating thoracolumbar fractures., Materials and Methods: This was a retrospective analysis of 92 patients with thoracolumbar fractures from December 2018 to February 2020. Patients had AO type A2, A3 thoracolumbar fractures. The patients were divided into two groups according to the screw insertion depth. The vertebral wedge angle (VWA), Cobb angle (CA), anterior vertebral body height (AVBH), middle vertebral body height (MVBH), visual analog scale (VAS) score, and Oswestry Disability Index (ODI) were compared preoperatively and at one week and 12 months postoperatively. The correlation between Vertebral height loss and potential risk factors, such as sex, age, BMD and BMI was evaluated., Results: Compared with the preoperative data, the postoperative clinical and radiographic findings were significantly different in both groups, But no significant difference between the two groups at 1 week. At 1 year postoperatively, there was a significant difference in the CA (p < 0.0001), VWA (p = 0.047), AVBH (p < 0.0001), MVBH (p < 0.0001), VAS score (p < 0.0001), and ODI (p < 0.0001) between the two groups, Except for age, bone density and other influencing factors the long screw group had better treatment results than the short screw group., Conclusion: A longer screw provides greater grip on the fractured vertebral body and stronger support to the vertebral plate. The optimal screw placement depth exceeds 60% of the vertebral body length on the lateral view., (© 2024. The Author(s).)

Background: The type II based CRISPR-Cas system remains restrictedly utilized in archaea, a featured domain of life that ranks parallelly with Bacteria and Eukaryotes. Methanococcus maripaludis, known for rapid growth and genetic tractability, serves as an exemplary model for studying archaeal biology and exploring CO 2- based biotechnological applications. However, tools for controlled gene regulation remain deficient and CRISPR-Cas tools still need improved in this archaeon, limiting its application as an archaeal model cellular factory., Results: This study not only improved the CRISPR-Cas9 system for optimizing multiplex genome editing and CRISPR plasmid construction efficiencies but also pioneered an effective CRISPR interference (CRISPRi) system for controlled gene regulation in M. maripaludis. We developed two novel strategies for balanced expression of multiple sgRNAs, facilitating efficient multiplex genome editing. We also engineered a strain expressing Cas9 genomically, which simplified the CRISPR plasmid construction and facilitated more efficient genome modifications, including markerless and scarless gene knock-in. Importantly, we established a CRISPRi system using catalytic inactive dCas9, achieving up to 100-fold repression on target gene. Here, sgRNAs targeting near and downstream regions of the transcription start site and the 5'end ORF achieved the highest repression efficacy. Furthermore, we developed an inducible CRISPRi-dCas9 system based on TetR/tetO platform. This facilitated the inducible gene repression, especially for essential genes., Conclusions: Therefore, these advancements not only expand the toolkit for genetic manipulation but also bridge methodological gaps for controlled gene regulation, especially for essential genes, in M. maripaludis. The robust toolkit developed here paves the way for applying M. maripaludis as a vital model archaeal cell factory, facilitating fundamental biological studies and applied biotechnology development of archaea., (© 2024. The Author(s).)

Background: Minimally invasive glaucoma surgery (MIGS) has experienced a surge in popularity in recent years. Glaucoma micro-stents serve as the foundation for these minimally invasive procedures. Nevertheless, the utilization of these stents still presents certain short-term and long-term complications. This study aims to elucidate the creation of a novel drainage stent implant featuring a diverging channel, produced through microfluidic template processing technology. Additionally, an analysis of the mechanical properties, biocompatibility, and feasibility of implantation is conducted., Results: The stress concentration value of the proposed stent is significantly lower, approximately two to three times smaller, compared to the currently available commercial XEN gel stent. This indicates a stronger resistance to bending in theory. Theoretical calculations further reveal that the initial drainage efficiency of the gradient diverging drainage stent is approximately 5.76 times higher than that of XEN stents. Notably, in vivo experiments conducted at the third month demonstrate a favorable biocompatibility profile without any observed cytotoxicity. Additionally, the drainage stent exhibits excellent material stability in an in vitro simulation environment., Conclusions: In summary, the diverging drainage stent presents a novel approach to the cost-effective and efficient preparation process of minimally invasive glaucoma surgery (MIGS) devices, offering additional filtering treatment options for glaucoma., (© 2024. The Author(s).)

Objective: To construct a nutrition support program for middle-aged and elderly patients with acute decompensated heart failure (ADHF) during hospitalization., Methods: Based on the JBI Evidence-Based Health Care Model as the theoretical framework, the best evidence was extracted through literature analysis and a preliminary nutrition support plan for middle-aged and elderly ADHF patients during hospitalization was formed. Two rounds of expert opinion consultation were conducted using the Delphi method. The indicators were modified, supplemented and reduced according to the expert's scoring and feedback, and the expert scoring was calculated., Results: The response rates of the experts in the two rounds of consultation were 86.7% and 100%, respectively, and the coefficient of variation (CV) for each round was between 0.00% and 29.67% (all < 0.25). In the first round of expert consultation, 4 items were modified, 3 items were deleted, and 3 items were added. In the second round of the expert consultation, one item was deleted and one item was modified. Through two rounds of expert consultation, expert consensus was reached and a nutrition support plan for ADHF patients was finally formed, including 4 first-level indicators, 7 s-level indicators, and 24 third-level indicators., Conclusion: The nutrition support program constructed in this study for middle-aged and elderly ADHF patients during hospitalization is authoritative, scientific and practical, and provides a theoretical basis for clinical development of nutrition support program for middle-aged and elderly ADHF patients during hospitalization., (© 2024. The Author(s).)

Background: Herpetospermum pedunculosum (Ser.) C. B. Clarke is a traditional Chinese herbal medicine that heavily relies on the lignans found in its dried ripe seeds (Herpetospermum caudigerum), which have antioxidant and hepatoprotective functions. However, little is known regarding the lignan biosynthesis in H. pedunculosum. In this study, we used metabolomic (non-targeted UHPLC-MS/MS) and transcriptome (RNA-Seq) analyses to identify key metabolites and genes (both structural and regulatory) associated with lignan production during the green mature (GM) and yellow mature (YM) stages of H. pedunculosum., Results: The contents of 26 lignan-related metabolites and the expression of 30 genes involved in the lignan pathway differed considerably between the GM and YM stages; most of them were more highly expressed in YM than in GM. UPLC-Q-TOF/MS confirmed that three Herpetospermum-specific lignans (including herpetrione, herpetotriol, and herpetin) were found in YM, but were not detected in GM. In addition, we proposed a lignan biosynthesis pathway for H. pedunculosum based on the fundamental principles of chemistry and biosynthesis. An integrated study of the transcriptome and metabolome identified several transcription factors, including HpGAF1, HpHSFB3, and HpWOX1, that were highly correlated with the metabolism of lignan compounds during seed ripening. Furthermore, functional validation assays revealed that the enzyme 4-Coumarate: CoA ligase (4CL) catalyzes the synthesis of hydroxycinnamate CoA esters., Conclusion: These results will deepen our understanding of seed lignan biosynthesis and establish a theoretical basis for molecular breeding of H. pedunculosum., (© 2024. The Author(s).)

Background: Numerous previous reports have demonstrated the efficacy of Lactic acid bacteria (LAB) in promoting growth and preventing disease in animals. In this study, Enterococcus faecium ZJUIDS-R1 and Ligilactobaciiius animalis ZJUIDS-R2 were isolated from the feces of healthy rabbits, and both strains showed good probiotic properties in vitro. Two strains (10 8 CFU/ml/kg/day) were fed to weaned rabbits for 21 days, after which specific bacterial infection was induced to investigate the effects of the strains on bacterial diarrhea in the rabbits., Results: Our data showed that Enterococcus faecium ZJUIDS-R1 and Ligilactobaciiius animalis ZJUIDS-R2 interventions reduced the incidence of diarrhea and systemic inflammatory response, alleviated intestinal damage and increased antibody levels in animals. In addition, Enterococcus faecium ZJUIDS-R1 restored the flora abundance of Ruminococcaceae1. Ligilactobaciiius animalis ZJUIDS-R2 up-regulated the flora abundance of Adlercreutzia and Candidatus Saccharimonas. Both down-regulated the flora abundance of Shuttleworthia and Barnesiella to restore intestinal flora balance, thereby increasing intestinal short-chain fatty acid content., Conclusions: These findings suggest that Enterococcus faecium ZJUIDS-R1 and Ligilactobaciiius animalis ZJUIDS-R2 were able to improve intestinal immunity, produce organic acids and regulate the balance of intestinal flora to enhance disease resistance and alleviate diarrhea-related diseases in weanling rabbits., (© 2024. The Author(s).)

Background: Triple-negative breast cancer (TNBC) is a life-threatening subtype of breast cancer with limited treatment options. Therefore, this network meta-analysis (NMA) aimed to evaluate and compare the effect of various neoadjuvant chemotherapy (NCT) options on the long-term survival of patients with TNBC., Methods: PubMed, Embase, Medline, Cochrane Library, Web of Science, and major international conference databases were systematically searched for randomized controlled trials (RCTs) on the efficacy of various NCT options in patients with TNBC. Searches were performed from January 2000 to June 2023. Study heterogeneity was assessed using the I 2 statistic. Hazard ratios (HRs) and 95% confidence intervals (CIs) were used to evaluate disease-free survival (DFS) and overall survival (OS). Odds ratios (ORs) and 95% CIs were used to evaluate the pathologic complete response (pCR). The primary outcome was DFS., Results: We conducted an NMA of 21 RCTs involving 8873 patients with TNBC. Our study defined the combination of anthracyclines and taxanes as the preferred treatment option. On this basis, the addition of any of the following new drugs is considered a new treatment option: bevacizumab (B), platinum (P), poly-ADP-ribose polymerase inhibitors (PARPi), and immune checkpoint inhibitor (ICI). Based on the surface under the cumulative ranking curve (SUCRA) values, the top three SUCRA area values of DFS were taxanes, anthracycline, and cyclophosphamide (TAC; 89.23%); CT (84.53%); and B (81.06%). The top three SUCRA area values of OS were CT (83.70%), TAC (62.02%), and B-containing regimens (60.06%). The top three SUCRA area values of pCR were B + P-containing regimens (82.7%), ICI + P-containing regimens (80.2%), and ICI-containing regimens (61.8%)., Conclusions: This NMA showed that standard chemotherapy is a good choice with respect to long-term survival. Moreover, B associated with P-containing regimens is likely to be the optimal treatment option for neoadjuvant TNBC in terms of pCR., (© 2024. The Author(s).)

Background: Treacher Collins syndrome (TCS; OMIM 154500) is a craniofacial developmental disorder., Methods: To investigate the genetic features of a four-generation Chinese family with TCS, clinical examinations, hearing tests, computed tomography, whole-exome sequencing (WES), Sanger sequencing, reverse transcription (RT)-PCR, and the Minigene assay were performed., Results: The probands, an 11-year-old male and his cousin exhibited typical clinical manifestations of TCS including conductive hearing loss, downward slanting palpebral fissures, and mandibular hypoplasia. Computed tomography revealed bilateral fusion of the anterior and posterior stapedial crura and malformation of the long crura of the incus. WES of both patients revealed a novel heterozygous intronic variant, i.e., c.4342 + 5&#95;4342 + 8delGTGA (NM&#95;001371623.1) in TCOF1. Minigene expression analysis revealed that the c.4342 + 5&#95;4342 + 8delGTGA variant in TCOF1 caused a partial deletion of exon 24 (c.4115&#95;4342del: p.Gly1373&#95;Arg1448del), which was predicted to yield a truncated protein. The deletion was further confirmed via RT-PCR and sequencing of DNA from proband blood cells. A heterozygous variant in the POLR1C gene (NM&#95;203290; exon6; c.525delG) was found almost co-segregated with the TCOF1 pathogenic variant., Conclusions: In conclusion, we identified a heterozygous TCOF1 splicing variant c.4342 + 5&#95;4342 + 8delGTGA (splicing) in a Chinese TSC family with ossicular chain malformations and facial anomalies. Our findings broadened the spectrum of TCS variants and will facilitate diagnostics and prognostic predictions., (© 2024. The Author(s).)

Objective: To observe the long-term effects of total hysterectomy on urinary function, evaluate the effects of preoperative nutritional status, urinary occult infection, and surgical factors on the induction of postoperative stress urinary incontinence (SUI), and explore the incidence and risk factors of SUI., Study Design: From January 2017 to December 2017, 164 patients with benign non-prolapsing diseases who underwent a laparoscopic total hysterectomy in the First People's Hospital of Taicang were selected as the analysis objects. The International Incontinence Standard Questionnaire for Female Lower Urinary Tract Symptoms (ICIQ-FLUTS) and Pelvic Floor Impact Questionnaire-short version 20 (PFDI-20) were used for telephone follow-up to subjectively assess the urinary function of patients, collect their medical records, and statistically analyze the number of postoperative SUI cases. Logistic multivariate analysis was used to analyze the influencing factors of postoperative female SUI, presented as adjusted odds ratios with 95% confidence intervals., Results: Only 97 out of 164 patients completed the ICIQ-FLUTS and PFDI-20 questionnaires. Among these participants, 28 patients (28.86%) were diagnosed with SUI (study group), while 69 patients (71.13%) were classified as women without SUI (control group). The age, menopause, parity ≥ 2 times, Body mass index (BMI) ≥ 28 kg/m 2 , neonatal weight ≥ 4000 g, history of chronic cough, preoperative hemoglobin ≤ 100 g/L, preoperative urine bacteria ≥ 100u/L, preoperative uterine volume ≥ 90 cm 3 , intraoperative blood loss, and operation time of the study group were compared with those of the control group. The differences were statistically significant (P < 0.05). Further Logistic multivariate analysis showed that menopause, preoperative hemoglobin ≤ 100 g/L, preoperative urine bacteria ≥ 100u/L, uterine volume ≥ 90 cm 3 , history of chronic cough, BMI ≥ 28 kg/m 2 were risk factors for postoperative SUI in patients undergoing hysterectomy (P < 0.05)., Conclusions: Hysterectomy for benign non-prolapse diseases has a long-term potential impact on the urinary system of patients, and the risk of postoperative SUI increases. The main risk factors of SUI are parity, menopausal status, obesity, preoperative nutritional status, and occult infection of the urinary system., (© 2024. The Author(s).)

Background: Overweight and obesity are established risk factors for various types of cancers including colorectal cancer (CRC). However the underlying molecular mechanisms remain unclear. An in-depth understanding of the oncologic characteristics of overweight and obese CRC at the single-cell level can provide valuable insights for the development of more effective treatment strategies for CRC., Methods: We conducted single-cell RNA sequencing (scRNA-seq) analysis on tumor and adjacent normal colorectal samples from 15 overweight/obese and 15 normal-weight CRC patients. Immunological and metabolic differences between overweight/obese CRC and non-obese CRC were characterized., Results: We obtained single-cell transcriptomics data from a total of 192,785 cells across all samples. By evaluating marker gene expression patterns, we annotated nine main cell types in the CRC ecosystem. Specifically, we found that the cytotoxic function of effector T cells and NK cells was impaired in overweight/obese CRC compared with non-obese CRC, relating to its metabolic dysregulation. CD4 + T cells in overweight/obese CRC exhibited higher expression of immune checkpoint molecules. The antigen-presenting ability of DCs and B cells is down-regulated in overweight/obese CRC, which may further aggravate the immunosuppression of overweight/obese CRC. Additionally, dysfunctional stromal cells were identified, potentially promoting invasion and metastasis in overweight/obese CRC. Furthermore, we discovered the up-regulated metabolism of glycolysis and lipids of tumor cells in overweight/obese CRC, which may impact the metabolism and function of immune cells. We also identified inhibitory interactions between tumor cells and T cells in overweight/obese CRC., Conclusions: The study demonstrated that overweight/obese CRC has a more immunosuppressive microenvironment and distinct metabolic reprogramming characterized by increased of glycolysis and lipid metabolism. These findings may have implications for the development of novel therapeutic strategies for overweight/obese CRC patients., (© 2024. The Author(s).)

Background: Gastric cancer is a highly prevalent cancer type and the underlying molecular mechanisms are not fully understood. Ubiquitin-specific peptidase (USP) 29 has been suggested to regulate cell fate in several types of cancer, but its potential role in gastric carcinogenesis remains unclear., Methods: The expression of USP29 in normal and gastric cancer tissues was analyzed by bioinformatics analysis, immunohistochemistry and immunoblot. Gene overexpression, CRISPR-Cas9 technology, RNAi, and Usp29 knockout mice were used to investigate the roles of USP29 in cell culture, xenograft, and benzo[a]pyrene (BaP)-induced gastric carcinogenesis models. We then delineated the underlying mechanisms using mass spectrometry, co-immunoprecipitation (Co-IP), immunoblot, ubiquitination assay, chromatin immunoprecipitation (ChIP), quantitative real-time PCR (qRT-PCR), and luciferase assays., Results: In this study, we found that USP29 expression was significantly upregulated in gastric cancers and associated with poor patient survival. Ectopic expression of USP29 promoted, while depletion suppressed the tumor growth in vitro and in vivo mouse model. Mechanistically, transcription factor far upstream element binding protein 1 (FUBP1) directly activates USP29 gene transcription, which then interacts with and stabilizes aurora kinase B (AURKB) by suppressing K48-linked polyubiquitination, constituting a FUBP1-USP29-AURKB regulatory axis that medicates the oncogenic role of USP29. Importantly, systemic knockout of Usp29 in mice not only significantly decreased the BaP-induced carcinogenesis but also suppressed the Aurkb level in forestomach tissues., Conclusions: These findings uncovered a novel FUBP1-USP29-AURKB regulatory axis that may play important roles in gastric carcinogenesis and tumor progression, and suggested that USP29 may become a promising drug target for cancer therapy., (© 2024. The Author(s).)

Background: Phasmatodea (stick and leaf insects) play a central role on the debate regarding wing reduction and loss, and its wings are putative reacquisition from secondarily wingless ancestors based solely on extant species. A pivotal taxon in this respect is the species-poor Timematodea, consisting of approximately 21 wingless extant species, which form the sister group of all remaining winged or wingless stick and leaf insects, the Euphasmatodea., Results: Herein, the new fossils of Timematodea from mid-Cretaceous Kachin amber are reported, with winged and wingless species co-occurring. The palaeogeographic distributions of all fossils of Holophasmatodea are summarized, showing their wide paleo-distributions. The phylogenetic analysis based on morphological characters confirms the earliest-diverging lineage of winged Breviala cretacea gen. et sp. nov. in Timematodea, and the possible relationships among all families of Holophasmatodea. These are critical for the reconstruction of patterns of wing evolution in early Phasmatodea., Conclusions: The new fossils suggest that Timematodea once had wings, at least during the mid-Cretaceous. The palaeogeographic occurrences imply that Timematodea probably have been widely distributed since at least the Jurassic. The phylogenetic analysis with the ancestral-state reconstruction of wings indicates that the common ancestors of Holophasmatodea were winged, the reductions and losses of wings among Timematodea and Euphasmatodea have occurred independently since at least the Cretaceous, and the reduction or loss of the forewing earlier than the hind wings., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Mitochondrion is the key respiratory organ and participate in multiple anabolism and catabolism pathways in eukaryote. However, the underlying mechanism of how mitochondrial membrane proteins regulate leaf and grain development remains to be further elucidated., Results: Here, a mitochondria-defective mutant narrow leaf and slender grain 1 (nlg1) was identified from an EMS-treated mutant population, which exhibits narrow leaves and slender grains. Moreover, nlg1 also presents abnormal mitochondria structure and was sensitive to the inhibitors of mitochondrial electron transport chain. Map-based cloning and transgenic functional confirmation revealed that NLG1 encodes a mitochondrial import inner membrane translocase containing a subunit Tim21. GUS staining assay and RT-qPCR suggested that NLG1 was mainly expressed in leaves and panicles. The expression level of respiratory function and auxin response related genes were significantly down-regulated in nlg1, which may be responsible for the declination of ATP production and auxin content., Conclusions: These results suggested that NLG1 plays an important role in the regulation of leaf and grain size development by maintaining mitochondrial homeostasis. Our finding provides a novel insight into the effects of mitochondria development on leaf and grain morphogenesis in rice., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: The increasing prevalence and severity of antimicrobial resistance (AMR) present a major challenge to our healthcare system. Rapid detection of AMR is essential for lifesaving under emergent conditions such as sepsis. The current gold standard phenotypic antibiotic susceptibility testing (AST) takes more than a day to obtain results. Genotypic ASTs are faster (hours) in detecting the presence of resistance genes but require specific probes/knowledge of each AMR gene and do not provide specific information at the phenotype level. To address this unmet challenge, we developed a new rapid phenotypic AST., Result: We designed a new electrochemical biosensor based on the concept of magnetically coupled LC sensors. The engineered LC sensors can be placed in 96-well plates and communicate the reading remotely with a receiver coil for signal analysis. The sensors were validated by monitoring the growth of Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa in the presence and absence of different antibiotics. Drug-resistant strains were used as controls. Bacterial growth was detected within 30 min after inoculation, allowing rapid determination of antibiotic susceptibility at the phenotype level. The sensor also functions in the presence of host proteins when tested with 2% FBS in growth media., Conclusions: With the compatibility with 96-well plates, this label-free rapid 30-min AST has the potential for low-cost applications with simple integration into the existing workflow in clinical settings., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Dendritic spines are the sites of excitatory synapses on pyramidal neurons, and their development is crucial for neural circuits and brain functions. The spine shape, size, or number alterations are associated with neurological disorders, including schizophrenia. DiGeorge syndrome critical region gene 2 (DGCR2) is one of the deleted genes within the 22q11.2 deletion syndrome (22q11DS), which is a high risk for developing schizophrenia. DGCR2 expression was reduced in schizophrenics. However, the pathophysiological mechanism of DGCR2 in schizophrenia or 22q11DS is still unclear., Results: Here, we report that DGCR2 expression was increased during the neurodevelopmental period and enriched in the postsynaptic densities (PSDs). DGCR2-deficient hippocampal neurons formed fewer spines. In agreement, glutamatergic transmission and synaptic plasticity were decreased in the hippocampus of DGCR2-deficient mice. Further molecular studies showed that the extracellular domain (ECD) of DGCR2 is responsible for its transcellular interaction with cell adhesion molecule Neurexin1 (NRXN1) and spine development. Consequently, abnormal behaviors, like anxiety, were observed in DGCR2-deficient mice., Conclusions: These observations indicate that DGCR2 is a novel cell adhesion molecule required for spine development and synaptic plasticity, and its deficiency induces abnormal behaviors in mice. This study provides a potential pathophysiological mechanism of DGCR2 in 22q11DS and related mental disorders., (© 2023. The Author(s).)

Background: Embolization is a common treatment method for tumor-targeting, anti-organ hyper-function, and hemostasis. However, the injection of embolic agents largely depends on the experiences of doctors, and doctors need to work in an X-ray environment that hurts their health. Even for a well-trained doctor, complications such as ectopic embolism caused by excessive embolic agents are always inevitable., Results: This paper established a flow control curve model for embolic injection based on local arterial pressure. The end-vessel network was simplified as a porous media. The hemodynamic changes at different injection velocities and embolization degrees were simulated and analyzed. Sponge, a typical porous medium, was used to simulate the blocking and accumulation of embolic agents by capillary networks in the in vitro experimental platform., Conclusions: The simulation and experimental results show that the local arterial pressure is closely related to the critical injection velocity of the embolic agent reflux at a certain degree of embolization. The feasibility of this method for an automatic embolic injection system is discussed. It is concluded that the model of the flow control curve of embolic injection can effectively reduce the risk of ectopic embolism and shorten the time of embolic injection. The clinical application of this model is of great value in reducing radiation exposure and improving the success rate of interventional embolization., (© 2023. The Author(s).)

Background: Immunocheckpoint inhibitors (ICIs) have been widely used in the clinical treatment of lung cancer. Although clinical studies and trials have shown that patients can benefit significantly after PD-1/PD-L1 blocking therapy, less than 20% of patients can benefit from ICIs therapy due to tumor heterogeneity and the complexity of immune microenvironment. Several recent studies have explored the immunosuppression of PD-L1 expression and activity by post-translational regulation. Our published articles demonstrate that ISG15 inhibits lung adenocarcinoma progression. Whether ISG15 can enhance the efficacy of ICIs by modulating PD-L1 remains unknown., Methods: The relationship between ISG15 and lymphocyte infiltration was identified by IHC. The effects of ISG15 on tumor cells and T lymphocytes were assessed using RT-qPCR and Western Blot and in vivo experiments. The underlying mechanism of PD-L1 post-translational modification by ISG15 was revealed by Western blot, RT-qPCR, flow cytometry, and Co-IP. Finally, we performed validation in C57 mice as well as in lung adenocarcinoma tissues., Results: ISG15 promotes the infiltration of CD4 + T lymphocytes. In vivo and in vitro experiments demonstrated that ISG15 induces CD4 + T cell proliferation and invalidity and immune responses against tumors. Mechanistically, we demonstrated that the ubiquitination-like modifying effect of ISG15 on PD-L1 increased the modification of K48-linked ubiquitin chains thus increasing the degradation rate of glycosylated PD-L1 targeting proteasomal pathway. The expression of ISG15 and PD-L1 was negatively correlated in NSCLC tissues. In addition, reduced accumulation of PD-L1 by ISG15 in mice also increased splenic lymphocyte infiltration as well as promoted cytotoxic T cell infiltration in the tumor microenvironment, thereby enhancing anti-tumor immunity., Conclusions: The ubiquitination modification of PD-L1 by ISG15 increases K48-linked ubiquitin chain modification, thereby increasing the degradation rate of glycosylated PD-L1-targeted proteasome pathway. More importantly, ISG15 enhanced the sensitivity to immunosuppressive therapy. Our study shows that ISG15, as a post-translational modifier of PD-L1, reduces the stability of PD-L1 and may be a potential therapeutic target for cancer immunotherapy., (© 2023. The Author(s).)

Background: This retrospective cohort study aimed to compare the clinical and radiological outcomes between two treatment strategies focusing on non-osteoporotic AOSpine-type A3 fractures of the thoracolumbar spine with neurological deficits at levels T11 to L2., Methods: In total, 67 patients between 18 and 60 years of age who were treated operatively with either of the two treatment strategies were included. One treatment strategy included open posterior stabilization and decompression, whereas the other was based on percutaneous posterior stabilization and decompression via a tubular retraction system. Demographic data, surgical variables, and further parameters were assessed. Patient-reported outcomes (PROs), including the Visual Analog Scale (VAS), the Oswestry Disability Index (ODI), and the American Spinal Injury Association (ASIA) impairment score, were measured to assess functional outcomes. The regional Cobb angle (CA), the anterior height ratio of the fractured vertebrae (AHRV), and the degree of canal encroachment (DCE) were assessed. The ASIA score was used to assess neurological function recovery. The follow-up period was at least 12 months., Results: Surgical time and postoperative hospital stay were significantly shorter in the minimally invasive surgery (MIS) group. Intraoperative blood loss was significantly less in the MIS group. Regarding radiological outcome, CA and AHRV at the time of follow-up did not show a significant difference. DCE at the time of follow-up was significantly improved in the MIS group. Lower VAS scores and better ODIs were observed in the MIS group at the 6-month follow-up, but similar outcomes were observed at the 12-month follow-up. The ASIA score was similar between both groups at the 12-month follow-up., Conclusions: Both treatment strategies are safe and effective; however, MIS could provide earlier pain relief and better functional outcomes compared with OS., (© 2023. The Author(s).)

Background: Next-generation sequencing (NGS) is maturely applied for gene fusion detection. Although tumor fusion burden (TFB) has been identified as an immune marker for cancer, the relationship between these fusions and the immunogenicity and molecular characteristics of gastric cancer (GC) patients remains unclear. GCs have different clinical significance depending on their subtypes, and thus, this study aimed to investigate the characteristics and clinical relevance of TFB in non-Epstein-Barr-virus-positive (EBV+) GC with microsatellite stability (MSS)., Methods: A total of 319 GC patients from The Cancer Genome Atlas stomach adenocarcinoma (TCGA-STAD) and a cohort of 45-case from ENA (PRJEB25780) were included. The cohort characteristics and distribution of TFB among the patients were analyzed. Additionally, the correlations of TFB with mutation characteristics, pathway differences, relative abundance of immune cells, and prognosis were examined in the TCGA-STAD cohort of MSS and non-EBV (+) patients., Results: We observed that in the MSS and non-EBV (+) cohort, the TFB-low group exhibited significantly lower gene mutation frequency, gene copy number, loss of heterozygosity score, and tumor mutation burden than in the TFB-high group. Additionally, the TFB-low group exhibited a higher abundance of immune cells. Furthermore, the immune gene signatures were significantly upregulated in the TFB-low group, 2-year disease-specific survival was markedly increased in the TFB-low group compared with to the TFB-high group. The rates of TFB-low cases were significantly higher TFB-than high cases in durable clinical benefit (DCB) and response groups with pembrolizumab treatment. Low TFB may serve as a predictor of GC prognosis, and the TFB-low group exhibits higher immunogenicity., Conclusion: In conclusion, this study reveals that the TFB-based classification of GC patient may be instructive for individualized immunotherapy regimens., (© 2023. The Author(s).)

Background: Birthing people with pre-pregnancy body mass indices (BMIs) ≥ 25 kg/m 2 , particularly those without prior breastfeeding experience, are at increased risk for suboptimal lactation outcomes. Antenatal milk expression (AME) may be one way to counteract the negative effects of early infant formula supplementation common in this population., Methods: This ongoing, randomized controlled trial in the United States evaluates the efficacy of a telelactation-delivered AME education intervention versus an attention control condition on lactation outcomes to 1 year postpartum among 280 nulliparous-to-primiparous, non-diabetic birthing people with pre-pregnancy BMI ≥ 25 kg/m 2 . The assigned study treatment is delivered via four weekly online video consultations between gestational weeks 37-40. Participants assigned to AME meet with study personnel and a lactation consultant to learn and practice AME. Instructions are provided for home practice of AME between study visits. Control group participants view videos on infant care/development at study visits. Participants complete emailed surveys at enrollment (34 0/7 -36 6/7 gestational weeks) and 2 weeks, 6 weeks, 12 weeks, 6 months, and 12 months postpartum. Surveys assess lactation and infant feeding practices; breastfeeding self-efficacy, attitudes, and satisfaction; perception of insufficient milk; onset of lactogenesis-II; lactation support and problems; and reasons for breastfeeding cessation. Surveys also assess factors associated with lactation outcomes, including demographic characteristics, health problems, birth trauma, racial discrimination, and weight stigma. Health information and infant feeding data are abstracted from the pregnancy and birth center electronic health record. Milk samples are collected from the intervention group at each study visit and from both groups at each postpartum follow-up for future analyses. Qualitative interviews are conducted at 6 weeks postpartum to understand AME experiences. Primary outcomes of interest are breastfeeding exclusivity and breastfeeding self-efficacy scores at 2 weeks postpartum. Outcomes will be examined longitudinally with generalized linear mixed-effects modeling., Discussion: This is the first adequately powered trial evaluating the effectiveness of AME among U.S. birthing people and within a non-diabetic population with pre-pregnancy BMI ≥ 25 kg/m 2 . This study will also provide the first evidence of acceptability and effectiveness of telelactation-delivered AME., Trial Registration: ClinicalTrials.gov: NCT04258709., (© 2023. The Author(s).)

Transfer RNAs (tRNAs) are a class of non-coding RNAs responsible for amino acid translocation during protein synthesis and are ubiquitously found in organisms. With certain modifications and under specific conditions, tRNAs can be sheared and fragmented into small non-coding RNAs, also known as tRNA-derived small RNAs (tDRs). With the development of high-throughput sequencing technologies and bioinformatic strategies, more and more tDRs have been identified and their functions in organisms have been characterized. tRNA and it derived tDRs, have been shown to be essential not only for transcription and translation, but also for regulating cell proliferation, apoptosis, metastasis, and immunity. Aberrant expression of tDRs is associated with a wide range of human diseases, especially with tumorigenesis and tumor progression. The tumor microenvironment (TME) is a complex ecosystem consisting of various cellular and cell-free components that are mutually compatible with the tumor. It has been shown that tDRs regulate the TME by regulating cancer stem cells, immunity, energy metabolism, epithelial mesenchymal transition, and extracellular matrix remodeling, playing a pro-tumor or tumor suppressor role. In this review, the biogenesis, classification, and function of tDRs, as well as their effects on the TME and the clinical application prospects will be summarized and discussed based on up to date available knowledge., (© 2023. The Author(s).)

Background: Post-traumatic massive hemorrhage demands immediately available first-aid supplies with reduced operation time and good surgical compliance. In-situ crosslinking gels that are flexibly adapting to the wound shape have a promising potential, but it is still hard to achieve fast gelation, on-demand adhesion, and wide feasibility at the same time., Methods: A white-light crosslinkable natural milk-derived casein hydrogel bioadhesive is presented for the first time. Benefiting from abundant tyrosine residues, casein hydrogel bioadhesive was synthesized by forming di-tyrosine bonds under white light with a ruthenium-based catalyst. We firstly optimized the concentration of proteins and initiators to achieve faster gelation and higher mechanical strength. Then, we examined the degradation, cytotoxicity, tissue adhesion, hemostasis, and wound healing ability of the casein hydrogels to study their potential to be used as bioadhesives., Result: Rapid gelation of casein hydrogel is initiated with an outdoor flashlight, a cellphone flashlight, or an endoscopy lamp, which facilitates its usage during first-aid and minimally invasive operations. The rapid gelation enables 3D printing of the casein hydrogel and excellent hemostasis even during liver hemorrhage due to section injury. The covalent binding between casein and tissue enables robust adhesion which can withstand more than 180 mmHg blood pressure. Moreover, the casein-based hydrogel can facilitate post-traumatic wound healing caused by trauma due to its biocompatibility., Conclusion: Casein-based bioadhesives developed in this study pave a way for broad and practical application in emergency wound management., (© 2023. The Author(s).)

Background: This study aimed to investigate FAM84B expression in glioma tissues and explore the role of FAM84B in promoting the proliferation of glioma cells and the mechanism of regulating the cell cycle pathways., Methods: The TCGA database was adopted to analyze FAM84B expression in glioma tissues. The FAM84B expression was detected by qRT-PCR in patients with glioma, especially that in glioma cells, U251, LN-229, U98, and U87. Two glioma cell lines U87 and T98 were selected for siRNA transfection, which were divided into si-NC si-FAM84B-1 and si-FAM84B-2 groups. The effect of FAM84B on the proliferation of glioma cells was detected with the MTT experiment and that on the glioma cell cycle was detected with the flow cytometry. The signaling pathways potentially regulated by FAM84B in glioma were analyzed through the bioinformatics analysis. The expression of proteins, Cyclin D1, CDK4, Cdk6, and p21, in the cell cycle-related pathways in cells of each group was detected by the Western blot., Results: TCGA database results showed a significantly higher FAM84B expression in glioma tissues than that in paracancerous tissues. According to the detection of qRT-PCR, FAM84B expressed the highest in the glioma cell line U87 (P < 0.05). Compared with the serum of healthy controls, FAM84B mRNA expression significantly increased in patients with gliomas. And compared with the si-NC group, the proliferation ability of U87 and T98 cells decreased and the cell cycle was blocked in the G0/G1 phase in both si-FAM84B transfection groups (P < 0.05). According to the bioinformatics analysis, FAM84B regulated the cell cycle pathways in glioma. FAM84B siRNA inhibited the expression of key proteins, Cyclin D1, CDK2, CDK4, and Cdk6, of the cell cycle pathways in glioma cells and promoted the expression of P53 and P21 proteins., Conclusions: In conclusion, FAM84B may inhibit the proliferation of glioma cells by regulating the cell cycle pathways., (© 2022. The Author(s).)

Background: The sudden outbreak of COVID-19 in early 2020 pushed the online health-care communities (OHCs) into the public eye in China. However, OHCs is an emerging service model, which still has many problems such as low patient trust and low patient utilization rate. Patients are the users and recipients of web-based medical services, as well as the core of medical services. Thus, based on cue utilization theory, this paper studies combination effect of influencing factors in patients' purchase of web-based medical services through the qualitative comparative analysis method of fuzzy sets (fsQCA)., Methods: This paper discards statistical methods based on variance theory-based relationships between explanatory and explained variables and uses a construct theory-based fuzzy set qualitative comparative analysis (fsQCA) approach to elucidate such complex relationships of patients' online purchasing behavior. We use a crawler to automatically download information from Haodf.com. This study crawled data in August 2020, involving 1210 physicians., Results: Service price, reputation and service quality are the key factors for patients' purchasing behavior. Physician's online reputation, online medical service price, number of published articles, mutual-help group, and appointment registration affect patients' purchasing behavior by means of weighted variation. Only when a high scope of internal attribute-related cue elements and a low scope of external attribute-related cue elements are combined with each other in a specific form, patients will generate purchase behavior., Conclusion: This paper clarifies the complex causes that promote to patients' purchasing behavior of web-based medical services, enriches and develops the relevant theories in the field of consumer purchasing behavior and online health-care communities market research, and has implications for governments, platforms, physicians and patients in the event of web-based medical service purchases., (© 2022. The Author(s).)

Background: Frailty and falls are two adverse characteristics of aging that impair the quality of life of senior people and increase the burden on the healthcare system. Various methods exist to evaluate frailty, but none of them are considered the gold standard. Technological methods have also been proposed to assess the risk of falling in seniors. This study aims to propose an objective method for complementing existing methods used to identify the frail state and risk of falling in older adults., Method: A total of 712 subjects (age: 71.3 ± 8.2 years, including 505 women and 207 men) were recruited from two Japanese cities. Two hundred and three people were classified as frail according to the Kihon Checklist. One hundred and forty-two people presented with a history of falling during the previous 12 months. The subjects performed a 45 s standing balance test and a 20 m round walking trial. The plantar pressure data were collected using a 7-sensor insole. One hundred and eighty-four data features were extracted. Automatic learning random forest algorithms were used to build the frailty and faller classifiers. The discrimination capabilities of the features in the classification models were explored., Results: The overall balanced accuracy for the recognition of frail subjects was 0.75 ± 0.04 (F1-score: 0.77 ± 0.03). One sub-analysis using data collected for men aged > 65 years only revealed accuracies as high as 0.78 ± 0.07 (F1-score: 0.79 ± 0.05). The overall balanced accuracy for classifying subjects with a recent history of falling was 0.57 ± 0.05 (F1-score: 0.62 ± 0.04). The classification of subjects relative to their frailty state primarily relied on features extracted from the plantar pressure series collected during the walking test., Conclusion: In the future, plantar pressures measured with smart insoles inserted in the shoes of senior people may be used to evaluate aspects of frailty related to the physical dimension (e.g., gait and balance alterations), thus allowing assisting clinicians in the early identification of frail individuals., (© 2022. The Author(s).)

Background: Compared to medium-density single nucleotide polymorphism (SNP) data, high-density SNP data contain abundant genetic variants and provide more information for the genetic evaluation of livestock, but it has been shown that they do not confer any advantage for genomic prediction and heritability estimation. One possible reason is the uneven distribution of the linkage disequilibrium (LD) along the genome, i.e., LD heterogeneity among regions. The aim of this study was to effectively use genome-wide SNP data for genomic prediction and heritability estimation by using models that control LD heterogeneity among regions., Methods: The LD-adjusted kinship (LDAK) and LD-stratified multicomponent (LDS) models were used to control LD heterogeneity among regions and were compared with the classical model that has no such control. Simulated and real traits of 2000 dairy cattle individuals with imputed high-density (770K) SNP data were used. Five types of phenotypes were simulated, which were controlled by very strongly, strongly, moderately, weakly and very weakly tagged causal variants, respectively. The performances of the models with high- and medium-density (50K) panels were compared to verify that the models that controlled LD heterogeneity among regions were more effective with high-density data., Results: Compared to the medium-density panel, the use of the high-density panel did not improve and even decreased prediction accuracies and heritability estimates from the classical model for both simulated and real traits. Compared to the classical model, LDS effectively improved the accuracy of genomic predictions and unbiasedness of heritability estimates, regardless of the genetic architecture of the trait. LDAK applies only to traits that are mainly controlled by weakly tagged causal variants, but is still less effective than LDS for this type of trait. Compared with the classical model, LDS improved prediction accuracy by about 13% for simulated phenotypes and by 0.3 to ~ 10.7% for real traits with the high-density panel, and by ~ 1% for simulated phenotypes and by - 0.1 to ~ 6.9% for real traits with the medium-density panel., Conclusions: Grouping SNPs based on regional LD to construct the LD-stratified multicomponent model can effectively eliminate the adverse effects of LD heterogeneity among regions, and greatly improve the efficiency of high-density SNP data for genomic prediction and heritability estimation., (© 2022. The Author(s).)

Introduction: Tobacco hazard is one of the most serious public health problems, accounting for up to 6 million deaths worldwide p.a. We aim to determine the efficacy and safety of acupuncture and/or nicotine replacement therapy on smoking cessation., Methods: We will recruit 96 participants who are willing to quit smoking by acupuncture and/or nicotine replacement therapy in Chengguan, Xigu and Heping Districts, Lanzhou city, for multicenter randomized, double-blind, double-dummy controlled clinical trial. Following obtained the informed consent forms, all eligible participants will be randomly divided into 4 groups: (1) acupuncture combined with nicotine patch, (2) acupuncture combined with sham nicotine patch, (3) sham acupuncture combined with nicotine patch, and (4) sham acupuncture combined with sham nicotine patch. These participants will be treated with different intervention modalities for 8 weeks and then will be followed-up for 8 weeks. The SPSS 26.0 software will be applied to analyze the clinical effects and adverse reactions of different intervention measures for smoking cessation., Discussion: This trial is a prospective, pragmatic, randomized, multicenter trial study protocol. The outcomes will illustrate the efficacy and safety of acupuncture and/or nicotine patches for smoking cessation. Provide smokers with a superior smoking cessation program., Trial Registration: Chinese Clinical Trial Registry ChiCTR2100042912 . Registered on January 31, 2021., (© 2022. The Author(s).)

Background: Low-density lipoprotein receptor-related protein 4 (LRP4) plays a critical role in the central nervous system (CNS), including hippocampal synaptic plasticity, maintenance of excitatory synaptic transmission, fear regulation, as well as long-term potentiation (LTP)., Results: In this study, we found that Lrp4 was highly expressed in layer II of the piriform cortex. Both body weight and brain weight decreased in Lrp4 ECD/ECD mice without TMD (Transmembrane domain) and ICD (intracellular domain) of LRP4. However, in the piriform cortical neurons of Lrp4 ECD/ECD mice, the spine density increased, and the frequency of both mEPSC (miniature excitatory postsynaptic current) and sEPSC (spontaneous excitatory postsynaptic current) was enhanced. Intriguingly, finding food in the buried food-seeking test was prolonged in both Lrp4 ECD/ECD mice and Lrp4 cKO (conditional knockout of Lrp4 in the piriform cortex) mice., Conclusions: This study indicated that the full length of LRP4 in the piriform cortex was necessary for maintaining synaptic plasticity and the integrity of olfactory function., (© 2022. The Author(s).)

Background: Chronic exposure to diesel exhaust has a causal link to cardiovascular diseases in various environmental and occupational settings. Arterial endothelial cell function plays an important role in ensuring proper maintenance of cardiovascular homeostasis and the endothelial cell dysfunction by circulatory inflammation is a hallmark in cardiovascular diseases. Acute exposure to diesel exhaust in controlled exposure studies leads to artery endothelial cells dysfunction in previous study, however the effect of chronic exposure remains unknown., Results: We applied an ex vivo endothelial biosensor assay for serum samples from 133 diesel engine testers (DETs) and 126 non-DETs with the aim of identifying evidence of increased risk for cardiovascular diseases. Environmental monitoring suggested that DETs were exposed to high levels of diesel exhaust aerosol (282.3 μg/m 3 PM 2.5 and 135.2 μg/m 3 elemental carbon). Surprisingly, chronic diesel exhaust exposure was associated with a pro-inflammatory phenotype in the ex vivo endothelial cell model, in a dose-dependent manner with CCL5 and VCAM as most affected genes. This dysfunction was not mediated by reduction in circulatory pro-inflammatory factors but significantly associated with a reduction in circulatory metabolites cGMP and an increase in primary DNA damage in leucocyte in a dose-dependent manner, which also explained a large magnitude of association between diesel exhaust exposure and ex vivo endothelial biosensor response. Exogenous cGMP addition experiment further confirmed the induction of ex vivo biosensor gene expressions in endothelial cells treated with physiologically relevant levels of metabolites cGMP., Conclusion: Serum-borne bioactivity caused the arterial endothelial cell dysfunction may attribute to the circulatory metabolites based on the ex vivo biosensor assay. The reduced cGMP and increased polycyclic aromatic hydrocarbons metabolites-induced cyto/geno-toxic play important role in the endothelial cell dysfunction of workers chronic exposure to diesel exhaust., (© 2022. The Author(s).)

Background: Integrin alpha 2 (ITGA2) has been recently reported to be an oncogene and to play crucial roles in tumor cell proliferation, invasion, metastasis, and angiogenesis. Our previous study showed that ITGA2 was overexpressed in pancreatic cancer and promoted its progression. However, the mechanism of ITGA2 overexpression and other mechanisms for promoting the progression of pancreatic cancer are still unclear., Methods: The GEPIA database was used to confirm the expression of ITGA2 in pancreatic cancer. To verify the influence of ITGA2 and TGF-β on the morphological changes of pancreatic cancer and tumor cell progression, we conduct CCK8 test, plate cloning, flow cytometry experiments and animal experiments. Then we conduct Western blot, RT-qPCR to explore the relationship between ITGA2 and TGF-β, and then find the key molecules which can regulate them by immunoprecipitation, Western blot, RT-qPCR, CHIP, nuclear and cytoplasmic separation test., Results: The results of the present study show that the abnormal activation of KRAS induced the overexpression of ITGA2 in pancreatic cancer. Moreover, ITGA2 expression significantly suppressed the activation of the TGF-β pathway. ITGA2 silencing enhanced the anti-pancreatic cancer proliferation and tumor growth effects of TGF-β. Mechanistically, ITGA2 expression suppressed the activation of the TGF-β pathway by inhibiting the SMAD2 expression transcriptionally. In addition, it interacted with and inhibited the nuclear translocation of TFCP2, which induced the SMAD2 expression as a transcription factor. Furthermore, TFCP2 also induced ITGA2 expression as a transcription factor, and the TFCP2 feedback regulated the ITGA2-TFCP2-SMAD2 pathway., Conclusions: Taken together, these results indicated that ITGA2 expression could inhibit the activation of the TGF-β signaling pathway in pancreatic cancer via the TFCP2-SMAD2 axis. Therefore, ITGA2, by effectively enhancing the anti-cancer effects of TGF- β, might be a potential clinical therapeutic target for pancreatic cancer., (© 2022. The Author(s).)

Background: Current guidelines for second stage management do not provide guidance for community birth providers about when best to transfer women to hospital care for prolonged second stage. Our goal was to increase the evidence base for these providers by: 1) describing the lengths of second stage labor in freestanding birth centers, and 2) determining whether proportions of postpartum women and newborns experiencing complications change as length of second stage labor increases., Methods: This study is a retrospective analysis of de-identified client-level data collected in the American Association of Birth Centers Perinatal Data Registry, including women giving birth in freestanding birth centers January 1, 2007 to December 31, 2016. We plotted proportions of postpartum women and newborns transferred to hospital care against length of the second stage of labor, and assessed significance of these with the Cochran-Armitage test for trend or chi-square test. Secondary maternal and newborn outcomes were compared for dyads with normal and prolonged second stages of labor using Fisher's exact test., Results: Second stage labor exceeded 3 hours for 2.3% of primiparous women and 2 hours for 6.6% of multiparous women. Newborn transfers increased as second stage increased from < 15 minutes to > 2 hours (0.6% to 6.33%, p for trend = 0.0008, for primiparous women, and 1.4% to 10.6%, p for trend < 0.0001, for multiparous women.) Postpartum transfers for multiparous women increased from 1.4% after second stage < 15 minutes to greater than 4% for women after second stage exceeding 2 hours (p for trend < 0.0001.) CONCLUSIONS: Complications requiring hospitalization of postpartum women and newborns become more common as the length of the second stage increases. Birth center guidelines should consider not just presence of progress but also absolute length of time as indications for transfer., (© 2022. The Author(s).)

Background: Tyrosine kinase inhibitors (TKIs) alone and in combination with immune checkpoint inhibitors (ICIs) have been shown to be beneficial for the survival of metastatic renal cell carcinoma (mRCC) patients, but resistance to targeted therapy and ICIs is common in the clinic. Understanding the underlying mechanism is critical for further prolonging the survival of renal cancer patients. Nuclear factor of activated T cell 1 (NFAT1) is expressed in immune and nonimmune cells, and the dysregulation of NFAT1 contributes to the progression of various type of malignant tumors. However, the specific role of NFAT1 in RCC is elusive. As a regulator of the immune response, we would like to systemically study the role of NFAT1 in RCC., Methods: TCGA-KIRC dataset analysis, Western blot analysis and RT-qPCR analysis was used to determine the clinic-pathological characteristic of NFAT1 in RCC. CCK-8 assays, colony formation assays and xenograft assays were performed to examine the biological role of NFAT1 in renal cancer cells. RNA-seq analysis was used to examine the pathways changed after NFAT1 silencing. ChIP-qPCR, coimmunoprecipitation analysis, Western blot analysis and RT-qPCR analysis were applied to explore the mechanism by NAFT1 was regulated in the renal cancer cells., Results: In our study, we found that NFAT1 was abnormally overexpressed in RCC and that NFAT1 overexpression was associated with an unfavorable prognosis. Then, we showed that NFAT1 enhanced tumor growth and regulated the immune response by increasing PD-L1 expression in RCC. In addition, we demonstrated that NFAT1 was stabilized in sunitinib-resistant RCC via hyperactivation of the PI3K/AKT/GSK-3β signaling pathway. Furthermore, our study indicated that downregulation of the expression of FBW7, which promotes NFAT1 degradation, was induced by FOXA1 and SETD2 in sunitinib-resistant RCC. Finally, FBW7 was found to contribute to modulating the immune response in RCC., Conclusions: Our data reveal a novel role for the FBW7/NFAT1 axis in the RCC response to TKIs and ICIs. NFAT1 and its associated signaling pathway might be therapeutic targets for RCC treatment, especially when combined with ICIs and/or TKIs., (© 2022. The Author(s).)

Background: In this study, we aimed to perform a comprehensive analysis on the metagenomic next-generation sequencing for the etiological diagnosis of septic patients, and further to establish optimal read values for detecting common pathogens., Methods: In this single-center retrospective study, septic patients who underwent pathogen detection by both microbial culture and metagenomic next-generation sequencing in the intensive care unit of the Second People's Hospital of Shenzhen from June 24, 2015, to October 20, 2019, were included., Results: A total of 193 patients with 305 detected specimens were included in the final analysis. The results of metagenomic next-generation sequencing showed significantly higher positive rates in samples from disparate loci, including blood, bronchoalveolar lavage fluid, and cerebrospinal fluid, as well as in the determination of various pathogens. The optimal diagnostic reads were 2893, 1825.5, and 892.5 for Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae, respectively., Conclusions: The metagenomic next-generation sequencing is capable of identifying multiple pathogens in specimens from septic patients, and shows significantly higher positive rates than culture-based diagnostics. The optimal diagnostic reads for frequently detected microbes might be useful for the clinical application of metagenomic next-generation sequencing in terms of timely and accurately determining etiological pathogens for suspected and confirmed cases of sepsis due to well-performed data interpretation., (© 2021. The Author(s).)

Background: Immunotherapy is an important treatment in oncology, but only a fraction of patients with head and neck squamous cell carcinoma (HNSCC) benefit from it. Therefore, the aim of this study was to identify predictive biomarkers of immunotherapy response for HNSCC in order to improve treatment outcomes., Methods: Survival analyses and comparative efficacy evaluation were performed to investigate prognostic and therapeutic impact factors in patients with advanced HNSCC following immunotherapy, and to examine the effects of factors including gene mutations, tumor mutational burden (TMB), mutant-allele tumor heterogeneity (MATH), and immune cell infiltration on the survival and efficacy., Results: Anti-PD-1 treatment led to a prolonged overall survival (OS) in HNSCC patients with gene mutations compared with those without the mutations, while no significant difference in the OS was found between the two groups of patients. And no marked association between the MATH value and OS was detected in HNSCC patients, whereas patients with either high TMB scores in tissues and blood or high immune cell infiltration displayed a significantly longer OS. Further analysis with efficacy as the primary endpoint revealed no significant differences in the tissue TMB, blood TMB, and MATH value between the patients who responded to immunotherapy and those who did not. Moreover, no significant differences in the expression percentages of positive immune cells in tumor, stroma, and total regions were identified between the above two groups of patients., Conclusion: HNSCC is characterized by high mutation rate, high mutation burden, and high level of immune cell infiltration, and a subset of HNSCC patients respond to immunotherapy. Here, we showed that high mutation burden and immune cell infiltration may improve the prognosis of HNSCC patients with immunotherapy, while there was no remarkable effect on the efficacy., (© 2021. The Author(s).)

Purpose: Some studies have shown that Immune checkpoint inhibitors (ICIs) have a favorable efficacy in advanced triple negative breast cancer (TNBC) patients, but the results are controversial in neoadjuvant chemotherapy (NACT) stage. The purpose of this study is to evaluate the efficacy and safety after NACT plus ICIs in early TNBC patients., Methods: After searching PubMed, EMBASE, the Cochrane library and several mainly oncology conferences up to 30 January 2021 systematically, and define randomized controlled trials (RCTs) exploring the efficacy and safety of programmed death protein-1/programmed cell death-Ligand 1(PD-1/PD-L1) inhibitors plus neoadjuvant chemotherapy in TNBC patients. The primary endpoint was the pathological complete response (pCR) in intention-to-treat populations (ITT), and the secondary endpoints were event-free survival (EFS) and safety analysis in the ITT populations., Results: Six RCTs (N = 2142) were included in our meta-analysis; NACT plus ICIs increased pCR rates compared with NACT in intention-to-treat (ITT) populations (OR: 1.91; 95% CI: 1.32-2.78, P < 0.001). The pCR rate also increased in both PD-L1 positive (OR: 1.65; 95% CI: 1.26-2.16, P < 0.001) and PD-L1 negative patients (OR: 1.56; 95% CI: 1.04-2.33, P = 0.03), especially in PD-L1 positive patients. The benefit was also observed in nodal-positive populations (OR: 2.52; 95% CI: 1.69-3.77, P < 0.001) and Eastern Cooperative Oncology Group performance-status score (ECOG PS) 0 subgroup (OR: 1.90; 95% CI: 1.42-2.53, P < 0.001). Three RCTs (N = 1615) reported EFS and the results showed that adding PD-1/PD-L1 inhibitors increased EFS (HR 0.65, 95% CI 0.50-0.83, P = 0.0007) in ITT populations with a short follow-up time. In the safety analysis of 2205 patients with early TNBC from five eligible studies, NACT plus ICIs had a higher risk of grade 3-4 diarrhea (OR: 2.54; 95% CI: 1.21-5.32; P = 0.01), any grade of adverse effects(AEs)including vomiting (OR: 1.37; 95% CI: 1.00-1.86; P = 0.05), hyperthyroidism (OR: 6.04; 95% CI: 2.39-15.29; P < 0.001), and hypothyroidism (OR: 5.04; 95% CI: 3.02-8.39; P < 0.001)., Conclusions: PD-1/PD-L1 inhibitors combined with chemotherapy can improve pCR rates and EFS, and with an increased incidence of some immune-related AEs compared with chemotherapy alone. NACT plus ICIs might be an option in patients with in PD-L1 positive and high-risk populations with positive nodal disease early TNBC., (© 2021. The Author(s).)

Background: Nonalcoholic fatty liver disease (NAFLD) is a disorder that extends from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH), which is effectively alleviated by lifestyle intervention. Nevertheless, DNA methylation mechanism underling the effect of environmental factors on NAFLD and NASH is still obscure. The aim of this study was to investigate the effect of exercise and diet intervention in NAFLD and NASH via DNA methylation of GAB2., Methods: Methylation of genomic DNA in human NAFLD was quantified using Infinium Methylation EPIC BeadChip assay after exercise (Ex), low carbohydrate diet (LCD) and exercise plus low carbohydrate diet (ELCD) intervention. The output Idat files were processed using ChAMP package. False discovery rate on genome-wide analysis of DNA methylation (q < 0.05), and cytosine-guanine dinucleotides (CpGs) which are located in promoters were used for subsequent analysis (|Δβ|≥ 0.1). K-means clustering was used to cluster differentially methylated genes according to 3D genome information from Human embryonic stem cell. To quantify DNA methylation and mRNA expression of GRB2 associated binding protein 2 (GAB2) in NASH mice after Ex, low fat diet (LFD) and exercise plus low fat diet (ELFD), MassARRAY EpiTYPER and quantitative reverse transcription polymerase chain reaction were used., Results: Both LCD and ELCD intervention on human NAFLD can induce same DNA methylation alterations at critical genes in blood, e.g., GAB2, which was also validated in liver and adipose of NASH mice after LFD and ELFD intervention. Moreover, methylation of CpG units (i.e., CpG&#95;10.11.12) inversely correlated with mRNA expression GAB2 in adipose tissue of NASH mice after ELFD intervention., Conclusions: We highlighted the susceptibility of DNA methylation in GAB2 to ELFD intervention, through which exercise and diet can protect against the progression of NAFLD and NASH on the genome level, and demonstrated that the DNA methylation variation in blood could mirror epigenetic signatures in target tissues of important biological function, i.e., liver and adipose tissue. Trial registration International Standard Randomized Controlled Trial Number Register (ISRCTN 42622771)., (© 2021. The Author(s).)

Background: T2* cardiovascular magnetic resonance (CMR) is commonly used in the diagnosis of intramyocardial hemorrhage (IMH). For quantifying IMH with T2* CMR, despite the lack of consensus studies, two different methods [subject-specific T2* (ssT2*) and absolute T2* thresholding (aT2* < 20 ms)] are interchangeably used. We examined whether these approaches yield equivalent information., Methods: ST elevation myocardial infarction (STEMI) patients (n = 70) were prospectively recruited for CMR at 4-7 days post revascularization and for 6-month follow up (n = 43). Canines studies were performed for validation purposes, where animals (n = 20) were subject to reperfused myocardial infarction (MI) and those surviving the MI (n = 16) underwent CMR at 7 days and 8 weeks and then euthanized. Both in patients and animals, T2* of IMH and volume of IMH were determined using ssT2* and aT2* < 20 ms. In animals, ex-vivo T2* CMR and mass spectrometry for iron concentration ([Fe] Hemo ) were determined on excised myocardial sections. T2* values based on ssT2* and absolute T2* threshold approaches were independently regressed against [Fe] Hemo and compared. A range of T2* cut-offs were tested to determine the optimized conditions relative to ssT2*., Results: While both approaches showed many similarities, there were also differences. Compared to ssT2*, aT2* < 20 ms showed lower T2* and volume of IMH in patients and animals independent of MI age (all p < 0.005). While T2* determined from both methods were highly correlated against [Fe] Hemo (R 2  = 0.9 for both), the slope of the regression curve for ssT2* was significantly larger as compared to aT2* < 20 ms (0.46 vs. 0.32, p < 0.01). Further, slightly larger absolute T2* cut-offs (patients: 23 ms; animals: 25 ms) showed similar IMH characteristics compared to ssT2*., Conclusion: Current quantification methods have excellent capacity to identify IMH, albeit the T2*of IMH and volume of IMH based on aT2* < 20 ms are smaller compared to ssT2*. Thus the method used to quantify IMH from T2* CMR may influence the diagnosis for IMH., (© 2021. The Author(s).)

Background: Although laccase has a good catalytic oxidation ability, free laccase shows a poor stability. Enzyme immobilization is a common method to improve enzyme stability and endow the enzyme with reusability. Adsorption is the simplest and common method. Modified biochar has attracted great attention due to its excellent performance., Results: In this paper, cetyltrimethylammonium bromide (CTAB)-KOH modified biochar (CKMB) was used to immobilize laccase by adsorption method (laccase@CKMB). Based on the results of the single-factor experiments, the optimal loading conditions of laccase@CKMB were studied with the assistance of Design-Expert 12 and response surface methods. The predicted optimal experimental conditions were laccase dosage 1.78 mg/mL, pH 3.1 and 312 K. Under these conditions, the activity recovery of laccase@CKMB was the highest, reaching 61.78%. Then, the CKMB and laccase@CKMB were characterized by TGA, FT-IR, XRD, BET and SEM, and the results showed that laccase could be well immobilized on CKMB, the maximum enzyme loading could reach 57.5 mg/g. Compared to free laccase, the storage and pH stability of laccase@CKMB was improved greatly. The laccase@CKMB retained about 40% of relative activity (4 °C, 30 days) and more than 50% of relative activity at pH 2.0-6.0. In addition, the laccase@CKMB indicated the reusability up to 6 reaction cycles while retaining 45.1% of relative activity. Moreover, the thermal deactivation kinetic studies of laccase@CKMB showed a lower k value (0.00275 min - 1 ) and higher t 1/2 values (252.0 min) than the k value (0.00573 min - 1 ) and t 1/2 values (121.0 min) of free laccase., Conclusions: We explored scientific and reasonable immobilization conditions of laccase@CKMB, and the laccase@CKMB possessed relatively better stabilities, which gave the immobilization of laccase on this cheap and easily available carrier material the possibility of industrial applications., (© 2021. The Author(s).)

Background: Intramyocardial hemorrhage (IMH) within myocardial infarction (MI) is associated with major adverse cardiovascular events. Bright-blood T2*-based cardiovascular magnetic resonance (CMR) has emerged as the reference standard for non-invasive IMH detection. Despite this, the dark-blood T2*-based CMR is becoming interchangeably used with bright-blood T2*-weighted CMR in both clinical and preclinical settings for IMH detection. To date however, the relative merits of dark-blood T2*-weighted with respect to bright-blood T2*-weighted CMR for IMH characterization has not been studied. We investigated the diagnostic capacity of dark-blood T2*-weighted CMR against bright-blood T2*-weighted CMR for IMH characterization in clinical and preclinical settings., Materials and Methods: Hemorrhagic MI patients (n = 20) and canines (n = 11) were imaged in the acute and chronic phases at 1.5 and 3 T with dark- and bright-blood T2*-weighted CMR. Imaging characteristics (Relative signal-to-noise (SNR), Relative contrast-to-noise (CNR), IMH Extent) and diagnostic performance (sensitivity, specificity, accuracy, area-under-the-curve, and inter-observer variability) of dark-blood T2*-weighted CMR for IMH characterization were assessed relative to bright-blood T2*-weighted CMR., Results: At both clinical and preclinical settings, compared to bright-blood T2*-weighted CMR, dark-blood T2*-weighted images had significantly lower SNR, CNR and reduced IMH extent (all p < 0.05). Dark-blood T2*-weighted CMR also demonstrated weaker sensitivity, specificity, accuracy, and inter-observer variability compared to bright-blood T2*-weighted CMR (all p < 0.05). These observations were consistent across infarct age and imaging field strengths., Conclusion: While IMH can be visible on dark-blood T2*-weighted CMR, the overall conspicuity of IMH is significantly reduced compared to that observed in bright-blood T2*-weighted images, across infarct age in clinical and preclinical settings at 1.5 and 3 T. Hence, bright-blood T2*-weighted CMR would be preferable for clinical use since dark-blood T2*-weighted CMR carries the potential to misclassify hemorrhagic MIs as non-hemorrhagic MIs., (© 2021. The Author(s).)

Background: The development of the minimum clinical important difference (MCID) can make it easier for researchers or doctors to judge the significance of research results and the effect of intervention measures, and improve the evaluation system of efficacy. This paper is aimed to calculate the MCID based on anchor and to develop MCID for esophageal cancer scale (QLICP-ES)., Methods: The item Q29 (How do you evaluate your overall health in the past week with 7 grades answers from 1 very poor to 7 excellent)of EORTC QLQ-C30 was used as the subjective anchor to calculate the score difference between each domain at discharge and admission. MCID was established according to two standards, "one grade difference"(A) and "at least one grade difference"(B), and developed by three methods: anchor-based method, ROC curve method and multiple linear regression models. In terms of anchor-based method, the mean of the absolute value of the difference before and after treatments is MCID. The point with the best sensitivity and specificity-Yorden index at the ROC curve is MCID for ROC curve method. In contrast, the predicted mean value based on a multiple linear regression model and the parameters of each factor is MCID., Results: Most of the correlation coefficients of Q29 and various domains of the QLICP-ES were higher than 0.30. The rank of MCID values determined by different methods and standards were as follows: standard B > standard A, anchor-based method > ROC curve method > multiple linear regression models. The recommended MCID values of physical domain, psychological domain, social domain, common symptom and side-effects domain, the specific domain and the overall of the QLICP-ES were 7.8, 9.7, 4.7, 3.6, 4.3, 2.3 and 2.9, respectively., Conclusion: Different methods have their own advantages and disadvantages, and also different definitions and standards can be adopted according to research purposes and methods. A lot of different MCID values were presented in this paper so that it can be easy and convenient to select by users.

Background: In tibial plateau fractures, the posterolateral segment of the tibia plateau is frequently affected and challenging to treat. Although there are many surgical approaches and fixation methods for the treatment of these fractures, all of these methods have limitations. We designed a new rotational support plate (RSP) and a special pressurizer that can fix the fracture directly via the anterolateral approach. This method is advantageous because it leads to little trauma, involves a simple operation, and has a reliable fixation effect. This study details the technique of treating these fractures with the RSP and special pressurizer and provides the outcomes., Methods: From May 2016 to January 2019, the data of 12 patients with posterolateral tibial plateau fractures treated with the RSP and special pressurizer in our hospital were retrospectively analyzed. Postoperative rehabilitation was advised, knee X-rays were taken at follow-ups, and fracture healing, complications, and knee range of motion were assessed. The Hospital for Special Surgery (HSS) knee score and Knee Injury and Osteoarthritis Outcome Score (KOOS) were used to evaluate knee function at the last follow-up., Results: The average follow-up time of all patients was 16.5 months (range, 12-25 months). The average bony union time was 3.2 months (range, 3-4.5 months). At the last follow-up, the average knee range of motion was 138° (range, 107-145°). The average HSS score was 91 (range, 64-98). The average KOOS Symptoms score was 90 (range, 75-96). The average KOOS Pain score was 91 (range, 72-97). The average KOOS ADL score was 91 (range, 74-97). The average KOOS sport/recreation score was 83 (range, 70-90). The average KOOS QOL score was 88 (range, 69-93). Skin necrosis, incision infections, and fixation failure did not occur during the follow-up period., Conclusions: With our newly designed RSP and special pressurizer, posterolateral tibial plateau fractures can be easily and effectively reduced and fixed through the anterolateral approach, which serves as a novel treatment for posterolateral tibial plateau fractures.

Background: The neuromuscular junction (NMJ) is a peripheral synapse critical to muscle contraction. Like acetylcholine receptors (AChRs), many essential proteins of NMJ are extremely concentrated at the postjunctional membrane. However, the mechanisms of synapse-specific concentration are not well understood; furthermore, it is unclear whether signaling molecules critical to NMJ formation and maintenance are also locally transcribed., Results: We studied the β-gal activity encoded by a lacZ cassette driven by the promoter of the Lrp4 gene. As reported for Lrp4 mRNA, β-gal was in the central region in embryonic muscles and at the NMJ after its formation. However, β-gal was no longer in the central areas of muscle fibers in Lrp4 or MuSK mutant mice, indicating a requirement of Lrp4/MuSK signaling. This phenotype could be rescued by transgenic expression of LRP4 with a transmembrane domain but not soluble ECD in Lrp4 mutant mice. β-gal and AChR clusters were distributed in a broader region in lacZ/ECD than that of heterozygous lacZ/+ mice, indicating an important role of the transmembrane domain in Lrp4 signaling. Synaptic β-gal activity became diffused after denervation or treatment with µ-conotoxin, despite its mRNA was increased, indicating synaptic Lrp4 mRNA enrichment requires muscle activity. β-gal was also diffused in aged mice but became re-concentrated after muscle stimulation. Finally, Lrp4 mRNA was increased in C2C12 myotubes by Wnt ligands in a manner that could be inhibited by RKI-1447, an inhibitor of ROCK in Wnt non-canonical signaling. Injecting RKI-1447 into muscles of adult mice diminished Lrp4 synaptic expression., Conclusions: This study demonstrates that synapse-specific enrichment of Lrp4 mRNA requires a coordinated interaction between Lrp4/MuSK signaling, muscle activity, and Wnt non-canonical signaling. Thus, the study provides a new mechanism for Lrp4 mRNA enrichment. It also provides a potential target for the treatment of NMJ aging and other NMJ-related diseases.

Background: C-C chemokine receptor 2 (CCR2) signaling plays a key role in pain associated with experimental murine osteoarthritis (OA) after destabilization of the medial meniscus (DMM). Here, we aimed to assess if CCR2 expressed by intra-articular sensory neurons contributes to knee hyperalgesia in the early stages of the model., Methods: DMM surgery was performed in the right knee of 10-week-old male wild-type (WT), Ccr2 null, or Ccr2 RFP C57BL/6 mice. Knee hyperalgesia was measured using a Pressure Application Measurement device. CCR2 receptor antagonist (CCR2RA) was injected systemically (i.p.) or intra-articularly (i.a.) at different times after DMM to test its ability to reverse knee hyperalgesia. In vivo Ca 2+ imaging of the dorsal root ganglion (DRG) was performed to assess sensory neuron responses to CCL2 injected into the knee joint cavity. CCL2 protein in the knee was measured by ELISA. Ccr2 RFP mice and immunohistochemical staining for the pan-neuronal marker, protein gene product 9.5 (PGP9.5), or the sensory neuron marker, calcitonin gene-related peptide (CGRP), were used to visualize the location of CCR2 on intra-articular afferents., Results: WT, but not Ccr2 null, mice displayed knee hyperalgesia 2-16 weeks after DMM. CCR2RA administered i.p. alleviated established hyperalgesia in WT mice 4 and 8 weeks after surgery. Intra-articular injection of CCL2 excited sensory neurons in the L4-DRG, as determined by in vivo calcium imaging; responses to CCL2 increased in mice 20 weeks after DMM. CCL2, but not vehicle, injected i.a. rapidly caused transient knee hyperalgesia in naïve WT, but not Ccr2 null, mice. Intra-articular CCR2RA injection also alleviated established hyperalgesia in WT mice 4 and 7 weeks after surgery. CCL2 protein was elevated in the knees of both WT and Ccr2 null mice 4 weeks after surgery. Co-expression of CCR2 and PGP9.5 as well as CCR2 and CGRP was observed in the lateral synovium of naïve mice; co-expression was also observed in the medial compartment of knees 8 weeks after DMM., Conclusions: The findings suggest that CCL2-CCR2 signaling locally in the joint contributes to knee hyperalgesia in experimental OA, and it is in part mediated through direct stimulation of CCR2 expressed by intra-articular sensory afferents.

Background: Sexual dimorphism is widespread in insects. The certain specialized structures may be used as weapons in male-male combats or as ornaments to enhance mating opportunities., Results: We report striking swollen first tarsal segments in two families, four genera and six species of scorpionflies from the Middle Jurassic Yanliao Biota of Northeastern China. Swollen tarsal segments are restricted to male specimens and to hind leg tarsi. The geometric morphometric analyses reveal that the degree of swelling within the orthophlebiid species possessing swollen first metatarsal segments is species-specific, which can be used as a diagnostic character for taxonomic and phylogenetic studies., Conclusions: The new findings indicate that swollen first metatarsal segments are relatively common in the family Orthophlebiidae during the Middle Jurassic. The tarsal swellings are considered to be sexually dimorphic, potentially associated with sexually display by males and/or camouflage of a "nuptial gift" in the mating process.

Background: WD repeat domain 3 (WDR3) is involved in a variety of cellular processes including gene regulation, cell cycle progression, signal transduction and apoptosis. However, the biological role of WDR3 in pancreatic cancer and the associated mechanism remains unclear. We seek to explore the immune-independent functions and relevant mechanism for WDR3 in pancreatic cancer., Methods: The GEPIA web tool was searched, and IHC assays were conducted to determine the mRNA and protein expression levels of WDR3 in pancreatic cancer patients. MTS, colony formation, and transwell assays were conducted to determine the biological role of WDR3 in human cancer. Western blot analysis, RT-qPCR, and immunohistochemistry were used to detect the expression of specific genes. An immunoprecipitation assay was used to explore protein-protein interactions., Results: Our study proved that overexpressed WDR3 was correlated with poor survival in pancreatic cancer and that WDR3 silencing significantly inhibited the proliferation, invasion, and tumor growth of pancreatic cancer. Furthermore, WDR3 activated the Hippo signaling pathway by inducing yes association protein 1 (YAP1) expression, and the combination of WDR3 silencing and administration of the YAP1 inhibitor TED-347 had a synergistic inhibitory effect on the progression of pancreatic cancer. Finally, the upregulation of YAP1 expression induced by WDR3 was dependent on an interaction with GATA binding protein 4 (GATA4), the transcription factor of YAP1, which interaction induced the nuclear translocation of GATA4 in pancreatic cancer cells., Conclusions: We identified a novel mechanism by which WDR3 plays a critical role in promoting pancreatic cancer progression by activating the Hippo signaling pathway through the interaction with GATA4. Therefore, WDR3 is potentially a therapeutic target for pancreatic cancer treatment.

Background: This study was done to observe the incidence of Osteo-line on the femur neck and to explore the clinical application of Osteo-line in osteotomy., Methods: Eighty-nine adult femur specimens were selected to observe the incidence of Osteo-line on the femur neck. From August 2015 to January 2019, a total of 278 patients who completed unilateral hip arthroplasty at the Third Hospital of Hebei Medical University were retrospectively included. Patients who accepted osteotomy via Osteo-line on the femur neck were defined as the experimental group (n = 139), and patients who accepted osteotomy via traditional method (The femoral distance 1.5 cm above the trochanter was retained for osteotomy by visual inspection.) were defined as the control group (n = 139). According to the postoperative pelvic X-ray, Photoshop was used to evaluate the leg length discrepancy (LLD) by the CFR-T-LT method., Results: Among the 89 specimens, the incidence of anterior Osteo-line was 75.28%, and the incidence of posterior Osteo-line was 100%. According to the clinical application results, the incidence of anterior Osteo-line on the femur neck was 80%, and the incidence of posterior Osteo-line was 100%. The Osteo-line was clearer than those on the femoral specimens. Twenty-six cases had LLD greater than 1 cm (9.29%), including 2 cases in the experimental group and 24 cases in the control group. The average postoperative LLD in the experimental group (0.19 ± 0.38 mm) was significantly shorter than in the control group (0.54 ± 0.51 mm)(P = 0.005)., Conclusion: The incidence of Osteo-line on the femur neck was high, and patients who accepted osteotomy via Osteo-line on the femur neck can achieve shorter postoperative LLD than the control group.

Background: Chronic kidney disease (CKD) are associated with acute myocardial infarction (AMI). High-sensitive cardiac troponin (hs-cTn) has been evidenced to enhance the early diagnostic accuracy of AMI, but hs-cTn levels are often chronically elevated in CKD patients, which reduces their diagnostic utility. The aim of this study was to derive optimal cutoff-values of hs-cTn levels in patients with CKD and suspected AMI., Methods: In this retrospective paper, a total of 3295 patients with chest pain (2758 in AMI group and 537 in Non-AMI group) were recruited, of whom 23.1% were had an estimated glomerular filtration rate (eGFR) of < 60 mL min -1 (1.73 m 2 ) -1 . Hs-cTnI values were measured at presentation., Results: AMI was diagnosed in 83.7% of all patients. The optimal value of hs-TnI in diagnosing AMI was 1.15 ng mL -1 , which were higher in males than females comparing different cutoff-values of subgroups divided by age, gender and renal function, and which increased monotonically with decreasing of eGFR because in patients with CKD without AMI, the correlation between hs-cTnI and renal function is low but significant (r 2  = 0.067, P < 0.001)., Conclusions: Different optimal cutoff-values of hs-cTnI in the diagnosis of AMI in patients with CKD were helpful to the clinical diagnosis of AMI in various populations and were higher in males than females, but which was needed to be validated by multicenter randomized controlled clinical studies in the future.