Efficacy of radiofrequency ablation combined with sorafenib for treating liver cancer complicated with portal hypertension and prognostic factors.

BACKGROUND: Patients with liver cancer complicated by portal hypertension present complex challenges in treatment. AIM: To evaluate the efficacy of radiofrequency ablation in combination with sorafenib for improving liver function and its impact on the prognosis of patients with this condition. METHODS: Data from 100 patients with liver cancer complicated with portal hypertension from May 2014 to March 2019 were analyzed and divided into a study group (n = 50) and a control group (n = 50) according to the treatment regimen. The research group received radiofrequency ablation (RFA) in combination with sorafenib, and the control group only received RFA. The short-term efficacy of both the research and control groups was observed. Liver function and portal hypertension were compared before and after treatment. Alpha-fetoprotein (AFP), glypican-3 (GPC-3), and AFP-L3 levels were compared between the two groups prior to and after treatment. The occurrence of adverse reactions in both groups was observed. The 3-year survival rate was compared between the two groups. Basic data were compared between the survival and non-surviving groups. To identify the independent risk factors for poor prognosis in patients with liver cancer complicated by portal hypertension, multivariate logistic regression analysis was employed. RESULTS: When comparing the two groups, the research group's total effective rate (82.00%) was significantly greater than that of the control group (56.00%; P < 0.05). Following treatment, alanine aminotransferase and aspartate aminotransferase levels increased, and portal vein pressure decreased in both groups. The degree of improvement for every index was substantially greater in the research group than in the control group (P < 0.05). Following treatment, the AFP, GPC-3, and AFP-L3 levels in both groups decreased, with the research group having significantly lower levels than the control group (P < 0.05). The incidence of diarrhea, rash, nausea and vomiting, and fatigue in the research group was significantly greater than that in the control group (P < 0.05). The 1-, 2-, and 3-year survival rates of the research group (94.00%, 84.00%, and 72.00%, respectively) were significantly greater than those of the control group (80.00%, 64.00%, and 40.00%, respectively; P < 0.05). Significant differences were observed between the survival group and the non-surviving group in terms of Child-Pugh grade, history of hepatitis, number of tumors, tumor size, use of sorafenib, stage of liver cancer, histological differentiation, history of splenectomy and other basic data (P < 0.05). Logistic regression analysis demonstrated that high Child-Pugh grade, tumor size (6-10 cm), history of hepatitis, no use of sorafenib, liver cancer stage IIIC, and previous splenectomy were independent risk factors for poor prognosis in patients with liver cancer complicated with portal hypertension (P < 0.05). CONCLUSION: Patients suffering from liver cancer complicated by portal hypertension benefit from the combination of RFA and sorafenib therapy because it effectively restores liver function and increases survival rates. The prognosis of patients suffering from liver cancer complicated by portal hypertension is strongly associated with factors such as high Child-Pugh grade, tumor size (6-10 cm), history of hepatitis, lack of sorafenib use, liver cancer at stage IIIC, and prior splenectomy.

The African swine fever virus MGF300-4L protein is associated with viral pathogenicity by promoting the autophagic degradation of IKKß and increasing the stability of IκBα.

African swine fever (ASF) is a highly contagious, often fatal viral disease caused by African swine fever virus (ASFV), which imposes a substantial economic burden on the global pig industry. When screening for the virus replication-regulating genes in the left variable region of the ASFV genome, we observed a notable reduction in ASFV replication following the deletion of the MGF300-4L gene. However, the role of MGF300-4L in ASFV infection remains unexplored. In this study, we found that MGF300-4L could effectively inhibit the production of proinflammatory cytokines IL-1ß and TNF-α, which are regulated by the NF-κB signaling pathway. Mechanistically, we demonstrated that MGF300-4L interacts with IKKß and promotes its lysosomal degradation via the chaperone-mediated autophagy. Meanwhile, the interaction between MGF300-4L and IκBα competitively inhibits the binding of the E3 ligase ß-TrCP to IκBα, thereby inhibiting the ubiquitination-dependent degradation of IκBα. Remarkably, although ASFV encodes other inhibitors of NF-κB, the MGF300-4L gene-deleted ASFV (Del4L) showed reduced virulence in pigs, indicating that MGF300-4L plays a critical role in ASFV pathogenicity. Importantly, the attenuation of Del4L was associated with a significant increase in the production of IL-1ß and TNF-α early in the infection of pigs. Our findings provide insights into the functions of MGF300-4L in ASFV pathogenicity, suggesting that MGF300-4L could be a promising target for developing novel strategies and live attenuated vaccines against ASF.

Isolation and characterization of a pangolin-borne HKU4-related coronavirus that potentially infects human-DPP4-transgenic mice.

We recently detected a HKU4-related coronavirus in subgenus Merbecovirus (named pangolin-CoV-HKU4-P251T) from a Malayan pangolin1. Here we report isolation and characterization of pangolin-CoV-HKU4-P251T, the genome sequence of which is closest to that of a coronavirus from the greater bamboo bat (Tylonycteris robustula) in Yunnan Province, China, with a 94.3% nucleotide identity. Pangolin-CoV-HKU4-P251T is able to infect human cell lines, and replicates more efficiently in cells that express human-dipeptidyl-peptidase-4 (hDPP4)-expressing and pangolin-DPP4-expressing cells than in bat-DPP4-expressing cells. After intranasal inoculation with pangolin-CoV-HKU4-P251, hDPP4-transgenic female mice are likely infected, showing persistent viral RNA copy numbers in the lungs. Progressive interstitial pneumonia developed in the infected mice, characterized by the accumulation of macrophages, and increase of antiviral cytokines, proinflammatory cytokines, and chemokines in lung tissues. These findings suggest that the pangolin-borne HKU4-related coronavirus has a potential for emerging as a human pathogen by using hDPP4.

Ubiquitin-specific peptidase 10 attenuates the ferroptosis to promote thyroid cancer malignancy by facilitating GPX4 via elevating SIRT6.

PURPOSE: Ubiquitin-specific peptidase 10 (USP10) has been found to have oncogenic activity in several human tumors. This study first revealed the exact function of USP10 on the progression of thyroid cancer (THCA) by researching its effect on the ferroptosis. METHODS: USP10 expression in THCA patients was analyzed by online data analysis and in 75 THCA cases was scrutinized by real-time quantitative reverse transcription-polymerase chain reaction and Western blot. Influence of USP10 on the viability, colony formation, migration and invasion of THCA cells was demonstrated by cell counting kit-8, colony formation, wound healing and Transwell invasion assays. Effect of USP10 on the Erastin-induced ferroptosis in THCA cells was evaluated by detecting the ferroptosis-related indicators. Intrinsic mechanism of USP10, glutathione peroxidase 4 (GPX4) and sirtuin 6 (SIRT6) in regulating THCA progression was identified. In vivo xenograft experiment was implemented. RESULTS: USP10 was abundantly expressed in THCA patients, linking to poor outcome. USP10 overexpression enhanced the viability, colony formation, migration and invasion of THCA cells. USP10 mitigated the Erastin-induced ferroptosis in THCA cells, decreased the levels of iron, Fe2+ , malondialdehyde, lipid reactive oxygen species, reduced mitochondrial superoxide level, and increased mitochondrial membrane potential. USP10 facilitated the expression of ferroptosis suppressor GPX4 by elevating SIRT6. Loss of USP10 repressed the in vivo growth of THCA cells. CONCLUSION: USP10 might attenuate the ferroptosis to promote thyroid cancer malignancy by facilitating GPX4 via elevating SIRT6. It might be novel target for the treatment of THCA.

Clonal Hematopoiesis of Indeterminate Potential in Chronic Thromboembolic Pulmonary Hypertension: A Multicenter Study.

BACKGROUND: The pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH) is multifactorial and growing evidence has indicated that hematological disorders are involved. Clonal hematopoiesis of indeterminate potential (CHIP) has recently been associated with an increased risk of both hematological malignancies and cardiovascular diseases. However, the prevalence and clinical relevance of CHIP in patients with CTEPH remains unclear. METHODS: Using stepwise calling on next-generation sequencing data from 499 patients with CTEPH referred to 3 centers between October 2006 and December 2021, CHIP mutations were identified. We associated CHIP with all-cause mortality in patients with CTEPH. To provide insights into potential mechanisms, the associations between CHIP and inflammatory markers were also determined. RESULTS: In total, 47 (9.4%) patients with CTEPH carried at least 1 CHIP mutation at a variant allele frequency of ≥2%. The most common mutations were in DNMT3A, TET2, RUNX1, and ASXL1. During follow-up (mean, 55 months), deaths occurred in 22 (46.8%) and 104 (23.0%) patients in the CHIP and non-CHIP groups, respectively (P<0.001, log-rank test). The association of CHIP with mortality remained robust in the fully adjusted model (hazard ratio, 2.190 [95% CI, 1.257-3.816]; P=0.006). Moreover, patients with CHIP mutations showed higher circulating interleukin-1ß and interleukin-6 and lower interleukin-4 and IgG galactosylation levels. CONCLUSIONS: This is the first study to show that CHIP mutations occurred in 9.4% of patients with CTEPH are associated with a severe inflammatory state and confer a poorer prognosis in long-term follow-up.

Marinicella marina sp. nov. and Marinicella gelatinilytica sp. nov., isolated from coastal sediment, and genome analysis and habitat distribution of the genus Marinicella.

Three Marinicella strains, X102, S1101T and S6413T, were isolated from sediment samples from different coasts of Weihai, PR China. All strains were Gram-stain-negative, rod-shaped and non-motile. The predominant fatty acids of all strains were iso-C15 : 0 and summed feature 3 (C16 : 1 ω7c/C16 : 1 ω6c) and the major polar lipids comprised phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. Strains X102 and S1101T shared 100 % 16S rRNA gene sequence similarity, and strains S1101T/X102 and S6413T had 95.4 % similarity. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between strains S1101T and X102 were 99.9 and 99.2 %, respectively. Strain S1101T had ANI values of 69.1-72.9% and dDDH values of 17.9-20.5 % to members of the genus Marinicella. Strain S6413T had ANI values of 69.1-77.5% and dDDH values of 17.6-21.5 % to members of the genus Marinicella. The results of phylogenetic and comparative genomic analysis showed that the three strains belong to two novel species in the genus Marinicella, and strains X102 and S1101T represented one novel species, and strain S6413T represented another novel species. The result of BOX-PCR and genomic analysis showed that X102 and S1101T were not the same strain. The phylogenetic analyses and genomic comparisons, combined with phylogenetic, phenotypic and chemotaxonomic features, strongly supported that the three strains should be classified as representing two novel species of the genus Marinicella, for which the names Marinicella marina sp. nov. and Marinicella gelatinilytica sp. nov. are proposed, respectively. The type strains of the two novel species are S1101T (=KCTC 92642T=MCCC 1H01359T) and S6413T (=KCTC 92641T=MCCC 1H01362T), respectively. In addition, all previously described isolates of Marinicella were isolated from marine environments, but our study showed that Marinicella is also distributed in non-/low-saline habitats (e.g. animal gut, soil and indoor surface), which broadened our perception of the environmental distribution of Marinicella.

The ideal treatment timing for diabetic retinopathy: the molecular pathological mechanisms underlying early-stage diabetic retinopathy are a matter of concern.

Diabetic retinopathy (DR) is a prevalent complication of diabetes, significantly impacting patients' quality of life due to vision loss. No pharmacological therapies are currently approved for DR, excepted the drugs to treat diabetic macular edema such as the anti-VEGF agents or steroids administered by intraocular route. Advancements in research have highlighted the crucial role of early intervention in DR for halting or delaying disease progression. This holds immense significance in enhancing patients' quality of life and alleviating the societal burden associated with medical care costs. The non-proliferative stage represents the early phase of DR. In comparison to the proliferative stage, pathological changes primarily manifest as microangiomas and hemorrhages, while at the cellular level, there is a loss of pericytes, neuronal cell death, and disruption of components and functionality within the retinal neuronal vascular unit encompassing pericytes and neurons. Both neurodegenerative and microvascular abnormalities manifest in the early stages of DR. Therefore, our focus lies on the non-proliferative stage of DR and we have initially summarized the mechanisms involved in its development, including pathways such as polyols, that revolve around the pathological changes occurring during this early stage. We also integrate cutting-edge mechanisms, including leukocyte adhesion, neutrophil extracellular traps, multiple RNA regulation, microorganisms, cell death (ferroptosis and pyroptosis), and other related mechanisms. The current status of drug therapy for early-stage DR is also discussed to provide insights for the development of pharmaceutical interventions targeting the early treatment of DR.

The mutations on the envelope glycoprotein D contribute to the enhanced neurotropism of the pseudorabies virus variant.

The pseudorabies virus (PRV) TJ strain, a variant of PRV, induces more severe neurological symptoms and higher mortality in piglets and mice than the PRV SC strain isolated in 1980. However, the mechanism underlying responsible for the discrepancy in virulence between these strains remains unclear. Our study investigated the differences in neurotropism between PRV TJ and PRV SC using both in vitro and in vivo models. We discovered that PRV TJ enters neural cells more efficiently than PRV SC. Furthermore, we found that PRV TJ has indistinguishable genomic DNA replication capability and axonal retrograde transport dynamics compared to the PRV SC. To gain deeper insights into the mechanisms underlying these differences, we constructed gene-interchanged chimeric virus constructs and assessed the affinity between envelope glycoprotein B, C, and D (gD) and corresponding receptors. Our findings confirmed that mutations in these envelope proteins, particularly gD, significantly contributed to the heightened attachment and penetration capabilities of PRV TJ. Our study revealed the critical importance of the gDΔR278/P279 and gDV338A in facilitating viral invasion. Furthermore, our observations indicated that mutations in envelope proteins have a more significant impact on viral invasion than on virulence in the mouse model. Our findings provide valuable insights into the roles of natural mutations on the PRV envelope glycoproteins in cell tropism, which sheds light on the relationship between cell tropism and clinical symptoms and offers clues about viral evolution.

3D Chiral Self-Assembling Matrixes for Regulating Polarization of Macrophages and Enhance Repair of Myocardial Infarction.

The regulation of inflammatory response at the site of injury and macrophage immunotherapy is critical for tissue repair. Chiral self-assemblies are one of the most ubiquitous life cues, which is closely related to biological functions, life processes, and even the pathogenesis of diseases. However, the role of supramolecular chiral self-assemblies in the regulation of immune functions in the internal environment of tissues has not been fully explored yet. Herein, 3D supramolecular chiral self-assembling matrixes are prepared to regulate the polarization of macrophages and further enhance the repair of myocardial infarction (MI). Experiments studies show that M-type (left-handed) self-assembling matrixes significantly inhibit inflammation and promote damaged myocardium repair by upregulating M2 macrophage polarization and downstream immune signaling compared with P-type (right-handed), and R-type (non-chirality) self-assembling matrixes. Classical molecular dynamics (MD) simulation demonstrates that M-type self-assembling matrixes display higher stereo-affinity to cellular binding, which enhances the clustering of mechanosensitive integrin ß1 (Itgß1) and activates focal adhesion kinase (FAK) and Rho-associated protein kinase (ROCK), as well as downstream PI3K/Akt1/mTOR signaling axes to promote M2 polarization. This study of designing a 3D chiral self-assembling matrixes microenvironment suitable for regulating the polarization of macrophages will provide devise basis for immunotherapy with biomimetic materials.

The MGF300-2R protein of African swine fever virus is associated with viral pathogenicity by promoting the autophagic degradation of IKKα and IKKß through the recruitment of TOLLIP.

The multigene family genes (MGFs) in the left variable region (LVR) of the African swine fever virus (ASFV) genome have been reported to be involved in viral replication in primary porcine alveolar macrophages (PAMs) and virulence in pigs. However, the exact functions of key MGFs in the LVR that regulate the replication and virulence of ASFV remain unclear. In this study, we identified the MGF300-2R gene to be critical for viral replication in PAMs by deleting different sets of MGFs in the LVR from the highly virulent strain ASFV HLJ/18 (ASFV-WT). The ASFV mutant lacking the MGF300-2R gene (Del2R) showed a 1-log reduction in viral titer, and induced higher IL-1ß and TNF-α production in PAMs than did ASFV-WT. Mechanistically, the MGF300-2R protein was found to interact with and degrade IKKα and IKKß via the selective autophagy pathway. Furthermore, we showed that MGF300-2R promoted the K27-linked polyubiquitination of IKKα and IKKß, which subsequently served as a recognition signal for the cargo receptor TOLLIP-mediated selective autophagic degradation. Importantly, Del2R exhibited a significant reduction in both replication and virulence compared with ASFV-WT in pigs, likely due to the increased IL-1ß and TNF-α, indicating that MGF300-2R is a virulence determinant. These findings reveal that MGF300-2R suppresses host innate immune responses by mediating the degradation of IKKα and IKKß, which provides clues to paving the way for the rational design of live attenuated vaccines to control ASF.

Application of 3D-printed osteotomy guide plates in proximal femoral osteotomy for DDH in children: a retrospective study.

BACKGROUND: Patients with developmental dysplasia of the hip (DDH) have complex proximal femoral deformities, and orthopedic surgery lacks objectivity. Expectations for surgical outcomes are often not achieved, and postoperative problems are common. Using 3D-printed technology in orthopedics offers a novel approach to precise and individualized treatment in modern orthopedics. The aim of this study was to investigate the value of the application of 3D-printed osteotomy guide plates in femoral osteotomy. The clinical indices of femoral osteotomy in children with DDH using 3D-printed osteotomy guide plates were compared with those of traditional osteotomy. METHODS: The clinical data of children with DDH who underwent open reduction and Salter pelvic osteotomy combined with femoral osteotomy from September 2010 to September 2020 were retrospectively collected and analyzed. Based on the inclusion and exclusion criteria, a total of 36 patients were included in the study: 16 in the guide plate group and 20 in the conventional group. Operation time (total), operation time (femoral side), X-ray fluoroscopy times (total), X-ray fluoroscopy times (femoral side) and intraoperative blood loss were analyzed and compared between the two groups. Comparison of treatment-related indicators such as postoperative neck-shaft angle, postoperative anteversion angle, hospitalization time, and hospitalization expenses is made between the two groups. The two groups of patients were evaluated at the last follow-up using the McKay clinical evaluation criteria. RESULTS: Between the two groups, there were significant differences in operation time (total), operation time (femoral side), X-ray fluoroscopy times (total), X-ray fluoroscopy times (femoral side) and intraoperative blood loss (P < 0.05). The postoperative neck-shaft angle, postoperative anteversion angle, hospitalization time and hospitalization expenses did not differ significantly (P > 0.05). The MacKay clinical evaluation did not significantly differ at the most recent follow-up (P > 0.05). CONCLUSIONS: Children with DDH undergoing proximal femoral osteotomy using 3D-printed osteotomy guide plates benefit from a simpler surgical procedure, shorter operative time, less bleeding and less radiation exposure during surgery. This technique is of great clinical value.

Natural Morin-Based Metal Organic Framework Nanoenzymes Modulate Articular Cavity Microenvironment to Alleviate Osteoarthritis.

Osteoarthritis (OA) is always characterized as excessive reactive oxygen species (ROS) inside articular cavity. Mimicking natural metalloenzymes with metal ions as the active centers, stable metal organic framework (MOF) formed by natural polyphenols and metal ions shows great potential in alleviating inflammatory diseases. Herein, a series of novel copper-morin-based MOF (CuMHs) with different molar ratios of Cu2+ and MH were employed to serve as ROS scavengers for OA therapy. As a result, CuMHs exhibited enhanced dispersion in aqueous solution, improved biocompatibility, and efficient ROS-scavenging ability compared to MH. On the basis of H2O2-stimulated chondrocytes, intracellular ROS levels were efficiently declined and cell death was prevented after treated by Cu6MH (Cu2+ and MH molar ratio of 6:1). Meanwhile, Cu6MH also exhibited efficient antioxidant and anti-inflammation function by down-regulating the expression of IL6, MMP13, and MMP3, and up-regulating cartilage specific gene expression as well. Importantly, Cu6MH could repair mitochondrial function by increasing mitochondrial membrane potential, reducing the accumulation of calcium ions, as well as promoting ATP content production. In OA joint model, intra-articular (IA) injected Cu6MH suppressed the progression of OA. It endowed that Cu6MH might be promising nanoenzymes for the prevention and treatment of various inflammatory diseases.

Molecular hallmarks of breast multiparametric magnetic resonance imaging during neoadjuvant chemotherapy.

PURPOSE: To identify molecular basis of four parameters obtained from dynamic contrast-enhanced magnetic resonance imaging, including functional tumor volume (FTV), longest diameter (LD), sphericity, and contralateral background parenchymal enhancement (BPE). MATERIAL AND METHODS: Pretreatment-available gene expression profiling and different treatment timepoints MRI features were integrated for Spearman correlation analysis. MRI feature-related genes were submitted to hypergeometric distribution-based gene functional enrichment analysis to identify related Kyoto Encyclopedia of Genes and Genomes annotation. Gene set variation analysis was utilized to assess the infiltration of distinct immune cells, which were used to determine relationships between immune phenotypes and medical imaging phenotypes. The clinical significance of MRI and relevant molecular features were analyzed to identify their prediction performance of neoadjuvant chemotherapy (NAC) and prognostic impact. RESULTS: Three hundred and eighty-three patients were included for integrative analysis of MRI features and molecular information. FTV, LD, and sphericity measurements were most positively significantly correlated with proliferation-, signal transmission-, and immune-related pathways, respectively. However, BPE did not show marked correlation relationships with gene expression alteration status. FTV, LD and sphericity all showed significant positively or negatively correlated with some immune-related processes and immune cell infiltration levels. Sphericity decreased at 3 cycles after treatment initiation was also markedly negatively related to baseline sphericity measurements and immune signatures. Its decreased status could act as a predictor for prediction of response to NAC. CONCLUSION: Different MRI features capture different tumor molecular characteristics that could explain their corresponding clinical significance.

Cardiac-specific Trim44 knockout in rat attenuates isoproterenol-induced cardiac remodeling via inhibition of AKT/mTOR pathway.

When pathological hypertrophy progresses to heart failure (HF), the prognosis is often very poor. Therefore, it is crucial to find new and effective intervention targets. Here, myocardium-specific Trim44 knockout rats were generated using CRISPR-Cas9 technology. Cardiac phenotypic observations revealed that Trim44 knockout affected cardiac morphology at baseline. Rats with Trim44 deficiency exhibited resistance to cardiac pathological changes in response to stimulation via isoproterenol (ISO) treatment, including improvement of cardiac remodeling and dysfunction by morphological and functional observations, reduced myocardial fibrosis and reduced expression of molecular markers of cardiac stress. Furthermore, signal transduction validation associated with growth and hypertrophy development in vivo and in vitro demonstrated that Trim44 deficiency inhibited the activation of signaling pathways involved in myocardial hypertrophy, especially response to pathological stress. In conclusion, the present study indicates that Trim44 knockout attenuates ISO-induced pathological cardiac remodeling through blocking the AKT/mTOR/GSK3ß/P70S6K signaling pathway. This is the first study to demonstrate the function and importance of Trim44 in the heart at baseline and under pathological stress. Trim44 could be a novel therapeutic target for prevention of cardiac hypertrophy and HF.

Redox-Neutral 1,4-Dicarbonfunctionalization of 1,3-Butadiene by Merging Photoredox and Nickel Catalysis.

The diverse functionalization of 1,3-butadiene provides wide applicability toward the synthesis of abundant and useful allylic compounds. Here, we describe a three-component and redox-neutral assembly of readily available C═X compounds, 1,3-butadiene, and various nucleophiles by merging photoredox and nickel catalysis, enabling the rapid synthesis of structurally diverse homoallyl amines and homoallylic alcohols.

Mathematical calculation of the difference in shortening length after two types of proximal femoral varus and an investigation of their applicable conditions: an own-pair design.

BACKGROUND: The shortening length of the lower extremity after the proximal femoral osteotomy is an important issue to be considered in preoperative planning of developmental dysplasia of the hip (DDH) in children. There is still a lack of research on shortening the length of the lower extremities in different proximal femoral osteotomy varus styles. We aimed to verify the relationship between the shortening length after "point-to-face" and "face-to-face" varus osteotomy and proposed a formula for calculating the difference in shortening length and verified its feasibility. METHODS: Fifty-five children with unilateral DDH were enrolled. The preoperative hip CT data were imported into mimics 21, 3-Matic 10 (Materialise, Leuven, Belgium) for femoral reconstruction and simulated osteotomy, and the difference (t) was calculated by directly measuring the length of the proximal femur after osteotomy. d* sinθ was measured in a three-dimensional environment to calculate the difference in femoral shortening length between the two osteotomy methods (t'). RESULTS: The results of the direct measurement method and the formula measurement method are shown in the table; the differences in the results of the femoral shortening length difference were not statistically significant (P > 0.05). The limits of agreement (95%) of the difference values using Bland-Altman analysis were between - 0.50 and 0.46 mm, with a mean of - 0.02 mm, indicating a high agreement between the two methods. r = 0.99 (P < 0.05) for the Pearson correlation analysis between the direct measurement method and the calculated method showed that the two methods were significantly correlated. CONCLUSIONS: The derived formula can accurately calculate the difference in the shortening length of the proximal femur after "point-to-face" and "face-to-face" varus osteotomy in children with DDH, which is suitable for clinical application.

Ammonium improved cell wall and cell membrane P reutilization and external P uptake in a putrescine and ethylene dependent pathway.

Ammonium promotes rice P uptake and reutilization better than nitrate, under P starvation conditions; however, the underlying mechanism remains unclear. In this study, ammonium treatment significantly increased putrescine and ethylene content in rice roots under P deficient conditions, by increasing the protein content of ornithine decarboxylase and 1-aminocyclopropane-1-carboxylic acid (ACC) oxidase compared with nitrate treatment. Ammonium treatment increased rice root cell wall P release by increasing pectin content and pectin methyl esterase (PME) activity, increased rice shoot cell membrane P release by decreasing phosphorus-containing lipid components, and maintained internal P homeostasis by increasing OsPT2/6/8 expression compared with nitrate treatment. Ammonium also improved external P uptake by regulating root morphology and increased rice grain yield by increasing the panicle number compared with nitrate treatment. The application of putrescine and ethylene synthesis precursor ACC further improved the above process. Our results demonstrate for the first time that ammonium increases rice P acquisition, reutilization, and homeostasis, and rice grain yield, in a putrescine- and ethylene-dependent manner, better than nitrate, under P starvation conditions.

PD-1 inhibitor induces myocarditis by reducing regulatory T cells, activating inflammatory responses, promoting myocardial apoptosis and autophagy.

The present study aimed to explore the pathogenesis of autoimmune myocarditis induced by PD-1 inhibitors and their potential therapeutic targets. Mouse models of autoimmune myocarditis induced by PD-1 inhibitor in mouse models of polymyositis were established. The expression level of PD-1 and regulatory T cells (Tregs), CD4, CD8 + T cells, inflammation, apoptosis and autophagy-related factors, including IL-6, TGF-ß, AMA-M2, Fas/FasL, LC3 and p62 were detected in peripheral blood, muscle or myocardium of mice in each group, using ELISA, RT-PCR, Western Blot and immunofluorescence. In addition, HE and TUNEL staining and ultrastructural scanning were performed on the myocardium of mice in each group. Results showed that the expression level of PD-1 in the two myositis groups was significantly lower than that in the control group, and the level of PD-1 was lower in the myocarditis group than that in the polymyositis group. In the myocardium, TGF-ß, p62, and Tregs proportion showed the same expression level trend as PD-1, while CD8, IL-6, IL-10 and LC3 showed the opposite trend. Levels of Fas/FasL were significantly higher in both myositis groups, but were slightly lower in the myocarditis group, as was AMA-M2. Inflammation, apoptosis, and autophagy were observed in both myositis groups, but were more severe in the myocarditis group. In summary, the decreased expression level of PD-1 leads to decreased Tregs level in the myocardium, aggravated inflammatory response, apoptosis and autophagy, which may be the pathological mechanism of myocarditis induced by PD-1 inhibitors.

Unearthing the alleviatory mechanisms of hydrogen sulfide in aluminum toxicity in rice.

Hydrogen sulfide (H2S) improves aluminum (Al) resistance in rice, however, the underlying mechanism remains unclear. In the present study, treatment with 30-µM Al significantly inhibited rice root growth and increased the total Al content, apoplastic and cytoplasm Al concentration in the rice roots. However, pretreatment with NaHS (H2S donor) reversed these negative effects. Pretreatment with NaHS significantly increased energy production under Al toxicity conditions, such as by increasing the content of ATP and nonstructural carbohydrates. In addition, NaHS stimulated the AsA-GSH cycle to decrease the peroxidation damage induced by Al toxicity. Pretreatment with NaHS significantly inhibited ethylene emissions in the rice and then inhibited pectin synthesis and increased the pectin methylation degree to reduce cell wall Al deposition. The phytohormones indole-3-acetic and brassinolide were also involved in the alleviation of Al toxicity by H2S. The transcriptome results further confirmed that H2S alleviates Al toxicity by increasing the pathways relating to material and energy metabolism, redox reactions, cell wall components, and signal transduction. These findings improve our understanding of how H2S affects rice responses to Al toxicity, which will facilitate further studies on crop safety.

Endovascular Treatment of Abdominal Infection-induced Aortoenteric Fistula.

Primary aortoenteric fistula is a rare clinical entity that often has a fatal outcome. It usually arises from an atherosclerotic aneurysm, and induction by abdominal infection is extremely rare. This report presents the case of 54-year-old man with a history of aortic arch replacement and elephant trunk stent implantation 6 years earlier for Stanford type A aortic dissection. At 11 months before his current presentation, he underwent enteroscopy, during which gastrointestinal perforation occurred. Since then, he had experienced episodes of syncope and hemorrhage. Finally, a fistula was found on imaging. Endovascular treatment and digestive tract repair were accomplished. At 13-month follow-up, he had not had a recurrence of hematochezia or fever.