Case report: From oral infection to life-threatening pneumonia: clinical considerations in Nocardia infection from a case.

Nocardia is an anthropozoonotic bacteria that occurs widely in the natural environment. However, because it is a gram-positive aerobic opportunistic pathogen, it rarely occurs in patients with no prior history of immune function disease. Since the symptoms are nonspecific the diagnosis of Nocardia pneumonia is challenging. Previous studies have not reported that this anthropozoonotic bacteria colonizing the human body could cause severe pneumonia by gingival pain and pharyngeal discomfort. This case report describes a previously healthy 60-year-old female farmer who presented to the doctor with gingival pain and pharyngeal discomfort. She was treated with a dental cleaning and oral metronidazole. The patient rapidly progressed to breathing difficulties. Lung shadow was found by computerized tomography examination. The radiologist diagnosed pulmonary tuberculosis as image-based. Through laboratory examination and culture of pathogenic microorganisms in the sputum and blood of the patient, no obvious positive findings were found. The disease progressed rapidly to tracheal intubation ventilator assisted breathing. Subsequently, the patient underwent alveolar lavatory examination under endotracheal intubation fiberbronchoscopy, and the culture of alveolar lavage fluid indicated Nocardia. According to this result, the patient's disease was quickly controlled after selecting the targeted drug compound sulfamethoxazole and intravenous meropenem for treatment. In view of the reason for the high misdiagnosis rate due to the low positive rate of Nocardia culture in most cases, the clinical thinking of diagnosis and treatment from oral infection symptoms to fatal pneumonia reported in this case has certain clinical popularization and enlighten significance, not only improved the diagnosis and treatment of rare diseases, but also be reduced medical disputes.

Exploring the heart-brain and brain-heart axes: Insights from a bidirectional Mendelian randomization study on brain cortical structure and cardiovascular disease.

INTRODUCTION: The bidirectional relationship between the brain cortex and cardiovascular diseases (CVDs) remains inadequately explored. METHODS: This study used bidirectional Mendelian randomization (MR) analysis to explore the interactions between nine phenotypes associated with hypertension, heart failure, atrial fibrillation (AF), and coronary heart disease (CHD), and brain cortex measurements. These measurements included total surface area (SA), average thickness (TH), and the SA and TH of 34 regions defined by the Desikan-Killiany atlas. The nine traits were obtained from sources such as the UK Biobank and FinnGen, etc., while MRI-derived traits of cortical structure were sourced from the ENIGMA Consortium. The primary estimate was obtained using the inverse-variance weighted approach. A false discovery rate adjustment was applied to the p-values (resulting in q-values) in the analyses of regional cortical structures. RESULTS: A total of 1,260 two-sample MR analyses were conducted. Existing CHD demonstrated an influence on the SA of the banks of the superior temporal sulcus (bankssts) (q=0.018) and the superior frontal lobe (q=0.018), while hypertension was associated with changes in the TH of the lateral occipital region (q=0.02). Regarding the effects of the brain cortex on CVD incidence, total SA was significantly associated with the risk of CHD. Additionally, 16 and 3 regions exhibited significant effects on blood pressure and AF risk, respectively (q<0.05). These regions were primarily located in the frontal, temporal, and cingulate areas, which are associated with cognitive function and mood regulation. CONCLUSION: The detection of cortical changes through MRI could aid in screening for potential neuropsychiatric disorders in individuals with established CVD. Moreover, abnormalities in cortical structure may predict future CVD risk, offering new insights for prevention and treatment strategies.

The value of 3D printing model combined PCNL in kidney stones: a systematic review and meta-analysis.

INTRODUCTION: With the continuous advancement of medical imaging, 3D printing technology is emerging. This technology allows for the representation of complex objects in a model form. This research aims to delve into the irreplaceable value of percutaneous nephrolithotomy (PCNL) in conjunction with 3D printed models in urinary stone surgery. This forward-looking approach provides doctors with a new perspective, enabling them to plan and execute surgeries with greater precision, ultimately delivering a safer and more efficient treatment experience for patients. We evaluated the literature on PCNL for the kidney stones with the introduction of 3D printing models and conducted a meta-analysis. The assessed parameters included stone clearance rate, operation time, hospital stay, blood loss, puncture accuracy, and the rate of complications. EVIDENCE ACQUISITION: We systematically searched the EMBASE, PubMed, Cochrane Library, SCIE, and Chinese Biomedical Literature Search databases for articles related to PCNL (Percutaneous Nephrolithotomy) with 3D printing models from January 2000 to January 2023. Data were managed and screened using Excel . Meta-analysis was performed for operation time, stone clearance rate, blood loss, puncture accuracy, length of hospital stay, and complications in PCNL combined with 3D printing model for kidney stone treatment. The quality of included articles was assessed using the risk of bias tool by the Cochrane Collaboration. Sensitivity analysis was conducted to assess the reliability of the results. Data were recorded using StataSE 17 software, and publication bias was examined using Egger's linear regression test. EVIDENCE SYNTHESIS: We followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to conduct a systematic search and screening of literature relevant to the use of 3D printed models in the treatment of kidney stones. We conducted an extensive literature search across several major academic databases, including EMBASE, PubMed, Cochrane Library, SCIE, and Chinese Biomedical Literature Search databases, to ensure comprehensive coverage of relevant studies. Following the PRISMA process of screening and analysis, we ultimately included 10 randomized controlled trials with a combined sample of 608 for systematic review. CONCLUSIONS: Across these studies, we identified the introduction of 3D printing models prior to surgery for kidney stones resulted in significant advantages for the experimental group compared to the control group in terms of operation time, stone clearance rates, puncture accuracy, hospital stay, blood loss, and the incidence of complications, providing valuable insights for further research and clinical practice.

Adaptive Tracking Control for Underactuated Double Pendulum Overhead Cranes With Variable Cable Length.

Although the literature on control of overhead crane systems is extensive and relatively mature, there is still a need to develop strategies that can simultaneously handle factors such as the double pendulum effect, variable cable length, input saturation, input dead zones, and external disturbances. This article is concerned with adaptive tracking control for underactuated overhead cranes in the presence of the above-mentioned challenging effects. The proposed controller is composed of the following two components. First, a tracking signal vector that effectively reduces system swing magnitudes is constructed to improve the transient performance and guarantee smooth operation of the system. Second, an adaptive law is designed to estimate and compensate for the overall effects of the friction, the external disturbances, and certain nonlinearities. The system stability has been proved rigorously via the Lyapunov method and Barbalat's lemma. Extensions to the cases with input saturation and dead zones have also been discussed. Extensive numerical simulations have been conducted to verify the performance and robustness of the proposed controller, in comparison to some existing methods.

Role of mitophagy in pulmonary hypertension: Targeting the mechanism and pharmacological intervention.

Mitophagy, a crucial pathway in eukaryotic cells, selectively eliminates dysfunctional mitochondria, thereby maintaining cellular homeostasis via mitochondrial quality control. Pulmonary hypertension (PH) refers to a pathological condition where pulmonary arterial pressure is abnormally elevated due to various reasons, and the underlying pathogenesis remains elusive. This article examines the molecular mechanisms underlying mitophagy, emphasizing its role in PH and the progress in elucidating related molecular signaling pathways. Additionally, it highlights current drug regulatory pathways, aiming to provide novel insights into the prevention and treatment of pulmonary hypertension.

Malignant glaucoma treated by low-dose laser cycloplasty: a 1-year multicenter prospective non-comparative study.

AIM: To report a one-year clinical outcomes of low-dose laser cycloplasty (LCP) among malignant glaucoma patients. METHODS: In this prospective, multicenter, non-comparative clinical study, participants with malignant glaucoma were recruited and underwent LCP at eight ophthalmic centers in China. Patients were followed up at 1wk, 1, 3, 6, and 12mo. Intraocular pressure (IOP), number of glaucoma medications, anterior chamber depth (ACD), and complications were recorded. Anatomical success was defined as the reformation of the anterior chamber based on slit-lamp biomicroscopy. Recurrence was defined by the presence of a shallow or flat anterior chamber after initial recovery from treatment. RESULTS: A total of 34 eyes received LCP. Mean IOP and medications decreased from 36.1±11.5 mm Hg with 3.3±1.5 glaucoma medications pre-treatment to 20.9±9.8 mm Hg (P<0.001) with 2.9±1.6 medications (P=0.046) at 1d, and 17.4±6.7 mm Hg (P<0.001) with 1.3±1.7 medications (P<0.001) at 12mo. The ACD increased from 1.1±0.8 mm at baseline to 1.7±1.0 mm and to 2.0±0.5 mm at 1d and 12mo, respectively. A total of 32 (94.1%) eyes achieved initial anatomical success. During follow-up, 2 (5.9%) eyes failed and 8 (23.5%) eyes relapsed, yielding a 12-month anatomical success rate of 64.3%. Complications including anterior synechia (8.82%), choroidal/ciliary detachment (5.88%) and hypopyon (2.94%) were observed within 1wk. CONCLUSION: LCP is simple, safe, and effective in reforming the anterior chamber in malignant glaucoma.

New evidence for a role of DANCR in cancers: a comprehensive review.

Cancer remains a leading cause of mortality and poses a substantial threat to public health. Studies have revealed that Long noncoding RNA DANCR is a cytoplasmic lncRNA whose aberrant expression plays a pivotal role in various cancer types. Within tumour biology, DANCR exerts regulatory control over crucial processes such as proliferation, invasion, metastasis, angiogenesis, inflammatory responses, cellular energy metabolism reprogramming, and apoptosis. By acting as a competitive endogenous RNA for miRNAs and by interacting with proteins and mRNAs at the molecular level, DANCR contributes significantly to cancer progression. Elevated DANCR levels have also been linked to heightened resistance to anticancer drugs. Moreover, the detection of circulating DANCR holds promise as a valuable biomarker for aiding in the clinical differentiation of different cancer types. This article offers a comprehensive review and elucidation of the primary functions and molecular mechanisms through which DANCR influences tumours.

Widely targeted metabolomics analysis of Sanghuangporus vaninii mycelia and fruiting bodies at different harvest stages.

Sanghuangprous vaninii is a medicinal macrofungus cultivated extensively in China. Both the mycelia and fruiting bodies of S. vaninii have remarkable therapeutic properties, but it remains unclear whether the mycelia may serve as a substitute for the fruiting bodies. Furthermore, S. vaninii is a perennial fungus with therapeutic components that vary significantly depending on the growing year of the fruiting bodies. Hence, it is critical to select an appropriate harvest stage for S. vaninii fruiting bodies for a specific purpose. With the aid of Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), metabolomics based on ultra-high performance liquid chromatography coupled to triple quadrupole mass spectrometry (UHPLC-QQQ-MS) was used to preliminarily determine 81 key active metabolites and 157 active pharmaceutical metabolites in S. vaninii responsible for resistance to the six major diseases. To evaluate the substitutability of the mycelia and fruiting bodies of S. vaninii and to select an appropriate harvest stage for the fruiting bodies of S. vaninii, we analyzed the metabolite differences, especially active metabolite differences, among the mycelia and fruiting bodies during three different harvest stages (1-year-old, 2-year-old, and 3-year-old). Moreover, we also determined the most prominent and crucial metabolites in each sample of S. vaninii. These results suggested that the mycelia show promise as a substitute for the fruiting bodies of S. vaninii and that extending the growth year does not necessarily lead to higher accumulation levels of active metabolites in the S. vaninii fruiting bodies. This study provided a theoretical basis for developing and using S. vaninii.

State Responses of Several Classes of Linear Systems Based on Fundamental Matrices.

State responses for several classes of linear systems are investigated in this article. The involved systems include state-delayed linear systems, and high-order linear systems. At first, the single-fundamental-matrix-based approach is extended to these systems, and their state responses are expressed by their fundamental matrices (FMs). In addition, the multiple-FMs-based approach is presented for these systems. Based on a group of FMs, the state responses for the considered time-invariant systems are derived. For the considered time-variant systems, their state responses are explicitly expressed by their transition matrices. As an application of the fundamental-matrix-based approach, a stabilizing control law is designed for a class of high-order fully actuated continuous-time linear systems with a single input-delay.

The etiology and differential diagnosis of "autoimmune hepatitis-like liver disease" in children: a single-center retrospective study.

Background: Children with autoimmune hepatitis (AIH) often present with symptoms similar to those of other liver diseases. This study consists of a comparison between the clinical and histological characteristics of AIH and those of other four AIH-like liver diseases [i.e., drug-induced liver injury (DILI), gene deficiency, infectious liver disease and other etiology of liver disease], as well as an evaluation of the AIH scoring system's diagnostic performance. Methods: All children with AIH-like liver disease at our center from January 2013 to December 2022 were included. The clinical and histological characteristics of the AIH group were retrospectively analyzed and compared with those of the other four groups. Results: A total of 208 children were included and divided into AIH group (18 patients), DILI group (38 patients), gene deficiency group (44 patients), infectious liver disease group (74 patients), and other etiology group (34 patients). The antinuclear antibodies (ANA) ≥ 1:320 rate was significantly higher in the AIH compared to the other four groups after multiple testing correction (p < 0.0125), while patients with positive antibodies to liver-kidney microsomal-1 (anti-LKM1, n = 3) and smooth muscle antibodies (SMA, n = 2) were only observed in the AIH group. The positive rates of antibodies to liver cytosol type1 (anti-LC1) and Ro52 were higher than those in the other four groups. The serum immunoglobulin G (IgG) and globulin levels, as well as the proportions of portal lymphoplasmacytic infiltration, lobular hepatitis with more than moderate interface hepatitis, and lobular hepatitis with lymphoplasmacytic infiltration, were significantly higher in the AIH group than in the other four groups after multiple testing correction (p < 0.0125). The cirrhosis rate in the AIH group was higher than that in the DILI and infectious liver disease groups (p < 0.0125). Both the simplified (AUC > 0.73) and the revised systems (AUC > 0.93) for AIH have good diagnostic performance, with the latter being superior (p < 0.05). Conclusion: Positive autoantibodies (ANA ≥ 1:320 or anti-LKM1 positive, or accompanied by SMA, anti-LC1 or Ro-52 positive) and elevated serum IgG or globulin levels contribute to early recognition of AIH. The presence of lobular hepatitis with more than moderate interface hepatitis and lymphoplasmacytic infiltration contribute to the diagnosis of AIH.

Nuclear factor Y-A3b binds to the SINGLE FLOWER TRUSS promoter and regulates flowering time in tomato.

The control of flowering time is essential for reproductive success and has a major effect on seed and fruit yield and other important agricultural traits in crops. Nuclear factors Y (NF-Ys) are transcription factors that form heterotrimeric protein complexes to regulate gene expression required for diverse biological processes, including flowering time control in plants. However, to our knowledge, there has been no report on mutants of individual NF-YA subunits that promote early flowering phenotype in plants. In this study, we identified SlNF-YA3b, encoding a member of the NF-Y transcription factor family, as a key gene regulating flowering time in tomato. Knockout of NF-YA3b resulted in an early flowering phenotype in tomato, whereas overexpression of NF-YA3b delayed flowering in transgenic tomato plants. NF-YA3b was demonstrated to form heterotrimeric protein complexes with multiple NF-YB/NF-YC heterodimers in yeast three-hybrid assays. Biochemical evidence indicated that NF-YA3b directly binds to the CCAAT cis-elements of the SINGLE FLOWER TRUSS (SFT) promoter to suppress its gene expression. These findings uncovered a critical role of NF-YA3b in regulating flowering time in tomato and could be applied to the management of flowering time in crops.

UPLC-ESI-MS/MS-based widely targeted metabolomics reveals differences in metabolite composition among four Ganoderma species.

The Chinese name "Lingzhi" refers to Ganoderma genus, which are increasingly used in the food and medical industries. Ganoderma species are often used interchangeably since the differences in their composition are not known. To find compositional metabolite differences among Ganoderma species, we conducted a widely targeted metabolomics analysis of four commonly used edible and medicinal Ganoderma species based on ultra performance liquid chromatography-electrospray ionization-tandem mass spectrometry. Through pairwise comparisons, we identified 575-764 significant differential metabolites among the species, most of which exhibited large fold differences. We screened and analyzed the composition and functionality of the advantageous metabolites in each species. Ganoderma lingzhi advantageous metabolites were mostly related to amino acids and derivatives, as well as terpenes, G. sinense to terpenes, and G. leucocontextum and G. tsugae to nucleotides and derivatives, alkaloids, and lipids. Network pharmacological analysis showed that SRC, GAPDH, TNF, and AKT1 were the key targets of high-degree advantage metabolites among the four Ganoderma species. Analysis of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes demonstrated that the advantage metabolites in the four Ganoderma species may regulate and participate in signaling pathways associated with diverse cancers, Alzheimer's disease, and diabetes. Our findings contribute to more targeted development of Ganoderma products in the food and medical industries.

Genetic Analysis of Two Novel GPI Variants Disrupting H Bonds and Localization Characteristics of 55 Gene Variants Associated with Glucose-6-phosphate Isomerase Deficiency.

OBJECTIVE: Glucose-6-phosphate isomerase (GPI) deficiency is a rare hereditary nonspherocytic hemolytic anemia caused by GPI gene variants. This disorder exhibits wide heterogeneity in its clinical manifestations and molecular characteristics, often posing challenges for precise diagnoses using conventional methods. To this end, this study aimed to identify the novel variants responsible for GPI deficiency in a Chinese family. METHODS: The clinical manifestations of the patient were summarized and analyzed for GPI deficiency phenotype diagnosis. Novel compound heterozygous variants of the GPI gene, c.174C>A (p.Asn58Lys) and c.1538G>T (p.Trp513Leu), were identified using whole-exome and Sanger sequencing. The AlphaFold program and Chimera software were used to analyze the effects of compound heterozygous variants on GPI structure. RESULTS: By characterizing 53 GPI missense/nonsense variants from previous literature and two novel missense variants identified in this study, we found that most variants were located in exons 3, 4, 12, and 18, with a few localized in exons 8, 9, and 14. This study identified novel compound heterozygous variants associated with GPI deficiency. These pathogenic variants disrupt hydrogen bonds formed by highly conserved GPI amino acids. CONCLUSION: Early family-based sequencing analyses, especially for patients with congenital anemia, can help increase diagnostic accuracy for GPI deficiency, improve child healthcare, and enable genetic counseling.

Clinical Analysis and Mental Health Survey of Hemophilia Carriers: a Cross-sectional Study.

OBJECTIVE: Hemophilia carriers (HCs), who are heterozygous for mutations in the clotting factor VIII/clotting factor IX gene (F8 or F9), may have a wide range of clotting factor levels, from very low, similar to afflicted males, to the upper limit of normal, and may experience mental health issues. The purpose of this study was to provide genetic information on mothers of hemophilia patients and to understand the clotting factor activity and phenotype of HCs. Additionally, we aimed to investigate the mental health status of HCs in China. METHODS: A total of 127 hemophilia mothers, including 93 hemophilia A (HA) mothers and 34 hemophilia B (HB) mothers, were enrolled in this study. Long distance PCR, multiplex PCR, and Sanger sequencing were used to analyze mutations in F8 or F9. Coagulation factor activity was detected by a one-stage clotting assay. The Symptom Checklist 90 (SCL-90, China/Mandarin version) was given to HCs at the same time to assess their mental health. RESULTS: A total of 90.6% of hemophilia mothers were diagnosed genetically as carriers, with inversion in intron 22 and missense mutations being the most common mutation types in HA and HB carriers, respectively. The median clotting factor level in carriers was 0.74 IU/mL (ranging from 0.09 to 1.74 IU/mL) compared with 1.49 IU/mL (ranging from 0.93 to 1.89 IU/mL) in noncarriers, of which 14.3% of HCs had clotting factor levels of 0.40 IU/mL or below. A total of 53.8% (7/13) of HA carriers with low clotting factor levels (less than 0.50 IU/mL) had a history of bleeding, while none of the HB carriers displayed a bleeding phenotype. The total mean score and the global severity index of the SCL-90 for surveyed HCs were 171.00 (±60.37) and 1.78 (±0.59), respectively. A total of 67.7% of the respondents had psychological symptoms, with obsessive-compulsive disorder being the most prevalent and severe. The pooled estimates of all nine factors were significantly higher than those in the general population (P<0.05). CONCLUSIONS: The detection rate of gene mutations in hemophilia mothers was 90.6%, with a median clotting factor level of 0.74 IU/mL, and 14.3% of HCs had a clotting factor level of 0.40 IU/mL or below. A history of bleeding was present in 41.2% of HCs with low clotting factor levels (less than 0.50 IU/mL). Additionally, given the fragile mental health status of HCs in China, it is critical to develop efficient strategies to improve psychological well-being.

Dissecting the molecular basis of spike traits by integrating gene regulatory networks and genetic variation in wheat.

Spike architecture influences both grain weight and grain number per spike, which are the two major components of grain yield in bread wheat (Triticum aestivum L.). However, the complex wheat genome and the influence of various environmental factors pose challenges in mapping the causal genes that affect spike traits. Here, we systematically identified genes involved in spike trait formation by integrating information on genomic variation and gene regulatory networks controlling young spike development in wheat. We identified 170 loci that are responsible for variations in spike length, spikelet number per spike, and grain number per spike through genome-wide association study and meta-QTL analyses. We constructed gene regulatory networks for young inflorescences at the double ridge stage and the floret primordium stage, in which the spikelet meristem and the floret meristem are predominant, respectively, by integrating transcriptome, histone modification, chromatin accessibility, eQTL, and protein-protein interactome data. From these networks, we identified 169 hub genes located in 76 of the 170 QTL regions whose polymorphisms are significantly associated with variation in spike traits. The functions of TaZF-B1, VRT-B2, and TaSPL15-A/D in establishment of wheat spike architecture were verified. This study provides valuable molecular resources for understanding spike traits and demonstrates that combining genetic analysis and developmental regulatory networks is a robust approach for dissection of complex traits.

Simultaneous SERS Sensing of Cysteine and Homocysteine in Blood Based on the CBT-Cys Click Reaction: Toward Precisive Diagnosis of Schizophrenia.

At present, there is a lack of sufficiently specific laboratory diagnostic indicators for schizophrenia. Serum homocysteine (Hcy) levels have been found to be related to schizophrenia. Cysteine (Cys) is a demethylation product in the metabolism of Hcy, and they always coexist with highly similar structures in vivo. There are few reports on the use of Cys as a diagnostic biomarker for schizophrenia in collaboration with Hcy, mainly because the rapid, economical, accurate, and high-throughput simultaneous detection of Cys and Hcy in serum is highly challenging. Herein, a click reaction-based surface-enhanced Raman spectroscopy (SERS) sensor was developed for simultaneous and selective detection of Cys and Hcy. Through the efficient and specific CBT-Cys click reaction between the probe containing cyan benzothiazole and Cys/Hcy, the tiny methylene difference between the molecular structures of Cys and Hcy was converted into the difference between the ring skeletons of the corresponding products that could be identified by plasmonic silver nanoparticle enhanced molecular fingerprint spectroscopy to realize discriminative detection. Furthermore, the SERS sensor was successfully applied to the detection in related patient serum samples, and it was found that the combined analysis of Cys and Hcy can improve the diagnostic accuracy of schizophrenia compared to a single indicator.

Effects of cluster nursing interventions on the prevention of pressure ulcers in intensive care units patients: A meta-analysis.

A meta-analysis was conducted to comprehensively evaluate the impact of cluster nursing interventions on the prevention of pressure ulcers (PUs) in intensive care unit (ICU) patients. Computer searches were performed in databases including Embase, Google Scholar, Cochrane Library, PubMed, Wanfang and China National Knowledge Infrastructure for randomized controlled trials (RCTs) implementing cluster nursing interventions for PUs prevention in ICU patients, with the search period covering the database inception to November 2023. Two researchers independently screened the literature, extracted data and conducted quality assessments. Stata 17.0 software was employed for data analysis. Overall, 17 RCTs involving 1463 ICU patients were included. The analysis showed that compared with conventional nursing, cluster nursing interventions significantly reduced the incidence of PUs (odds ratio: 0.24, 95% confidence intervals [CI]: 0.17-0.34, p < 0.001) and also significantly improved the levels of anxiety (standardized mean difference [SMD]: -1.39, 95% CI: -1.57 to 1.22, p < 0.001) and depression (SMD: -1.64, 95% CI: -2.02 to 1.26, p < 0.001) in ICU patients. This study indicates that the application of cluster nursing interventions in ICU patients can effectively reduce the incidence of PUs, as well as improve patients' anxiety and depression levels, thereby enhancing their quality of life, which is worth clinical promotion and application.

Expression and regulation of HIF-1a in hypoxic pulmonary hypertension: Focus on pathological mechanism and Pharmacological Treatment.

Hypoxia inducible factor-1(HIF-1), a heterodimeric transcription factor, is composed of two subunits (HIF-1α and HIF-1ß). It is considered as an important transcription factor for regulating oxygen changes in hypoxic environment, which can regulate the expression of various hypoxia-related target genes and play a role in acute and chronic hypoxia pulmonary vascular reactions. In this paper, the function and mechanism of HIF-1a expression and regulation in hypoxic pulmonary hypertension (HPH) were reviewed, and current candidate schemes for treating pulmonary hypertension by using HIF-1a as the target were introduced, so as to provide reference for studying the pathogenesis of HPH and screening effective treatment methods.

Failure mechanical properties of lumbar intervertebral disc under high loading rate.

BACKGROUND: Lumbar disc herniation (LDH) is the main clinical cause of low back pain. The pathogenesis of lumbar disc herniation is still uncertain, while it is often accompanied by disc rupture. In order to explore relationship between loading rate and failure mechanics that may lead to lumbar disc herniation, the failure mechanical properties of the intervertebral disc under high rates of loading were analyzed. METHOD: Bend the lumbar motion segment of a healthy sheep by 5° and compress it to the ultimate strength point at a strain rate of 0.008/s, making a damaged sample. Within the normal strain range, the sample is subjected to quasi-static loading and high loading rate at different strain rates. RESULTS: For healthy samples, the stress-strain curve appears collapsed only at high rates of compression; for damaged samples, the stress-strain curves collapse both at quasi-static and high-rate compression. For damaged samples, the strengthening stage becomes significantly shorter as the strain rate increases, indicating that its ability to prevent the destruction is significantly reduced. For damaged intervertebral disc, when subjected to quasi-static or high rates loading until failure, the phenomenon of nucleus pulposus (NP) prolapse occurs, indicating the occurrence of herniation. When subjected to quasi-static loading, the AF moves away from the NP, and inner AF has the greatest displacement; when subjected to high rates loading, the AF moves closer to the NP, and outer AF has the greatest displacement. The Zhu-Wang-Tang (ZWT) nonlinear viscoelastic constitutive model was used to describe the mechanical behavior of the intervertebral disc, and the fitting results were in good agreement with the experimental curve. CONCLUSION: Experimental results show that, both damage and strain rate have a significant effect on the mechanical behavior of the disc fracture. The research work in this article has important theoretical guiding significance for preventing LDH in daily life.