Clinical Significance Research Articles

A new approach to quantify asymmetry in human movement

In this perspective paper, we propose a new approach to quantify the asymmetries in human movement. Before describing this approach, we delve into the asymmetry in human movement, often defined as the opposite of symmetry, and its implications for studying human movement. We critically examine the various methods available to quantify and describe bilateral differences, from arbitrary thresholds (such as the commonly employed 10–15% difference) to the measure of the smallest meaningful changes, and we stress the need for consideration of interindividual variability in the analysis. Our proposal centers on a straightforward metric, the probability of agreement, and a corresponding plot summarizing the agreement between measures from two limbs. Critically, the agreement between two limbs depends on the value of the clinically acceptable difference. The agreement will increase with larger values of clinically acceptable difference and decrease with smaller values of clinically acceptable difference. Data from various movements and conditions in athletes’ sports training and rehabilitation are used to illustrate this approach. Our perspective provides valuable insights into the nature of asymmetry in human movement, considering that a rational understanding of asymmetry in human movement requires a thoughtful approach encompassing both statistical and clinical significance. The data and codes employed in our research are openly accessible in the supplementary materials, enabling others in the field to replicate and build upon our findings.

Gender-driven thyroid dysfunction in systemic lupus erythematosus patients: Clinical significance of an overlooked association and global stance

Aim of the workThis study aimed to determine the association of thyroid dysfunction in systemic lupus erythematosus (SLE) patients Patients and methodsOut of a cohort including 312 adult SLE patients those with thyroid dysfunction (n = 53) were further evaluated. The medical history, clinical examination, laboratory investigations and medications received were recorded. The SLICC damage index (SLICC-DI) was assessed. ResultsThyroid dysfunction formed 17 % of the patients and their mean age was 39.5 ± 11.5 years and disease duration 5.6 ± 3.3 years were comparable to those without thyroid disorder, however female gender was predominantly higher (F:M 52:1 vs 6.2:1, p < 0.0001). The frequency of thyroid dysfunction was alike in Saudi (16 %) and non-Saudi (17.9 %) patients (p = 0.66). The majority of cases (96.2 %) had hypothyroidism, one with autoimmune thyroiditis, while only 2 (3.8 %) had hyperthyroidism. There was a significantly increased frequency of associated neuropsychiatric manifestations (64.2 % vs 45.2 %;p = 0.012), and hematological involvement (32.1 % vs 14.3 %; p = 0.011) and less complement (C4) consumption (15.1 % vs 23.6 %; p = 0.048) in those with thyroid dysfunction compared to those without. The frequency of anti-double stranded deoxyribonucleic acid (anti-dsDNA) positivity tended to be higher (71.7 % vs 66.8 %) and its titre significantly lower (316.3 ± 319.8 IU/ml vs 461.3 ± 459.1; p = 0.013). The SLICC-DI and mortality rate were comparable between groups. Only the presence of proteinuria inversely significantly correlated with the level of T4 (r = -0.31, p = 0.007). ConclusionThyroid dysfunction forms a notable percentage of SLE patients with a prominent female gender propensity. The significant relation of thyroid disorders to neuropsychiatric manifestations, hematological involvement, C4 consumption and anti-dsDNA deserves recognition.

Systemic hypertension with VEGFR inhibitor (axitinib) therapy in cancer patients: A meta-analysis and systematic review of randomized controlled trials

Vascular endothelial growth factor receptor inhibitors (VEGFRi), namely axitinib, are commonly used chemotherapeutic agents in patients with cancer; however, this medication has a significant cardiovascular side effect profile, such as high-grade hypertension. We performed this updated meta-analysis of RCTs to compile cardiovascular adverse events, such as all-grade and high-grade (>3) hypertension, the risk for thrombosis (DVT and PE), and peripheral edema. A systematic search was performed on PubMed, Cochrane, and Embase from inception until October 2023 for studies using axitinib to treat various cancers. Trials with patients randomly allocated for VEGFRi drug therapy with axitinib and reported all-grade hypertension as an outcome were included. Statistical analysis was performed using Cochrane Review Manager to calculate pooled proportions of odds ratios (OR) with a 95 % confidence interval (CI) using the random-effects model, Mantel−Haenszel method. A total of 8 RCTs and 2502 patients were included in the review. Compared with the placebo group, the VEGFRi (Axitinib) therapy group was associated with a higher risk of all-grade and high-grade hypertension, hand–foot syndrome, and fatigue. Furthermore, there was no increased risk of thromboembolism (DVT/PE) or hypothyroidism. However, a lower risk of peripheral edema was noted between the two groups. Screening for patients with preexisting hypertension, identifying risk factors for cardiovascular diseases before the initiation of VEGFRi therapy, and careful monitoring of high-risk patients during VEGFRi therapy, as well as prompt treatment with antihypertensive drugs, will help mitigate the adverse effects. Further evaluation using prospective designs is required to study the clinical significance and develop mitigation strategies.

FOXS1 acts as an oncogene and induces EMT through FAK/PI3K/AKT pathway by upregulating HILPDA in prostate cancer.

Prostate cancer (PCa) is a widespread global health concern characterized by elevated rates of occurrence, and there is a need for novel therapeutic targets to enhance patient outcomes. FOXS1 is closely linked to different cancers, but its function in PCa is still unknown. The expression of FOXS1, its prognostic role, clinical significance in PCa, and the potential mechanism by which FOXS1 affects PCa progression were investigated through bioinformatics analysis utilizing public data. The levels of FOXS1 and HILPDA were evaluated in clinical PCa samples using various methods, such as western blotting, immunohistochemistry, and qRT-PCR. To examine the function and molecular mechanisms of FOXS1 in PCa, a combination of experimental techniques including CCK-8 assay, flow cytometry, wound-healing assay, Transwell assay, and Co-IP assay were employed. The FOXS1 expression levels were significantly raised in PCa, correlating strongly with tumor aggressiveness and an unfavorable prognosis. Regulating FOXS1 expression, whether upregulating or downregulating it, correspondingly enhanced or inhibited the growth, migration, and invasion capabilities of PCa cells. Mechanistically, we detected a direct interaction between FOXS1 and HILPDA, resulting in the pathway activation of FAK/PI3K/AKT and facilitation EMT in PCa cells. FOXS1 collaborates with HILPDA to initiate EMT, thereby facilitating the PCa progression through the FAK/PI3K/AKT pathway activation.

Effect of manual manipulation on mechanical gait parameters.

A variety of manual manipulation techniques are utilized in clinical practice to alleviate pain and improve musculoskeletal function. Many manual practitioners analyze gait patterns and asymmetries in their assessment of the patient, and an increasing number of gait motion capture studies are taking place with recent improvements in motion capture technology. This study is the first systematic review of whether these manual modalities have been shown to produce an objectively measurable change in gait mechanics. This study was designed to perform a systematic review of the literature to assess the impact of manual medicine modalities on biomechanical parameters of gait. A master search term composed of keywords and Medical Subject Headings (MeSH) search terms from an initial scan of relevant articles was utilized to search six databases. We screened the titles and abstracts of the resulting papers for relevance and then assessed their quality with the Cochrane Risk of Bias Tool. Clinical trials that featured both a manual manipulation intervention and multiple mechanical gait parameters were included. Case reports and other studies that only measured gait speed or other subjective measures of mobility were excluded. We included 20 studies in our final analysis. They utilize manipulation techniques primarily from osteopathic, chiropractic, massage, and physiotherapy backgrounds. The conditions studied primarily included problems with the back, knee, and ankle, as well as healthy patients and Parkinson's patients. Control groups were highly variable, if not absent. Most studies measured their gait parameters utilizing either multicamera motion capture systems or force platforms. Twelve of 20 papers included in the final analysis demonstrated a significant effect of manipulation on gait variables, many of which included either step length, walking speed, or sagittal range of motion (ROM) in joints of the lower extremity. However, the results and study design are too heterogeneous to draw robust conclusions from these studies as a whole. While there are initial indications that certain modalities may yield a change in certain gait parameters, the quality of evidence is low and there is insufficient evidence to conclude that manual therapies induce changes in biomechanical gait parameters. Studies are heterogeneous with respect to the populations studied and the interventions performed. Comparators were variable or absent across the studies, as were the outcome variables measured. More could be learned in the future with consistent methodology around blinding and sham treatment, and if the gait parameters measured were standardized and of a more robust clinical significance.

Clinical significance and prognostic value of right bundle branch block in permanent pacemaker patients.

In patients undergoing pacemaker implantation with no prior history of heart failure (HF), the presence of left bundle branch block (LBBB) has been identified as an independent predictor of HF-related death or hospitalization, while the prognostic significance of right bundle branch block (RBBB) remains uncertain. We aimed to assess the long-term risk of all-cause mortality in patients with a standard indication for permanent pacing and normal or moderately depressed left ventricular function when RBBB is detected at the time of implantation. We retrospectively enrolled 1348 consecutive patients who had undergone single- or dual-chamber pacemaker implantation at the study center, from January 1990 to December 2022. Patients with a left ventricular ejection fraction ≤35% or a prior diagnosis of HF were excluded. The baseline 12-lead electrocardiogram revealed an RBBB in 241 (18%) and an LBBB in 98 (7%) patients. During a median follow-up of 65 [25th-75th percentile: 32-117] months, 704 (52%) patients died. The combined endpoint of cardiovascular death or HF hospitalization was reached by 173 (13%) patients. On multivariate analysis, RBBB was confirmed as an independent predictor of death [hazard ratio, 1.33; 95% confidence interval (CI), 1.09-1.63; P = 0.005]. However, when considering the combined endpoint of cardiovascular death and HF hospitalization, this endpoint was independently associated with LBBB (hazard ratio, 2.13; 95% CI, 1.38-3.29; P < 0.001), but not with RBBB. In patients with standard pacemaker indications and normal or moderately depressed left ventricular function, the presence of basal RBBB was an independent predictor of mortality. However, it was not associated with the combined endpoint of cardiovascular death and HF hospitalization.

Higher expression of SALL4-A isoform is correlated with worse outcomes and progression of the disease in subtype of testicular germ cell tumors.

The transcription factor SALL4 is associated with embryonic pluripotency and has proposed as a novel immunohistochemistry (IHC) marker for diagnosing germ cell tumors. SALL4 comprises three isoforms, and SALL4-A being the full-length isoform. Studying its isoforms could revolutionize testicular cancer prognosis and subtype differentiation. The expression and clinical significance of isoform "A" of SALL4 was evaluated in 124 testicular germ cell tumors (TGCTs) subtypes, adjacent normal tissues and 22 benign tumors, using immunohistochemistry on tissue microarrays (TMA). A statistically significant higher expression of nuclear and cytoplasmic SALL4-A was detected in TGCTs histological subtypes and benign tumors compared to the normal tissues. Seminoma and yolk sac tumors had the highest nuclear and cytoplasmic expression of SALL4-A. A significant correlation was detected between the higher nuclear expression of SALL4-A and increased pT stages (P = 0.026) in seminomas. Whereas in embryonal carcinomas, cytoplasmic expression of SALL4-A was associated with the tumor recurrence (P= 0.04) and invasion of the epididymis (P = 0.011). SALL4-A isoform expression in the cytoplasm and nucleus of TGCTs may be associated with histological differentiation. In the seminoma subtype of TGCTs, higher expression of SALL4-A may be used as a predictive indicator of poorer outcomes and prognosis.

Polyurethane-based three-dimensional printing for biological mesh carriers

Repair and reconstruction of the myopectineal orifice area using meshes is the mainstay of surgical treatment of inguinal hernias. However, the limitations of existing meshes are becoming increasingly evident in clinical applications; thus, the idea of using three-dimensionally (3D)-printed biological meshes was put forward. According to the current level of the 3D printing technology and the inherent characteristics of biological materials, the direct use of the 3D printing technology for making biological materials into finished products suitable for clinical applications is not yet supported, but synthetic materials can be first printed into 3D form carriers, compounded with biological materials, and finally made into finished products. The purpose of this study was to develop a technical protocol for making 3D-printed biomesh carriers using polyurethane as a raw material. In our study: raw material, polyurethane; weight, 20–30 g/m2; weaving method, hexagonal mesh; elastic tension aspect ratio, 2:1; diameters of pores, 0.1–1 mm; surface area, 8 × 12 cm2; the optimal printing layer height, temperature and velocity were 0.1 mm, 210–220 °C and 60 mm/s. Its clinical significance lies in: (1) applied to preoperative planning and design a detailed surgical plan; (2) applied to special types of surgery including patients in puberty, recurrent and compound inguinal hernias; (3) significantly improve the efficiency of doctor-patient communication; (4) it can shorten the operation and recovery period by about 1/3 and can save about 1/4 of the cost for patients; (5) the learning curve is significantly shortened, which is conducive to the cultivation of reserve talents.

Gastric microbiome and gastric cancer: Relationship, mechanism, and clinical significance

Gastric microbiome and gastric cancer: Relationship, mechanism, and clinical significance

Prognostic impact of suspicious extraabdominal lymph nodes on patient survival in advanced ovarian cancer.

To evaluate the clinical impact of suspicious extra-abdominal lymph nodes (EALNs) identified preoperatively on CT and/or PET/CT images in advanced ovarian cancer. A retrospective study was conducted with 122 patients diagnosed with stage III or IV ovarian cancer with preoperative CT and/or PET/CT images from 2006 to 2022. Imaging studies were evaluated for the presence, size and location of suspicious EALNs. Suspicious lymph node enlargement was defined by a cut-off ≥5mm short-axis dimension on CT and/or lesions with maximum standardized uptake values of ≥2.5 on PET/CT. This study only included patients who did not have their EALNs surgically removed. A total 109 patients met the inclusion criteria; 36 (33%) had suspicious EALNs and were categorized as "node-positive". The median overall survival (OS) was 45.73 months for the "node-positive" and 46.50 months for the "node-negative" patients (HR 1.17, 95% CI 0.68-2.00, p = 0.579). In multivariate analysis, after adjusting for other variables selected by process of backward elimination using a significance level of p<0.20, suspicious EALNs still showed no clinical significance on OS (aHR 1.20, 95% CI 0.67-2.13, p = 0.537) as well as progression-free survival (aHR 1.43, 95% CI 0.85-2.41, p = 0.174). Old age (aHR 2.23, 95% CI 1.28-3.89, p = 0.005) and platinum resistance (aHR 1.92, 95% CI 1.10-3.36, p = 0.023) affects adversely on OS. Suspicious EALNs did not worsen the prognosis of patients with advanced ovarian cancer. However, its impact on survival is not yet clarified. Further investigation is required to assess the clinical significance of suspicious EALNs on preoperative imaging studies.

Adenosine in Interventional Cardiology: Physiopathologic and Pharmacologic Effects in Coronary Artery Disease

This review article focuses on the role of adenosine in coronary artery disease (CAD) diagnosis and treatment. Adenosine, an endogenous purine nucleoside, plays crucial roles in cardiovascular physiology and pathology. Its release and effects, mediated by specific receptors, influence vasomotor function, blood pressure regulation, heart rate, and platelet activity. Adenosine therapeutic effects include treatment of the no-reflow phenomenon and paroxysmal supraventricular tachycardia. The production of adenosine involves complex cellular pathways, with extracellular and intracellular synthesis mechanisms. Adenosine’s rapid metabolism underscores its short half-life and physiological turnover. Furthermore, adenosine’s involvement in side effects of antiplatelet therapy, particularly ticagrelor and cangrelor, highlights its clinical significance. Moreover, adenosine serves as a valuable tool in CAD diagnosis, aiding stress testing modalities and guiding intracoronary physiological assessments. Its use in assessing epicardial stenosis and microvascular dysfunction is pivotal for treatment decisions. Overall, understanding adenosine’s mechanisms and clinical implications is essential for optimizing CAD management strategies, encompassing both therapeutic interventions and diagnostic approaches.

A study on construction of a prognosis model for liver cancer based on analgesic targets and screening therapeutic drugs.

Liver cancer is one of the most malignant liver diseases in the world, and the 5-year survival rate of such patients is low. Analgesics are often used to cure pain prevalent in liver cancer. The expression changes and clinical significance of the analgesic targets (ATs) in liver cancer have not been deeply understood. The purpose of this study is to clarify the expression pattern of ATs gene in liver cancer and its clinical significance. Through the comprehensive analysis of transcriptome data and clinical parameters, the prognosis model related to ATs gene is established, and the drug information sensitive to ATs is mined. The study primarily utilized transcriptomic data and clinical information from liver cancer patients sourced from The Cancer Genome Atlas (TCGA) database. These data were employed to analyze the expression of ATs, conduct survival analysis, gene set variation analysis (GSVA), immune cell infiltration analysis, establish a prognostic model, and perform other bioinformatic analyses. Additionally, data from liver cancer patients in the International Cancer Genome Consortium (ICGC) were utilized to validate the accuracy of the model. Furthermore, the impact of analgesics on key genes in the prognostic model was assessed using data from the Comparative Toxicogenomics Database (CTD). The study investigated the differential expression of 58 ATs genes in liver cancer compared to normal tissues. Patients were stratified based on ATs expression, revealing varied survival outcomes. Functional enrichment analysis highlighted distinctions in spindle organization, centrosome, and spindle microtubule functions. Prognostic modeling identified low TP53 expression as protective, while elevated CCNA2, NEU1, and HTR2C levels posed risks. Commonly used analgesics, including acetaminophen and others, were found to influence the expression of these genes. These findings provide insights into potential therapeutic strategies for liver cancer and shed light on the molecular mechanisms underlying its progression. The collective analysis of gene signatures associated with ATs suggests their potential as prognostic predictors in hepatocellular carcinoma patients. These findings not only offer insights into cancer therapy but also provide novel avenues for the development of indications for analgesics.

Pre- and Post-Exposure Prophylaxis for HIV in Patients Taking Anti-Seizure Medications

The prevention of human immunodeficiency virus (HIV) infection has recently emphasized the use of pre- and post-exposure prophylaxis (PrEP and PEP), both of which were highly effective in prevention of HIV infection. Since the last published guidance regarding the cotreatment of people with anti-seizure medications (ASM) and antiretroviral treatments (ARTs) in 2012, both fields have numerous new medication options. Historically, cotreatment of HIV and seizures could be challenging with increased risk of virologic failure and barriers in access to health care due to global availability, social determinants of health, and stigma of both HIV and seizures. In this narrative review, we describe the data-driven and expected bidirectional pharmacokinetic (PK) interactions between guideline-based PrEP and PEP treatment and ASM, as well as overlapping side effects. There are many ASMs with no known interaction with PrEP or PEP regimens. The interactions focus on enzyme inducing ASMs, valproate, and lamotrigine. Most prominently, enzyme inducing ASMs lower serum levels of tenofovir-containing PrEP regimens and elements of PEP (dolutegravir, raltegravir, and ritonavir), which increased risk of virologic treatment failure in people with HIV but have unclear clinical significance on the effectiveness of PrEP and PEP. In addition, ritonavir treatment in PEP may significantly lower lamotrigine serum levels even during the 4 weeks of treatment, which may increase risk for breakthrough seizures during PEP and skin reactions after discontinuation of ritonavir. In addition to PK interactions, overlapping side effects are common including osteopenia, hepatic toxicity, and other gastrointestinal effects. This narrative review aims to be a resource for all clinicians prescribing ASMs so that they can create a welcoming environment to enable successful treatment of seizures and reduce the risk of HIV infection in people at risk. In addition, we highlight knowledge gaps and areas of unmet need that can be addressed with future studies.

Quantified Metrics of Gastric Emptying Delay by Glucagon-Like Peptide-1 Agonists: A Systematic Review and Meta-Analysis With Insights for Periprocedural Management.

Divergent recommendations for periprocedural management of glucagon-like peptide-1 (GLP-1) receptor agonist (GLP-1 RA) medications rely on limited evidence. We performed a systematic review and meta-analysis to provide quantitative measures of gastric emptying relevant to mechanisms of weight loss and to periprocedural management of GLP-1 RA. We hypothesized that the magnitude of gastric emptying delay would be low and of limited clinical significance to procedural sedation risks. A protocolized search identified studies on GLP-1 RA that quantified gastric emptying measures. Pooled estimates using random effects were presented as a weighted mean difference with 95% confidence intervals (CIs). Univariate meta-regression was performed to assess the influence of GLP-1 RA type, short-acting vs long-acting mechanism of action, and duration of treatment on gastric emptying. Fifteen studies met the inclusion criteria. Five studies (n = 247) utilized gastric emptying scintigraphy. Mean T 1/2 was 138.4 minutes (95% CI 74.5-202.3) for GLP-1 RA vs 95.0 minutes (95% CI 54.9-135.0) for placebo, with a pooled mean difference of 36.0 minutes (95% CI 17.0-55.0, P < 0.01, I2 = 79.4%). Ten studies (n = 411) utilized the acetaminophen absorption test, with no significant delay in gastric emptying measured by T max , area under the curve (AUC) 4hr , and AUC 5hr with GLP-1 RA ( P > 0.05). On meta-regression, the type of GLP-1 RA, mechanism of action, and treatment duration did not impact gastric emptying ( P > 0.05). While a gastric emptying delay of ∼36 minutes is quantifiable on GLP-1 RA medications, it is of limited magnitude relative to standard periprocedural fasting periods. There were no substantial differences in gastric emptying on modalities reflective of liquid emptying (acetaminophen absorption test), particularly at time points relevant to periprocedural care.

Immunohistochemical Expression and Clinical Significance of WWP1 Protein in Nasopharyngeal Cancer.

Nasopharyngeal carcinoma (NPC) is a common malignant tumor of the head and neck. Its pathogenesis is complicated and needs further investigation. The aim of this study was to investigate the expression and clinical significance of WWP1 in NPC. Bioinformatics approaches were used to evaluate the expression and functions of WWP1 in NPC. WWP1 protein expression was then detected by immunohistochemistry on a tissue microarray in an NPC cohort and its association with clinical features and prognosis was determined. In addition, WWP1 expression was knocked down in NPC cells using RNA interference, and their colony formation and invasion abilities were assessed. A total of 25 genes closely related to WWP1, which may be enriched in different pathways, were filtered out. WWP1 expression was significantly higher in NPC cells than in normal controls. High WWP1 expression was correlated with lymph node metastasis, tumor recurrence, clinical stage and poor prognosis. Knockdown of WWP1 resulted in attenuated proliferation and invasion of NPC cells. The results suggest that WWP1 may serve as a novel biomarker and prognostic factor for NPC and a potential therapeutic target worthy of further investigation.

Erratum to: Clinical significance of Notch receptors in triple negative breast cancer

Erratum to: Clinical significance of Notch receptors in triple negative breast cancer

The Effect of Anesthesia on Passive Ankle Dorsiflexion.

Equinus contractures can commonly be due to contractures of gastrocnemius muscle or combined contractures of the gastrocnemius-soleus Achilles tendon complex. The decision to release part or all of the gastrocnemius-soleus Achilles tendon complex is often assessed intraoperatively while the patient is under anesthesia. It remains unknown whether the administration of general anesthesia affects the measurement of passive ankle dorsiflexion. The unaffected, nonoperative limb on 46 foot and ankle patients underwent a Silfverskiold test measuring passive ankle dorsiflexion preoperatively and intraoperatively after administration of general anesthesia using an instrumented force-angular displacement goniometer. To determine clinical significance, we surveyed experienced surgeons to estimate the perceived minimally detectable clinical accuracy for measuring passive ankle dorsiflexion. Forty-six subjects were included with mean age of 42 ± 14.8 years, mean body mass index of 26.2 ± 4.9, and 52% female. The mean change in dorsiflexion values from before anesthesia to after the administration of general anesthesia was 1.9 degrees with 10 lb of pressure with knee extended (E10), 2.3 degrees with 20 lb of pressure with knee extended (E20), 2.8 degrees with 10 lb of pressure with knee flexed (F10), and 2.3 degrees with 20 lb of pressure with knee flexed (F20) (all P < .001). Thirty-three of 45 (73%) surgeons responded to the survey; all thought their minimally detectable clinical accuracy was 5 degrees or greater. After the administration of general anesthesia, a small but likely not clinically detectable increase in passive ankle dorsiflexion occurs. The common clinical practice of making intraoperative treatment decisions regarding the presence of a gastrocnemius-soleus driven equinus contractures after general anesthesia without use of paralytic agents appears reasonable given the magnitude of the changes identified in this study. Level II, prospective cohort study.

Effect of the extrahepatic bile duct anatomy on choledocholithiasis and its clinical significance

BACKGROUND A comprehensive understanding of the extrahepatic bile duct anatomy is vital to guide surgical procedures and perform endoscopic retrograde cholangiography. Anatomical irregularities within the extrahepatic bile duct may increase susceptibility to bile duct stones. AIM To investigate the anatomical risk factors associated with extrahepatic bile ducts in patients diagnosed with choledocholithiasis, with a specific focus on preventing stone recurrence after surgical intervention and endoscopic lithotomy. METHODS We retrospectively analyzed the medical records of 124 patients without choledocholithiasis and 108 with confirmed choledocholithiasis who underwent magnetic resonance cholangiopancreatography examinations at our center between January 2022 and October 2022. Logistic regression analyses were conducted to identify the anatomical risk factors influencing the incidence of common bile duct stones. RESULTS Multivariate logistic regression analysis revealed that several factors independently contributed to choledocholithiasis risk. Significant independent risk factors for choledocholithiasis were diameter of the common hepatic [adjusted odds ratio (aOR) = 1.43, 95% confidence interval (CI): 1.07-1.92, adjusted P value = 0.016] and common bile (aOR = 1.68, 95%CI: 1.27-2.23, adjusted P value &lt; 0.001) ducts, length of the common hepatic duct (aOR = 0.92, 95%CI: 0.84-0.99, adjusted P value = 0.034), and angle of the common bile duct (aOR = 0.92, 95%CI: 0.89–0.95, adjusted P value &lt; 0.001). CONCLUSION The anatomical features of the extrahepatic bile duct were directly associated with choledocholithiasis risk. Key risk factors include an enlarged diameter of the common hepatic and bile ducts, a shorter length of the common hepatic duct, and a reduced angle of the common bile duct.

Incidental Apical Pleuroparenchymal Scarring on Computed Tomography: Diagnostic Yield, Progression, Morphologic Features and Clinical Significance.

Apical pleuroparenchymal scarring (APPS) is commonly seen on chest computed tomography (CT), though the imaging and clinical features, to the best of our knowledge, have never been studied. The purpose was to understand APPS's typical morphologic appearance and associated clinical features. A random generator selected 1000 adult patients from all 21516 chest CTs performed at urban outpatient centers from January 1, 2016 to December 31, 2016. Patients with obscuring apical diseases were excluded to eliminate confounding factors. After exclusions, 780 patients (median age: 64y; interquartile range: 56 to 72y; 55% males) were included for analysis. Two radiologists evaluated the lung apices of each CT for the extent of abnormality in the axial plane (mild: <5mm, moderate: 5 to 10mm, severe: >10mm), craniocaudal plane (extension halfway to the aortic arch, more than halfway, vs below the arch), the predominant pattern (nodular vs reticular and symmetry), and progression. Cohen kappa coefficient was used to assess radiologists' agreement in scoring. Ordinal logistic regression was used to determine associations of clinical and imaging variables with APPS. APPS was present on 65% (507/780) of chest CTs (54% mild axial; 80% mild craniocaudal). The predominant pattern was nodular and symmetric. Greater age, female sex, lower body mass index, greater height, and white race were associated with more extensive APPS. APPS was not found to be associated with lung cancer in this cohort. Classifying APPS by the extent of disease in the axial or craniocaudal planes, in addition to the predominant pattern, enabled statistically significant associations to be determined, which may aid in understanding the pathophysiology of apical scarring and potential associated risks.

The Glabridin from Huangqin Decoction Prevents the Development of Ulcerative Colitis into Colitis-Associated Colorectal Cancer by Modulating MMP1/MMP3 Activity

Background and AimHuangqin decoction (HQD) is a Chinese medicine used to treat colitis and colorectal cancer (CRC). However, the specific compounds and mechanisms of HQD remain unclear despite its good curative clinical results. Through bioinformatics, network pharmacology, and experiments, this study aims to explore the progressive mechanisms of colitis-associated colorectal cancer (CAC) from ulcerative colitis (UC) while examining the protective effects of HQD and its compounds against this. MethodsBioinformatics was utilized to identify the hub genes between UC and CRC, and their clinical predictive significance, function, and expression were validated. Employing network pharmacology in combination with hub genes, key targets of HQD for preventing the development of UC into CAC were identified. Molecular docking and molecular dynamics (MD) were utilized to procure compounds that effectively bind to these targets and their transcription factors (TFs). Finally, the expression and mechanism of key targets were demonstrated in mice with UC or CAC. Results(1) Joint analysis of UC and CRC gene sets resulted in 14 hub genes, mainly related to extracellular matrix receptor binding, biological processes in the extracellular matrix, focal adhesion and neutrophil migration; (2) Network pharmacology results show HQD has 133 core targets for treating UC and CRC, acting on extracellular matrix, inflammatory bowel disease, chemical carcinogen receptor activation and other pathways; (3) The intersection of hub genes and core targets yielded two key targets, MMP1 and MMP3; (4) STAT3 is a shared TF of MMP1 and MMP3. (5) Molecular docking and MD verified that the dockings between Glabridin and STAT3/MMP1/MMP3 are stable and reliable; (6) In murine vivo experiments verified that Glabridin reduces inflammation, extracellular matrix degradation, and the occurrence of epithelial-mesenchymal transition to prevent UC transforming into CAC by inhibiting the phosphorylation of STAT3 and regulating the activity of MMP1/3.