Terlipressin versus placebo or noradrenalin in the treatment of hepatorenal syndrome: a systematic review and meta-analysis.

Background: Hepatorenal syndrome (HRS) bears a very poor prognosis with unmet need for safe and effective therapies. This systematic review and meta-analysis aimed to re-assess safety and efficacy of terlipressin versus placebo or noradrenaline for HRS, based on previous randomized controlled trials (RCTs). Methods: PubMed, EMBASE, MEDLINE (OvidSP) and Cochrane registers were searched for trials reporting HRS treatment by terlipressin or noradrenaline. Search terms included: "hepatorenal syndrome", "terlipressin", "noradrenaline", and corresponding synonyms. Comparisons between terlipressin, noradreanaline, placebo and albumin were included. Meta-analysis was conducted for treatment response (both HRS reversal and complete response), mortality and adverse events. Results: 15 RCTs were included, enrolling 1236 HRS patients (type 1: 1166, type 2: 70). Treatment with terlipressin+albumin resulted in significantly higher treatment response than placebo+albumin or albumin alone (risk ratio [RR]:2.75, 95% confidence interval [CI]:1.96 to 3.84; I2 = 28%, p = 0.23; n = 6). Noradrenaline was equally effective in treatment response compared to terlipressin (RR:1.19, 95% CI:0.96 to 1.46; I2 = 16%, p = 0.31; n = 7), but trials were limited by its non-blind design and small size. Sensitivity analysis showed no survival benefit with terlipressin compared to either placebo (RR:1.03, 95% CI:0.83 to 1.28; I2 = 0%, p = 0.72; n = 3) or noradreanline (RR:0.83, 95% CI:0.69 to 1.00; I2 = 4%, p = 0.39; n = 7) at 30 days of follow-up. Terlipressin carried higher risk of treatment-related adverse events compared to either placebo (RR:2.92, 95% CI:1.48 to 5.77; I2 = 0%, p = 0.75; n = 3) or noradrenaline (RR:2.45, 95% CI:1.37 to 4.37; I2 = 0%, p = 0.92; n = 5). Conclusion: Terlipressin is superior to placebo, and comparable to noradreanline in treatment response, but survival benefit is lacking. Noradrenaline, with low certainty, may be a better alternative for HRS.

Incorporation of small extracellular vesicles in PEG/HA-Bio-Oss hydrogel composite scaffold for bone regeneration.

Stem cell derived small extracellular vesicles (sEVs) have emerged as promising nanomaterials for the repair of bone defects. However, low retention of sEVs affects their therapeutic effects. Clinically used natural substitute Bio-Oss bone powder lack high compactibility and efficient osteo-inductivity that limit its clinical application in repairing large bone defects. In this study, a poly ethylene glycol/hyaluronic acid (PEG/HA) hydrogel was used to stabilize Bio-Oss and incorporate rat bone marrow stem cell-derived sEVs (rBMSCs-sEVs) to engineer a PEG/HA-Bio-Oss (PEG/HA-Bio) composite scaffold. Encapsulation and sustained release of sEVs in hydrogel scaffold can enhance the retention of sEVs in targeted area, achieving long-lasting repair effect. Meanwhile, synergistic administration of sEVs and Bio-Oss in cranial defect can improve therapeutic effects. The PEG/HA-Bio composite scaffold showed good mechanical properties and biocompatibility, supporting the growth of rBMSCs. Furthermore, sEVs enhanced in vitro cell proliferation and osteogenic differentiation of rBMSCs. Implantation of sEVs/PEG/HA-Bio in rat cranial defect model promoted in vivo bone regeneration, suggesting the great potential of sEVs/PEG/HA-Bio composite scaffold for bone repair and regeneration. This will hopefully provide a strategy for combining hydrogel composite scaffold systems and stem cell-derived sEVs in the field of applied tissue engineering repair. .

Classification of coronary artery disease using radial artery pulse wave analysis via machine learning.

BACKGROUND: Coronary artery disease (CAD) is a major global cardiovascular health threat and the leading cause of death in many countries. The disease has a significant impact in China, where it has become the leading cause of death. There is an urgent need to develop non-invasive, rapid, cost-effective, and reliable techniques for the early detection of CAD using machine learning (ML). METHODS: Six hundred eight participants were divided into three groups: healthy, hypertensive, and CAD. The raw data of pulse wave from those participants was collected. The data were de-noised, normalized, and analyzed using several applications. Seven ML classifiers were used to model the processed data, including Decision Tree (DT), Random Forest (RF), Gradient Boosting Decision Tree (GBDT), Extra Trees (ET), Extreme Gradient Boosting (XGBoost), Light Gradient Boosting (LightGBM), and Unbiased Boosting with Categorical Features (CatBoost). RESULTS: The Extra Trees classifier demonstrated the best classification performance. After tunning, the results performance evaluation on test set are: 0.8579 accuracy, 0.9361 AUC, 0.8561 recall, 0.8581 precision, 0.8571 F1 score, 0.7859 kappa coefficient, and 0.7867 MCC. The top 10 feature importances of ET model are w/t1, t3/tmax, tmax, t3/t1, As, hf/3, tf/3/tmax, tf/5, w and tf/3/t1. CONCLUSION: Radial artery pulse wave can be used to identify healthy, hypertensive and CAD participants by using Extra Trees Classifier. This method provides a potential pathway to recognize CAD patients by using a simple, non-invasive, and cost-effective technique.

The Immunosuppressive Receptor CD32b Regulation of Macrophage Polarization and Its Implications in Tumor Progression.

Macrophages, pivotal components of the immune system, orchestrate host defense mechanisms in humans and mammals. Their polarization into classically activated macrophages (CAMs or M1) and alternatively activated macrophages (AAMs or M2) dictates distinct functional roles in immunity and tissue homeostasis. While the negative regulatory role of CD32b within the FC gamma receptor (FCγR) family is recognized across various immune cell types, its influence on macrophage polarization remains elusive. This study aimed to elucidate the regulatory role of CD32b in macrophage polarization and discern the differential expression markers between the M1 and M2 phenotypes following CD32b siRNA transfection. The results revealed a decrease in the CD32b levels in lipopolysaccharide (LPS)-treated M1 and an increase in interleukin-4 (IL-4)-treated M2 macrophages, as observed in macrophage Raw264.7 cells. Furthermore, CD32b siRNA transfection significantly downregulated the M2 markers (IL-10, VEGF, Arg-1, and STAT6), while upregulating the M1 markers (IL-6, NF-κB, NOS2, and STAT1) in the Raw264.7 cells. Similar findings were recapitulated in macrophage-rich adherent cells isolated from mouse spleens. Additionally, the cytopathological analysis of pleural effusions and ascitic fluids from patients with cancer revealed a positive correlation between advanced tumor stages, metastasis, and elevated CD32b levels. In conclusion, this study highlights the regulatory influence of CD32b in suppressing M1 expression and promoting M2 polarization. Moreover, heightened M2 activation and CD32b levels appear to correlate with tumor progression. A targeted CD32b blockade may serve as a novel therapeutic strategy to inhibit M2 macrophage polarization and is promising for anti-tumor intervention.

Causal pathways in preeclampsia: a Mendelian randomization study in European populations.

Purpose: Our study utilizes Mendelian Randomization (MR) to explore the causal relationships between a range of risk factors and preeclampsia, a major contributor to maternal and perinatal morbidity and mortality. Methods: Employing the Inverse Variance Weighting (IVW) approach, we conducted a comprehensive multi-exposure MR study analyzing genetic variants linked to 25 risk factors including metabolic disorders, circulating lipid levels, immune and inflammatory responses, lifestyle choices, and bone metabolism. We applied rigorous statistical techniques such as sensitivity analyses, Cochran's Q test, MR Egger regression, funnel plots, and leave-one-out sensitivity analysis to address potential biases like pleiotropy and population stratification. Results: Our analysis included 267,242 individuals, focusing on European ancestries and involving 2,355 patients with preeclampsia. We identified strong genetic associations linking increased preeclampsia risk with factors such as hyperthyroidism, BMI, type 2 diabetes, and elevated serum uric acid levels. Conversely, no significant causal links were found with gestational diabetes, total cholesterol, sleep duration, and bone mineral density, suggesting areas for further investigation. A notable finding was the causal relationship between systemic lupus erythematosus and increased preeclampsia risk, highlighting the significant role of immune and inflammatory responses. Conclusion: This extensive MR study sheds light on the complex etiology of preeclampsia, underscoring the causal impact of specific metabolic, lipid, immune, lifestyle, and bone metabolism factors. Our findings advocate for a multidimensional approach to better understand and manage preeclampsia, paving the way for future research to develop targeted preventive and therapeutic strategies.

Analysis of the Improvement Sequence in Insomnia Symptoms and Factors Influencing the Treatment Outcomes of Smartphone-Delivered CBT in Patients with Insomnia Disorder.

Background: The effectiveness of medication combined with smartphone-delivered cognitive behavioral therapy for insomnia (CBT-I) has been well verified, but there are few studies on the sequence of remission of insomnia symptoms. This study aims to understand the sequence of symptom improvement and the factors influencing the treatment effectiveness in patients with insomnia. Methods: Smartphone-delivered CBT, as a form of Online CBT, allows for training through mobile devices at any time and place. We utilized the Good Sleep 365 app to conduct a survey, involving 2820 patients who met the baseline inclusion criteria. These patients were assessed using a general demographic questionnaire and the Pittsburgh Sleep Quality Index (PSQI) to evaluate general demographic information and insomnia symptoms, and subsequently underwent CBT training using the Good Sleep 365 app. A total of 1179 patients completed follow-ups at 4 weeks, 8 weeks, 16 weeks, and 24 weeks. Results: At 4 weeks and 8 weeks, the descending order of the reduction rates of PSQI components (excluding component 6: use of sleeping medication) was: sleep latency, subjective sleep quality, sleep efficiency, sleep disturbance, sleep maintenance, and daytime dysfunction. At 16 weeks and 24 weeks, the descending order was subjective sleep quality, sleep latency, sleep efficiency, daytime dysfunction, sleep maintenance, and sleep disturbance. There were significant differences in the reduction rates of PSQI components (excluding component 6: use of sleeping medication) both at the same follow-up times and at different follow-up times (all P<0.05). Multivariable logistic regression analysis showed that patients older than 30 years and those with a college degree or above had better treatment outcomes, whereas those with a disease duration of more than three years had worse outcomes. Conclusion: The sequence of symptom improvement in patients with insomnia changes over time, and age, educational level, and duration of disease are factors influencing treatment outcomes.

Preoperative Structural Risk Factors for Glaucoma After Penetrating Keratoplasty for Congenital Corneal Opacity: An Observational Study.

INTRODUCTION: Post-keratoplasty glaucoma (PKG) is a major complication following penetrating keratoplasty (PKP) for congenital corneal opacity (CCO). This study aims to assess the preoperative structural risk factors for PKG following PKP for CCO using ultrasound biomicroscopy (UBM). METHODS: Pediatric patients with CCO who underwent preoperative UBM and primary PKP were enrolled. Patients with anterior segment operation history or with a follow-up duration less than 12 months were excluded. The structural features of the anterior segment including central corneal thickness, anterior chamber depth, angle closure range (ACR), anterior synechia range, maximum iridocorneal adhesion length, abnormal iridocorneal synechia, and lens anomalies were identified on UBM images. The medical histories were reviewed to identify clinical features. The incidence of PKG was assessed to determine significant structural and clinical risk factors. RESULTS: Fifty-one eyes of 51 pediatric patients with CCO were included. The median age at surgery was 8.0 months, and the mean follow-up duration was 33 ± 9 months. Eleven (21.6%) eyes developed PKG. The main structural risk factors were abnormal iridocorneal synechia (P = 0.015), lens anomaly (P = 0.001), and larger ACR (P = 0.045). However, a larger range of normal anterior synechia without involvement of the angle was not a significant risk factor. Preoperative glaucoma (P < 0.001) and higher intraocular pressure (P = 0.015) were clinical risk factors. A shallow anterior chamber was a unique risk factor for sclerocornea (P = 0.019). CONCLUSIONS: Detailed preoperative examination of iridocorneal synechia, lens, and angle closure using UBM is critical for PKG risk assessment, surgical prognosis evaluation, and postoperative management in patients with CCO.

Association between obstructive sleep apnea and 24-h urine protein quantification in patients with hypertension.

The association between obstructive sleep apnea (OSA) and proteinuria is undetermined, with few studies on hypertension, a high-risk group for renal impairment. Therefore, we aimed to explore whether OSA is an independent risk factor for proteinuria in patients with hypertension. We investigated the cross-sectional association between OSA and proteinuria. Participants were divided into groups by apnea hypopnea index (AHI) category. Multivariable Logistic regression analysis was used to evaluate the association between OSA severity, objectively measured sleep dimensions, and proteinuria which is mainly defined by 24-h urine protein quantification > 300 mg/24 h. Sensitivity analyses were performed by excluding those with comorbidities (primary aldosteronism and homocysteine ≥ 15 µmol/L). Of the 2106 participants, the mean age was 47.57 ± 10.50 years, 67.2% were men, and 75.9% were OSA patients. In total participants, compared with those without OSA, patients with mild OSA, moderate OSA, and severe OSA showed 1.09 (95% CI 0.80-1.40), 1.24 (95% CI 0.89-1.74) and 1.47 (95% CI 1.04-2.08) fold risk for proteinuria with a trend test P trend < 0.05. Each 10-unit increase in the AHI, oxygen desaturation index (ODI), and time spent with oxygen saturation < 90% (T90) was found to be associated with 13%, 10%, and 2% higher likelihood of proteinuria in the crude model, significant in adjusted models. The more severe the OSA is, the higher the risk of proteinuria. AHI and T90 are independently associated with a higher risk of structural renal damage in the population with hypertension.

Emulation of neuron and synaptic functions in spin-orbit torque domain wall devices.

Neuromorphic computing (NC) architecture has shown its suitability for energy-efficient computation. Amongst several systems, spin-orbit torque (SOT) based domain wall (DW) devices are one of the most energy-efficient contenders for NC. To realize spin-based NC architecture, the computing elements such as synthetic neurons and synapses need to be developed. However, there are very few experimental investigations on DW neurons and synapses. The present study demonstrates the energy-efficient operations of neurons and synapses by using novel reading and writing strategies. We have used a W/CoFeB-based energy-efficient SOT mechanism to drive the DWs at low current densities. We have used the concept of meander devices for achieving synaptic functions. By doing this, we have achieved 9 different resistive states in experiments. We have experimentally demonstrated the functional spike and step neurons. Additionally, we have engineered the anomalous Hall bars by incorporating several pairs, in comparison to conventional Hall crosses, to increase the sensitivity as well as signal-to-noise ratio (SNR). We have performed micromagnetic simulations and transport measurements to demonstrate the above-mentioned functionalities.

Exploring the relationship between depressive symptoms, problematic smartphone use, and cumulative risk factors in nursing students: A cross sectional study.

BACKGROUND: No single risk factor is decisive in shaping an individual's healthy development. This study aimed to analyze the relationship between depressive symptoms and a cumulative risk index comprising individual, family, and social variables among nursing students. METHODS: We enrolled 1716 Chinese nursing students from three universities in a paperless survey that assessed a range of individual, family, and social risk factors associated with depressive symptoms. Multiple risk analysis was conducted to create a composite risk score for each individual. A test for trend was employed to assess the relationship between the multiple risk classification and depressive symptoms individually. Additionally, a 2-step cluster analysis and χ2 tests were used to examine the relationship between the different clusters and the level of depressive symptoms. RESULTS: The mean scores of depressive symptoms increased significantly as the number of risk factors increased, regardless of their combination. As the number of risk factors increased, the proportion of nursing students in the normal group decreased, while the proportion in the group with depressive symptoms of varying severity tended to increase (P < 0.001). A high-risk cluster characterized by poor sleep quality combined with problematic smartphone use was associated with higher levels of depressive symptoms (P < 0.001). CONCLUSION: Based on these findings that cumulative exposure to multiple risk factors is more harmful than cumulative exposure to fewer risk factors, then interventions that isolate only one risk factor are less likely to be effective than those that are multifaceted.

Comprehensive molecular characterization of collecting duct carcinoma for therapeutic vulnerability.

Collecting duct carcinoma (CDC) is an aggressive rare subtype of kidney cancer with unmet clinical needs. Little is known about its underlying molecular alterations and etiology, primarily due to its rarity, and lack of preclinical models. This study aims to comprehensively characterize molecular alterations in CDC and identify its therapeutic vulnerabilities. Through whole-exome and transcriptome sequencing, we identified KRAS hotspot mutations (G12A/D/V) in 3/13 (23%) of the patients, in addition to known TP53, NF2 mutations. 3/13 (23%) patients carried a mutational signature (SBS22) caused by aristolochic acid (AA) exposures, known to be more prevalent in Asia, highlighting a geologically specific disease etiology. We further discovered that cell cycle-related pathways were the most predominantly dysregulated pathways. Our drug screening with our newly established CDC preclinical models identified a CDK9 inhibitor LDC000067 that specifically inhibited CDC tumor growth and prolonged survival. Our study not only improved our understanding of oncogenic molecular alterations of Asian CDC, but also identified cell-cycle machinery as a therapeutic vulnerability, laying the foundation for clinical trials to treat patients with such aggressive cancer.

Progressive conjunctival invasion of cornea in a child with Warburg-Cinotti Syndrome: a case report.

BACKGROUND: Warburg-Cinotti syndrome is a rare syndrome caused by de novo or inherited variants in discoding domain receptor tyrosine kinase 2 (DDR2). Only six cases have been reported worldwide and our knowledge of this disease remained sparse especially from an ophthalmological perspective, since previous literature mostly focused on systemic malformations or genetics. CASE PRESENTATION: A seven-year-old boy developed a gelatinous vascularized conjunctiva-like mass secondary to trauma. The mass enlarged and gradually invaded the cornea. With each surgical intervention, the mass recurred and grew even larger rapidly. The patient ended up with the mass covering the entire cornea along with symblepharon formation. Whole exome sequencing revealed a hemizygous variant in the DDR2 gene, which is consistent with Warburg-Cinotti syndrome. CONCLUSIONS: Considering Warburg-Cinotti syndrome, we should be vigilant of patients exhibiting progressive conjunctival invasion of the cornea, even those without systemic manifestations or a positive family history.

The affective factors of depression symptoms in hypertensive patients and the protective effect of physical activity.

OBJECTIVE: To investigate the potential affective factors of depressive symptoms in patients with hypertension and explore the protective effects of physical activity. METHODS: 211 hypertensive patients aged over 18 years were consecutively recruited. All patients completed a self-designed questionnaire and the Hospital Anxiety and Depression Scale (HADS) to assess the coexistence of depressive symptoms, and psychiatrists were invited to diagnose depression when necessary. Full-night polysomnography was performed to detect the sleep pattern. The association between sleep structure and depressive symptoms was tested by using logistic regression analysis, and contributing factors as well as the effect of physical activity were assessed among patients with and without depressive symptoms. RESULTS: Of the 211 subjects, 33.6% of cases were coexistent with depressive symptoms. Female gender [OR (95%CI): 2.83 (1.44-5.57), P = 0.003) and the greater percentage of REM stage [OR (95%CI): 1.09 (1.01-1.18), P = 0.024] were the risk factors of depressive symptoms, while doing physical activity showed as the protective factor. Patients with REM stage ≥ 20% showed a higher score on HADS-D than those with REM stage < 20% [(4.9 ± 3.8) vs. (3.7 ± 3.1), P = 0.018]. Compared to individuals who never did physical activity, those who did physical activity 1-2 times per week and ≥ 3 times per week had a 52% and 62% risk reduction in depressive symptoms respectively. Patients who did physical activity had lower levels of high-sensitivity C-reactive protein (hs-CRP) compared to those who never did physical activity. CONCLUSION: Female gender and a higher percentage of REM stage are risk factors for depressive symptoms in hypertension, while physical activity may benefit depressive symptoms by reducing serum levels of hs-CRP.

Plasma aldosterone concentrations elevation in hypertensive patients: the dual impact on hyperuricemia and gout.

Background: Prior research has highlighted the association between uric acid (UA) and the activation of the renin-angiotensin-aldosterone system (RAAS). However, the specific relationship between aldosterone, the RAAS's end product, and UA-related diseases remains poorly understood. This study aims to clarify the impact of aldosterone on the development and progression of hyperuricemia and gout in hypertensive patients. Methods: Our study involved 34534 hypertensive participants, assessing plasma aldosterone concentration (PAC)'s role in UA-related diseases, mainly hyperuricemia and gout. We applied multiple logistic regression to investigate the impact of PAC and used restricted cubic splines (RCS) for examining the dose-response relationship between PAC and these diseases. To gain deeper insights, we conducted threshold analyses, further clarifying the nature of this relationship. Finally, we undertook subgroup analyses to evaluate PAC's effects across diverse conditions and among different subgroups. Results: Multivariate logistic regression analysis revealed a significant correlation between the occurrence of hyperuricemia and gout and the elevation of PAC levels. Compared to the first quartile (Q1) group, groups Q2, Q3, and Q4 all exhibited a significantly increased risk of occurrence. Moreover, the conducted RCS analysis demonstrated a significant nonlinear dose-response relationship, especially when PAC was greater than 14 ng/dL, with a further increased risk of hyperuricemia and gout. Finally, comprehensive subgroup analyses consistently reinforced these findings. Conclusion: This study demonstrates a close association between elevated PAC levels and the development of UA-related diseases, namely hyperuricemia and gout, in hypertensive patients. Further prospective studies are warranted to confirm and validate this relationship.

Associations between thyroid function, thyroid diseases, and primary aldosteronism.

OBJECTIVE: Previous studies focusing on primary aldosteronism (PA) and thyroid diseases were controversial. Hence, this study aimed to examine associations between thyroid function, thyroid diseases, and PA and its subtypes. DESIGN AND METHODS: This was a cross-sectional study, which enrolled 1023 patients with PA and 6138 patients with essential hypertension (EH) admitted to Hypertension Center of People's Hospital of Xinjiang Uygur Autonomous Region from August 2011 to June 2022. All patients with PA were accurately classified into aldosterone-producing adenoma (APA) and idiopathic hyperaldosteronism (IHA) by adrenal vein sampling (AVS). Multivariate logistic regression analysis was used to assess the relationship of thyroid function, thyroid nodules, and PA and its subtypes. RESULTS: A total of 7161 patients (327 APA and 696 IHA, and 6138 EH) were included with a mean age of 48.20 ± 8.83 years. PA patients and PA subtypes showed lower FT4, FT3, TT4, TT3, and prevalence of positive TPOAb, meanwhile higher prevalence of thyroid nodules than EH patients (PA: 56.10%, IHA: 56.90%, APA: 54.80%, and EH: 48.90%, respectively). PA (adjusted OR: 1.290, 95% CI: 1.035-1.607, P = .02) and its subtype (IHA) (adjusted OR: 1.316, 95% CI: 1.005-1.724, P = .04) were significantly associated with thyroid nodules. Compared to patients with lower plasma aldosterone concentration (PAC) levels (<12 ng/dL), patients with PAC levels ≥ 12 ng/dL presented a higher prevalence of thyroid nodules. CONCLUSIONS: PA patients had lower thyroid function and higher prevalence of thyroid nodules compared to EH patients. Therefore, the screening of thyroid function and thyroid nodules may be indispensable for PA patients.

SARS-CoV-2 reinfection broadens the antibody responses and promotes the phenotypic differentiation of virus-specific memory T cells in adolescents.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants raises concerns regarding the effectiveness of immunity acquired from previous Omicron subvariants breakthrough infections (BTIs) or reinfections (RIs) against the current circulating Omicron subvariants. In this study, we prospectively investigate the dynamic changes of virus-specific antibody and T cell responses among 77 adolescents following Omicron BA.2.3 BTI with or without subsequent Omicron BA.5 RI. Notably, the neutralizing antibodies (NAbs) titers against various detected SARS-CoV-2 variants, especially the emerging Omicron CH.1.1, XBB.1.5, XBB.1.16, EG.5.1, and JN.1 subvariants, exhibited a significant decrease along the time. A lower level of IgG and NAbs titers post-BTI was found to be closely associated with subsequent RI. Elevated NAbs levels and shortened antigenic distances were observed following Omicron BA.5 RI. Robust T cell responses against both Omicron BA.2- and CH.1.1-spike peptides were observed at each point visited. The exposure to Omicron BA.5 promoted phenotypic differentiation of virus-specific memory T cells, even among the non-seroconversion adolescents. Therefore, updated vaccines are needed to provide effective protection against newly emerging SARS-CoV-2 variants among adolescents.

Spatially Resolved Niche and Tumor Microenvironmental Alterations in Gastric Cancer Peritoneal Metastases.

BACKGROUND AND AIMS: Peritoneal metastasis (PM) in gastric cancer (GC) is associated with poor prognosis and significant morbidity. We sought to understand the genomic, transcriptomic, and tumor microenvironment (TME) features that contribute to peritoneal organotropism in GC. METHODS: We conducted a comprehensive multi-omic analysis of 548 samples from 326 patients, including primary tumors, matched normal tissues; peritoneal metastases, and adjacent-normal peritoneal tissues. We used whole exome sequencing, whole transcriptome sequencing, and digital spatial profiling to investigate molecular alterations, gene expression patterns, and TME characteristics associated with PM. RESULTS: Our analysis identified specific genomic alterations in primary tumors, including mutations in ELF3, CDH1, and PIGR, and TME signatures, such as stromal infiltration and M2 macrophage enrichment, associated with increased risk of PM. We observed distinct transcriptional programs and immune compositions in GCPM compared with liver metastases, highlighting the importance of the TME in transcoelomic metastasis. We found differential expression of therapeutic targets between primary tumors and PM, with lower CLDN18.2 and FGFR2b expression in PM. We unravel the roles of the TME in niche reprogramming within the peritoneum, and provide evidence of pre-metastatic niche conditioning even in early GC without clinical PM. These findings were further validated using a humanized mouse model, which demonstrated niche remodeling in the peritoneum during transcoelomic metastasis. CONCLUSION: Our study provides a comprehensive molecular characterization of GCPM and unveils key biological principles underlying transcoelomic metastasis. The identified predictive markers, therapeutic targets, and TME alterations offer potential avenues for targeted interventions and improved patient outcomes.

Improvement of the Diagnostic Method for the Detection of Parasite Eggs Using the Formalin Ethyl Acetate Concentration Technique.

PURPOSE: The formalin-ethyl acetate (FEA) concentration method is commonly used in routine clinical practice to detect parasite eggs in feces. This procedure involves extraction of oil with the organic solvent ethyl acetate (EA), which reduces fecal sediment and provides a cleaner background for microscopic analysis. However, clinically, some sediment failed to float after EA treatment. METHODS: Hexane, commonly used in the food oil extraction from oilseeds did not float the feces. Gas chromatography-mass spectrometry (GC-MS) analysis showed that neither the amount of the oil nor the classes of the oil determined was differed whether hexane or EA was used to float the feces. Oil red, Bodipy and Calcofluor staining showed that the unabsorbed oil droplets in the fecal sediment were trapped within the leaf structure. HCl or acetic acid was added to see if the acid residue could dissolve the cellulose of the leaf to promote the bulk float. RESULTS: Our result showed that the fecal bulk contained the loosened mesophyll cell wall. The addition of acid residues improved fecal bulk float. The proximity of cellulose fiber to EA, but not hexane, may enhance the efficacy of oil extraction from cellulose. CONCLUSION: This is the first report that the interaction of cellulose with ethyl acetate in fecal solution has an effect on bulk float. This study improves the understanding of fecal bulk flotation and may assist in the visualization of parasite eggs in clinical practice with non-floating fecal samples in the FEA concentration method.

Clinical research progress on acupuncture for the treatment of otogenic vertigo.

Otogenic vertigo is a common disorder that affects the vestibular system, which often results in considerable discomfort and impaired daily functioning. Traditional Chinese medicine (TCM), including acupuncture and moxibustion, has been historically utilized to manage the symptoms of vertigo. However, the effectiveness and methodology of these treatments have rarely been investigated in the medical literature. This study reviews the existing literature on the point selection, method, and therapeutic effect of acupuncture and moxibustion to provide a reference for the TCM treatment of otogenic vertigo. A literature search was performed using the PubMed search engine. The terms used included otogenic vertigo, acupuncture treatment, and acupuncture point selection. A total of 34 relevant articles were retrieved from PubMed. These suggest that the clinical treatment of otogenic vertigo should consider the functions of zang-fu organs and meridians and select different acupuncture treatment methods according to syndrome differentiation based on the difference between deficiency and excess. Acupuncture and moxibustion therapy should be based on acupoint selection, considering the syndrome differentiation, supplemented with experience. The treatment of otogenic vertigo with acupuncture and moxibustion refers to the selection of appropriate acupuncture methods under the guidance of TCM theory and following the principles of syndrome, disease, and meridian differentiation. Common acupuncture methods include body acupuncture, auricular acupuncture, scalp acupuncture, acupoint injection, electroacupuncture, and moxibustion. There are many acupuncture and moxibustion acupoints selected for the treatment of otogenic vertigo. Individualized treatment according to the patient's specific condition is effective and safe, which can help to improve the patient's vertigo symptoms and cerebral blood perfusion.

Decoding connections in the European population: serum uric acid, sex hormone-binding globulin, total testosterone, estradiol, and female infertility - advanced bidirectional and mediative Mendelian randomization.

Background: Despite observational links between serum uric acid (SUA), sex hormone-related phenotypes, and female infertility, the causality behind these associations remains uncertain. Objective: This study utilizes Bidirectional Two-Sample and Mediation Mendelian Randomization to explore the causal relationships and mediation effects of sex hormone-binding globulin (SHBG), total testosterone (TT), and estradiol on these associations. Methods: We analyzed single-nucleotide polymorphisms (SNPs) associated with SUA and sex hormone levels using data from large-scale GWAS of European populations. Female infertility data were sourced from 6,481 cases and 75,450 controls in the FinnGen Consortium. We employed methods including Inverse Variance Weighted (IVW), Weighted Median, and MR-Egger regression to assess causality. Results: We found that elevated SUA levels causally increase the risk of female infertility (IVW OR: 1.13, P=0.047). Elevated SUA levels significantly decrease SHBG levels (ß=-0.261; P=2.177e-04), with SHBG mediating 27.93% of the effect of SUA on infertility (OR=0.854; 95%CI, 0.793-0.920; P=2.853e-05). Additionally, elevated TT levels, which were associated with decreased SUA levels (ß=-0.127), showed an indirect effect on infertility mediated by SUA (ß=-0.0187; 95% CI, -0.041 to -0.003; P=0.046). Conclusion: Our findings demonstrate causal links between high SUA and increased risk of female infertility mediated by hormonal factors such as SHBG and TT. These insights suggest new avenues for infertility treatment and highlight the need for further research into these mechanisms.