The ability to control the catalytic activity of enzymes in chemical transformations is essential for the design and development of artificial catalysts. Herein, we report the synthesis and characterization of functional ligands featuring two 1,4,7,10-tetraazacyclododecane units linked by an azobenzene group and their corresponding dinuclear Zn(II) complexes. We show that the configuration switching (E/Z) of the azobenzene spacer in the ligands and their dinuclear Zn(II) complexes is reversibly controlled by irradiation with UV and visible light. The Zn(II)-metal complexes are light-responsive catalysts for the hydrolytic cleavage of nerve agent simulants, i.e., p-nitrophenyl diphenyl phosphate and methyl paraoxon. The catalytic activity of the Z-isomers of the dinuclear Zn(II) complexes outperformed that of the E-counterparts. Moreover, combining the less active E-isomers with gold nanoparticles induced an enhancement in the hydrolysis rate of p-nitrophenyl diphenyl phosphate. Kinetic analysis has shown that the catalytic site appears to involve a single metal ion. We explain our results by considering the different desolvation effects occurring in the catalyst's configurations in the solution and the catalytic systems involving gold nanoparticles.
The effect of strong metal-support interaction (SMSI) has never been systematically studied in the field of nanozyme-based catalysis before. Herein, by coupling two different Pd crystal facets with MnO2, i.e., (100) by Pd cube (Pdc) and (111) by Pd icosahedron (Pdi), we observed the reconstruction of Pd atomic structure within the Pd-MnO2 interface, with the reconstructed Pdc (100) facet more disordered than Pdi (111), verifying the existence of SMSI in such coupled system. The rearranged Pd atoms in the interface resulted in enhanced uricase-like catalytic activity, with Pdc@MnO2 demonstrating the best catalytic performance. Theoretical calculations suggested that a more disordered Pd interface led to stronger interactions with intermediates during the uricolytic process. In vitro cell experiments and in vivo therapy results demonstrated excellent biocompatibility, therapeutic effect, and biosafety for their potential hyperuricemia treatment. Our work provides a brand-new perspective for the design of highly efficient uricase-mimic catalysts.
Ruthenium complexes are one of the most promising anticancer drugs and ferroptosis is a novel form of regulated cell death, the study on the effect of Ru complexes on ferroptosis is helpful to find more effective antitumor drugs. Here, the synthesis and characterization of two Ru complexes containing 8-hydroxylquinoline and triphenylphosphine as ligands, [Ru(L1) (PPh3)2Cl2] (Ru-1), [Ru(L2) (PPh3)2Cl2] (Ru-2), were reported. Complexes Ru-1 â¼ Ru-2 showed good anticancer activity in Hep-G2 cells. Researches indicated that complexes Ru-1 â¼ Ru-2 could be enriched and appear as red fluorescence in the mitochondria, arouse dysfunction of mitochondria, induce the accumulation of reactive oxygen species (ROS) and lipid peroxidation (LPO), while the morphology of nuclei and cell apoptosis had no significant change. Further experiments proved that GPX4 and Ferritin were down-regulated, which eventually triggered ferroptosis in Hep-G2 cells. Remarkably, Ru-1 showed high inhibitory activity against xenograft tumor growth in vivo (TGIR = 49%). This study shows that the complex Ru-1 could act as a novel drug candidate by triggering cell ferroptosis.
The study assessed the effect of salinity and lead (Pb(II)) on the anammox sludge for nitrogen removal from saline wastewater. Results showed decreased nitrogen removal and specific anammox activity (SAA) with elevated salinity and Pb(II). SAA reduced from 541.3 ± 4.3 mg N g-1 VSS d-1 at 0.5 mg/L Pb(II) to 436.0 ± 0.2 mg N g-1 VSS d-1 at 30 g/L NaCl, further to 303.6 ± 7.1 mg N g-1 VSS d-1 under 30 g/L NaCl + 0.5 mg/L Pb(II). Notably, the combined inhibition at salinity (15-20 g/L NaCl) and Pb(II) (0.3-0.4 mg/L) exhibited synergistic effect, while higher salinity and Pb(II) aligned with independent inhibition models. Combined inhibition decreased protein/polysaccharides ratio, indicating more severe negative effect on anammox aggregation capacity. Metagenomics confirmed decreased Candidatus Kuenenia, and enhanced denitrification under elevated salinity and Pb(II) conditions. This study offers insights into anammox operation for treating saline wastewater with heavy metals.
The enormous and widespread use of organoboronic acids has prompted the development of innovative synthetic methodologies to meet the demands on structural diversity and functional group tolerance. The existing photoinduced defunctionalization radical borylation, typically focused on the conversion of one C-X bond (X= Br, I, or other leaving group) into only one C-B bond. Herein, we disclose a divergent radical dechloroborylation reaction enabled by dinuclear gold catalysis with visible light irradiation. A wide range of structurally diverse alkyl boronic, α-chloroboronic, and gem-diboronic esters can be synthesized in moderate to good yields (up to 92%). Its synthetic robustness is further demonstrated on a preparative scale and applied to late-stage diversification of complex molecules. The process hinges on a C-Cl bond relay activation in readily available gem-dichloroalkanes through inner-sphere electron transfer, overcoming the redox potential limits of unreactive alkyl chlorides.
Current human health risk assessments of soil arsenic (As) contamination rarely consider bioaccessibility (IVBA), which may overestimate the health risks of soil As. The IVBA of As (As-IVBA) may differ among various soil types. This investigation of As-IVBA focused As from geological origin in a typical subtropical soil, lateritic red soil, and its risk control values. The study used the SBRC gastric phase in vitro digestion method and As speciation sequential extraction based upon phosphorus speciation extraction method. Two construction land sites (CH and HD sites) in the Pearl River Delta region were surveyed. The results revealed a high content of residual As (including scorodite, mansfieldite, orpiment, realgar, and aluminum arsenite) in the lateritic red soils at both sites (CH: 84.9%, HD: 91.7%). The content of adsorbed aluminum arsenate (CH: 3.24%, HD: 0.228%), adsorbed ferrum arsenate (CH: 8.55%, HD: 5.01%), and calcium arsenate (CH: 7.33%, HD: 3.01%) were found to be low. The bioaccessible As content was significantly positively correlated with the As content in adsorbed aluminum arsenate, adsorbed ferrum arsenate, and calcium arsenate. A small portion of these sequential extractable As speciation could be absorbed by the human body (CH: 14.9%, HD: 3.16%), posing a certain health risk. Adsorbed aluminum arsenate had the highest IVBA, followed by calcium arsenate, and adsorbed ferrum arsenate had the lowest IVBA. The aforementioned speciation characteristics of As from geological origin in lateritic red soil contributed to its lower IVBA compared to other soils. The oxidation state of As did not significantly affect As-IVBA. Based on As-IVBA, the carcinogenic and non-carcinogenic risks of soil As in the CH and HD sites decreased greatly in human health risk assessment. The results suggest that As-IVBA in lateritic red soil should be considered when assessing human health risks on construction land.
Background: Intracardiac echocardiography (ICE) is a novel technology with certain advantages in treatment of atrial fibrillation (AF), yet there is limited research on the use of ICE in radiofrequency ablation for AF treatment in China. The aim of this study was to investigate the total fluoroscopy time and dose, safety, and effectiveness of ICE guided vs. traditional fluoroscopy (non-ICE) guided radiofrequency ablation for AF in China. Methods: We conducted a single-center retrospective analysis of patients who underwent ICE or traditional fluoroscopy-guided radiofrequency ablation for AF. The primary endpoint of this study was total fluoroscopy time, and the secondary endpoints included total fluoroscopy dose, acute surgery failure, transseptal puncture time, ablation time, total procedure time, and 6-month surgery success (no AF recurrence or atrial flutter). As an exploratory analysis, outcomes of interest by different types of AF were examined. Results: A total of 97 patients were included in the analysis. Forty-eight were in the ICE group and 49 were in the non-ICE group with comparable demographic and clinical characteristics at the baseline. None of patients experienced acute surgery failure with no major procedure-related complications occurred. The fluoroscopic time and dose were significantly lower in the ICE group compared to the non-ICE group (0.00 vs. 9.67±4.88 min, P<0.001; 0.00 vs. 77.10±44.28 mGy/cm2, P<0.001, respectively). There were no statistically significant differences in transseptal puncture time, ablation time and total procedure time between the two groups. There were two AF recurrences observed during the 6-month follow-up in each group (P>0.99). Conclusions: ICE significantly reduced the fluoroscopic time and dose for radiofrequency catheter ablation in AF patients. There were no significant differences in safety or effectiveness outcomes between the ICE and non-ICE groups.
Cardiovascular aging is a progressive remodeling process constituting a variety of cellular and molecular alterations that are closely linked to mitochondrial dysfunction. Therefore, gaining a deeper understanding of the changes in mitochondrial function during cardiovascular aging is crucial for preventing cardiovascular diseases. Cardiac aging is accompanied by fibrosis, cardiomyocyte hypertrophy, metabolic changes, and infiltration of immune cells, collectively contributing to the overall remodeling of the heart. Similarly, during vascular aging, there is a profound remodeling of blood vessel structure. These remodeling present damage to endothelial cells, increased vascular stiffness, impaired formation of new blood vessels (angiogenesis), the development of arteriosclerosis, and chronic vascular inflammation. This review underscores the role of mitochondrial dysfunction in cardiac aging, exploring its impact on fibrosis and myocardial alterations, metabolic remodeling, immune response remodeling, as well as in vascular aging in the heart. Additionally, we emphasize the significance of mitochondria-targeted therapies in preventing cardiovascular diseases in the elderly.
BACKGROUND: Bexagliflozin and dapagliflozin are sodium-glucose cotransporter-2 (SGLT2) inhibitors. No direct comparison of SGLT2 inhibitors in a randomized controlled trial has been reported to date. METHODS: This was a multicenter, randomized, double-blind, active-controlled trial comparing bexagliflozin to dapagliflozin for the treatment of type 2 diabetes mellitus in adults with disease inadequately controlled by metformin. Subjects (n = 406) were randomized to receive bexagliflozin (20 mg) or dapagliflozin (10 mg) plus metformin. The primary endpoint was noninferiority of bexagliflozin to dapagliflozin for the change in glycated hemoglobin (HbA1c) from baseline to week 24. Secondary endpoints included intergroup differences in fasting plasma glucose (FPG), 2-h-postprandial glucose (PPG), body weight, and systolic blood pressure (SBP) from baseline to week 24. The trial also evaluated the safety profiles. RESULTS: The model-adjusted mean change from baseline to week 24 HbA1c was -1.08% for bexagliflozin and -1.10% for dapagliflozin. The intergroup difference of 0.03% (95% confidence interval [CI] -0.14% to 0.19%) was below the prespecified margin of 0.4%, confirming the noninferiority of bexagliflozin. The changes from baseline in FPG, PPG, body weight, and SBP were -1.95 mmol/L, -3.24 mmol/L, -2.52 kg, and -6.4 mm Hg in the bexagliflozin arm and -1.87 mmol/L, -3.07 mmol/L, -2.22 kg, and -6.3 mm Hg in the dapagliflozin arm. Adverse events were experienced in 62.6% and 65.0% and serious adverse events affected 4.4% and 3.5% of subjects in the bexagliflozin and dapagliflozin arm, respectively. CONCLUSIONS: Bexagliflozin showed nearly identical effects and a similar safety profile to dapagliflozin when used in Chinese patients on metformin.
Benzhydryl Compounds , Diabetes Mellitus, Type 2 , Glucosides , Metformin , Pyrans , Adult , Humans , Metformin/adverse effects , Hypoglycemic Agents/adverse effects , Glycated Hemoglobin , Body Weight , Double-Blind Method , Drug Therapy, Combination , Glucose , China , Blood Glucose , Treatment Outcome
BACKGROUND: Schwannomas are rare peripheral neural myelin sheath tumors that originate from Schwann cells. Of the different types of schwannomas, pelvic sciatic nerve schwannoma is extremely rare. Definite preoperative diagnosis of pelvic schwannomas is difficult, and surgical resection is the gold standard for its definite diagnosis and treatment. CASE SUMMARY: We present a case of pelvic schwannoma arising from the sciatic nerve that was detected in a 40-year-old man who underwent computed tomography for intermittent right lower back pain caused exclusively by a right ureteral calculus. Subsequently, successful transperitoneal laparoscopic surgery was performed for the intact removal of the stone and en bloc resection of the schwannoma. The total operative time was 125 min, and the estimated blood loss was inconspicuous. The surgical procedure was uneventful. The patient was discharged on postoperative day 5 with the simultaneous removal of the urinary catheter. However, the patient presented with motor and sensory disorders of the right lower limb, caused by partial damage to the right sciatic nerve. No tumor recurrence was observed at the postoperative appointment. CONCLUSION: Histopathological examination of the specimen confirmed the diagnosis of a schwannoma. Thus, laparoscopic surgery is safe and feasible for concomitant extirpation of pelvic schwannomas and other pelvic and abdominal diseases that require surgical treatment.
BACKGROUND: Numerous studies highlight the genetic underpinnings of mental disorders comorbidity, particularly in anxiety, depression, and schizophrenia. However, their shared genetic loci are not well understood. Our study employs Mendelian randomization (MR) and colocalization analyses, alongside multi-omics data, to uncover potential genetic targets for these conditions, thereby informing therapeutic and drug development strategies. METHODS: We utilized the Consortium for Linkage Disequilibrium Score Regression (LDSC) and Mendelian Randomization (MR) analysis to investigate genetic correlations among anxiety, depression, and schizophrenia. Utilizing GTEx V8 eQTL and deCODE Genetics pQTL data, we performed a three-step summary-data-based Mendelian randomization (SMR) and protein-protein interaction analysis. This helped assess causal and comorbid loci for these disorders and determine if identified loci share coincidental variations with psychiatric diseases. Additionally, phenome-wide association studies, drug prediction, and molecular docking validated potential drug targets. RESULTS: We found genetic correlations between anxiety, depression, and schizophrenia, and under a meta-analysis of MR from multiple databases, the causal relationships among these disorders are supported. Based on this, three-step SMR and colocalization analyses identified ITIH3 and CCS as being related to the risk of developing depression, while CTSS and DNPH1 are related to the onset of schizophrenia. BTN3A1, PSMB4, and TIMP4 were identified as comorbidity loci for both disorders. Molecules that could not be determined through colocalization analysis were also presented. Drug prediction and molecular docking showed that some drugs and proteins have good binding affinity and available structural data. CONCLUSIONS: Our study indicates genetic correlations and shared risk loci between anxiety, depression, and schizophrenia. These findings offer insights into the underlying mechanisms of their comorbidities and aid in drug development.
Schizophrenia , Humans , Schizophrenia/genetics , Depression/genetics , Molecular Docking Simulation , Anxiety/genetics , Anxiety Disorders/genetics , Genome-Wide Association Study , Polymorphism, Single Nucleotide/genetics , Proteasome Endopeptidase Complex , Butyrophilins , Antigens, CD
Methylene blue (MB) was found to exert neuroprotective effect on different brain diseases, such as ischemic stroke. This study assessed the MB effects on ischemia induced brain edema and its role in the inhibition of aquaporin 4 (AQP4) and metabotropic glutamate receptor 5 (mGluR5) expression. Rats were exposed 1 h transient middle cerebral artery occlusion (tMCAO), and MB was injected intravenously following reperfusion (3 mg/kg). Magnetic resonance imaging (MRI) and 2,3,5-triphenyltetrazolium chloride (TTC) staining was performed 48 h after the onset of tMCAO to evaluate the brain infarction and edema. Brain tissues injuries as well as the glial fibrillary acidic protein (GFAP), AQP4 and mGluR5 expressions were detected. Oxygen and glucose deprivation/reoxygenation (OGD/R) was performed on primary astrocytes (ASTs) to induce cell swelling. MB was administered at the beginning of reoxygenation, and the perimeter of ASTs was measured by GFAP immunofluorescent staining. 3,5-dihydroxyphenylglycine (DHPG) and fenobam were given at 24 h before OGD to examine their effects on MB functions on AST swelling and AQP4 expression. MB remarkably decreased the volumes of T2WI and ADC lesions, as well as the cerebral swelling. Consistently, MB treatment significantly decreased GFAP, mGluR5 and AQP4 expression at 48 h after stroke. In the cultivated primary ASTs, OGD/R and DHPG significantly increased ASTs volume as well as AQP4 expression, which was reversed by MB and fenobam treatment. The obtained results highlight that MB decreases the post-ischemic brain swelling by regulating the activation of AQP4 and mGluR5, suggesting potential applications of MB on clinical ischemic stroke treatment.
The endophytic microbial community reassembles to participate in plant immune balance when the host plants are stressed by pathogens. However, it remains unclear whether this assembly is pathogen-specific and how regulatory pathways are coordinated in multi-pathogens. In order to investigate the effects of infection with Colletotrichum gloeosporioides (Cg treatment) and Fusarium proliferatum (Fp treatment) on walnut leaf endophytic microbiome in their assembly, co-occurrence pattern, and on comprehensive chemical function of the internal environment of leaf, an interaction system of the walnut-pathogenic fungi was constructed using seed embryo tissue culture technology. The study showed differences in the assembly of endophytic microbial communities in walnut trees across three groups (control group, Ck; Cg; Fp) after Cg and Fp treatments. Despite changes in relative abundances, the dominant communities in phyla and genera remained comparable during the infection of the two pathogens. Endophyte fungi were more sensitive to the pathogen challenge than endophyte bacteria. Both promoted the enrichment of beneficial bacteria such as Bacillus and Pseudomonas, changed the modularity of the community, and reduced the stability and complexity of the endophyte community. Pathogenic fungi infection mainly affects the metabolism of porphyrin and chlorophyll, purine metabolism, phenylpropane metabolism, and amino acid metabolism. However, there was no significant difference in the secondary metabolites for the different susceptible plants. By screening endogenous antagonistic bacteria, we further verified that Pseudomonas psychrotolerans and Bacillus subtilis had inhibitory effects on the two pathogenic fungi and participated in the interaction between the leaves and pathogenic fungi. The antibacterial substances may be 1-methylnaphthalene, 1,3-butadiene, 2,3-butanediol, and toluene aldehyde.
L/D-Phenylglycine amphiphiles and metal ions with peroxidase-like activity self-assembled into chiral nanoribbons, which act as efficient chiral supramolecular nanozymes for catalyzing the 3,4-dihydroxy-L/D-phenylalanine (L/D-DOPA) oxidation reactions. The catalytic efficiency and enantioselectivity are dominated by the chirality transfer and the synergistic effect between the metal ions and chiral nanoribbons.
Purpose: We prospectively evaluate the short-term clinical and radiographic outcomes of the only Chinese domestically produced trabecular titanium acetabular cup(3D ACT™ cup) in primary total hip arthroplasty (THA), aiming to provide evidence-based support for its clinical application. Methods: A total of 236 patients, who underwent primary THA using 3D ACT™ cup in the Department of Joint Surgery at our hospital between January 2017 and June 2019, were included in this study. General patient data, imaging information, functional scores, and complications were collected to evaluate the early clinical efficacy. Results: All patients were followed up for 33-52 months, with an average of (42.2 ± 9.2) months. At the last follow-up, the preoperative HHS score increased significantly from 43.7 ± 6.8 to 85.6 ± 9.3 points (P < 0.01). Similarly, the preoperative WOMAC scores showed significant improvement from 59.2 ± 5.8 to 13.1 ± 3.5 points (P < 0.01). 92.3% of the patients expressed satisfaction or high satisfaction with the clinical outcome. Furthermore, 87.7% of the acetabular cups were positioned within the Lewinnek safe zone, achieving successful reconstruction of the acetabular rotation center. The cup survival rate at the last follow-up was 100%. Conclusions: The utilization of the only Chinese domestically manufactured 3D printing trabecular titanium acetabular cup in primary THA demonstrated favorable short-term clinical and radiographic outcomes. The acetabular cup exhibits excellent initial stability, high survival rate, and favorable osseointegration, leading to a significant enhancement in pain relief and functional improvement. In the future, larger sample sizes and multicenter prospective randomized controlled trials will be required to validate the long-term safety and effectiveness of this 3D ACT™ cup.
Exosomes carry large cargo of proteins, lipids, and nucleic acids, serving as versatile biomarkers for disease diagnosis and vehicles for drug delivery. However, up to date, no well recognized standard procedures for exosome storage were available for clinical application. This study aimed to determine the optimal storage conditions and the anticoagulants for plasma-derived exosome isolation. Fresh whole blood samples were collected from healthy participants and preserved in four different anticoagulants including sodium citrate (SC1/4), sodium citrate (SC1/9), lithium heparin (LH), or Ethylenediamine tetraacetic acid (EDTA), respectively. Exosomes were extracted from the plasma by differential ultracentrifugation and stored at three different temperatures, 4°C, -20°C or - 80°C for a duration ranging from one week to six months. All plasma samples for storage conditions comparison were pretreated with LH anticoagulant. Exosome features including morphological characteristics, pariticles size diameter, and surface protein profiles (TSG101, CD63, CD81, CD9, CALNEXIN) were assessed by transmission electron microscopy, Nanoparticle Tracking Analysis, and Western Blotting, respectively. Exosomes preserved in LH and SC1/4 group tended to remain intact microstructure with highly abundant protein biomarkers. Exosomes stored at 4°C for short time were prone to be more stable compared to thos at -80°C. Exosomes stored in plasma were superior in terms of ultrastructure, size diameter and surface protein expression to those stored in PBS. In conclusion, plasma-dervied exosome characteristics strictly depend on the anticoagulants and storage temperature and duration.
What is the context? Effective isolation of exosomes is a prerequisite for subsequent investigation into its involvemnt in disease development as well as potentialtherapeutic applications.Anticoagulants, storage temperature and durations might change the microscopical structure, integrity and also the stability of plasma-derived exosomes. However, no internationally recognized standard of exosome storage procedure was available for clinical use.What is new? Our finding evaluated the effect of anticoagulants and storage on plasma exosome characteristics.Exosomes isolated from plasma preserved with Li-heparin and sodium citrate (1/4) showed better physical properties and surface marker protein expression.Isolated exosomes appeared more stable in a short time for 4°C compared to −80°C. Storage of exosomes in plasma showed better physical properties and surface marker protein expression than in PBS.What is the impact? Our findings inform the significance of standardizing procedure of exosome isolation and preservation.
Exosomes , Humans , Sodium Citrate , Temperature , Anticoagulants/pharmacology , Anticoagulants/therapeutic use , Heparin , Membrane Proteins , Biomarkers
Background: Myeloid-derived suppressor cells (MDSCs) have crucial immunosuppressive role in T cell dysfunction in various disease processes. However, the role of MDSCs and their impact on Tregs in COPD have not been fully understood. The aim of the present study is to investigate the immunomodulatory role of MDSCs and their potential impact on the expansion and function of Tregs in COPD patients. Methods: Peripheral blood samples were collected to analyze circulating MDSCs, Tregs, PD-1/PD-L1 expression to assess the immunomodulatory role of MDSC and their potential impact on the expansion and function of Treg in COPD. A total of 54 COPD patients and 24 healthy individuals were enrolled in our study. Flow cytometric analyses were performed to identify granulocytic MDSCs (G-MDSCs), monocytic MDSCs (M-MDSCs), Tregs, and the expression of PD-1/PD-L1(L2) on MDSCs and Tregs in peripheral blood. Results: Our results revealed a significantly higher percentage of G-MDSCs and M-MDSCs (p < 0.001) in COPD patients compared to the healthy controls. Additionally, a significantly higher proportion of peripheral blood Tregs was observed in COPD patients. Furthermore, an increased expression of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) on Tregs (p < 0.01) was detected in COPD patients. The expression of PD-1 on CD4+ Tcells and Tregs, but not CD8+Tcells, was found to be increased in patients with COPD compared to controls. Furthermore, an elevated expression of PD-L1 on M-MDSCs (p < 0.01) was also observed in COPD patients. A positive correlation was observed between the accumulation of M-MDSCs and Tregs in COPD patients. Additionally, the percentage of circulating M-MDSCs is positively associated with the level of PD-1 (r = 0.51, p < 0.0001) and CTLA-4 (r = 0.42, p = 0.0014) on Tregs in COPD. Conclusion: The recruitment of MDSCs, accumulation of Tregs, and up-regulation of CTLA-4 on Treg in COPD, accompanied by an increased level of PD-1/PD-L1, suggest PD-1/PD-L1 axis may be potentially involved in MDSCs-induced the expansion and activation of Treg at least partially in COPD.
Myeloid-Derived Suppressor Cells , Pulmonary Disease, Chronic Obstructive , Humans , B7-H1 Antigen/metabolism , CTLA-4 Antigen , Myeloid-Derived Suppressor Cells/metabolism , Programmed Cell Death 1 Receptor , T-Lymphocytes, Regulatory/metabolism
BACKGROUND: Droplet digital PCR (ddPCR) is increasingly used in diagnosing clinical pathogens, but its effectiveness in cirrhosis patients with suspected ascites infection remains uncertain. METHODS: The diagnostic performance of ddPCR was assessed in 305 ascites samples, utilizing culture and clinical composite standards. The quantitative value and potential clinical impact of ddPCR were further analyzed in patients with spontaneous bacterial peritonitis. RESULTS: With culture standards, ddPCR demonstrated a sensitivity of 86.5% and specificity of 83.2% for bacterial or fungal detection. After adjustment of clinical composite criteria, specificity increased to 96.4%. Better diagnostic performance for all types of targeted pathogens, particularly fungi, was observed with ddPCR compared to culture, and more polymicrobial infections were detected (30.4% versus 5.7%, p < 0.001). Pathogen loads detected by ddPCR correlated with white blood cell count in ascites and blood, as well as polymorphonuclear cell (PMN) count in ascites, reflecting infection status rapidly. A positive clinical impact of 55.8% (43/77) was observed for ddPCR, which was more significant among patients with PMN count ≤ 250/mm3 in terms of medication adjustment and new diagnosis. ddPCR results for fungal detection were confirmed by clinical symptoms and other microbiological tests, which could guide antifungal therapy and reduce the risk of short-term mortality. CONCLUSIONS: ddPCR, with appropriate panel design, has advantages in pathogen detection and clinical management of ascites infection, especially for patients with fungal and polymicrobial infections. Patients with atypical spontaneous bacterial peritonitis benefited more from ddPCR.
INTRODUCTION: Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive lipid metabolism disorder. It is caused by a defect in the sterol-27-hydroxylase gene, leading to the deposition of cholesteryl and bile alcohol in large amounts, causing a variety of clinical manifestations; however, tremor as the main manifestation of CTX has not been reported. PATIENTS CONCERNS AND CLINICAL FINDINGS: Herein, we report a 27-year-old woman, who developed head and body tremors at the age of 12 years. Many hospitals misdiagnosed her condition as idiopathic tremor and Parkinson disease, with a poor curative effect. PRIMARY DIAGNOSIS AND INTERVENTION: We diagnosed her with CTX and treated with chenodeoxycholic acid and clonazepam. CONCLUSION: The patient's condition considerably improved. This case could help avoid misdiagnosis and mistreatment in clinical practice.
Chenodeoxycholic Acid , Tremor , Xanthomatosis, Cerebrotendinous , Humans , Xanthomatosis, Cerebrotendinous/diagnosis , Xanthomatosis, Cerebrotendinous/complications , Xanthomatosis, Cerebrotendinous/drug therapy , Xanthomatosis, Cerebrotendinous/genetics , Female , Adult , Tremor/etiology , Tremor/diagnosis , Chenodeoxycholic Acid/therapeutic use , Clonazepam/therapeutic use , Diagnosis, Differential
BACKGROUND: TikTok is emerging as a vital platform for health information dissemination. Despite myopia being a global public health issue, the high-quality myopia information shared by health educators often fails to go viral. It is imperative to analyze the factors influencing video quality and popularity, especially from diverse perspectives of researchers, health educators, and audiences. METHODS: TikTok myopia-related videos were retrieved using TikTok's default comprehensive search (DCS) and most liked search (MLS) strategies. Venn diagrams were employed to illustrate the relationships and commonalities between the two strategies across four sample sizes (top 200, 150, 100, and 50). Video metadata, including details such as creator information, production properties, upload time, video duration, and viewer engagement, were collected. Video quality was assessed using the DISCERN tool. Video content covering six aspects of myopia were evaluated. The impact of search strategies, video sample sizes, production properties, and myopia content on video quality and audience engagement was analyzed through single-factor or multi-factor analysis. RESULTS: DCS and MLS retrieval strategies, as well as varying sample sizes, resulted in differences in audience engagement for myopia videos (P < 0.039), while The DISCERN quality scores remained comparable (P > 0.221). Videos published by healthcare professionals (HCPs) and non-profit organizations (NPOs) were associated with high-quality (P ≤ 0.014) but comparatively lower popularity (P < 0.033). Videos that reported contents of risk factors, management, and outcomes showed high popularity (P < 0.018), while longer video duration (> 60s) exhibited the opposite trend (P < 0.032). Content on myopia evaluation (P ≤ 0.001) and management (P ≤ 0.022) and video duration were positively correlated with higher DISCERN quality. CONCLUSION: Videos created by HCPs and NPOs deserve greater attention. Rather than pursuing entertaining effects, professional educators should emphasize producing concise, and high-quality myopia content that readily resonates with the audience and has the potential to go viral on the platform.
Myopia , Video Recording , Humans , Myopia/therapy , Information Dissemination/methods
