Biliary stents for active materials and surface modification: Recent advances and future perspectives.

Demand for biliary stents has expanded with the increasing incidence of biliary disease. The implantation of plastic or self-expandable metal stents can be an effective treatment for biliary strictures. However, these stents are nondegradable and prone to restenosis. Surgical removal or replacement of the nondegradable stents is necessary in cases of disease resolution or restenosis. To overcome these shortcomings, improvements were made to the materials and surfaces used for the stents. First, this paper reviews the advantages and limitations of nondegradable stents. Second, emphasis is placed on biodegradable polymer and biodegradable metal stents, along with functional coatings. This also encompasses tissue engineering & 3D-printed stents were highlighted. Finally, the future perspectives of biliary stents, including pro-epithelialization coatings, multifunctional coated stents, biodegradable shape memory stents, and 4D bioprinting, were discussed.

Genetic analysis of pregnancy loss and fetal structural anomalies by whole exome sequencing.

BACKGROUND: Whole exome sequencing (WES) has been recommended to investigate the genetic cause of fetal structural anomalies. In this retrospective study, we aimed to evaluate the diagnostic yield of WES in our cohort of families with pregnancy loss or termination of pregnancy due to structural anomalies. METHODS: As aneuploidy, triploidy and copy number variations (CNVs) could be detected by exome-based CNV analysis, only WES is performed in this study. And the results of 375 cases assessed by WES were analyzed. RESULTS: The overall detection rate was 32.3% (121/375), including aneuploidy and triploidy (7.5%, 28/375), CNVs (5.1%, 19/375) and single-nucleotide variants (SNVs) /insertions or deletions (Indels) (19.7%, 74/375). Among these, the diagnostic yield for likely pathogenic (LP) or pathogenic (P) CNVs is 4.8% (18/375), and the diagnostic yield for LP or P SNVs/Indels is 15.2% (57/375). And an additional 4.8% (18/375) of cases had CNVs or SNVs/Indels classified as variants of uncertain significance (VUS) with potential clinical significance. CONCLUSIONS: Our findings expand the known mutation spectrum of genetic variants related to fetal abnormalities, increase our understanding of prenatal phenotypes, and enable more accurate counseling of recurrence risk for future pregnancies.

Li4Ti5O12@carbon nanotube arrays as high-performance anode for Li-ion batteries.

The innovation of advanced high-rate anodes is of great significance for the development of high-power and fast-charging lithium-ion batteries (LIBs). In this work, self-supported Li4Ti5O12@carbon (LTO@C) nanotube arrays as a high-quality anode are fabricated via anodizing and hydrothermal processes. Owing to the structure having a high contact surface area and good stability, as well as the incorporation of carbon, the LTO@C exhibits a remarkable rate capability (a reversible capability of 290 mA h g-1, 251.9 mA h g-1, 228.8 mA h g-1, and 208.7 mA h g-1 at 1C, 5C, 10C, and 20C, respectively) and cycling performance (71.7% capacity retention after 1000 cycles at 10C), which is superior to LTO. These features suggest the promising application of LTO@C in high-power energy storage areas.

Bioresponsive Nanoparticles Boost Starvation Therapy and Prevent Premetastatic Niche Formation for Pulmonary Metastasis Treatment.

In the process of tumor metastasis, tumor cells can acquire invasion by excessive uptake of nutrients and energy and interact with the host microenvironment to shape a premetastatic niche (PMN) that facilitates their colonization and progression in the distal sites. Pyruvate is an essential nutrient that engages in both energy metabolism and remodeling of the extracellular matrix (ECM) in the lungs for PMN formation, thus providing a target for tumor metastasis treatment. There is a paucity of strategies focusing on PMN prevention, which is key to metastasis inhibition. Here, we design a bioresponsive nanoparticle (HP/GU) based on a disulfide-cross-linked hyperbranched polyethylenimine (D-PEI) core and a hyaluronic acid (HA) shell with a reactive oxygen species (ROS)-sensitive cross-linker between them to encapsulate glucose oxidase (GOX) and a mitochondrial pyruvate carrier (MPC) inhibitor via electrostatic interaction, which reinforces starvation therapy and reduces PMN formation in the lungs via inhibiting pyruvate metabolism. In tumor cells, GOX and MPC inhibitors can be rapidly released and synergistically reduce the energy supply of tumor cells by consuming glucose and inhibiting pyruvate uptake to decrease tumor cell invasion. MPC inhibitors can also reduce ECM remodeling by blocking cellular pyruvate metabolism to prevent PMN formation. Consequently, HP/GU achieves an efficient inhibition of both primary and metastatic tumors and provides an innovative strategy for the treatment of tumor metastases.

Emergence and transmission of the high-risk ST78 clone of OXA-48-producing Enterobacter hormaechei in a single hospital in Taiwan.

Carbapenem-resistant Enterobacter cloacae complex is a significant global healthcare threat, particularly carbapenemase-producing Enterobacter hormaechei (CPEH). From January 2017 to January 2021, twenty-two CPEH isolates from a regional teaching hospital in central Taiwan were identified with the carriage of carbapenemase genes blaKPC-2, blaIMP-8, and predominantly blaOXA-48. Over 80% of these CPEH strains clustered into the high-risk ST78 lineage, carrying a blaOXA-48 IncL plasmid (pOXA48-CREH), nearly identical to the endemic plasmid pOXA48-KP in ST11 Klebsiella pneumoniae. This OXA-48-producing ST78 lineage disseminated clonally from 2018 to 2021 and transferred pOXA48-CREH to ST66 and ST90 E. hormaechei. An IMP-8-producing ST78 strain harbouring a blaIMP-8-carrying pIncHI2 plasmid appeared in 2018, and by late 2020, a KPC-2-producing ST78 strain was identified after acquiring a novel blaKPC-2-carrying IncFII plasmid. These findings suggest that the high-risk ST78 lineage of E. hormaechei has emerged as the primary driver behind the transmission of CPEH. ST78 has not only acquired various carbapenemase-gene-carrying plasmids but has also facilitated the transfer of pOXA48-CREH to other lineages. Continuous genomic surveillance and targeted interventions are urgently needed to control the spread of emerging CPEH clones in hospital settings.

Structural basis of the human transcriptional Mediator regulated by its dissociable kinase module.

The eukaryotic transcriptional Mediator comprises a large core (cMED) and a dissociable CDK8 kinase module (CKM). cMED recruits RNA polymerase II (RNA Pol II) and promotes pre-initiation complex formation in a manner repressed by the CKM through mechanisms presently unknown. Herein, we report cryoelectron microscopy structures of the complete human Mediator and its CKM. The CKM binds to multiple regions on cMED through both MED12 and MED13, including a large intrinsically disordered region (IDR) in the latter. MED12 and MED13 together anchor the CKM to the cMED hook, positioning CDK8 downstream and proximal to the transcription start site. Notably, the MED13 IDR obstructs the recruitment of RNA Pol II/MED26 onto cMED by direct occlusion of their respective binding sites, leading to functional repression of cMED-dependent transcription. Combined with biochemical and functional analyses, these structures provide a conserved mechanistic framework to explain the basis for CKM-mediated repression of cMED function.

Acceptability and usability of a WeChat-based intervention for depression in China: A mixed-methods study.

Background: As research on the use of mobile technology to deliver mental health support grows, the research from China is still very limited. How to design an acceptable and usable mobile mental health service model suitable for China's social and cultural environment remains to be studied. Objective: To understand the acceptability and usability of a WeChat-based intervention among Chinese patients with depression, and to provide insights to promote future development of user-centered mobile mental health services design. Methods: The research team developed a multi-theoretical intervention that includes seven modules: recovery lessons, recovery journal, coaching sessions, mindfulness, personalized support, regular assessments and feedback collection. Forty-two patients diagnosed with depressive disorder were recruited, with a mixed sample of patients who were using an antidepressant medication (n = 29) and patients who were not using an antidepressant medication (n = 13). A single-arm mixed-methods study was conducted to understand engagement, satisfaction, usability and potential clinical effectiveness of the intervention. Results: There was a retention rate of 83.33% - 22 participants who used an antidepressant medication and 13 participants who did not use an antidepressant medication completed the final assessments. The median (upper quartile-lower quartile) of the completed 60 recovery journals and 7 coaching sessions was 56 (59-46) and 6 (7-4) times, respectively. Participants' satisfaction regarding their recovery progress, and on perceived helpfulness on different modules were high. The overall score of the user version of the Mobile Application Rating Scale was 4.23 (SD 0.44, range 1-5), indicating high acceptability and usability. Qualitative feedback identified three key themes: an efficient access to professional help, a personalized source of social support, and a facilitator of cognitive and behavioral change. Conclusions: This study demonstrated that a WeChat-based intervention for depression was acceptable, and has the potential to promote personal recovery. More studies are needed to understand the efficacy and implementation of this model in real world.

A Retrospective Study of Brain-Heart Syndrome in Patients with Acute Cerebrovascular Diseases.

Objective: To investigate the clinical characteristics, risk factors and outcomes of brain-heart syndrome (BHS) in patients with acute cerebrovascular diseases (ACVDs). Methods: A retrospective analysis was conducted of 100 patients who were admitted to our hospital with ACVDs between January 2023 and December 2023. The demographic, clinical, laboratory and imaging data of the patients were collected, and the presence and severity of BHS were evaluated. The neurological and cardiac outcomes of the patients at discharge and at 12-month follow-up were also assessed. Results: Out of the 100 patients, 38% had BHS, classified as mild (18%), moderate (12%) and severe (8%). The most prevalent ACVDs were cerebral infarction (58%), cerebral haemorrhage (32%) and subarachnoid haemorrhage (10%). Cardiac complications included arrhythmia (26%), myocardial ischaemia (18%) and heart failure (10%). Patients with BHS had higher results for blood pressure, heart rate, white blood cell count, C-reactive protein, IL-6, D-dimer and troponin, more severe neurological deficits, higher mortality and poorer functional outcomes. Multivariable analysis identified age, hypertension, diabetes, coronary artery disease, prior cardiovascular events, cerebral haemorrhage, brainstem infarction and hypothalamic or insular lesions as independent risk factors for BHS. Conclusion: Brain-heart syndrome is a frequent, severe complication in patients with ACVD, linked with multiple risk factors and poor prognosis. Prompt diagnosis and treatment are crucial for improving patient outcomes.

Corticosteroid-dependent immune checkpoint inhibitor-induced enterocolitis treated with vedolizumab: a case report.

Background: Immune checkpoint inhibitors (ICIs) have greatly improved the survival in several cancers. Immune-related adverse events (irAEs) are common in patients on ICI therapy, as inhibition of cytotoxic T-lymphocyte antigen 4 (CTLA-4) or programmed cell death protein 1 (PD-1) leads to non-selective activation of the immune system. ICI-induced enterocolitis is highly prevalent and corticosteroid administration is the first-line treatment. Selective immunosuppressive therapy was employed for steroid-refractory patients. The monoclonal antibody vedolizumab exhibits gut-specific immunosuppressive effects by targeting the α4ß7 integrin. Case Description: We report a case of corticosteroid-dependent camrelizumab-induced enterocolitis in a 58-year-old man with hepatocellular carcinoma (HCC) who was treated with vedolizumab. The patient's diarrhea resolved following the administration of two doses of vedolizumab (300 mg), and he was able to stop using corticosteroids. He later underwent surgery and HCC treatment, including appropriate management of ICI-induced enterocolitis, and achieved a complete pathological response. Conclusions: This report illustrates the valuable role of vedolizumab in treating ICI-induced enterocolitis that is refractory to corticosteroid treatment.

Dyslipidemia-induced renal fibrosis related to ferroptosis and endoplasmic reticulum stress.

Dyslipidemia may induce chronic kidney disease and trigger both ferroptosis and endoplasmic reticulum (ER) stress, but the instigating factors are incompletely understood. We tested the hypothesis that different models of dyslipidemia engage distinct kidney injury mechanisms. Wild-type (WT) or proprotein-convertase subtilisin/kexin type-9 (PCSK9)-gain-of-function (GOF) Ossabaw pigs were fed with a 6-month normal diet (ND) or high-fat diet (HFD) (n = 5-6 each). Renal function and fat deposition were studied in vivo using CT, and blood and kidney tissue studied ex-vivo for lipid profile, systemic and renal vein FFAs levels, and renal injury mechanisms including lipid peroxidation, ferroptosis, and ER stress. Compared with WT-ND pigs, both HFD and PCSK9-GOF elevated triglyceride levels, which were highest in WT-HFD, whereas total and LDL cholesterol levels rose only in PCSK9-GOF pigs, particularly in PCSK9-GOF/HFD. The HFD groups had worse kidney function than the ND groups. The WT-HFD kidneys retained more FFA than other groups, but all kidneys developed fibrosis. Furthermore, HFD-induced ferroptosis in WT-HFD indicated by increased free iron, lipid peroxidation, and decreased glutathione peroxidase-4 mRNA expression, while PCSK9-GOF induced ER stress with upregulated GRP94 and CHOP protein expression. In vitro, pig kidney epithelial cells treated with palmitic acid and oxidized LDL to mimic HFD and PCSK9-GOF showed similar trends to those observed in vivo. Taken together, HFD-induced hypertriglyceridemia promotes renal FFA retention and ferroptosis, whereas PCSK9-GOF-induced hypercholesterolemia elicits ER stress, both resulting in renal fibrosis. These observations suggest different targets for preventing and treating renal fibrosis in subjects with specific types of dyslipidemia.

SIRT3 sulfhydration using hydrogen sulfide inhibited angiotensin II-induced atrial fibrosis and vulnerability to atrial fibrillation via suppression of the TGF-ß1/smad2/3 signalling pathway.

Atrial fibrosis is associated with the occurrence of atrial fibrillation (AF) and regulated by the transforming growth factor-ß1 (TGF-ß1)/Smad2/3 signalling pathway. Unfortunately, the mechanisms of regulation of TGF-ß1/Smad2/3-induced atrial fibrosis and vulnerability to AF remain still unknown. Previous studies have shown that sirtuin3 (SIRT3) sulfhydration has strong anti-fibrotic effects. We hypothesised that SIRT3 sulfhydration inhibits angiotensin II (Ang-II)-induced atrial fibrosis via blocking the TGF-ß1/Smad2/3 signalling pathway. In this study, we found that SIRT3 expression was decreased in the left atrium of patients with AF compared to that in those with sinus rhythm (SR). In vitro, SIRT3 knockdown by small interfering RNA significantly expanded Ang-II-induced atrial fibrosis and TGF-ß1/Smad2/3 signalling pathway activation, whereas supplementation with Sodium Hydrosulfide (NaHS, exogenous hydrogen sulfide donor and sulfhydration agonist) and SIRT3 overexpression using adenovirus ameliorated Ang-II-induced atrial fibrosis. Moreover, we observed suppression of the TGF-ß1/Smad2/3 pathway when Ang-II was combined with NaHS treatment, and the effect of this co-treatment was consistent with that of Ang-II combined with LY3200882 (Smad pathway inhibitor) on reducing atrial fibroblast proliferation and cell migration in vitro. Supplementation with dithiothreitol (DTT, a sulfhydration inhibitor) and adenovirus SIRT3 shRNA blocked the ameliorating effect of NaHS and AngII co-treatment on atrial fibrosis in vitro. Finally, continued treatment with NaHS in rats ameliorated atrial fibrosis and remodelling, and further improved AF vulnerability induced by Ang-II, which was reversed by DTT and adenovirus SIRT3 shRNA, suggesting that SIRT3 sulfhydration might be a potential therapeutic target in atrial fibrosis and AF.

Human liver derived mesenchymal stromal cells ameliorate murine ischemia-induced inflammation through macrophage polarization.

Introduction: The immunomodulatory properties of mesenchymal stromal cells (MSC) have been well-characterized in in-vitro and in-vivo models. We have previously shown that liver MSC (L-MSC) are superior inhibitors of T-cell activation/proliferation, NK cell cytolytic function, and macrophage activation compared to adipose (A-MSC) and bone marrow MSC (BM-MSC) in-vitro. Method: To test these observations in-vivo, we infused these types of MSC into mice with unilateral renal artery stenosis (RAS), an established model of kidney inflammation. Unilateral RAS was induced via laparotomy in 11-week-old, male 129-S1 mice under general anesthesia. Control mice had sham operations. Human L-MSC, AMSC, and BM-MSC (5x105 cells each) or PBS vehicle were injected intra-arterially 2 weeks after surgery. Kidney morphology was studied 2 weeks after infusion using micro-MRI imaging. Renal inflammation, apoptosis, fibrosis, and MSC retention were studied ex-vivo utilizing western blot, immunofluorescence, and immunohistological analyses. Results: The stenotic kidney volume was smaller in all RAS mice, confirming significant injury, and was improved by infusion of all MSC types. All MSC-infused groups had lower levels of plasma renin and proteinuria compared to untreated RAS. Serum creatinine improved in micetreated with BM- and L-MSC. All types of MSC located to and were retained within the stenotic kidneys, but L-MSC retention was significantly higher than A- and BM-MSC. While all groups of MSC-treated mice displayed reduced overall inflammation and macrophage counts, L-MSC showed superior potency in-vivo at localizing to the site of inflammation and inducing M2 (reparative) macrophage polarization to reduce inflammatory changes. Discussion: These in-vivo findings extend our in-vitro studies and suggest that L-MSC possess unique anti-inflammatory properties that may play a role in liver-induced tolerance and lend further support to their use as therapeutic agents for diseases with underlying inflammatory pathophysiology.

Biosensor-based active ingredient recognition system for screening potential small molecular Severe acute respiratory syndrome coronavirus 2 entry blockers targeting the spike protein from Rugosa rose.

The traditional formulation Hanchuan zupa granules (HCZPs) have been widely used for controlling coronavirus disease 2019 (COVID-19). However, its active components remain unknown. Here, HCZP components targeting the spike receptor-binding domain (S-RBD) of SARS-CoV-2 were investigated using a surface plasmon resonance (SPR) biosensor-based active ingredient recognition system (SPR-AIRS). Recombinant S-RBD proteins were immobilized on the SPR chip by amine coupling for the prescreening of nine HCZP medicinal herbs. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) identified gallic acid (GA) and methyl gallate (MG) from Rosa rugosa as S-RBD ligands, with KD values of 2.69 and 0.95 µM, respectively, as shown by SPR. Molecular dynamics indicated that GA formed hydrogen bonds with G496, N501, and Y505 of S-RBD, and MG with G496 and Y505, inhibiting S-RBD binding to angiotensin-converting enzyme 2 (ACE2). SPR-based competition analysis verified that both compounds blocked S-RBD and ACE2 binding, and SPR demonstrated that GA and MG bound to ACE2 (KD = 5.10 and 4.05 µM, respectively), suggesting that they blocked the receptor and neutralized SARS-CoV-2. Infection with SARS-CoV-2 pseudovirus showed that GA and MG suppressed viral entry into 293T-ACE2 cells. These S-RBD inhibitors have potential for drug design, while the findings provide a reference on HCZP composition and its use for treating COVID-19.

[The Causes of Platelet Aggregation in Version 6.4 Trima Accel Automated Blood Collection System and the Comparison of Two Intervention Measures].

OBJECTIVE: To explore the causes of platelet aggregation in version 6.4 Trima Accel automated blood collection system and the effect of 2 intervention measures. METHODS: The data on platelet aggregation (n=61) and non-aggregation (n=323) of 61 donors in 2020 were collected and the causes of aggregation were analyzed. Then the 72 donors with platelet aggregation in 2021 were randomized into intervention group A (increasing the anticoagulant-to-blood ratio) and intervention group B (wrapping the donor's arm with an electric blanket to keep warm and improve the blood flow speed). The collection time, average blood flow speed, number of machine alarms, anticoagulant usage, deaggregation and citrate reaction of the two groups were compared. RESULTS: Platelet aggregation was negatively correlated with the average blood flow speed (r =-0.394) and positively correlated with the collection time (r =0.458). The equations for predicting aggregation and non-aggregation were constructed based on Bayesian and Fisher discriminant analysis, and the predicted accuracy was 77.1%. The comparison of the effects of two intervention measures showed that the average blood flow speed in group B was higher than that in group A; the collection time, number of machine alarms, anticoagulant usage and proportion of citrate reaction in blood donors in group B were all lower than those in Group A, all these differences were significant (P < 0.05). In the entire cohort in 2021, 90.28% of the products were immediately deaggregated after collection, and 9.72% of the products were deaggregated within 4 hours. There was no statistically significant difference in deaggregation between the two intervention groups (P >0.05). CONCLUSION: During apheresis platelet collection, the predictive equations for aggregation and non-aggregation can be used to predict the occurrence probability of aggregation, and the intervention can be made in advance. Both intervention measures are effective in reducing platelet aggregation, however, measure B has the advantages of improving the speed of blood collection, shortening the collection time, reducing the alarm frequency and the anticoagulant usage, and reducing the incidence of citrate reaction in blood donors.

Leidenfrost Effect-Induced Chaotic Vortex Flow for Efficient Mixing of Highly Viscous Droplets.

Efficiently mixing highly viscous liquids in microfluidic systems is appealing for green chemistry such as chemical synthesis and catalysis, but it is a long-standing challenge owing to the unfavorable diffusion kinetics. In this work, a new strategy is explored for mixing viscous droplets by harnessing a peculiar Leidenfrost state, where the substrate temperature is above the boiling point of the liquid without apparent liquid evaporation. Compared to the control experiment where the droplet stays at a similar temperature but in the contact boiling regime, the mixing time can be reduced significantly. Moreover, it is demonstrated that the liquid mixing originates from the chaotic convection flow in the Leidenfrost droplet, characterized by the internal vortex motion evidenced by the microscale visualization. A correlation between mixing time and droplet volume is also proposed, showing a good agreement with experimental results. It is further shown that Leidenfrost droplets can be used to synthesize nanoparticles of the desired morphology, and it is anticipated that this simple and scalable fabrication approach will find applications in the biological, pharmaceutical, and chemical industries.

Unraveling RNA contribution to the molecular origins of bacterial surface-enhanced Raman spectroscopy (SERS) signals.

Surface-enhanced Raman spectroscopy (SERS) is widely utilized in bacterial analyses, with the dominant SERS peaks attributed to purine metabolites released during sample preparation. Although adenosine triphosphate (ATP) and nucleic acids are potential molecular origins of these metabolites, research on their exact contributions remains limited. This study explored purine metabolite release from E. coli and RNA integrity following various sample preparation methods. Standard water washing generated dominant SERS signals within 10 s, a duration shorter than the anticipated RNA half-lives under starvation. Evaluating RNA integrity indicated that the most abundant ribosomal RNA species remained intact for hours post-washing, whereas messenger RNA and transfer RNA species degraded gradually. This suggests that bacterial SERS signatures observed after the typical washing step could originate from only a small fraction of endogenous purine-containing molecules. In contrast, acid depurination led to degradation of most RNA species, releasing about 40 times more purine derivatives than water washing. Mild heating also instigated the RNA degradation and released more purine derivatives than water washing. Notably, differences were also evident in the dominant SERS signals following these treatments. This work provides insights into SERS-based studies of purine metabolites released by bacteria and future development of methodologies.

Tailoring Energy Transfer in Mixed Eu/Tb Metal-Organic Frameworks for Ratiometric Temperature Sensing.

Eu/Tb metal-organic frameworks (Eu/Tb-MOFs), exhibiting Eu3+ and Tb3+ emissions, stand out as some of the most fascinating luminescent thermometers. As the relative thermal sensitivity model is limited to its lack of precision for fitting ratio of Eu3+ and Tb3+ emissions, accurately predicting the sensing performance of Eu/Tb-MOFs remains a significant challenge. Herein, we report a series of luminescent Eu/Tb-MOF thermometers, EuxTb1-xL, with excellent thermal sensitivity around physiological levels, achieved through the tuning energy transfer from ligands to Eu3+ and Tb3+ and between the Ln ions. It was found that the singlet lowest-energy excited state (S1) of the ligand and the higher triplet energy level (Tn) are crucial in the energy transfer processes of ligand→Tb3+ and ligand→Eu3+. This enables EuxTb1-xL to serve as an effective platform for exploring the impact of these energy transfer processes on the temperature-sensing properties of luminescent Eu/Tb-MOF thermometers. The relative thermal sensitivity is comparable to that of dual-center MOF-based luminescent thermometers operating at physiological levels. This study provides valuable insights into the design of new Eu/Tb thermometers and the accurate prediction of their sensing performance.

Exploration of potential biomarkers for prurigo nodularis based on plasma-metabolome analysis.

Prurigo nodularis (PN) is a chronic and debilitating skin disease with severe itching that negatively impacts patients' quality of life and mental state. However, the treatment options for PN remain limited. Global metabolomics analysis can offer effective information on energy metabolism, pathogenesis and potential diagnostic biomarkers. No study on metabolomic analysis of PN has been reported. To further understand the mechanisms of PN and analyse the plasma metabolite profiles in patients with PN. Targeted-metabolome analysis of 306 metabolites in plasma from 18 patients with PN and 19 healthy controls was performed using Liquid Chromatography-tandem Mass Spectrometer analysis. We identified 31 differential metabolites. Most acylcarnitines, long-chain fatty acids, alpha-aminobutyric acid, hydroxybutyric acid and lactic acid among these metabolites were up-regulated in patients with PN; in contrast, glucaric acid, suberic acid, bile acid derivatives and most amino acids were down-regulated. Positive correlations exist between glucaric acid and itching severity and acylcarnitines and insomnia. Suberic acid and the Investigator's Global Assessment (IGA) scores correlate negatively. Metabolite variation reflects the dysregulation of energy metabolism and chronic systematic inflammation in PN. Several metabolites, such as glucaric acid, suberic acid and acylcarnitines, merit further study as potential biomarkers of disease severity in PN.

WT1 And DNMT3A Mutations in Prognostic Significance of Acute Myeloid Leukemia: A Meta-Analysis.

Background: Adult acute leukemia most commonly manifests as acute myeloid leukemia (AML), a highly heterogeneous malignant tumor of the blood system. The application of genetic diagnostic technology is currently prevalent in numerous clinical sectors. According to recent research, the presence of specific gene mutations or rearrangements in leukemia cells is the primary cause of the disease. As different types of leukemia are caused by atypical mutated genes, testing for these mutations or rearrangements can help diagnose leukemia and identify the disease's molecular targets for treatment. Methods: Using the search fields "WT1," "DNMT3A," "Acute myeloid leukemia," and "survival," the CBM, Cochrane Library, Scopus, EMBASE, and PUBMED databases were separately reviewed. The methodology for evaluating the risk of bias developed by the Cochrane Collaboration was used in conjunction with a methodical evaluation of pertinent literature. Excluded studies with the following characteristics: (1) incomplete and repetitive publications, (2) unable to retrieve or convert data, (3) non-English or Chinese articles. Results: This analysis included 13 studies covering a total of 3478 subjects. The frequency of Wilms' Tumor 1 (WT1) mutations is 6.7%-35.73%, and the frequency of DNMT3A mutations is 12.06%-51.1%. The remission rate of patients with WT1 mutations was less than that of patients without WT1 mutations (OR = 0.22; 95% confidence interval [CI]: 0.14, 0.36; p < 0.00001; I2 = 55%). The DNMT3A mutation has no statistical significance for the prognosis of AML (OR = 1.21; 95% CI: 0.93, 1.58; p = 0.16; I2 = 80%). After removing one study, the heterogeneity of the indicator (mitigation rate) among other studies of DNMT3A mutation was dramatically reduced (OR = 0.63; 95% CI: 0.43, 0.93; p = 0.02; I2 = 0%). Conclusions: Our meta-analysis shows that WT1 mutations hurt the remission rate of AML. Moreover, the impact of DNMT3A mutations on AML needs to be treated with caution. Gene diagnosis is critical for the prognosis and clinical management of AML.

The Effect of Fractional Carbon Dioxide Laser on Melanogenesis in Human Melanocytes and Vitiligo Mouse Models.

Introduction: Vitiligo is an acquired skin pigmentation disorder, the cause of which is poorly understood. Researchers in this field are dedicated to exploring novel treatments for achieving re-pigmentation. Methods: Mice were randomly selected and divided into control, model, and model+laser groups. Evaluate the impact of different levels of carbon dioxide laser irradiation on tyrosinase activity, melanocyte viability, and melanin content. Results: In this study, it was found that the cell viability and melanin content were significantly enhanced in human melanocytes after treatment with different energy densities of fractional carbon dioxide laser. In addition, laser-treated vitiligo mouse models showed mild pathological changes. Discussion: Therefore, we believe that fractional carbon dioxide laser may be a potential adjunctive modality for treating vitiligo.