NLRP4E regulates actin cap formation through SRC and CDC42 during oocyte meiosis.

BACKGROUND: Members of the nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing (NLRP) family regulate various physiological and pathological processes. However, none have been shown to regulate actin cap formation or spindle translocation during the asymmetric division of oocyte meiosis I. NLRP4E has been reported as a candidate protein in female fertility, but its function is unknown. METHODS: Immunofluorescence, reverse transcription polymerase chain reaction (RT-PCR), and western blotting were employed to examine the localization and expression levels of NLRP4E and related proteins in mouse oocytes. small interfering RNA (siRNA) and antibody transfection were used to knock down NLRP4E and other proteins. Immunoprecipitation (IP)-mass spectrometry was used to identify the potential proteins interacting with NLRP4E. Coimmunoprecipitation (Co-IP) was used to verify the protein interactions. Wild type (WT) or mutant NLRP4E messenger RNA (mRNA) was injected into oocytes for rescue experiments. In vitro phosphorylation was employed to examine the activation of steroid receptor coactivator (SRC) by NLRP4E. RESULTS: NLRP4E was more predominant within oocytes compared with other NLRP4 members. NLRP4E knockdown significantly inhibited actin cap formation and spindle translocation toward the cap region, resulting in the failure of polar body extrusion at the end of meiosis I. Mechanistically, GRIN1, and GANO1 activated NLRP4E by phosphorylation at Ser429 and Thr430; p-NLRP4E is translocated and is accumulated in the actin cap region during spindle translocation. Next, we found that p-NLRP4E directly phosphorylated SRC at Tyr418, while p-SRC negatively regulated p-CDC42-S71, an inactive form of CDC42 that promotes actin cap formation and spindle translocation in the GTP-bound form. CONCLUSIONS: NLRP4E activated by GRIN1 and GANO1 regulates actin cap formation and spindle translocation toward the cap region through upregulation of p-SRC-Tyr418 and downregulation of p-CDC42-S71 during meiosis I.

MiRNA-224-5p regulates the defective permeability barrier in sensitive skin by targeting claudin-5.

BACKGROUND: Sensitive skin is hypersensitive to various external stimuli and a defective epidermal permeability barrier is an important clinical feature of sensitive skin. Claudin-5 (CLDN5) expression levels decrease in sensitive skin. This study aimed to explore the impact of CLDN5 deficiency on the permeability barrier in sensitive skin and the regulatory role of miRNAs in CLDN5 expression. MATERIALS AND METHODS: A total of 26 patients were retrospectively enrolled, and the CLDN5 expression and permeability barrier dysfunction in vitro were assessed. Then miRNA-224-5p expression was also assessed in sensitive skin. RESULTS: Immunofluorescence and electron microscopy revealed reduced CLDN5 expression, increased miR-224-5p expression, and disrupted intercellular junctions in sensitive skin. CLDN5 knockdown was associated with lower transepithelial electrical resistance (TEER) and Lucifer yellow penetration in keratinocytes and organotypic skin models. The RNA-seq and qRT-PCR results indicated elevated miR-224-5p expression in sensitive skin; MiR-224-5p directly interacted with the 3`UTR of CLDN5, resulting in CLDN5 deficiency in the luciferase reporter assay. Finally, miR-224-5p reduced TEER in keratinocyte cultures. CONCLUSION: These results suggest that the miR-224-5p-induced reduction in CLDN5 expression leads to impaired permeability barrier function, and that miR-224-5p could be a potential therapeutic target for sensitive skin.

GPR55 activation improves anxiety- and depression-like behaviors of mice during methamphetamine withdrawal.

Methamphetamine is a potent and highly addictive neurotoxic psychostimulant that triggers a spectrum of adverse emotional responses during withdrawal. G-protein coupled receptor 55 (GPR55), a novel endocannabinoid receptor, is closely associated with mood regulation. Herein, we developed a murine model of methamphetamine-induced anxiety- and depressive-like behavior during abstinence which showed a decreased GPR55 expression in the hippocampus. Activation of GPR55 mitigated these behavioral symptoms, concomitantly ameliorating impairments in hippocampal neurogenesis and reducing neuroinflammation. These findings underscore the pivotal role of GPR55 in mediating the neuropsychological consequences of methamphetamine withdrawal, potentially via mechanisms involving the modulation of hippocampal neurogenesis and inflammation.

Integrative analyses of bulk and single-cell transcriptomics reveals the infiltration and crosstalk of cancer-associated fibroblasts as a novel predictor for prognosis and microenvironment remodeling in intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a highly malignant neoplasm and characterized by desmoplastic matrix. The heterogeneity and crosstalk of tumor microenvironment remain incompletely understood. METHODS: To address this gap, we performed Weighted Gene Co-expression Network Analysis (WGCNA) to identify and construct a cancer associated fibroblasts (CAFs) infiltration biomarker. We also depicted the intercellular communication network and important receptor-ligand complexes using the single-cell transcriptomics analysis of tumor and Adjacent normal tissue. RESULTS: Through the intersection of TCGA DEGs and WGCNA module genes, 784 differential genes related to CAFs infiltration were obtained. After a series of regression analyses, the CAFs score was generated by integrating the expressions of EVA1A, APBA2, LRRTM4, GOLGA8M, BPIFB2, and their corresponding coefficients. In the TCGA-CHOL, GSE89748, and 107,943 cohorts, the high CAFs score group showed unfavorable survival prognosis (p < 0.001, p = 0.0074, p = 0.028, respectively). Additionally, a series of drugs have been predicted to be more sensitive to the high-risk group (p < 0.05). Subsequent to dimension reduction and clustering, thirteen clusters were identified to construct the single-cell atlas. Cell-cell interaction analysis unveiled significant enhancement of signal transduction in tumor tissues, particularly from fibroblasts to malignant cells via diverse pathways. Moreover, SCENIC analysis indicated that HOXA5, WT1, and LHX2 are fibroblast specific motifs. CONCLUSIONS: This study reveals the key role of fibroblasts - oncocytes interaction in the remodeling of the immunosuppressive microenvironment in intrahepatic cholangiocarcinoma. Subsequently, it may trigger cascade activation of downstream signaling pathways such as PI3K-AKT and Notch in tumor, thus initiating tumorigenesis. Targeted drugs aimed at disrupting fibroblasts-tumor cell interaction, along with associated enrichment pathways, show potential in mitigating the immunosuppressive microenvironment that facilitates tumor progression.

Ir(III) Metal Emitters with Cyano-Modified Imidazo[4,5-b]pyridin-2-ylidene Chelates for Deep-Blue Organic Light-Emitting Diodes.

Ir(III) carbene complexes have been explored as one of the best blue phosphors for their high performance. Herein, the authors designed and synthesized a series of blue-emitting Ir(III) phosphors (f-ct9a-c), featuring fac-coordinated cyano-imidazo[4,5-b]pyridin-2-ylidene cyclometalates. These Ir(III) complexes exhibit true-blue emission with a peak maximum spanning 448-467 nm, with high photoluminescence quantum yields of 81-88% recorded in degassed toluene. Moreover, OLED devices bearing phosphors f-ct9a and f-ct9b deliver maximum external quantum efficiencies (EQEmax) of 25.9% and 30.3%, together with Commission Internationale de L'Eclairage (CIEx,y) coordinates of (0.157, 0.225) and (0.142, 0.169), respectively. Remarkably, the f-ct9b-based device displays an incredible EQE of 29.0% at 5000 cd·m-2. The hyper-OLED device based on f-ct9b and ν-DABNA exhibits an EQEmax of 34.7% and CIEx,y coordinates of (0.122, 0.131), affirming high potentials in achieving efficient blue electroluminescence.

Continuous catalytic production of 1,3-dihydroxyacetone: Sustainable approach combining perfusion cultures and immobilized cells.

Currently, the predominant method for the industrial production of 1,3-dihydroxyacetone (DHA) from glycerol involves fed-batch fermentation. However, previous research has revealed that in the biocatalytic synthesis of DHA from glycerol, when the DHA concentration exceeded 50 g·L-1, it significantly inhibited microbial growth and metabolism, posing a challenge in maintaining prolonged and efficient catalytic production of DHA. In this study, a new integrated continuous production and synchronous separation (ICSS) system was constructed using hollow fiber columns and perfusion culture technology. Additionally, a cell reactivation technique was implemented to extend the biocatalytic ability of cells. Compared with fed-batch fermentation, the ICSS system operated for 360 h, yielding a total DHA of 1237.8 ± 15.8 g. The glycerol conversion rate reached 97.7 %, with a productivity of 3.44 g·L-1·h-1, representing 485.0 % increase in DHA production. ICSS system exhibited strong operational characteristics and excellent performance, indicating significant potential for applications in industrial bioprocesses.

Temperature Dependence of the Dynamic Contact Angles of Water on a Smooth Stainless-Steel Surface under Elevated Pressures.

The temperature dependence of the dynamic contact angles (DCAs) of water on a metallic surface remains unclear, especially under elevated pressures. Here in this work, the advancing and receding contact angles (RCAs), as well as the contact angle hysteresis (CAH), of water on stainless-steel 316 (SS316) surfaces were studied using the dynamic sessile drop method for temperatures up to 300 °C and pressures up to 10 MPa. It was found that the temperature dependence of the DCAs exhibits a different pattern as compared to the piecewise linear decline of static contact angles. The advancing contact angle (ACA) remains nearly constant and does not decrease until the temperature becomes close to the saturated temperature. The decrease in ACA is attributed to evaporation, which reduces the advancement of energy barrier. The RCA linearly declines below 120 °C and remains stable above 120 °C. The increasing temperature enhances the pinning effect and changes the droplet receding mode. Under all pressures tested, the CAH demonstrates a "increase-constant-decrease" trilinear relationship with temperature. Furthermore, the mean solid surface entropy and solid-gas interfacial tension of SS316 were estimated to be 0.1152 mJ/(m2·°C) and 61.49 mJ/m2, respectively.

Fluorine-Containing Ionogels with Stretchable, Solvent-Resistant, Wide Temperature Tolerance, and Transparent Properties for Ionic Conductors.

Stretchable ionogels, as soft ion-conducting materials, have generated significant interest. However, the integration of multiple functions into a single ionogel, including temperature tolerance, self-adhesiveness, and stability in diverse environments, remains a challenge. In this study, a new class of fluorine-containing ionogels was synthesized through photo-initiated copolymerization of fluorinated hexafluorobutyl methacrylate and butyl acrylate in a fluorinated ionic liquid 1-butyl-3-methyl imidazolium bis (trifluoromethylsulfonyl) imide. The resulting ionogels demonstrate good stretchability with a fracture strain of ~1300%. Owing to the advantages of the fluorinated network and the ionic liquid, the ionogels show excellent stability in air and vacuum, as well as in various solvent media such as water, sodium chloride solution, and hexane. Additionally, the ionogels display impressive wide temperature tolerance, functioning effectively within a wide temperature range from -60 to 350 °C. Moreover, due to their adhesive properties, the ionogels can be easily attached to various substrates, including plastic, rubber, steel, and glass. Sensors made of these ionogels reliably respond to repetitive tensile-release motion and finger bending in both air and underwater. These findings suggest that the developed ionogels hold great promise for application in wearable devices.

NLRP3 inflammasome-mediated premature immunosenescence drives diabetic vascular aging dependent on the induction of perivascular adipose tissue dysfunction.

AIMS: The vascular aging process accelerated by type 2 diabetes mellitus (T2DM) is responsible for the elevated risk of associated cardiovascular diseases (CVDs). Metabolic disorder-induced immune senescence has been implicated in multi-organ/tissue damage. Herein, we sought to determine the role of immunosenescence in diabetic vascular aging and to investigate the underlying mechanisms. METHODS AND RESULTS: Aging hallmarks of the immune system appear prior to the vasculature in streptozotocin (STZ)/high-fat diet (HFD)-induced T2DM mice or db/db mice. Transplantation of aged splenocytes or diabetic splenocytes into young mice triggered vascular senescence and injury compared to normal control splenocyte transfer. RNA-seq profile and validation in immune tissues revealed that the Toll-like receptor 4 (TLR4)- Nuclear factor-kappa B (NF-κB) -NLRP3 axis might be the mediator of diabetic premature immunosenescence. The absence of Nlrp3 attenuated immune senescence and vascular aging during T2DM. Importantly, senescent immune cells, particularly T cells, provoked perivascular adipose tissue (PVAT) dysfunction and alternations in its secretome, which in turn impair vascular biology. In addition, senescent immune cells may uniquely affect vasoconstriction via influencing PVAT. Lastly, rapamycin alleviated diabetic immune senescence and vascular aging, which may be partly due to NLRP3 signaling inhibition. CONCLUSION: These results indicated that NLRP3 inflammasome-mediated immunosenescence precedes and drives diabetic vascular aging. The contribution of senescent immune cells to vascular aging is a combined effect of their direct effects and induction of PVAT dysfunction, the latter of which can uniquely affect vasoconstriction. We further demonstrated that infiltration of senescent T cells in PVAT was increased and associated with PVAT secretome alterations. Our findings suggest that blocking the NLRP3 pathway may prevent early immunosenescence and thus mitigate diabetic vascular aging and damage, and targeting senescent T cells or PVAT might also be the potential therapeutic approach.

Guideline for diagnosis and management of congenital dysfibrinogenemia.

INTRODUCTION: Congenital dysfibrinogenemia (CD) is characterized by dysfunction induced by an abnormal fibrinogen molecule structure that results in blood coagulation dysfunction. The clinical manifestations of CD patients are asymptomatic, bleeding and thrombosis. The majority of patient are asymptomatic. However, the single fibrinogen detection method is easy to cause missed diagnosis or misdiagnosis of CD patients. The treatment strategies of CD patients with different clinical manifestations are also different. METHODS: Combing existing experimental technologies and studies, a simple and practical CD diagnostic criteria was proposed. And based on the relevant literature and existing treatment guidelines, more comprehensive treatment recommendations are summarized. RESULTS: In this new criteria, combination Clauss method and PT derived method was proposed to detect fibrinogen and its ratio was used to diagnose for CD. Diagnosis also needs to be combined the clinical manifestations, family investigation and genetic testing. According to different clinical manifestation (bleeding, thrombosis or asymptomatic), treatment methods and strategies are different. The treatment of CD patients should consider the patient's personal and family history of bleeding or thrombosis. Treatment of thrombosis and pregnancy may be more challenging. The risk of bleeding and thrombosis should be evaluated and balanced at all times during clinical treatment. These detailed treatment recommendations can provide reference for patients with different clinical manifestations of CD. CONCLUSIONS: The new CD diagnosis criteria and comprehensive treatment recommendations can effectively improve the diagnosis and treatment of CD.

[Multi-scenario Simulation of Construction Land Expansion and Its Impact on Ecosystem Carbon Storage in Beijing-Tianjin-Hebei Urban Agglomeration].

It is of great practical significance for regional sustainable development and ecological construction to quantitatively analyze the impact of construction land expansion on terrestrial ecosystem carbon storage and to explore the optimization scheme of simulating construction land expansion to improve future ecosystem carbon storage. Based on the land use and cover change (LUCC) and other geospatial data of the Beijing-Tianjin-Hebei Urban Agglomeration from 2000 to 2020, this study utilized the Integrated Valuation of Ecosystem Services and Tradeoffs (InVEST) model and the patch-generating land-use simulation (PLUS) model to assess and analyze the changes in ecosystem carbon stocks and spatial patterns regionally. In this study, we performed linear regression analysis to investigate the relationship between urban land expansion and changes in ecosystem carbon stocks for varying urban land proportion levels during two distinct time intervals, 2000-2010 and 2010-2020, which was conducted at a spatial resolution of 2 km. Three distinct urban land expansion scenarios were subjected to simulation to forecast the prospective land use pattern by 2030. Subsequently, we quantified the ramifications of these scenarios on ecosystem carbon stocks during the period from 2020 to 2030. The results were as follows:① In the Beijing-Tianjin-Hebei Urban Agglomeration, the ecosystem carbon stocks exhibited notable variations over the study period, with values of 2 088.02, 2 106.78, and 2 121.25 Tg recorded for the years 2000, 2010, and 2020, respectively, resulting in a cumulative carbon sequestration of 33.23 Tg C during the study duration. It is noteworthy that forest carbon storage emerged as the dominant contributor, with an increase from 1 010.17 Tg in 2000 to 1 136.53 Tg in 2020. Throughout the study period, the spatial distribution of carbon stocks displayed relative stability. Regions characterized by lower carbon content were concentrated in the vicinity of the Bohai Rim region and in proximity to cities such as Beijing, Tianjin, and Shijiazhuang, as well as rural settlements. In contrast, grid units with moderate and high carbon stocks were predominantly situated in the western Taihang Mountain and the northern Yanshan Mountain. Additionally, there was a tendency of increasing carbon stocks in the Taihang Mountain and Yanshan Mountain region, whereas those surrounding major urban centers such as Beijing, Tianjin, Shijiazhuang, and Tangshan experienced a notable decline in carbon stocks. Such reductions were most pronounced in regions undergoing urban land expansion during the study period. ② In grid units with an urban land proportion exceeding 10% at each level, a strong correlation was observed between urban land expansion and changes in carbon stocks during both the 2000-2010 and 2010-2020 periods. The changes in urban land proportion adequately explained the variations in carbon stocks. However, the explanatory power of urban land on carbon stocks decreased during the 2010-2020 period, indicating that other factors played a more substantial role in influencing carbon stocks during this time. The regression coefficients for both periods exhibited a fluctuating upward trend. In comparison to that during the 2000-2010 period, the impact of urban land expansion on carbon stocks was relatively smaller during 2010-2020, indicating a weakening influence. ③ In light of three distinct development scenarios, namely natural development (Scenario Ⅰ), a 15% reduction in the rate of urban land expansion (Scenario Ⅱ), and a 30% reduction in the rate of urban land expansion (Scenario Ⅲ), the projected ecosystem carbon stocks for the Beijing-Tianjin-Hebei Urban Agglomeration in the year 2030 were estimated to be 2 129.12, 2 133.55, and 2 139.10 Tg, respectively. These projections indicated an increase of 7.88, 12.30, and 17.85 Tg in comparison to the current carbon stocks. All scenarios demonstrated that the terrestrial ecosystem would play a role of carbon sink, particularly with the greatest carbon sink observed in the scenario with a 30% reduction in urban land expansion. The fit performance between urban land expansion and carbon stock changes during the 2020-2030 period was significantly better than that during the 2000-2010 and 2010-2020 periods, and the regression coefficients showed a fluctuating increase with an increase in urban land proportion. Across grid units with different urban land proportion levels, the regression coefficients exhibited the order of Scenario Ⅰ < Scenario Ⅱ < Scenario Ⅲ. In pursuit of the carbon peaking and carbon neutrality goals, the Beijing-Tianjin-Hebei Urban Agglomeration should prioritize scenarios with reduced rates of urban land expansion, especially in regions with higher urban land proportions.

Interfering with reconsolidation by rimonabant results in blockade of heroin-associated memory.

Drug-associated pathological memory remains a critical factor contributing to the persistence of substance use disorder. Pharmacological amnestic manipulation to interfere with drug memory reconsolidation has shown promise for the prevention of relapse. In a rat heroin self-administration model, we examined the impact of rimonabant, a selective cannabinoid receptor indirect agonist, on the reconsolidation process of heroin-associated memory. The study showed that immediately administering rimonabant after conditioned stimuli (CS) exposure reduced the cue- and herion + cue-induced heroin-seeking behavior. The inhibitory effects lasted for a minimum of 28 days. The effect of Rimonabant on reduced drug-seeking was not shown when treated without CS exposure or 6 hours after CS exposure. These results demonstrate a disruptive role of rimonabant on the reconsolidation of heroin-associated memory and the therapeutic potential in relapse control concerning substance use disorder.

Flash healing of laser-induced graphene.

The advancement of laser-induced graphene (LIG) technology has streamlined the fabrications of flexible graphene devices. However, the ultrafast kinetics triggered by laser irradiation generates intrinsic amorphous characteristics, leading to high resistivity and compromised performance in electronic devices. Healing graphene defects in specific patterns is technologically challenging by conventional methods. Herein, we report the rapid rectification of LIG's topological defects by flash Joule heating in milliseconds (referred to as F-LIG), whilst preserving its overall structure and porosity. The F-LIG exhibits a decreased ID/IG ratio from 0.84 - 0.33 and increased crystalline domain from Raman analysis, coupled with a 5-fold surge in conductivity. Pair distribution function and atomic-resolution imaging delineate a broader-range order of F-LIG with a shorter C-C bond of 1.425 Å. The improved crystallinity and conductivity of F-LIG with excellent flexibility enables its utilization in high-performance soft electronics and low-voltage disinfections. Notably, our F-LIG/polydimethylsiloxane strain sensor exhibits a gauge factor of 129.3 within 10% strain, which outperforms pristine LIG by 800%, showcasing significant potential for human-machine interfaces.

[Correlation of nutritional status with clinical characteristics and lung function in children with cystic fibrosis]. / å›Šæ€§çº¤ç»´åŒ–å„¿ç«¥è¥å »çŠ¶å†µä¸Žä¸´åºŠç‰¹å¾å’Œè‚ºåŠŸèƒ½çš„ç›¸å ³æ€§åˆ†æž.

OBJECTIVES: To investigate the nutritional status of children with cystic fibrosis (CF) and understand the correlation between malnutrition and clinical characteristics as well as lung function. METHODS: A retrospective analysis was performed on clinical data of CF children admitted from January 2016 to June 2023. Clinical characteristics of CF children with different nutritional statuses were compared, and the correlation between malnutrition and lung function was analyzed. RESULTS: A total of 52 CF children were included, comprising 25 boys (48%) and 27 girls (52%), aged between 7 months and 17 years. Respiratory symptoms were the predominant clinical manifestations (96%, 50/52). The prevalence of malnutrition was 65% (34/52), with moderate/severe malnutrition being the most common (65%, 22/34). The malnutrition group had a longer duration of illness, higher proportion of digestive system symptoms, and lower levels of serum albumin (P<0.05). Pulmonary function parameters, including forced expiratory volume in one second as a percentage of the predicted value, ratio of forced expiratory volume in one second to forced vital capacity, forced expiratory flow at 25% of forced vital capacity exhaled, forced expiratory flow at 50% of forced vital capacity exhaled, forced expiratory flow at 75% of forced vital capacity exhaled, and maximum mid-expiratory flow as a percentage of the predicted value, were lower in the malnutrition group compared to the normal nutrition group (P<0.05). Correlation analysis showed body mass index Z-score was positively correlated with the above six pulmonary function parameters (P<0.05). CONCLUSIONS: The prevalence of malnutrition is high in CF children and is associated with decreased lung function. CF children with higher body mass index have better lung function. Therefore, screening and evaluation of nutritional status as well as appropriate nutritional intervention should be emphasized in CF children.

Study on the Effect of Electrolytes on Processing Efficiency and Accuracy of Titanium Alloy Utilizing Laser and Shaped Tube Electrochemical Machining.

Electrochemical machining (ECM) has become more prevalent in titanium alloy processing. However, the presence of the passivation layer on the titanium alloys significantly impacts the performance of ECM. In an attempt to overcome the passivation effects, a high-temperature electrolyte or the addition of halogen ions to the electrolyte has been used. Still, it often results in compromised machining accuracy and surface roughness. This study applied laser and shaped tube electrolytic machining (Laser-STEM) for titanium alloy drilling, where the laser was guided to the machining zone via total internal reflection. The performance of Laser-STEM using different types of electrolytes was compared. Further, the effects of laser power and pulse voltage on the machining side gap, material removal rate (MRR), and surface roughness were experimentally studied while drilling small holes in titanium alloy. The results indicated that the use of passivating electrolytes improved the machining precision, while the MRR decreased with an increase in laser power during Laser-STEM. The MRR showed an increase while using aggressive electrolytes; however, at the same time, the machining precision deteriorated with the increase in laser power. Particularly, the maximum feeding rate of 6.0 mm/min for the tool electrode was achieved using NaCl solution as the electrolyte during Laser-STEM, marking a 100% increase compared to the rate without the use of a laser. Moreover, the model and equivalent circuits were also established to illustrate the material removal mechanisms of Laser-STEM in different electrolytes. Lastly, the processing of deep small holes with a diameter of 1.5 mm, a depth of 38 mm, and a surface roughness of Ra 2 µm was achieved via Laser-STEM without the presence of a recast layer and heat-affected zones. In addition, the cross-inner flow channels in the titanium alloys were effectively processed.

Dynamic change in the peritoneal cancer index based on CT after chemotherapy in the overall survival prediction of gastric cancer patients with peritoneal metastasis.

PURPOSE: The purpose of this research was to investigate the efficacy of the CT-based peritoneal cancer index (PCI) to predict the overall survival of patients with peritoneal metastasis in gastric cancer (GCPM) after two cycles of chemotherapy. METHODS: This retrospective study registered 112 individuals with peritoneal metastasis in gastric cancer in our hospital. Abdominal and pelvic enhanced CT before and after chemotherapy was independently analyzed by two radiologists. The PCI of peritoneal metastasis in gastric cancer was evaluated according to the Sugarbaker classification, considering the size and distribution of the lesions using CT. Then we evaluated the prognostic performance of PCI based on CT, clinical characteristics, and imaging findings for survival analysis using multivariate Cox proportional hazard regression. RESULTS: The PCI change ratio based on CT after treatment (ΔPCI), therapy lines, and change in grade of ascites were independent factors that were associated with overall survival (OS). The area under the curve (AUC) value of ΔPCI for predicting OS with 0.773 was higher than that of RECIST 1.1 with 0.661 (P < 0.05). Patients with ΔPCI less than -15% had significantly longer OS. CONCLUSION: CT analysis after chemotherapy could predict OS in patients with GCPM. The CT-PCI change ratio could contribute to the determination of an appropriate strategy for gastric cancer patients with peritoneal metastasis.

Application of tandem mass spectrometry in the screening and diagnosis of mucopolysaccharidoses.

Mucopolysaccharidoses (MPSs) are caused by a deficiency in the enzymes needed to degrade glycosaminoglycans (GAGs) in the lysosome. The storage of GAGs leads to the involvement of several systems and even to the death of the patient. In recent years, an increasing number of therapies have increased the treatment options available to patients. Early treatment is beneficial in improving the prognosis, but children with MPSs are often delayed in their diagnosis. Therefore, there is an urgent need to develop a method for early screening and diagnosis of the disease. Tandem mass spectrometry (MS/MS) is an analytical method that can detect multiple substrates or enzymes simultaneously. GAGs are reliable markers of MPSs. MS/MS can be used to screen children at an early stage of the disease, to improve prognosis by treating them before symptoms appear, to evaluate the effectiveness of treatment, and for metabolomic analysis or to find suitable biomarkers. In the future, MS/MS could be used to further identify suitable biomarkers for MPSs for early diagnosis and to detect efficacy.

Combining HD-tDCS with music stimulation for patients with prolonged disorders of consciousness: Study protocol for an RCT trial.

BACKGROUND: Patients with prolonged disorders of consciousness (pDOC) pose significant challenges to healthcare workers due to their severe motor impairments and limited interaction with the environment. Non-invasive brain stimulation such as high-definition transcranial direct current stimulation (HD-tDCS) and music stimulation show promise in awakening this population. OBJECTIVE: In this study, we present a protocol aiming at investigating the efficacy of combined HD-tDCS and music stimulation in awakening patients with pDOC through a single-blind, randomized controlled trial. METHODS: Ninety patients with pDOC will be randomly divided into three groups: active HD-tDCS with music stimulation, active HD-tDCS, and sham HD-tDCS. All participants will receive 20 treatment sessions over a period of 10 days and the Coma Recovery Scale-Revised, Glasgow Outcome Scale and electroencephalogram will be used as assessment measures to evaluate their level of consciousness throughout the study. Adverse events and complications will be recorded during treatment. Within-group pre-post comparisons and between-group efficacy comparisons will be conducted to identify the most effective intervention approach. Statistical analysis will be performed using SPSS software with a significance level set at P < 0.05. CONCLUSION: The pursuit of awakening therapy for patients with pDOC remains a clinical research challenge. This study protocol is designed with the aim of introducing an innovative non-pharmacological approach which combined HD-tDCS and music stimulation to facilitate the reinstatement of consciousness in patients with pDOC.