Role of savolitinib in advanced gastric adenocarcinoma with meningeal carcinomatosis and cerebellar metastasis: A case report.

BACKGROUND: Brain metastases (BM) are very rare in gastric adenocarcinoma (GaC), and patients with BMs have a higher mortality rate due to stronger tumor aggressiveness. However, its pathogenesis remains unclear. Genetic testing revealed cellular-mesenchymal epithelial transition factor receptor (MET) amplification. Therefore, treatment with savolitinib, a small molecule inhibitor of c-Met, was selected. CASE SUMMARY: A 66-year-old woman was diagnosed with advanced GaC 6 months prior to presentation due to back pain. Cerebellar and meningeal metastases were observed during candonilimab combined with oxaliplatin and capecitabine therapy. The patient experienced frequent generalized seizures and persistent drowsiness in the emergency department. Genetic testing of cerebrospinal fluid and peripheral blood revealed increased MET amplification. After discussing treatment options with the patient, savolitinib tablets were administered. After a month of treatment, the intracranial lesions shrank considerably. CONCLUSION: BM is very rare in advanced GaC, especially in meningeal cancer, that is characterized by rapid disease deterioration. There are very few effective treatment options available; however, technological breakthroughs in genomics have provided a basis for personalized treatment. Furthermore, MET amplification may be a key driver of BM in gastric cancer; however, this conclusion requires further investigation.

Electroacupuncture at different intensities inhibits nociceptive discharges of wide dynamic range neurons in spinal dorsal horn of rats. / ä¸åŒå¼ºåº¦ç”µé’ˆå¯¹å¤§é¼ è„Šé«“èƒŒè§’å¹¿åŠ¨åŠ›ç¥žç»å ƒä¼¤å®³æ€§æ”¾ç”µçš„æŠ‘åˆ¶ä½œç”¨.

OBJECTIVES: To observe the effect of electroacupuncture (EA) at different intensities on nociceptive discharges of wide dynamic range (WDR) neurons in the spinal dorsal horns (DHs) of rats, so as to explore its regulatory characteristics on nociceptive signals at the spinal level. METHODS: A total of 25 male SD rats were used in the present study. A microelectrode array was used to record the discharge activity of WDR neurons in the lumbar spinal DHs of normal rats. After finding the WDR neuron, electrical stimulation (pulse width of 2 ms) was administered to the plantar receptive field (RF) for determining its response component of discharges according to the latency of action potential generation (Aß ï¼»0 to 20 msï¼½, Aδ ï¼»20 to 90 msï¼½, C ï¼»90 to 500 msï¼½ and post-discharge ï¼»500 to 800 msï¼½). High-intensity electrical stimulation was continuously applied to the RF at the paw's plantar surface to induce DHs neuronal windup response. Subsequently, EA stimulation at different intensities (1 mA and 2 mA) was applied to the left "Zusanli"(ST36) at a frequency of 2 Hz/15 Hz for 10 min. The induction of WDR neuronal windup was then repeated under the same conditions. The quantity of nociceptive discharge components and the windup response of WDR neurons before and after EA stimulations at different intensities were compared. RESULTS: Compared to pre-EA, both EA1 mA and EA2 mA significantly reduced the number of Aδ and C component discharges of WDR neurons during stimulation, as well as post-discharge (P<0.01, P<0.001). The inhibitory rate of C component by EA2 mA was significantly higher than that by EA1 mA (P<0.05). Meanwhile, both EA1 mA and EA2 mA attenuated the windup response of WDR neurons (P<0.05, P<0.01), and the effect of EA2 mA was stronger than that of EA1 mA (P<0.05). Further analysis showed that when EA1 mA and EA2 mA respectively applied to both non-receptive field (non-RF) and RF, a significant reduction in the number of Aδ component, C component and post-discharge was observed (P<0.05, P<0.01). EA2 mA at the non-RF and RF demonstrated a significant inhibitory effect on the windup response of WDR neurons (P<0.01, P<0.05), but EA1 mA only at the non-RF showed a significant inhibitory effect on the windup response (P<0.01). CONCLUSIONS: EA can suppress nociceptive discharges of spinal DHs WDR neurons in rats. The inhibitory impact of EA is strongly correlated with the location and intensity of EA stimulation, and EA2 mA has a stronger inhibitory effect than EA1 mA.

Improving precision management of anxiety disorders: a Mendelian randomization study targeting specific gut microbiota and associated metabolites.

Background: There is growing evidence of associations between the gut microbiota and anxiety disorders, where changes in gut microbiotas may affect brain function and behavior via the microbiota-gut-brain axis. However, population-level studies offering a higher level of evidence for causality are lacking. Our aim was to investigate the specific gut microbiota and associated metabolites that are closely related to anxiety disorders to provide mechanistic insights and novel management perspectives for anxiety disorders. Method: This study used summary-level data from publicly available Genome-Wide Association Studies (GWAS) for 119 bacterial genera and the phenotype "All anxiety disorders" to reveal the causal effects of gut microbiota on anxiety disorders and identify specific bacterial genera associated with anxiety disorders. A two-sample, bidirectional Mendelian randomization (MR) design was deployed, followed by comprehensive sensitivity analyses to validate the robustness of results. We further conducted multivariable MR (MVMR) analysis to investigate the potential impact of neurotransmitter-associated metabolites, bacteria-associated dietary patterns, drug use or alcohol consumption, and lifestyle factors such as smoking and physical activity on the observed associations. Results: Bidirectional MR analysis identified three bacterial genera causally related to anxiety disorders: the genus Eubacterium nodatum group and genus Ruminococcaceae UCG011 were protective, while the genus Ruminococcaceae UCG011 was associated with an increased risk of anxiety disorders. Further MVMR suggested that a metabolite-dependent mechanism, primarily driven by tryptophan, tyrosine, phenylalanine, glycine and cortisol, which is consistent with previous research findings, probably played a significant role in mediating the effects of these bacterial genera to anxiety disorders. Furthermore, modifying dietary pattern such as salt, sugar and processed meat intake, and adjusting smoking state and physical activity levels, appears to be the effective approaches for targeting specific gut microbiota to manage anxiety disorders. Conclusion: Our findings offer potential avenues for developing precise and effective management approaches for anxiety disorders by targeting specific gut microbiota and associated metabolites.

Curcumin inhibits the growth and invasion of gastric cancer by regulating long noncoding RNA AC022424.2.

BACKGROUND: Gastric cancer, characterized by a multifactorial etiology and high heterogeneity, continues to confound researchers in terms of its pathogenesis. Curcumin, a natural anticancer agent, exhibits therapeutic promise in gastric cancer. Its effects include promoting cell apoptosis, curtailing tumor angiogenesis, and enhancing sensitivity to radiation and chemotherapy. Long noncoding RNAs (lncRNAs) have garnered significant attention as biomarkers for early screening, diagnosis, treatment, and drug response because of their remarkable specificity and sensitivity. Recent investigations have revealed an association between aberrant lncRNA expression and early diagnosis, clinical staging, metastasis, drug sensitivity, and prognosis in gastric cancer. A profound understanding of the intricate mechanisms through which lncRNAs influence gastric cancer development can provide novel insights for precision treatment and tailored management of patients with gastric cancer. This study aimed to unravel the potential of curcumin in suppressing the malignant behavior of gastric cancer cells by upregulating specific lncRNAs and modulating gastric cancer onset and progression. AIM: To identify lncRNAs associated with curcumin treatment and investigate the role of lncRNA AC022424.2 in the effects of curcumin on gastric cancer cell apoptosis, proliferation, and invasion. Furthermore, these findings were validated in clinical samples. METHODS: The study employed CCK-8 assays to assess the impact of curcumin on gastric cancer cell proliferation, flow cytometry to investigate its effects on apoptosis, and scratch and Transwell assays to evaluate its influence on the migration and invasion of BGC-823 and MGC-803 cells. Western blotting was used to gauge changes in the protein expression levels of CDK6, CDK4, Bax, Bcl-2, caspase-3, P65, and the PI3K/Akt/mTOR pathway in gastric cancer cell lines after curcumin treatment. Differential expression of lncRNAs before and after curcumin treatment was assessed using lncRNA sequencing and validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR) in BGC-823 and MGC-803 cells. AC022424.2-1 knockdown BGC-823 and MGC-803 cells were generated to scrutinize the impact of lncRNA AC022424.2 on apoptosis, proliferation, migration, and invasion of gastric cancer cells. Western blotting was performed to ascertain changes in the expression of proteins implicated in the PI3K/Akt/mTOR and NF-κB signaling pathways. RT-PCR was employed to measure lncRNA AC022424.2 expression in clinical gastric cancer tissues and to correlate its expression with clinical pathological characteristics. RESULTS: Curcumin induced apoptosis and hindered proliferation, migration, and invasion of gastric cancer cells in a dose- and time-dependent manner. LncRNA AC022424.2 was upregulated after curcumin treatment, and its knockdown enhanced cancer cell aggressiveness. LncRNA AC022424.2 may have affected cancer cells via the PI3K/Akt/mTOR and NF-κB signaling pathways. LncRNA AC022424.2 downregulation was correlated with lymph node metastasis, making it a potential diagnostic and prognostic marker. CONCLUSION: Curcumin has potential anticancer effects on gastric cancer cells by regulating lncRNA AC022424.2. This lncRNA plays a significant role in cancer cell behavior and may have clinical implications in diagnosis and prognosis evaluation. The results of this study enhance our understanding of gastric cancer development and precision treatment.

Association between irritable bowel syndrome and Parkinson's disease by Cohort study and Mendelian randomization analysis.

This study aimed to investigate the association between irritable bowel syndrome (IBS) and Parkinson's disease (PD) utilizing prospective cohort study and Mendelian randomization. The dataset contained a substantial cohort of 426,911 participants from the UK Biobank, discussing the association between IBS and PD with Cox proportional hazards models and case-control analysis while adjusting for covariates such as age, gender, ethnicity and education level. In univariate Cox regression model, the risk of PD was reduced in IBS patients (HR: 0.774, 95%CI: 0.625-0.956, P = 0.017), but the statistical significance diminished in the three models after adjusting for other variables. In a few subgroup analyses, IBS patients are less likely to develop into PD, and patients diagnosed with IBS after 2000 also had a lower risk (HR: 0.633, 95%CI: 0.403-0.994, P = 0.047) of subsequently developing PD. In addition, we matched five healthy control participants based on gender and age at the end of the study for each IBS patient diagnosed during the follow-up period, and logistic regression results (OR:1.239, 95%CI: 0.896-1.680, P = 0.181) showed that IBS was not associated with the risk of PD. Mendelian randomization did not find significant evidence of the causal relationship between IBS and Parkinson's disease (OR: 0.801, 95%CI: 0.570-1.278, P = 0.204). Overall, we suggest that IBS status is not associated with the risk of developing PD, and that these findings provide valuable insights into the clinical management and resource allocation of patients with IBS.

hOGG1: A novel mediator in nitrosamine-induced esophageal tumorigenesis.

BACKGROUND: The effect of human 8-Oxoguanine DNA Glycosylase (hOGG1) on exogenous chemicals in esophageal squamous cell carcinoma (ESCC) remain unclear. The study plans to determine hOGG1 expression levels in ESCC and possible interactions with known environmental risk factors in ESCC. MATERIAL AND METHODS: We analyzed levels of exposure to urinary nitrosamines in volunteers from high and low prevalence areas by GC-MS. And we performed the interaction between hOGG1 gene and nitrosamine disinfection by-products by analyzing hOGG1 gene expression in esophageal tissues. RESULTS: In ESCC, nitrosamine levels were significantly increased and hOGG1 mRNA expression levels were significantly decreased. There was a statistically significant interaction between reduced hOGG1 mRNA levels and non-tap drinking water sources in ESCC. The apparent indirect association between ESCC and NMEA indicated that 33.4% of the association between ESCC and NMEA was mediated by hOGG1. CONCLUSION: In populations which exposed to high levels of environmental pollutants NDMA, low expression of hOGG1 may promote the high incidence of esophageal cancer in Huai'an. hOGG1 may be a novel mediator in nitrosamine-induced esophageal tumorigenesis.

Temporal changes in biomarkers of neutrophil extracellular traps and NET-promoting autoantibodies following adenovirus-vectored, mRNA, and recombinant protein COVID-19 vaccination.

Neutrophil extracellular traps (NETs) play a role in innate pathogen defense and also trigger B-cell response by providing antigens. NETs have been linked to vaccine-induced thrombotic thrombocytopenia. We postulated a potential link between NET biomarkers, NET-promoting autoantibodies, and adverse events (AEs) after COVID-19 vaccine boosters. Healthy donors (HDs) who received ChAdOx1-S (A), mRNA-1273 (M), or recombinant protein (MVC-COV1901) vaccines at the National Taiwan University Hospital between 2021 and 2022 were recruited. We measured serial NET-associated biomarkers, citrullinated-histone3 (citH3), and myeloperoxidase (MPO)-DNA. Serum citH3 and MPO-DNA were significantly or numerically higher in HDs who reported AEs (n = 100, booster Day 0/Day 30, p = 0.01/p = 0.03 and p = 0.30/p = 0.35, respectively). We also observed a positive correlation between rash occurrence in online diaries and elevated citH3. A linear mixed model also revealed significantly higher citH3 levels in mRNA-1273/ChAdOx1-S recipients than MVC-COV1901 recipients. Significant positive correlations were observed between the ratios of anti-heparin platelet factor 4 and citH3 levels on Booster Day 0 and naïve and between the ratios of anti-NET IgM and citH3 on Booster Day 30/Day 0 in the AA-M and MM-M group, respectively. The increased levels of citH3/MPO-DNA accompanied by NET-promoting autoantibodies suggest a potential connection between mRNA-1273/ChAdOx1-S vaccines and cardiovascular complications. These findings provide insights for risk assessments of future vaccines.

[Clinical Efficacy of Hypomethylating Agent Therapy in Patients with Chronic Myelomonocytic Leukemia].

OBJECTIVE: To observe the clinical efficacy and safety of hypomethylating agent therapy in chronic myelomonocytic leukemia (CMML). METHODS: From February 2014 to June 2021, the clinical data, efficacy, survival time and safety of CMML patients diagnosed in the Second Hospital of Hebei Medical University and treated with hypomethylating agent therapy were retrospectively analyzed. RESULTS: A total of 25 CMML patients received hypomethylating agent therapy, including 18 cases treated with decitabine (DEC) and 7 cases treated with azacytidine (AZA) as the basic treatment. Among them, 20 patients responded, and 7 patients got complete remission (CR). All patients with CR were treated with DEC as the basic treatment. Five cases of CR occurred in the first 4 courses of treatment. After a median follow-up of 16.4 (9.4-20.5) months, 4 patients with CR progressed to acute myeloid leukemia (AML). The median overall survival (OS) time of 25 CMML patients was 17.4 months (95%CI: 12.437-22.363). According to MD Anderson prognostic scoring system (MDAPS), CMML-specific prognostic scoring system (CPSS), CPSS molecular (CPSS-mol), Mayo molecular model (MMM), risk stratification of patients was performed, and the difference only between different risk stratification of MDAPS and survival time was statistically significant. Common adverse reactions of hypomethylating agent therapy in CMML patients included infection, gastrointestinal reaction, hematological toxicity, skin allergy and liver function damage. All patients' symptoms were improved after corresponding treatment. CONCLUSION: Hypomethylating agent therapy is effective and safe for CMML patients. CR mostly occurs in the first 4 courses of treatment, and hypomethylating agent therapy combined with low-dose chemotherapy can be used for patients who do not respond. Hypomethylating agent therapy can delay the disease, but can't prevent progression.

Inhibitory effect of acupoint electrostimulation with different layers and intensities on muscular inflammatory pain and spinal WDR neuron activity. / ç©´ä½ä¸åŒå±‚æ¬¡å’Œå¼ºåº¦ç”µåˆºæ¿€ç¼“è§£è‚Œè‚‰ç‚Žæ€§ç—›åŠå¯¹è„Šé«“èƒŒè§’å¹¿åŠ¨åŠ›ç¥žç»å ƒçš„æŠ‘åˆ¶ä½œç”¨.

OBJECTIVES: To observe the analgesic effects of different levels and intensities of electrical stimulation on the local acupoints in the pain source area and their impact on wide dynamic range (WDR) neurons in the spinal dorsal horn, in order to provide a basis for selecting appropriate parameters for electroacupuncture (EA) stimulation. METHODS: Wistar rats were used in 3 parts of the experiment. Complete Freund's adjuvant was used to establish a model of inflammation-induced pain in the gastrocnemius muscle. After modeling, 6 rats were randomly selected for multi-channel extracellular electrophysiological recording of the electrical activity of WDR neurons, to determine the threshold for activating the A-component (Ta) and the C-component (Tc), which were used as the intervention intensities for skin transcutaneous electrical acupoint stimulation (TEAS) or EA. Thirty-six rats were randomly divided into normal , model , TEAS-Ta , TEAS-Tc, EA-Ta , and EA-Tc groups, with 6 rats in each group. In the pain source area , Ta or Tc intensity of TEAS or EA intervention at"Chengshan"(BL57) was performed for 30 min each time, once a day, for 3 consecutive days. A small animal pressure pain measurement instrument was used to measure the mechanical pressure pain threshold of the gastrocnemius muscle in rats, and the Von Frey filament was used to measure the mechanical pain threshold of the footpad. Thirteen rats were randomly selected to observe the immediate responsiveness of WDR neurons to Ta/Tc intensity of EA or TEAS in BL57. RESULTS: The thresholds of TEAS to activate WDR neuron A-component or C-component were (2.43±0.57) mA and (7.00±1.34) mA, respectively, while the thresholds for EA to activate muscle WDR neuron A-component or C-component were (0.72±0.34) mA and (1.58±0.35) mA, respectively. After injection of CFA into the gastrocnemius muscle, compared with the normal group both the mechanical pressure pain threshold of the gastrocnemius muscle and the mechanical pain threshold of the footpad of rats in the model group were significantly decreased (P<0.001). After TEAS-Ta, TEAS-Tc or EA-Ta intervention in the BL57, both the mechanical pressure pain threshold of the gastrocnemius muscle and the mechanical pain threshold of the footpad were significantly higher than those in the model group (P<0.05, P<0.001). Compared with the normal group, the electrical threshold for evoking WDR neuron C-component discharge was significantly decreased (P<0.001) in the model group, while increased after TEAS-Ta, TEAS-Tc, or EA-Ta intervention (P<0.01) compared with the model group. The evoked discharge frequency of muscle WDR neurons decreased significantly after immediate intervention with TEAS-Ta, TEAS-Tc, or EA-Ta (P<0.01, P<0.05). EA-Tc had no significant improvement on the evoked electrical activity of WDR neurons or pain behavior. CONCLUSIONS: TEAS-Ta, TEAS-Tc, or EA-Ta can all alleviate the local and footpad mechanical pain in rats with muscle inflammation and inhibit the responsiveness of WDR neurons, indicating that different intensities are required for analgesic effects at different levels of acupoints in the pain source area.

Development and validation of a prognostic model for 90-day survival in patients with alcohol-associated cirrhosis and acute decompensation.

BACKGROUND/PURPOSE: Patients with alcohol-associated cirrhosis and acute decompensation are considered critically ill and have a higher risk of short-term mortality. This study aimed to establish a nomogram to evaluate their 90-day survival and identify factors that affect disease progression. METHODS: We included patients from September 2008 to December 2016 (n = 387 in the derivation group) and from January 2017 to August 2020 (n = 157 in the validation group). LASSO regression and Cox multivariate risk regression were used to analyze the influencing factors of the 90-day mortality risk, and a nomogram was constructed. The performance of a model was analyzed based on the C-index, area under the receiver operating curve, calibration curve, and decision curve analysis. RESULTS: Total bilirubin >10 upper limit of normal, high-density lipoprotein cholesterol, lymphocyte and monocyte ratios ≤2.33, white blood cells, and hemoglobin were identified as independent risk factors affecting the 90-day mortality risk of patients and the nomogram was developed. A nomogram demonstrated excellent model predictive accuracy in both the derivation and validation cohorts (C-index: 0.976 and 0.945), which was better than other commonly used liver scoring models (p < 0.05). The nomogram also performed good calibration ability and more clinical net benefit. According to the nomogram score, patients were divided into high- and low-risk groups. Mortality was significantly higher in the high-risk group than in the low-risk group (p < 0.0001). CONCLUSION: The nomogram could accurately predict the 90-day mortality risk in patients with alcohol-associated cirrhosis and acute decompensation, helping to identify high-risk patients and personalize treatment at their first admission.

Adduction induces large optic nerve head deformations in subjects with normal-tension glaucoma.

PURPOSE: To assess intraocular pressure (IOP)-induced and gaze-induced optic nerve head (ONH) strains in subjects with high-tension glaucoma (HTG) and normal-tension glaucoma (NTG). DESIGN: Clinic-based cross-sectional study. METHODS: The ONH from one eye of 228 subjects (114 subjects with HTG (pre-treatment IOP≥21 mm Hg) and 114 with NTG (pre-treatment IOP<21 mm Hg)) was imaged with optical coherence tomography (OCT) under the following conditions: (1) OCT primary gaze, (2) 20° adduction from OCT primary gaze, (3) 20° abduction from OCT primary gaze and (4) OCT primary gaze with acute IOP elevation (to approximately 33 mm Hg). We then performed digital volume correlation analysis to quantify IOP-induced and gaze-induced ONH tissue deformations and strains. RESULTS: Across all subjects, adduction generated high effective strain (4.4%±2.3%) in the LC tissue with no significant difference (p>0.05) with those induced by IOP elevation (4.5%±2.4%); while abduction generated significantly lower (p=0.01) effective strain (3.1%±1.9%). The lamina cribrosa (LC) of HTG subjects exhibited significantly higher effective strain than those of NTG subjects under IOP elevation (HTG: 4.6%±1.7% vs NTG: 4.1%±1.5%, p<0.05). Conversely, the LC of NTG subjects exhibited significantly higher effective strain than those of HTG subjects under adduction (NTG: 4.9%±1.9% vs HTG: 4.0%±1.4%, p<0.05). CONCLUSION: We found that NTG subjects experienced higher strains due to adduction than HTG subjects, while HTG subjects experienced higher strain due to IOP elevation than NTG subjects-and that these differences were most pronounced in the LC tissue.

Integrating land-sea coordination into construction of an ecological security pattern for urban agglomeration: a case study in the Guangdong-Hong Kong-Macao Greater Bay Area.

The construction of ecological security pattern (ESP) is of great scientific significance for solving the problem of habitat fragmentation in urban environment. However, previous studies mainly focused on the ESP in land area, leaving the sea area to be ignored. This study took the Guangdong-Hong Kong-Macao Greater Bay Area (GBA) and its offshore area as an example and integrated the land-sea coordination into the construction of ESP based on the minimum resistance model, gravity model, and graph theory centrality. The results showed that there are 171 and 56 ecological sources for land area and offshore area, accounting for 31.46% and 21.51% of total area, respectively. Twenty-four important ecological corridors with a total length of 2738.05 km were identified in GBA, and the width is proposed to be less than 100 m. Moreover, the α, ß, and γ index of the ecological network in the study area is 0.19, 1.33, and 0.5, respectively, indicating that the ecological network structure is complex and the connectivity between ecological nodes is good. The ecological restoration area includes 286.6 km2 of ecological pinch points and 140.44 km2 of ecological barrier. The overall ESP of the study area is "one ring, two belts, and four zones." The main body of the area with a superior ecological environment is distributed in a ring-like pattern near the outer edge of the study area, and two belts (important ecological corridor and ecological corridor) are distributed in a network. According to the ecological characteristics, the study area was divided into four zones: ecological preservation areas, ecological restoration areas, limited construction areas, and optimized construction areas. The ESP established herein institute provides a reference for the revision of ecological space control and optimization measures in the GBA. It also provides effective and systematic means to solve ecological problems in the current territorial spatial planning and territorial ecological restoration of coastal urban agglomeration.

Comparation of the outcomes between ProGlide based post-closure technique and arteriotomy repair for veno-arterial extracorporeal membrane oxygenation decannulation.

PURPOSE: To compare outcomes between post-closure technique based on ProGlide and arteriotomy repair for veno-arterial extracorporeal membrane oxygenation (VA-ECMO) decannulation in this study. MATERIALS AND METHODS: Patients who received VA-ECMO treatment and successfully removed from its support in Changhai Hospital from January 2018 to December 2021 were included in this study. Patients was divided into post-closure group and surgical repair group according to the artery access closure method used. Clinical data of these patients were retrospectively collected and analyzed. RESULTS: A total of 58 patients were eventually enrolled in this study, including 26 (44.83%) patients in post-closure group and 32 (55.17%) patients in surgical repair group. Post-closure group had shorter procedure time, less minor bleeding events, estimated blood loss and packed cells transfused compared with the surgical repair group. The intensive care unit (ICU) length of stay after decannulation and the hospital length of stay after ICU in post-closure group were both shorter than surgical repair group. Nine patients (15.52%) died of multiple system organ failure after decannulation in this cohort and there were no significant differences between two groups. CONCLUSIONS: Our study showed the post-closure technique based on ProGlide for VA-ECMO decannulation is feasible, safe and effective.

Construction and validation of a personalized prediction model for postpartum anxiety in pregnant women with preeclampsia.

BACKGROUND: Preeclampsia is a pregnancy-specific multi-system disease with multi-factor and multi-mechanism characteristics. The cure for preeclampsia is to terminate the pregnancy and deliver the placenta. However, it will reduce the perinatal survival rate, prolong the pregnancy cycle, and increase the incidence of maternal complications. With relaxation of the birth policy, the number of elderly pregnant women has increased significantly, and the prevalence rate of preeclampsia has increased. Inappropriate treatment can seriously affect the normal postpartum life of pregnant women. Studies have shown that postpartum anxiety in women with preeclampsia can affect physical and mental health, as well as infant growth and development. AIM: To analyze the factors influencing preeclampsia in pregnant women complicated with postpartum anxiety, and to construct a personalized predictive model. METHODS: We retrospectively studied 528 pregnant women with preeclampsia who delivered in Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine between January 2018 and December 2021. Their basic data were collected, and various physiological and biochemical indicators were obtained by laboratory examination. The self-rating anxiety scale was used to determine whether the women had postpartum anxiety 42 d after delivery. The independent factors influencing postpartum anxiety in early pregnant women with eclampsia were analyzed with multifactor logistic regression and a predictive model was constructed. The Hosmer-Lemeshow test and receiver operating characteristic (ROC) curve were used to evaluate the calibration and discrimination of the predictive model. Eighty pregnant women with preeclampsia admitted to our hospital from January 2022 to May 2022 were retrospectively selected to verify the prediction model. RESULTS: We excluded 46 of the 528 pregnant women with preeclampsia because of loss to follow-up and adverse outcomes. A total of 482 cases completed the assessment of postpartum anxiety 42 d after delivery, and 126 (26.14%) had postpartum anxiety. Bad marital relationship, gender discrimination in family members, hematocrit (Hct), estradiol (E2) hormone and interleukin (IL)-6 were independent risk factors for postpartum anxiety in pregnant women with preeclampsia (P < 0.05). Prediction model: Logit (P) = 0.880 × marital relationship + 0.870 × gender discrimination of family members + 0.130 × Hct - 0.044 × E2 + 0.286 × IL-6 - 21.420. The area under the ROC curve of the model was 0.943 (95% confidence interval: 0.919-0.966). The threshold of the model was -1.507 according to the maximum Youden index (0.757), the corresponding sensitivity was 84.90%, and the specificity was 90.70%. Hosmer-Lemeshow χ2 = 5.900, P = 0.658. The sensitivity, specificity and accuracy of the model were 81.82%, 84.48% and 83.75%, respectively. CONCLUSION: Poor marital relationship, family gender discrimination, Hct, IL-6 and E2 are the influencing factors of postpartum anxiety in preeclampsia women. The constructed prediction model has high sensitivity and specificity.

[Groundwater Pollution Risk Assessment in Plain Area of Barkol-Yiwu Basin].

Groundwater pollution risk assessment is an important part of groundwater pollution prevention and control. Taking groundwater in the plain area of Barkol-Yiwu Basin as the research object, the DRSTIW model was constructed to evaluate groundwater vulnerability. According to the survey data of contaminated sites and land use types, point source and non-point source pollutions were classified, and the groundwater pollution load was evaluated. The primary value, economic value, and ecological value of groundwater were considered to evaluate the functional value of groundwater. The groundwater pollution risk assessment map was generated by using the map algebra function of ArcGIS software. The ROC curve was used to verify the risk assessment results of groundwater pollution. The spatial distribution of cold and hot spots of groundwater pollution risk was obtained by calculating the G index, and the change in hot spots was quantitatively analyzed by combining the center of gravity and standard deviation ellipse. The results showed that the groundwater vulnerability was generally low. The gentle terrain slope, shallow groundwater depth, and strong aquifer permeability made it easy for pollutants to enter the aquifer, resulting in high groundwater vulnerability in the northwest of Santanghu Town, the southeast of Dahongliuxia Township, and Kuisu Town in Barkol County. The groundwater pollution load and groundwater functional value were generally low, whereas the point source and non-point source pollution caused by industrial and agricultural production and life would increase the groundwater pollution load in local areas, and the human economic activities and habitat quality levels would affect the distribution of high groundwater function value areas. Groundwater pollution risk was generally low; very high and high pollution risk areas only accounted for 6.8% of the study area, mainly distributed in Naomaohu Town and Yanchi Town of Yiwu County, Kuisu Town, Shirenzi Township, Huayuan Township of Barkol County, and Hongshan Farm of Corps. The shallow groundwater depth, strong permeability of soil surface and vadose zone media, poor adsorption capacity, and concentrated distribution of pollution sources made it easy for pollutants to migrate and enrich in these areas. Under the dual influence of high vulnerability and high pollution load of groundwater, the risk of groundwater pollution in local areas increased. Affected by human activities, there was a certain spatial agglomeration of groundwater pollution risk, and the overall trend was from northwest to southeast. The results of groundwater pollution risk assessment provided a scientific reference for the division of groundwater pollution prevention and control areas.

Aligned grains and scattered light found in gaps of planet-forming disk.

Polarized (sub)millimetre emission from dust grains in circumstellar disks was initially thought to be because of grains aligned with the magnetic field1,2. However, higher-resolution multi-wavelength observations3-5 and improved models6-10 found that this polarization is dominated by self-scattering at shorter wavelengths (for example, 870 µm) and by grains aligned with something other than magnetic fields at longer wavelengths (for example, 3 mm). Nevertheless, the polarization signal is expected to depend on the underlying substructure11-13, and observations until now have been unable to resolve polarization in multiple rings and gaps. HL Tau, a protoplanetary disk located 147.3 ± 0.5 pc away14, is the brightest class I or class II disk at millimetre-submillimetre wavelengths. Here we show deep, high-resolution polarization observations of HL Tau at 870 µm, resolving polarization in both the rings and the gaps. We find that the gaps have polarization angles with a notable azimuthal component and a higher polarization fraction than the rings. Our models show that the disk polarization is due to both scattering and emission from the aligned effectively prolate grains. The intrinsic polarization of aligned dust grains is probably more than 10%, which is much higher than that expected in low-resolution observations (about 1%). Asymmetries and dust features that are not seen in non-polarimetric observations are seen in the polarization observations.

Thyroid dysfunction associated with iodine-contrast media: A real-world pharmacovigilance study based on the FDA adverse event reporting system.

Objective: To comprehensively analyze characteristics of thyroid dysfunction associated with iodine contrast media (ICM) based on data from the FDA adverse event reporting system (FAERS). Methods: Disproportionate analysis was employed to identify signals of thyroid dysfunction caused by ICM, and descriptive analysis was performed to examine the clinical characteristics of reported cases involving ICM-related thyroid dysfunctions. Results: A total of 83 adverse event reports were identified, documenting thyroid dysfunctions associated with ICM agents. Treatment with ICM was significantly associated with higher reporting of hypothyroidism ([ROR] = 2.21, 95 % CI: 1.59-3.08; IC025 = 0.58) and hyperthyroidism (ROR = 3.49, 95 % CI: 2.37-5.13; IC025 = 1.14). Among the six ICM agents investigated, iodixanol demonstrated the highest signal strength in both hypothyroidism (ROR = 9.47) and hyperthyroidism (ROR = 5.44). Hypothyroidism and hyperthyroidism almost occurred in the first 30 days after ICM administration (76.9 % and 70 % of patients, respectively). Furthermore, the proportion of severe outcomes in hyperthyroidism was significantly higher than that in hypothyroidism (12/26 vs. 2/35, P = 0.009). Conclusion: The present study highlights the varying risks of thyroid dysfunction associated with different ICM agents, with iodixanol exhibiting the highest signal intensity. Hypothyroidism and hyperthyroidism associated with ICM generally manifest within the first month following administration. Consequently, monitoring of thyroid function during this period is strongly recommended for ICM agents presenting higher risk profiles.

Caveolin-1 is critical for hepatic iron storage capacity in the development of nonalcoholic fatty liver disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is associated with disordered lipid and iron metabolism. Our previous study has substantiated the pivotal role of Caveolin-1 (Cav-1) in protecting hepatocytes and mediating iron metabolism in the liver. This study aimed to explore the specific mechanisms underlying the regulation of iron metabolism by Cav-1 in NAFLD. METHODS: Hepatocyte-specific Cav-1 overexpression mice and knockout mice were used in this study. Cav-1-knockdown of RAW264.7 cells and mouse primary hepatocytes were performed to verify the changes in vitro. Moreover, a high-fat diet and palmitic acid plus oleic acid treatment were utilized to construct a NAFLD model in vivo and in vitro, respectively, while a high-iron diet was used to construct an in vivo iron overload model. Besides, iron concentration, the expression of Cav-1 and iron metabolism-related proteins in liver tissue or serum were detected using iron assay kit, Prussian blue staining, Western blotting, immunofluorescence staining, immunohistochemical staining and ELISA. The related indicators of lipid metabolism and oxidative stress were evaluated by the corresponding reagent kit and staining. RESULTS: Significant disorder of lipid and iron metabolism occurred in NAFLD. The expression of Cav-1 was decreased in NAFLD hepatocytes (P < 0.05), accompanied by iron metabolism disorder. Cav-1 enhanced the iron storage capacity of hepatocytes by activating the ferritin light chain/ferritin heavy chain pathway in NAFLD, subsequently alleviating the oxidative stress induced by excess ferrous ions in the liver. Further, CD68+CD163+ macrophages expressing Cav-1 were found to accelerate iron accumulation in the liver, which was contrary to the effect of Cav-1 in hepatocytes. Positive correlations were also observed between the serum Cav-1 concentration and the serum iron-related protein levels in NAFLD patients and healthy volunteers (P < 0.05). CONCLUSIONS: These findings confirm that Cav-1 is an essential target protein that regulates iron and lipid metabolic homeostasis. It is a pivotal molecule for predicting and protecting against the development of NAFLD.

GDU-952, a novel AhR agonist ameliorates skin barrier abnormalities and immune dysfunction in DNFB-induced atopic dermatitis in mice.

The aryl hydrocarbon receptor (AhR) is widely expressed in the skin. It controls immune-mediated skin responses to various external environmental signals, promote terminal differentiation of epidermal keratinocytes and participates the maintenance of the skin barrier function. As a therapeutic target, AhR activation modulates many diseases progression driven by immune/inflammatory processes such as atopic dermatitis (AD) and psoriasis. In this study, we revealed that GDU-952 is a novel AhR agonist, which is able to decreases IgE serum levels, to inhibit pro-inflammatory cytokines such as IL-6 and TNF-α and to induce immunoregulatory effects through restoring Th1/Th2 immune balance and promoting CD4+FOXP3+regulatory T (Treg) populations in AD skin lesions. Furthermore, GDU-952 can strengthen the skin barrier function through upregulating epidermal differentiation-related and tight junction proteins. This may alleviate AD symptoms, such as dermatitis scores, epidermal hyperplasia and mast cell infiltration. These results offer a rationale for further preclinical/clinical studies to evaluate the possible use of GDU-952 in the management of AD.