Are children with IgA nephropathy different from adult patients?

BACKGROUND: Previously, several studies have indicated that pediatric IgA nephropathy (IgAN) might be different from adult IgAN, and treatment strategies might be also different between pediatric IgAN and adult IgAN. METHODS: We analyzed two prospective cohorts established by pediatric and adult nephrologists, respectively. A comprehensive analysis was performed investigating the difference in clinical and pathological characteristics, treatment, and prognosis between children and adults with IgAN. RESULTS: A total of 1015 children and 1911 adults with IgAN were eligible for analysis. More frequent gross hematuria (88% vs. 20%, p < 0.0001) and higher proteinuria (1.8 vs. 1.3 g/d, p < 0.0001) were seen in children compared to adults. In comparison, the estimated glomerular filtration rate (eGFR) was lower in adults (80.4 vs. 163 ml/min/1.73 m2, p < 0.0001). Hypertension was more prevalent in adult patients. Pathologically, a higher proportion of M1 was revealed (62% vs. 39%, p < 0.0001) in children than in adults. S1 (62% vs. 28%, p < 0.0001) and T1-2 (34% vs. 8%, p < 0.0001) were more frequent in adults. Adjusted by proteinuria, eGFR, and hypertension, children were more likely to be treated with glucocorticoids than adults (87% vs. 45%, p < 0.0001). After propensity score matching, in IgAN with proteinuria > 1 g/d, children treated with steroids were 1.87 (95% CI 1.16-3.02, p = 0.01) times more likely to reach complete remission of proteinuria compared with adults treated with steroids. CONCLUSIONS: Children present significantly differently from adults with IgAN in clinical and pathological manifestations and disease progression. Steroid response might be better in children.

Comparing ChatGPT's and surgeon's responses to thyroid-related questions from patients.

BACKGROUND: For some common thyroid-related conditions with high prevalence and long follow-up times, ChatGPT can be used to respond to common thyroid-related questions. In this cross-sectional study, we assessed the ability of ChatGPT (version GPT-4.0) to provide accurate, comprehensive, compassionate, and satisfactory responses to common thyroid-related questions. STUDY DESIGN: First, we obtained 28 thyroid-related questions from the Huayitong app, which together with the two interfering questions eventually formed 30 questions. Then, these questions were responded to by ChatGPT (on July 19, 2023), junior specialist and senior specialist (on July 20, 2023) separately. Finally, 26 patients and 11 thyroid surgeons evaluated those responses on four dimensions: accuracy, comprehensiveness, compassion, and satisfaction. RESULTS: Among the 30 questions and responses, ChatGPT's speed of response was faster than that of the junior specialist (8.69 [7.53-9.48] vs. 4.33 [4.05-4.60], P <.001) and senior specialist (8.69 [7.53-9.48] vs. 4.22 [3.36-4.76], P <.001). The word count of the ChatGPT's responses was greater than that of both junior specialist (341.50 [301.00-384.25] vs. 74.50 [51.75-84.75], P <0.001) and senior specialist (341.50 [301.00-384.25] vs. 104.00 [63.75-177.75], P <0.001). ChatGPT received higher scores than junior specialist and senior specialist in terms of accuracy, comprehensiveness, compassion and satisfaction in responding to common thyroid-related questions. CONCLUSIONS: ChatGPT performed better than junior specialist and senior specialist in answering common thyroid-related questions, but further research is needed to validate the logical ability of the ChatGPT for complex thyroid questions.

Psychological impacts of thermal ablation and conventional thyroidectomy in BTN patients: a prospective observational study.

BACKGROUND: Thermal ablation and conventional thyroidectomy are effective therapeutic methods for treating benign thyroid nodules (BTNs), but the psychological impacts of these methods in BTN patients are largely unknown. MATERIALS AND METHODS: This survey study prospectively enrolled patients who were admitted to our hospital between July 2021 and July 2022. The four validated scales were applied to quantify psychological distress and sleep quality at five points (the day admitted to the hospital, the day discharged from the hospital, and 1, 3, and 6 months after treatment). Participants who were diagnosed with BTNs and completed the questionnaires were ultimately enrolled and divided into thermal ablation and conventional thyroidectomy groups. A propensity score matching (PSM) cohort was subsequently developed to evaluate longitudinal and cross-sectional changes in psychological-related indicators. RESULTS: Among 548 eligible BTN patients, 460 patients completed all the questionnaires throughout the follow-up (response rate: 83.94%), including 368 (80.00%) patients who underwent thermal ablation and 92 (20.00%) patients who underwent conventional thyroidectomy. After PSM, a total of 342 patients were enrolled (256 patients underwent thermal ablation, and 86 patients underwent conventional thyroidectomy). The psychological-related indicators of patients in the thermal ablation group remained relatively stable during the 6-month follow-up, but patients in the conventional thyroidectomy group may have experienced greater anxiety and sleep quality concerns in the longitudinal assessment. Additionally, in the cross-sectional evaluation, the sleep quality of the thermal ablation group was also better than that of the conventional thyroidectomy group postoperatively. CONCLUSIONS: Thermal ablation is superior to conventional thyroidectomy for BTN patients in terms of psychological-related indicators.

Radioactive iodine therapy improves overall survival outcome in oncocytic carcinoma of the thyroid by reducing death risks from noncancer causes: A competing risk analysis of 4641 patients.

BACKGROUND: Oncocytic carcinoma of the thyroid (OCA) is an independent type of thyroid cancer. Radioactive iodine (RAI) therapy was frequently administered to OCA patients, but its contribution to improving survival is indefinite. METHODS: 4641 OCA patients from 2000 to 2018 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Cox proportional hazard regression and competing risk analysis were applied. RESULTS: Tumor size, SEER stage, primary surgery, and neck dissection were prognostic factors for cancer-specific survival. The results of competing risk analysis demonstrated that age over 55 years dramatically increased non-OCA death risks. Treatments that improve non-OCA survival (including total thyroidectomy, RAI therapy, and systemic therapy) should be recommended in OCA patients older than 55 years of age. Neck lymphadenectomy should not be recommended for OCA, since the metastatic lymph node ratio was low (about 3%). CONCLUSIONS: RAI therapy can improve survival in OCA by reducing noncancer death risks.

Years of life lost due to insufficient sleep and associated economic burden in China from 2010-18.

Background: Research on the health and economic costs due to insufficient sleep remains scant in developing countries. In this study we aimed to estimate the years of life lost (YLLs) due to short sleep and quantify its economic burden in China. Methods: We estimated both individual and aggregate YLLs due to short sleep (ie, ≤6 hours) among Chinese adults aged 20 years or older by sex and five-year age groups in 2010, 2014, and 2018. YLL estimates were derived from 1) the prevalence of short sleep using three survey waves of the China Family Panel Studies, 2) relative mortality risks from meta-analyses, and 3) life tables in China. YLL was the difference between the estimated life expectancy of an individual in the short sleep category vs in the recommended sleep category. We estimated the economic cost using the human capital approach. Results: The sample sizes of the three survey waves were 31 393, 31 207, and 28 618. Younger age groups and men had more YLLs due to short sleep compared to their counterparts. For individuals aged 20-24, men had an average YLL of nearly 0.95, in contrast to the approximate 0.75 in women across the observed years of 2010, 2014, and 2018. The trend in individual YLLs remained consistent over these years. In aggregate, China experienced a rise from 66.75 million YLLs in 2010 to 95.29 million YLLs in 2014, and to 115.05 million YLLs in 2018. Compared to 2010 (USD 191.83 billion), the associated economic cost in 2014 increased to USD 422.24 billion, and the cost in 2018 more than tripled (USD 628.15 billion). The percentage of cost to Chinese gross domestic product in corresponding years was 3.23, 4.09, and 4.62%. Conclusions: Insufficient sleep is associated with substantial YLLs in China, potentially impacting the population's overall life expectancy. The escalating economic toll attributed to short sleep underscores the urgent need for public health interventions to improve sleep health at the population level.

Reduced graphene oxide/MXene hybrid decorated graphite felt as an effective electrode for vanadium redox flow battery.

Vanadium redox flow battery (VRFB) is a highly suitable technology for energy storage and conversion in the application of decoupling energy and power generation. However, the sluggish reaction kinetics of redox couples is one of the bottlenecks hindering the commercialization of VFFBs. Developing efficient electrode is a promising method to improve the battery performance. In this work, a reduced graphene oxide/Mxene hybrid-decorated graphite felt (rGO/Mxene@GF) is designed to facilitate the kinetics of redox reaction. The electrocatalytic activity and mass transfer of the prepared electrode are investigated through experiment and simulation methods. The results indicate that the favorable mass transfer and the synergistic effect between rGO and Ti3C2Tx Mxene remarkably improve the performance of electrode. The flow cell with rGO/Mxene@GF delivers a good stability up to 100 cycles with a coulombic, voltage, and energy efficiency of 91.6%, 82.7%, and 75.8%, respectively, at a current density of 80 mA cm-2. These findings suggest that the as-prepared rGO/Mxene@GF holds a good application potential in VRFB and provides a promising approach to design efficient electrode for electrochemical devices.

Effect of multi-interface electron transfer on water splitting and an innovative electrolytic cell for synergistic hydrogen production and degradation.

The cleaning and utilization of industry wastewater are still a big challenge. In this work, we mainly investigate the effect of electron transfer among multi-interfaces on water electrolysis reaction. Typically, the CoS2, Co3S4/CoS2 (designated as CS4-2) and Co3S4/Co9S8/CoS2 (designated as CS4-8-2) samples are prepared on a large scale by one-step molten salt method. It is found that because of the different work functions (designated as WF; WF(Co3S4) = 4.48eV, WF(CoS2) = 4.41eV, WF(Co9S8) = 4.18 eV), the effective heterojunctions at the multi-interfaces of CS4-8-2 sample, which obviously improve interface charge transfer. Thus, the CS4-8-2 sample shows an excellent oxygen evolution reaction (OER) activity (134 mV/10 mA cm-2, 40 mV dec-1). The larger double-layer capacitance (Cdl = 17.1 mF cm-2) of the CS4-8-2 sample indicates more electrochemical active sites, compared to the CoS2 and CS4-2 samples. Density functional theory (DFT) calculation proves that due to interface polarization under electric field, the multi-interfaces effectively promote electron transfer and regulate electron structure, thus promoting the adsorption of OH- and dissociation of H2O. Moreover, an innovative norfloxacin (NFX) electrolytic cell (EC) is developed through introducing NFX into the electrolyte, in which efficient NFX degradation and hydrogen production are synergistically achieved. To reach 50 mA cm-2, the required cell voltage of NFX-EC has decreased by 35.2%, compared to conventional KOH-EC. After 2h running at 1 V, 25.5% NFX was degraded in the NFX EC. This innovative NFX-EC is highly energy-efficient, which is promising for the synergistic cleaning and utilization of industry wastewater.

Influence of Zn Addition on the Aging Precipitate Behavior and Mechanical Properties of Al-Cu-Li Alloy.

In the present work, the effect of Zn on the aging precipitates and mechanical properties of Al-Cu-Li alloys was investigated by Vickers hardness, tensile tests, transmission electron microscopy (TEM) and differential scanning calorimetry (DSC). The results indicated that the addition of Zn reduced the activation energy of the T1 phase and makes it easier to precipitate. The activation energy of the T1 phase, which was 107.02 ± 1.8 KJ/mol, 94.33 ± 1.7 KJ/mol, 90.33 ± 1.7 KJ/mol and 90.28 ± 1.6 KJ/mol for 0Zn, 0.4Zn, 0.8Zn and 1.2Zn alloy, respectively. The area number density of the T1 precipitate ranged from 97.0 ± 4.4 pcs/µm2 to 118.2 ± 2.8 pcs/µm2 as the Zn content increased from 0 to 1.2 wt.%. Consequently, the addition of Zn promoted the precipitation of the T1 phase. Therefore, the peak hardness and tensile strength of the alloy also increased with the increase in the Zn content, and the hardness of the alloy with Zn content of 1.2 wt.% increased by 16.5 ± 1.4 HV; meanwhile, the ultimate tensile strength increased by 46.5 ± 2.5 MPa. Therefore, the area number density of precipitates increased and improved the strength of the Zn-containing alloy.

A broadband multi-frequency microwave combined biological exposure setup.

With the rapid popularization of wireless electronic devices, there has been an increasing concern about the impacts of the electromagnetic environment on health. However, most research reports on the biological effects of microwaves have focused on a single frequency point. In reality, people are exposed to complex electromagnetic environments that consist of multiple frequency microwave signals in their daily lives. It is important to investigate whether multi-frequency combined microwave energies have different biological effects compared with single frequency microwave energy. Unfortunately, there are limited reports on this topic due to the lack of suitable platforms for research on multi-frequency microwave energy combined with biological exposure. To address this issue, this study presents a setup that has a very wide working frequency bandwidth and can be compatible with single frequency and multi-frequency microwave combined exposure. Moreover, it can achieve relatively equal exposure to multiple biological samples at any frequency point in the working frequency range, which is crucial for electromagnetic biology research. The experimental results are in good agreement with the simulation results, confirming its capability to facilitate the study of complex electromagnetic environment effects on organisms.

Interferon-γ+ Th1 activates intrahepatic resident memory T cells to promote HBsAg loss by inducing M1 macrophage polarization.

The immune mechanism underlying hepatitis B surface antigen (HBsAg) loss, particularly type I inflammatory response, during pegylated interferon-α (PEG-IFN) therapy remains unclear. In this study, we aimed to elucidate such immune mechanisms. Overall, 82 patients with chronic hepatitis B (CHB), including 41 with HBsAg loss (cured group) and 41 uncured patients, received nucleos(t)ide analogue and PEG-IFN treatments. Blood samples from all patients, liver tissues from 14 patients with CHB, and hepatic perfusate from 8 liver donors were collected for immune analysis. Jurkat, THP-1 and HepG2.2.15 cell lines were used in cell experiments. The proportion of IFN-γ+ Th1 cells was higher in the cured group than in the uncured group, which was linearly correlated with HBsAg decline and alanine aminotransferase (ALT) levels during treatment. However, CD8+ T cells were weakly associated with HBsAg loss. Serum and intrahepatic levels of Th1 cell-associated chemokines (C-X-C motif chemokine ligand [CXCL] 9, CXCL10, CXCL11, IFN-γ) were significantly lower in the cured patients than in patients with a higher HBsAg quantification during therapy. Serum from cured patients induced more M1 (CD68+CD86+ macrophage) cells than that from uncured patients. Patients with chronic HBV infection had significantly lower proportions of CD86+ M1 and CD206+ M2 macrophages in their livers than healthy controls. M1 polarization of intrahepatic Kupffer cells promoted HBsAg loss by upregulating the effector function of tissue-resident memory T cells with increased ALT levels. IFN-γ+ Th1 activates intrahepatic resident memory T cells to promote HBsAg loss by inducing M1 macrophage polarization.

Association between concurrence of multiple risk factors and under-5 mortality: a pooled analysis of data from Demographic and Health Survey in 61 low-and-middle-income countries.

Background: Exposure to multiple risk factors is prevalent in low-and middle-income countries (LMICs), challenging one-directional strategies to address preventable under-5 mortality (U5M). This study aims to assess the associations between concurrence of multiple risk factors and U5M in LMICs. Methods: We extracted data from the Demographic and Health Surveys conducted between 2010 and 2021 across 61 LMICs. Our primary outcome was U5M, defined as deaths from birth to 59 months. Binary logistic regression model was applied to ascertain the association between U5M and a total of 20 critical risk factors. Upon identifying the risk factors demonstrating the strongest associations, we investigated the simultaneous presence of multiple risk factors in each individual and assessed their combined effects on U5M with logistic regression models. Findings: Of the 604,372 under-5 children, 18,166 (3.0%) died at the time of the survey. Unsatisfied family planning needs was the strongest risk factor for U5M (odds ratio [OR]: 2.0, 95% confidence interval [CI]: 1.9-2.1), followed by short birth interval (<18 months; OR: 2.0, 95% CI: 1.9-2.1), small birth size (OR: 2.0, 95% CI: 1.8-2.1), never breastfed or delayed breastfeeding (OR: 2.0, 95% CI: 1.9-2.0), and low maternal education (OR: 1.6, 95% CI: 1.4-1.8). 66.7% (66.6%-66.8%) of the children had 2 or more leading risk factors simultaneously. Simultaneous presence of multiple leading risk factors was significantly associated with elevated risk of U5M and children presenting with all 5 leading risk factors exhibited an exceedingly high risk of U5M (OR: 5.2, 95% CI: 4.3-6.3); a dose-response relationship between the number of risk factors and U5M was also observed-with the increment of numbers of leading risk factors, the U5M showed an increasing trend (p-trend < 0.001). Interpretation: Exposure to multiple risk factors is very common in LMICs and underscores the necessity of developing multisectoral and integrated approaches to accelerate progress in reducing U5M in line with the SDG 3.2. Funding: This research is funded by Research Fund, Vanke School of Public Health, Tsinghua University.

Performance Evaluation of Newly-Developed Tumor Markers Assay Kit Based on Flow Fluorescence Assay.

BACKGROUND: The purpose of this study is to evaluate the performance of recently developed tumor marker clinical kits in China, with the aim of encouraging local medical technology innovation and thus narrowing the research and development gap with foreign kits. METHODS: The newly established reagent kits were analyzed on the TESMI F3999-Luminex200 flow lattice instrument to verify precision, sensitivity (blank limit), linearity, anti-interference ability, carry-over contamination rate, hook effect, and reference interval verification. Additionally, the newly established reagent kits were compared to other commercially available detection kits (reference reagent kits) to analyze the correlation between the two types of kits. RESULTS: The intra-assay and inter-assay precision had coefficients of variations (CVs) less than 3.50% and 6.91%, respectively. The tumor marker blank limits were lower than the manufacturer's statement. The newly established reagent kits demonstrated excellent linearity (r > 0.99). Rheumatoid factor, triglycerides, bilirubin, and hemoglobin did not have significant interference with the determination of tumor markers. The carry-over contamination rates were all much lower than 3%. At extremely high concentrations of AFP (277,335 ng/mL and 1,031,424 ng/mL), the measured tumor marker values were higher than the upper limit of the linear range and no hook effect occurred. The reference interval was suitable for use in clinical laboratory settings. Correlation analysis indicated a satisfactory relevance and consistency between the newly developed reagent kits and reference reagent kits, with correlation coefficients of r > 0.967 among 654 patients and healthy individuals. CONCLUSIONS: The newly developed reagent kits for tumor markers performed well in all evaluated parameters, having the potential for clinical promotion and application.

Comparative study between poorly differentiated thyroid cancer and anaplastic thyroid cancer: real-world pathological distribution, death attribution, and prognostic factor estimation.

Background: The clinic-pathological boundary between poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC) is unclear due to a wide spectrum of histopathological features and the rarity of the disease. In addition to that, with the highest mortality rate and non-standard treatment modality, the PDTC/ATC population has not been subjected to comprehensive description and comparison with the extent of histological characteristics, therapeutic response, prognostic factors, and death attribution analysis. Method: A total of 4,947 PDTC/ATC patients from 2000 to 2018 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier survival curve estimation and Cox proportional hazard regression were applied. Results: Overall, the 5- and 10-year DSS for PDTC were 71.9% and 68.0%, respectively, whereas the 5- and 10-year OS are 59.3% and 51.2%, respectively. The median survival time for ATC patients was 3 months with 1-year OS being 26.9% and 1-year DSS being 31.2%. During the follow-up period, 68.1% of the PDTC/ATC cohort were dead, 51.6% of which were attributed to thyroid malignancies and 16.5% to non-thyroid causes. The top three common non-thyroid causes of death were miscellaneous cancers, lower respiratory system disease, and heart disease. The histological feature of papillary thyroid cancer (PTC) was the leading pathological category for PDTC patients (51.7%), whereas 76.7% of ATC patients' pathological feature was characterized as unidentifiable. Sarcoma histological characteristics found in ATC cases suffer the highest overall mortality (vs. PTC, HR = 2.61, 95% CI 1.68-4.06, P < 0.001). Older age unidentifiable histology feature, more advanced AJCC N1b, AJCC M1, and SEER stage, tumor size larger than 5 cm, and more invasive tumor extension were independent bad outcome predictors. Conclusion: The populational analysis of the PDTC/ATC cohort has provided reliable support for better understanding of the difference between PDTC and ATC cases and the guidance of clinical practice and further studies.

Clinical outcomes and implication of radioactive iodine therapy on cancer-specific survival in WHO classification of FTC.

BACKGROUND: The clinical outcomes and implications of radioactive iodine therapy (RAIT) on cancer-specific survival (CSS) in World Health Organization (WHO) classification of follicular thyroid carcinoma (FTC) are not well established. MATERIAL AND METHODS: The data of eligible patients with minimally invasive FTC (mi-FTC), encapsulated angioinvasive FTC (ea-FTC), or widely invasive FTC (wi-FTC) between 2000 and 2020 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Cancer-specific survival (CSS), the primary outcome, was compared among the three subtypes of FTC patients before and after adjusting for differences using propensity score matching (PSM). The FTC patients in different subtypes were then divided into two groups: the RAIT group and the no-RAIT group. Cox proportional hazards regression analyses were applied to discover the relationships of factors associated with CSS in the each PSM cohort. RESULTS: A total of 2433 mi-FTC patients, 216 ea-FTC patients, and 554 wi-FTC patients were enrolled in the original cohorts, respectively. Patients with mi-FTC or ea-FTC had similar CSS (p =0.805), which was better than that of patients with wi-FTC (p <.001; p =0.021). Cox proportional hazards regression analysis revealed that RAIT was not associated with improved CSS in either the mi-FTC PSM cohort (HR =1.21, 95% CI=0.46-3.18, p =0.705) or the wi-FTC PSM cohort (HR =0.56, 95% CI=0.35-1.08, p =0.086). However, subgroup analysis demonstrated that wi-FTC patients with N1 stage (HR =0.44, 95% CI=0.20-0.99, p =0.018) or M1 stage (HR =0.25, 95% CI=00.11-0.53, p <.001) could gain CSS advantage from RAIT. CONCLUSIONS: The RAIT can provide a CSS advantage for wi-FTC patients who with N1-stage or M1-stage disease.

Sarcopenic obesity is part of obesity paradox in dementia development: evidence from a population-based cohort study.

BACKGROUND: Sarcopenic obesity, a clinical and functional condition characterized by the coexistence of obesity and sarcopenia, has not been investigated in relation to dementia risk and its onset. METHODS: We included 208,867 participants from UK biobank, who aged 60 to 69 years at baseline. Dementia diagnoses were identified using hospital records and death register data. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models to evaluate the associations of obesity, sarcopenia, and sarcopenic obesity with dementia risk, stratified by sex. Stratified analyses were performed across dementia-related polygenic risk score (PRS). Restricted mean survival time models were established to estimate the difference and 95%CIs of dementia onset across different status. Additionally, linear regression models were employed to estimate associations of different status with brain imaging parameters. The mediation effects of chronic diseases were also examined. RESULTS: Obese women with high PRS had a decreased risk (HR = 0.855 [0.761-0.961]), but obese men with low PRS had an increased risk (HR = 1.223 [1.045-1.431]). Additionally, sarcopenia was associated with elevated dementia risk (HRwomen = 1.323 [1.064-1.644]; HRmen = 2.144 [1.753-2.621]) in those with low PRS. Among those with high PRS, however, the association was only significant in early-life (HRwomen = 1.679 [1.355-2.081]; HRmen = 2.069 [1.656-2.585]). Of note, sarcopenic obesity was associated with higher dementia risk (HRwomen = 1.424 [1.227-1.653]; HRmen = 1.989 [1.702-2.323]), and results remained similar stratified by PRS. Considering dementia onset, obesity was associated with dementia by 1.114 years delayed in women, however, 0.170 years advanced in men. Sarcopenia (women: 0.080 years; men: 0.192 years) and sarcopenic obesity (women: 0.109 years; men: 0.511 years) respectively advanced dementia onset. Obesity, sarcopenia, and sarcopenic obesity were respectively related to alterations in different brain regions. Association between sarcopenic obesity and dementia was mediated by chronic diseases. CONCLUSIONS: Sarcopenic obesity and sarcopenia were respectively associated with increased dementia risk and advanced dementia onset to vary degree. The role of obesity in dementia may differ by sex and genetic background.

Fibroblast growth factor 23 during septic shock and myocardial injury in ICU patients.

Objective: Fibroblast growth factor 23 (FGF23) has been recognized as an important biomarker of cardiovascular disease and is closely related to inflammation over the past decade. This study aimed to assess the relationship between FGF23 and myocardial injury in patients with sepsis. Methods: We sequentially measured serum FGF23, Klotho, biomarkers of inflammation (CRP, IL-6 and WBC), myocardial injury (cTnI and N-terminal B-type natriuretic peptide) and sepsis (procalcitonin) at peak of intercurrent septic shock and after complete resolution or before death in a series of 29 patients with septic shock. 29 healthy adults without infections were used as controls. Results: There was a difference in serum FGF23 level between patients with septic shock and healthy adults (p < 0.0001), and the peak level of FGF23 in septic shock in the survivor group was higher than that after complete remission (p < 0.0001). No statistical difference was found in the level of FGF23 before and after treatment in the death group (p = 0.0947). At the peak of septic shock, FGF23 was significantly correlated with inflammatory markers, CRP (r = 0.8063, p < 0.0001), PCT (r = 0.6091, p = 0.0005) and WBC (r = 0.8312, p < 0.0001), while the correlation with IL-6 was not statistically significant (r = 0.0098, p = 0.9598). At the same time, it was found that FGF23 was significantly correlated with myocardial injury markers, cTNI (r = 0.8475, p < 0.0001) and NTproBNP (r = 0.8505, p < 0.0001). Nevertheless, FGF23 and klotho are not correlated (r = 0.2609, p = 0.1717). Conclusion: In conclusion, in patients with septic shock and myocardial injury, the exacerbation of inflammation in the septic process was accompanied by a abnormal increase of circulating FGF23 level. FGF23 also subsided after the improvement of inflammation, and the opposite was true for patients who did not survive. The up-regulation of FGF23 may be involved in the response of patients to septic shocks, and it is also speculated that FGF23 is involved in the myocardial injury of septic shock.

Influence of cancer-directed surgery on the prognosis of liver metastases from gastric cancer

There are controversial about the application of cancer-directed surgery (CDS) in patients with liver metastases from gastric cancer, with improved responses to chemotherapy and targeted treatments, the role of CDS in metastatic gastric cancer to the liver needs to be revisited. This study aimed to evaluate the effect of CDS on patients with liver metastases from gastric cancer. Data for patients with liver metastases from gastric cancer were extracted from the population-based Surveillance, Epidemiology, and End Results (SEER) database. A total of 958 individuals were enrolled, 285 in the CDS group and 673 in the non-cancer guided surgery (Non-CDS) group. Following propensity score matching (PSM) analysis at 1:1 in the two groups,285 were included in the survival analysis for each group. Kaplan–Meier values and Cox proportional risk models were used to estimate the effect of CDS on patients' prognoses. Compared with the Non-CDS group, the CDS group significantly prolonged the median overall survival from 4 months (95% confidence interval [CI] 3–5) to 11 months (95% CI 8–12), p value < 0.001. Overall survival (OS) at 1 year was higher in the CDS group than in the Non-CDS group, at 44% (95 CI 38–50) and 25% (95 CI 20–30), respectively. OS at 3 years was also higher in the CDS group than in the Non-CDS group, at 24% (95 CI 19–29) and 6% (95 CI 3–9), respectively. Multivariate analysis showed that Non-CDS (hazard ratio[HR] = 2.26, 95% CI 1.88–2.72, p value < 0.001) was an adverse independent prognostic factor for patients (AU)

Causal effect of gut microbiota of Defluviitaleaceae on the clinical pathway of "Influenza-Subacute Thyroiditis-Hypothyroidism".

Introduction: Hypothyroidism has been found to be influenced by gut microbiota. However, it remains unclear which a taxon of gut microbiota plays a key role in this function. Identifying the key bacteria affects hypothyroidism and through what mechanism will be helpful for the prevention of hypothyroidism through specific clinical pathways. Materials and methods: In Study A, 35 families and 130 genera of gut microbiota are used as exposures, with hypothyroidism as the outcome. The causal effect of the gut microbiota on hypothyroidism is estimated through two-sample Mendelian randomization. Combining the results of the two taxonomical levels, key taxa are selected, which in Study B are investigated for their causal association with multiple generally admitted causes of hypothyroidism and their more upstream factors. For validating and revealing the potential mechanism, enrichment analyses of the related genes and interacting transcription factors were performed. Results: In Study A, Defluviitaleaceae (OR: 0.043, 95% CI: 0.005-0.363, P = 0.018)/Defluviitaleaceae_UCG_011 (OR: 0.385, 95% CI: 0.172-0.865, P = 0.021) are significantly causally associated with hypothyroidism at both taxonomical levels. In Study B, Defluviitaleaceae family and Defluviitaleaceae_UCG_011 genus show the causal association with decreased thyroiditis (Family: OR: 0.174, 95% CI: 0.046-0.653, P = 0.029; Genus: OR: 0.139, 95% CI: 0.029-0.664, P = 0.043), decreased subacute thyroiditis (Family: OR: 0.028, 95% CI: 0.004-0.213, P = 0.007; Genus: OR: 0.018, 95% CI: 0.002-0.194, P = 0.013), decreased influenza (Family: OR: 0.818, 95% CI: 0.676-0.989, P = 0.038; Genus: OR: 0.792, 95% CI: 0.644-0.974, P = 0.027), and increased anti-influenza H3N2 IgG levels (Family: OR: 1.934, 95% CI: 1.123-3.332, P = 0.017; Genus: OR: 1.675, 95% CI: 0.953-2.943, P = 0.073). The results of the enrichment analysis are consistent with the findings and the suggested possible mechanisms. Conclusion: Defluviitaleaceae of the gut microbiota displays the probability of causally inhibiting the clinical pathway of "Influenza-Subacute Thyroiditis-Hypothyroidism" and acts as the potential probiotics to prevent influenza, subacute thyroiditis, and hypothyroidism.

Multiple exposures to low-dose ionizing radiation induced the initiation and progression of pro-atherosclerotic phenotypes in mice and vascular endothelial cell damage.

OBJECTIVE: This study aimed to investigate the effects of low-dose radiation on the abdominal aorta of mice and vascular endothelial cells. METHODS: Wild-type and tumor-bearing mice were exposed to 15 sessions of low-dose irradiation, resulting in cumulative radiation doses of 187.5, 375, and 750 mGy. The effect on the cardiovascular system was assessed. Immunohistochemistry analyzed protein expressions of PAPP-A, CD62, P65, and COX-2 in the abdominal aorta. Microarray technology, Gene Ontology analysis, and pathway enrichment analysis evaluated gene expression changes in endothelial cells exposed to 375 mGy X-ray. Cell viability was assessed using the Cell Counting Kit 8 assay. Immunofluorescence staining measured γ-H2AX levels, and real-time polymerase chain reaction quantified mRNA levels of interleukin-6 (IL-6), ICAM-1, and Cx43. RESULTS: Hematoxylin and eosin staining revealed thickening of the inner membranes and irregular arrangement of smooth muscle cells in the media membrane at 375 and 750 mGy. Inflammation was observed in the inner membranes at 750 mGy, with a clear inflammatory response in the hearts of tumor-bearing mice. Immunohistochemistry indicated increased levels of PAPP-A, P65, and COX-2 post-irradiation. Microarray analysis showed 425 up-regulated and 235 down-regulated genes, associated with processes like endothelial cell-cell adhesion, IL-6, and NF-κB signaling. Cell Counting Kit 8 assay results indicated inhibited viability at 750 mGy in EA.hy926 cells. Immunofluorescence staining demonstrated a dose-dependent increase in γ-H2AX foci. Reverse transcription quantitative PCR results showed increased expression of IL6, ICAM-1, and Cx43 in EA.hy926 cells post 750 mGy X-ray exposure. CONCLUSION: Repeated low-dose ionizing radiation exposures triggered the development of pro-atherosclerotic phenotypes in mice and damage to vascular endothelial cells.