pH-Responsive Calcium Ions and Crocetin Releasing Hydrogel for Accelerating Skin Wound Healing.

The ideal and highly anticipated dressing for skin wounds should provide a moist environment, possess antibacterial properties, and ensure sustained drug release. In the present work, a hyaluronic acid-based hydrogel was formed by cross-linking crocetin and CaCO3@polyelectrolyte materials (CaCO3@PEM) microspheres with HA hydrogels via hydrogen bond and amido bonding (CaCO3@PEM@Cro@HA hydrogel, CPC@HA hydrogel). Moreover, the CPC@HA hydrogel had the capability of sustained, controlled release of calcium ions and crocetin via pH-sensitive and accelerated skin wound healing. The experiment results showed that the CPC@HA hydrogel exhibited porous network structures, stable physical properties, and had antibacterial properties and biocompatibility in vitro. In addition, the CPC@HA hydrogel covering on the skin wound could reduce inflammation and promote wound healing. The high expression of angiogenic cytokines (CD31) and epidermal terminal differentiation markers (Loricrin) of wound healing tissue suggested the CPC@HA hydrogel also had the function of promoting the remodeling of regenerated skin. Overall, CPC@HA hydrogel has promising potential for clinical applications in accelerating skin wound repair.

pH-Sensitive Glucose-Powered Nanomotors for Enhanced Intracellular Drug Delivery and Ferroptosis Efficiency.

We propose a glucose-powered Janus nanomotor where two faces are functionalized with glucose oxidase (GOx) and polydopamine-Fe3+ chelates (PDF), respectively. In the glucose fuel solution, the GOx on the one side of these Janus nanomotors catalytically decomposes glucose fuels into gluconic acid and hydrogen peroxide (H2 O2 ) to drive them at a speed of 2.67 µm/s. The underlying propulsion mechanism is the glucose-based self-diffusiophoresis owing to the generated local glucose concentration gradient by the enzymatic reaction. Based on the enhanced diffusion motion, such nanomotors with catalytic activity increase the uptake towards cells and subsequently exhibit excellent capabilities for Fe3+ ions delivery and H2 O2 generation for enhancing ferroptosis efficiency for inducing cancer cell death. In particular, the Fe3+ ions are released from nanomotors in a slightly acidic environment, and subsequently generate toxic hydroxyl radicals via Fenton reactions, which accumulation reactive oxygen species (ROS) level (~300 %) and further lipid peroxidation (LPO) strengthened ferroptosis therapy for cancer treatment. The as-developed glucose-powered Janus nanomotor with efficient diffusion and Fe ions delivery capabilities show great promise as a potential in biomedical applications.

Biomonitoring of glyphosate and aminomethylphosphonic acid: Current insights and future perspectives.

Glyphosate is one of the most widely used herbicides globally, raising concerns about its potential impact on human health. Biomonitoring studies play a crucial role in assessing human exposure to glyphosate and providing valuable insights into its distribution and metabolism in the body. This review aims to summarize the current trends and future perspectives in biomonitoring of glyphosate and its major degradation product of aminomethylphosphonic acid (AMPA). A comprehensive literature search was conducted, focusing on studies published between January 2000 and December 2022. The findings demonstrated that glyphosate and AMPA have been reported in different human specimens with urine as the dominance. Sample pretreatment techniques of solid-phase and liquid-liquid extractions coupled with liquid/gas chromatography-tandem mass spectrometry have achieved matrix elimination and accurate analysis. We also examined and compared the exposure characteristics of these compounds among different regions and various populations, with significantly higher levels of glyphosate and AMPA observed in Asian populations and among occupational groups. The median urinary concentration of glyphosate in children was 0.54 ng/mL, which was relatively higher than those in women (0.28 ng/mL) and adults (0.12 ng/mL). It is worth noting that children may exhibit increased susceptibility to glyphosate exposure or have different exposure patterns compared to women and adults. A number of important perspectives were proposed in order to further facilitate the understanding of health effects of glyphosate and AMPA, which include, but are not limited to, method standardization, combined exposure assessment, attention for vulnerable populations, long-term exposure effects and risk communication and public awareness.

A salting-out assisted liquid-liquid extraction method for 25 emerging pesticides in follicular fluid.

Emerging pesticides of neonicotinoids (NEOs) and "Universal Pesticides" (UPs) are a growing global concern due to their growing commercial importance and potential risks to human health. The currently available analytical methods for these pesticides in biomonitoring were usually tailored for limited number of analytes, or were time consuming and costly. In this study, an efficient and sensitive method for the analysis of 16 NEOs and nine UPs in human follicular fluid (FF) was developed by using a salting-out assisted liquid-liquid extraction (SALLE) method and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Method performance was evaluated by calibration linearity (r > 0.99), sensitivity at limits of quantification (0.01-0.50 ng/mL), accuracy at relative recoveries (81-117%) and precision at relative standard deviations (≤16%). The developed method was further validated by analyzing 21 human FF samples that were collected from a hospital in Guangzhou, China. Among the 25 study analytes, two NEOs and six UPs had their detection rates over 85% and medians at 0.048-0.808 ng/mL in the FF samples. Considering the well-known toxicity of these pesticides and their metabolites, it is urgent to figure out exposure profiles of study pesticides and potential reproductive risk for women. To the best of our knowledge, this study is the first to develop and apply the SALLE method in the extraction of 16 NEOs and nine UPs simultaneously in human FF.

Neonicotinoid insecticides and their metabolites: Specimens tested, analytical methods and exposure characteristics in humans.

The use of neonicotinoid insecticides (NEOs) has been rising globally due to their broad-spectrum insecticidal activity, unique mode of neurotoxic action and presumed low mammalian toxicity. Given their growing ubiquity in the environment and neurological toxicity to non-target mammals, human exposure to NEOs is flourishing and now becomes a big issue. In the present work, we demonstrated that 20 NEOs and their metabolites have been reported in different human specimens with urine, blood and hair as the dominance. Sample pretreatment techniques of solid-phase and liquid-liquid extractions coupled with high performance liquid chromatography-tandem mass spectrometry have successfully achieved matrix elimination and accurate analysis. We also discussed and compared exposure characteristics of these compounds among types of specimens and different regions. A number of important knowledge gaps were also identified in order to further facilitate the understanding of health effects of NEO insecticides, which include, but are not limited to, identification and use of neuro-related human biological samples for better elucidating neurotoxic action of NEO insecticides, adoption of advanced non-target screening analysis for a whole picture in human exposure, and expanding investigations to cover non-explored but NEO-used regions and vulnerable populations.

Neonicotinoids residues in cow milk and health risks to the Chinese general population.

The application of neonicotinoid insecticides (NEOs) has increased dramatically in the world since being introduced in 1990s, yet the extent of human exposure and potential health risk is not fully unraveled. In this study, the residues were analyzed of 16 NEOs and their metabolites in 205 commercial cow milk samples circulating in Chinese market. All the milk samples contained at least one quantified NEO, and over 90% of samples contained a cocktail of NEOs. Acetamiprid, N-desmethyl acetamiprid, thiamethoxam, clothianidin and imidaclothiz were the most commonly detected analytes with detection frequencies of 50-88% and medians of 0.011-0.038 ng/mL in milk. Geographical origin was an important factor to influence abundances and levels of NEOs contamination in milk. Chinese local milk bore a significant higher risk from NEOs contamination than the imported milk. In China, the northwest presented the greatest concentrations of the insecticides relative to the north or south. Organic farming, ultra heat treatment and skimming could significantly reduce levels of NEOs contamination in milk. A relative potency factor method was used to evaluate estimated daily intake of NEO insecticides, and found the children had 3.5-5 times higher exposed risk via milk ingestion than the adults. The high frequency of NEOs detection in milk offers us a snapshot of the ubiquity of NEOs in milk, with possible health implications especially for children.

Occurrence of multiple bisphenol S analogues in children from Shantou, China.

Emerging bisphenol S analogues (BPSs) have gained their application perspectives to replace bisphenol A (BPA) and BPA analogues (BPAs). However, the extent of human exposure and potential health risk from BPSs is rarely known yet. We hypothesized that children living in Shantou, China, a well-known e-waste recycling city, may expose to emerging BPSs together with BPA and BPAs. In this study, BPA, six commonly used BPAs and 11 emerging BPSs were determined simultaneously in 240 urine samples collected from children residing in Shantou. BPA, BPS, bisphenol F, bisphenol AF and three BPSs of 2,4'-bis(hydroxyphenyl)sulfone, 4-((4-(allyloxy)phenyl)sulfonyl)phenol and diphenylsulfone (DPS) were the urinary predominant bisphenols with detection frequencies of 67-100% in the children. BPA was found at the highest median concentration (3.36 µg/g creatinine) followed by BPS (0.313) and DPS (0.187). It is interesting to find that the girls and children in the younger group (2 ≤ age < 5) had consistently higher concentrations of the seven dominant bisphenols than the boys and these of the older group (5 ≤ age ≤ 10), respectively. The children with under/overweight suffered higher burdens of bisphenol exposure based on medians of estimated daily intakes. Association analysis results indicated that the Shantou children exposed themselves to multiple BPSs along with BPA and BPAs from assumed consumer products and/or contaminated environments.

Occurrence of emerging bisphenol S analogues in urine from five occupational populations in South China.

Bisphenol S (BPS) and its 11 emerging analogues were investigated in 325 urine samples from five occupational populations in South China. Besides BPS, ten emerging BPS analogues were newly identified and detected in the urine. It should be noted that urinary concentrations of dominant BPS analogues of 2,4'-bis(hydroxyphenyl)sulfone (2,4-BPS), bis(3-allyl-4-hydroxyphenyl)sulfone (TGSA) and diphenylsulfone (DPS) were 1.1-2.3 times higher than that of BPS, with overall detection frequencies at 74-91 %. The median sum concentrations of the target 12 bisphenols (ng/mL) were found highest in urine from cashiers (1.12), followed by water plant staffs (0.994), teachers (0.552), doctors (0.408) and power plant staffs (0.333). The composition profile of the urinary dominant bisphenols was occupational-dependent, with 2,4-BPS accounting for 45-73 % in cashiers and power plant staffs, and with DPS and TGSA for 74-82 % among doctors, teachers and water plant staffs. Significant correlations were found among the most frequently detected bisphenols in cashiers, indicating their common application and emission pathways. The median exposures based on estimated daily intakes (EDIs, ng/kg bw/day) for the 12 bisphenols in cashiers and water plant staffs (31.6-35.6) were 1.8-3.4 times higher than those of teachers, doctors and power plant staffs (10.6-17.5). This is the first study to identify multiple emerging BPS analogues in urine from occupational populations, especially cashiers and water plant staffs.

Ultrahigh-Loaded Fe Single Atoms and Fe3C Nanoparticle Catalysts as Air Cathodes for High-Performance Zn-Air Batteries.

Fe-based materials containing Fe-Nx sites have emerged as promising electrocatalysts in the oxygen reduction reaction (ORR), but they still suffer structural instability which may lead to loss of catalytic activity. Herein, a novel electrocatalyst Fe3C-FeSA@3DCN with the coexistence of Fe3C nanoparticles and Fe single atoms (FeSA) in a three-dimensional conductive network (3DCN) is prepared via lattice confinement and defect trapping strategies with an Fe atomic loading of as high as 4.36%. In the ORR process, the limiting current density of Fe3C-FeSA@3DCN reaches 5.72 mA cm-2, with an onset potential of 0.926 V and a Tafel slope of 66 mV/decade, showing better catalytic activity and stability than Pt/C catalysts. Notably, its assembled aqueous and solid-state Zn-air batteries (ZABs) achieve peak power densities of 166 and 56 mW cm-2, respectively, with a long service life of up to 200 h at a current density of 5 mA cm-2. In addition, the assembled ZAB can provide a constant voltage on activated carbon electrodes to perform capacitive deionization to adsorb different ions. The importance of the Fe species active sites generated by Fe3C and FeSA in the material for ORR activity to boost the electron transfer and mass transfer is demonstrated by a simple selective poisoning experiment.

ZIF-8-derived N-doped porous carbon wrapped in porous carbon films as an air cathode for flexible solid-state Zn-air batteries.

Metal-organic frameworks are a new type of catalyst precursor with high specific surface area and controllable composition, which can be modified by post-treatment and are suitable for use as cathode catalysts for Zn-air batteries (ZABs). Here, a self-doped nitrogen nanocatalyst (N-PC@CF) with a double-layered porous structure is rationally designed for flexible solid-state ZABs. The outer porous carbon shell of the N-PC@CF is highly hydrophilic and O2 permeable, while the layered porous structure exposes sufficient active sites to shorten the mass transfer distance, which would promote electrocatalytic performance and increase flexibility efficiently. The obtained N-PC@CF has an onset potential of 0.926 V and a half-wave potential of 0.843 V in the oxygen reduction reaction test, which is equivalent to commercial Pt/C. Most importantly, the maximum power density of the assembled ZAB is 134.7 mW cm-2 and it exhibits a specific capacity of 776.8 mA h g-1 at 10 mA cm-2, which is better than the 99.9 mW cm-2 of the Pt/C-based battery. An obvious improvement in the constant current discharge-charge cycle durability of the ZAB is found when compared with Pt/C. The specific capacities of ZAB with N-PC@CF as the air cathode at 5, 10 and 15 mA cm-2 are 842.7, 776.8 and 715.0 mAh g-1 (calculated by the mass of zinc consumed), respectively, corresponding to high energy densities of 1089.7, 977.3 and 842.2 Wh kg-1. A flexible solid-state battery is assembled with excellent flexibility and stability, even if the battery is folded into a large angle (160°). This work provides a new strategy for the design and synthesis of metal-free air cathodes.

Double-edged role of interlayer water on Li+ extraction from ultrahigh Mg2+/Li+ ratio brines using Li/Al-LDHs.

Lithium-aluminum layered double hydroxides (Li/Al-LDHs) are the only industrial adsorbents for Li+ extraction from Mg2+/Li+ ratio brines dependent on the special neutral desorption without dissolution damage. In this work, Li/Al-LDHs with different interlayer water contents were designed for the investigation of correlation between interlayer water and Li+ adsorption performances in high Mg2+/Li+ ratio brines. On the one hand, the Li+ adsorption capacity of Li/Al-LDHs in the Qarham Salt Lake old brine with a Mg2+/Li+ ratio exceeding 300 presented a positive correlative relation with the interlayer water content, rising from 1.05 mg/g to 7.89 mg/g as the interlayer water content increased from 5.52% to 18.18%. On the other hand, the interlayer water content would not affect the structure stability of Li/Al-LDHs, while the interlayer spacing was lessened with less interlayer water resulting in an uptrend to the adsorption selectivity on account of the depressed confinement effect. The density functional theory (DFT) calculation further indicated that LiCl was easier to enter the structure of Li/Al-LDHs with more interlayer water in view of the greater interaction energy.

Advanced Maternal Age Impairs Myelination in Offspring Rats.

The effects of advanced maternal age (AMA) on the neurodevelopment of offspring are becoming increasingly important. Myelination is an important aspect of brain development; however, a limited number of studies have focused on the effects of AMA on myelination in offspring. The current study aims to evaluate the association between AMA and myelin sheath development in offspring. We studied the learning and memory function of immature offspring using the novel object recognition test. Then, we investigated the expression of myelin basic protein (MBP) in the immature offspring of young (3-month-old) and old (12-month-old) female rats at different time points (14, 28, and 60 days) after birth with immunofluorescence and western blotting. The myelin sheath ultrastructure was observed with transmission electron microscopy in immature and mature offspring. Extracellular signal-regulated kinase 1 and 2 (ERK1/2) and phosphorylated ERK1/2 (p-ERK1/2) were investigated by western blot in immature offspring at the above time points. AMA impaired the memory function of offspring during early postnatal days. The MBP expression level gradually increased with postnatal development in the offspring of both the AMA and Control (Ctl) groups, but the MBP level in the offspring of the AMA group was lower than that of the Ctl group at 14 days after birth. In addition, the ultrastructure of the myelin sheath was defective in AMA offspring during the early postnatal period; however, the myelin sheath was not significantly affected in offspring during adulthood. Interestingly, ERK phosphorylation at 14 days after birth was lower in AMA offspring than in Ctl offspring. However, ERK phosphorylation at 28 days after birth was higher in AMA offspring than in Ctl offspring. The peak of ERK phosphorylation in the AMA group was abnormal and delayed. Our results indicated that AMA is associated with poor developmental myelin formation in offspring. The ERK signaling pathway may play an essential role in the adverse effects of AMA on the offspring myelin sheath development.

The Role and Mechanism of AMIGO3 in the Formation of Aberrant Neural Circuits After Status Convulsion in Immature Mice.

Leucine rich repeat and immunoglobulin-like domain-containing protein 1 (Lingo-1) has gained considerable interest as a potential therapy for demyelinating diseases since it inhibits axonal regeneration and myelin production. However, the results of clinical trials targeted at Lingo-1 have been unsatisfactory. Amphoterin-induced gene and open reading frame-3 (AMIGO3), which is an analog of Lingo-1, might be an alternative therapeutic target for brain damage. In the present study, we investigated the effects of AMIGO3 on neural circuits in immature mice after status convulsion (SC) induced by kainic acid. The expression of both AMIGO3 and Lingo-1 was significantly increased after SC, with levels maintained to 20 days after SC. Following SC, transmission electron microscopy revealed the impaired microstructure of myelin sheaths and Western blot analysis showed a decrease in myelin basic protein expression, and this damage was alleviated by downregulation of AMIGO3 expression. The ROCK/RhoA signaling pathway was inhibited at 20 days after SC by downregulating AMIGO3 expression. These results indicate that AMIGO3 plays important roles in seizure-induced damage of myelin sheaths as well as axon growth and synaptic plasticity via the ROCK/RhoA signaling pathway.

Associations of Prenatal Exposure to Per- and Polyfluoroalkyl Substances with the Neonatal Birth Size and Hormones in the Growth Hormone/Insulin-Like Growth Factor Axis.

Toxicological data suggest a significant developmental toxicity of per- and polyfluoroalkyl substances (PFASs); however, evidence in humans remains inconclusive. Furthermore, the effects of prenatal exposure to PFASs on hormones in the growth hormone (GH)/insulin-like growth factor (IGF) axis of newborns remain largely unclear. We aimed to investigate the associations of prenatal exposure to PFASs with the neonatal birth size, GH, IGF-1, and IGF-binding protein 3 (IGFBP-3). The concentrations of 22 PFASs were measured in the plasma of 224 pregnant women collected within 3 days before delivery (39.3 weeks) in Guangzhou, China, and the anthropometric data were gathered from medical records. Paired cord blood was collected at delivery to determine GH, IGF-1, and IGFBP-3 levels. Multivariable linear regression models revealed the inverse associations of several long-chain PFASs with birth weight and ponderal index as well as the significant associations of perfluorobutanoic acid and perfluorooctanoic acid (PFOA) with IGFBP-3 levels. The Bayesian kernel machine regression confirmed the association of perfluorooctane sulfonate with birth weight and ponderal index and of PFOA with IGFBP-3 and identified an inverse joint effect of exposure to a mixture of multiple PFASs on birth weight. The findings provide the first comprehensive evidence on the individual and joint effects of multiple PFASs on the neonatal birth size and hormones in the GH/IGF axis, which requires further confirmation.

Clinical and genetic characteristics of epilepsy of infancy with migrating focal seizures in Chinese children.

OBJECTIVE: Epilepsy of infancy with migrating focal seizures (EIMFS) is a rare and severe developmental epileptic encephalopathy. The aim of this study was to improve our understanding of EIMFS by using phenotype-genotype correlation. METHODS: We recruited, performed clinical genetic testing, and summarized the clinical features and genetic characteristics in five patients with EIMFS in China. RESULTS: The five recruited patients included 2 males and 3 females. The median age of seizure onset was 2 months (range, day 3 to 3 months). All patients exhibited the characteristics of clinically migrating focal motor (tonic or clonic) seizures. Typical migrating ictal electrical patterns were found in 1 patient; the remaining four patients presented with overlapping seizures with different areas of ictal onset in differing hemispheres. All the patients had the associated variants, including KCNT1, SCN1A, SCN2A, TBC1D24 and ALG1. All patients received two or more antiseizure medications, and 1 patient became seizure-free, 1 reported >75 % seizure reduction, 2 reported >50 % seizure reduction, and 1 patient showed no improvement. Varying degrees of psychomotor developmental delays were observed in all patients. CONCLUSIONS: The course of EIMFS could be related to the type of gene variant present, and different genes may have specific clinical features. Larger cohorts are required to elucidate such potential phenotype-genotype correlations.

Autoimmune encephalitis after Japanese encephalitis in children: A prospective study.

OBJECTIVE: To explore anti-neuronal surface antibodies and identify associated serum predictors of autoimmune encephalitis after Japanese encephalitis (JE). METHODS: This prospective study first detected anti-neuronal surface antibodies and cytokines in the serum and cerebrospinal fluid (CSF) of JE patients within one week of symptom onset. Anti-neuronal surface antibodies and cytokines in the serum were detected on day 21 post-JE. If the patients relapsed during the convalescent phase, we simultaneously detected JE virus RNA and cytokines in the CSF, as well as anti-neuronal surface antibodies in the serum and CSF. RESULTS: All 31 patients were negative for anti-neuronal surface antibodies at the onset of JE in the serum and CSF. During the convalescent phase, five patients developed autoimmune encephalitis (two had anti-N-methyl-d-aspartate receptor [NMDAR] antibodies, one had γ-aminobutyric acid-B receptor [GABABR] antibodies, and two had other antibodies against unknown neuronal surface antigens). Patients who developed autoimmune encephalitis experienced more severe outcomes than those who did not at the one-year follow-up (p = 0.044). The levels of serum CXCL13 and IL-6, as well as CXCL13, BAFF, CXCL10, and MMP-9 in the CSF were increased in the convalescent phase compared to the acute phase in patients who developed autoimmune encephalitis (p < 0.05). CONCLUSION: In addition to anti-NMDAR antibodies, anti-GABABR antibodies and antibodies against unknown neuronal surface antigens can trigger autoimmune encephalitis following JE. Patients who developed autoimmune encephalitis had a poorer prognosis at the one-year follow-up. Serum CXCL13 may represent a predictor of autoimmune encephalitis after JE.

Role of PKA/CREB/BDNF signaling in PM2.5-induced neurodevelopmental damage to the hippocampal neurons of rats.

Exposure to fine particulate matter (PM2.5) is implicated in neurodevelopmental disorders including cognitive decline, attention-deficit/hyperactivity disorder, and autism spectrum disorder. However, the specific molecular mechanisms by which PM2.5 impacts neurodevelopment are poorly understood. Accordingly, in the present study, the role of protein kinase A (PKA)/cAMP response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling in PM2.5-induced neurodevelopmental damage was investigated using primary cultured hippocampal neurons. When hippocampal neurons cultured for 3 days in vitro (DIV3) were exposed to PM2.5 for 24 h and 96 h, neuronal viability decreased by 18.8% and 32.7% respectively, percentage of TUNEL-positive neurons increased by 78.5% and 64.0% separately, caspase-9 expression increased, lower postsynaptic density and shorter active zones were observed by transmission electron microscopy, expression of synapse-related proteins including postsynaptic density-95 (PSD95), growth associated protein-43 (GAP43), and synaptophysin (SYP) were decreased, and the phosphorylation levels of PKA, CREB, and BDNF expression also decreased. However, the PM2.5-induced neuronal damage could be ameliorated or aggravated to varying degrees by up- or down-regulation of the PKA/CREB/BDNF signaling pathway, respectively. Our results indicate that PM2.5 exposure exerts neurodevelopmental toxicity as indicated by lower viability, apoptosis, and synaptic damage in primary cultured hippocampal neurons, and that the PKA/CREB/BDNF pathways could play a vital role in PM2.5-mediated neurodevelopmental toxicity.

Association of systemic inflammation and body mass index with survival in patients with resectable gastric or gastroesophageal junction adenocarcinomas.

Objective: The systemic inflammation index and body mass index (BMI) are easily accessible markers that can predict mortality. However, the prognostic value of the combined use of these two markers remains unclear. The goal of this study was therefore to evaluate the association of these markers with outcomes based on a large cohort of patients with gastric cancer. Methods: A total of 2,542 consecutive patients undergoing radical surgery for gastric or gastroesophageal junction adenocarcinoma between 2009 and 2014 were included. Systemic inflammation was quantified by the preoperative neutrophil-to-lymphocyte ratio (NLR). High systemic inflammation was defined as NLR ≥ 3, and underweight was defined as BMI < 18.5 kg/m2. Results: Among 2,542 patients, NLR ≥ 3 and underweight were common [627 (25%) and 349 (14%), respectively]. In the entire cohort, NLR ≥ 3 or underweight independently predicted overall survival (OS) [hazard ratio (HR): 1.236, 95% confidence interval (95% CI): 1.069-1.430; and HR: 1.600, 95% CI: 1.350-1.897, respectively] and recurrence-free survival (RFS) (HR: 1.230, 95% CI: 1.054-1.434; and HR: 1.658, 95% CI: 1.389-1.979, respectively). Patients with both NLR ≥ 3 and underweight (vs. neither) had much worse OS (HR: 2.445, 95% CI: 1.853-3.225) and RFS (HR: 2.405, 95% CI: 1.802-3.209). Furthermore, we observed similar results in subgroup analyses according to pathological stage, age, and postoperative chemotherapy. Conclusions: Our results showed that preoperative elevated NLR and decreased BMI had a significant negative effect on survival. Underweight combined with severe inflammation could enhance prognostication. Taking active therapeutic measures to reduce inflammation and increase nutrition may help improve outcomes.

Functional constipation is associated with alterations in thalamo-limbic/parietal structural connectivity.

BACKGROUND: Functional constipation (FCon) is a common functional gastrointestinal disorder (FGID) with a high prevalence in clinical practice. Previous studies have identified that FCon is associated with functional and structural alterations in the primary brain regions involved in emotional arousal processing, sensory processing, somatic/motor-control, and self-referential processing. However, whether FCon is associated with abnormal structural connectivity (SC) among these brain regions remains unclear. METHODS: We selected the brain regions with functional and structural abnormalities as seed regions and employed diffusion tensor imaging (DTI) with probabilistic tractography to investigate SC changes in 29 patients with FCon and 31 healthy controls (HC). KEY RESULTS: Results showed lower fractional anisotropy (FA) in the fibers connecting the thalamus, a region involved in sensory processing, with the amygdala (AMY), hippocampal gyrus (HIPP), precentral (PreCen) and postcentral gyrus (PostCen), supplementary motor area (SMA) and precuneus in patients with FCon compared with HC. FCon had higher mean diffusivity (MD) and radial diffusivity (RD) in the thalamus connected to the AMY and HIPP. In addition, FCon had significantly increased RD of the thalamus-SMA tract. Sensation of incomplete evacuation was negatively correlated with FA of the thalamus-PostCen and thalamus-HIPP tracts, and there was a negative correlation between difficulty of defecation and FA of the thalamus-SMA tract. CONCLUSIONS AND INFERENCES: These findings reflected that FCon is associated with alterations in SC between the thalamus and limbic/parietal cortex, highlighting the integrative role of the thalamus in brain structural network.