BACKGROUND: Depression among older adults is an important public health issue, and air and noise pollution have been found to contribute to exacerbation of depressive symptoms. This study examined the association of exposure to air and noise pollutants with clinically-newly-diagnosed depressive disorder. The mediating role of individual pro-inflammatory markers was explored. METHODS: We linked National Health Insurance claim data with 2998 healthy community-dwellers aged 55 and above who participated in the Healthy Aging Longitudinal Study between 2009 and 2013. Newly diagnosed depressive disorder was identified using diagnostic codes from the medical claim data. Pollutants were estimated using nationwide land use regression, including PM_2.5 and PM₁₀, carbon monoxide, ozone, nitrogen dioxide, sulfur dioxide, and road traffic noise. Cox proportional hazard models were employed to examine the association between pollutants and newly developed depressive disorders. The mediating effect of serum pro-inflammatory biomarkers on the relationship was examined. RESULTS: Among the 2998 participants, 209 had newly diagnosed depressive disorders. In adjusted Cox proportional hazard models, one interquartile range increase in PM_2.5 (8.53 µg/m³) was associated with a 17.5% increased hazard of developing depressive disorders. Other air pollutants and road traffic noise were not linearly associated with depressive disorder incidence. Levels of serum tumor necrosis factor receptor 1 mediated the relationship between PM_2.5 and survival time to newly onset depressive disorder. CONCLUSION PM_2.5 is related to an increased risk of newly developed depressive disorder among middle-aged and older adults, and the association is partially mediated by the pro-inflammatory marker TNF-R1.
Humans ; Particulate Matter/analysis* ; Male ; Female ; Middle Aged ; Longitudinal Studies ; Aged ; Incidence ; Air Pollutants/analysis* ; Environmental Exposure/adverse effects* ; Taiwan/epidemiology* ; Receptors, Tumor Necrosis Factor, Type I/blood* ; Proportional Hazards Models ; Biomarkers/blood* ; Depression/epidemiology* ; Aged, 80 and over ; Depressive Disorder/chemically induced* ; Risk Factors ; Air Pollution/adverse effects*

OBJECTIVES: To determine the pharmacological impact of hesperidin, the main component of Citri Reticulatae Pericarpium, on depressive behavior and elucidate the mechanism by which hesperidin treats depression, focusing on the gut-brain axis. METHODS: Fifty-four Sprague Dawley male rats were randomly allocated to 6 groups using a random number table, including control, model, hesperidin, probiotics, fluoxetine, and Citri Reticulatae Pericarpium groups. Except for the control group, rats in the remaining 5 groups were challenged with chronic unpredictable mild stress (CUMS) for 21 days and housed in single cages. The sucrose preference test (SPT), immobility time in the forced swim test (FST), and number in the open field test (OFT) were performed to measure the behavioral changes in the rats. Enzyme-linked immunosorbent assay was used to determine the levels of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) in brain tissue, and the histopathology was performed to evaluate the changes of colon tissue, together with sequencing of the V3-V4 regions of 16S rRNA gene on feces to explore the changes of intestinal flora in the rats. RESULTS: Compared to the control group, the rats in the model group showed notable reductions in body weight, SPF, and number in OFT (P<0.01). Hesperidin was found to ameliorate depression induced by CUMS, as seen by improvements in body weight, SPT, immobility time in FST, and number in OFT (P<0.05 or P<0.01). Regarding neurotransmitters, it was found that at a dose of 50 mg/kg hesperidin treatment upregulated the levels of 5-HT and BDNF in depressed rats (P<0.05). Compared to the control group, the colon tissue of the model group exhibited greater inflammatory cell infiltration, with markedly reduced numbers of goblet cells and crypts and were significantly improved following treatment with hesperidin. Simultaneously, the administration of hesperidin demonstrated a positive impact on the gut microbiome of rats treated with CUMS, such as Shannon index increased and Simpson index decreased (P<0.01), while the abundance of Pseudomonadota and Bacteroidota increased in the hesperidin-treated group (P<0.05). CONCLUSION The mechanism responsible for the beneficial effects of hesperidin on depressive behavior in rats may be related to inhibition of the expressions of BDNF and 5-HT and preservation of the gut microbiota.
Animals ; Hesperidin/therapeutic use* ; Rats, Sprague-Dawley ; Depression/drug therapy* ; Male ; Stress, Psychological/drug therapy* ; Brain/metabolism* ; Brain-Derived Neurotrophic Factor/metabolism* ; Serotonin/metabolism* ; Gastrointestinal Microbiome/drug effects* ; Behavior, Animal/drug effects* ; Rats ; Brain-Gut Axis/drug effects* ; Chronic Disease ; Colon/drug effects*

Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

BACKGROUND:The application of miniscrew in adolescents is increasing day by day,but at present,there are few studies on bone mass in the external oblique line of the mandible in adolescents at home and abroad,and there is no systematic study on bone mass in the external oblique line of the mandible in adolescents in different growth and development periods. OBJECTIVE:To measure the bone mass in the external oblique line of the mandible in adolescents with different cervical vertebral bone ages using a cone-beam CT and to investigate the difference of bone mass in the external oblique line of the mandible in adolescents with different cervical vertebral bone ages and the correlation between bone mass in this area and the cervical vertebral bone age. METHODS:The cone-beam CT data of 105 adolescent patients before orthodontic treatment were collected and divided into CS3 group(n=24),CS4 group(n=26),CS5 group(n=29)and CS6 group(n=26)using the cervical vertebral maturation method.The adolescent mandibular buccal shelf was reconstructed by Mimics Medical 21.0 software.The width of buccal bone at 6 and 11 mm under the cemento-enamel junction and the bone height at 4 and 5 mm buccal to the cemento-enamel junction of right mandibular first and second molars were measured.The measured data were statistically analyzed.The measurement was made on four planes:plane 1 is the plane where the proximal mesial root of the mandibular right first molar is located;plane 2 is the plane where the distal mesial root of the mandibular right first molar is located;plane 3 is the plane where the proximal mesial root of the mandibular right second molar is located;and plane 4 is the plane where the distal mesial root of the mandibular right second molar is located. RESULTS AND CONCLUSION:In each group,the bone width on the buccal side of the external oblique line increased gradually from the first molar proximally to the second molar distally in adolescents,and the width of buccal bone at 6 and 11 mm under the cemento-enamel junction showed significant difference among different layers(P<0.05).The bone width of buccal bone at 11 mm under the cemento-enamel junction was greater than that at 6 mm.The bone height on the buccal side of the external oblique line increased gradually from the first molar proximally to the second molar distally in all four groups,and the bone height at 4 and 5 mm buccal to the cemento-enamel junction showed significant differences at different layers(P<0.05).The bone height at 4 mm buccal to the cemento-enamel junction was greater than that at 5 mm.On the fourth plane,the bone width at 11 mm buccal to the cemento-enamel junction was smaller in the CS3,CS4,and CS5 groups than in the CS6 group(P<0.05).On the third plane,the bone heights at 4 mm and 5 mm buccal to the cemento-enamel junction were smaller in the CS3 and CS4 groups than in the CS6 group(P<0.05).On the fourth plane,the bone height at 5 mm buccal to the cemento-enamel junction was smaller in the CS3 and CS4 groups than in the CS6 group(P<0.05).On the fourth plane,the bone height at 4 mm buccal to the cemento-enamel junction was smaller in the CS3 group than in the CS6 group(P<0.05).Spearman correlation analysis showed that there was no correlation between bone mass and the cervical vertebral bone age,except that there was a weak correlation between bone mass at some measurement sites and cervical vertebral bone age.To conclude,the bone mass in the external oblique area of the mandible in adolescents does not change significantly with the increase of cervical vertebral bone age.The buccal side of the mesial root and distal root of the mandibular second molar in the external oblique area of CS3-CS6 adolescents meets the requirement of bone mass for miniscrew implantation,which is a site available for miniscrew implantation.

BACKGROUND:Traditional lateral cephalometric radiographs always suffer from some problems,such as magnification distortion,left and right overlap inconsistency and so on,while the cone-beam CT can truly display the three-dimensional structure of the craniofacial region.Performing three-dimensional reconstruction of cone-beam CT and then transforming the cone-beam CT in the selected area into the two-dimensional image can make the overlap between the left and right sides consistent and reduce the influence of surrounding tissue structures. OBJECTIVE:To explore the consistency of quantitative analysis of cervical vertebral bone age between two kinds of cone-beam CT transformed two-dimensional images with different integrated thicknesses and traditional lateral cephalometric radiographs. METHODS:The cone-beam CT and lateral cephalometric radiograph data of 118 adolescent orthodontic patients were collected.Firstly,the cone-beam CT image was reconstructed in 3D imaging software.After reconstruction,two types of cone-beam CT images with different integrated thicknesses were selected in the sagittal interface and transformed into two-dimensional images,which were named ICB-1 and ICB-2,respectively.The Zhibeiyun system was used to measure and calculate the angle between the concave base of the second cervical vertebra and the lower edge of the vertebral body(@2),the ratio of the third cervical spine to the posterior height(AH3/PH3),the ratio of height to width of the fourth cervical spine(H4/W4)in lateral cephalometric radiograph,ICB-1,ICB-2 and the cervical vertebral bone age.After an interval of two weeks,20 adolescents were randomly selected to repeat the above measurements.The intraclass correlation coefficient(ICC)method was used to evaluate the repeatability of the three images in measuring cervical bone age.Paired t-test was used to analyze the consistency of cervical bone age measurements between the three images.The Kappa test was used to analyze the consistency of cervical vertebral bone age staging assessment between the three images. RESULTS AND CONCLUSION:(1)ICC of AH3/PH3 in the lateral cephalometric radiograph group was<0.9,and the ICC of other measurement items in each group was>0.9.(2)Paired t-test results showed that there were statistical differences in AH3/PH3 and H4/W4 between the ICB-1 group and lateral cephalometric radiograph group and between the ICB-1 group and ICB-2 group(P<0.05),and there were no statistically significant differences in the other items between the three groups(P>0.05).(3)The Kappa test results showed that the Kappa coefficients of the two groups were all more than 0.8 according to the staging of cervical vertebral bone age in three groups(P<0.001).(4)It is indicated that the repeatability of ICB-1 and ICB-2 in the measurement of cervical vertebral bone age is better than that of lateral cephalometric radiographs.Lateral cephalometric radiographs,ICB-1 and ICB-2 have good consistency in the measurement of cervical vertebral bone age,but considering the integrity of cervical vertebra structure,ICB-2 is more suitable for quantitative analysis of cervical vertebral bone age than ICB-1.

Aim To investigate the effects of the phos-phodiesterase 8(PDE8)inhibitor PF-04957325 on learning and memory,anxiety and depression in Alzhe-imer's disease(AD)mice induced by Okadaic acid(OA),and to explore its mechanism.Methods Twenty-one 2-month-old male C57BL/6J mice were se-lected for the experiment and randomly divided into the control group,AD model group,and PDE8 inhibitor group(0.1 mg·kg-1).AD model was induced by bi-lateral hippocampal localization injection of OA(50 ng on each side)in the model and PDE8 inhibitor groups of mice.Two days after the injection of OA,PDE8 in-hibitor group was given 0.1 mg·kg-1 drug,while the AD model groups and control group were given with the same volume of vehicle for 21 consecutive days.On day 13 of inhibitor administration,behavioral tests re-lated to learning and memory abilities,anxiety and de-pressive behaviors were performed in mice.HE stai-ning was used to observe the morphology of neuronal cells in the DG,CA1,and CA3 regions of the hippo-campus of mice,and Western blot was used to detect the levels of phosphorylated Tau proteins at different sites within the hippocampus of mice as well as the ex-pression of proteins related to the PDE8/cAMP/CREB pathway.Results Compared with the control group,the Y-maze Spontaneous alternation,Recognition index of NOR and Latency of PAT were significantly shorter(P＜0.01),and Entries times、Time in the target quadrant of MWM were reduced(P＜0.05)in the AD model group,which showed a decrease in the ability of learning and memory,whereas the administration of PF-04957325 significantly improved the ability of learning and memory in the AD mice;mice in the AD model group showed a significant decrease in the num-ber of entries into the central area of the OFT and the time spent in the central area(P＜0.05),and a sig-nificant increase in the Immobility time of TST(P＜0.01),suggesting that the mice had anxiety and de-pression,and the administration of PF-04957325 did not improve the anxious behavior of the mice,but im-proved the depressed behavior to a certain extent;the hippocampus of the AD model group mice showed ker-nel solidification in the DG,CA1 and CA3 regions,and neurons were not neatly arranged,and the admin-istration of PF-04957325 could alleviate the damage of hippocampal nerve cells in mice.Compared with the control group,the phosphorylation levels of Tau protein Ser1 99,Ser396 and Ser202 sites in the hippocampus of mice in the AD model group were significantly in-creased(P＜0.01),the expression of PDE8A and PDE8B proteins was significantly increased(P＜0.01),and the expression of p-PKA/PKA and BDNF proteins was decreased(P＜0.05),after administra-tion of PF-04957325,the phosphorylation levels of Tau protein Ser396 and Ser202 sites were significantly re-duced(P＜0.01),PDE8A and PDE8B protein ex-pression was significantly decreased(P＜0.01),and p-PKA/PKA,p-CREB/CREB and BDNF protein ex-pression was significantly increased(P＜0.01).Con-clusion PDE8 inhibitor PF-04957325 can improve learning memory ability,reduce cognitive dysfunction,restore Tau protein function,and attenuate neuronal cell damage in the hippocampus of AD mice with amel-iorative effects.The mechanism of action may be relat-ed to the activation of PDE8/cAMP/CREB pathway and inhibition of Tau protein phosphorylation.

As a recognized rare and highly fatal disease, hereditary angioedema (HAE) is difficult to diagnose and characterized by recurrent edema involving the head, limbs, genitals and larynx, etc. Diagnosis of HAE is not difficult. However, low incidence and lack of clinical characteristics lead to difficulty of doctors on timely diagnosis and correct intervention for HAE patients. Therefore, it is crucial to improve the awareness of this disease and prevent its recurrence. for HAE patients. In view of absent cognition of doctors and the general public on HAE, patients often suffer from sudden death or become disabled due to laryngeal edema which cannot be treated in time. Thus, based on the Internet mobile terminal platform, the team set up an all-day rapid emergency response system which is provided for HAE patients by setting up "one-click help". The aim is to offer optimization on overall management of HAE and designed the intelligent follow-up management to provide timely assistance and specialized suggestion for patients with acute attacks.
Humans ; Angioedemas, Hereditary/drug therapy*

Allergic diseases affect about 40% of the world's population. Environmental factors are important in the occurrence and development of allergic diseases. Dust mites are one of the most important allergens in the indoor environment. The World Health Organization proposes the "four-in-one, combination of prevention and treatment" treatment principle for allergic diseases, in which environmental control to avoid or reduce allergens is the first choice for treatment. Modern people spend much more time at home (including sleeping) than outdoors, and the control of the home environment is particularly critical. This practice introduces the hypoallergenic home visit program, which including home environment assessment, environmental and behavioral intervention guidance, and common household hypoallergenic supplies and service guidance for the patient's home environment. The real-time semi-quantitative testing of dust mite allergens, qualitative assessments of other indoor allergens, record of patients' household items and lifestyle, and precise, individualized patient prevention and control education will be conducted. The hypoallergenic home visit program improves the doctors' diagnosis and treatment data dimension, and becomes a patient management tool for doctors outside the hospital. It also helps patients continue to scientifically avoid allergens and irritants in the environment, effectively build a hypoallergenic home environment, reduce exposure to allergens in the home environment, and achieve the goal of combining the prevention and treatment of allergic diseases.
Humans ; Hospitals ; Life Style ; Sleep

As a recognized rare and highly fatal disease, hereditary angioedema (HAE) is difficult to diagnose and characterized by recurrent edema involving the head, limbs, genitals and larynx, etc. Diagnosis of HAE is not difficult. However, low incidence and lack of clinical characteristics lead to difficulty of doctors on timely diagnosis and correct intervention for HAE patients. Therefore, it is crucial to improve the awareness of this disease and prevent its recurrence. for HAE patients. In view of absent cognition of doctors and the general public on HAE, patients often suffer from sudden death or become disabled due to laryngeal edema which cannot be treated in time. Thus, based on the Internet mobile terminal platform, the team set up an all-day rapid emergency response system which is provided for HAE patients by setting up "one-click help". The aim is to offer optimization on overall management of HAE and designed the intelligent follow-up management to provide timely assistance and specialized suggestion for patients with acute attacks.
Humans ; Angioedemas, Hereditary/drug therapy*

Allergic diseases affect about 40% of the world's population. Environmental factors are important in the occurrence and development of allergic diseases. Dust mites are one of the most important allergens in the indoor environment. The World Health Organization proposes the "four-in-one, combination of prevention and treatment" treatment principle for allergic diseases, in which environmental control to avoid or reduce allergens is the first choice for treatment. Modern people spend much more time at home (including sleeping) than outdoors, and the control of the home environment is particularly critical. This practice introduces the hypoallergenic home visit program, which including home environment assessment, environmental and behavioral intervention guidance, and common household hypoallergenic supplies and service guidance for the patient's home environment. The real-time semi-quantitative testing of dust mite allergens, qualitative assessments of other indoor allergens, record of patients' household items and lifestyle, and precise, individualized patient prevention and control education will be conducted. The hypoallergenic home visit program improves the doctors' diagnosis and treatment data dimension, and becomes a patient management tool for doctors outside the hospital. It also helps patients continue to scientifically avoid allergens and irritants in the environment, effectively build a hypoallergenic home environment, reduce exposure to allergens in the home environment, and achieve the goal of combining the prevention and treatment of allergic diseases.
Humans ; Hospitals ; Life Style ; Sleep