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.

OBJECTIVES: To observe the effects of acupoint application with turmeric blistering moxibustion plaster on pain, shoulder range of motion (ROM) and upper limb motor function in the patients with post-stroke hemiplegic shoulder pain (PSHSP). METHODS: Eighty-two patients with PSHSP were randomly divided into an observation group (41 cases, 1 case was eliminated, 4 cases dropped out) and a control group (41 cases, 2 cases were eliminated and 2 cases dropped out). The routine treatment, nursing care and rehabilitation training were performed in the control group. On the basis of the intervention as the control group, in the observation group, the turmeric blistering moxibustion plaster was applied to bilateral ashi points, Jianyu (LI 15), Jianliao (TE 14), Binao (LI 14), Shousanli (LI 10) and Hegu (LI 4), once a day, remained for 6 hours each time. This moxibustion therapy was operated 5 times weekly, one course of treatment consisted of 2 weeks and 2 courses were required. Separately, before treatment and after 2 and 4 weeks of treatment, the score of visual analogue scale (VAS), shoulder ROM and the score of upper limbs in Fugl-Meyer assessment (U-FMA) were observed in the two groups. RESULTS: VAS scores were lower (P<0.05), ROM in shoulder flexion, abduction, internal rotation and external rotation was larger (P<0.05), and U-FMA scores were higher (P<0.05) after 2 and 4 weeks of treatment when compared with those before treatment in the two groups. After 4 weeks of treatment, VAS score decreased (P<0.05), and ROM in shoulder flexion, abduction, internal rotation, external rotation and U-FMA score increased (P<0.05) in comparison with those after 2 weeks of treatment in either group. In the observation group, VAS scores were dropped (P<0.05) after 2 and 4 weeks of treatment respectively, and ROM of shoulder flexion and abduction enlarged after 2 weeks of treatment (P<0.05) when compared with those in the control group. After 4 weeks of treatment, ROM in shoulder flexion, abduction, internal rotation and external rotation in the observation group was larger (P<0.05) and U-FMA score was higher (P<0.05) than those in the control group. CONCLUSIONS Acupoint application with turmeric blistering moxibustion plaster may effectively reduce the degree of shoulder pain and improve the shoulder range of motion and the upper limb motor function in the patients with post-stroke hemiplegic shoulder pain.
Humans ; Shoulder ; Moxibustion ; Shoulder Pain/therapy* ; Acupuncture Points ; Curcuma ; Hemiplegia/therapy* ; Treatment Outcome

Nonobstructive azoospermia (NOA) is a severe condition in infertile men, and increasing numbers of causative genes have been identified during the last few decades. Although certain causative genes can explain the presence of NOA in some patients, a proportion of NOA patients remain to be addressed. This study aimed to investigate potential high-risk genes associated with spermatogenesis in idiopathic NOA patients by whole-exome sequencing. Whole-exome sequencing was performed in 46 male patients diagnosed with NOA. First, screening was performed for 119 genes known to be related to male infertility. Next, further screening was performed to determine potential high-risk causative genes for NOA by comparisons with 68 healthy male controls. Finally, risk genes with high/specific expression in the testes were selected and their expression fluctuations during spermatogenesis were graphed. The frequency of cystic fibrosis transmembrane conductance regulator (CFTR) gene pathogenic variant carriers was higher in the NOA patients compared with the healthy controls. Potential risk genes that may be causes of NOA were identified, including seven genes that were highly/specifically expressed in the testes. Four risk genes previously reported to be involved in spermatogenesis (MutS homolog 5 [MSH5], cilia- and flagella-associated protein 54 [CFAP54], MAP7 domain containing 3 [MAP7D3], and coiled-coil domain containing 33 [CCDC33]) and three novel risk genes (coiled-coil domain containing 168 [CCDC168], chromosome 16 open reading frame 96 [C16orf96], and serine protease 48 [PRSS48]) were identified to be highly or specifically expressed in the testes and significantly different in the 46 NOA patients compared with 68 healthy controls. This study on clinical NOA patients provides further evidence for the four previously reported risk genes. The present findings pave the way for further functional investigations and provide candidate risk genes for genetic diagnosis of NOA.
Humans ; Male ; Azoospermia/pathology* ; East Asian People ; Exome Sequencing ; Mutation ; Proteins/genetics*

This study aimed to investigate the therapeutic effect of Yunkang Oral Solution on the improvement of spleen deficiency and pregnancy outcomes in pregnant mice with spleen deficiency syndrome induced by irregular diet and over consumption of cold and bitter foods. To simulate human irregular diet and over consumption of cold and bitter foods leading to spleen deficiency, the pregnant mice with spleen deficiency syndrome were prepared using an alternate-day fasting and high-fat diet combined with oral administration of Sennae Folium. During the experiment, spleen deficiency-related indicators and diarrhea-related parameters were measured. Gastric and intestinal motility(gastric emptying rate and intestinal propulsion rate) were evaluated. The levels of serum ghrelin, growth hormone(GH), gastrin(Gas), total cholesterol(TC), low-density lipoprotein cholesterol(LDL-c), chorionic gonadotropin β(β-CG), progesterone(P), and estradiol(E_2) were measured. Intestinal barrier function in pregnant mice with spleen deficiency syndrome was assessed. Conception rate, ovarian coefficient, litter-bearing uterine coefficient, number of live fetuses, average fetal weight, and fetal length were calculated. The results showed that Yunkang Oral Solution significantly improved spleen deficiency-related indicators and diarrhea in pregnant mice with spleen deficiency syndrome, increased gastric emptying rate and intestinal propulsion rate, elevated the levels of gastrointestinal hormones(ghrelin, GH, and Gas) in the serum, and reduced lipid levels(TC and LDL-c), thereby improving lipid metabolism disorders. It also improved colonic tissue morphology, increased the number of goblet cells, and promoted the mRNA and protein expression of occludin and claudin-1 in colonic tissues, thereby alleviating intestinal barrier damage. Yunkang Oral Solution also regulated the levels of pregnancy hormones(β-CG, P, and E_2) in the serum of pregnant mice with spleen deficiency syndrome. Moreover, it increased the conception rate, ovarian coefficient, litter-bearing uterine coefficient, number of live fetuses, average fetal weight, and fetal length. These findings suggest that Yunkang Oral Solution can improve spleen deficiency-related symptoms in pregnant mice before and during pregnancy, regulate pregnancy-related hormones, and improve pregnancy outcomes.
Pregnancy ; Female ; Mice ; Humans ; Animals ; Spleen ; Ghrelin ; Fetal Weight ; Cholesterol, LDL ; Diarrhea

OBJECTIVE: To observe the effect of standardized Jin's three-needle therapy on limb motor function and nerve function defect in stroke patients, and to evaluate the placebo control method. METHODS: A total of 66 patients with stroke were randomly divided into a Jin's three-needle group (33 cases, 3 cases dropped off) and a placebo needle group (33 cases, 4 cases dropped off). All the patients were treated with conventional medication and rehabilitation treatment. In addition, the patients in the Jin's three-needle group were treated with standardized Jin's three-needle therapy at temporal three points, spirit four points, hand three points, foot three points, upper extremity spasm three points, lower extremity spasm three points, etc.; while the patients in the placebo needle group were treated with placebo needling at identical points. All the treatments were given once a day, 5 days a week, and 3-week treatment was given with an interval of 2 days between weeks. The scores of Fugl-Meyer assessment scale (FMA) and National Institutes of Health stroke scale (NIHSS) were observed before treatment, 10 d and 21 d into treatment, and the blind evaluation was conducted after treatment. RESULTS: On the 10 d and 21 d into treatment, the FMA scores in both groups were higher than those before treatment (P<0.01), and the NIHSS scores were lower than those before treatment (P<0.01). On the 10 d and 21 d into treatment, the FMA scores in the Jin's three-needle group were higher than those in the placebo needle group (P<0.05); on the 10 d into treatment, the NIHSS score in the Jin's three-needle group was were lower than that in the placebo needle group (P<0.05). There was no significant difference between the two groups on judging the type of treatment (P>0.05), and the consistency with the real situation was poor (Cohen's kappa coefficient<0.20). CONCLUSION The standardized Jin's three-needle therapy could effectively improve the limb motor function and nerve function defect in stroke patients. The placebo control method used in this study shows good clinical operability and masking effect.
Humans ; Acupuncture Therapy/methods* ; Acupuncture Points ; Stroke/therapy* ; Lower Extremity ; Needles ; Treatment Outcome ; Stroke Rehabilitation