1.Research on The Role of Dopamine in Regulating Sleep and Wakefulness Through Exercise
Li-Juan HOU ; Ya-Xuan GENG ; Ke LI ; Zhao-Yang HUANG ; Lan-Qun MAO
Progress in Biochemistry and Biophysics 2025;52(1):88-98
Sleep is an instinctive behavior alternating awakening state, sleep entails many active processes occurring at the cellular, circuit and organismal levels. The function of sleep is to restore cellular energy, enhance immunity, promote growth and development, consolidate learning and memory to ensure normal life activities. However, with the increasing of social pressure involved in work and life, the incidence of sleep disorders (SD) is increasing year by year. In the short term, sleep disorders lead to impaired memory and attention; in the longer term, it produces neurological dysfunction or even death. There are many ways to directly or indirectly contribute to sleep disorder and keep the hormones, including pharmacological alternative treatments, light therapy and stimulus control therapy. Exercise is also an effective and healthy therapeutic strategy for improving sleep. The intensities, time periods, and different types of exercise have different health benefits for sleep, which can be found through indicators such as sleep quality, sleep efficiency and total sleep time. So it is more and more important to analyze the mechanism and find effective regulation targets during sleep disorder through exercise. Dopamine (DA) is an important neurotransmitter in the nervous system, which not only participates in action initiation, movement regulation and emotion regulation, but also plays a key role in the steady-state remodeling of sleep-awakening state transition. Appreciable evidence shows that sleep disorder on humans and rodents evokes anomalies in the dopaminergic signaling, which are also implicated in the development of psychiatric illnesses such as schizophrenia or substance abuse. Experiments have shown that DA in different neural pathways plays different regulatory roles in sleep behavior, we found that increasing evidence from rodent studies revealed a role for ventral tegmental area DA neurons in regulating sleep-wake patterns. DA signal transduction and neurotransmitter release patterns have complex interactions with behavioral regulation. In addition, experiments have shown that exercise causes changes in DA homeostasis in the brain, which may regulate sleep through different mechanisms, including cAMP response element binding protein signal transduction, changes in the circadian rhythm of biological clock genes, and interactions with endogenous substances such as adenosine, which affect neuronal structure and play a neuroprotective role. This review aims to introduce the regulatory effects of exercise on sleep disorder, especially the regulatory mechanism of DA in this process. The analysis of intracerebral DA signals also requires support from neurophysiological and chemical techniques. Our laboratory has established and developed an in vivo brain neurochemical analysis platform, which provides support for future research on the regulation of sleep-wake cycles by movement. We hope it can provide theoretical reference for the formulation of exercise prescription for clinical sleep disorder and give some advice to the combined intervention of drugs and exercise.
2.Relationships between color Doppler ultrasound parameters and insulin sensitivity index and clinical efficacy in rats with polycystic ovary syndrome complicated with hyperinsulinemia
Xizhen SUN ; Linlin GENG ; Juan CHEN ; Wei ZHANG ; Deming SUN ; Nan LI
Chinese Journal of Comparative Medicine 2025;35(3):82-89
Objective To analyze the relationships between color Doppler ultrasound parameters and insulin sensitivity index(ISI)and clinical efficacy in rats with polycystic ovary syndrome(PCOS)combined with hyperinsulinemia(HI).Methods A total of 140 3-week-old female SD SPF-grade rats were divided randomly into a PCOS without HI model(control group,n=70)and a PCOS combined with HI model(study group,n=70).After successful modeling,we used color Doppler ultrasound to detect the physical indicators,hemodynamic indicators,and ultrasound features of rat ovaries,and draw venous blood to evaluate ISI.Rats in the study group were treated with metformin by intragastric administration.The color Doppler ultrasound parameters of the good-effect and the poor-effect group were compared and a receiver operating characteristic curve(ROC)was drawn to analyze the value of the color Doppler ultrasound parameters for evaluating the curative effect of metformin in rats with PCOS combined with HI.Results The total ovarian area(TA),ovarian volume(OV),ovarian interstitial area(SA),vascularization index(VI),blood flow index(FI),fasting insulin(FINS),and fasting blood glucose(BFG)of the research group were all greater than those of the control group,while the resistance index,pulsatility index and ISI were observed significantly lower compared with contrast,there were obvious difference(P<0.05).The color Doppler ultrasound parameters TA and SA were negatively correlated with ISI(r=-0.501,r=-0.492,respectively,P<0.05),and ovarian RI and PI were positively correlated with ISI(r=0.504,r=0.485,respectively,P<0.05).TA,OV,SA,VI,FI,VFI,PSV,PDV,low-density lipoprotein cholesterol,FPG,FINS,LH,and FSH were all significantly lower while RI and PI were significantly higher in the good-curative-effect group compared with the poor-curative-effect group(all P<0.05).According to ROC curve analysis,the sensitivity and specificity of color Doppler ultrasound parameters combined with clinical efficacy were 90.9%and 90.2%,respectively,and the area under the curve(AUC)was 0.901.Conclusions Color Doppler ultrasound parameters are closely related to ISI and therapeutic efficacy in rats with PCOS combined with HI,and may thus predict clinical efficacy in patients with these conditions.
3.Relationships between color Doppler ultrasound parameters and insulin sensitivity index and clinical efficacy in rats with polycystic ovary syndrome complicated with hyperinsulinemia
Xizhen SUN ; Linlin GENG ; Juan CHEN ; Wei ZHANG ; Deming SUN ; Nan LI
Chinese Journal of Comparative Medicine 2025;35(3):82-89
Objective To analyze the relationships between color Doppler ultrasound parameters and insulin sensitivity index(ISI)and clinical efficacy in rats with polycystic ovary syndrome(PCOS)combined with hyperinsulinemia(HI).Methods A total of 140 3-week-old female SD SPF-grade rats were divided randomly into a PCOS without HI model(control group,n=70)and a PCOS combined with HI model(study group,n=70).After successful modeling,we used color Doppler ultrasound to detect the physical indicators,hemodynamic indicators,and ultrasound features of rat ovaries,and draw venous blood to evaluate ISI.Rats in the study group were treated with metformin by intragastric administration.The color Doppler ultrasound parameters of the good-effect and the poor-effect group were compared and a receiver operating characteristic curve(ROC)was drawn to analyze the value of the color Doppler ultrasound parameters for evaluating the curative effect of metformin in rats with PCOS combined with HI.Results The total ovarian area(TA),ovarian volume(OV),ovarian interstitial area(SA),vascularization index(VI),blood flow index(FI),fasting insulin(FINS),and fasting blood glucose(BFG)of the research group were all greater than those of the control group,while the resistance index,pulsatility index and ISI were observed significantly lower compared with contrast,there were obvious difference(P<0.05).The color Doppler ultrasound parameters TA and SA were negatively correlated with ISI(r=-0.501,r=-0.492,respectively,P<0.05),and ovarian RI and PI were positively correlated with ISI(r=0.504,r=0.485,respectively,P<0.05).TA,OV,SA,VI,FI,VFI,PSV,PDV,low-density lipoprotein cholesterol,FPG,FINS,LH,and FSH were all significantly lower while RI and PI were significantly higher in the good-curative-effect group compared with the poor-curative-effect group(all P<0.05).According to ROC curve analysis,the sensitivity and specificity of color Doppler ultrasound parameters combined with clinical efficacy were 90.9%and 90.2%,respectively,and the area under the curve(AUC)was 0.901.Conclusions Color Doppler ultrasound parameters are closely related to ISI and therapeutic efficacy in rats with PCOS combined with HI,and may thus predict clinical efficacy in patients with these conditions.
4.Research progress on circadian rhythm of immune response and autoimmune diseases
Yankang FEI ; Geng SUN ; Juan LIU
Chinese Journal of Immunology 2025;41(3):698-703
The immune system is the cornerstone of the human body to resist danger and maintain homeostasis.The dysfunc-tion of the immune system leads to autoimmune diseases,tumors and other immune-related diseases.The mechanisms of the activation and regulation of the immune system is the frontier research field of life science and medicine.Circadian rhythms control individual ac-tivities and behaviors at various levels such as cells,tissues,organs,and play a key regulatory role in the immune system.Innate im-munity and adaptive immunity are strictly regulated by the biological clock,and the clock control genes in immune cells have diversi-fied effects on cell migration,development,functional differentiation and activation.This article summarizes the circadian regulation of innate and adaptive immunity,and discusses the association and potential intervention value of the biological clock with immune-re-lated diseases as a representative of autoimmune diseases.
5.Construction and evaluation of a cell model simulating the change of testicular microenvironment mediated by hypoxic and high-pressure conditions in varicocele mice
Shu-lin LIANG ; Li-guo GENG ; Ling HAN ; Chu-nan RONG ; Zhan QIN ; Juan DU ; Chao-ba HE ; Shao-ying YUAN
National Journal of Andrology 2025;31(6):483-491
Objective:Varicocele(VC)induces male infertility by mediating changes in the testicular microenvironment,in which testicular hypoxia and high-pressure are important pathological conditions.This study aims to compare the mouse spermatogenesis(GC-2spd)cells and Sertoli(TM4)cells of mouse testis after hypoxic modeling and hypoxic and high-pressure combined modeling,and to explore the feasibility of establishing a hypoxic and high-pressure combined cell model.Methods:On the basis of cell hypoxia induced by CoCl2,the complex model of testicular cell hypoxia and high pressure was constructed by changing the osmotic pressure of GC-2 and TM4 cell medium with a high concentration of NaCl solution.After selecting the intervention concentration of CoCl2 by MTT test and detecting the expression level of HIF-1α for the determination of the optimal osmotic pressure conditions of the cell model,the cells were divided into normal group,hypoxia model group and composite model group.And the levels of OS,programmed cell death,inflammatory factors,and the expression levels of pyroptosis-related proteins were compared between the normal group and the groups with different modeling methods.Results:The optimal intervention concentration of CoCl2 in GC-2 and TM4 cells was 150 and 250μmol/L,respectively,and the expression of HIF-1α was the highest in both cells under osmotic pressure of 500 mOsmol/kg(P<0.05).Compared with the normal group,the SOD levels of GC-2 and TM4 cells decreased(all P<0.05),CAT level decreased(all P<0.05),and MDA level increased(all P<0.01),and the OS level of GC-2 and TM4 cells was more obvious than that of the hy-poxia model group(all P<0.05).Compared with the normal group,apoptosis occurred in GC-2 and TM4 cells after composite model-ing(all P<0.05).Compared with the normal group,the mRNA expressions of IL-1β,IL-18,TNF-α and COX-2 in GC-2 and TM4 cells significantly increased(P<0.01)and higher than those in hypoxia model group(P<0.05)and induced pyroptosis(P<0.01).The expression level of GSDMD increased(P<0.05).Conclusion:The cell model with hypoxia and high pressure com-bined modeling can not only induce oxidative stress and apoptosis of cells better than that with hypoxia alone,but also further cause in-flammatory response damage and pyroptosis,which simulates the changes of testis microenvironment mediated by hypoxia and high pressure combined conditions in VC.This cell model can be used for studying the pathogenesis of VC-associated male infertility,evalu-ating drug efficacy,and exploring pharmacological mechanisms.
6.Brain functional magnetic resonance imaging changes in patients with depression after acupuncture treatment: ALE meta-analysis
Jing TANG ; Juan YU ; Ziyao GENG ; Yating YUE ; Jingxia ZHANG
Chinese Journal of Behavioral Medicine and Brain Science 2025;34(11):1005-1011
Objective:Through the meta-analysis of activation likelihood estimation (ALE), the functional magnetic resonance imaging research evidence of acupuncture in the treatment of depression was systematically integrated to analyze the effect of acupuncture on brain activity in patients with depression and systematically reveal its potential neural mechanism.Methods:The literatures which used functional magnetic resonance imaging to explore brain image changes of patients with depression after receiving acupuncture intervention were retrieved from CNKI, VIP database, Wanfang database, PubMed, Embase, EBSCO host MEDLINE and Web of Science database. The retrieval time is from the establishment of the database to March 2025. Data processing was performed using the ALE method by the Ginger ALE 2.3 software. The coordinates of the subjects included in the study were extracted, and the brain regions with abnormal spontaneous brain activity in patients with depression were integrated and analyzed.Results:A total of 28 articles involving 770 subjects were included. Depressed patients receiving acupuncture exhibited increased brain activity in the bilateral medial frontal gyrus and bilateral anterior cingulate cortex. Exploratory analysis revealed that depressed patients receiving acupuncture exhibited reduced activation in the left posterior cerebellar lobe (MNI: x, y, z = -6, -68, -21; x, y, z = -9, -81, -9) compared to healthy controls (voxel sum=5 824 mm 3,P<0.05). Conclusion:Patients with depression who received acupuncture intervention exhibited relatively consistent activation in brain regions compared to depressed patients who did not receive acupuncture and healthy individuals. Compared to healthy individuals, patients with depression who received acupuncture showed reduced activation in the left posterior cerebellum. It is suggested that acupuncture intervention may play a therapeutic role by regulating the functional state of emotion-related brain regions and brain networks.
7.Clinical application of metagenomic next-generation sequencing technology in pediatric urinary tract infections
Jinshan SUN ; Chaoying CHEN ; Juan TU ; Haiyun GENG ; Huarong LI ; Ling WAN ; Hongyang WANG
Chinese Journal of Applied Clinical Pediatrics 2025;40(4):268-272
Objective:To explore the diagnostic value and clinical application of metagenomic next-generation sequencing (mNGS) technology in pediatric urinary tract infections (UTI).Methods:In this retrospective study, the clinical data of children with UTI admitted to the Department of Nephrology, Children′s Hospital, Capital Institute of Pediatrics, from March 2023 to March 2024 were collected.The positive detection rates, timeliness, and consistency of mNGS technology were compared with those of urine culture.Measurement data were subject to test of normality.The independent sample t test, Chi-square test or Fisher′s exact probability test were used for comparison between groups. Results:A total of 193 patients were included.The positive detection rate of urine culture was 36.3% (70/193).Among 42 patients who underwent mNGS testing, 37 cases (88.1%) tested positive.The positive detection rate of mNGS was significantly higher than that of urine culture ( χ2=37.357, P<0.001).It took significantly less time to report mNGS results than to report urine culture results ( Z=3.524, P<0.001).In the 42 cases that underwent mNGS testing, 5 cases (11.9%) were negative for urine pathogens by both methods, and 21 cases (50.0%) were positive by mNGS but negative by urine culture.Among the remaining 16 cases (38.1%) positive by both mNGS and urine culture, 14 cases (33.3%) achieved fully matching results, 1 case (2.4%) was fully mismatched, and 1 case (2.4%) was partially matched.Comparison of the positive detection rate and the duration of anti-infective treatment prior to specimen collection between urine culture and mNGS showed that the median durations for urine culture and mNGS positivity were 5 and 20 days, and the difference was statistically significant ( χ2=0.537, P<0.001). Conclusions:mNGS technology has high sensitivity for diagnosing pathogens in pediatric UTI.Compared with urine culture, mNGS provides good consistency and significantly shortens the detection time.The positive detection rate is less affected by antimicrobial treatment.For children with UTI, especially those who have failed empirical anti-infective treatment and whose pathogen cannot be identified by urine culture, mNGS testing is recommended as early as possible.
8.Clinical efficacy and safety of a domestic calcipotriol/betamethasone dipropionate ointment in the treatment of stable plaque psoriasis: a multicenter, randomized, double-blind, controlled study
Lixin XIA ; Guang XIANG ; Qingchun DIAO ; Kun HUANG ; Shoumin ZHANG ; Shanshan LI ; Yumei LI ; Zhiqiang SONG ; Qing SUN ; Xiumin YANG ; Meng PAN ; Yuling SHI ; Shuping GUO ; Huiping WANG ; Tiechi LEI ; Xiaoyong ZHOU ; Songmei GENG ; Suchun HOU ; Juan SU ; Yong CUI ; Rixin CHEN ; Yanyan FENG ; Hongxia FENG ; Rushan XIA ; Zudong MENG ; Fang YIN ; Jingjing WANG ; Xinghua GAO
Chinese Journal of Dermatology 2025;58(11):1020-1026
Objective:To evaluate the clinical equivalence between a domestic calcipotriol/betamethasone dipropionate ointment and the originator product in the treatment of stable plaque psoriasis.Methods:A multicenter, randomized, double-blind, three-arm, parallel-group, active- and placebo-controlled study was conducted, and 449 patients aged 18 - 65 years with stable plaque psoriasis were enrolled from 25 hospitals (such as the First Affiliated Hospital of China Medical University). Eligible patients had a baseline physician's global assessment (PGA) score of ≥ 3 points, baseline body surface area (BSA) involvement of 5% - 30%, and a target lesion psoriasis area and severity index (TL-PASI) for plaque elevation of ≥ 3 points. Participants were randomly assigned in a 2:2:1 ratio to the test group ( n = 179), reference group ( n = 180), and placebo group ( n = 90), and applied the domestic calcipotriol/betamethasone dipropionate ointment, originator product, and ointment base respectively, once daily in the evening for 4 weeks. Efficacy and safety were assessed at weeks 1, 2, and 4. The primary efficacy endpoints were the treatment success rates and clinical success rates in each group at week 4. The per-protocol set (PPS) was used for the primary efficacy analysis, and the intention-to-treat (ITT) set for supplementary efficacy analysis. Equivalence between the test and reference preparations was tested using the Cochran-Mantel-Haenszel method adjusted for randomization strata. Superiority of the test and reference preparations over the placebo was also tested. Measurement data were compared among the 3 groups using analysis of variance or non-parametric tests, while treatment success rates, clinical success rates, and incidence rates of adverse reactions were compared using the chi-square test. Results:The ITT, PPS, and safety sets included 447, 420, and 448 patients, respectively. In the ITT set, patients were aged 43.6 ± 12.8 years, including 320 (71.6%) males and 127 (28.4%) females, and the disease duration was 11.21 ± 9.05 years; 316 (70.7%) had a PGA score of 3 points and 131 (29.3%) had a PGA score of 4 - 5 points. No significant differences in the baseline characteristics (including age, sex, disease duration and disease severity) were observed among the 3 groups (all P > 0.05). Based on the PPS analysis, the treatment success rates were 57.9% (99/171) in the test group, 50.3% (86/171) in the reference group, and 7.7% (6/78) in the placebo group, and the clinical success rates were 57.9% (99/171), 50.3% (86/171), and 10.3% (8/78), respectively; both the test and reference groups were superior to the placebo group in both treatment and clinical success rates (all P < 0.001) ; the rate differences for treatment success (90% confidence interval [ CI]: -1.3% - 16.4%) and clinical success (90% CI: -1.3% - 16.3%) between the test and reference groups were entirely within the pre-defined equivalence margin (-20% - 20%). Subgroup analyses by baseline PGA scores: for patients with a baseline PGA score of 3 points, the treatment success rates in the test, reference, and placebo groups were 60.8% (73/120), 52.1% (62/119), and 11.1% (6/54), respectively, and the corresponding clinical success rates were 61.7% (74/120), 53.8% (64/119), and 13% (7/54), respectively; the test and reference groups did not differ significantly in treatment or clinical success rates (both P > 0.05), but both showed higher success rates than the placebo group (all P < 0.001) ; the results of statistical comparisons among the 3 groups in patients with a baseline PGA score of 4 - 5 points were consistent with those observed in patients with a baseline PGA score of 3 points. The percentage reductions in PGA and TL-PASI scores from baseline to weeks 1, 2, and 4 showed significant differences among the 3 groups, which were significantly higher in the test and reference groups than in the placebo group (all P < 0.001), but did not differ between the test and reference groups (all P > 0.05). The primary adverse reactions were local skin reactions, such as pruritus, pain, and erythema. The incidence rates of adverse reactions were 8.9% (16/179) in the test group, 7.3% (13/179) in the reference group, and 7.8% (7/90) in the placebo group, with no significant difference among the 3 groups ( P > 0.05) . Conclusions:The domestic calcipotriol/betamethasone dipropionate ointment demonstrated clinical equivalence to the originator product in the treatment of stable plaque psoriasis, and the two agents exhibited comparable efficacy for patients with varying degrees of disease severity, and were comparable in the speed and degree of clinical improvement, with similar favorable safety profiles.
9.Clinical application of metagenomic next-generation sequencing technology in pediatric urinary tract infections
Jinshan SUN ; Chaoying CHEN ; Juan TU ; Haiyun GENG ; Huarong LI ; Ling WAN ; Hongyang WANG
Chinese Journal of Applied Clinical Pediatrics 2025;40(4):268-272
Objective:To explore the diagnostic value and clinical application of metagenomic next-generation sequencing (mNGS) technology in pediatric urinary tract infections (UTI).Methods:In this retrospective study, the clinical data of children with UTI admitted to the Department of Nephrology, Children′s Hospital, Capital Institute of Pediatrics, from March 2023 to March 2024 were collected.The positive detection rates, timeliness, and consistency of mNGS technology were compared with those of urine culture.Measurement data were subject to test of normality.The independent sample t test, Chi-square test or Fisher′s exact probability test were used for comparison between groups. Results:A total of 193 patients were included.The positive detection rate of urine culture was 36.3% (70/193).Among 42 patients who underwent mNGS testing, 37 cases (88.1%) tested positive.The positive detection rate of mNGS was significantly higher than that of urine culture ( χ2=37.357, P<0.001).It took significantly less time to report mNGS results than to report urine culture results ( Z=3.524, P<0.001).In the 42 cases that underwent mNGS testing, 5 cases (11.9%) were negative for urine pathogens by both methods, and 21 cases (50.0%) were positive by mNGS but negative by urine culture.Among the remaining 16 cases (38.1%) positive by both mNGS and urine culture, 14 cases (33.3%) achieved fully matching results, 1 case (2.4%) was fully mismatched, and 1 case (2.4%) was partially matched.Comparison of the positive detection rate and the duration of anti-infective treatment prior to specimen collection between urine culture and mNGS showed that the median durations for urine culture and mNGS positivity were 5 and 20 days, and the difference was statistically significant ( χ2=0.537, P<0.001). Conclusions:mNGS technology has high sensitivity for diagnosing pathogens in pediatric UTI.Compared with urine culture, mNGS provides good consistency and significantly shortens the detection time.The positive detection rate is less affected by antimicrobial treatment.For children with UTI, especially those who have failed empirical anti-infective treatment and whose pathogen cannot be identified by urine culture, mNGS testing is recommended as early as possible.
10.Clinical analysis of pediatric renal abscess
Jinshan SUN ; Chaoying CHEN ; Juan TU ; Haiyun GENG ; Huarong LI ; Ling WAN ; Yuchun YAN
Chinese Journal of Pediatrics 2025;63(5):524-528
Objective:To analyze the clinical characteristics of renal abscess in children and provide suggestions for early diagnosis and treatment.Methods:The clinical data including general information, laboratory data, imaging results, treatment and prognosis of 20 pediatric patients with renal abscess admitted to the Department of Nephrology, Capital Center for Children's Health Capital Medical University were analyzed retrospectively.Results:A total of 8 males and 12 females were enrolled. The age of onset was 3.0 (0.8, 9.0) years. All cases had fever. Six cases presented with abdominal pain, 6 cases had poor appetite, 5 cases had vomiting and 5 cases urinary tract irritation symptoms. Laboratory data showed elevated white blood cells 20.4 (17.4,26.3)×10 9/L, C-reactive protein 126 (77, 154)mg/L, erythrocyte sedimentation rate 60 (41,73) mm/1 h in 20 cases and procalcitonin 4.7 (1.2,33.5)μg/L in 10 cases. Totally 18 cases had pyuria. Urine culture was positive in 8 cases. Enterococcus faecium and Pseudomonas aeruginosa was detected in 2 cases. Klebsiella pneumoniae was found in 1 case after performing blood culture. Renal abscess was confirmed in all cases by doing contrast-enhanced CT scan, while only 9 cases with abscesses were identified by using renal ultrasound. There were 14 cases with renal abscess formation confirmed at onset by performing magnetic resonance imaging. Nine cases were accompanied with congenital anomalies of the kidney and urinary tract. All cases received conservative medical treatment. Intravenous broad-spectrum antibiotics were administered for 23 (14, 39) d initially, while the medication in 11 cases were upgraded to meropenem or imipenem. Oral antibiotics were continued for 23 (14, 28) d after discharge in all cases. Within 1 year of follow-up, except for 1 case of recurrence, the others had a favorable prognosis. Conclusions:Renal abscess should be suspected for children presenting with unexplained fever, vomiting, abdominal pain, elevated white blood cell count, C-reactive protein, erythrocyte sedimentation rate and pyuria. Ultrasonography is suitable for screening and follow-up, while CT or magnetic resonance imaging can be used to confirm the diagnosis. Conservative management with broad-spectrum antibiotics is effective and can be considered the first-line therapy for pediatric renal abscess.

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