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.

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.

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.

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.

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.

This study developed a core outcome set(COS) for traditional Chinese medicine(TCM) interventions in diabetic peripheral neuropathy(DPN), standardizing evaluation metrics for TCM efficacy and providing a new framework for DPN treatment and management. A systematic search was conducted across databases, including CNKI, Wanfang, and PubMed, targeting clinical trial literature published between January 1, 2013, and January 1, 2023. The search focused on extracting outcome indicators and measurement tools used in TCM treatments for DPN. Retrospective data collection was performed from January 2018 to June 2023, involving 200 DPN patients hospitalized at the Department of Endocrinology of the First Affiliated Hospital of Anhui University of Chinese Medicine. Additionally, semi-structured interviews were conducted with inpatients, outpatients, their families, and nursing staff to further refine and enhance the list of outcome indicators. After two rounds of Delphi questionnaire survey and consensus meeting, a consensus was reached. The study initially retrieved 3 421 publications, of which 170 met the inclusion criteria after review. These publications, combined with retrospective analysis and semi-structured interviews, supplemented the list of indicators. After two rounds of Delphi surveys, experts agreed on 24 indicators and 6 measurement tools. The final COS determined by expert consensus meeting included 5 domains and 13 outcome indicators: neurological function signs, quality of life, TCM syndrome score, nerve conduction velocity, current perception threshold test, fasting blood glucose, 2 h postprandial blood glucose, glycated hemoglobin, complete blood count, urinalysis, liver function test, kidney function test, and electrocardiogram.
Humans ; Diabetic Neuropathies/drug therapy* ; Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal/therapeutic use* ; Retrospective Studies ; Treatment Outcome ; Male ; Female

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.

OBJECTIVE To prepare hyaluronic acid(HA)-modified emodin(EMD)-contained multi-walled carbon nanotubes(MWCNTs)drug delivery system(HA-MWCNTs-EMD)and explore its in vitro inhibitory effect on breast cancer cells.METHODS EMD was loaded onto MWCNTs to prepare a drug delivery system MWCNTs-EMD;subsequently,the system was further modified with HA to obtain the drug delivery system HA-MWCNTs-EMD.The two drug delivery systems mentioned above were characterized.With free EMD as the reference,the drug release in vitro of the above two drug delivery systems was investigated;the uptake of EMD by two breast cancer cells(MCF-7,MDA-MB-231 cells)was detected.The impacts of the above two drug delivery systems on the expression of surface glycoprotein differentiation group 44(CD44),activity,apoptosis and lactate dehydrogenase(LDH)release of two breast cancer cells were detected.RESULTS The encapsulation efficiencies of MWCNTs-EMD and HA-MWCNTs-EMD were both(63.52±2.74)%,with drug loading rates of(25.01±1.83)%and(12.13±1.96)%,particle sizes of(865.95±2.16)and(351.86±1.68)nm,polydispersity indexes of 0.54±0.02 and 0.23±0.01,and Zeta potentials of(23.87±0.14)and(-42.79±0.39)mV,respectively.The 2,4,6,8,10,12 and 24-hour cumulative release rates of EMD in MWCNTs-EMD and HA-MWCNTs-EMD were significantly lower than those in free EMD,while the cumulative release rate of HA-MWCNTs-EMD was significantly higher than that of MWCNTs-EMD(P＜0.05);the EMD uptakes of MWCNTs-EMD and HA-MWCNTs-EMD by the two types of breast cancer cells were significantly higher than their uptake of free EMD(P＜0.05).Compared with the free EMD group,the MWCNTs-EMD and MWCNTs-EMD groups showed significantly higher apoptosis rate and LDH release,significantly lower surface CD44 expression(except for the MWCNTs-EMD group)and cell viability in both cell types,and the effect of HA-MWCNTs-EMD was more pronounced(P＜0.05).CONCLUSIONS A novel drug delivery system HA-MWCNTs-EMD loaded with EMD is developed successfully;the drug delivery system has a certain slow-release effect,which can significantly reduce the activity of breast cancer cells,promote their apoptosis and increase the release of LDH,and the above anti-breast cancer effect is significantly stronger than that of free EMD and MWCNTs-EMD.