OBJECTIVE: To assess the safety and topical efficacy of prim-O-glucosylcimifugin (POG) and investigate the molecular mechanisms of its therapeutic effects in atopic dermatitis (AD). METHODS: The effects of POG on human keratinocyte cell viability and its anti-inflammatory properties were evaluated using cell counting kit-8 assay and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Subsequently, the impact of POG on the differentiation of cluster of differentiation (CD) 4⁺ T cell subsets, including T-helper type (Th) 1, Th2, Th17, and regulatory T (Treg), was examined through in vitro experiments. Network pharmacology analysis was used to elucidate POG's therapeutic mechanisms. Furthermore, the therapeutic potential of topically applied POG was further evaluated in a calcipotriol-induced mouse model of AD. The protein and transcript levels of inflammatory markers, including cytokines, lymphocyte-specific protein tyrosine kinase (Lck) mRNA, and LCK phosphorylation (p-LCK), were quantified using immunohistochemistry, RT-qPCR, and Western blot analysis. RESULTS: POG was able to suppress cell proliferation and downregulate the transcription of interleukin 4 (Il4) and Il13 mRNA. In vitro experiments indicated that POG significantly inhibited the differentiation of Th2 cells, whereas it exerted negligible influence on the differentiation of Th1, Th17 and Treg cells. Network pharmacology identified LCK as a key therapeutic target of POG. Moreover, the topical application of POG effectively alleviated skin lesions in the calcipotriol-induced AD mouse models without causing pathological changes in the liver, kidney or spleen tissues. POG significantly reduced the levels of Il4, Il5, Il13, and thymic stromal lymphopoietin (Tslp) mRNA in the AD mice. Concurrently, POG enhanced the expression of p-LCK protein and Lck mRNA. CONCLUSION Our research revealed that POG inhibits Th2 cell differentiation by promoting p-LCK protein expression and hence effectively alleviates AD-related skin inflammation. Please cite this article as: Zhao H, Ma X, Wang H, Ding XJ, Kuai L, Song JK, Zhang Z, Yang D, Gao CJ, Li B, Zhou M. Prim-O-glucosylcimifugin mitigates atopic dermatitis by inhibiting Th2 differentiation through LCK phosphorylation modulation. J Integr Med. 2025; 23(3): 309-319.
Dermatitis, Atopic/drug therapy* ; Animals ; Humans ; Cell Differentiation/drug effects* ; Phosphorylation/drug effects* ; Mice ; Th2 Cells/drug effects* ; Keratinocytes/drug effects* ; Disease Models, Animal ; Mice, Inbred BALB C ; Calcitriol/analogs & derivatives*

Objective:To explore the diagnostic value of routine magnetic resonance imaging (MRI) findings for early detection of dural arteriovenous fistulas (DAVF).Methods:A retrospective collection of 53 patients with DAVF confirmed by digital subtraction angiography (DSA) at the Affiliated Hospital of Qingdao University from September 2018 to June 2023 was conducted. All patients underwent routine non-enhanced and enhanced MRI scans before treatment, with 30 patients also receiving magnetic resonance angiography (MRA) examination. Medical records were reviewed, and basic patient information, clinical symptoms, and imaging markers [pial venous engorgement (PVE), cerebral hemorrhage, subarachnoid hemorrhage, vasogenic edema, venous infarction, medullary veins engorgement (MVE), parenchymal enhancement, encephalopathy mimics] were recorded. The Cognard grading was carried out in accordance with the manifestations shown by DSA.Results:Seventy-seven percent (41/53) of patients exhibited PVE on the brain surface, with 95% (39/41) of these cases showing localized PVE on one hemisphere or even within a single brain lobe. Approximately 64% (34/53) of these PVEs were detectable on conventional T 2-weighted imaging. Among the 30 patients who underwent MRA, only 50% (15/30) showed evidence of PVE on both T 2WI and MRA, while an additional 23% (7/30) had PVE only on MRA. About 38% (20/53) of patients presented with isolated vasogenic edema, with 70% (14/20) of these cases demonstrating PVE on T 2WI. Twenty-six percent (14/53) of patients had intracranial hemorrhage, and 11 of these patients demonstrated positive signs of PVE. Parenchymal enhancement was primarily observed in subarachnoid structures in 11% (6/53) of patients, with 5/6 showing PVE on the brain surface or spinal cord surface. Venous infarction (4%, 2/53) and MVE (4%, 2/53) were more commonly seen in high Cognard grade DAVF, whereas encephalopathy mimics (4%, 2/53) were frequently encountered in low Cognard grade DAVF. Conclusions:PVE on the brain surface is a direct sign for the diagnosis of DAVF on routine MRI, yet it is often subtle. Familiarity with common indirect signs is of great importance for the early diagnosis of DAVF.

Objective:To explore the diagnostic value of routine magnetic resonance imaging (MRI) findings for early detection of dural arteriovenous fistulas (DAVF).Methods:A retrospective collection of 53 patients with DAVF confirmed by digital subtraction angiography (DSA) at the Affiliated Hospital of Qingdao University from September 2018 to June 2023 was conducted. All patients underwent routine non-enhanced and enhanced MRI scans before treatment, with 30 patients also receiving magnetic resonance angiography (MRA) examination. Medical records were reviewed, and basic patient information, clinical symptoms, and imaging markers [pial venous engorgement (PVE), cerebral hemorrhage, subarachnoid hemorrhage, vasogenic edema, venous infarction, medullary veins engorgement (MVE), parenchymal enhancement, encephalopathy mimics] were recorded. The Cognard grading was carried out in accordance with the manifestations shown by DSA.Results:Seventy-seven percent (41/53) of patients exhibited PVE on the brain surface, with 95% (39/41) of these cases showing localized PVE on one hemisphere or even within a single brain lobe. Approximately 64% (34/53) of these PVEs were detectable on conventional T 2-weighted imaging. Among the 30 patients who underwent MRA, only 50% (15/30) showed evidence of PVE on both T 2WI and MRA, while an additional 23% (7/30) had PVE only on MRA. About 38% (20/53) of patients presented with isolated vasogenic edema, with 70% (14/20) of these cases demonstrating PVE on T 2WI. Twenty-six percent (14/53) of patients had intracranial hemorrhage, and 11 of these patients demonstrated positive signs of PVE. Parenchymal enhancement was primarily observed in subarachnoid structures in 11% (6/53) of patients, with 5/6 showing PVE on the brain surface or spinal cord surface. Venous infarction (4%, 2/53) and MVE (4%, 2/53) were more commonly seen in high Cognard grade DAVF, whereas encephalopathy mimics (4%, 2/53) were frequently encountered in low Cognard grade DAVF. Conclusions:PVE on the brain surface is a direct sign for the diagnosis of DAVF on routine MRI, yet it is often subtle. Familiarity with common indirect signs is of great importance for the early diagnosis of DAVF.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective:Trigeminal neuralgia(TN)is a severe chronic neuropathic pain that mainly affects the distribution area of the trigeminal nerve with limited treating efficacy.There are numerous treatments for TN,but currently the main clinical approach is to suppress pain by carbamazepine(CBZ).Brain-derived neurotrophic factor(BDNF)is closely related to chronic pain.This study aims to determine the effects of CBZ treatment on BDNF expression in both the trigeminal ganglion(TG)and serum of TN via a chronic constriction injury of the infraorbital nerve(ION-CCI)rat model. Methods:The ION-CCI models were established in male Sprague-Dawley rats and were randomly divided into a sham group,a TN group,a TN+low-dose CBZ treatment group(TN+20 mg/kg CBZ group),a TN+medium-dose CBZ treatment group(TN+40 mg/kg CBZ group),and a TN+high-dose CBZ treatment group(TN+80 mg/kg CBZ group).The mechanical pain threshold in each group of rats was measured regularly before and after surgery.The expressions of BDNF and tyrosine kinase receptor B(TrkB)mRNA in TGs of rats in different groups were determined by real-time PCR,and the expression of BDNF protein on neurons in TGs was observed by immunofluorescence.Western Blotting was used to detect the protein expression of BDNF,TrkB,extracellular regulated protein kinases(ERK),and phospho-extracellular regulated protein kinases(p-ERK)in TGs of rats in different groups.The expression of BDNF in the serum of rats in different groups was detected by enzyme-linked immunosorbent assay(ELISA). Results:The results of mechanical pain sensitivity showed that there was no significant difference in the mechanical pain threshold in the right facial sensory area of the experimental rats in each group before surgery(all P>0.05).From the 3rd day after operation,the mechanical pain threshold of rats in the TN group was significantly lower than that in the sham group(all P<0.01),and the mechanical pain threshold of rats in the TN+80 mg/kg CBZ group,the TN+40 mg/kg CBZ group,and the TN+20 CBZ mg/kg group was higher than that in the TN group(all P<0.05).The BDNF and TrkB mRNA and protein expressions in TGs of rats in the TN group were higher than those in the sham group(all P<0.05),and those in the TN+80 mg/kg CBZ group,the TN+40 mg/kg CBZ group,and the TN+20 mg/kg CBZ group were lower than the TN group(all P<0.05).The p-ERK levels in TG of rats in the TN+80 mg/kg CBZ group,the TN+40 mg/kg CBZ group,and the TN+20 mg/kg CBZ group were significantly decreased compared with the TN group(all P<0.05).The BDNF and neuron-specific nuclear protein(NeuN)were mainly co-expressed in neuron of TGs in the TN group and they were significantly higher than those in the sham group(all P<0.05).The co-labeled expressions of BDNF and NeuN in TGs of the TN+ 80 mg/kg CBZ group,the TN+40 mg/kg CBZ group,and the TN+20 mg/kg CBZ group were lower than those in the TN group(all P<0.05).The results of ELISA showed that the level of BDNF in the serum of the TN group was significantly higher than that in the sham group(P<0.05).The levels of BDNF in the TN+80 mg/kg CBZ group,the TN+40 mg/kg CBZ group,and the TN+20 mg/kg CBZ group were lower than those in the TN group(all P<0.05).Spearman correlation analysis showed that the BDNF level in serum was negatively correlated with mechanical pain threshold(r=-0.650,P<0.01). Conclusion:CBZ treatment can inhibit the expression of BDNF and TrkB in the TGs of TN rats,reduce the level of BDNF in serum of TN rats and the phosphorylation of ERK signaling pathway,so as to inhibit TN.The serum level of BDNF can be considered as an indicator for the diagnosis and prognosis of TN.

Traumatic dental injuries(TDIs)of teeth occur frequently in children and adolescents.TDIs that impact the periodontal tissues and alveolar tissue can be classified into concussion,subluxation,extrusive luxation,intrusive luxation,lateral luxation,and avulsion.In these TDIs,management of injured soft tissue,mainly periodontal ligament,and dental pulp,is crucial in maintaining the function and longevity of the injured teeth.Factors that need to be considered for management in laxation injuries include the maturation stage of the traumatic teeth,mobility,direction of displacement,distance of displacement,and whether there are alveolar fractures.In avulsion,the maturation stage of the permanent tooth,the out-socket time,storage media/condition of the avulsed tooth,and management of the PDL should also be considered.Especially,in this review,we have subdivided the immature tooth into the adolescent tooth(Nolla stage 9)and the very young tooth(Nolla stage 8 and below).This consensus paper aimed to discuss the impacts of those factors on the trauma management and prognosis of TDI to provide a streamlined guide for clinicians from clinical evaluation,diagnostic process,management plan decision,follow-up,and orthodontic treatment for tooth luxation and avulsion injuries.

Traumatic dental injuries(TDIs)of teeth occur frequently in children and adolescents.TDIs that impact the periodontal tissues and alveolar tissue can be classified into concussion,subluxation,extrusive luxation,intrusive luxation,lateral luxation,and avulsion.In these TDIs,management of injured soft tissue,mainly periodontal ligament,and dental pulp,is crucial in maintaining the function and longevity of the injured teeth.Factors that need to be considered for management in laxation injuries include the maturation stage of the traumatic teeth,mobility,direction of displacement,distance of displacement,and whether there are alveolar fractures.In avulsion,the maturation stage of the permanent tooth,the out-socket time,storage media/condition of the avulsed tooth,and management of the PDL should also be considered.Especially,in this review,we have subdivided the immature tooth into the adolescent tooth(Nolla stage 9)and the very young tooth(Nolla stage 8 and below).This consensus paper aimed to discuss the impacts of those factors on the trauma management and prognosis of TDI to provide a streamlined guide for clinicians from clinical evaluation,diagnostic process,management plan decision,follow-up,and orthodontic treatment for tooth luxation and avulsion injuries.

OBJECTIVE: To investigate the effects and mechanisms of Kindlin-2 on uterus development and reproductive capacity in female mice. METHODS: Cdh16-Cre tool mice and Kindlin-2^flox/flox mice were used to construct the mouse model of uterus specific knockout of Kindlin-2, and the effects of Kindlin-2 deletion on uterine development and reproduction capacity of female mice were observed. High expression and knockdown of Kindlin-2 in endometrial cancer cell lines HEC-1 and Ish were used to detect the regulation of mammalian target of rapamycin (mTOR) signaling pathway. In addition, uterine proteins of the female mice with specific knockout of Kindlin-2 and female mice in the control group were extracted to detect the protein levels of key molecules of mTOR signaling pathway and Hippo signaling pathway. RESULTS: The mouse model of uterine specific knockout of Kindlin-2 was successfully constructed. The knockout efficiency of Kindlin-2 in mouse uterus was identified and verified by mouse tail polymerase chain reaction (PCR), Western blot protein identification, immunohistochemical staining (IHC) and other methods. Compared with the control group, the female mice with uterus specific deletion of Kindlin-2 lost weight, seriously impaired reproductive ability, and the number of newborn mice decreased, but the proportion of the female mice and male mice in the newborn mice did not change. Hematoxylin eosin staining (HE) experiment showed that the endometrium of Kindlin-2 knockout group was incomplete and the thickness of uterine wall became thinner. In terms of mechanism, the deletion of Kindlin-2 in endo-metrial cancer cell lines HEC-1 and Ish could downregulate the protein levels of mTOR, phosphorylated mTOR, adenosine monophosphate-activated protein kinase (AMPK), phosphorylated AMPK and phosphorylated ribosomal protein S6 (S6), and the mTOR signal pathway was inhibited. It was found that the specific deletion of Kindlin-2 could upregulate the protein levels of Mps one binding 1 (MOB1) and phosphorylated Yes-associated protein (YAP) in the uterus of the female mice, and the Hippo signal pathway was activated. CONCLUSION Kindlin-2 inhibits the development of uterus by inhibiting mTOR signal pathway and activating Hippo signal pathway, thereby inhibiting the fertility of female mice.
AMP-Activated Protein Kinases/metabolism* ; Adenosine Monophosphate/metabolism* ; Animals ; Cadherins/metabolism* ; Cytoskeletal Proteins/metabolism* ; Endometrium/metabolism* ; Eosine Yellowish-(YS)/metabolism* ; Female ; Hematoxylin/metabolism* ; Hippo Signaling Pathway ; Male ; Mammals/metabolism* ; Mice ; Muscle Proteins ; Ribosomal Protein S6/metabolism* ; Sirolimus/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; YAP-Signaling Proteins

Objective Circular RNAs (circRNAs) are non-coding RNAs (ncRNA) circularized without a 3' polyadenylation [poly-(A)] tail or a 5' cap, resulting in a covalently closed loop structure. circRNAs were first discovered in RNA viruses in the 1970s, but only a small number of circRNAs were discovered at that time due to limitations in traditional polyadenylated transcriptome analyses. With the development of specific biochemical and computational methods, recent studies have shown the presence of abundant circRNAs in eukaryotic transcriptomes. circRNAs play vital roles in many physiological and pathological processes, such as acting as miRNA sponges, binding to RNA-binding proteins (RBPs), acting as transcriptional regulatory factors, and even serving as translation templates. Current evidence has shown that circRNAs can be potentially used as excellent biomarkers for diagnosis, therapeutic effect evaluation, and prognostic assessment of a variety of diseases, and they may also provide effective therapeutic targets due to their stability and tissue and development-stage specificity. This review focuses on the properties of circRNAs and their immune relationship to disease, and explores the role of circRNAs in immune-related diseases and the directions of future research.
Biomarkers ; MicroRNAs/genetics* ; RNA, Circular ; Transcriptome

Objective:To investigate the distribution and morphological characteristics of brain magnetic resonance imaging (MRI) lesions in patients with myelin oligodendrocyte glycoprotein (MOG) antibody related demyelinating diseases and aquaporin-4 (AQP4) antibody positive neuromyelitis optica spectrum disorders (NMOSD) and their clinical value in early diagnosis.Methods:A total of 35 patients with MOG antibody related demyelinating diseases [20 males and 15 females; aged 31 (25, 43) years] and 36 patients with AQP4 antibody positive NMOSD [3 males and 33 females; aged 42 (29, 54) years] were collected retrospectively from September 2018 to June 2021 in Chenzhou First People′s Hospital and the Affiliated Hospital of Qingdao University which were classified as MOG group and AQP4 positive group respectively. All patients underwent routine cranial MRI scanning before treatment and the location, shape and quantity of intracranial lesions were recorded. Wilcoxon rank sum test was used to compare the number of different types of lesions between the two groups. Logistic regression analysis was used to evaluate the significance of different lesions for the two diseases.Results:There were 7 types of lesions with significant differences in different parts and shapes. Stepwise Logistic regression showed that cortical and juxtacortical lesions ( OR=21.91, 95% CI 3.09-61.69, P<0.05) and infratentorial peripheral white matter lesions ( OR=10.48, 95% CI 2.00-18.89, P<0.05) were the most important risk factors in the MOG group. The incidence of cortical and juxtacortical lesions in the MOG group was 51.4% (18/35), which was higher than that in the AQP4 positive group (2.8%, 1/36; χ2=19.02, P<0.01). The incidence of infratentorial peripheral white matter lesions in the MOG group was 31.4% (11/35), which was higher than that in the AQP4 positive group (5.6%, 2/36; χ2=6.31, P<0.05). Receiver operating characteristic (ROC) curve showed that peripheral lesions [including 6 types of lesions such as supratentorial soft meningitis, cortical encephalitis, cortical and juxtacortical lesions, infratentorial soft meningitis, infratentorial soft meningeal demyelination and infratentorial peripheral lesions, area under curve (AUC)=0.93] were more important than cortical and juxtacortical lesions (AUC=0.75) and central lesions (supratentorial paraventricular white matter lesions, diencephalon, infratentorial paraventricular lesions,AUC=0.64), which had higher diagnostic efficiency. Conclusions:The incidence of intracranial lesions in MOG antibody related demyelinating disease was higher than that in AQP4 positive NMOSD, and the distribution and morphology of intracranial MRI lesions in the two diseases had their characteristic manifestations. Identifying the distribution patterns of peripheral lesions (distributed along pia mater) and central lesions (distributed along ependyma) had a certain reference significance for distinguishing the two groups of diseases.