ObjectiveTo explore the distribution pattern of tongue image characteristics in patients with glucolipid metabolic disorders and its main syndromes. MethodsA total of 841 patients with glucolipid metabolic disorders （disease group）， and 380 healthy subjects （control group） were included. The disease group was classified into three syndrome types： 283 cases of liver depression and spleen deficiency syndrome， 311 cases of phlegm-dampness obstruction syndrome， and 247 cases of qi stagnation and blood stasis syndrome. Tongue image data were collected using the TFDA-1 Tongue Diagnosis Instrument， and the TDAS V3.0 software was used to analyze the color， texture， and morphological features of the tongue body （TB） and tongue coating （TC） in patents with different syndromes of disease group （including lightness （L）， red-green axis （a）， yellow-blue axis （b）， luminance （Y）， difference between red signal and brightness （Cr）， difference between blue signal and brightness （Cb）， contrast （CON）， angular second moment （ASM）， entropy （ENT）， mean value （MEAN）， tongue coating area/tongue surface area （perAll）， and tongue coating area/non-coated area （perPart））. Logistic regression analysis was conducted to identify influencing factors for different syndrome types of glucolipid metabolic disorders. ResultsThe tongue body indicators TB-L， TB-Y， and TB-Cb in the disease group were significantly higher than those in the control group， while TB-a， TB-b， and TB-Cr were significantly lower. The tongue coating indicators TC-L， TC-Y， TC-Cb， perAll， and perPart in the disease group were significantly higher than those in the control group， while TC-a， TC-b， and TC-Cr were significantly lower （P＜0.05）. Comparing with the different syndromes in disease group， the TB-L and TB-Y of the liver depression and spleen deficiency syndrome， and the phlegm-damp obstruction syndrome were higher than those of the qi stagnation and blood stasis syndrome； the TB-a and TB-Cr of the phlegm-damp obstruction syndrome were lower than those of the qi stagnation and blood stasis syndrome； the perAll of the phlegm-damp obstruction syndrome was higher than that of the qi stagnation and blood stasis syndrome （P＜0.05）. In the analysis of the morphological characteristics of tongue signs， more spotted tongue in disease group compared with control group， more teeth-marked tongue in liver depression and spleen deficiency syndrome than the other two syndromes， more greasy coating in phlegm-damp obstruction syndrome， and more stasis spots of tongue in qi stagnation and blood stasis syndrome （P＜0.05）. Logistic regression analysis identified that greasy coating， spotted tongue， stasis spots of tongue， tooth-marked tongue， perAll， and TB-Cb are the influencing factors of liver depression and spleen deficiency syndrome； greasy coating， tooth-marked tongue， TC-Cb， and TC-Cr are the influencing factors of phlegm-damp obstruction syndrome； cracked tongue， stasis spots of tongue， tooth-marked tongue， and TB-Y are the influencing factors of qi stagnation and blood stasis syndrome （P＜0.05）. ConclusionCompared to healthy individuals， patients with glycolipid metabolic disorder have darker tongue color and thicker， greasy tongue coating. Glycolipid metabolic disorder patients of liver depression and spleen deficiency syndrome exhibit a reddish tongue with finer textures and more tooth marks； patients of phlegm-damp obstruction syndrome have lighter tongue coating with a coarser texture and a higher prevalence of greasy coating； patients of qi stagnation and blood stasis syndrome display lower tongue brightness with a higher prevalence of blood stasis spots.

Objective To investigate the gene expression profile of cervical exfoliated cells from woman treated by artificial cycle,and their potential association with endometrial receptivity in order to screen specific biomarkers closely related to the receptivity.Methods A total of 19 female patients were enrolled from those preparing for frozen embryo transfer(FET)at the Reproductive Center of First Medical Center of Chinese PLA General Hospital from February 2024 to October 2024.Under the artificial cycle frozen embryo transfer protocol,the endometrial tissues were collected on the 4th day after progesterone administration(P+4)to verify their endometrial receptivity status.Additionally,cervical exfoliated cells were collected on the 4th day(P+4)and the 6th day(P+6)after progesterone administration.RNA sequencing(RNA-Seq)was used to detect gene expression profiles.Differentially expressed genes(DEGs)were identified using the criteria of|log2fold change|＞1 and a false discovery rate(FDR)＜0.05,followed by bioinformatics analysis.The protein-protein interaction(PPI)network of DEGs was constructed using R software(4.4.1)and analyzed with gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)analyses.The candidate genes were identified based on the PPI network using Cytoscape software.Quantitative reverse transcription PCR(RT-qPCR)was employed to validate the target candidate genes both in vitro and in vivo.Results The rsERT confirmed that all 19 women were in state of endometrial receptivity at P+6.RNA-Seq identified 3 458 DEGs in cervical exfoliated cells between P+4 and P+6.The up-regulated DEGs were mainly enriched in the pathways associated with immune response and cell differentiation,and the down-regulated ones were mainly enriched in the pathways associated with lipid metabolism and cell proliferation.Using maximal clique Centrality(MCC)algorithm in the PPI network,the top 20 genes were selected.Among them,6 genes,such as IFIT2,OASL,MX1,RSAD2,IFIT1 and IFIT3,tied for the first place,and the 6 genes all belong to interferon-stimulated genes(ISGs).qRT-PCR indicated that the above 6 genes showed significantly higher expression levels in the cervical exfoliated cells at the P+4 stage than the cells at the P+6 stage(P＜0.05).Conclusion There are changes in the expression levels of the genes related to immunity and cytoskeleton remodeling in cervical exfoliated cells during the endometrial receptivity phase.The decrease in the expression of ISGs may serve as a potential biomarker for endometrial receptivity.

Objective To investigate the mediating role of anxiety and depression in social sup-port and burnout among primary caregivers of stroke patients.Methods A convenience sampling method was employed to select 506 primary caregivers of stroke patients as research subjects.The Gen-eral Information Questionnaire,Caregiver Burnout Inventory for Stroke Patients,Multidimensional Scale of Perceived Social Support,and Hospital Anxiety and Depression Scale were used for data col-lection.Results The total scores for caregiver burnout,social support,anxiety,and depression a-mong primarycaregivers of stroke patients were(72.83±14.32),(47.79±7.74),(10.49±3.00),and(10.45±3.06),respectively.Correlation analysis revealed a negative correlation between caregiver burnout and social support(r=-0.245,P＜0.001),and positive correlations with anxiety and depression(r=0.178,0.216,P＜0.001).Anxiety and depression partially media-ted the relationship between social support and caregiver burnout,accounting for 7.9％and 10.7％of the total effect,respectively.Conclusion Social support,anxiety,depression,and burnout are closely interrelated.Social support can directly or indirectly influence the occurrence of burnoutthrough anxiety and depression.Medical staff should pay attention to the anxiety and depression status of primary caregivers of stroke patients and enhance social support levels to reduce the incidence of burnout by alleviating anxiety and depression.

OBJECTIVE: To explore the clinical features and genetic etiology of a child with a SETD1B gene variant causing seizures and language delay. METHODS: A child with a SETD1B gene variant admitted to the Department of Pediatric Neurology at the Third Affiliated Hospital of Zhengzhou University in September 2022 was selected as the study subject. Clinical data of the child were collected, and peripheral blood samples from the child and her parents were obtained. Whole exome sequencing (WES) was performed for genetic testing, and Sanger sequencing was used for familial validation of the candidate variant. Using "SETD1B" and "epilepsy" as the Chinese and English keywords, relevant cases were retrieved from databases including CNKI, Wanfang Data, OMIM and PubMed, with the search period spanning from database inception to June 2024. RESULTS: The child was a 6-year-old female presenting with myoclonic seizures accompanied by global developmental delay. WES and Sanger sequencing revealed that the child has carried a de novo SETD1B gene variant, namely c.5582G>A (p.Cys1961Tyr). According to the American College of Medical Genetics and Genomics (ACMG) guidelines for sequence variant interpretation, this variant was classified as likely pathogenic (PS2+PM2_Supporting+PP2+PP3). The child was not controlled with effective doses of valproate, levetiracetam, or clonazepam but was successfully managed with low-dose lamotrigine. Follow-up electroencephalography showed normal results, and developmental progress gradually improved. A total of 37 epilepsy cases with SETD1B gene variants were reported across six studies. The predominant seizure types included absence seizures and myoclonic absence seizures, accompanied by delayed language development. The response to pharmacological treatment was generally poor, with no significant difference in incidence between males and females. CONCLUSION SETD1B gene variants may cause neurological disorders with drug-resistant epilepsy and severe clinical manifestations. Lamotrigine is effective in controlling the epileptic seizures.
Humans ; Female ; Child ; Epilepsy/genetics* ; Language Development Disorders/genetics* ; Histone-Lysine N-Methyltransferase/genetics* ; Exome Sequencing ; Male

Objective:To analyze the status quo of type D personality, intolerance of uncertainty and family support in first-episode stroke patients, and to explore the mediating role of family support between type D personality and intolerance of uncertainty in first-episode stroke patients, in order to provide reference for formulating relevant clinical intervention measures to promote the physical and mental health of first-episode stroke patients.Methods:This study was a cross-sectional investigation. A total of 300 patients with acute first-episode stroke who met the inclusion and exclusion criteria in the Department of Neurology of the General Hospital of Ningxia Medical University and the First People′s Hospital of Yinchuan from May 2023 to September 2023 were selected as the study objects by convenience sampling method. The general data questionnaire, Type D personality Scale-14, Family Caring Index Scale and the Intolerance of Uncertainty Scale were used to investigate them. Pearson correlation analysis was used to test the correlation between variables, and SPSS plug-in PROCESS 3.5 was used to test the mediation effect.Results:Finally, 300 questionnaires were effectively collected, including 228 males and 72 females. Patients aged ≥ 60 years old were the majority, accounting for 49.3% (148/300). The detection rate of type D personality in the first stroke patients was 37.3% (112/300), and the total score of Type D personality inventory, family support and intolerance of uncertainty of type D personality in the first stroke patients were (22.16 ± 9.95), (6.40 ± 2.23), (27.82 ± 7.93) points. The correlation analysis results showed that the intolerance of uncertainty of type D personality in the first stroke patients was positively correlated with type D personality scores ( r=0.675, P<0.001). There was a negative correlation with family support score ( r=-0.644, P<0.001). The results of mediating effect analysis showed that family support played a partial mediating role in the relationship between type D personality and intolerability of uncertainty in first-stroke patients, and the mediating effect accounted for 34.94% of the total effect. Conclusions:The mediating role of family support between type D personality and intolerability of uncertainty in first-stroke patients is established. In the future, the level of family support of patients can be continuously improved to reduce their intolerability of uncertainty, so as to promote the physical and mental health of patients and improve their quality of life.

ObjectiveTo explore the possible mechanism of the Yiqi Jiedu formula （YQ） in treating ischemic stroke （IS） from the perspective of the microbial-gut-brain axis （MGBA）. MethodRats were randomly divided into five groups， with six in each group， including sham surgery group， model group， and low， medium， and high dose YQ groups （1， 5， and 25 mg·kg^-1）. Except for the sham surgery group， all other groups were established with a middle cerebral artery occlusion （MCAO） model using the thread occlusion method. The success of modeling was determined through neurobehavioral scoring， and the protective effect of YQ on IS was evaluated. Then， the changes in gut microbiota before and after MCAO modeling and YQ administration were compared using 16S rDNA sequencing technology， and the possible biological pathways related to the effect of this formula were analyzed. The expression of inflammatory factors such as interleukin-6 （IL-6）， interleukin-17A （IL-17A）， and interleukin-10 （IL-10） in serum was detected by enzyme-linked immunosorbent assay （ELISA）. Western blot was used to detect the expression of tight junction proteins ZO-1 and Occludin in brain and intestinal tissue， and hematoxylin-eosin staining （HE） was used to observe pathological changes in the cerebral cortex and colon， so as to validate the possible mechanism of action. ResultYQ significantly improved the neurobehavioral score of MCAO rats （P<0.01） and played a good regulatory role in intestinal microbial disorders caused by enriched pathogens and opportunistic pathogens during the acute phase. Among them， significantly changed microorganisms include Morgentia， Escherichia Shigella， Adlercreutzia， and Androbacter. Bioinformatics analysis found that these bacteria may be related to the regulation of inflammation in the brain. Compared with the blank group， the detection of inflammatory factors in the serum of IS model rats showed an increase in inflammatory factors IL-6 and IL-17A （P<0.01） and a decrease in the content of anti-inflammatory factor IL-10 （P<0.01）. Compared with the model group， the content of inflammatory factors IL-6 and IL-17A in the serum of the treatment group decreased （P<0.05）， and that of anti-inflammatory factor IL-10 increased （P<0.01）. The expression results of barrier proteins ZO-1 and Occludin in brain and intestinal tissue showed that the expression levels of both decreased in IS model rats （P<0.05）， while the expression levels of both increased in the treatment group （P<0.05）. ConclusionAcute cerebral ischemia can lead to an imbalance of intestinal microbiota and damage to the intestinal barrier， and it can increase intestinal permeability. YQ can regulate intestinal microbiota imbalance caused by ischemia， inhibit systemic inflammatory response， and improve the disruption of the gut-blood brain barrier， preventing secondary cascade damage to brain tissue caused by inflammation. The MGBA may be an important mechanism against the IS.

ObjectiveTo analyze the effects of new integration processing method in producing area and traditional method on the composition and pharmacological action of Polygoni Multiflori Radix Praeparata（PMRP）， and to illustrate the advantages of toxicity reducing and efficacy enhancing of the decoction pieces prepared by the new method. MethodFresh Polygoni Multiflori Radix（PMR） was taken from Dao-di producing area， and was processed by new integration processing method in producing area（steaming with black bean juice under pressure of 0.1 MPa and temperature at 120 ℃ for 10.5 h） and traditional method（steaming with black bean juice under water for 36 h）， respectively. Samples were collected during the processing process of the two methods， For new method， the samples were collected at 0.5， 3， 5.5， 8， 10.5 h， separately. For traditional method， the samples were collected every 4 h. High performance liquid chromatography（HPLC） was used to establish fingerprint and identify common peaks， the content of polysaccharides was determined by anthrone-sulfuric acid colorimetry at 627 nm， and the contents of anthraquinones and stilbene glycosides in different processed products were determined according to the methods under the item of determination of PMR and PMRP in the 2020 edition of Chinese Pharmacopoeia. In pharmacological experiments， 90 SD rats were randomly divided into 9 groups with 10 in each group（half of male and half of female）， including the blank group， and raw products， 24 h processed products under atmospheric pressure， 30 h processed products under atmospheric pressure， 8 h processed products under high pressure groups with low and high dosages（4.125， 16.5 g·kg^-1）. Rats were given the drug by gavage for 29 d with once a day， blood was collected from the abdominal aorta after the last administration， and the serum was isolated， the body mass and liver mass of rats were weighed and the organ index was calculated. The pathological change of liver tissue was observed by hematoxylin-eosin（HE） staining， and biochemical methods were used to detect the contents of aspartate aminotransferase（AST）， alanine aminotransferase（ALT）， alkaline phosphatase（ALP）， γ-glutamyltransferase（GGT）， lactic dehydrogenase（LDH） in serum which used as liver function indicators and the levels of superoxide dismutase（SOD）， malondialdehyde（MDA）， glutathione peroxidase（GSH-Px） in brain tissues which used as oxidation indicators. ResultA total of 14 common peaks were identified in the fingerprint of PMR， PMRP prepared by new method and traditional method， and three of the peaks were designated as stilbene glycoside， emodin and emodin methyl ether， respectively. The characteristic peak areas of each processed products changed significantly from 0 min to 25 min， indicating that different processing methods had an effect on the contents of components with high polarity in PMRP， and the trend of the changes of the two methods was similar， with the higher degree of change in the new method. The determination results showed that compared with the traditional method， the content of polysaccharide（a kind of beneficial component in PMRP obtained by the new method） significantly increased， while the contents of stilbene glycoside and bound anthraquinone（liver-damaging ingredients） significantly decreased. The pharmacological results showed that compared with the blank group， AST and LDH levels of male rats in the low and high dose groups of 24 h processed products under atmospheric pressure and AST level of male rats in the low and high dose groups of 8 h processed products under high pressure were significantly reduced（P<0.05， P<0.01）， while compared with the raw product groups with the same dose， AST and LDH levels of male rats in the low dose group of 30 h processed products under atmospheric pressure were significantly reduced（P<0.05， P<0.01）， the AST levels of male rats in the low and high dose groups of 8 h processed products under high pressure were significantly decreased（P<0.01）， and there was no statistical significance in the differences of biochemical indexes of female rats in each administration group as compared with those of the blank group. ConclusionThe new integration processing method in producing area of PMRP can reach the quality of relevant regulations in 8 h. The processed products obtained by this method have more advantages than the traditional method in terms of toxicity reducing and efficacy enhancing， and energy saving to avoid the loss of ingredients， which can provide ideas for the production of high-quality decoction pieces of PMRP， and the integration processing method in producing area of other roots and rhizomes of traditional Chinese medicines.

ObjectiveTo investigate the mechanism of neferine（Nef） in promoting vascular regeneration against cerebral ischemia through modulation of mitochondrial calcium uniporter（MCU） ion channel. MethodTaking the area of subintestinal vessels in microvascular deficiency zebrafish as an index， the vascular regenerative efficacy of Nef was evaluated， and the median effective concentration（EC₅₀） was calculated. Rats were randomly divided into a sham operation group， a model group， a positive drug group（butylphthalide， 6 mg·kg^-1）， and Nef low， medium， and high dose groups（0.125， 0.625， 3.125 μg·kg^-1）. Except for the sham operation group， the middle cerebral artery occlusion（MCAO） model was established in other groups. After modeling， the groups were administered the corresponding dose of drugs by gavage， while the sham operation and model groups received equal volumes of saline， once a day for 7 consecutive days. Neurobehavioral scores were assessed for each group of rats， and the infarct rate of ischemic brain tissue was calculated by 2，3，5-triphenyltetrazolium chloride（TTC） staining. The regional cerebral blood flow（rCBF） of each group was measured using a speckle contrast imaging. Immunofluorescence and Western blot were conducted to detect the expression of vascular endothelial growth factor（VEGF）， platelet endothelial cell adhesion molecule-1（CD31）， and hypoxia-inducible factor-1α（HIF-1α） proteins in each group. Human umbilical vein endothelial cells（HUVECs） were divided into the normal group， model group， positive drug group（astragaloside Ⅳ， 10 μmol·L^-1）， and Nef group （32 nmol·L^-1）. In the verification of mitochondrial protection of Nef and its mechanism in promoting vascular regeneration， the spermine（MCU agonist） and Nef+spermine group were added. HUVECs model of oxygen-glucose deprivation（OGD） was established in all groups except the normal group， the cell viability was assessed using 3-（4，5-dimethylthiazol-2-yl）-2，5-diphenyltetrazolium bromide（MTT） assay， and cell migration ability was evaluated through scratch and tube formation assays. Fluorescent probes（Rhod-2 AM， Fluo-3 AM， JC-1， Calcein AM） and a cellular energy metabolism analyzer were used to analyze the mitochondrial protective effects of Nef. Molecular docking was performed to predict the binding ability of Nef with MCU and HIF-1α， and Western blot was used to detect the effects of Nef on the protein expressions of MCU， B-cell lymphoma-2 associated X protein（Bax）， Caspase-3 and HIF-1α in the OGD model HUVECs. ResultThe results of vascular regeneration in microvascular deficiency zebrafish showed that compared to the normal group， the area of subintestinal vessels in the model group significantly decreased（P<0.01）. Compared to the model group， different concentrations of Nef could significantly increase the area of subintestinal vessels（P<0.01）， with the maximum tolerated concentration of 10.24 μmol·L^-1 and the EC₅₀ of 0.23 μmol·L^-1. Anti-cerebral ischemia results on MCAO rats showed that compared to the sham operation group， the model group had a significant decrease in rCBF and a significant increase in infarct rate， while CD31 expression significantly decreased（P<0.01）， and VEGF and HIF-1α protein expressions significantly increased（P<0.05）. Compared to the model group， the treated groups showed significant increases in rCBF， significant reductions in infarct volume， and significant increases in CD31， VEGF， and HIF-1α protein expression（P<0.01）. Cell experiment results showed that compared to the normal group， the model group had decreased cell viability and migration ability， increased intracellular Ca²⁺ and mitochondrial Ca²⁺ levels， reduced mitochondrial permeability transition pore（MPTP） opening， and decreased mitochondrial energy metabolism capability， with increased expressions of MCU， Bax， Caspase-3 and HIF-1α proteins（P<0.05， P<0.01）. Compared to the model group， the Nef group showed increased cell viability and migration ability， decreased intracellular Ca²⁺ and mitochondrial Ca²⁺ levels， increased MPTP opening， enhanced mitochondrial energy metabolism capability， decreased expressions of MCU， Bax and Caspase-3 proteins， and increased HIF-1α protein expression（P<0.05， P<0.01）. ConclusionNef can stabilize mitochondrial membrane potential and inhibit mitochondrial apoptosis. By down-regulating the expression of MCU， it suppresses the activation of intracellular Bax and Caspase-3 while activating the HIF-1α signaling pathway， enhancing the expression of VEGF and CD31， thereby promoting vascular regeneration to treat ischemic brain injury.

The technology of three-dimensional(3D)printing emerged in the late 1970s and has since undergone considerable development to find numerous applications in mechanical engineering,industrial design,and biomedicine.In biomedical science,several studies have initially found that 3D printing technology can play an important role in the treatment of diseases in hepatopancreatobiliary surgery.For example,3D printing technology has been applied to create detailed anatomical models of disease organs for preoperative personalized surgical strategies,surgical simulation,intraoperative navigation,medical training,and patient education.Moreover,cancer models have been created using 3D printing technology for the research and selection of chemotherapy drugs.With the aim to clarify the development and application of 3D printing technology in hepatopancreatobiliary surgery,we introduce seven common types of 3D printing technology and review the status of research and application of 3D printing technology in the field of hepatopancreatobiliary surgery.

Following the principles of evidence-based medicine,in accordance with the structure and drafting rules of standardized documents,based on literature research,according to the characteristics of chronic cough in children and issues that need to form a consensus,the TCM Guidelines for Diagnosis and Treatment of Chronic Cough in Children was formulated based on the Delphi method,expert discussion meetings,and public solicitation of opinions.The guideline includes scope of application,terms and definitions,eti-ology and diagnosis,auxiliary examination,treatment,prevention and care.The aim is to clarify the optimal treatment plan of Chinese medicine in the diagnosis and treatment of this disease,and to provide guidance for improving the clinical diagnosis and treatment of chronic cough in children with Chinese medicine.