Objective To study the effect and molecular mechanism of vitamin D(VitD)on Tfh cells of MRL/lpr lupus mice.Methods C57/B6 mice and MRL/lpr lupus mice were transfected with siRNA to construct VDR knockout mouse models.Splenic Tfh cells of C57/B6 mice and MRL/lpr lupus mice were divided into control group,lupus group and VDRsiRNA lupus group(treated with vitamin D 0,1 and 10 nmol·L-1,respectively)by siRNA transfection.The percentage of Tfh cells was detected by flow cytometry.MRL/lpr lupus mice Peyer node Tfh cells were randomly divided into 7 groups,blank control group,vitamin D dose groups of 1 and 10 nmol·L-1,paricalcitol group(VitD 10 nmol·L-1+PA),VDRsiRNA control group,VDRsiRNA group(VitD 10 nmol·L-1),CaN inhibitor group(VitD 10 nmol·L-1+CsA),and incubated for 72 h.The concentration of calcium ions in Tfh of each group was detected.The expressions of AT1R,NFAT,CaN and P-CaN in Tfh cells were determined by Western blotting.Results The percentage of Tfh cells decreased significantly with the increase of vitamin D dose.Vitamin D CaN reduce the intracellular calcium concentration of Tfh,up-regulate the expression of AT1 protein in Tfh cells,and down-regulate the expression of CAN,P-CaN and NFAT protein in a dose-dependent manner,and the effect is more obvious when combined with PA.Conclusion Vitamin D may regulate the activation of follicular T helper cells in MRL/lpr mice via the Ca-CaN-NFAT pathway.

Objective To reveal the detailed histological characteristics of pyramidal neuron cell bodies and their axonal projections along the corticospinal tract in the primary motor cortex(M1)of the brain,by using the biotinylated dextran amine(BDA)neural tracing technique combined with panoramic and local microscopic imaging technologies.Methods A total of 100 nL of 10％BDA(10,000 molecular weight)was injected into M1 region using stereotaxic system.The distribution of BDA labeling along the corticospinal tract was continuously tracked with panoramic tissue scanning analysis system.Detailed observations of the histological characteristics of BDA labeling were carried out with laser confocal microscope.Results It is more convenient to observe the overall distribution of BDA neural labeling by using the panoramic tissue scanning analysis system.Around the injection site in M1,the BDA labeling was shown in the somas of pyramidal neurons in layer V.In the M1 region corresponding to the contralateral site of the injection site and ipsilateral primary sensory cortex,BDA showed predominantly the anterograde labeled nerve fibers accompanied by a few retrograde labeled neurons.Besides,BDA labeled nerve fibers-including bundles and terminals-projecting to regions such as the ipsilateral striatum,thalamus,internal capsule,cerebral peduncle,and pons,and further reaching the contralateral spinal cord via the brainstem pyramidal decussation.Confocal microscopy and its 3D reconstruction system facilitated detailed analysis of the local microscopic features of BDA labeling,revealing retrograde labeled neuron cell bodies,dendrites and their spines,as well as anterograde labeled nerve fibers and their terminals.Conclusions These findings demonstrated that the integration of traditional BDA neural tracing with panoramic tissue scanning analysis and confocal microscopy provided an effective approach to the observation and analysis of long-projection neural circuits from panoramic to local perspectives,with broad application prospects.

Objective To study the effect and molecular mechanism of vitamin D(VitD)on Tfh cells of MRL/lpr lupus mice.Methods C57/B6 mice and MRL/lpr lupus mice were transfected with siRNA to construct VDR knockout mouse models.Splenic Tfh cells of C57/B6 mice and MRL/lpr lupus mice were divided into control group,lupus group and VDRsiRNA lupus group(treated with vitamin D 0,1 and 10 nmol·L-1,respectively)by siRNA transfection.The percentage of Tfh cells was detected by flow cytometry.MRL/lpr lupus mice Peyer node Tfh cells were randomly divided into 7 groups,blank control group,vitamin D dose groups of 1 and 10 nmol·L-1,paricalcitol group(VitD 10 nmol·L-1+PA),VDRsiRNA control group,VDRsiRNA group(VitD 10 nmol·L-1),CaN inhibitor group(VitD 10 nmol·L-1+CsA),and incubated for 72 h.The concentration of calcium ions in Tfh of each group was detected.The expressions of AT1R,NFAT,CaN and P-CaN in Tfh cells were determined by Western blotting.Results The percentage of Tfh cells decreased significantly with the increase of vitamin D dose.Vitamin D CaN reduce the intracellular calcium concentration of Tfh,up-regulate the expression of AT1 protein in Tfh cells,and down-regulate the expression of CAN,P-CaN and NFAT protein in a dose-dependent manner,and the effect is more obvious when combined with PA.Conclusion Vitamin D may regulate the activation of follicular T helper cells in MRL/lpr mice via the Ca-CaN-NFAT pathway.

Objective To reveal the detailed histological characteristics of pyramidal neuron cell bodies and their axonal projections along the corticospinal tract in the primary motor cortex(M1)of the brain,by using the biotinylated dextran amine(BDA)neural tracing technique combined with panoramic and local microscopic imaging technologies.Methods A total of 100 nL of 10％BDA(10,000 molecular weight)was injected into M1 region using stereotaxic system.The distribution of BDA labeling along the corticospinal tract was continuously tracked with panoramic tissue scanning analysis system.Detailed observations of the histological characteristics of BDA labeling were carried out with laser confocal microscope.Results It is more convenient to observe the overall distribution of BDA neural labeling by using the panoramic tissue scanning analysis system.Around the injection site in M1,the BDA labeling was shown in the somas of pyramidal neurons in layer V.In the M1 region corresponding to the contralateral site of the injection site and ipsilateral primary sensory cortex,BDA showed predominantly the anterograde labeled nerve fibers accompanied by a few retrograde labeled neurons.Besides,BDA labeled nerve fibers-including bundles and terminals-projecting to regions such as the ipsilateral striatum,thalamus,internal capsule,cerebral peduncle,and pons,and further reaching the contralateral spinal cord via the brainstem pyramidal decussation.Confocal microscopy and its 3D reconstruction system facilitated detailed analysis of the local microscopic features of BDA labeling,revealing retrograde labeled neuron cell bodies,dendrites and their spines,as well as anterograde labeled nerve fibers and their terminals.Conclusions These findings demonstrated that the integration of traditional BDA neural tracing with panoramic tissue scanning analysis and confocal microscopy provided an effective approach to the observation and analysis of long-projection neural circuits from panoramic to local perspectives,with broad application prospects.

Objective To study the effect of Qingke Pingchuan Granule on the clinical efficacy in patients with phlegm-heat obstructing lung syndrome(AECOPD).Methods A total of 80 patients with acute exacerbation of chronic obstructive pulmonary disease(syndrome of phlegm-heat stagnation in the lung)hospitalized in the respiratory department of our hospital were selected and divided into the conventional group and the combinational group,with 40 cases in each group.The CAT score,TCM syndrome score,serum IL-6,CRP,lung function FEV1%pred,and FEV1/FVC were retrospectively observed before treatment,at the end of the second week of treatment,and at the follow-up after 1 month of treatment in the two groups.Results The total effective rate was significantly better in the combinational group than that of the conventional group(92.5%vs.75.0%,P＜0.05).At the end of the second week of treatment,the CAT score,each single syndrome score,serum IL-6 and CRP levels were all improved than those before treatment in the two groups(P＜0.05),and the improvement degree was better in the combined group than that of the conventional group(P＜0.05).The severity of airflow limitation and respiratory failure were significantly improved compared with those before treatment in both groups.At the follow-up after 1 month of treatment,the recovery rate of scores of each single syndrome score and CAT score were significantly lower in the combined group than those in the routine group(P＜0.05).There were no significant differences in adverse drug reactions between the two groups(12.5%and 2.5%,P＞0.05).Conclusion Qingke Pingchuan Granule can effectively relieve the symptoms and improve lung function and the quality of life of AECOPD patients.

Objective To investigate the mechanism of Yiqi Tongmai Powder(Ginseng Radix et Rhizoma,Salviae Miltiorrhizae Radix et Rhizoma,Notoginseng Radix et Rhizoma,Hirudo,Eupolyphaga Steleophaga,Rhei Radix et Rhizoma)against cerebral ischemia-reperfusion injury(CIRI)based on network pharmacology,molecular docking and experimental verification.Methods(1)The active components of Yiqi Tongmai Powder and their action targets were screened by TCMSP,TCMID and ETCM databases,the disease related targets of CIRI were screened by GeneCards,OMIM and TTD disease databases,and the intersection targets of the above targets were obtained through Venny 2.1 online platform,that is,the potential targets of Yiqi Tongmai Powder in the treatment of CIRI.The"drugs-active components-targets"network was constructed by Cytoscape 3.7.1 software,and the potential active components of Yiqi Tongmai Powder in the treatment of CIRI were screened.Protein-protein interaction(PPI)analysis of potential targets was carried out by STRING 11.0 database to screen core targets.The GO function and KEGG pathway enrichment of potential targets were analyzed by Metascape database.AutoDockTools 1.5.7 software was used to verify the molecular docking between the key active components and the core targets.(2)The rat model of CIRI was established by middle cerebral artery occlusion and reperfusion(MCAO/R).SD rats were randomly divided into sham operation group,model group,Yiqi Tongmai Powder low-dose group(0.27 g·kg-1),Yiqi Tongmai Powder high-dose group(1.08 g·kg-1)and Nimodipine group(30 mg·kg-1),with 10 rats in each group.Pre-administration began three days before the establishment of the model,once a day for seven days.The neurological deficit of MCAO/R rats was evaluated by modified neurological deficit score(mNSS).The volume of cerebral infarction was measured by TTC staining.Nissl staining was used to observe the damage of neurons in brain tissue.ELISA method was used to detect serum inflammatory factors and oxidative stress related indexes.TUNEL staining was used to detect brain tissue apoptosis.Western Blot method was used to detect the protein expressions of Bax and Bcl-2 in brain tissue.Results(1)A total of 46 active components and 178 potential targets of Yiqi Tongmai Powder in the treatment of CIRI were obtained.The key active components such as quercetin,digitalis flavonoids,kaempferol,valine and uracil were analyzed,and the core targets such as TNF,IL-6,STAT3,VEGFA,AKT1,IL-1β,CASP3,TP53,MAPK3 and EGFR were analyzed.The potential targets are involved in inflammation,oxidative stress,cell proliferation and differentiation,apoptosis and other biological processes,including cAMP,NF-κB,PI3K-Akt and other signal pathways.The main active components quercetin,flavonoids of digitalis,kaempferol and valine have good binding activity to target proteins such as TNF,IL-6,STAT3 and VEGFA.(2)Compared with the model group,the neurological deficit score of rats in each treatment group was significantly decreased(P＜0.05,P＜0.01),the area of cerebral infarction was significantly decreased(P＜0.01),and the pathological changes of ischemic necrotic area of brain tissue were improved.The number of neurons in ischemic area of brain tissue was significantly increased(P＜0.01),and the rate of neuronal apoptosis was significantly decreased(P＜0.01).The levels of serum IL-1β,IL-6,TNF-α and MDA were significantly decreased,while the activities of SOD and GSH-Px were significantly increased(P＜0.05).The protein expression of Bax in brain tissue were significantly decreased and the protein expression of Bcl-2 significantly increased(P＜0.05).Conclusion Yiqi Tongmai Powder may play an anti-CIRI effect by reducing inflammation and oxidative stress,inhibiting cell apoptosis.

This paper reviews the origin, content and framework, evaluation tools, and application status of Snyder hope theory in clinical nursing practice both domestically and internationally, and explores the application prospects of Snyder hope theory, aiming to provide a basis for promoting its development in nursing.

The bone-touching acupuncture method, as one of the five-body acupuncture techniques, is widely used and highly effective in the treatment of brain diseases, though its theoretical foundation has been lacking. This paper explores the close connection between bones and the brain in both physiological and pathological states, as described in traditional Chinese medicine (TCM) classics, and explains the "bone-brain axis" concept within the framework of TCM. It summarizes the effects and characteristics of the five-body acupuncture techniques, traces the origins and modern applications of the bone-touching acupuncture method, and discusses its theoretical basis for treating brain diseases. The aim is to provide a reference for future clinical and mechanistic research on bone-touching acupuncture in brain disease treatment and to offer new perspectives and approaches for acupuncture treatment of brain diseases.
Humans ; Acupuncture Therapy/methods* ; Brain/physiopathology* ; Brain Diseases/physiopathology* ; Bone and Bones/physiopathology* ; Medicine, Chinese Traditional/methods*

Humans ; Amyotrophic Lateral Sclerosis/drug therapy* ; Benzofurans/therapeutic use* ; Double-Blind Method ; Treatment Outcome

Background::Familial hypercholesterolemia (FH) is underrecognized, and its association with coronary artery disease (CAD) remains limited, especially in China. We aimed to investigate the prevalence of FH and its relationship with CAD in a large Chinese cohort.Methods::FH was defined using the Make Early Diagnosis to Prevent Early Death (MEDPED) criteria. The crude and age-sex standardized prevalence of FH were calculated based on surveys of the Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) project during 2007-2008. The associations of FH with incident CAD and its major subtypes were estimated with the cohort-stratified multivariate Cox proportional hazard models based on the data from the baseline to the last follow-up (2018-2020).Results::Among 98,885 included participants, 190 participants were defined as FH. Crude and age-sex standardized prevalence and 95% confidence interval (CI) of FH were 0.19% (0.17%–0.22%) and 0.13% (0.10%–0.16%), respectively. The prevalence varied across age groups and peaked in the group of 60–<70 years (0.28%), and the peak prevalence (0.18%) in males was earlier, yet lower than the peak crude prevalence in females (0.41%). During a mean follow-up of 10.7 years, 2493 cases of incident CAD were identified. After multivariate adjustment, FH patients had a 2.03-fold greater risk of developing CAD compared to non-FH participants.Conclusions::The prevalence of FH was estimated to be 0.19% in the participants, and it was associated with an elevated risk of incident CAD. Our study suggests that early screening of FH has certain public health significance for the prevention of CAD.