Objective:To investigate the effects of Zhuanggu Zhitong Capsules on JNK signaling molecules and their phosphorylated proteins in postmenopausal osteoporosis model female mice.Methods:The rats were divided into sham-operation group, blank group, model group, positive drug group, and Zhuanggu Zhitong Capsules group according to the random number table method, with 10 rats in each group. The model group, the positive drug group and the Zhuanggu Zhitong Capsules group were prepared by bilateral ovarian detomy to prepare a female mouse model of postmenopausal osteoporosis. The positive drug group was given 0.9 mg/kg of alendronate sodium, the Zhuanggu Zhitong Capsules group was given was Zhuanggu Zhitong Capsules 1.944 g/kg for gavage, and the blank group, sham-operation group, and model group were given the same volume of normal saline for gavage, once a day for a total of 13 weeks. Rat vaginal exfoliated cells were stained with Wright's staining; serum Omentin-1 and 25(OH)D 3 levels were determined by ELISA; renal tissue and femoral structure were observed by HE staining; JNK and p-JNK protein expressions were detected by immunohistochemical staining; JNK mRNA levels were detected by PCR. Results:Compared with the model group, the serum levels of 25(OH)D3 and Omentin-1 in the Zhuanggu Zhitong Capsules group and the positive drug group increased ( P<0.01), the mean gray values of JNK and p-JNK protein in bone and kidney tissues decreased ( P<0.01), and the mRNA levels of JNK in bone and kidney tissues decreased ( P<0.01). Conclusion:Zhuanggu Zhitong Capsules can effectively improve the bone microstructure of postmenopausal osteoporotic rats, and its mechanism may be related to the regulation of JNK signaling pathway.

Objective To evaluate the changes in cerebral perfusion after moyamoya disease revascularization using two-phase arterial spin labeling(ASL)combined with territorial arterial spin labeling(t-ASL).Methods A retrospective selection was conducted on 34 moy-amoya disease patients with 37 cerebral hemispheres who underwent revascularization surgery.ASL[post labeling delay(PLD)of 1.5 s and 2.5 s],t-ASL,and digital subtraction angiography(DSA)were performed before and after surgery.The cerebral blood flow(CBF)and relative cerebral blood flow(rCBF)values in the middle cerebral artery(MCA)supply area from ASL were com-pared before and after surgery.t-ASL and DSA were used to score the area of revascularization on a 3-point scale,and weighted Kappa was used to compare the consistency of the revascularization area assessments.A DSA score greater than 1 point was classified as good revascularization.The diagnostic efficacy of ASL(PLD 1.5 s,2.5 s)and t-ASL for revascularization were compared.Results In ASL PLD 1.5 s,the preoperative and postoperative CBF values were(32.65±12.71)mL·100 g-1·min-1 and(43.09±18.05)mL·100 g-1·min-1,respectively,and the rCBF values were 0.76±0.23 and 1.02±0.31;In ASL PLD 2.5 s,the preoperative and postoperative CBF val-ues were(47.07±13.28)mL·100 g-1·min-1and(52.85±14.98)mL·100 g-1·min-1,respectively,and the rCBF values were 1.21±0.31 and 1.33±0.29.There were statistically significant differences between preoperative values and postoperative values above(P<0.05).The revascularization area score showed strong consistency(weighted Kappa coefficient=0.729).Receiver operating charac-teristic(ROC)curve analysis revealed that t-ASL reflected the revascularization area with area under the curve(AUC)of 0.982,while ASL PLD 1.5 s and 2.5 s CBF reflected the revascularization area with AUC of 0.813 and 0.794,espectively.Conclusion The com-bination of two-phase ASL and t-ASL more effectively evaluates cerebral blood after moyamoya disease revascularization.Furthermore,t-ASL demonstrates higher efficacy in evaluating postoperative revascularization.

Tenascin-C (TNC), an extracellular matrix glycoprotein, is lowly expressed in normal adult tissues while significantly upregulated under pathological conditions such as injury, inflammation, or tumors. Recent studies have shown that TNC plays an important role in Alzheimer's disease (AD) development: it is not only closely related to the formation of β-amyloid (Aβ) plaque, but also involved in neuroinflammation regulation and Aβ clearance process. This article reviews the effect of TNC on AD pathology in aspects of neuroinflammation, synaptic function, autophagy and Aβ load, aiming to provide theoretical basis for TNC-targeted AD treatment and drug development.

Objective This study aimed to investigate the effects of sleep interruption(SI)cycles on emotional behavior in ICR mice,and to establish a mouse model of comorbid anxiety and depression induced by SI.Methods Seventy-two male ICR mice(4～5 weeks old)were divided randomly into a blank group and a model group.Mice in the model group were subjected to SI stress modeling for 1,2,and 3 weeks,respectively.After modeling,emotional behaviors were evaluated using open-field,elevated plus maze,light-dark box,marble-burying,and forced-swimming tests.Serum corticosterone levels were detected by enzyme-linked immunosorbent assay.Results Mice in the model group buried significantly more marbles after 1 week of SI stress,compared with the blank group(P＜0.05).After 2 weeks of stress,mice in the model group also showed a significant decrease in the number of crossings in the light-dark box(P＜0.05)and a significant increase in the number of marbles buried(P＜0.01)compared with the control group.After 3 weeks of stress,mice in the model group showed a significant increase in the number of marbles buried(P＜0.05),a significant decrease in the number of crossings in the light-dark box(P＜0.05),and a significant increase in immobility time in the forced-swim test(P＜0.01).Conclusions ICR mice exhibited significant anxiety-related behaviors after 2 weeks of SI modeling and significant anxiety-and depressive-related behavioral changes after 3 weeks.Three weeks of SI stress can be used to establish a model of comorbid anxiety and depression.

Objective To evaluate the changes in cerebral perfusion after moyamoya disease revascularization using two-phase arterial spin labeling(ASL)combined with territorial arterial spin labeling(t-ASL).Methods A retrospective selection was conducted on 34 moy-amoya disease patients with 37 cerebral hemispheres who underwent revascularization surgery.ASL[post labeling delay(PLD)of 1.5 s and 2.5 s],t-ASL,and digital subtraction angiography(DSA)were performed before and after surgery.The cerebral blood flow(CBF)and relative cerebral blood flow(rCBF)values in the middle cerebral artery(MCA)supply area from ASL were com-pared before and after surgery.t-ASL and DSA were used to score the area of revascularization on a 3-point scale,and weighted Kappa was used to compare the consistency of the revascularization area assessments.A DSA score greater than 1 point was classified as good revascularization.The diagnostic efficacy of ASL(PLD 1.5 s,2.5 s)and t-ASL for revascularization were compared.Results In ASL PLD 1.5 s,the preoperative and postoperative CBF values were(32.65±12.71)mL·100 g-1·min-1 and(43.09±18.05)mL·100 g-1·min-1,respectively,and the rCBF values were 0.76±0.23 and 1.02±0.31;In ASL PLD 2.5 s,the preoperative and postoperative CBF val-ues were(47.07±13.28)mL·100 g-1·min-1and(52.85±14.98)mL·100 g-1·min-1,respectively,and the rCBF values were 1.21±0.31 and 1.33±0.29.There were statistically significant differences between preoperative values and postoperative values above(P<0.05).The revascularization area score showed strong consistency(weighted Kappa coefficient=0.729).Receiver operating charac-teristic(ROC)curve analysis revealed that t-ASL reflected the revascularization area with area under the curve(AUC)of 0.982,while ASL PLD 1.5 s and 2.5 s CBF reflected the revascularization area with AUC of 0.813 and 0.794,espectively.Conclusion The com-bination of two-phase ASL and t-ASL more effectively evaluates cerebral blood after moyamoya disease revascularization.Furthermore,t-ASL demonstrates higher efficacy in evaluating postoperative revascularization.

Objective This study aimed to investigate the effects of sleep interruption(SI)cycles on emotional behavior in ICR mice,and to establish a mouse model of comorbid anxiety and depression induced by SI.Methods Seventy-two male ICR mice(4～5 weeks old)were divided randomly into a blank group and a model group.Mice in the model group were subjected to SI stress modeling for 1,2,and 3 weeks,respectively.After modeling,emotional behaviors were evaluated using open-field,elevated plus maze,light-dark box,marble-burying,and forced-swimming tests.Serum corticosterone levels were detected by enzyme-linked immunosorbent assay.Results Mice in the model group buried significantly more marbles after 1 week of SI stress,compared with the blank group(P＜0.05).After 2 weeks of stress,mice in the model group also showed a significant decrease in the number of crossings in the light-dark box(P＜0.05)and a significant increase in the number of marbles buried(P＜0.01)compared with the control group.After 3 weeks of stress,mice in the model group showed a significant increase in the number of marbles buried(P＜0.05),a significant decrease in the number of crossings in the light-dark box(P＜0.05),and a significant increase in immobility time in the forced-swim test(P＜0.01).Conclusions ICR mice exhibited significant anxiety-related behaviors after 2 weeks of SI modeling and significant anxiety-and depressive-related behavioral changes after 3 weeks.Three weeks of SI stress can be used to establish a model of comorbid anxiety and depression.

Tenascin-C (TNC), an extracellular matrix glycoprotein, is lowly expressed in normal adult tissues while significantly upregulated under pathological conditions such as injury, inflammation, or tumors. Recent studies have shown that TNC plays an important role in Alzheimer's disease (AD) development: it is not only closely related to the formation of β-amyloid (Aβ) plaque, but also involved in neuroinflammation regulation and Aβ clearance process. This article reviews the effect of TNC on AD pathology in aspects of neuroinflammation, synaptic function, autophagy and Aβ load, aiming to provide theoretical basis for TNC-targeted AD treatment and drug development.

OBJECTIVE To investigate the ameliorating effect and mechanism of the effective substance groups from Artemisia ordosica(Abbreviated as HSH)on rheumatoid arthritis(RA)based on cluster of differentiation 4/lymphocyte cell-specific protein-tyrosine kinase/zeta-chain-associated protein kinase of 70 kDa/interleukin-17(CD4/LCK/ZAP70/IL-17)signaling pathway.METHODS The rats were divided into normal group,model group,HSH low-dose,medium-dose and high-dose groups(2.7,10.8,21.6 mg/kg)and positive control group(Tripterygium glycosides tablet,6.3 mg/kg),with 10 rats in each group.Except for normal group,RA rat model was induced by complete Freund's adjuvant in other groups.After modeling,each group was given relevant medicine or normal saline intragastrically,once a day,for 28 consecutive days.The changes in ankle joint swelling and arthritis index in rats were determined;the pathological changes of ankle joint tissue were observed;the levels of inflammatory factors[IL-1β,IL-21,IL-17A,IL-2,interferon-γ(IFN-γ)and IL-6]in serum and joint fluid of rats were determined;the levels of Th1,Th17 and Treg cells in the whole blood and spleen of rats were detected;protein and mRNA expressions of LCK,proto-oncogene tyrosine-protein kinase Fyn(Fyn),ZAP70,CD45,RAR-related orphan receptor γt(RORγt),and forkhead box protein 3(Foxp3)in ankle synovial tissue were determined.RESULTS Compared with normal group,the changes in ankle joint swelling,arthritis index,the levels of IL-1β,IL-21,IL-17A,IL-2,IFN-γ and IL-6 in serum and joint fluid,the levels of Th1,Th17 cells and Th17/Treg value in whole blood and spleen,and the protein and mRNA expression levels of LCK,Fyn,ZAP70,CD45,and RORγt in ankle joint synovium were all significantly increased/elevated(P＜0.05).The level of Treg cells in the spleen,as well as the protein and mRNA expression levels of Foxp3 in the ankle joint synovium were significantly decreased(P＜0.05).Compared with model group,most of the above-mentioned indicators were significantly reversed in the positive control group and all dose groups of HSH(P＜0.05).The degree of pathological changes in ankle joint tissues was markedly improved,and inflammation was alleviated.CONCLUSIONS HSH can regulate the cascade reactions in the CD4/LCK/ZAP70/IL-17 pathway within the T-cell receptor signaling pathway,thereby modulating the Th17/Treg balance.This leads to the suppression of inflammatory responses and the alleviation of synovial tissue damage in rats with RA.

OBJECTIVE Microgravity exerts several negative effects on the learning and memory of astro-nauts during space flight.Rg1 and Rb1,the key steroidal components of ginseng,have shown potent neuroprotec-tive effects with a high safety profile.The object of the current study is to investigate the influence of Rg1 and Rb1 on simulated microgravity-induced memory and learning dysfunction in the hindlimb suspension(HLS)rat model.METHODS The HLS rats were orally administered Rg1(30 and 60 μmol·kg-1)or Rb1(30 and 60 μmol·kg-1)for four weeks.The Morris water maze test(MWM)and reward operating conditioning reflex test(ROCR)were conducted to evaluate spatial and associative learning and memory.After the behavior tests,the serum and the prefrontal cortex(PFC)were dissected to measure the mechanism.RESULTS Rg1 and Rb1 treatment amelio-rated the cognitive deficits of HLS-exposure rats in MWM and ROCR,reduced reactive oxygen species generation and increased antioxidant enzyme activity.Rg1 and Rb1 also assisted in the recovery of mitochondrial complex Ⅰ(NADH dehydrogenase)activities and Mfn2,and decrea-sed Drp-1 expression.Furthermore,Rg1 and Rb1 reduced the ratio of Bax/Bcl-2 and the expression of cleaved-cas-pase 3,cytochrome c,increased the levels of SYN,PSD95 and activated BDNF-TrkB/PI3K-Akt pathway in the PFC.CONCLUSION Rg1 and Rb1 treatment attenuated cog-nitive deficits induced by HLS,mitigated mitochondrial dysfunction,attenuated oxidative stress,inhibited apopto-sis,and increased the synaptic plasticity,which was partly mediated by the modulation of the BDNF-TrkB/PI3K-Akt signaling.

The essence-qi-spirit theory is an important part of traditional Chinese medicine， whose steady state is the material and functional basis for the balance of yin and yang in the body， making the essence， qi and spirit integrated， and body and spirit harmonized. Based on this theory， it is proposed that essence and qi depletion， spirit dissipation and qi dispersion， disharmony between yin and yang is the main pathogenesis of sleep disorders. Therefore， the method of regulating and harmonzing yin and yang by essence gathering， qi nourishing and spirit storing can be used to treat sleep disorder. The biological clock system of the circadian rhythm of sleep is regulated by the molecular oscillation that is generated by the transcription of the biological clock gene， and is a clock gradually formed by orga-nisms constantly adapting to the laws of nature. As the material basis， power， and embodiment of sound and peaceful sleep， essence， qi and spirit can perceive and transmit natural signals， whose functions are similar to what is recognized by modern science that oscillation amplifies the rhythm signal， and synchronously regulates the expression signal of the biological clock gene， thereby forming a biological clock system with “input-oscillation-output” as the feedback cycle. It is believed that the regulation method of yin and yang by essence gathering， qi nourishing and spirit storing may comprehensively regulate the physiological activities through brain/ muscle aryl hydrocarbon receptor nuclear translocator-like protein 1 （BMAL1）/circadian locomotor output cycles kaput （CLOCK）-period protein （PER）/ cryptochrome （CRY） transcriptional feedback loop， thereby adapting to the natural environment changes， playing an active role in the treatment of sleep disorders， and provideing a new idea for traditional Chinese medicine to reshape the molecular regulation system of the endogenous biological clock to prevent and treat sleep disorders.