ObjectiveBased on ultra-high performance liquid chromatography-quadrupole-electrostatic field orbital trap-linear ion-trap mass spectrometry（UPLC-Orbitrap Fusion Lumos Tribrid-MS）， the plasma concentration of ziyuglycoside Ⅰ was determined at different time points after oral administration， and its pharmacokinetic characteristics in normal rats and rats with acute kidney injury were compared. MethodsRats were randomly divided into normal group and model group， the model group received intraperitoneal cisplatin（10 mg·kg^-1） to establish the acute kidney injury model， the normal group was given the same volume of saline. After successful modeling， rats in the normal and model groups were randomly divided into the normal low， medium and high dose groups（2.5， 5， 7.5 mg·kg^-1） and the model low， medium and high dose groups（2.5， 5， 7.5 mg·kg^-1）， 6 rats in each group， and the plasma was collected at different time points after receiving the corresponding dose of ziyuglycoside Ⅰ. Then， the concentration of ziyuglycoside Ⅰ in rat plasma was determined by UPLC-Orbitrap Fusion Lumos Tribrid-MS， and the drug-time curve was poltted. The pharmacokinetic parameters were calculated by Kinetica 5.1 software， and the differences in pharmacokinetic parameters between different administration groups were compared by independent sample t-test with SPSS 22.0. ResultsThe pharmacokinetic results showed that after receiving the different doses of ziyuglycoside Ⅰ， its concentration increased first and then decreased， and all of them reached the maximum plasma concentration at about 0.5 h. The area under the curve（AUC_0-t） and mean retention time（MRT_0-t） of normal and model rats increased with the increased dose， and the clearance（CL） decreased with the increasing dose. Compared with the normal group， the AUC_0-t was significantly increased（P<0.01）， peak concentration（C_max） and CL decreased in model rats at different doses， indicating that the physiological state of the rats could affect the absorption and elimination of ziyuglycoside Ⅰ in vivo. ConclusionThe pharmacokinetic characteristics of ziyuglycoside Ⅰ are quite different in normal rats and acute kidney injury model rats， which may be due to the change of the body environment in the pathological state， then lead to changes in absorption and metabolic processes.

ObjectiveTo explore the syndrome elements and evolving patterns of patients with hepatitis B virus-related acute on chronic liver failure （HBV-ACLF） at different stages. MethodsClinical information of 1,058 hospitalized HBV-ACLF patients， including 618 in the early stage， 355 in the middle stage， and 85 in the late stage， were collected from 18 clinical centers across 12 regions nationwide from January 1， 2012 to February 28， 2015. The “Hepatitis B-related Chronic and Acute Liver Failure Chinese Medicine Clinical Questionnaire” were designed to investigate the basic information of the patients， like the four diagnostic information （including symptoms， tongue， pulse） of traditional Chinese medicine （TCM）， and to count the frequency of the appearance of the four diagnostic information. Factor analysis and cluster analysis were employed to determine and statistically analyze the syndrome elements and patterns of HBV-ACLF patients at different stages. ResultsThere were 76 four diagnostic information from 1058 HBV-ACLF patients， and 53 four diagnostic information with a frequency of occurrence ≥ 5% were used as factor analysis entries， including 36 symptom information， 12 tongue information， and 5 pulse information. Four types of TCM patterns were identified in HBV-ACLF， which were liver-gallbladder damp-heat pattern， qi deficiency and blood stasis pattern， liver-kidney yin deficiency pattern， and spleen-kidney yang-deficiency pattern. In the early stage， heat （39.4%， 359/912） and dampness （27.5%， 251/912） were most common， and the pattern of the disease was dominated by liver-gallbladder damp-heat pattern （74.6%， 461/618）； in the middle stage， dampness （30.2%， 187/619） and blood stasis （20.7%， 128/619） were most common， and the patterns of the disease were dominated by liver-gallbladder damp-heat pattern （53.2%， 189/355）， and qi deficiency and blood stasis pattern （27.6%， 98/355）； and in the late stage， the pattern of the disease was dominated by qi deficiency （26.3%， 40/152） and yin deficiency （20.4%， 31/152）， and the patterns were dominated by qi deficiency and blood stasis pattern （36.5%， 31/85）， and liver-gallbladder damp-heat pattern （25.9%， 22/85）. ConclusionThere are significant differences in the distribution of syndrome elements and patterns at different stages of HBV-ACLF， presenting an overall trend of evolving patterns as "from excess to deficiency， transforming from excess to deficiency"， which is damp-heat → blood stasis → qi-blood yin-yang deficiency.

Liquid chromatography-electrospray ionization tandem mass spectrometry(LC-ESI-MS)is a widely utilized technique for in vivo pharmaceutical analysis.Ionization interference within electrospray ion source,occurring between drugs and metabolites,can lead to signal variations,potentially compromising quantitative accuracy.Currently,method validation often overlooks this type of signal interference,which may result in systematic errors in quantitative results without matrix-matched calibration.In this study,we conducted an investigation using ten different groups of drugs and their corresponding me-tabolites across three LC-ESI-MS systems to assess the prevalence of signal interference.Such in-terferences can potentially cause or enhance nonlinearity in the calibration curves of drugs and metabolites,thereby altering the relationship between analyte response and concentration for quanti-fication.Finally,we established an evaluation scheme through a step-by-step dilution assay and employed three resolution methods:chromatographic separation,dilution,and stable labeled isotope internal standards correction.The above strategies were integrated into the method establishment process to improve quantitative accuracy.

Objective:To discuss the effects of walking function-guided interactive Tuina(Chinese therapeutic massage)on spatiotemporal gait parameters in children with spastic cerebral palsy(CP). Methods:Fifty children with spastic diplegic CP were divided into an observation group and a control group following a paired design and random number principle,with 25 cases in each group.The observation group was treated with the walking function-guided interactive Tuina,and the control group was offered the"six methods of spine and back"Tuina,20 min for each session and 5 sessions weekly for 3 consecutive months.The children's changes were assessed using the percentage of dimension E(walking,running,and jumping)of the gross motor function measure-88(GMFM-88)and three-dimensional gait analysis. Results:After treatment,the percentage of GMFM-88 dimension of dimension E(walking,running,and jumping)changed significantly in both groups(P<0.05),and the between-group difference was also statistically significant(P<0.05).After treatment,the step length,walking speed,and step frequency changed markedly in the observation group(P<0.05)and were significantly different from those in the control group(P<0.05).After the intervention,the stance phase and double support extended,and the swing phase became shorter in the observation group(P<0.05);the between-group differences were statistically significant(P<0.05).The maximal knee flexion angle and maximal posterior pelvic tilt angle decreased After treatment in the observation group,and the maximal anterior pelvic tilt angle increased,all showing statistical significance(P<0.05);the between-group differences were statistically significant(P<0.05). Conclusion:Compared with the passive Tuina manipulations,the"six methods of the spine and back",walking function-guided interactive Tuina has its advantage in improving walking function in children with spastic CP,manifesting as better lower-limb force line and walking efficiency.

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Humans ; Asthma/drug therapy* ; Biological Therapy

Heart failure is the leading cause of death worldwide. Compound Danshen Dripping Pill (CDDP) or CDDP combined with simvastatin has been widely used to treat patients with myocardial infarction and other cardiovascular diseases in China. However, the effect of CDDP on hypercholesterolemia/atherosclerosis-induced heart failure is unknown. We constructed a new model of heart failure induced by hypercholesterolemia/atherosclerosis in apolipoprotein E (ApoE) and LDL receptor (LDLR) dual deficient (ApoE^-/-LDLR^-/-) mice and investigated the effect of CDDP or CDDP plus a low dose of simvastatin on the heart failure. CDDP or CDDP plus a low dose of simvastatin inhibited heart injury by multiple actions including anti-myocardial dysfunction and anti-fibrosis. Mechanistically, both Wnt and lysine-specific demethylase 4A (KDM4A) pathways were significantly activated in mice with heart injury. Conversely, CDDP or CDDP plus a low dose of simvastatin inhibited Wnt pathway by markedly up-regulating expression of Wnt inhibitors. While the anti-inflammation and anti-oxidative stress by CDDP were achieved by inhibiting KDM4A expression and activity. In addition, CDDP attenuated simvastatin-induced myolysis in skeletal muscle. Taken together, our study suggests that CDDP or CDDP plus a low dose of simvastatin can be an effective therapy to reduce hypercholesterolemia/atherosclerosis-induced heart failure.

Objective:To investigate the dynamic functional connectivity (dFC) of bilateral precuneus at resting-state in obsessive-compulsive disorder (OCD).Methods:Fifty patients with OCD who matched the criteria of ICD-10 and 50 healthy controls (HCs) were examined by the resting-state functional magnetic resonance imaging scanning. Voxel-based whole-brain dFC method was used to analyze the dFC of bilateral precuneus at resting-state in OCD; Pearson correlation analyses was used to analyze the relationship between the abnormal dFC values and clinical symptoms in OCD; support vector machine analyses was used to explore whether abnormal dFC could be used to identify OCD.Results:Compared with HCs, patients with OCD showed decreased dFC values between left precuneus and left medial prefrontal cortex (MPFC) (0.23±0.02 vs. 0.26±0.03, t=-6.23, P<0.05, GRF corrected), left cuneus (0.24±0.03 vs. 0.28±0.04, t=-5.30, P<0.05, GRF corrected), and left paracentral lobule (0.23±0.03 vs. 0.27±0.04, t=-5.36, P<0.05, GRF corrected); and decreased dFC values between right precuneus and left postcentral gyrus (0.23±0.04 vs. 0.27±0.04, t=-5.12, P<0.05, GRF corrected). The decreased dFC values between left precuneus and left MPFC was positively correlated with the total score of Yale-Brown obsessive compulsive scale (Y-BOCS)( r=0.289, P<0.05, uncorrected); the decreased dFC values between right precuneus and left posterior central gyrus was positively correlated with Y-BOCS total scores ( r=0.292, P<0.05, uncorrected) and obsessive subscale scores ( r=0.304, P<0.05, uncorrected). The area under the curve value of the decreased dFC values between right precuneus and left posterior central gyrus was 0.856; the Youden Index was 0.52; the sensitivity was 100%, and the specificity was 52%. Conclusions:The dFC of bilateral precuneus decreases at resting-state in patients with OCD. The abnormal dFC value between the right precuneus and the left posterior central gyrus may have implications to identify OCD.

Objective:To investigate the dynamic functional connectivity (dFC) of bilateral precuneus at resting-state in obsessive-compulsive disorder (OCD).Methods:Fifty patients with OCD who matched the criteria of ICD-10 and 50 healthy controls (HCs) were examined by the resting-state functional magnetic resonance imaging scanning. Voxel-based whole-brain dFC method was used to analyze the dFC of bilateral precuneus at resting-state in OCD; Pearson correlation analyses was used to analyze the relationship between the abnormal dFC values and clinical symptoms in OCD; support vector machine analyses was used to explore whether abnormal dFC could be used to identify OCD.Results:Compared with HCs, patients with OCD showed decreased dFC values between left precuneus and left medial prefrontal cortex (MPFC) (0.23±0.02 vs. 0.26±0.03, t=-6.23, P<0.05, GRF corrected), left cuneus (0.24±0.03 vs. 0.28±0.04, t=-5.30, P<0.05, GRF corrected), and left paracentral lobule (0.23±0.03 vs. 0.27±0.04, t=-5.36, P<0.05, GRF corrected); and decreased dFC values between right precuneus and left postcentral gyrus (0.23±0.04 vs. 0.27±0.04, t=-5.12, P<0.05, GRF corrected). The decreased dFC values between left precuneus and left MPFC was positively correlated with the total score of Yale-Brown obsessive compulsive scale (Y-BOCS)( r=0.289, P<0.05, uncorrected); the decreased dFC values between right precuneus and left posterior central gyrus was positively correlated with Y-BOCS total scores ( r=0.292, P<0.05, uncorrected) and obsessive subscale scores ( r=0.304, P<0.05, uncorrected). The area under the curve value of the decreased dFC values between right precuneus and left posterior central gyrus was 0.856; the Youden Index was 0.52; the sensitivity was 100%, and the specificity was 52%. Conclusions:The dFC of bilateral precuneus decreases at resting-state in patients with OCD. The abnormal dFC value between the right precuneus and the left posterior central gyrus may have implications to identify OCD.

Objective:To investigate the spontaneous neural activities and the whole-brain functional connectivity(FC) patterns at rest in patients with obsessive-compulsive disorder (OCD).Methods:40 drug-naive patients with OCD matched the diagnostic criteria of ICD-10 (OCD group), and 38 genders, age, education-matched healthy controls (controls group) underwent resting-state functional magnetic resonance imaging scan. The fractional amplitude of low-frequency fluctuations (fALFF) approach was used to explore spontaneous neural activities. The brain region with abnormal fALFF value (right orbitofrontal cortex (OFC)) was used as the interested region to carry out the whole-brain FC analysis. We analyzed the correlation of clinical symptoms with the abnormal fALFF and FC values by partial correlation analysis in patients with OCD.Results:Compared with controls group, increased fALFF were found in the right OFC and right dorsolateral prefrontal gyrus ( t=4.45, 5.25; P<0.05, GRF corrected), and increased FC were observed between the right OFC and left OFC, and left cerebellum crus Ⅱ ( t=5.39, 4.94; P<0.05, GRF corrected) in OCD group. The increased FC between right OFC and left cerebellum crus Ⅱ positively correlated with 17-Items Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale scores ( r=0.401, P=0.015; r=0.389, P=0.019; uncorrected). Conclusions:The local spontaneous neural activities and FC in the cortical-striatal-thalamic-cortical and OFC-cerebellar circuits were abnormal at rest in patients with OCD.