To investigate the protective effects and underlying mechanisms of Qin-Zhu-Liang-Xue decoction (QZLX) in atopic dermatitis (AD) and glucocorticoid resistance, we conducted a single-blinded, randomized controlled clinical trial to evaluate the efficacy and safety of this concoction. Network pharmacology analysis was performed and validated through clinical studies. The efficacy, safety, and mechanism of action of QZLX and glucocorticoid receptor (GR) α recombinant protein were assessed in AD mice induced by 2,4-dinitrofluorobenzene (DNFB). Correlation analysis was performed to determine the clinical relevance of GRα. The trial demonstrated that patients who received QZLX showed considerable improvements in their Scoring Atopic Dermatitis (SCORAD) and Dermatology Life Quality Index (DLQI) scores compared with those who received mizolastine at week 4. Network pharmacological analysis identified GRα as a key target for QZLX in AD treatment. QZLX administration increased the serum GRα expression in AD patients, alleviated AD symptoms in mice, decreased inflammatory cytokine expression, and increased GRα expression without affecting liver or kidney function. In addition, GRα recombinant protein improved AD-like skin lesions in DNFB-induced mice. A negative correlation was observed between GRα expression and clinical parameters, including SCORAD, DLQI, and serum IgE levels. QZLX alleviates AD symptoms through the upregulation of GRα and thus presents a novel therapeutic strategy for the prevention of glucocorticoid resistance in AD management.
Dermatitis, Atopic/drug therapy* ; Animals ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Mice ; Network Pharmacology ; Male ; Female ; Adult ; Receptors, Glucocorticoid/metabolism* ; Disease Models, Animal ; Single-Blind Method ; Middle Aged ; Young Adult

Objective:To investigate the prognostic value of myocardial flow reserve (MFR) measured by SPECT myocardial blood flow (MBF) quantitative technique in patients with intermediate stenoses of coronary arteries.Methods:From September 2019 to May 2021, patients with intermediate stenoses (50% to 80%) identified by invasive coronary angiography in Fuwai Hospital, Chinese Academy of Medical Sciences, Fuwai Center China Cardiovascular Hospital, and TEDA International Cardiovascular Hospital were prospectively included. All patients underwent a one-day rest/stress SPECT myocardial perfusion imaging (MPI) and SPECT MBF quantification. The radioactivity distribution of each segment of the MPI bullseye polar maps were obtained according to the standard 5-point method to obtain the summed stress score (SSS) and the summed difference score (SDS) to determine the existence of abnormality. ROC curve analysis was used to obtain the optimal prognostic cut-off value for MFR. The primary endpoint was defined as cardiovascular endpoint events. Survival and prognostic analyses were conducted by Kaplan-Meier method and Cox proportional hazard models. The difference of AUCs was analyzed by Delong test.Results:A total of 314 patients (194 males, 120 females; age (59.4±8.6) years) were enrolled. Over a median follow-up duration of 754 (range: 628-914) d, 54 patients had endpoint events. ROC curve showed that the prediction ability of MFR was significantly better than that of conventional MPI (AUCs: 0.713 and 0.512; z=3.76, P<0.001). The optimal prognostic cut-off value for MFR to predict endpoint events in patients with intermediate stenoses was 2.04. Cox multivariate analysis showed that MFR (hazard ratio ( HR)=0.434, 95% CI: 0.282-0.669, P<0.001) was an independent predictor of endpoint events in patients with intermediate stenoses. Kaplan-Meier survival analysis showed that the prevalence of endpoint events in patients with MFR≤2.04 was significantly higher than that in patients with MFR>2.04 (25.4%(43/169) vs 7.6%(11/145); χ2=21.27, P<0.001). Conclusion:The MFR measured by SPECT MBF quantitative technique has an independent predictive value for cardiovascular endpoint events in patients with intermediate stenoses.

Objective To investigate the effect of very-long-chain saturated fatty acids on Tau protein phosphorylation and membrane fluidity in human neuroblastoma SH-SY5Y cells,and to explore its role in the pathogenesis of Alzheimer's disease(AD).Methods Human neuroblastoma SH-SY5Y cells in logarithmic growth phase were randomly divided into control group,C22∶0 group,and C24:0 group.Cells in the control group were routinely cultured,while cells in the C22:0 and C24:0 groups were treated with culture medium containing 10 μmol·L-1very-long-chain saturated fatty acids C22:0 and C24:0,respectively.After 24 hours of incubation,cells were collected.The expression levels of total Tau protein,phosphorylated Tau protein at serine 396 site(p-Tau-ser396),glycogen synthase kinase 3β(GSK-3β),and phosphorylated GSK-3 β protein at serine 9 site(p-GSK-3β-Ser9)in cells of each group were detected by using Western blot.The malondialdehyde(MDA)level in cells of each group was determined by using the thiobarbituric acid method.The fluorescence recovery rate and diffusion coefficient of cell membranes were measured by using fluorescence recovery after photobleaching technique,and the fluidity of cell membranes was evaluated.Results The total Tau protein level in SH-SY5Y cells showed no statistically significant difference among the three groups(F=1.807,P＞0.05).However,there was a statistically significant difference in the level of p-Tau-ser396 in SH-SY5Y cells among the three groups(F=18.397,P＜0.05).Specifically,the level of p-Tau-ser396 in SH-SY5Y cells in the C22:0 and C24:0 groups was significantly higher than that in the control group(P＜0.05),and the level of p-Tau-ser396 in SH-SY5Y cells in the C24:0 group was significantly higher than that in the C22:0 group(P＜0.05).There was no statistically significant difference in the GSK-3 β protein level in SH-SY5Y cells among the three groups(F=0.351,P＞0.05).However,there was a statistically significant difference in the level of p-GSK-3β-Ser9 in SH-SY5Y cells among the three groups(F=13.330,P＜0.05).Specifically,the level of p-GSK-3β-ser9 in SH-SY5Y cells in the C22:0 and C24:0 groups was significantly lower than that in the control group(P＜0.05),and there was no statistically significant difference in the level of p-GSK-3β-ser9 in SH-SY5Y cells between the C22:0 group and C24:0 group(P＞0.05).The MDA level in SH-SY5Y cells in the C24:0 group was significantly higher than that in the control group and C22:0 group(P＜0.05);there was no statistically significant difference in the MDA level in SH-SY5Y cells between the control group and C22:0 group(P＞0.05).The fluorescence recovery rate and diffusion coefficient of SH-SY5Y cells in the C22:0 and C24:0 groups showed a decreasing trend compared to the control group,but there was no statistically significant difference in the fluorescence recovery rate and diffusion coefficient of SH-SY5Y cells among the three groups(F=3.891,3.649,P＞0.05).Conclusion Very-long-chain saturated fatty acids C22:0 and C24:0 can promote hyperphosphorylation of Tau protein,induce cellular oxidative damage,and tend to reduce the fluidity cell membranes.Very-long-chain saturated fatty acids may be one of the factors that cause the onset of AD.

Objective To investigate the possible mechanism of action of Jinqi Qingshu granules(JQQSG)in the treatment of community-acquired pneumonia(CAP)by network pharmacology and molecular docking technology.Methods The TCMSP database and SwissTargetPrediction database were used to obtain and screen the active ingredients and targets of JQQSG,and GeneCards,OMIM,TTD,and DisGeNET databases were used to search for the predicted targets of CAP,and the two targets were mapped and then imported into STRING database to construct a PPI network to screen the key targets,and then the GO and KEGG pathway enrichment were analyzed by the DAVID database,and molecular docking was carried out by the AutoDock Tools software.Results 209 active ingredients and 1 041 targets of JQQSG were obtained after screening;312 targets were co-activated with CAP,and 64 core targets were obtained after PPI network screening.571 biological processes,68 cellular components,and 199 molecular functions were analyzed by GO enrichment,and 165 KEGG pathways were analyzed by KEGG pathway enrichment,mainly involved in protein action,apoptosis and MAPK signaling pathway.Molecular docking suggests that the core target and the core components all have good binding ability.Conclusion The mechanism of action of JQQSG in the treatment of CAP may be related to its regulation of Akt,MAPK signaling pathway,improvement of oxidative stress,and other pathways to exert anti-inflammatory and antioxidant effects,which could lay the foundation for further in-depth study of its specific mechanism of action.

Purpose: This study aims to evaluate the efficacy and safety of a new combination treatment of vinorelbine and pyrotinib in human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer (MBC) and provide higher level evidence for clinical practice. Materials and Methods: This was a prospective, single-arm, phase 2 trial conducted at three institutions in China. Patients with HER2-positive MBC, who had previously been treated with trastuzumab plus a taxane or trastuzumab plus pertuzumab combined with a chemotherapeutic agent, were enrolled between March 2020 and December 2021. All patients received pyrotinib 400 mg orally once daily plus vinorelbine 25 mg/m2 intravenously or 60-80 mg/m2 orally on day 1 and day 8 of 21-day cycle. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival, and safety. Results: A total of 39 patients were enrolled. All patients had been pretreated with trastuzumab and 23.1% (n=9) of them had accepted trastuzumab plus pertuzumab. The median follow-up time was 16.3 months (95% confidence interval [CI], 5.3 to 27.2), and the median PFS was 6.4 months (95% CI, 4.0 to 8.8). The ORR was 43.6% (95% CI, 27.8% to 60.4%) and the DCR was 84.6% (95% CI, 69.5% to 94.1%). The median PFS of patients with versus without prior pertuzumab treatment was 4.6 and 8.3 months (p=0.017). The most common grade 3/4 adverse events were diarrhea (28.2%), neutrophil count decreased (15.4%), white blood cell count decreased (7.7%), vomiting (5.1%), and anemia (2.6%). Conclusion Pyrotinib plus vinorelbine showed promising efficacy and tolerable toxicity as second-line treatment in patients with HER2-positive MBC.

Atypical sensory responsivity is widely reported in autistic individuals and is related to elevated functional difficulties. Dynamically, altered initial responses and/or habituation rates could underlie their atypical averaged responses to repeated sensory stimuli. In this study we aimed to measure the arousal level in response to different types of auditory stimuli and the dynamic change of atypical arousal level using pupillometry in autistic children. In Experiment 1, 43 autistic children and 49 neurotypical (NT) children were asked to passively listen to a mild sound and an aversive sound repeatedly. In Experiment 2, 39 autistic children and 44 NT children who went through Experiment 1 listened to a gradually emerging non-startling sound and a suddenly emerging startling sound in a random order. We found that the autistic group showed hyper-arousal in response to the aversive sound and the startling sound as reflected by their larger change in pupil area. In comparison, these autistic children demonstrated normal arousal in response to the mild sound and the non-startling sound. Dynamically, the autistic group had a larger peak pupil area change than the NT group in the first trial and a normal habituation rate to the aversive sound. In summary, our results suggest hyper-arousal to aversive and startling stimuli and the role of larger initial responses in hyper-arousal in autism. Minimizing aversive and startling sensory stimuli or gradually increasing the volume of aversive auditory stimuli to allow autistic children to adapt using the principle of habituation is recommended to reduce the arousal level and problematic behaviors of autistic children.
Humans ; Male ; Child ; Female ; Acoustic Stimulation ; Autistic Disorder/physiopathology* ; Arousal/physiology* ; Pupil/physiology* ; Habituation, Psychophysiologic/physiology* ; Auditory Perception ; Child, Preschool

As the "star product" of Shanghai, Shanghai herbal paste has played an irreplaceable role both in the treatment of diseases and nurturing health. The concept of Shanghai regional culture, Shanghai style Chinese medicine and Shanghai herbal paste were introduced by the combination of literature search and practical experience. The historical developments of Shanghai herbal paste were summarized in order to understand Shanghai herbal paste comprehensively and provide a historical and empirical basis for the inheritance and innovation of Shanghai herbal paste.

Objective To study the curative effects of traditional Chinese medicine paste combined with Baduanjin in treatment of osteoporotic vertebral compression fracture (OVCF) after percutaneous vertebroplasty (PVP). Methods 120 OVCF patients treated with PVP in our hospital from January 2016 to September 2017 were divided into the observation group (60 cases) and the control group (60 cases) according to the random number table method. The control group was given calcium carbonate D₃ chewable tablets orally with routine guidance. In addition to the same treatment as the control group, the observation group received the traditional Chinese medicine paste orally with Baduanjin exercise. Both groups were treated for 6 months and followed-up for 3 years. The curative effects in the two groups after 6 months treatment and the low back pain after 1, 3 and 6 months of treatment were recorded. The changes of bone mineral density (BMD), kyphosis angle (Cobb angle), anterior wall height of vertebral body (AVBH) and level of bone metabolism indexes in the two groups were compared before and after treatment for 6 months. The follow-up times and the incidences of push-back fracture after PVP during follow-up were recorded. Results After 6 months of treatment, the clinical cure rate of the observation group was 73.33%, which was higher than 53.33% of the control group(P<0.05). Compared with pretreatment, the scores of visual analogue scale (VAS) in the two groups gradually decreased after 3 and 6 months of treatment, and the observation group had a lower scores than the control group (P<0.05). After 6 months treatment, BMD and AVBH of lumbar vertebrae and femoral neck in both groups increased, and the observation group was higher than that in the control group. The Cobb angle and serum levels of Type I procollagen degradation products (β-Cross I), the n-terminal middle osteocalcin (N-MID Ost) and parathyroid hormone (PTH) decreased in both groups, and the observation group was lower than those in the control group (P<0.05). There was no significant difference in fracture incidence after PVP in the year 1, year 1 to 3 follow up between the two groups (P>0.05). During the 3 years follow-up, the incidence of push-body fracture after PVP in the observation group was 3.33%, which was lower than that in the control group 20.00%( P<0.05). Conclusion Traditional Chinese medicine paste combined with Baduanjin reduced the serum levels of β-Cross I, N-MID Ost and PTH, regulated bone metabolism, improved BMD and AVBH of lumbar vertebrae and femoral neck, reduced Cobb angle, promoted the recovery of lumbar function, alleviated patients' back pain, lowered the incidence of push-body fracture after PVP. The curative effects were remarkable.

Objective To establish a method and study the pharmacokinetics for concentration determination of effective components in Xiakucao Xiaoliu mixture in Normal Rat Plasma By LC-MS/MS. Methods The mobile phase was methanol-water (0.1% formic acid) system under the positive ion mode of C18 chromatographic column, gradient elution was adopted, and the flow rate was 0.3 ml/min. In the negative ion mode, the mobile phase was acetonitrile-water (0.1% formic acid) system, gradient elution, with a flow rate of 0.4 ml/min. Caffeic acid, rosmarinic acid, syringic acid, rutin in positive ion mode and Atractylodes lactone II and Atractylodes lactone III in negative ion mode were respectively determined. Normal rats were intragastrically given Xiakucao Xiaoliu Mixture 7.8 ml/kg, and blood was taken from the orbit at different time points after the administration. The blood concentration was determined by the validated LC-MS/MS method and the non-standard DAS2.0 software was used. The pharmacokinetic parameters of rats after administration were calculated by the compartment model. Results The pharmacokinetic parameters belonged to non atrioventricular model. The pharmacokinetic characteristics of the four main anti-cancer active ingredients of Caffeic acid, Rosmarinic acid, Syringic acid and Atractylodes Ⅲ in rats after administration of Xiakucao Xiaoliu Mixture were significantly different from those reported in the literature after the administration of monomers. Conclusion The established method was simple, accurate and sensitive, which could be suitable for the content determination of effective components in Xiakucao Xiaoliu mixture in Normal Rat Plasma, which would be a valuable information for the study on main anticancer active substances.

Objective:To explore the changes of right ventricular myocardial perfusion in pulmonary arterial hypertension (PAH) pig models with a quantitative analysis technique based on dynamic SPECT myocardial perfusion imaging, and analyze the relationship between myocardial blood flow, hemodynamics and right ventricular function.Methods:Eleven Chinese miniature pigs (all males, 6-8 months old) weighing 25-30 kg were selected. The PAH models were established by ligating the main pulmonary artery and embolizing the right lower pulmonary artery. After the models were established, dynamic myocardial perfusion imaging with one-day resting/adenosine stress 99Tc m-methoxyisobutylisonitrile (MIBI) SPECT was performed, and the quantitative parameters of left and right ventricles were obtained, including stress myocardial blood flow (SMBF), rest myocardial blood flow (RMBF) and myocardial flow reserve (MFR: the ratio of stress to rest myocardial blood flow). Right heart catheterization was performed to evaluate the mean pulmonary arterial pressure (mPAP), and the right heart function index tricuspid annular plane systolic excursion (TAPSE) was measured by transthoracic echocardiography. According to TAPSE, animals were divided into right heart function preserved group ( n=5, TAPSE≥17 mm) and right heart dysfunction group ( n=4, TAPSE<17 mm). Pearson correlation analysis and the independent-sample t test were used for data analysis. Results:Nine experimental pig models were established with increased mPAP of (38.1 ± 11.6 ) mmHg (1 mmHg=0.133 kPa). Myocardial perfusion imaging showed clear radiotracer uptake in the right heart and myocardial hypertrophy. There was a significant positive correlation between right ventricular myocardial RMBF ((0.71±0.13) ml·min -1·g -1) and mPAP ( r=0.94, P< 0.001). The SMBF in the decreased right ventricular function group was significantly lower than that in the preserved right ventricular function group ((1.66±0.35) vs (2.24±0.30) ml·min -1·g -1;t=2.68, P=0.032). Conclusion:SPECT myocardial blood flow quantification can be used to evaluate the right ventricular myocardial blood flow in pig models of PAH.