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Objective Data mining technology was used to mine the medication rules of the prescriptions used in the treatment of pediatric atopic dermatitis by Chinese medical master XUAN Guo-Wei.Methods The medical records of effective cases of pediatric atopic dermatitis treated by Professor XUAN Guo-Wei at outpatient clinic were collected,and then the medical data were statistically analyzed using frequency statistics,association rule analysis and cluster analysis.Results A total of 242 prescriptions were included,involving 101 Chinese medicinals.There were 23 commonly-used herbs,and the 16 high-frequency herbs(frequency>100 times)were Glycyrrhizae Radix et Rhizoma,Saposhnikoviae Radix,Glehniae Radix,Perillae Folium,Ophiopogonis Radix,Cynanchi Paniculati Radix et Rhizoma,Microctis Folium,Dictamni Cortex,Scrophulariae Radix,Coicis Semen,Cicadae Periostracum,Lilii Bulbus,Rehmanniae Radix,Kochiae Fructus,Sclerotium Poriae Pararadicis,and Euryales Semen.The analysis of the medicinal properties showed that most of the herbs were sweet and cold,and mainly had the meridian tropism of the spleen,stomach and liver meridians.The association rule analysis yielded 24 commonly-used drug combinations and 20 association rules.Cluster analysis yielded 2 core drug combinations.Conclusion For the treatment of pediatric atopic dermatitis,Professor XUAN Guo-Wei focuses on the clearing,supplementing and harmonizing therapies,and the medication principle of"supporting the healthy-qi to eliminate the pathogen,and balancing the yin and yang"is applied throughout the treatment.
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Objectives: To explore the antitumor effects of redox-responsive nanoparticles containing platinum(Ⅳ)-NP@Pt(Ⅳ) in ovarian cancer. Methods: Redox-responsive polymer carriers were synthesized. Polymer carriers and platinum(Ⅳ)-Pt(Ⅳ) can self-assemble into NP@Pt(Ⅳ). Inductively coupled plasma mass spectrometry was performed to detect the platinum release from NP@Pt(Ⅳ) in reducing environment and the platinum content in ovarian cancer cells ES2 treated with cisplatin, Pt(Ⅳ) and NP@Pt(Ⅳ). The proliferation ability of the ovarian cancer cells were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cellular apoptosis was assessed by flow cytometry. Collection of primary ovarian cancer tissues from patients with primary high-grade serous ovarian cancer who were surgically treated at the Cancer Hospital of the Chinese Academy of Medical Sciences from October to December 2022. The high-grade serous ovarian cancer patient-derived xenograft (PDX) mice were intravenously injected with Cy7.5 labeled NP@Pt(Ⅳ) followed by in vivo imaging system. Mice were treated with PBS, cisplatin and NP@Pt(Ⅳ). Tumor volume and weight were measured in each group. Necrosis, apoptosis and cell proliferation of tumor tissues were detected by hematoxylin-eosin (HE) staining, TUNEL fluorescence staining and Ki-67 immunohistochemistry staining. Body weight and HE staining of heart, liver, spleen, lung and kidney of mice in each group were measured. Results: The platinum release of NP@Pt(Ⅳ) after 48 hours in reducing environment was 76.29%, which was significantly higher than that of 26.82% in non-reducing environment (P<0.001). The platinum content in ES2 cells after 4 hours and 7 hours of treatment with NP@Pt(Ⅳ) (308.59, 553.15 ng/million cells) were significantly higher than those of Pt(Ⅳ) (100.21, 180.31 ng/million cells) and cisplatin (43.36, 50.36 ng/million cells, P<0.05). The half inhibitory concentrations of NP@Pt(Ⅳ) in ovarian cancer cells ES2, A2780, A2780DDP were 1.39, 1.42 and 4.62 μmol/L, respectively, which were lower than those of Pt(IV) (2.89, 7.27, and 16.74 μmol/L) and cisplatin (5.21, 11.85, and 71.98 μmol/L). The apoptosis rate of ES2 cells treated with NP@Pt(Ⅳ) was (33.91±3.80)%, which was significantly higher than that of Pt(Ⅳ) [(16.28±2.41)%] and cisplatin [(15.01±1.17)%, P<0.05]. In high-grade serous ovarian cancer PDX model, targeted accumulation of Cy7.5 labeled NP@Pt(Ⅳ) at tumor tissue could be observed. After the treatment, the tumor volume of mice in NP@Pt(IV) group was (130±98) mm3, which was significantly lower than those in control group [(1 349±161) mm3, P<0.001] and cisplatin group [(715±293) mm3, P=0.026]. The tumor weight of mice in NP@Pt(IV) group was (0.17±0.09)g, which was significantly lower than those in control group [(1.55±0.11)g, P<0.001] and cisplatin group [(0.82±0.38)g, P=0.029]. The areas of tumor necrosis and apoptosis in mice treated with NP@Pt(Ⅳ) were higher than those in mice treated with cisplatin. Immunohistochemical staining revealed that there were low expressions of Ki-67 at tumor tissues of mice treated with NP@Pt(Ⅳ) compared with cisplatin. The change in body weight of mice in NP@Pt(Ⅳ) group was not significantly different from that of the control group [(18.56±2.04)g vs.(20.87±0.79)g, P=0.063]. Moreover, the major organs of the heart, liver, spleen, lung, and kidney were also normal by HE staining. Conclusion: Redox-responsive NP@Pt(Ⅳ), produced in this study can enhance the accumulation of cisplatin in ovarian cancer cells and improve the efficacy of ovarian cancer chemotherapy.
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Humains , Femelle , Animaux , Souris , Tumeurs de l'ovaire/traitement médicamenteux , Platine , Cisplatine/pharmacologie , Lignée cellulaire tumorale , Antigène KI-67 , Carcinome épithélial de l'ovaire , Cystadénocarcinome séreux , Modèles animaux de maladie humaine , Éosine jaunâtre , Nécrose , Polymères , PoidsRésumé
Objectives: To explore the antitumor effects of redox-responsive nanoparticles containing platinum(Ⅳ)-NP@Pt(Ⅳ) in ovarian cancer. Methods: Redox-responsive polymer carriers were synthesized. Polymer carriers and platinum(Ⅳ)-Pt(Ⅳ) can self-assemble into NP@Pt(Ⅳ). Inductively coupled plasma mass spectrometry was performed to detect the platinum release from NP@Pt(Ⅳ) in reducing environment and the platinum content in ovarian cancer cells ES2 treated with cisplatin, Pt(Ⅳ) and NP@Pt(Ⅳ). The proliferation ability of the ovarian cancer cells were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cellular apoptosis was assessed by flow cytometry. Collection of primary ovarian cancer tissues from patients with primary high-grade serous ovarian cancer who were surgically treated at the Cancer Hospital of the Chinese Academy of Medical Sciences from October to December 2022. The high-grade serous ovarian cancer patient-derived xenograft (PDX) mice were intravenously injected with Cy7.5 labeled NP@Pt(Ⅳ) followed by in vivo imaging system. Mice were treated with PBS, cisplatin and NP@Pt(Ⅳ). Tumor volume and weight were measured in each group. Necrosis, apoptosis and cell proliferation of tumor tissues were detected by hematoxylin-eosin (HE) staining, TUNEL fluorescence staining and Ki-67 immunohistochemistry staining. Body weight and HE staining of heart, liver, spleen, lung and kidney of mice in each group were measured. Results: The platinum release of NP@Pt(Ⅳ) after 48 hours in reducing environment was 76.29%, which was significantly higher than that of 26.82% in non-reducing environment (P<0.001). The platinum content in ES2 cells after 4 hours and 7 hours of treatment with NP@Pt(Ⅳ) (308.59, 553.15 ng/million cells) were significantly higher than those of Pt(Ⅳ) (100.21, 180.31 ng/million cells) and cisplatin (43.36, 50.36 ng/million cells, P<0.05). The half inhibitory concentrations of NP@Pt(Ⅳ) in ovarian cancer cells ES2, A2780, A2780DDP were 1.39, 1.42 and 4.62 μmol/L, respectively, which were lower than those of Pt(IV) (2.89, 7.27, and 16.74 μmol/L) and cisplatin (5.21, 11.85, and 71.98 μmol/L). The apoptosis rate of ES2 cells treated with NP@Pt(Ⅳ) was (33.91±3.80)%, which was significantly higher than that of Pt(Ⅳ) [(16.28±2.41)%] and cisplatin [(15.01±1.17)%, P<0.05]. In high-grade serous ovarian cancer PDX model, targeted accumulation of Cy7.5 labeled NP@Pt(Ⅳ) at tumor tissue could be observed. After the treatment, the tumor volume of mice in NP@Pt(IV) group was (130±98) mm3, which was significantly lower than those in control group [(1 349±161) mm3, P<0.001] and cisplatin group [(715±293) mm3, P=0.026]. The tumor weight of mice in NP@Pt(IV) group was (0.17±0.09)g, which was significantly lower than those in control group [(1.55±0.11)g, P<0.001] and cisplatin group [(0.82±0.38)g, P=0.029]. The areas of tumor necrosis and apoptosis in mice treated with NP@Pt(Ⅳ) were higher than those in mice treated with cisplatin. Immunohistochemical staining revealed that there were low expressions of Ki-67 at tumor tissues of mice treated with NP@Pt(Ⅳ) compared with cisplatin. The change in body weight of mice in NP@Pt(Ⅳ) group was not significantly different from that of the control group [(18.56±2.04)g vs.(20.87±0.79)g, P=0.063]. Moreover, the major organs of the heart, liver, spleen, lung, and kidney were also normal by HE staining. Conclusion: Redox-responsive NP@Pt(Ⅳ), produced in this study can enhance the accumulation of cisplatin in ovarian cancer cells and improve the efficacy of ovarian cancer chemotherapy.
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Humains , Femelle , Animaux , Souris , Tumeurs de l'ovaire/traitement médicamenteux , Platine , Cisplatine/pharmacologie , Lignée cellulaire tumorale , Antigène KI-67 , Carcinome épithélial de l'ovaire , Cystadénocarcinome séreux , Modèles animaux de maladie humaine , Éosine jaunâtre , Nécrose , Polymères , PoidsRésumé
Octapeptin has strong antibacterial activity against Gram-negative bacteria such as Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii, while it also has activity against some Gram-positive bacteria. This study used natural octapeptin A3 and B3 as lead compounds for structural modification. Twenty-one peptide derivatives (including A3 and B3) containing eight amino acid residues were prepared by solid-phase synthesis, and evaluated for antibacterial activity and renal cytotoxicity. Among them, three compounds 6, 7 and 17 exhibited broad-spectrum antibacterial activity and significantly enhanced the activity for Gram-positive bacteria while maintaining the activity of Gram-negative bacteria. Several compounds improved the activity for Pseudomonas aeruginosa. Compound 7 was active against all test strains and had relatively low renal cytotoxicity. The results provide a basis for the further development of novel polypeptide antibiotics.
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To explore the quality consistency evaluation method for multi-component traditional Chinese medicine and establish a dissolution evaluation method suitable for the characteristics of multi-component Chinese patent medicine, this study discussed the characteristics and advantages of the flow-through cell method in the dissolution evaluation of Chinese patent medicine by comparing the impact of the small cup method and the flow-through cell method on the dissolution behavior of water-soluble and lipid-soluble major active components of Danshen Tablets. Dissolution tests were performed using the small cup method as described in the 2020 edition of the Chinese Pharmacopoeia and the newly introduced flow-through cell method(closed-loop method) with water solution containing 0.5% SDS as dissolution medium. Cumulative dissolution curves of the water-soluble component salvianolic acid B and the lipid-soluble component tanshinone Ⅱ_A in Danshen Tablets were plotted, and fitting and similarity analysis of the dissolution models was conducted to identify the characteristics and advantages of the flow-through cell method. For the small cup method, 150 mL of water containing 0.5% SDS was used as the dissolution medium, with a rotation speed of 75 r·min~(-1) and a temperature of(37±0.5) ℃, and 3 mL of samples were taken at 15, 30 min, 1, 2, and 4 h, with fresh dissolution medium added at the same temperature and volume. For the flow-through cell method, a closed-loop system was used. Danshen Tablets were placed in the flow-through cell with approximately 6.7 g of glass beads, and 150 mL of water containing 0.5% SDS was used as the dissolution medium. The flow rate was set at 20 mL·min~(-1), and the temperature and sampling were the same as the small cup method. The results showed that compared with the small cup method, the flow-through cell method had stronger discriminative power and higher sensitivity in distinguishing the dissolution behavior of the two components, and could better reflect the differences in formulation quality, especially for water-insoluble lipid-soluble components. Given that there were no essential differences in the in vitro release kinetics between the two methods, the flow-through cell method could not only replace the traditional small cup method but also better guide the formulation development and identify quality issues of formulations.
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Salvia miltiorrhiza , Médecine traditionnelle chinoise , Comprimés , Eau , Lipides , SolubilitéRésumé
PURPOSE@#Different arch structures may cause different foot function injuries. In the past, the arch structure and flexibility of the foot were often defined by the height of the arch, and there was no three-dimensional (3D) structure classification method. In order to form a more complete 3D description, we propose a new classification system of arch volume flexibility (AVF), and then use this new classification system to investigate the relationship between the AVF and arch index (AI), and the arch height flexibility (AHF) and AI, respectively.@*METHODS@#It is proposed to recruit 180 young male adults for the test. We obtained arch volume and AI through 3D scanning and obtained the navicular height through manual measurement. Based on these data, we calculated the AHF and the AVF. Using the quintile method, these arches are divided into very stiff, stiff, neutral, flexible, and very flexible. According to AI value, all arches were divided into cavus, rectus, and planus. The distribution of AVF was compared using χ2 goodness of fit test. The spearman correlation test was used to compare the AHF and AVF. A p < 0.05 indicates that the difference is statistically significant.@*RESULTS@#All participants' plantar data was obtained through 3D scanning, but only 159 of them were complete, so only 318 feet had valid data. The left AHF is (21.23 ± 12.91) mm/kN, and the right AHF is (21.71 ± 12.69) mm/kN. The AVF of the left foot arch is (207.35 ± 118.28) mm3/kg, while the right one is (203.00 ± 117.92) mm3/kg, and the total AVF of the arch was (205.17 ± 117.94) mm3/kg. There was no statistical difference in the AVF between the left and right feet for the same participant (n = 159, p = 0.654). In cavus, the percentage of arch with AVF is 21.4% (very stiff), 21.4% (stiff), 14.3% (neutral), 7.1% (flexible), and 35.7% (very flexible). In rectus, the percentage of arch with AVF is 23.9% (very stiff), 19.6% (stiff), 14.7% (neutral), 24.5% (flexible), and 17.2% (very flexible). In planus, the percentage of arch with AVF is 14.9% (very stiff), 20.6% (stiff), 27.0% (neutral), 16.3% (flexible), and 21.3% (very flexible). Moreover, the correlation between AHF and AVF is not significant (p = 0.060).@*CONCLUSION@#In cavus, rectus, and planus, different AVF accounts different percentage, but the difference is not statistically significant. AVF is evenly distributed in the arches of the feet at different heights. We further found the relationship between AHF and AVF is not significant. As a 3D index, AVF may be able to describe the flexibility of the arch more comprehensively than AHF.
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Adulte , Humains , Mâle , Pied , Traumatismes du pied , Phénomènes biomécaniquesRésumé
The present study aimed to investigate the effect of diosgenin on mammalian target of rapamycin(mTOR), fatty acid synthase(FASN), hypoxia inducible factor-1α(HIF-1α), and vascular endothelial growth factor A(VEGFA) expression in liver tissues of rats with non-alcoholic fatty liver disease(NAFLD) and explore the mechanism of diosgenin on lipogenesis and inflammation in NAFLD. Forty male SD rats were divided into a normal group(n=8) fed on the normal diet and an experimental group(n=32) fed on the high-fat diet(HFD) for the induction of the NAFLD model. After modeling, the rats in the experimental group were randomly divided into an HFD group, a low-dose diosgenin group(150 mg·kg~(-1)·d~(-1)), a high-dose diosgenin group(300 mg·kg~(-1)·d~(-1)), and a simvastatin group(4 mg·kg~(-1)·d~(-1)), with eight rats in each group. The drugs were continuously given by gavage for eight weeks. The levels of triglyceride(TG), total cholesterol(TC), low-density lipoprotein cholesterol(LDL-C), alanine transaminase(ALT), and aspartate transaminase(AST) in the serum were detected by the biochemical method. The content of TG and TC in the liver was detected by the enzyme method. Enzyme-linked immunosorbent assay(ELISA) was used to measure interleukin 1β(IL-1β) and tumor necrosis factor α(TNF-α) in the serum. Lipid accumulation in the liver was detected by oil red O staining. Pathological changes of liver tissues were detected by hematoxylin-eosin(HE) staining. The mRNA and protein expression levels of mTOR, FASN, HIF-1α, and VEGFA in the liver of rats were detected by real-time fluorescence-based quantitative polymerase chain reaction(PCR) and Western blot, respectively. Compared with the normal group, the HFD group showed elevated body weight and levels of TG, TC, LDL-C, ALT, AST, IL-1β, and TNF-α(P<0.01), increased lipid accumulation in the liver(P<0.01), obvious liver steatosis, up-regulated mRNA expression levels of mTOR, FASN, HIF-1α, and VEGFA(P<0.01), and increased protein expression levels of p-mTOR, FASN, HIF-1α, and VEGFA(P<0.01). Compared with the HFD group, the groups with drug treatment showed lowered body weight and levels of TG, TC, LDL-C, ALT, AST, IL-1β, and TNF-α(P<0.05, P<0.01), reduced lipid accumulation in the liver(P<0.01), improved liver steatosis, decreased mRNA expression levels of mTOR, FASN, HIF-1α, and VEGFA(P<0.05, P<0.01), and declining protein expression levels of p-mTOR, FASN, HIF-1α, and VEGFA(P<0.01). The therapeutic effect of the high-dose diosgenin group was superior to that of the low-dose diosgenin group and the simvastatin group. Diosgenin may reduce liver lipid synthesis and inflammation and potentiate by down-regulating the mTOR, FASN, HIF-1α, and VEGFA expression, playing an active role in preventing and treating NAFLD.
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Rats , Mâle , Animaux , Stéatose hépatique non alcoolique/métabolisme , Facteur de croissance endothéliale vasculaire de type A/métabolisme , Facteur de nécrose tumorale alpha/métabolisme , Cholestérol LDL , Rat Sprague-Dawley , Foie , Inflammation/métabolisme , Alimentation riche en graisse/effets indésirables , Sérine-thréonine kinases TOR/métabolisme , ARN messager/métabolisme , Poids , MammifèresRésumé
This study aimed to explore the effect of Ganmai Dazao Decoction on the ethology of rats with posttraumatic stress disorder(PTSD) and study the related mechanism through the changes in magnetic resonance imaging and protein expression. Sixty rats were randomly divided into 6 groups, namely the normal group, the model group, the low(1 g·kg~(-1)), medium(2 g·kg~(-1)), and high-dose Ganmai Dazao Decoction groups(4 g·kg~(-1)), and the positive control group(intragastric administration with 10.8 mg·kg~(-1) of fluoxetine), with 10 rats in each group. Two weeks after inducing PTSD by single-prolonged stress(SPS) in rats, the positive control group was given fluoxetine hydrochloride capsule by gavage, the low, medium, and high-dose groups were given Ganmai Dazao Decoction by gavage, and both the normal group and the model group were given the same volume of normal saline by gavage, each for 7 days. The open field experiment, elevated cross elevated maze, forced swimming experiment, and new object recognition test were carried out for the behavioral test. Three rats in each group were selected to detect the expression of neuropeptide receptor Y1(NPY1R) protein in the hippocampus by Western blot. Then, the other three rats in each group were selected to use the 9.4T magnetic resonance imaging experiment to observe the overall structural changes in the brain region and the anisotropy fraction of the hippocampus. The results of the open field experiment showed that the total distance and central distance of rats in the model group were significantly lower than those in the normal group, and the total distance and central distance of rats in the middle and high-dose Ganmai Dazao Decoction groups were higher than those in the model group. The results of the elevated cross maze test showed that medium and high-dose Ganmai Dazao Decoction remarkably increased the number of open arm entries and the residence time of open arm of rats with PTSD. The results of the forced swimming experiment showed that the immobility time in the water of the model group rats was significantly higher than that of the normal group, and Ganmai Dazao Decoction hugely reduced the immobility time in the water of rats with PTSD. The results of the new object recognition test showed that Ganmai Dazao Decoction significantly increased the exploration time of new objects and familiar objects in rats with PTSD. The results of Western blot showed that Ganmai Dazao Decoction significantly reduced the expression of NYP1R protein in the hippocampus of rats with PTSD. The 9.4T magnetic resonance examination found that there was no significant difference in the structural image among the groups. In the functional image, the fractional anisotropy(FA value) of the hippocampus in the model group was significantly lower than that in the normal group. The FA value of the hippocampus in the middle and high-dose Ganmai Dazao Decoction groups was higher than that in the model group. Ganmai Dazao Decoction reduces the injury of hippocampal neurons by inhibiting the expression of NYP1R in the hippocampus of rats with PTSD, thereby improving the nerve function injury of rats with PTSD and playing a neuroprotective role.
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Animaux , Rats , Éthologie , Troubles de stress post-traumatique , Fluoxétine , Hippocampe , Apprentissage du labyrintheRésumé
Duodenal-type follicular lymphoma (DFL) is a unique subtype of follicular lymphoma (FL), which often involves the second portion of duodenum (descending part of duodenum). Due to its specific pathological features, such as lack of follicular dendritic cells meshwork and disappearance of activation-induced cytidine deaminase expression, DFL presents an inert clinical course and is often confined to the intestinal tract. Inflammation-related biomarkers suggest that the microenvironment may play a likely role in the pathogenesis and favorable prognosis of DFL. Since patients generally have no obvious clinical symptoms and low progression rate, the treatment regimen for DFL is mainly observation and waiting (W&W) strategy. This study will review the latest research progress of epidemiology, diagnosis, treatment and prognosis of DFL in recent years.
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Humains , Lymphome folliculaire/traitement médicamenteux , Tumeurs du duodénum/anatomopathologie , Pronostic , Microenvironnement tumoralRésumé
The clinical tumor therapy was greatly challenged due to the complex characteristics of tumor microenvironment, however, which also provide arena for novel therapeutic strategies. In this study, poly(2-ethyl-2-oxazoline)-poly(lactic acid)-SS-poly(β-amino ester (PEOz-PLA-SS-PBAE) triblock copolymers with pH and GSH double response were synthesized, polymer micelles were prepared by thin film hydration method for loading of silybin to improve its antitumor activity. The critical micelle concentration was determined by pyrene fluorescence method as 1.8 μg·mL-1. The particle size was 155.30 ± 1.80 nm as determined by dynamic light scattering, with polydispersity index of 0.168 ± 0.004. The drug loading and entrapment efficiency of the micelles were determined by HPLC as (5.48 ± 0.04)% and (68.52 ± 0.48)%, respectively. The in vitro drug release profiles showed that the micelles have low pH sensitivity and high GSH responsiveness, and exhibited sustained release profiles. The good biocompatibility of the material was proved by measuring the hemolysis rate and cytotoxicity of the blank micelle. The cytotoxicity and apoptosis rate of tumor cells showed that the drug loaded PEOz-PLA-SS-PBAE micelles had significant inhibitory effect and apoptosis-inducing effect on MDA-MB-231 cells. The results of wounding healing assay and Transwell invasion test showed that the drug loaded PEOz-PLA-SS-PBAE micelles could significantly inhibit the metastasis of MDA-MB-231 cells. The PEOz-PLA-SS-PBAE drug-loaded micelles prepared in this study have good inhibitory effect on tumor growth and anti-tumor metastasis in vitro, which lays the foundation for the further application of silybin.
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Background/Aims@#Stigma related with antidepressants is prevalent in patients with functional dyspepsia. It affects medication compliance and efficacy.Herbal medicine acquired a deep-rooted cultural identity in relieving dyspeptic symptoms in Asians. The research was designed to compare the effectiveness of Zhizhu Kuanzhong capsules (ZZKZ) versus doxepin hydrochloride (doxepin) on alleviating stigma and medication nonadherence among patients with refractory FD (rFD). @*Methods@#Patients with rFD from February 2021 to February 2022 were randomly allocated to receive either doxepin (n = 56) or ZZKZ (n = 57) combined with omeprazole for 4 weeks. Medication possession ratio (MPR), the disease- and medication-associated stigma were analyzed. The scales were utilized to assess dyspeptic symptoms (Leeds Dyspepsia Questionnaire) and psychological conditions (Generalized Anxiety Disorder Questionnaire and Patient Health Questionnaire). @*Results@#The MPR values for ZZKZ were significantly higher than those for doxepin (P < 0.001). The stigma scores decreased in ZZKZ group while increased in doxepin group compared to baseline after treatment. The proportion of patients showing ZZKZ-associated stigma was significantly lower than doxepin-associated stigma (P < 0.001). The MPR values were negatively correlated with posttreatment stigma scores in both groups (P < 0.001). Dyspeptic symptoms and psychological condition were improved in both groups after treatment, with no significant difference on post-treatment Leeds Dyspepsia Questionnaire, Generalized Anxiety Disorder Questionnaire, or Patient Health Questionnaire scores between 2 groups. @*Conclusion@#ZZKZ is superior to doxepin in alleviating stigma and medication non-adherence, with comparable efficacy in improving dyspeptic symptoms and psychological condition of patients with rFD.
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Objective: To investigate the mechanism of signal transducer and activator of transcription 3 (STAT3) and cancer associated fibroblasts (CAF) jointly generate chemo-resistance in epithelial-ovarian cancer and their effect on prognosis. Methods: A total of 119 patients with high-grade ovarian serous cancer who received surgery in Cancer Hospital of Chinese Academy of Medical Sciences from September 2009 to October 2017 were collected. The clinico-pathological data and follow-up data were complete. Multivariate Cox regression model was used to analyze the prognostic factors. Ovarian cancer tissue chips of patients in our hospital were prepared. EnVision two-step method immunohistochemistry was used to detect the protein expression levels of STAT3, the specific markers of CAF activation, fibroblast activating protein (FAP), and type Ⅰ collagen (COL1A1) secreted by CAF. The relationship between the expression of STAT3, FAP, COL1A1 protein and drug resistance and prognosis of ovarian cancer patients was analyzed, and the correlation between the expression of three proteins was analyzed. These results were verified through the gene expression and prognostic information of human ovarian cancer tissues collected in the GSE26712 dataset of gene expression omnibus (GEO) database. Results: (1) Multivariate Cox regression model analysis showed that chemotherapy resistance was an independent risk factor for overall survival (OS) of ovarian cancer (P<0.001). (2) The expression levels of STAT3, FAP, and COL1A1 proteins in chemotherapy resistant patients were significantly higher than those in chemotherapy sensitive patients (all P<0.05). Patients with high expression of STAT3, FAP, and COL1A1 had significantly shorter OS than those with low expression (all P<0.05). According to the human ovarian cancer GSE26712 dataset of GEO database, patients with high expression of STAT3, FAP, and COL1A1 also showed shorter OS than patients with low expression (all P<0.05), the verification results were consistent with the detection results of ovarian cancer patients in our hospital. (3) Correlation analysis showed that the protein level of STAT3 was positively correlated with FAP and COL1A1 in our hospital's ovarian cancer tissue chips (r=0.47, P<0.001; r=0.30, P=0.006), the analysis of GEO database GSE26712 dataset showed that the expression of STAT3 gene and FAP, COL1A1 gene were also significantly positively correlated (r=0.31, P<0.001; r=0.52, P<0.001). Conclusion: STAT3 and CAF could promote chemotherapy resistance of ovarian cancer and lead to poor prognosis.
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Femelle , Humains , Fibroblastes associés au cancer/anatomopathologie , Carcinome épithélial de l'ovaire , Tumeurs de l'ovaire/anatomopathologie , Pronostic , Facteur de transcription STAT-3/métabolisme , Résistance aux médicaments antinéoplasiquesRésumé
Aim To explore the neuroproteetion of Chuanxiong injection on post-stroke depression (PSD) and its effeet on cAMP-p-CREB-BDNF pathway in hip¬pocampus.Methods Hats were randomly divided into four groups of sham, model, low-dose ( 0.1 g • kg ~1 ) of Chuanxiong injection and high-dose (0.2 g • kg 1 ) of it.The PSD model was established by middle cere-bral artery occlusion ( MCAO) combined with chronic stress stimulation.After the treatment, the behaviors of rats were observed by the tests of sugar consumption, open-field and Morris water maze.The function and status of neurons in hippocampus CA1 area were detec¬ted by Nissl staining and Neun immunofluorescence.The expressions of cAMP-p-CREB-BDNF pathway pro¬teins in hippocampus were observed by Western blot.Results Both Chuanxiong injection groups of low-dose and high-dose significantly increased consumption of sugar water, horizontal anrl vertical movement scores, decreased total route distance and route near the plat, elevated the number of Nissl body in CA1 area, re¬stored the morphology of Nissl body, and enhanced the expressions of cAMP and p-CREB in hippocampus.Additionally, the high dose group shortened swimming duration, reduced distance ratio of near plat to far from plat, and increased the expressions of Neun and BD- NF.Conclusions Chuanxiong injection has the po¬tential of improving the behavior and neurological func¬tion of PSD rats via up-regulating cAMP-CREB-BDNF pathway, protecting the neurons in hippocampal CA1 area, and ultimately alleviating the cognitive deficiency of PSD rats.
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OBJECTIVE@#Numerous studies have demonstrated the close relationship between chronic stress and blood pressure (BP). Hypertensive subjects exhibit exaggerated reactions to stress, especially higher BP. The mechanisms by which stress affects pre-existing hypertension still need to be explored. Danzhi Xiaoyao Powder (DP), a historical traditional Chinese medicine formula, is a promising treatment for BP control in hypertensive patients under stress. The present study investigated the metabolomic disruption caused by chronic stress and the treatment effect and mechanism of DP.@*METHODS@#Spontaneously hypertensive rats (SHRs) were subjected to chronic restraint stress (CRS) for 4 weeks. BP was measured via the tail-cuff method, and anxiety-like behavior was quantified using the elevated-plus-maze test. Meanwhile, DP was administered intragastrically, and its effects were observed. Global metabolomic analysis was performed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry, followed by multivariate statistical analysis to detect differential metabolites and pathways.@*RESULTS@#DP alleviated the CRS-induced increase in BP and anxiety-like behavior. Systematic metabolic differences were found among the three study groups. A total of 29 differential plasma metabolites were identified in both positive- and negative-ion modes. These metabolites were involved in triglyceride metabolism, amino acid (phenylalanine, tryptophan, and glycine) metabolism, and steroid hormone pathways.@*CONCLUSION@#These findings expose the metabolomic disturbances induced by chronic stress in SHRs and suggest an innovative treatment for this disorder.
Sujets)
Animaux , Humains , Rats , Chromatographie en phase liquide à haute performance , Médicaments issus de plantes chinoises/pharmacologie , Médecine traditionnelle chinoise , Poudres , Rats de lignée SHRRésumé
The rational medication in pregnant women is a clinical issue that clinicians and pharmacists must take seriously. Most tissues and organs undergo anatomical and physiological changes during pregnancy that affect the absorption, distribution, metabolism, and excretion of drugs in vivo, which ultimately lead to changes in bioavailability. In order to achieve an effective therapeutic concentration, dose adjustment might be required during this period. In the past ten years, the application of modeling and simulation methods in the field of drug development and clinical therapy has continued to expand, for instance, using population pharmacokinetic (PPK) and physiologically based pharmacokinetic (PBPK) modeling to adjust dosage regimen in special populations. Rigorously designed and validated models will effectively make up for the deficiencies of clinical trials, provide valuable references for the design of clinical research, and even replace part of them. This article will introduce the physiological changes that affect the pharmacokinetic properties of the drug during pregnancy and review the progress in the application of PBPK modeling in pharmacokinetic studies in pregnant women.
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ObjectiveTo collect and screen records concerning the spleen and stomach diseases and syndromes in ancient books of traditional Chinese medicine (TCM) using an automated framework and to systematically explore the concept evolution of spleen and stomach diseases and syndromes using the visualization method. MethodA total of 1 224 kinds of ancient book data in the Ancient Books of Traditional Chinese Medicine Database (V2.1) were analyzed using the automated testing tool Selenium WebDriver with the Python 3.8 programming language and the etree library of Lxml for automatic collection and statistics of the "book title" "author" "classification" "dynasty" "completion time", and "informative abstract". After being checked and collated, the collected data were visually analyzed with Tableau (V2020.1.3) for figuring out the concept evolution of spleen and stomach diseases and syndromes in the past dynasties from the perspectives of symptoms and signs, etiology and pathogenesis, principle-method-recipe-medicinal, and prognosis. ResultA total of 7 203 clauses were automatically collected from 989 ancient books. It was found that in the pre-Qin period, there were few ancient books related to the spleen and stomach diseases and syndromes, and the understandings were confined to the superficial symptoms or signs and the basic etiology and pathogenesis. From the Han to Sui and Tang dynasties, the related concepts gradually increased and the descriptions about the manifestations are more detailed than those in previous dynasties. The etiology, diagnosis, and treatment system of the spleen and stomach diseases and syndromes were further perfected. In the Song, Jin, and Yuan dynasties, such concepts as independent signs,symptoms, as well as nature and location of spleen and stomach diseases and syndromes were enriched. In the Ming and Qing dynasties, a TCM syndrome differentiation and treatment system for spleen and stomach diseases and syndromes was formed, and the related concepts were gradually simplified and unified. ConclusionThe concepts of spleen and stomach diseases and syndromes have undergone an evolution from simplicity to complexity and then back to simplicity. There are numerous ancient books discussing the concepts of spleen and stomach diseases and syndromes, exhibiting a fluctuating yet rising trend with time. The automated framework enables the construction of a lightweight database of spleen and stomach diseases and syndromes. Based on data visualization, the concept evolution of the spleen and stomach diseases and syndromes from ancient times to the present has been efficiently uncovered, which is conducive to tracing the origin and development of spleen and stomach diseases and syndromes in TCM. This has provided reference for related research of spleen and stomach diseases in modern Chinese medicine.
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ObjectiveTo study the in vitro kinetics of Jiaojiang cataplasms and evaluate its pharmacodynamics, so as to provide a feasible basis for the development of this preparation. MethodThe improved Franz diffusion cell was used for the in vitro release in semipermeable membrane and transdermal absorption in in vitro mouse skins. The contents of hydroxy-α-sanshool, 6-gingerol, ginsenoside Rb1 were determined by high performance liquid chromatography (HPLC), to evaluate the in vitro release and transdermal absorption of Jiaojiang cataplasms. The mobile phase of 6-gingerol and hydroxy-α-sanshool was water-acetonitrile-methanol (2∶1∶1) with the detection wavelength of 280 nm. The mobile phase of ginsenoside Rb1 was acetonitrile-0.1% phosphoric acid aqueous solution (31∶69) with the detection wavelength of 203 nm. A mouse intestinal paralysis model was established, and mice were randomly divided into five groups, namely sham operation group, model group, domperidone group (3.9 mg·kg-1) and high- and low-dose groups of Jiaojiang cataplasms (6.2, 3.1 g·kg-1, measured by crude drug dosage), to observe the effect of this preparation on gastrointestinal propulsion function. ResultAverage release rates of hydroxy-α-sanshool, 6-gingerol and ginsenoside Rb1 at 24 h were 16.41, 4.23, 4.15 μg∙cm-2∙h-1, the average transdermal rates of them at 24 h were 2.31, 0.64, 0.29 μg∙cm-2∙h-1, their skin retention values were 19.56, 3.59, 1.61 μg, respectively. According to the Ritger-Peppas equation, the release of hydroxy-α-sanshool, 6-gingerol, ginsenoside Rb1 was non-Fick diffusion. The high-dose group of Jiaojiang cataplasms could improve intestinal function of model mice after small intestinal friction injury, and promote intestinal peristalsis and small intestinal propulsion rate (P<0.05). ConclusionJiaojiang cataplasms has in vitro release and transdermal properties, the in vitro release conforms to Higuchi equation, and transdermal absorption behavior conforms to zero-order kinetic equation, which can improve the postoperative function of the small intestine and the propulsion function of small intestine. It preliminarily indicates that the preparation has certain clinical development value.
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@#Abstract: Objective To explore the value of real-time shear wave elastography in evaluating the severity of liver fibrosis in hepatitis B, and to analyze the factors that affecting its accuracy. Methods A total of 196 chronic hepatitis B patients, who admitted to the Third Affiliated Hospital of Chengdu Medical College from February 2018 to October 2020, were selected for retrospective analysis. Demographic indicators such as gender, age, body mass index(BMI), and laboratory indicators such as fasting blood glucose, liver function, and blood lipid composition were collected. The patients were detected by real-time shear wave elastography. Taking the pathological test results as the gold standard, the diagnostic value of real-time shear wave elastography in the severity of liver fibrosis in chronic hepatitis B was analyzed, and the comprehensive effect of various factors on the diagnostic accuracy of real-time shear wave elastography was evaluated by Logistic regression analysis. Results The differences in real-time shear wave elastography of patients with different severity of liver fibrosis in hepatitis B were statistically significant, and F0 grade <F1 grade <F2 grade <F3 grade <F4 grade (all P<0.05). ROC analysis showed that the cut-off values of real-time shear wave elastography for patients with liver fibrosis in hepatitis B ≥ F1, ≥ F2, ≥ F3 and F4 were 6.15 kPa, 7.03 kPa, 8.15 kPa and 10.09 kPa respectively; the area under the curve (AUC) was 0.759, 0.806, 0.900 and 0.930 respectively (P<0.05). Results of multivariate Logistic regression analysis based on univariate analysis showed that glutamic alanine transaminase (ALT), glutamic oxalacetic transaminase (AST), fatty liver and inflammation levels were independent factors affecting the accuracy of real-time shear wave elastography in evaluating the severity of liver fibrosis in hepatitis B (P<0.05). Conclusions Real-time shear wave elastography technology can be used to evaluate the severity of liver fibrosis in hepatitis B, and its accuracy is mainly affected by ALT, AST, inflammation levels and fatty liver.
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Background/Aims@#Antidepressants are effective in patients with functional dyspepsia (FD). However, stigma associated with FD and antidepressants may affect treatment adherence. This study aims to explore possible communication strategies to alleviate stigma and improve adherence in patients with FD. @*Methods@#In this randomized, single-center, and single-blind trial, 160 patients with FD initiating antidepressant treatment were recruited. Different communication strategies were performed when prescribing antidepressants. Participants in Group 1 were told that brain is the “headquarters” of gut, and that antidepressants could act as neuromodulators to relieve symptoms of FD through regulating the functions of gut and brain. Participants in Group 2 were told that antidepressants were empirically effective for FD. Stigma scores, medication-related stigma, treatment compliance, and efficacy were analyzed. @*Results@#After 8-week antidepressant treatment, the proportion of patients with FD with decreased stigma scores in Group 1 was significantly higher than in Group 2 (internalized stigma: 64.10% vs 12.00%; perceived stigma: 55.13% vs 13.33%; P < 0.01). Medication-related stigma was lower in Group 1 than in Group 2 (P < 0.05 for 3 of 4 questions). Concurrently, patients in Group 1 had better treatment compliance (0.71 ± 0.25 vs 0.60 ± 0.25, P < 0.01) and efficacy. In Group 1, participants with decreased post-treatment stigma scores showed better treatment compliance and efficacy than those with non-decreased scores. Decrease in stigma scores positively correlated with treatment compliance. @*Conclusion@#Improving knowledge of patients with FD of the disease and antidepressants via proper communication may be an effective way to alleviate stigma and promote adherence.
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Neutrophil extracellular traps (NETs) are an important part of the innate immunity. They are mainly involved in the occurrence of gout disease through NADPH oxidase 2-dependent pathways and it is related to the spontaneous remission of gouty arthritis and the formation of tophi. These pathological features can be analyzed by methods such as electron microscopy and immunohistochemical staining. In order to further explore the molecular mechanism of NETs and discover potential drug targets for gouty arthritis, this article summarizes its role in gouty diseases and related detection techniques.