Feedback regulation of ubiquitination and phase separation of HECT E3 ligases.

Lipid homeostasis is essential for normal cellular functions and dysregulation of lipid metabolism is highly correlated with human diseases including neurodegenerative diseases. In the ubiquitin-dependent autophagic degradation pathway, Troyer syndrome-related protein Spartin activates and recruits HECT-type E3 Itch to lipid droplets (LDs) to regulate their turnover. In this study, we find that Spartin promotes the formation of Itch condensates independent of LDs. Spartin activates Itch through its multiple PPAY-motif platform generated by self-oligomerization, which targets the WW12 domains of Itch and releases the autoinhibition of the ligase. Spartin-induced activation and subsequent autoubiquitination of Itch lead to liquid-liquid phase separation (LLPS) of the poly-, but not oligo-, ubiquitinated Itch together with Spartin and E2 both in vitro and in living cells. LLPS-mediated condensation of the reaction components further accelerates the generation of polyubiquitin chains, thus forming a positive feedback loop. Such Itch-Spartin condensates actively promote the autophagy-dependent turnover of LDs. Moreover, we show that the catalytic HECT domain of Itch is sufficient to interact and phase separate with poly-, but not oligo-ubiquitin chains. HECT domains from other HECT E3 ligases also exhibit LLPS-mediated the promotion of ligase activity. Therefore, LLPS and ubiquitination are mutually interdependent and LLPS promotes the ligase activity of the HECT family E3 ligases.

Effects of Kaixinjieyu, a Chinese herbal medicine preparation, on neurovascular unit dysfunction in rats with vascular depression.

BACKGROUND: Kaixinjieyu (KJ), derived from Kaixin and Sini powder, is an effective Chinese herbal medicine preparation used in the treatment of vascular depression (VD). We hypothesize that broad antidepressant effect of KJ results from the improved neurovascular unit (NVU) function via neurogenesis, permeability of blood-brain barrier (BBB) and balance of the fibrinolytic system. METHODS: A VD model of rat was established by chronic unpredictable mild stress and separation after ligation of the bilateral common carotid arteries. The rats were treated with KJ and fluoxetine hydrochloride (FLU) for 21 days, respectively. The behavior and cerebral perfusion were investigated and then NVU functions including neurogenesis, permeability of BBB and balance of the fibrinolytic system were studied using a number of biomarkers and TUNEL assay. RESULTS: KJ significantly increased sucrose preference, moving distance, number of rearing and cortical blood flow. NVU functions measured by brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB) and tissue plasminogen activator (t-PA) proteins and mRNA, zona occludens protein-1 (ZO-1), occludin and claudin-5 proteins increased significantly, whereas, plasminogen activator inhibitor-1 (PAI-1), matrix metalloproteinase-2 (MMP-2) proteins, mRNA and apoptotic rates of neurons decreased significantly with treatment of KJ. FLU has a function similar to KJ in behavior, regulation of BDNF, TrkB, MMP-2, occludin and apoptotic rates of cells. CONCLUSIONS: KJ has function of reducing depression-like behavior and improving cerebral hypoperfusion, which might be mediated by the up-regulation of neurogenesis and tight junction of BBB, and balance of the fibrinolytic system. The results imply that KJ is better than FLU in improving cerebral hypoperfusion and the fibrinolytic system.

Bilayer matrix tablets for prolonged actions of metformin hydrochloride and repaglinide.

A combination therapy of metformin hydrochloride (MH) and repaglinide (RG) achieves a perfect glycemic control; however, the combination formulation of immediate release must be taken several times a day, compromising the therapeutic benefits and causing inconveniences to the patients. Herein, a bilayer matrix tablet that aimed at continuously releasing both MH and RG over time was developed, in which the two drugs were formulated into two separated layers. The tablets were prepared by wet granulation method, and the optimized formulation was obtained by evaluating the factors that affected the drug release. The bilayer tablets simultaneously released the two drugs over 12 h; and a better in vivo performance with a steady plasma concentration, markedly lower Cmax, prolonged Tmax, and perfect absorption was obtained. Summarily, the bilayer matrix tablets sustained both MH and RG release over time, thereby prolonging the actions for diabetic therapy and producing better health outcomes.

[Study on protective and haemodynamic effects of Danshen Tongluo capsule on rats with myocardial infarction].

To study the protective effect of Danshen Tongluo capsule on rat hearts in the myocardial infarction (MI) model. After being fed with high fat diets for one month, the SD rats were randomly divided into the sham group and the model group according to the left ventricular ejection fraction (EF). The MI model group was duplicated by ligating coronary artery and then divided into five groups: the model group, the positive control group (model + captopril), the small dose group (model + Danshen Tongluo), the medium dose group (model + Danshen Tongluo) and the high dose group (model + Danshen Tongluo). Four weeks later, changes in myocardium ultra-structure were observed by hemodynamics, cardiac ultrasound and electron microscope. The results showed: (1) All doses of Danshen Tongluo capsule could significantly reduce the left ventricular end diastolic pressure (LVEDP) (P <0.01), increase the maximum internal pressure of the left ventricle (+ dp/dtmax), and lower the drop rate of left ventricular pressure (- dp/dtmax), with statistical significances in medium and high dose groups; (2) The B ultrasound results showed increase in EF and left ventricular shortening fraction (FS) in all dose groups of Danshen Tongluo capsule; (3) The medium dose group showed significant decrease in myocardial infarction index (P <0.01) and injured and fractured myofilament and sarcomere of ischemic myocardium in myocardial ultra-structure; All of Danshen Tongluo capsule-treated groups revealed reduction in myocardial injury and myocardial infraction area. The study preliminarily proves that Danshen Tongluo capsule can improve hemodynamic function, and has a protective effect on myocardial ischemia.

Comparison of Infection Risks Between Various Inhaled and Intranasal Corticosteroids: A Pharmacovigilance Analysis Based on the FAERS Database.

Purpose: This study conducted a pharmacovigilance analysis based on the FDA Adverse Event Reporting System (FAERS) database to compare the infection risk of inhaled or nasal Beclomethasone, Fluticasone, Budesonide, Ciclesonide, Mometasone, and Triamcinolone Acetonide. Methods: We used proportional imbalance analysis to evaluate the correlation between ICS /INCs and infection events. The data was extracted from the FAERS database from April 2015 to September 2023. Further analysis was conducted on the clinical characteristics, site of infection, and pathogenic bacteria of ICS and INCs infection adverse events (AEs). We used bubble charts to display their top 5 infection adverse events. Results: We analyzed 21,837 reports of infection AEs related to ICS and INCs, with an average age of 62.12 years. Among them, 61.14% of infection reports were related to females. One-third of infections reported to occur in the lower respiratory tract with Fluticasone, Budesonide, Ciclesonidec, and Mometasone; over 40% of infections reported by Triamcinolone Acetonide were eye infections; the rate of oral infections caused by Beclomethasone were 7.39%. The reported rates of fungal and viral infections caused by beclomethasone were 21.15% and 19.2%, respectively. The mycobacterial infections caused by Budesonide and Ciclesonidec account for 3.29% and 2.03%, respectively. Bubble plots showed that the ICS group had more fungal infections, oral infections, pneumonia, tracheitis, etc. The INCs group had more eye symptoms, rhinitis, sinusitis, nasopharyngitis, etc. Conclusion: Women who use ICS and INCs are more prone to infection events. Compared to Budesonide, Fluticasone seemed to have a higher risk of pneumonia and oral candidiasis. Mometasone might lead to more upper respiratory tract infections. The risk of oral infection was higher with Beclomethasone. Beclomethasone causes more fungal and viral infections, while Ciclesonide and Budesonide are more susceptible to mycobacterial infections.

mInsc coordinates Par3 and NuMA condensates for assembly of the spindle orientation machinery in asymmetric cell division.

As a fundamental process governing the self-renewal and differentiation of stem cells, asymmetric cell division is controlled by several conserved regulators, including the polarity protein Par3 and the microtubule-associated protein NuMA, which orchestrate the assembly and interplay of the Par3/Par6/mInsc/LGN complex at the apical cortex and the LGN/Gαi/NuMA/Dynein complex at the mitotic spindle to ensure asymmetric segregation of cell fate determinants. However, this model, which is well-supported by genetic studies, has been challenged by evidence of competitive interaction between NuMA and mInsc for LGN. Here, the solved crystal structure of the Par3/mInsc complex reveals that mInsc competes with Par6ß for Par3, raising questions about how proteins assemble overlapping targets into functional macromolecular complexes. Unanticipatedly, we discover that Par3 can recruit both Par6ß and mInsc by forming a dynamic condensate through phase separation. Similarly, the phase-separated NuMA condensate enables the coexistence of competitive NuMA and mInsc with LGN in the same compartment. Bridge by mInsc, Par3/Par6ß and LGN/NuMA condensates coacervate, robustly enriching all five proteins both in vitro and within cells. These findings highlight the pivotal role of protein condensates in assembling multi-component signalosomes that incorporate competitive protein-protein interaction pairs, effectively overcoming stoichiometric constraints encountered in conventional protein complexes.

Excessive STAU1 condensate drives mTOR translation and autophagy dysfunction in neurodegeneration.

The double-stranded RNA-binding protein Staufen1 (STAU1) regulates a variety of physiological and pathological events via mediating RNA metabolism. STAU1 overabundance was observed in tissues from mouse models and fibroblasts from patients with neurodegenerative diseases, accompanied by enhanced mTOR signaling and impaired autophagic flux, while the underlying mechanism remains elusive. Here, we find that endogenous STAU1 forms dynamic cytoplasmic condensate in normal and tumor cell lines, as well as in mouse Huntington's disease knockin striatal cells. STAU1 condensate recruits target mRNA MTOR at its 5'UTR and promotes its translation both in vitro and in vivo, and thus enhanced formation of STAU1 condensate leads to mTOR hyperactivation and autophagy-lysosome dysfunction. Interference of STAU1 condensate normalizes mTOR levels, ameliorates autophagy-lysosome function, and reduces aggregation of pathological proteins in cellular models of neurodegenerative diseases. These findings highlight the importance of balanced phase separation in physiological processes, suggesting that modulating STAU1 condensate may be a strategy to mitigate the progression of neurodegenerative diseases with STAU1 overabundance.

[A research of Chinese medicine diagnosis and treatment standard procedure for patients with HIV associated pruritus based on experts' questionnaires].

OBJECTIVE: To establish Chinese medicine diagnosis and treatment standard procedure for patients with HIV associated pruritus. METHODS: A Chinese medicine diagnosis and treatment standard procedure for patients with HIV associated pruritus was established by literature retrieval and peer review. Two questionnaires were carried out to investigate the confirmation and advice of in-group specialists to key points of the draft including diagnosis, treatment and nursing. Then the procedures were revised accordingly. RESULTS: The recovery rate of complete questionnaires in the 1st survey was 96%. Specialists confirmed more on case history and physical examinations, syndrome differentiation of three syndrome types, treatment of blood deficiency wind dryness syndrome (BDWDS) and nursing. They held different opinions on the outlines, auxiliary examinations, treatment of blood heat induced wind evil syndrome (BHWES) and wind cold and dampness accumulation syndrome (WCDAS), of which the coefficient of variations (CVs) was within 0.1603 -0.2473. The procedures were revised and the 2nd survey was launched. The recovery rate of complete questionnaires in the 2nd survey was 100%. Specialists confirmed more on case history and physical examinations, diagnostic criteria, syndrome differentiation of BDWDS and WCDAS, and treatment of BDWDS, of which CVs was 0. All indicated high agreement and good compliance. The CVs of other items were within 0.0638-0.1439, less than those of the 1st survey. The consistency of experts' opinions were somewhat improved. The contribution by one single item showed less difference in assessing the overall results in the two surveys. A new revision of the procedure was preliminarily established according to results of two surveys. CONCLUSIONS: Experts' activeness, concentration, and coordination were good in the two surveys. They had reached consensus in key points of the draft including diagnosis, treatment, and nursing.

[Application of cultivating Yuan and clearing blockage method on HIV/AIDS].

According to HIV/AIDS being infectious and have a very long period of incubation, leading to immune system weakened and infected easily, we summarized its pathmechanism including Yuan Qi deficiency (vigour deficiency)and constraint (Qi depression,blood stagnancy, phlegm coagulation, poison accumulation), consequently treatment principle were raised--cultivates the Yuan and clear blockage. From viscera and Qi, blood, Yin and Yang perspective, we elaborate corresponding clinical application method and train of thought, that cultivating the Yuan method means tonify Qi firstly which emphasizes on the spleen and the kidney; Clear blockage method contains relieving liver for smooth Qi, invigorating spleen to remove phlem, promoting blood circulation and detoxification. In addition, cultivating the Yuan and clear blockage should cooperate closely based on traditional Chinese medicine diffrentiation, tonify deficiency should not used individually and vice verse.

[Establish proposal of diagnosis and treatment of traditional Chinese medicine in AIDS patients with recurrent oral ulcerations].

The pathogenesis of acquired immune deficiency syndrome-associated recurrent oral ulcerations (AIDS-ROU) remained obscure and these was no specific treatment for it. Syndrome differentiation in traditional Chinese medicine (TCM) focus on integral regulation and has an advantage of the disease that etiology and pathogenesis remain obscure. A draft of Chinese medicine diagnosis and treatment standard procedure for AIDS-ROU was established by literature retrieval and peer review. Two questionnaires were carried out to investigate the confirmation and advice of in-group specialist to key points of the draft including diagnosis, treatment and nursing. Then the procedures were revised accordingly. The preliminary results showed the recovery rate of complete questionnaires in the 1st survey was 96%. Specialists confirmed more on outline, case history and physical examinations, syndrome differentiation of hyperactivity of fire due to Yin deficiency syndrome (HFYDS), treatment of heat accumulated in heart and spleen syndrome (HAHSS) and HFYDS, treatment of western medicine and nursing. They held different opinions on incidence, treatment of deficiency of spleen-QI and stomach-QI syndrome (DSSS) and criterion of therapeutical evaluation. Cronbach coefficient alpha (CCA) was 0.998 and split-half reliability R was 0.91. Recovery rate of complete questionnaires in 2nd survey was 100%. Specialists confirmed more on outline, etiology and pathogenesis, case history and physical examination, auxiliary examination, diagnostic criteria, syndrome differentiation and treatment of HAHSS and HFYDS. They held different opinions on syndrome differentiation and treatment of intermingled cold and heat syndrome and DSSS, nursing and the other therapies. CCA was 0.428 and split-half reliability R was 0.96. Coefficient of variations of the 2nd survey were less than those of the 1st survey, which mean coordination was improved. Each single item in two surveys contributed less difference in overall results according to weight coefficients. A new revision of the procedure was preliminarily established according to results of two surveys. Experts'activeness, concentration and coordination were good in two surveys. They had reached consensus in key points of the draft including diagnosis, treatment and nursing on the whole.

[Construction and analysis of questionnaires on AIDS cough in traditional Chinese medicine diagnosis and treatment procedures].

OBJECTIVE: To norm the behavior of AIDS cough in traditional Chinese medicine diagnosis and treatment and improve the clinical level of cough treatment for HIV/AIDS, and build AIDS cough diagnosis and treatment procedures in traditional Chinese medicine. METHOD: Combined with clinical practice,to formulate questionnaire on AIDS cough in traditional Chinese medicine diagnosis and treatment by both English and Chinese literature research to expertise consultation and verify the results of the questionnaires on the statistics using the Delphi method. RESULT: Questionnaire contents consist of overview, pathogeny, diagnosis standard, dialectical medication (phlegm heat resistance pulmonary lung and kidney Yin deficiency lung spleen-deficiency), treating spleen-deficiency (lung), moxibustion treatment and aftercare care and diet and mental, average (2.93-3.00), full mark rate (93.10%-100%) ranks average (9.91-10.67) and (287.50-309.50) of which are the most high value, and the variation coefficient is 0.00, the Kendall coefficient (Kendalls W) is 0.049 which is statistical significance, the questionnaire reliability value of alpha was 0.788. CONCLUSION: Preliminary standarded concept, etiology and pathogenesis, diagnosis and syndrome differentiation treatment of AIDS cough, basically recognised by the experts in this field, and laid the foundation of traditional Chinese medicine diagnosis and treatment on develop the AIDS cough specifications.

Parkinson's Disease Related Depression and Anxiety: A 22-Year Bibliometric Analysis (2000-2022).

Background: Parkinson's disease (PD) is one of the common neurodegenerative diseases. Depression and anxiety are the most common psychiatric symptoms of PD. It is important to study the potential relationship between PD and depression or anxiety. Aim: This study aimed to use bibliometrics to analyze the papers about parkinson's disease related depression and anxiety over the last 22 years, and to characterize the current status of research and predict future hotspots. Methods: In the Web of Science Core Collection (WoSCC) from 2000 to 2022, documents are searched according to specific subject words. The selected literature was retrospectively analyzed and mapped using CiteSpace and Vosviewer software. We analyzed countries, institutions, journals, authors, references and keywords. Results: A total of 7368 papers were included from 2000 to 2022, and the number of publications has shown an upward trend year by year. Movement Disorder is the journal with the highest number of publications (391 publications, 5.31%) and citations (30,549 times), with the United States (2055 publications, 27.9%) and the University of Toronto (158 publications) being the countries and institutions with the highest number of publications. The high-frequency keywords focused on "quality of life", "deep brain stimulation" and "non-motor symptoms". "Functional connectivity", "gut microbiota" and "inflammation" may be at the forefront of future research. Conclusion: Parkinson's disease related depression and anxiety have been increasingly studied over the past 22 years. Functional connectivity, gut microbiota, and inflammation will be the subject of active research hotspots in the future, and these findings may provide new research ideas for researchers.

Kaixin Jieyu Granule attenuates neuroinflammation-induced depressive-like behavior through TLR4/PI3K/AKT/FOXO1 pathway: a study of network pharmacology and experimental validation.

BACKGROUND: Kaixin Jieyu Granule (KJG), an improved formula of Kai-xin-san and Si-ni-san, is a highly effective formula with demonstrated efficacy in preventing depression in previous studies. However, the underlying molecular mechanisms of KJG's antidepressant effects on inflammatory molecules remain unclear. This study aimed to explore the therapeutic effects of KJG on depression using network pharmacology and experimental validation. METHODS: We employed a multi-faceted approach, combining high-performance liquid chromatography (HPLC), network pharmacology, and molecular docking, to unravel the underlying mechanisms of KJG's anti-depressant effects. To confirm our findings, we conducted at least two independent in vivo experiments on mice, utilizing both the chronic unpredictable mild stress (CUMS)-induced and lipopolysaccharide (LPS)-induced models. Furthermore, the results of in vivo experiments were verified by in vitro assays. Behavioral tests were utilized to evaluate depression-like behaviors, while Nissl staining was used to assess morphological changes in the hippocampus. Pro-inflammatory cytokines and pathway-related protein expressions were determined using a combination of immunofluorescence staining, enzyme-linked immunosorbent assay (ELISA), and Western Blotting (WB). RESULTS: Our network-based approaches indicated that ginsenoside Rg1 (GRg1) and saikosaponin d (Ssd) are the major constituents of KJG that exert an anti-depressant effect by regulating TLR4, PI3K, AKT1, and FOXO1 targets through the toll-like receptor, PI3K/AKT, and FoxO pathways. In vivo, KJG can attenuate depression-like behaviors, protect hippocampal neuronal cells, and reduce the production of pro-inflammatory mediators (TNF-α, IL-6, and IL-1ß) by repressing TLR4 expression, which was regulated by the inhibition of FOXO1 through nuclear exportation. Furthermore, KJG increases the expression levels of PI3K, AKT, p-PI3K, p-AKT, and p-PTEN. Our in vitro assays are consistent with our in vivo studies. On the other hand, the above effects can be reversed by applying TAK242 and LY294002. CONCLUSION: Our findings suggest that KJG can exert anti-depressant effects by regulating neuroinflammation through the PI3K/AKT/FOXO1 pathway by suppressing TLR4 activation. The study's findings reveal novel mechanisms underlying the anti-depressant effects of KJG, presenting promising avenues for the development of targeted therapeutic approaches for depression.

The fibroblast growth factor system in cognitive disorders and dementia.

Cognitive impairment is the core precursor to dementia and other cognitive disorders. Current hypotheses suggest that they share a common pathological basis, such as inflammation, restricted neurogenesis, neuroendocrine disorders, and the destruction of neurovascular units. Fibroblast growth factors (FGFs) are cell growth factors that play essential roles in various pathophysiological processes via paracrine or autocrine pathways. This system consists of FGFs and their receptors (FGFRs), which may hold tremendous potential to become a new biological marker in the diagnosis of dementia and other cognitive disorders, and serve as a potential target for drug development against dementia and cognitive function impairment. Here, we review the available evidence detailing the relevant pathways mediated by multiple FGFs and FGFRs, and recent studies examining their role in the pathogenesis and treatment of cognitive disorders and dementia.

How do online users perceive health risks during public health emergencies? Empirical evidence from China.

Background: The global COVID-19 pandemic has posed a major threat to human life and health, and new media technologies have intensified the spread of risk perception. Purpose: This study aimed to explore the impact of risk information ground on online users' perceived health risks, and further explore the mediating role of psychological distance and the moderating role of self-efficacy. Methods: A total of 25 Internet users from different provinces in China were interviewed in-depth, NVIVO.11 was used to qualitatively analyze the interview text data and construct a theoretical model. A total of 492 interviewees were recruited in order to complete a scenario questionnaire, SPSS-27 was used to perform orthogonal experiments, generate eight combinatorial scenarios, analyze demographic data, and clean and prepare data for testing hypotheses. SmartPLS 3.0 was used to test the conceptual model using the structural equation model (SEM) of the partial least squares (PLS). Results: The analysis of the SEM model shows that all planned hypotheses (Information fluency → Information diagnosability, Information extensibility → Information diagnosability, Information diagnosability → Psychological distance, Platform interactivity → Scenario embeddedness, Network connectivity → Scenario embeddedness, Scenario embeddedness → Psychological distance, Psychological distance → Risk perception, Psychological distance → Self-efficacy → Risk perception, Information fluency → Information diagnosability → Psychological distance → Risk perception, Information extensibility → Information diagnosability → Psychological distance → Risk perception, Platform interactivity → Scenario embeddedness → Psychological distance → Risk perception, Network connectivity → Scenario embeddedness → Psychological distance → Risk perception) are confirmed. Conclusion: This study found that the information ground factors significantly affect online users' perceptions of health risks, psychological distance mediates the effect of information ground factors on risk perception, and self-efficacy negatively moderates the effect of psychological distance on risk perception.

One-Pot Tandem Alcoholysis-Hydrogenation of Polylactic Acid to 1,2-Propanediol.

The chemical recycling of end-of-life polylactic acid (PLA) plays roles in mitigating environmental pressure and developing circular economy. In this regard, one-pot tandem alcoholysis and hydrogenation of PLA was carried out to produce 1,2-propanediol, which is a bulk chemical in polymer chemistry. In more detail, the commercially available Raney Co was employed as the catalyst, and transformation was conducted in ethanol, which acted as nucleophilic reagent and solvent. Single-factor analysis and Box-Behnken design were used to optimize the reaction conditions. Under the optimized condition, three kinds of PLA materials were subjected to degradation. Additionally, 74.8 ± 5.5%, 76.5 ± 6.2%, and 71.4 ± 5.7% of 1,2-propanediol was yielded from PLA powder, particle, and straws, respectively, which provided a recycle protocol to convert polylactic acid waste into value-added chemicals.

A paternal protein facilitates sperm RNA delivery to regulate zygotic development.

Sperm contributes essential paternal factors, including the paternal genome, centrosome, and oocyte-activation signals, to sexual reproduction. However, it remains unresolved how sperm contributes its RNA molecules to regulate early embryonic development. Here, we show that the Caenorhabditis elegans paternal protein SPE-11 assembles into granules during meiotic divisions of spermatogenesis and later matures into a perinuclear structure where sperm RNAs localize. We reconstitute an SPE-11 liquid-phase scaffold in vitro and find that SPE-11 condensates incorporate the nematode RNA, which, in turn, promotes SPE-11 phase separation. Loss of SPE-11 does not affect sperm motility or fertilization but causes pleiotropic development defects in early embryos, and spe-11 mutant males reduce mRNA levels of genes crucial for an oocyte-to-embryo transition or embryonic development. These results reveal that SPE-11 undergoes phase separation and associates with sperm RNAs that are delivered to oocytes during fertilization, providing insights into how a paternal protein regulates early embryonic development.

In vitro and in vivo studies on a novel solid dispersion of repaglinide using polyvinylpyrrolidone as the carrier.

In order to improve the dissolution and absorption of the water insoluble drug repaglinide, a solid dispersion was developed by solvent method using polyvinylpyrrolidone K30 (PVP K30) as the hydrophilic carrier for the first time. Studies indicated that both solubility and the dissolution rate of repaglinide were significantly increased in the solid dispersion system compared with that of repaglinide raw material or physical mixtures. The repaglinide solid dispersions with PVP K30 solid state was characterized by polarizing microscopy, differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FT-IR). DSC and XRD studies indicated that repaglinide existed in an amorphous form in the solid dispersion. FT-IR analysis demonstrated the presence of intermolecular hydrogen bonding between repaglinide and PVP K30 in the solid dispersion. In the in situ gastrointestinal perfusion experiment, solid dispersion was shown to remarkably enhance the absorption of repaglinide in stomach and all segments of intestine. In vivo pharmacokinetic study in rats showed that immediate and complete release of repaglinide from the solid dispersion resulted in rapid absorption that significantly increased the bioavailability and the maximum plasma concentration over repaglinide raw material. These results demonstrated PVP K30 was an appropriate carrier for solid dispersion of repaglinide, with increased dissolution and oral absorption.

[Diagnosis and treatment standard operating procedure of traditional Chinese medicine for HIV/AIDS diarrhea by questionnaire building].

OBJECTIVE: To establish the diagnosis and treatment standard operating procedure of Chinese medicine for HIV/AIDS diarrhea and to carry out preliminary assessment. METHODS: Under the guidance of Chinese medical theory, domestic and foreign literatures correlated to the diagnosis and treatment of HIV/AIDS diarrhea by Chinese medicine were summarized. The specialist questionnaire of clinical diagnosis and treatment standard operating procedures of Chinese medicine for HIV/AIDS diarrhea was designed by focus group discussions, and the national specialist questionnaire survey was carried out twice. RESULTS: The standard operating procedure of clinical diagnosis, treatment, nursing,and therapeutic efficacy assessment of Chinese medicine for HIV/AIDS diarrhea was preliminarily established. CONCLUSIONS: In the regulations, the concepts of the disease and symptoms and their pathogenesis were defined, and the standardization of Chinese medicine diagnosis and treatment was highlighted. Meanwhile, emphasized were the features of propaganda and education, follow-ups, consecutive diagnosis and treatment outside or inside hospitals.

[Species differentiation and quality assessment of Ziziphus jujuba var. spinosa based on the HPLC fingerprint and quantitative analysis].

OBJECTIVE: To establish an HPLC method of a characteristical chemical fingerprint analysis in combination with simultaneous determination of four bioactive components for species differentiation and quality assessment of Ziziphus jujuba var. spinosa. METHODS: The chromatographic separation was performed on an Agilent TC-C18 BDS (250 mm x 4.6 mm, 5 microm) column. The mobile phase consisted of acetonitrile and water in a linear gradient elution procedure. The evaporator tube temperature of ELSD was set at 110.5 degrees C with the nebulizing gas flow rate of 3.1 mL/min and the flow rate of mobile phase was 1.0 mL/min. The column was maintained at 30 degrees C. The injection volume was 20 microL. RESULTS: HPLC methodology for both chemical fingerprint analysis and quantitative determination of four active ingredients were validated, respectively. According to the contents of the four ingredients and the chemical fingerprints of Ziziphus jujuba var. spinosa using principal component analysis, Ziziphus jujuba var. spinosa was different from the fake derived from the seeds of Ziziphus mauritiana. CONCLUSION: The developed HPLC method is exclusive and repetitive for the species identification and quality evaluation of Ziziphus jujuba var. spinosa.