Objective To investigate the occurrence of adverse events of lurasidone in the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database by using Open Vigil FDA2.1,to enrich the experience and provide the basis for the clinical use of the drug in China.Methods Using Open Vigil FDA2.1,adverse event data were extracted from the FAERS database for a total of 51 quarters from the 4th quarter of 2010 to the 3rd quarter of 2023,and the ratio of reporting ratio(ROR)method and the proportional reporting ratio(PRR)method were used for data mining and analysis.Results A total of 32 728 adverse event reports with lurasidone as the first suspected drug was obtained,with a larger proportion of females(54.26％)and occurring mostly in adults(18 to 59 years).After the screening,326 preferred term(PT)signals were obtained,involving 20 system-organ classifications(injury,poisoning and procedural complications,general disorders and administration site conditions,psychiatric disorders,etc.).Among them,PTs with the higher frequency of occurrence included off label use,feeling abnormal,crying,anxiety,depression,insomnia,etc.PTs with stronger signal strength included activation syndrome,mania,tongue movement disturbance,hypoprolactinaemia,akathisia,etc.Multiple new suspected adverse drug reactions were unearthed,including hypoprolactinaemia,emotional poverty,stiff tongue,etc.Conclusion Lurasidone has a favorable safety profile,and women need to closely monitor prolactin levels when taking this medication.The drug is relatively safe for use in pregnant,puerperal and perinatal women and patients with poor metabolic function.Hypoprolactinaemia and restless leg syndrome are new rare suspected adverse events with lurasidone.

Objective To investigate the nutritional status of children with Crohn's Disease (CD) at diagnosis and its association with clinical characteristics. Methods A retrospective analysis was performed for the clinical data and nutritional status of 118 children with CD who were admitted to Beijing Children's Hospital,Capital Medical University,from January 2016 to January 2024. A multivariate logistic regression analysis was used to investigate the risk factors for malnutrition. Results A total of 118 children with CD were included,among whom there were 68 boys (57.6％) and 50 girls (42.4％),with a mean age of (11±4) years. Clinical symptoms mainly included recurrent abdominal pain (73.7％,87/118),diarrhea (37.3％,44/118),and hematochezia (32.2％,38/118),and 63.6％ (75/118) of the children had weight loss at diagnosis. The incidence rate of malnutrition was 63.6％ (75/118),and the children with moderate or severe malnutrition accounted for 67％ (50/75). There were 50 children (42.4％) with emaciation,8 (6.8％) with growth retardation,and 9 (7.6％) with overweight or obesity. Measurement of nutritional indices showed a reduction in serum albumin in 83 children (70.3％),anemia in 74 children (62.7％),and a reduction in 25 hydroxyvitamin D in 15 children (60％,15/25). The children with malnutrition had significantly higher disease activity,proportion of children with intestinal stenosis,and erythrocyte sedimentation rate and a significant reduction in serum albumin (P<0.05). The multivariate logistic regression analysis showed that intestinal stenosis was an independent risk factor for malnutrition in children with CD (OR=4.416,P<0.05). Conclusions There is a high incidence rate of malnutrition in children with CD at diagnosis,which is associated with disease activity and disease behavior. The nutritional status of children with CD should be closely monitored.

The modernization and development of traditional Chinese medicine has led to higher standards for the quality of traditional Chinese medicine products. The extraction process is a crucial component of traditional Chinese medicine production, and it directly impacts the final quality of the product. However, the currently relied upon methods for quality assurance of the extraction process, such as simple wet chemical analysis, have several limitations, including time consumption and labor intensity, and do not offer precise control of the extraction process. As a result, there is significant value in incorporating near-infrared spectroscopy (NIRS) in the production process of traditional Chinese medicine to improve the quality control of the final products. In this study, we focused on the extraction process of Xiao'er Xiaoji Zhike oral liquid (XXZOL), using near-infrared spectra collected by both a Fourier transform near-infrared spectrometer and a portable near-infrared spectrometer. We used the concentration of synephrine, a quality control index component specified by the pharmacopoeia, to achieve rapid and accurate detection in the extraction process. Moreover, we developed a model transfer method to facilitate the transfer of models between the two types of near-infrared spectrometers (analytical grade and portable), thus resolving the low resolution, poor performance, and insufficient prediction accuracy issues of portable instruments. Our findings enable the rapid screening and quality analysis of XXZOL onsite, which is significant for quality monitoring during the traditional Chinese medicine production process.

Type 2 diabetes is a hypermetabolic disease characterized with disorders of glucose/lipid metabolism, absolute or relative lack of insulin, and can induce skeletal muscle atrophy. Hyperglycemia, hyperlipidemia, insulin resistance, and abnormal release of inflammatory factors can lead to abnormal signal transduction in skeletal muscle, thus make protein synthesis and degradation imbalance and eventually causing muscle atrophy. Under normal conditions, insulin-like growth factor 1 (IGF-1)/insulin can activate phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT). AKT not only increases protein synthesis through mammalian target protein of rapamycin (mTOR), but also phosphorylates forkhead box O (FoxO) transcription factor and then inhibits the transcription of several ubiquitin ligases (such as MAFbx/atrogin-1 and MuRF1), or autophagy related genes. The weakened IGF-1/PI3K/AKT pathway in type 2 diabetes is an important factor leading to skeletal muscle atrophy. Studies have shown that the commonly used anti-type 2 diabetic drugs have different effects in regulating the synthesis and degradation of skeletal muscle protein. Studies reported that drugs with effect of anti-diabetic muscle atrophy include thiazolidinediones, glucagon-like peptide analogs, glucose-sodium cotransporter 2 inhibitors, etc.; drugs that are still in controversial or even promote skeletal muscle atrophy include metformin, and some sulfonylurea or non-sulfonylurea insulin secretagogues. This article overviewed and analyzed the currently commonly used drugs for type 2 diabetes and summarized the related mechanisms, with the aim to provide references for the rational applications of drugs for type 2 diabetes.

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*

Objective: To explain the "multi-components, multi-targets, multi-pathways" mechanism of Erzhiwan in treating benign prostatic hyperplasia(BPH) based the network pharmacology. Method: Ingenuity pathway analysis(IPA) was used to construct components-targets-diseases network and PPI network, then the classified enrichment analysis of gene ontology (GO) and pathway enrichment analysis (KEGG) were carried out on the main function of its gene sets, so as to discuss the mechanism of Erzhiwan in the treatment of BPH. Result: Erzhiwan has 19 components in IPA; and apigenin,luteolin,oleanolic acid and quercitrin were common components of Ligustri Lucidi Fructus and Echiptae Herba and the main component of Erzhiwan. Muscarinic acetylcholine receptor M3 (CHRM3), muscarinic acetylcholine receptor M2 (CHRM2), urokinase plasminogen activator receptor (PLAUR), kinin releasing enzyme 3 (KLK3), cadherin 1 (CDH1), chemokines 3 (CCL3) and metalloproteinase-1 (MMP-1) were important targets for Erzhiwan to treat BPH. The target proteins in PPI network were enriched with 20 GO functions and 5 main KEGG pathways, and Docking was verified for relevant targets. Conclusion: Erzhiwan may play a role in treating BPH by activating MMP-1 and inhibiting KLK3 and CCL3 protein expressions, inducing apoptosis, inhibiting cell proliferation and intervening relevant pathways of mitogen-activated protein kinase/extracellular signal-regulated kinase(MAPK/ERK) and nuclear factor(NF)-κB(NF-κB).

OBJECTIVE: To investigate the effects of endothelial progenitor cells (EPCs) under shear stress on the biological function such as proliferation, adhesion, migration, apoptosis and expression of α-smooth muscle actin (α-SMA), collagen-I and collagen-Ⅲ of hepatic stellate cells (HSCs). METHODS: HSCs and EPCs were inoculated into the upper and lower layers of the co-culture chamber respectively and co-incubated for 24 hours. Then, 12 dyne/cm shear stress was applied to EPCs cells for another 24 hours. After that, proliferation, adhesion, migration and apoptosis of HSCs were detected by cell counting kit-8 (CCK-8) kit, cell adherent assay, Boyden cell migration assay and flow cytometry respectively. Fluorescence quantitative PCR and Western blot were used to detect the mRNA and protein expression of alpha -SMA, collagen I and collagen-Ⅲ in HSCs. RESULTS: Under shear stress, EPCs ecological niche could obviously inhibit the proliferation, adhesion and migration of HSCs, promote the apoptosis of HSCs, and down-regulate the mRNA and protein expression of collagen-I, collagen-Ⅲ in HSC cells. CONCLUSIONS Under shear stress, EPCs ecological niche could inhibit the fibrosis development of HSCs to a certain extent.
Actins ; Apoptosis ; Cell Proliferation ; Cells, Cultured ; Collagen Type I ; Endothelial Progenitor Cells ; Hepatic Stellate Cells

Traditional Chinese medicine (TCM) prescription is the main therapies for disease prevention and treatment in Chinese medicine. Following the guidance of the theory of TCM and developing drug by composing prescriptions of TCM materials and pieces, it is a traditional application mode of TCM, and still widely used in clinic. TCM prescription has theoretical advantages and rich clinical application experience in dealing with multi-factor complex diseases, but scientific research is relatively weak. The lack of scientific cognition of the effective substances and mechanism of Chinese medicine leads to insufficient understanding of the efficacy regularity, which affects the stability of effect and hinders the improvement of quality of Chinese medicinal products. Component-based Chinese medicine (CCM) is an innovation based on inheritance, which breaks through the tradition of experience-based prescription and realize the transformation of compatibility from herbal pieces to components. CCM is an important achievement during the research process of modernization of Chinese medicine. Under the support of three national "973" projects, in order to reveal the scientific connotation of the prescription compatibility theory and develop innovative Chinese drugs, we have launched theoretical innovation and technological innovation around the "two relatively clear", and opened up the research field of CCM. CCM is an innovation based on inheritance, breaking through the tradition of experience based prescription, and realizing the transformation from compatibility of herbal pieces to component compatibility, which is an important achievement of the modernization of traditional Chinese medicine. In the past more than 10 years, with the deepening of research and the expansion of application, the theory and methods of CCM and efficacy-oriented compatibility have been continuously improved. The value of CCM is not only in developing new drug, more important is to build a communication bridge between traditional Chinese medicine and modern science and construct the system of key technologies which meet the need of innovation and development of TCM. This paper focused on the research progress, related concepts and technology development of CCM, as well as its application prospect in the theory research of Chinese medicine, development of innovative Chinese drugs, secondary development of Chinese patent medicine and upgrading of pharmaceutical technology.

Chitinases(EC3.2.1.14), which are present in various organisms, catalyze the hydrolytic cleavage of chitin and play a vital role in plant defense mechanisms against fungal pathogens.In addition, the chitinases are well known to regulate plant growth and development and are involved in programmed cell death(PCD).A chitinase expressed sequence tag(EST) was isolated from Panax notoginseng, and the full-length cDNA of this EST was cloned with the method of rapid amplification of cDNA ends and named as PnCHI1. PnCHI1 was 1 022 bp in length and contained an intact open reading frame(ORF) of 822 bp, a 26 bp 5'-untranslated region(UTR), and a 174 bp 3'-UTR.The predicted protein of PnCHI1 with 273 amino acid residues belongs to glycoside hydrolase family 19 and fell into the class IV of chitinases through phylogenetic analysis.QRT-PCR analysis showed that the expression of PnCHI1 was induced by methyl jasmonate, ethylene, H2O2, and salicylic acid.PnCHI1 was quickly induced after inoculation with Alternaria panax.Moreover, the expression level of PnCHI1 was increased after pretreatment with methyl jasmonate, and then the transcription level of PnCHI1was sharp increased after inoculation with Fusarium solani,and the highest transcription level was achieved at 4 h post inoculation.But the expression level of PnCHI1 in the sterile water pretreated P.notoginseng was increased gradually after inoculation with F.solani, and the highest expression level was achieved at 48 h post inoculation.All the results of present study indicated that PnCHI1 was involved in defense response of P.notoginseng against the F.solani and A.panax.

To study effects of APG, Span-Tween and A6/25 emulsifier cream system on transdermal absorption in vitro of baicalin, matrine, glycyrrhetinic acid and emodin in emulsifier. Permeations studies were carried out in vitro with excised mice skin by improved Franz diffusion cells. The cumulative penetration amounts and the retention amounts of Chinese herbal medicinal ingredients in three kinds of emulsifier cream systems were determined by HPLC. The effects of different Chinese herbal medicinal ingredients in the same emulsifier system and the same herbal medicinal ingredients in different emulsifier systems on cumulative permeation amount, skin retention amount and permeation rate were investigated. According to the results, the order of different Chinese herbal medicinal ingredients in same kinds of emulsifier system by the cumulative permeation amount and the permeation rate were matrine>baicalin>glycyrrhetinic acid>emodin. With respect to the effect of different emulsifier systems on cumulative permeation amount and permeation rate of the same herbal medicinal ingredients, glycyrrhetinic acid and emodin showed no significant difference, Span-Tween emulsifier cream system had higher cumulative permeation amount and permeation rate. The cumulative permeation amount and the permeation rate of Chinese herbal medicinal ingredients in the three kinds of emulsifier cream systems had an identical regularity. However, the cumulative permeation amount, the skin retension amount and the permeation rate of the same herbal medicinal ingredients in different emulsifier systems had no regularity.