1.Biosensor analysis technology and its research progress in drug development of Alzheimer's disease
Shu-qi SHEN ; Jia-hao FANG ; Hui WANG ; Liang CHAO ; Piao-xue YOU ; Zhan-ying HONG
Acta Pharmaceutica Sinica 2024;59(3):554-564
Biosensor analysis technology is a kind of technology with high specificity that can convert biological reactions into optical and electrical signals. In the development of drugs for Alzheimer's disease (AD), according to different disease hypotheses and targets, this technology plays an important role in confirming targets and screening active compounds. This paper briefly describes the pathogenesis of AD and the current situation of therapeutic drugs, introduces three biosensor analysis techniques commonly used in the discovery of AD drugs, such as surface plasmon resonance (SPR), biolayer interferometry (BLI) and fluorescence analysis technology, explains its basic principle and application progress, and summarizes their advantages and limitations respectively.
2.Clinical trial of Morinda officinalis oligosaccharides in the continuation treatment of adults with mild and moderate depression
Shu-Zhe ZHOU ; Zu-Cheng HAN ; Xiu-Zhen WANG ; Yan-Qing CHEN ; Ya-Ling HU ; Xue-Qin YU ; Bin-Hong WANG ; Guo-Zhen FAN ; Hong SANG ; Ying HAI ; Zhi-Jie JIA ; Zhan-Min WANG ; Yan WEI ; Jian-Guo ZHU ; Xue-Qin SONG ; Zhi-Dong LIU ; Li KUANG ; Hong-Ming WANG ; Feng TIAN ; Yu-Xin LI ; Ling ZHANG ; Hai LIN ; Bin WU ; Chao-Ying WANG ; Chang LIU ; Jia-Fan SUN ; Shao-Xiao YAN ; Jun LIU ; Shou-Fu XIE ; Mao-Sheng FANG ; Wei-Feng MI ; Hong-Yan ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(6):815-819
Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P<0.05).After continuation treatment,the remission rate was 54.59%(202 cases/370 cases),and the recurrence rate was 6.49%(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35%(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.
3.Role and mechanism of cysteine and glycine-rich protein 2 in the malignant progres-sion of neuroblastoma
Yao ZHANG ; Jinxin GUO ; Shijia ZHAN ; Enyu HONG ; Hui YANG ; Anna JIA ; Yan CHANG ; Yongli GUO ; Xuan ZHANG
Journal of Peking University(Health Sciences) 2024;56(3):495-504
Objective:To investigate the function and underlying mechanism of cysteine and glycine-rich protein 2(CSRP2)in neuroblastoma(NB).Methods:The correlation between the expression level of CSRP2 mRNA and the prognosis of NB children in NB clinical samples was analyzed in R2 Genomics Analysis and Visualization Platform.The small interfering RNA(siRNA)targeting CSRP2 or CSRP2 plasmid were transfected to NB cell lines SK-N-BE(2)and SH-SY5Y.Cell proliferation was observed by crystal violet staining and real-time cellular analysis.The ability of colony formation of NB cells was ob-served by colony-forming unit assay.Immunofluorescence assay was used to detect the expression of the proliferation marker Ki-67.Flow cytometry analysis for cell cycle proportion was used with cells stained by propidium iodide(PI).Annexin V/7AAD was used to stain cells and analyze the percentage of cell apoptosis.The ability of cell migration was determined by cell wound-healing assay.The level of protein and mRNA expression of CSRP2 in NB primary tumor and NB cell lines were detected by Western blot and quantitative real-time PCR(RT-qPCR).Results:By analyzing the NB clinical sample databases,it was found that the expression levels of CSRP2 in high-risk NB with 3/4 stages in international neuroblas-toma staging system(INSS)were significantly higher than that in low-risk NB with 1/2 INSS stages.The NB patients with high expression levels of CSRP2 were shown lower overall survival rate than those with low expression levels of CSRP2.We detected the protein levels of CSRP2 in the NB samples by Western blot,and found that the protein level of CSRP2 in 3/4 INSS stages was significantly higher than that in 1/2 INSS stages.Knockdown of CSRP2 inhibited cell viability and proliferation of NB cells.Overexpression of CSRP2 increased the proliferation of NB cells.Flow cytometry showed that the proportion of sub-G1,G0/G1 and S phase cells and Annexin V positive cells were increased after CSRP2 deficiency.In the cell wound-healing assay,the healing rate of NB cells was significantly attenuated after knockdown of CSRP2.Further mechanism studies showed that the proportion of the proliferation marker Ki-67 and the phospho-rylation levels of extracellular signal-regulated kinases 1/2(ERK1/2)were significantly decreased after CSRP2 knockdown.Conclusion:CSRP2 is highly expressed in high-risk NB with 3/4 INSS stages,and the expression levels of CSRP2 are negatively correlated with the overall survival of NB patients.CSRP2 significantly increased the proliferation and cell migration of NB cells and inhibited cell apoptosis via the activation of ERK1/2.All these results indicate that CSRP2 promotes the progression of NB by activating ERK1/2,and this study will provide a potential target for high-risk NB therapy.
4.Genomic and cellular infection characteristics of a newly isolated Mangshi virus in China
Heng YANG ; Zhan-Hong LI ; Lei XIAO ; Zhuo-Ran LI ; Jia-Rui XIE ; De-Fang LIAO ; Lin GAO ; Hua-Chun LI
Chinese Journal of Zoonoses 2024;40(6):504-511,528
The genomic characteristics and cellular tropism of a Mangshi virus(MSV)isolated in China were investigated,thereby establishing a robust foundation for further research on the evolution and pathogenicity of MSV.The genome sequence of MSV strain V301/YNJH/2019 was obtained by next-generation sequencing,followed by phylogenetic tree construction and rearrangement assessment using software IQtree,RPD4,and Simplot.Viral proliferation was assessed in C6/36(Aedes albop-ictus),Vero(African green monkey kidney),and BHK(baby hamster kidney)cells.An initial epidemiological investigation of MSV in local cattle and goats was conducted using the serum neutralization test.The genome of MSV strain V301/YNJ H/2019 was 20623 bp in length,encompassing 12 segments of double-stranded RNA(Seg-1 to Seg-12).Sequence analysis confirmed genomic rearrangement of the Seg-1 and Seg-11 sequences,ex-hibiting high similarity to MSV isolated from lake sediment in China in 2022,while Seg-2 to Seg-10 and Seg-12 were most closely related to a MSV strain isolated from mosquitoes in China in 2013.The virus efficiently proliferated and induced sig-nificant cytopathic effects(CPE)in both C6/36 and BHK cells,but limited replication and no observable CPE in Vero cells.No detectable neutralizing antibodies against MSV were detected in 20 goat serum samples collected in Mangshi,while 2 of 20 bo-vine serum samples were positive with neutralizing antibody titers of 1:128 and 1:54.Whole genome sequencing revealed re-assortment events of the V301/YNJH/2019 strain,which is capable of infecting C6/36,BHK,and Vero cells.MSV infection was confirmed in cattle in Mangshi.
5.Advances in liquid-phase microextraction technology and its application in biological sample pretreatment
Liang CHAO ; Yu-zhen HE ; Jia-hao FANG ; Hui WANG ; Zhan-ying HONG
Acta Pharmaceutica Sinica 2023;58(2):298-312
Liquid-phase microextraction is a novel pretreatment technique for biological samples developed on the basis of liquid-phase extraction technology, which is simple, rapid, economical, and environmentally friendly, and has been widely used in the analysis of biological matrix samples such as blood, urine, and saliva. In this paper, we review the basic principles of the main modes of liquid-phase microextraction techniques, i.e., single-drop microextraction, dispersive liquid-liquid microextraction, and hollow-fiber liquid-phase microextraction, and the progress of their applications in biological sample pretreatment by reviewing the literature in the past five years, with a view to providing technical support and reference for sample pretreatment in the fields of
6.Significance of anti-Jo-1 antibody's clinical stratification in idiopathic inflammatory myopathy and disease spectrum.
Jia Chen LI ; Zhan Hong LAI ; Miao SHAO ; Yue Bo JIN ; Xiao Juan GAO ; Ke ZHANG ; Jing HOU ; Yan Ying ZHANG ; Zhan Guo LI ; Yu Hui LI
Journal of Peking University(Health Sciences) 2023;55(6):958-965
OBJECTIVE:
To investigate the significance of anti-histidyl tRNA synthetase (Jo-1) antibody in idiopathic inflammatory myopathies (IIM) and its diseases spectrum.
METHODS:
We enrolled all the patients who were tested positive for anti-Jo-1 antibody by immunoblotting in Peking University People's Hospital between 2016 and 2022. And the patients diagnosed with anti-synthetase antibody syndrome (ASS) with negative serum anti-Jo-1 antibody were enrolled as controls. We analyzed the basic information, clinical characteristics, and various inflammatory and immunological indicators of the patients at the onset of illness.
RESULTS:
A total of 165 patients with positive anti-Jo-1 antibody were enrolled in this study. Among them, 80.5% were diagnosed with connective tissue disease. And 57.6% (95/165) were diagnosed with IIM, including ASS (84/165, 50.9%), immune-mediated necrotizing myopathy (7/165, 4.2%) and dermatomyositis (4/165, 2.4%). There were 23.0% (38/165) diagnosed with other connective tissue disease, mainly including rheumatoid arthritis (11/165, 6.7%), undifferentiated connective tissue disease (5/165, 3.0%), interstitial pneumonia with autoimmune features (5/165, 3.0%), undifferentiated arthritis (4/165, 2.4%), Sjögren's syndrome (3/165, 1.8%), systemic lupus erythematosus (3/165, 1.8%), systemic vasculitis (3/165, 1.8%), and so on. Other cases included 3 (1.8%) malignant tumor patients, 4 (2.4%) infectious cases and so on. The diagnoses were not clear in 9.1% (15 /165) of the cohort. In the analysis of ASS subgroups, the group with positive serum anti-Jo-1 antibody had a younger age of onset than those with negative serum anti-Jo-1 antibody (49.9 years vs. 55.0 years, P=0.026). Clinical manifestations of arthritis (60.7% vs. 33.3%, P=0.002) and myalgia (47.1% vs. 22.2%, P=0.004) were more common in the ASS patients with positive anti-Jo-1 antibody. With the increase of anti-Jo-1 antibody titer, the incidence of the manifestations of arthritis, mechanic hands, Gottron sign and Raynaud phenomenon increased, and the proportion of abnormal creatine kinase and α-hydroxybutyric dehydrogenase index increased in the ASS patients. The incidence of myalgia and myasthenia were significantly more common in this cohort when anti-Jo-1 antibody-positive ASS patients were positive for one and more myositis specific antibodies/myositis associated autoantibodies (P < 0.05).
CONCLUSION
The disease spectrum in patients with positive serum anti-Jo-1 antibody includes a variety of diseases, mainly ASS. And anti-Jo-1 antibody can also be found in many connective tissue diseases, malignant tumor, infection and so on.
Humans
;
Middle Aged
;
Myalgia
;
Myositis/epidemiology*
;
Autoantibodies
;
Connective Tissue Diseases
;
Arthritis, Rheumatoid
;
Neoplasms
7.Clinical features of intestinal polyps and risk factors for secondary intussusception in children: an analysis of 2 669 cases.
Can-Lin LI ; Yan-Hong LUO ; Hong-Juan OUYANG ; Li LIU ; Wen-Ting ZHANG ; Na JIANG ; Jia-Qi DUAN ; Mei-Zheng ZHAN ; Cheng-Xi LIU ; Jie-Yu YOU ; Yong LI ; Hong-Mei ZHAO
Chinese Journal of Contemporary Pediatrics 2022;24(5):530-535
OBJECTIVES:
To study the clinical features of intestinal polyps and the risk factors for secondary intussusception in children.
METHODS:
A retrospective analysis was performed for the medical data of 2 669 children with intestinal polyps. According to the presence or absence of secondary intussusception, they were divided into two groups: intussusception (n=346) and non-intussusception (n=2 323). Related medical data were compared between the two groups. The multivariate logistic regression analysis was used to identify the risk factors for secondary intussusception.
RESULTS:
Among the children with intestinal polyps, 62.42% were preschool children, and the male/female ratio was 2.08∶1; 92.66% had hematochezia as disease onset, and 94.34% had left colonic polyps and rectal polyps. There were 346 cases of secondary intussusception, with an incidence rate of 12.96% (346/2 669). Large polyps (OR=1.644, P<0.001), multiple polyps (≥2) (OR=6.034, P<0.001), and lobulated polyps (OR=93.801, P<0.001) were the risk factors for secondary intussusception.
CONCLUSIONS
Intestinal polyps in children often occur in preschool age, mostly in boys, and most of the children have hematochezia as disease onset, with the predilection sites of the left colon and the rectum. Larger polyps, multiple polyps, and lobulated polyps may increase the risk of secondary intussusception, and endoscopic intervention is needed as early as possible to improve prognosis.
Child, Preschool
;
Female
;
Gastrointestinal Hemorrhage
;
Humans
;
Intestinal Polyps/complications*
;
Intussusception/complications*
;
Male
;
Retrospective Studies
;
Risk Factors
8.Textual Research on Nelumbinis in Famous Classical Formulas
Hui-hui LIU ; Shi-bin CHEN ; Jia-chen ZHAO ; Yi-han WANG ; Yan JIN ; Wei ZHANG ; Hua-sheng PENG ; Qiu-jie CAI ; Bing LI ; Hong-jun YANG ; Hua-min ZHANG ; Zhi-lai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(10):42-54
The name, origin, place of origin, medicinal parts, harvesting and processing of lotus are verified by consulting ancient Chinese herbal medicines and medical books, combined with modern literature, providing a basis for the development of famous classical formulas containing lotus. According to textual research, the original base of lotus is Nelumbo nucifera since ancient times, rhizome (Nelumbinis Rhizomatis Nodus), leaf (Nelumbinis Folium), seed (Nelumbinis Semen), embryo (Nelumbinis Plumula), receptacle (Nelumbinis Receptaculum), stamen (Nelumbinis Stamen) and other medicinal parts of N. nucifera can be used as medicine and have different clinical effects. Nelumbinis Semen was originally produced in Henan, and then gradually expanded to Jiangnan. Today, it can be cultivated and planted throughout the country, with Fujian, Hunan, and Jiangxi as the authentic production areas. After combing the medicinal parts of N. nucifera and the historical evolution of its processing, it is suggested that the dried and mature fruits of N. nucifera taking in autumn and removing the shell and Nelumbinis Plumula should be used in Qingxin Lianziyin. Nelumbinis Folium in Erdongtang should be harvested in summer and autumn, and the raw products was used as medicine and processed in accordance with the provision of the 2020 edition of Chinese Pharmacopoeia.
9.Textual Research on Perillae in Famous Classical Formulas
Jin-xiu QIAN ; Wu-wei MENG ; Hui -hui LIU ; Shi-bin CHEN ; Jia-chen ZHAO ; Yi-han WANG ; Yan JIN ; Wei ZHANG ; Hua-sheng PENG ; Qiu-jie CAI ; Bing LI ; Hong-jun YANG ; Hua-min ZHANG ; Zhi-lai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(10):55-67
Based on the ancient literature of all dynasties, this article makes a systematic textual research on the name, origin, producing area, quality, harvesting and processing of Zisu (Perillae) in the famous classical formulas, so as to clarify the information of the drug in different historical periods and provide a reference for the development and utilization of the related formulas. The main origin of Perillae in the ancient literature was Perilla frutescens var. frutescens (purple leaf type), followed by P. frutescens var. acuta (purple leaf type), but not Baisu. Modern chemical composition studies also show that there are obvious differences between Perillae and Baisu, which provides a scientific basis for distinguishing them. Although they are often treated as a species in plant classification, P. frutescens var. frutescens (purple leaf type) is recommended in the development of famous classical formulas, and Baisu should be avoided. Perillae is widely distributed, but its producing area did not record in most of the literature in the past dynasties, or the producing area is described as everywhere today. In the period of the Southern and Northern dynasties, the medicinal parts of Perillae included stems, leaves and seeds, and doctors in the Ming dynasty began to pay attention to the differentiation of different medicinal parts. The harvesting and processing methods of Perillae in the past dynasties are close to that of today. Perillae Fructus is mostly stir-fried and ground into medicine, Perillae Folium and Perillae Caulis are mainly simple cleansing. In production, we can refer to the 2020 edition of Chinese Pharmacopoeia.
10.Herbal Textual Research on Dendrobii Caulis in Famous Classical Formulas
Ju-run ZHAO ; Jia-chen ZHAO ; Yi-han WANG ; Yan JIN ; Wei ZHANG ; Hua-sheng PENG ; Qiu-jie CAI ; Bing LI ; Hong-jun YANG ; Hua-min ZHANG ; Zhi-lai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(10):215-228
Through consulting the ancient herbal and medical books, combined with the field investigation, the name, origin, collection and processing of Dendrobium medicinal materials were researched, which provided a basis for the development of famous classical formulas containing this kind of herbs. Due to the wide distribution of D. officinale, the Dendrobium species represented by D. officinale and D. huoshanense, which are short, fleshy and rich in mucus, should be the most mainstream of Dendrobium medicinal materials in previous dynasties. Compared with Shihu, Muhu with loose texture, long and hollow is born on trees. According to the characteristic description, it should be D. nobile, D. fimbriatum and so on, of which D. nobile was the mainstream. The Chinese meaning of Jinchai was confused in the past dynasties, so it was not suitable to be treated as a plant name. The production areas of Dendrobium medicinal materials in the past dynasties have changed with the discovery of varieties, artificial cultivation and other factors. Lu'an, Anhui province, was the earliest recorded in the Han and Wei dynasties. Since the Tang and Song dynasties, it had been extended to Guangdong and Guangxi, and it was considered that "Dendrobii Caulis in Guangnan was the best". In the Ming dynasty, Sichuan and Zhejiang products were highly praised, and in the Qing dynasty, Huoshan products were highly praised. Dendrobium medicinal materials had been used as medicine by stems in all dynasties. The medicinal materials were divided into fresh products and dry products. The fresh products can be used immediately after removing the sediment from the roots. The dry products need further processing, most of them used wine as auxiliary materials for steaming, simmer to paste or decoction into medicine. D. officinale and D. huoshanense have special processing specifications since the middle of Qing dynasty, that is, "Fengdou". According to the research results, in Ganluyin, the effect of Dendrobium medicinal materials is mainly heat clearing, and D. nobile with bitter taste can be selected. The main effect of Dendrobium medicinal materials in Dihuang Yinzi is tonic, D. officinale or D. huoshanense can be selected.

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