1.Evolution of chemistry and selection technology for DNA-encoded library.
Peixiang MA ; Shuning ZHANG ; Qianping HUANG ; Yuang GU ; Zhi ZHOU ; Wei HOU ; Wei YI ; Hongtao XU
Acta Pharmaceutica Sinica B 2024;14(2):492-516
DNA-encoded chemical library (DEL) links the power of amplifiable genetics and the non-self-replicating chemical phenotypes, generating a diverse chemical world. In analogy with the biological world, the DEL world can evolve by using a chemical central dogma, wherein DNA replicates using the PCR reactions to amplify the genetic codes, DNA sequencing transcripts the genetic information, and DNA-compatible synthesis translates into chemical phenotypes. Importantly, DNA-compatible synthesis is the key to expanding the DEL chemical space. Besides, the evolution-driven selection system pushes the chemicals to evolve under the selective pressure, i.e., desired selection strategies. In this perspective, we summarized recent advances in expanding DEL synthetic toolbox and panning strategies, which will shed light on the drug discovery harnessing in vitro evolution of chemicals via DEL.
2.Influence of exercise rehabilitation based on psycho-cardiology medical model on patients with coro-nary heart disease after PCI
He-Lin ZHANG ; Yi-Chun ZHANG ; Chong-Huai GU ; Zhi-Xiang PENG
Chinese Journal of cardiovascular Rehabilitation Medicine 2024;33(1):20-25
Objective:To study influence of exercise rehabilitation based on psycho-cardiology medical model on pa-tients with coronary heart disease(CHD)after percutaneous coronary intervention(PCI).Methods:A total of 164 CHD patients undergoing PCI in our hospital were randomly and equally divided into routine nursing group and exer-cise rehabilitation group(received exercise rehabilitation based on psycho-cardiology medical model based on rou-tine nursing group).Both groups were intervened for six months.General clinical data,score of somatic symptoms scale(SSS),cardiac function indexes:LVEF and LVEDV,6min walking distance(6MWD)and score of 36-item short-form heath survey(SF-36)were compared between two groups.Results:During follow-up,there were three cases lost in routine nursing group,and two cases lost and four cases stopped follow-up in exercise rehabilita-tion group.Compared with routine nursing group,six months after intervention,there were significant reductions in SSS score[(33.97±5.76)scores vs.(25.76±4.79)scores]and LVEDV[(125.33±16.14)ml vs.(119.53± 16.82)ml],and significant rise in LVEF[(56.28±4.46)%vs.(59.28±4.90)%],6MWD[(410.42±20.08)m vs.(439.69±20.66)m],scores of physical functioning[(19.20±4.22)scores vs.(23.76±3.98)scores],bodily pain[(7.42±1.99)scores vs.(8.84±1.94)scores],general health[(16.42±4.73)scores vs.(19.09±4.37)scores],vitality[16.0(7.0)scores vs.19.0(6.8)scores],role-emotional[(4.86±1.10)scores vs.(5.18± 0.86)scores],mental health[20.0(5.0)scores vs.24.0(8.8)scores]of SF-36 in exercise rehabilitation group(P<0.05 or<0.01).Conclusion:Exercise rehabilitation based on psycho-cardiology medical model can signifi-cantly improve cardiac function and psychological status,and improve quality of life in patients with coronary heart disease after PCI.
3.Ywhab inhibits growth of mouse B-cell lymphoma 38B9 cells by targeting HSP90aa1
Zichen WEI ; Yi ZHANG ; Han XU ; Xin WANG ; Ting GU ; Lei PANG ; Mingchao ZHAO ; Duonan YU
Chinese Journal of Pathophysiology 2024;40(3):395-403
AIM:To investigate the role of Ywhab in the growth of mouse B-cell lymphoma,and to explore the potential underlying mechanisms.METHODS:The correlation between Ywhab and human diffuse large B-cell lymphoma(DLBCL)was investigated by bioinformatics analysis.Infection with retroviral vector was performed to establish stable mouse B-cell lymphoma 38B9 cell line with overexpression of Ywhab gene,which was verified by RT-qPCR and Western blot.The impact of Ywhab overexpression on 38B9 cell growth both in vitro and in vivo was detected by cell counting,CCK-8 assay,and subcutaneous tumor loading experiments.The expression of apoptosis-related proteins was detected by RT-qPCR and Western blot.Co-immunoprecipitation combined with mass spectrometry(CoIP-MS)was employed to search for proteins specifically binding to Ywhab gene product 14-3-3β,which was confirmed by Western blot and molecu-lar docking analysis.RESULTS:The Ywhab gene exhibited low expression in DLBCL,which was correlated with poor clinical prognosis of DLBCL patients.Compared with normal mouse bone marrow B cells,Ywhab expression was low in 38B9 cells.Overexpression of Ywhab induced apoptosis of 38B9 cells both in vitro and in vivo,promoted the expression of pro-apoptotic proteins Puma,Noxa and Bax at both mRNA and protein levels,and inhibited the mRNA and protein expres-sion of anti-apoptotic protein Bcl2(P<0.05).The 14-3-3β protein specifically bound to Hsp90aa1 and reduced Hsp90aa1 protein levels,thereby suppressing the growth of 38B9 cells.CONCLUSION:Ywhab promotes the apoptosis of B-cell lymphoma cells by binding to Hsp90aa1 and thereby inhibiting the function of Hsp90aa1.
4.Molecular tracing of Biomphalaria straminea in China
Lei DUAN ; Lei QU ; Yunhai GUO ; Wenbiao GU ; Shan LÜ ; Yi ZHANG ; Xiaonong ZHOU
Chinese Journal of Schistosomiasis Control 2024;36(3):272-278
Objective To investigate the origin of Biomphalaria straminea in China, so as to provide insights into assessment of schistosomiasis mansoni transmission risk and B. straminea control. Methods Guanlan River, Dasha River, Shenzhen Reservoir, upper and lower reaches of Kuiyong River, and Xinzhen River in Shenzhen, China, were selected as sampling sites. Ten Biomphalaria samples were collected from each site, and genomic DNA was extracted from Biomphalaria samples. DNA samples were obtained from 15 B. straminea sampled from 5 sampling sites in Minas Gerais State, Pará State, Federal District, Pernambuco State, and Sao Paulo State in Brazil, South America. Cytochrome c oxidase I (COI) and mitochondrial 16S ribosomal RNA (16S rRNA) genes were sampled using the above DNA templates, and the amplified products were sequenced. The COI and 16S rRNA gene sequences were downloaded from GenBank, and the sampling sites were acquired. All COI and 16S rRNA gene sequences were aligned and evolutionary trees of B. straminea were created based on COI and 16S rRNA gene sequences to identify the genetic similarity and evolutionary relationship between B. straminea samples from China and South America. Results A total of 60 COI gene sequences with a length of 529 bp and 3 haplotypes were obtained from B. straminea sampled from China. There were 165 COI gene sequences of B. straminea retrieved from GenBank, and following alignment with the above 60 gene sequences, a total of 33 haplotypes were obtained. Phylogenetic analysis showed that the three haplotypes of B. straminea from China were clustered into one clade, among which the haplotype China11 and three B. straminea samples from Brazil retrieved from GenBank belonged to the same haplotype. Geographical evolution analysis showed that the B. straminea samples from three sampling sites along eastern coasts of Brazil had the same haplotype with China11, and B. straminea samples from other two sampling sites were closely, genetically related to China11. A total of 60 16S rDNA gene sequences with approximately 322 bp in length were amplified from B. straminea in China, with 2 haplotypes identified. A total of 70 16S rDNA gene sequences of B. straminea were captured from GenBank. Phylogenetic analysis showed that Biomphalaria snails collected from China were clustered into a clade, and the haplotype China64 and the haplotype 229BS from Brazil shared the same haplotype. The 49 16S rDNA gene sequences of B. straminea from 25 sampling sites in southern Brazil, which were captured from GenBank, were included in the present analysis, and the B. straminea from 3 sampling sites shared the same haplotype with China64 in China. Geographical evolution analysis based on COI and 16S rRNA gene sequences showed that B. straminea sampled from eastern coastal areas of Brazil shared the same haplotypes in two gene fragment sequences with Biomphalaria snails collected from China. Conclusions The Biomphalaria snails in China are characterized as B. straminea, which have a low genetic diversity. The Biomphalaria snails in China have a high genetic similarity with B. straminea sampled from eastern coastal areas of Brazil, which may have originated from the eastern coastal areas of Brazil.
5.Trends and regional differences in blood lipid levels among adults in Anhui Province from 2017 to 2021
HU Yi ; GU Huaicong ; ZHANG Bo ; WANG Weiqiang
China Tropical Medicine 2024;24(2):176-
Objective To understand the trends of serum lipid concentration and the prevalence of dyslipidemia in adults aged 35 years and older, and to compare the regional differences in lipids. Methods Based on the data of Anhui Province in the Early Screening and Comprehensive Intervention Project for High-risk Groups of Cardiovascular Disease in China from 2017 to 2021, the change trend of blood lipid level and the prevalence rate of each region were plotted according to the year and different regions in the province, and the influencing factors of dyslipidemia were analyzed by multivariate regression model. Results The overall average levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and non-high-density lipoprotein cholesterol (non-HDL-C) demonstrated an increase followed by a slight decrease with age annually, while the levels of high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) fluctuated minimally. From 2017 to 2020, TC levels improved annually but increased again in 2021. Similar to TG and non-HDL-C, the average LDL-C level decreased annually from 2017 to 2019, while rebounded in 2020 and 2021 compared with the previous three years. In contrast, the HDL-C level continued to decline. With the exception of HDL-C, the overall blood lipid levels in the northern Anhui (n=31 716) were higher than those in the southern Anhui (n=50 681), and the lowest levels were found in the central Anhui (n=38 246). The prevalence of hypercholesterolemia (7.400%, 2 347/31 716), high LDL-C (5.228%, 1 658/31 716), low HDL-C (9.935%, 3 151/31 716), hypertriglyceridemia (18.212%, 5 776/31 716), and high non-HDL-C (5.789%, 1 836/31 716) were highest in the northern Anhui. Age, region, senior high school or above, smoking, drinking, systolic blood pressure, blood glucose, and body mass index were independent factors for dyslipidemia (P<0.05). Conclusion The blood lipid level and prevalence of dyslipidemia in adults aged ≥35 years in Anhui Province have not yet reached an ideal control level, especially in the northern part of Anhui Province where there is a need for enhanced awareness and timely intervention measures for lipid-related diseases to effectively extend the life expectancy of residents.
6.Periconceptional maternal homocysteine and birth weight outcomes in offspring: a prospective cohort study
Yi ZHANG ; Xiaotian CHEN ; Qinyu YAO ; Hongyan CHEN ; Mengru LI ; Dingmei WANG ; Yalan DOU ; Yuanzhou PENG ; Xiaoyan GU ; Weili YAN ; Guoying HUANG
Chinese Journal of Pediatrics 2024;62(2):120-128
Objective:To quantify the associations between periconceptional maternal homocysteine (HCY) and offspring′s birth weight and risk of small for gestational age (SGA) infant.Methods:The 19 984 mother-child pairs in this prospective cohort study were recruited from the Shanghai preconception cohort; the infants were delivered from 1 st September 2016 to 11 th November 2022. A standardized questionnaire was used to collect the mothers′ demographic information, medical history, dietary supplement use, and maternal complications during pregnancy, and their serum samples were collected. Serum HCY, folate, and vitamin B 12 were measured using chemiluminescent microparticle immunoassay based on serum sample drawn at enrollment. Birth weight data were obtained from medical records. Multiple imputation methods were applied to handle missing data in key variables. Multivariable linear regression and Poisson regression models were used to analyze the relationship between maternal HCY concentration during the periconceptional period and the birth weight and SGA risk of the offspring. Results:A total of 9 452 pairs were enrolled preconceptionally and the remaining 10 532 pairs were enrolled in early pregnancy. The proportion of mothers whose pregnancy age was greater than 35 years was 9.2% (1 832/19 984), the proportion of primiparous women was 76.5% (15 283/19 984), the proportion of pre-pregnancy overweight and obesity was 14.0% (2 804/19 984), the proportion of using folic acid supplements before pregnancy was 21.4% (4 272/19 984), and the proportion of those who supplemented with folic acid during early pregnancy was 85.2% (8 976/10 532); gestational diabetes mellitus was in 6.2% (1 245/19 984), gestational hypertensive syndrome in 3.6% (711/19 984). The birth weight of the offspring was (3 297±468) g, and there were 1 962 SGA children (9.8%). The HCY concentration in the overall population in appropriate for gestational age during the periconceptional period was (7.9±3.2) μmol/L, with (8.3±3.7) μmol/L in the preconception subgroup and (7.3±2.4) μmol/L in the early pregnancy subgroup. After adjustment for the covariates of perinatal demographic information, adverse pregnancy outcomes, serum folate and vitamin B 12, increased maternal periconceptional HCY was significantly associated with lower offspring birth weight ( β=-2.30, 95% CI -4.43--0.16, P=0.035). Only the early pregnancy subgroup was significantly associated with lower offspring birth weight ( β=-7.39, 95% CI-11.50--3.21, P<0.001). No association was found between peripregnancy HCY and offspring SGA risk. However, elevated HCY in early pregnancy was associated with an increased risk of SGA in the offspring ( RR=1.05, 95% CI 1.01-1.08, P=0.002). Periconceptional vitamin B 12 was a mediator of the association between HCY and offspring birth weight, accounting for 16.5%, 41.2% and 5.4% of its total effect in the overall periconceptional population, the pre-pregnancy subgroup and the early pregnancy subgroup, respectively. Conclusions:Maternal periconceptional HCY level is associated with lower birth weight in offspring, but not with the risk of SGA. Elevated maternal HCY in early pregnancy subgroup may be associated with increased risk of SGA in offspring.
7.Environmental and occupational health move forward together to create a new era of health: Minutes of the Eighteenth National Postgraduates Symposium on Environmental and Occupational Medicine
Yunjia ZHAO ; Yuan WANG ; Jiao CHEN ; Chenchen ZHANG ; Xinyi GU ; Di YI ; Xiaoyu WANG
Journal of Environmental and Occupational Medicine 2024;41(11):1297-1300
The 18th National Postgraduate Symposium on Environmental and Occupational Medicine, co-sponsored by the Editorial Board of Journal of Environmental and Occupational Medicine and the School of Public Health of Sun Yat-sen University, was successfully held on August 22 to 25, 2024 in Guangzhou, Guangdong Province, China. Adhering to the theme of “Research and practice: Healing the schism”, the symposium aims to enliven academic thinking, expand research horizons, encourage innovation, enhance inter-university exchanges, and strengthen talent cultivation, especially to promote the close integration of academic research and public health practice. A total of 105 papers were received from 38 universities. The symposium also gathered about 160 participants, mainly authors postgraduates from universities and experts and professors in the field of environmental and occupational medicine. All the participants discussed the latest research advances and future development trends of environmental and occupational medicine, and endeavor to apply the research results in public health practice.
8.Application of mitoxantrone hydrochloride in lymph node imaging during radical thyroidectomy
Yu CHENG ; Shuang ZHANG ; Zhiwei LIU ; Lili LIU ; Yi WANG ; Jianhua GU
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2024;59(10):1064-1071
Objective:To investigate the clinical application value of the new tracer mitoxantrone hydrochloride in imaging of cervical lymph nodes and identifying of parathyroid, recurrent laryngeal nerve during thyroid cancer radical surgery.Methods:A prospective controlled study was conducted between January 2022 and April 2024 at Tianjin First Central Hospital, recruiting 180 patients with thyroid cancer, including 54 males and 126 females, aged from 26 to 69 years. The patients were randomly divided into three groups: the mitoxantrone hydrochloride lymph node tracing group (MHI group), the nanocarbon lymph node tracing group (nanocarbon group), and the control group without lymph node tracers, with 60 cases in each group. All patients underwent total thyroid resection and regional lymph node dissection. The number of detected lymph nodes and positive metastatic lymph nodes and surgical field clarity scores and the identification rate of parathyroid glands and the instances of inadvertent excision were compared between the groups. Serum calcium and parathyroid hormone (PTH) levels at different perioperative time points and treatment-related complications were analyzed. One-way ANOVA, chi-square test and two independent sample non-parametric tests, were employed for statistical analyses.Results:The mean operation time, neck drainage volume and hospital stay in the MHI group and the nanocarbon group were respectively significantly lower than those in the control group ( P<0.05). The mean staining intensity score, tracer success rate and surgical field clarity score in MHI group were respectively significantly higher than those in nanocarbon group ( P<0.05). The mean numbers of dissected lymph nodes positive metastatic nodes and identification rates of parathyroid glands in MHI group were respectively significantly higher than those in both the nanocarbon and control groups ( P<0.05). The rates of inadvertent parathyroid excision in both MHI group and nanocarbon group were significantly lower than those in control group ( P<0.05). On postoperative day 1 and day 5, mean serum calcium and PTH levels in MHI group were respectively significantly higher than those in nanocarbon group and control groups. However, on postoperative day 1, there was no difference in mean serum calcium levels between the nanocarbon group and the control group ( P>0.05), though PTH level in the nanocarbon group was higher than that in the control group. By postoperative day 5, both serum calcium and PTH levels were higher in the nanocarbon group compared to the control group ( P<0.05). On postoperative days 30, there were no differences in serum calcium and PTH levels between the MHI group and the nanocarbon group ( P>0.05). The risks of facial numbness, hand and foot tetany and choking during drinking were lower in both the MHI and nanocarbon groups compared to the control group ( P<0.05). Conclusion:MHI demonstrates advantages in rapid targeted delivery and clear staining of the surgical field during regional lymph node dissection in radical thyroidectomy for thyroid cancer, effectively reducing the risk of collateral damage to the recurrent laryngeal nerve and parathyroid glands.
9.Construction of self-assembled nanoparticle tumor vaccine OVA257-264-mi3 and evaluation of its protective efficacy
Yuan CHEN ; Chen GAO ; Yuhang LI ; Zhiyuan CUI ; Xin CHENG ; Yi ZHANG ; Bo YU ; Jiang GU ; Xian YANG
Journal of Army Medical University 2024;46(12):1361-1368
Objective To construct SpyCatcher-mi3 nanoparticle vaccine delivery vectors,evaluate their role in enhancing the immunogenicity of the ovalbumin CD8+T-cell epitope peptide,OVA257-264,and determine its protective effect in a model which mice were immunized and subcutaneously challenged with E.G7-OVA tumor cells.Methods SpyCatcher-mi3 proteins were expressed by E.coli and purified by affinity chromatography and anion exchange chromatography sequentially.OVA257-264-SpyTag peptide was obtained by synthesis.The OVA257-264-mi3 nanoparticles were produced by the SpyTag/SpyCatcher system.The toxicity of OVA257-264-mi3 was evaluated using hemolysis assay,CCK-8 assay and mouse experiment.A total of 42 female SPF-grade C57BL/6 mice(6~8 weeks old,18~20 g)were randomly divided into OVA257-264-mi3,OVA257-264,and control groups,with 14 mice in each group.Then the mice in each group were immunized on days 0,14 and 28.In 14 d after the last immunization,the amounts of spot-forming cells(SFCs,indicating IFN-γ secreting cells in splenic lymphocytes)were determined using ELISpot assay to evaluate their immunogenicity.After the immunized mice were subcutaneously implanted with E.G7-OVA tumor cells,the antitumor effect of the vaccine in prophylactic xenograft tumor model was evaluate by observing tumor volumes with a caliper and tumor growth with MRI.Results Both SpyCatcher-mi3 and OVA257-264-mi3 could be self-assembled to form homogeneous and stable nanoparticles,with an average particle size of about 43.8 and 91.3 nm,respectively.The OVA257-264-mi3 was safe for in vitro and in vivo toxicity evaluation.The number of IFN--y secreting cells per 1 × 106 splenic lymphocytes reached 253 in the OVA257-264-mi3 group of mice,significantly higher than that in the OVA257-264 group and the Control group(P<0.05).The tumor volume of mice in the OVA257-264-mi3 group was about 151.1 mm3 on day 22,which was significantly smaller than that of the OVA257-264 group and the Control group(P<0.05),and the survival rate during the observation period reached 60%,which was significantly higher than that of the OVA257-264 groups(P<0.05).Conclusion Nanoparticle vaccine OVA257-264-mi3 is successfully constructed,and it shows enhancing effect on the immunogenicity of the antigen epitope peptide,and exerts protective effect on prophylactic xenograft tumor model,providing a theoretical basis for the research of tumor neoantigen vaccines.
10.Protocol for the Traditional Chinese Medicine Diagnosis and Treatment Guidelines for Children with Upper Airway cough Syndrome
Lingyun ZHANG ; Xiyou WANG ; Daxin LIU ; Qiang HE ; Xuefeng WANG ; Xun LI ; Yutong FEI ; Yi XIAO ; Xiaoxue LAN ; Yuanwen LIANG ; Xiaoxuan LIN ; Rong ZHOU ; Sirui GU ; Ying ZHANG ; Yue WANG ; Xingzhu YE ; Wenke LIU ; Hong CHEN ; Changhe YU
International Journal of Traditional Chinese Medicine 2024;46(8):961-966
In order to standardize the clinical diagnosis and treatment of upper airway cough syndrome (UACS) for children in China, Dongzhimen Hospital of Beijing University of Chinese Medicine and Affiliated Hospital of Liaoning University of Traditional Chinese Medicine initiated the development of this Traditional Chinese Medicine Diagnosis and Treatment Guidelines for Children with Upper Airway cough Syndrome based on evidence-based medical evidence. This guideline will process registration, write a plan, and develop relevant processes and writing norms, develop and publish official documents. This plan mainly introduces the scope of the guidelines, the purpose and significance, the composition of the guidelines working group, the management of conflicts of interest, the collection, selection and determination of clinical problems, the retrieval, screening and rating of evidence, and the consensus of recommendations. Registration information: This study has been registered in the international practice guidelines registry platform with the registration code of PREPARE-2023CN087.

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