1.Discovery of Yersinia LcrV as a novel biased agonist of formyl peptide receptor 1 to bi-directionally modulate intracellular kinases in triple-negative breast cancer.
Yunjun GE ; Huiwen GUAN ; Ting LI ; Jie WANG ; Liang YING ; Shuhui GUO ; Jinjian LU ; Richard D YE ; Guosheng WU
Acta Pharmaceutica Sinica B 2025;15(7):3646-3662
G protein-coupled receptors (GPCRs) are significant drug targets, but their potential in cancer therapy remains underexplored. Conventional GPCR agonists or antagonists have shown limited effectiveness in cancer treatment, necessitating new GPCR-targeting strategies for more effective therapies. This study discovers that Yersinia pestis LcrV, a crucial linker protein for plague infection, acts as a biased agonist of a GPCR, the formyl peptide receptor 1 (FPR1). The LcrV protein induces unique conformational changes in FPR1, resulting in G proteins being activated in a distinctive state without subunit dissociation. This leads to a biased signaling profile characterized by cyclic adenosine monophosphate (cAMP) responses and β-arrestin2 recruitment, but not calcium mobilization. In FPR1-expressing triple-negative breast cancer (TNBC) cells, LcrV bi-directionally modulates intracellular signaling pathways, downregulating extracellular signal-regulated kinases (ERK1/2) and Akt pathways while upregulating Jun N-terminal kinase (JNK) and p38 pathways. This dual modulation results in cell cycle arrest and the inhibition of TNBC cell proliferation. In TNBC xenograft mouse models, long-term LcrV treatment inhibits tumor growth more effectively than a conventional FPR1 antagonist. Additionally, LcrV treatment reprograms tumor cells by reducing stemness-associated proteins OCT4 and c-MYC. Our findings highlight the potential of biased GPCR agonists as a novel GPCR-targeting strategy for cancer treatment.
3.Legal risks of face recognition technology in medical field
Shengming JI ; Youli HU ; Hong YUAN ; Wei WANG ; Hongjing WANG ; Jun LIU ; Shuhui SUN
Chinese Journal of Hospital Administration 2022;38(3):217-221
Under the background of " Internet+ medical treatment" and the continuous deepening of face recognition technology research, the face recognition industry has continued to mature, and face recognition has been initially applied in medical fields such as hospital management, auxiliary medical care, and epidemic prevention and control. At the same time, face recognition technology brings problems including error risk, technical cracking risk, privacy risk, equality risk, abuse risk, and other issues in practice, which seriously threaten the personal and property rights and interests of the public. On the basis of summarizing the specific application direction of face recognition technology in hospitals, the authors sorted out the legal regulation of face recognition in China, and proposed that it should be based on technology research and development, strengthen the " gatekeeper" responsibility of medical institutions, improve legal system and recommendations for strengthening judicial leadership in order to improve the legal regulations of face recognition technology, reduce the risk of infringement by medical institutions in the application of face recognition technology, and protect the legitimate rights and interests of citizens.
4.Whole Genome Analyses of Chinese Population and De Novo Assembly of A Northern Han Genome.
Zhenglin DU ; Liang MA ; Hongzhu QU ; Wei CHEN ; Bing ZHANG ; Xi LU ; Weibo ZHAI ; Xin SHENG ; Yongqiao SUN ; Wenjie LI ; Meng LEI ; Qiuhui QI ; Na YUAN ; Shuo SHI ; Jingyao ZENG ; Jinyue WANG ; Yadong YANG ; Qi LIU ; Yaqiang HONG ; Lili DONG ; Zhewen ZHANG ; Dong ZOU ; Yanqing WANG ; Shuhui SONG ; Fan LIU ; Xiangdong FANG ; Hua CHEN ; Xin LIU ; Jingfa XIAO ; Changqing ZENG
Genomics, Proteomics & Bioinformatics 2019;17(3):229-247
To unravel the genetic mechanisms of disease and physiological traits, it requires comprehensive sequencing analysis of large sample size in Chinese populations. Here, we report the primary results of the Chinese Academy of Sciences Precision Medicine Initiative (CASPMI) project launched by the Chinese Academy of Sciences, including the de novo assembly of a northern Han reference genome (NH1.0) and whole genome analyses of 597 healthy people coming from most areas in China. Given the two existing reference genomes for Han Chinese (YH and HX1) were both from the south, we constructed NH1.0, a new reference genome from a northern individual, by combining the sequencing strategies of PacBio, 10× Genomics, and Bionano mapping. Using this integrated approach, we obtained an N50 scaffold size of 46.63 Mb for the NH1.0 genome and performed a comparative genome analysis of NH1.0 with YH and HX1. In order to generate a genomic variation map of Chinese populations, we performed the whole-genome sequencing of 597 participants and identified 24.85 million (M) single nucleotide variants (SNVs), 3.85 M small indels, and 106,382 structural variations. In the association analysis with collected phenotypes, we found that the T allele of rs1549293 in KAT8 significantly correlated with the waist circumference in northern Han males. Moreover, significant genetic diversity in MTHFR, TCN2, FADS1, and FADS2, which associate with circulating folate, vitamin B12, or lipid metabolism, was observed between northerners and southerners. Especially, for the homocysteine-increasing allele of rs1801133 (MTHFR 677T), we hypothesize that there exists a "comfort" zone for a high frequency of 677T between latitudes of 35-45 degree North. Taken together, our results provide a high-quality northern Han reference genome and novel population-specific data sets of genetic variants for use in the personalized and precision medicine.
5. Intracellular location of severe fever with thrombocytopenia syndrome bunyavirus NP protein with correlative light and electron microscopy based on miniSOG
Guoyu NIU ; Zun ZHANG ; Baicheng XIA ; Shuhui LIU ; Xu GAO ; Wei WU ; Xiaohui ZOU ; Zhuozhuang LU ; Tao HONG
Chinese Journal of Experimental and Clinical Virology 2018;32(1):75-79
Objective:
To study the intracellular location and characteristic of SFTSV NP protein in different phases using mini singlet oxygen generator (miniSOG) labeling technique.
Methods:
MiniSOG is a recently-invented genetically-encoded tag for EM. MiniSOG-fused SFTSV NP (NPSOG) gene was cloned by PCR, and inserted into pcDNA3.0 plasmid to form pTPL-NPSOG, which was used to transfect 293 cells. The transfected cells of different phases were fixed in 2.5% glutaraldehyde in situ, stained with DAB through the photooxidation activity of miniSOG, and used to prepare ultrathin sections. Intracellular location and characteristic of SFTSV NP protein in different phases were studied by observing the sections under transmission electron microscope.
Results:
After transfecting the plasmid with NPSOG to 293 cells, NP protein was expressed in cytoplasm and peri nucleus, and gradually aggregated, which connected with endoplasmic reticulum and Golgi apparatus to form larger volume and irregular inclusion bodies in cytoplasm. No obvious subcellular structure changes were found.
Conclusions
The SFTSV nucleoprotein can be expressed separately to form inclusion bodies without the assistance of other viral proteins. The formation of inclusion bodies requires the directional movement and aggregation of a certain number of NP proteins, which may involve the interaction of NP protein and host organelles during this period.
6. Prognostic factors in newly diagnosed multiple myeloma patients with 1q21 amplification/gain treated with bortezomib-based regimens followed by autologous hematopoietic stem cell transplantation
Wenyang HUANG ; Dehui ZOU ; Wei LIU ; Gang AN ; Yan XU ; Weiwei SUI ; Shuhui DENG ; Chengwen LI ; Hong LIU ; Jian LI ; Lugui QIU
Chinese Journal of Hematology 2018;39(6):496-500
Objective:
To explore the prognostic factors in newly diagnosed multiple myeloma (NDMM) patients with 1q21 amplification/gain treated with bortezomib-based regimens followed by autologous hematopoietic stem cell transplantation (ASCT) .
Methods:
We retrospectively assayed 35 NDMM patients with 1q21 amplification/gain who received bortezomib-based chemotherapy followed by ASCT and maintenance therapy between January 2008 and August 2015.
Results:
①The median age of 35 patients were 49(33-63)years old. Ratio of male to female was 22∶13. Monosomy1q21 amplification/gain was only seen in 3(8.6%) patients, the other 32 patients were with additional cytogenetic abnormalities including 13q14 deletion, t(11,14), t(4,14), t(14,16), 17p deletion and complex karyotype aberrations. ②The complete remission (CR) rate was 57.0% (20/35), the very good partial remission(VGPR) rate was 37.1%(13/35) and the partial remission (PR) rate was 5.7%(2/35) after ASCT. At a median follow-up of 24 (8-85) months, 3-year estimated progression free survival (PFS) and overall survival (OS) rate were (66.5±9.7)% and (69.6±9.9)%, respectively. ③As 13 patients with high-risk cytogenetic abnormalities, the median PFS and OS time was 26 and 28 months. The 3-year estimated PFS and OS was (28.0±15.9)% and (36.5±16.4)%, respectively. Another 22 patients without other high-risk cytogenetic abnormalities, the median PFS and OS time was 54 months and not reached. The 3-year estimated PFS and OS was (71.5±12.7)% and (92.3±7.4)% in this group, respectively. The presence of additional other high-risk cytogenetic abnormalities resulted in significantly shortened PFS (
7.Analysis of 575 cases of gastric cardia pathological changes in Chaoshan gastric cardia cancer high risk area
Guangcan CHEN ; Shuhui LIU ; Liangli HONG
Chinese Journal of Primary Medicine and Pharmacy 2017;24(6):801-804
Objective To observe the clinical features of 575 patients with cardiac diseases from the First Affiliated Hospital of Shantou University Medical College,and to get a preliminary understanding of the incidence of cardia cancer in high incidence area of Chaoshan cardia lesions.Methods Recorded the clinical data of the patients with pathological changes of gastric cardia diagnosed in the First Affiliated Hospital of Shantou University Medical College from 2007 to 2011.Analyzed the distributions of these patients by sex,age and pathological changes.Results There were 575 cases with all kinds of pathological changes of gastric cardia enrolled in this hospital,including 16.34% of chronic inflammation,3.3% of low grade intraepithelial neoplasia,2.26% of high grade intraepithelial neoplasia and 78.09% of gastric cardia cancer.Most patients were gastric cardia cancer.Trend χ2 test results showed that the numbers of gastric cardia cancer patients increased with age(P =0.000).The prevalence of pathological changes of gastric cardia in males was obviously higher than that in females.In gastric cardia cancer the ratio of male to female was 4.76∶1.Conclusion Most of the patients with gastric cardia pathological changes admitted in the First Affiliated Hospital of Shantou University Medical College are middle -aged and elderly men,and gastric cardia cancer is common with a higher frequency in males than that in females.
8.The effect of expression level of IL-23R mRNA on Th17/IL-17 immune response in mycobacterium tuberculosis infection
Liu JIN ; Desheng ZHAO ; Heng ZHANG ; Zhiguo ZHANG ; Shuhui CAO ; Wei WANG ; Jun JIN ; Xiaonan ZHANG ; Hong SU
Chinese Journal of Disease Control & Prevention 2017;21(9):904-908
Objective To investigate the effect of interleukin 23 receptor (IL-23R) on T helper cell 17 (Th17) call-mediated immune response in mycobacterium tuberculosis (TB) infection,and to explore the role of IL-23R in the pathogenesis of pulmonary tuberculosis.Methods 21 active lung tuberculosis (ATB) patients were enrolled in Beijing chest hospital from July to October in 2015,21 cases of latent tuberculosis infection (LTBI) and 21 healthy Healthy Donors (HD) were selected from Beijing Changping center for tuberculosis control and prevention from May to July in 2015.The peripheral blood mononuclear cells (PBMCs) were isolated and cultured.The expression of IL-23R mRNA in PBMCs was detected,IL-23 and IL-17A levels in the supernatant of PBMCs were measured.The expression of IL-23R mRNA in different groups and the effect of IL-23R expression on IL-17A level were analyzed.Results The expression of IL-23R mRNA in ATB group was lower than that in LTBI group (Z =-2.528,P =0.011),and in ATB group was higher than that in HD group (Z =-3.849,P < 0.001).The expression of IL-17A in ATB group was lower than that in LTB group (t =2.238,P =0.031),and ATB group was higher than that in HD group (t =4.733,P < 0.001).There was no significant difference in IL-23 level between the three groups (F =0.432,P =0.651).IL-23R mRNA expression was positively correlated with IL-17A level (rs =0.438,P =0.047).Conclusions The expression level of IL-23R in mycobacterium tuberculosis infection can regulate the immune response mediated by Th17 cells,which may affect the susceptibility and infection outcome of pulmonary tuberculosis.
9. Long-term follow-up of multiple myeloma after autologous hematopoietic stem cell transplantation: a single center results
Weiwei SUI ; Dehui ZOU ; Gang AN ; Shuhua YI ; Shuhui DENG ; Wenyang HUANG ; Tingyu WANG ; Jian LI ; Hong LIU ; Mingwei FU ; Rui LYU ; Wei LIU ; Yan XU ; Zengjun LI ; Yaozhong ZHAO ; Lugui QIU
Chinese Journal of Hematology 2017;38(6):499-504
Objective:
To evaluate the efficacy and long-term outcome of a combined protocol for multiple myeloma (MM) , including induction therapy, autologous hematopoietic stem cell transplantation (ASCT) and consolidation and maintenance therapy.
Methods:
Clinical records of 144 patients with MM from January 1, 2005 to February 1, 2016 were retrospectively analyzed.
Results:
The overall response rate (ORR) after ASCT was 100.0%, in which the complete remission (CR) was 64.1% and the best treatment response rate of superior to PR was 89.4%. During a median follow-up of 47 months, patients with an overall survival (OS) and progression free survival (PFS) was 120.9 and 56.9 months respectively. 5y-OS (73.7±4.7) %, 7y-OS (60.5±6.3) %; 3y-PFS (69.2±4.2) %, 5y-PFS (47.8±5.3) %. The median OS and PFS between the first line transplantation group and salvage transplantation group were 120.9 months
10. Clinical and bacteriological analysis of lymphoid tissue neoplasms patients with bacteria bloodstream infections
Tingyu WANG ; Zengjun LI ; Qingsong LIN ; Dong SU ; Rui LYU ; Shuhui DENG ; Weiwei SUI ; Mingwei FU ; Wenyang HUANG ; Wei LIU ; Hong LIU ; Lugui QIU
Chinese Journal of Hematology 2017;38(12):1043-1048
Objective:
To investigate the clinical status of lymphoid tissue neoplasms patients with bacteria bloodstream infections, bacteriology and drug susceptibility results, and provide the basis for rational clinical anti-infection option.
Methods:
A retrospectively analysis of clinical data and bacterial susceptibility test results of patients with bacteria bloodstream infections from September 2010 to December 2014 was conducted.
Results:
A total of 134 cases including 107 patients with bloodstream infections were enrolled. 84 cases were male, 50 cases were female, the median age was 31 (12-71) years old. 112 cases were agranulocytosis, and 106 cases were severe agranulocytosis (ANC<0.1×109/L) . 27 cases underwent hematopoietic stem cell transplantation, 100 cases received chemotherapy[33 cases with VD (I) CP±L (vincristine+daunorubicin/idarubicin + cyclophosphamide + prednison±asparaginasum) induction chemotherapy, 41 cases with intensive chemotherapy of Hyper-CVAD/MA or MA (mitoxantrone+cytarabine) , 26 cases with other chemotherapy regimens], and 7 cases were infected without chemotherapy. 10 patients discharged from hospital owing to treatment abandoning, 120 cases were cured through anti-infective therapy, 2 patients died of bacteria bloodstream infections, 1 patient died of sudden cardiac, and 1 patient died of GVHD after allogenic hematopoietic stem cell transplantation. A total of 144 strains were isolated, including 108 strains (75.0%) of Gram-negative bacteria and 36 strains (25.0%) of Gram-positive cocci. The susceptibility of Gram-negative bacteria to the carbapenems was 98.00%, and the adjustment treatment rate of carbapenems was 3.0%. The susceptibility of Gram-negative bacteria to the other antibiotics was 60.30%, and the adjustment treatment rate was 90.5%. The susceptibility of Grampositive cocci to the carbapenems was 49.3%, and to glycopeptides and linezolid was 100.0%. Comparing all patients’empirical use of antimicrobial agents with the drugs susceptibility results of blood cultures, 80.1% of the patients’initial drug selection was sensitive.
Conclusion
The lymphoid neoplasms patients experienced bacteria bloodstream infections most often after receiving the chemotherapy regimens of treating acute lymphoblastic leukemia. The majority type of bacteria was Gram-negative bacteria. Drug susceptibility test showed that susceptibility of Gram-negative bacteria to the carbapenems was the highest, and the treatment adjustment rate was obviously lower. The susceptibility of Gram-positive cocci to glycopeptides and linezolid was high, and which could be applied to the patients with Gram-positive cocci sepsis on basis of susceptibility results in general.

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