1.Status and Progress of Research on Metabolomics of Cervical Cancer
Shaojun CHEN ; Ling GAN ; Xinkang CHEN ; Lingling XIONG ; Die LONG ; Lulu CHEN ; Mengzhuan WEI ; Li HUA ; Haixin HUANG
Cancer Research on Prevention and Treatment 2025;52(7):630-636
Cervical cancer is one of the most common gynecological malignant tumors in China. Given their lack of obviously early symptoms, more than half of patients with cervical cancer are diagnosed in the middle and late stages of this malignancy, resulting in poor prognosis. Finding new therapeutic targets is the current research direction. Metabolomics, as a new omics technology, is expected to provide new targets for tumor precision diagnosis and treatment through the analysis of the changes and potential mechanisms of metabolites in tumor occurrence and development by chromatography, mass spectrometry, and other technologies. Herein, we review the research methods of metabolomics; metabolic characteristics of cervical cancer; and progress of the research on metabolomics in cervical cancer diagnosis, curative effect prediction, and prognosis evaluation to provide new ideas for the precise diagnosis and treatment of cervical cancer.
2.Analysis of T7 RNA Polymerase: From Structure-function Relationship to dsRNA Challenge and Biotechnological Applications
Wei-Chen NING ; Yu HUA ; Hui-Ling YOU ; Qiu-Shi LI ; Yao WU ; Yun-Long LIU ; Zhen-Xin HU
Progress in Biochemistry and Biophysics 2025;52(9):2280-2294
T7 RNA polymerase (T7 RNAP) is one of the simplest known RNA polymerases. Its unique structural features make it a critical model for studying the mechanisms of RNA synthesis. This review systematically examines the static crystal structure of T7 RNAP, beginning with an in-depth examination of its characteristic “thumb”, “palm”, and “finger” domains, which form the classic “right-hand-like” architecture. By detailing these structural elements, this review establishes a foundation for understanding the overall organization of T7 RNAP. This review systematically maps the functional roles of secondary structural elements and their subdomains in transcriptional catalysis, progressively elucidating the fundamental relationships between structure and function. Further, the intrinsic flexibility of T7 RNAP and its applications in research are also discussed. Additionally, the review presents the structural diagrams of the enzyme at different stages of the transcription process, and through these diagrams, it provides a detailed description of the complete transcription process of T7 RNAP. By integrating structural dynamics and kinetics analyses, the review constructs a comprehensive framework that bridges static structure to dynamic processes. Despite its advantages, T7 RNAP has a notable limitation: it generates double-stranded RNA (dsRNA) as a byproduct. The presence of dsRNA not only compromises the purity of mRNA products but also elicits nonspecific immune responses, which pose significant challenges for biotechnological and therapeutic applications. The review provides a detailed exploration of the mechanisms underlying dsRNA formation during T7 RNAP catalysis, reviews current strategies to mitigate this issue, and highlights recent progress in the field. A key focus is the semi-rational design of T7 RNAP mutants engineered to minimize dsRNA generation and enhance catalytic performance. Beyond its role in transcription, T7 RNAP exhibits rapid development and extensive application in fields, including gene editing, biosensing, and mRNA vaccines. This review systematically examines the structure-function relationships of T7 RNAP, elucidates the mechanisms of dsRNA formation, and discusses engineering strategies to optimize its performance. It further explores the engineering optimization and functional expansion of T7 RNAP. Furthermore, this review also addresses the pressing issues that currently need resolution, discusses the major challenges in the practical application of T7 RNAP, and provides an outlook on potential future research directions. In summary, this review provides a comprehensive analysis of T7 RNAP, ranging from its structural architecture to cutting-edge applications. We systematically examine: (1) the characteristic right-hand domains (thumb, palm, fingers) that define its minimalistic structure; (2) the structure-function relationships underlying transcriptional catalysis; and (3) the dynamic transitions during the complete transcription cycle. While highlighting T7 RNAP’s versatility in gene editing, biosensing, and mRNA vaccine production, we critically address its major limitation—dsRNA byproduct formation—and evaluate engineering solutions including semi-rationally designed mutants. By synthesizing current knowledge and identifying key challenges, this work aims to provide novel insights for the development and application of T7 RNAP and to foster further thought and progress in related fields.
3.Role of intestinal flora in hypertension complicated with osteoporosis
Mei-Long SI ; Hua JIN ; Min-Ke LIU ; Shuang-Fang LIU ; Bi-Shi LING ; Shang-Wen QI ; Xue-Li MA
The Chinese Journal of Clinical Pharmacology 2024;40(3):449-453
Hypertension and osteoporosis(OP)are common diseases in middle-aged and elderly people,and the number of patients with both diseases has gradually increased in recent years.Because the onset of the disease is hidden,it is easy to cause fractures and serious complications of heart,brain and kidney in the later stage,which not only seriously damages the quality of life of patients,but also increases the difficulty of clinical treatment.Therefore,it is particularly necessary to strengthen the research on this disease.More and more studies have found that the disorder of intestinal flora will lead to the occurrence of OP,while the intestinal flora of patients with hypertension is obviously out of balance.Therefore,this paper thinks that intestinal flora may be the key influencing factor of hypertension complicated with OP,and the imbalance of intestinal flora will lead to the imbalance of short-chain fatty acid metabolism,immune inflammatory reaction and increased sympathetic nerve activity,thus causing the imbalance of bone homeostasis and promoting the occurrence of OP.Therefore,it is suggested that regulating intestinal flora may be a new way to intervene hypertension complicated with OP.
4.Clinical trial of spironolactone combined with sacubitril/valsartan in the treatment of patients with hypertensive nephropathy
Lin-Lin WANG ; Jia-Li FENG ; Sheng-Jun LIU ; Zhen-Hua QIAO ; Xiu-Ling JIA ; Xiao-Li HAN
The Chinese Journal of Clinical Pharmacology 2024;40(8):1091-1095
Objective To observe the clinical efficacy and safety of spironolactone combined with sacubitril/valsartan in the treatment of patients with hypertensive nephropathy.Methods The patients with hypertensive nephropathy were randomly divided into control group and treatment group.The control group was treated with sacubitril/valsartan(100-200 mg·d-1 in the morning),and treatment group was combined with low-dose spironolactone treatment(20 mg·d-1 in the morning)on the basis of control group.Both groups were treated continuously for 12 weeks.The clinical efficacy was compared;the blood pressure,urinary microalbumin(mAlb),urinary β2 microglobulin(β2-MG)and serum cystatin C(Cys-C),transforming growth factor-β1(TGF-β1),connective tissue growth factor(CTGF)and angiotensin Ⅱ(Ang Ⅱ)and adverse drug reactions were observed before and after treatment.Results There were 87 cases in treatment group and 86 cases in control group were included respectively.After treatment,the total effective rates in treatment group and control group were 95.40%(83 cases/87 cases)and 82.56%(71 cases/86 cases),with significant difference(P<0.05).After treatment,the systolic blood pressure values in treatment group and control group were(124.65±9.65)and(130.27±8.93)mmHg,the diastolic blood pressure values were(75.08±7.14)and(80.45±7.35)mmHg,urinary mAlb levels were(42.58±5.65)and(51.28±6.64)mg·L-1,urinary β2-MG levels were(0.46±0.17)and(0.75±0.25)mg·L-1,24 h urinary protein quantitation levels were(138.49±46.64)and(216.48±65.27)mg,serum Cys-C levels were(0.63±0.26)and(0.85±0.24)mg·L-1,TGF-β1 levels were(98.67±21.43)and(112.46±26.72)pg·mL-1,CTGF levels were(1 206.54±236.56)and(1 340.51±248.25)pg·mL-1,Ang Ⅱ levels were(101.55±17.62)and(115.65±20.08)pg·mL-1,all with significant difference(all P<0.05).The incidence of adverse drug reactions in treatment group and control group were 6.90%(6 cases/87 cases)and 2.33%(2 cases/86 cases),with no significant difference(P>0.05).Conclusion Compared with sacubitril/valsartan alone,spironolactone combined with sacubitril/valsartan can better reduce blood pressure,improve renal function and delay progression of renal fibrosis in the treatment of hypertensive nephropathy,and has definite efficacy,with good safety.
5.Mechanism and research progress of S100A8/A9 in the microenvironment before high-risk tumor metastasis
Hai-Xia MING ; Zhao-Hua LIU ; Yan-Jun WANG ; Ming SHEN ; Yan-Wen CHEN ; Yang LI ; Ling-Ling YANG ; Qian-Kun LIANG
The Chinese Journal of Clinical Pharmacology 2024;40(13):1991-1995
S100 calc-binding protein A8/A9(S100A8/A9)can induce the migration of primary tumor cells to distant target organs by binding multiple channel proteins,promote the formation of tumor metastasis microenvironment,and play an important role in the immune and inflammatory response of the body.It provides a new target and idea for the prevention and treatment of tumor metastasis and invasion.This paper mainly reviewed the expression and mechanism of S100A8/A9 on related channel proteins in a variety of high incidence tumors,in order to provide a new strategy for tumor prevention,diagnosis and treatment.
6.Mechanism of salvianolic acid B protecting H9C2 from OGD/R injury based on mitochondrial fission and fusion
Zi-xin LIU ; Gao-jie XIN ; Yue YOU ; Yuan-yuan CHEN ; Jia-ming GAO ; Ling-mei LI ; Hong-xu MENG ; Xiao HAN ; Lei LI ; Ye-hao ZHANG ; Jian-hua FU ; Jian-xun LIU
Acta Pharmaceutica Sinica 2024;59(2):374-381
This study aims to investigate the effect of salvianolic acid B (Sal B), the active ingredient of Salvia miltiorrhiza, on H9C2 cardiomyocytes injured by oxygen and glucose deprivation/reperfusion (OGD/R) through regulating mitochondrial fission and fusion. The process of myocardial ischemia-reperfusion injury was simulated by establishing OGD/R model. The cell proliferation and cytotoxicity detection kit (cell counting kit-8, CCK-8) was used to detect cell viability; the kit method was used to detect intracellular reactive oxygen species (ROS), total glutathione (t-GSH), nitric oxide (NO) content, protein expression levels of mitochondrial fission and fusion, apoptosis-related detection by Western blot. Mitochondrial permeability transition pore (MPTP) detection kit and Hoechst 33342 fluorescence was used to observe the opening level of MPTP, and molecular docking technology was used to determine the molecular target of Sal B. The results showed that relative to control group, OGD/R injury reduced cell viability, increased the content of ROS, decreased the content of t-GSH and NO. Furthermore, OGD/R injury increased the protein expression levels of dynamin-related protein 1 (Drp1), mitofusions 2 (Mfn2), Bcl-2 associated X protein (Bax) and cysteinyl aspartate specific proteinase 3 (caspase 3), and decreased the protein expression levels of Mfn1, increased MPTP opening level. Compared with the OGD/R group, it was observed that Sal B had a protective effect at concentrations ranging from 6.25 to 100 μmol·L-1. Sal B decreased the content of ROS, increased the content of t-GSH and NO, and Western blot showed that Sal B decreased the protein expression levels of Drp1, Mfn2, Bax and caspase 3, increased the protein expression level of Mfn1, and decreased the opening level of MPTP. In summary, Sal B may inhibit the opening of MPTP, reduce cell apoptosis and reduce OGD/R damage in H9C2 cells by regulating the balance of oxidation and anti-oxidation, mitochondrial fission and fusion, thereby providing a scientific basis for the use of Sal B in the treatment of myocardial ischemia reperfusion injury.
7.Exploration of Correlation Between Psoraleae Fructus and Precocious Puberty in Children Based on Network Pharmacology
Ling-Ling XIA ; Yao CHEN ; Shun-Li TANG ; Ying ZHANG ; Hua LIU
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(4):981-987
Objective The network pharmacological methods and molecular docking technology were used for investigating the possibility of Psoraleae Fructus in promoting precocious puberty in children and its potential mechanism.Methods The main active ingredients of Psoraleae Fructus and their therapeutic targets were obtained from BATMAN-TCM online platform.The disease targets related with precocious puberty were obtained from GeneCards database.A visualized network of active ingredients-disease targets was constructed by Cytoscape 3.7.1 software.Protein-protein interaction(PPI)network diagrams were constructed based on the STRING online database.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were conducted using Metascape online tool.The structures of the main active ingredients were obtained from PubChem database,the structures of core targets were obtained from RCSB PDB database,and then the structures were imported into Autodock for molecular docking.Finally,the mimic diagrams of the molecular docking were drawn using PYMOL software.Results A total of 12 active ingredients of Psoraleae Fructus were obtained,involving 274 targets.And there were 11 active ingredients and 98 targets associated with precocious puberty.The main active compounds were stigmasterol,bakuchiol,angelicin,bavachalcone,isobavachalcone,and xanthotoxin.The main targets were estrogen receptor 1(ESR1),estrogen receptor 2(ESR2),insulin-like growth factor 1(IGF1),and progesterone receptor(PGR),which were mainly involved in the ovarian steroidogenic pathway and Hippo signaling pathway.The molecular docking results showed that the active compounds were well binded to the targets.Conclusion It is possible that Psoraleae Fructus can promote the sexual development in children and has its potential pharmacological mechanism.The results will provide theoretical references for the clinical prevention and treatment of precocious puberty and early pubertal development in children.
8.Effects of MYD88 overexpression on proliferation and apoptosis of diffuse large B cell lymphoma cells and its mechanism
Piaopiao HU ; Chengrui XUAN ; Hua DU ; Shirong LI ; Lixin WENG ; Ling HAI ; Yunga WU ; Xiaoyan XU
Chinese Journal of Clinical and Experimental Pathology 2024;40(1):44-50
Purpose To investigate the effect of MYD88 gene overexpression on the proliferation and apoptosis of human diffuse large B cell lymphoma(DLBCL)cells,and to prelimi-narily explore the mechanism of MYD88 gene action.Methods PEGFP-C2-MYD88 overexpressing MYD88 L265P gene was transfected into DLBCL cells by plasmid transfection.The exper-iment was divided into blank control group,negative control group and MYD88 L265P overexpression group.The fluores-cence expression of MYD88 L265P after overexpression was ob-served under inverted fluorescence microscope.RT-PCR and Western blot were used to detect the mRNA and protein expres-sion of MYD88 L265P,IRAK4,NF-κB and BCL2 in DLBCL cells before and after overexpression of MYD88 L265.CCK8 method was used to detect DLBCL cells proliferation and Ho-echst staining was used to detect DLBCL cells apoptosis.Re-sults After overexpression of MYD88 L265P,compared with the blank control group(0.670 4±0.017 5)and the negative control group(0.715 3±0.019 6),the MYD88L265P overex-pression group(1.157 2±0.010 2)increased significantly,with statistical significance(all P<0.05).After overexpression of MYD88 L265P,compared with the blank control group(0.69 ±0.04)and the negative control group(0.81±0.07),the MYD88L265P overexpression group(0.48±0.05)was signifi-cantly decreased,with statistical significance(all P<0.05).After overexpression of MYD88 L265P,compared with the blank control group(mRNA:1.0158±0.0115,0.987 3±0.010 2,1.007 6±0.015 3,protein:0.183 4±0.058 9,0.096 8± 0.015 7,0.147 5±0.0418)and negative control group(mR-NA:0.9132±0.0098,1.0032±0.0156,0.9327± 0.011 2,protein:0.187 9±0.042 3,0.088 9±0.0513,0.134 8±0.050 1),the mRNA(3.243 2±0.013 6,2.976 6 ±0.0213,1.585 9±0.019 8)and protein expressions(0.452 7±0.052 4,0.218 9±0.047 5,0.301 4±0.059 8)of IRAK4,NF-κB and anti-apoptosis protein BCL2 in MYD88L265P overexpression group were significantly increased,which was statistically significant(all P<0.05).Conclusion After overexpression of MYD88 L265P,the apoptosis rate of DLBCL cells decreased and the cell proliferation rate increased.The mechanism may be related to the mutation of MYD88 L265P gene,activation and amplification of NF-κB pathway,and pro-motion of the overexpression of antiapoptotic protein BCL2.
9.Clinical Analysis of 311 Cases with Giant Ovarian Mass
Hua LIU ; Jingxian LING ; Xianghong ZHU ; Rong LI ; Xiaoqiu TANG ; Yan ZHANG ; Huaijun ZHOU
Journal of Practical Obstetrics and Gynecology 2024;40(1):73-77
Objective:To analyze the clinicopathological features of giant ovarian masses(mean diameter≥10 cm)and analyze the clinical characteristics of patients in different age groups.Methods:The clinicopathological characteristics of 311 patients diagnosed with giant ovarian masses by surgery at Nanjing Drum Tower Hospital,Affiliated Hospital of Medical School,Nanjing University from January 2014 to December 2022 were retrospectively analyzed.Patients were further stratified by age and mass size to compare the differences of clinical and patho-logical features among different age groups and different mass diameter groups.Results:①The median age of thepatients were 44(24,60)years old.The first symptoms were as follows:ovarian mass discovered during physi-cal examination,abdominal pain,bloating,conscious abdominal distension,and symptoms of compression.②The surgical methods were as follows:unilateral oophorectomy(30.5%,95/311),ovarian cystectomy(28.9%,90/311),tumor staging or cytoreductive surgery(28.0%,87/311),total hysterectomy with bilateral adnexectomy(12.5%,39/311).③The pathological types were benign(49.5%,154/311),malignant(31.8%,99/311)and borderline(18.7%,58/311).④ Patients complained abdominal distension in<20 years old group were signifi-cantly higher than the other two groups(P<0.05).The ovarian resection rate in the>50-year-old group was higher than that of the other two groups(P<0.05),and the rate of unilateral ovarian resection in the<20-year-old group was still as high as 30.1%(15/49).⑤ The size of the mass correlated with the duration of the disease.When the disease course was between 1 to 6 months,the mass diameter line>30 cm was the most common(P<0.05).The incidence of borderline tumors in the>30 cm group was significantly higher than that in the other two groups,and the difference was statistically significant(P<0.05).Conclusions:Ovarian mucinous and mucinous borderline tumors are the most common types of giant adnexal masses.The size of the mass tends to increase with the prolongation of the disease course.The incidence of borderline tumors increases with the in-crease of mass.Health education for young people should be strengthened.When abdominal pain,abdominal bloating,especially lower abdominal distension occurs,they should seek medical treatment in time to avoid adnex-ectomy due to borderline tumors.
10.Prediction of preeclampsia in twin-pregnant women
LU Yan ; LI Qiongshan ; MENG Diyun ; MEI Lina ; DING Zhongying ; LI Wenwen ; CHU Hua ; QIN Ling
Journal of Preventive Medicine 2024;36(4):283-287
Objective:
To construct a prediction model for preeclampsia (PE) risk in twin-pregnant women, so as to provide the basis for early screening and prevention of PE.
Methods:
A total of 467 twin-pregnant women who underwent prenatal examination and delivered at Huzhou Maternal and Child Health Hospital were selected. Sixty cases with preeclampsia (PE) were included in the case group, and 60 women without PE were included in the control group. General information, blood biochemical indicators and uterine artery resistance index (UtA-RI) were collected. A logistic regression model was used to screen predictive factors and establish a nomogram. The Bootstrap method was performed for the internal validation; the receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis were employed to evaluate the discrimination, calibration and clinical utility of the nomogram, respectively.
Results:
In the case group, there were 47 individuals (78.33%) aged younger than 35 years, 21 individuals (35.00%) with pre-pregnancy body mass index (BMI) of 25 kg/m2 and above, and 33 individuals (55.00%) with in vitro fertilization. In the control group, there were 57 individuals (95.00%) aged younger than 35 years, 8 individuals (13.33%) with pre-pregnancy BMI of 25 kg/m2 and above, and 39 individuals (65.00%) with natural pregnancy. Multivariable logistic regression analysis identified age, pre-pregnancy BMI, method of conception, placental growth factor (PLGF) and UtA-RI as risk prediction factors for PE in twin-pregnant women. The established nomogram had an area under the ROC curve of 0.827 (95%CI: 0.755-0.899), a sensitivity of 0.767, a specificity of 0.733, a good discrimination and calibration, and a relatively high clinical net benefit.
Conclusion
The nomogram established by age, pre-pregnancy BMI, method of conception, PLGF and UtA-RI has a good predictive value for the risk of PE in twin-pregnant women.


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