1.Quality evaluation of Chinese and global guidelines/consensus for TDM of anti-TNF-α agents in patients with inflammatory bowel disease
Tanghui JIN ; Mengxin ZHU ; Cheng XIE ; Fan XIA ; Di YU ; Yue LI ; Yun LI ; Qinhua XI ; Jianguo ZHU
China Pharmacy 2024;35(4):481-487
OBJECTIVE To evaluate the quality of guidelines/consensus on therapeutic drug monitoring (TDM) of anti-tumor necrosis factor-α (TNF-α) in patients with inflammatory bowel disease (IBD) in China and globally. METHODS PubMed, Embase, CNKI, Wanfang data, VIP, and release websites of guidelines/consensus in China and globally were searched to collect guidelines/expert consensus on TDM with anti-TNF-α for IBD patients. The search period was from database establishment to June 2023. After two investigators independently screened the literature and extracted the data, the methodological quality of the included guidelines/consensuses was evaluated using the Appraisal of Guidelines for Research and Evaluation Ⅱ. The main recommendations of the included guidelines/consensuses were summarized. RESULTS A total of 9 articles were included, 3 were guidelines and 6 were expert consensus. The standardized percentages of the 9 guidelines/consensus in the 6 dimensions (scope and aims, participants, rigor of formulation, clarity of expression, application, and editorial independence) were 90.43%, 41.98%, 52.55%, 85.49%, 19.00%, and 76.85%, respectively. Eight guidelines/consensus had a recommendation of grade B and one consensus of grade C. The main recommendations involve TDM application scenarios, threshold ranges, strategy adjustments, detection methods, and interpretation of results. Most guidelines/consensus recommend passive TDM for non-responders. It is recommended to set the TDM concentration range according to the expected treatment results and make strategy adjustments in combination with the disease condition and TDM results. Additionally, the same test method is recommended for the same patient. Some guidelines/consensus hold that no differences were noted in the interpretation of results between biosimilar and original drug. CONCLUSIONS The overall quality of the included guidelines/consensus was fair, with relatively consistent recommendation. Clinicians need to understand the characteristics and limitations of TDM with this class of drugs, and interpret and apply results of TDM in combination with specific clinical treatment goals.
2.Establishment of SHERLOCK-HBA Detection Method and Its Application in Blood Identification
Qian-Wei YAO ; Hong-Xia HE ; Sheng HU ; Yi-Xia ZHAO ; Yu LUO ; An-Quan JI ; Qi-Fan SUN
Progress in Biochemistry and Biophysics 2024;51(8):1971-1982
ObjectiveRapid and accurate identification of body fluid traces at crime scenes is crucial for case investigation. Leveraging the speed and sensitivity of nucleic acid detection technology based on SHERLOCK, our research focuses on developing a peripheral blood SHERLOCK-HBA detection system to detect mRNA in forensic practice. MethodsShort crRNA fragments targeting the blood-specific mRNA gene HBA were designed and screened, alongside RPA primers. Optimal RPA primers were selected based on specificity and amplification efficiency, leading to the establishment of the RPA system. The most efficient crRNA was chosen based on relative fluorescence units (RFU) generated by the Cas protein reaction, and the Cas protein reaction system was constructed to establish the SHERLOCK-HBA detection method. The RPA and Cas protein reaction systems in the SHERLOCK detection system were then individually optimized. A total of 79 samples of five body fluids were tested to evaluate the method’s ability to identify blood, with further verification through species-specific tests, sensitivity tests, mixed spots detection, aged samples, UV-irradiated samples, and actual casework samples. ResultsThe SHERLOCK reaction system for the peripheral blood-specific marker HBA was successfully established and optimized, enabling detection within 30 min. The method demonstrated a detection limit of 0.001 ng total RNA, better than FOB strip method and comparable to RT-PCR capillary electrophoresis. The system could detect target body fluids in mixed samples and identify blood in samples stored at room temperature for three years and exposed to UV radiation for 32 h. Detection of 11 casework samples showed performance comparable to RT-PCR capillary electrophoresis. ConclusionThis study presents a CRISPR/Cas-based SHERLOCK-HBA detection system capable of accurately, sensitively, and rapidly identifying blood samples. Introducing CRISPR/Cas technology to forensic body fluid identification represents a significant advancement in applying cutting-edge molecular biology techniques to forensic science.The method’s simplicity, shorter detection time, and independence from specialized equipment make it promising for rapid blood sample identification in forensic cases.
3.Sonogenetics and its application in military medicine
Ying-Tan ZHUANG ; Bo-Yu LUO ; Xiao-Dong ZHANG ; Tuo-Yu LIU ; Xin-Yue FAN ; Guo-Hua XIA ; Qing YUAN ; Bin ZHENG ; Yue TENG
Medical Journal of Chinese People's Liberation Army 2024;49(3):360-366
Sonogenetics is an emerging synthetic biology technique that uses sound waves to activate mechanosensitive ion channel proteins on the cell surface to regulate cell behavior and function.Due to the widespread presence of mechanically sensitive ion channel systems in cells and the advantages of non-invasion,strong penetrability,high safety and high accuracy of sonogenetics technology,it has great development potential in basic biomedical research and clinical applications,especially in neuronal regulation,tumor mechanism research,sonodynamic therapy and hearing impairment.This review discusses the basic principles of sonogenetics,the development status of sonogenetics and its application in the prevention and treatment of noise-induced hearing loss,summarizes and analyzes the current challenges and future development direction,thus providing a reference for further research and development of sonogenetics in the field of military medicine.
4.Application of Bayesian probabilistic linkage model in birth and death data linking
Huiting YU ; Renzhi CAI ; Weixiao LIN ; Jingyi NI ; Naisi QIAN ; Tian XIA ; Fan WU
Shanghai Journal of Preventive Medicine 2024;36(1):98-103
ObjectiveTo elucidate the principles and methods of the Bayesian probabilistic linkage model, and to demonstrate the effect of applying the model in linking birth and death data. MethodsThrough the Shanghai birth and death registration system, data of 199 025 infants born in 2017 and 1 512 infants who died in 2017 and 2018 were collected. After cleaning the data, the data were divided into monthly blocks and fully linked. The Jaro-Winkler algorithm and Euclidean distance were employed to measure the similarity of fields for matching. A Bayesian probabilistic linkage model was constructed and the linking effect was evaluated using a confusion matrix. ResultsUsing the Bayesian probabilistic linkage model, the birth and death data of infants were effectively linked, revealing that 36.71% of infants who died in Shanghai were born outside the city, and the probability of infant death was 2.6‰. The confusion matrix of the test set showed a recall rate of 0.86, precision of 0.76, and an F-score of 0.81. ConclusionThe practical application of Bayesian probabilistic linkage demonstrates a good model performance, enabling the establishment of birth-death cohorts that more accurately reflect the true levels of infant mortality. Utilizing this technique to integrate data from different departments can effectively improve research efficiency in the field of public health.
5.Study on the role of genetic counseling and follow-up mode of medical cooperation in the health management of carriers of genetic gynecological tumor variants
Hui WANG ; Fang-Qin FAN ; Xia WANG ; Yu KANG
Fudan University Journal of Medical Sciences 2024;51(6):970-976
Objective To establish a genetic counseling and follow-up model for hereditary gynecologic tumor variant gene carriers in medical and nursing cooperation,and to evaluate its practical effect.Methods A total of 70 hereditary gynecologic tumor carriers who were admitted to the Gynecologic Cancer Genetic Counseling Clinic,Obstetrics and Gynecology Hospital,Fudan University from Jan 2021 to Jun 2023 were randomly divided into control group and observation group,with 35 cases in each group.The control group underwent routine outpatient management of tumor genetic counseling,and the observation group underwent the genetic counseling and follow-up mode of medical and nursing cooperation.Before and 6 months after intervention,the degree of psychological anxiety-depression,psychological crisis,quality of life and related clinical indicators of the two groups of mutant gene carriers were evaluated.Results In terms of the degree of psychological anxiety and depression,the observation group was significantly lower than the control group after 6 months of intervention(P<0.05).In terms of psychological crisis,the scores of all dimensions in the observation group were lower than those in the control group after 6 months of intervention(P<0.05).In terms of quality of life.After 6 months of intervention,the scores of the observation group in all seven dimensions were higher than those in the control group(P<0.05).After 6 months of intervention,8 patients in the observation group underwent prophylactic salpingo-oophorectomy,4 patients in the childbearing age carrier successfully underwent preimplantation genetic testing,and the number of cases in the control group was 0.Conclusion The genetic counseling and follow-up mode of hereditary gynecologic tumor variant gene carriers can provide a full-cycle,standardized and intelligent management for mutant gene carriers,reduce the degree of psychological anxiety-depression,psychological crisis,improve their quality of life,and guide them to adopt scientific methods to prevent the occurrence of hereditary tumors,which provides a practical basis for the management of hereditary gynecologic tumor variant gene carriers.
6.Application Progress of RNA Fluorescence Aptamers in Biosensing and Imaging
Xing-Chen QIU ; Cun-Xia FAN ; Rui BAI ; Yu GU ; Chang-Ming LI ; Chun-Xian GUO
Chinese Journal of Analytical Chemistry 2024;52(4):481-491
RNA fluorescence aptamers are RNA sequences that can specifically bind to non-toxic,cell permeable,and self-fluorescent target molecules and activate their luminescent properties.These aptamers provide powerful tools for biosensing and imaging researches due to their simple structure,easy synthesis,and easy transfection.This article summarized the characteristics and development history of various RNA fluorescent aptamers,including Malachite Green,Spinach,Broccoli,Mango,Corn,and Pepper family,as well as their corresponding fluorescent groups.The applications of RNA fluorescent aptamers were also reviewed from two aspects:extracellular detection and cell imaging.This review might provide guidance for labeling,detection and interactions of molecules from proof of concept and clinical assessment to practical clinical and biomedical applications.
7.LINC00626 promotes the malignant process of colorectal cancer metastasis through the JAK1/STAT3/KHSRP axis
Yanyan YU ; Xia KANG ; Linlin FAN ; Haifeng ZHANG ; Xiaolong WANG ; Haitao WEI ; Li LI
The Journal of Practical Medicine 2024;40(12):1643-1650
Objective To examine the regulation of malignant progression of colorectal cancer by LINC00626 via the JAK1/STAT3/KHSRP signaling axis and its molecular mechanism.Methods 96 individuals diagnosed with colorectal cancer at our hospital during June 11,2021 and June 11,2023 were chosen as research subjects,and their cancerous tissue and nearby normal tissue were collected.Cultivate colorectal cancer cell lines(SW620,HCT116,HT29,DLD-1,LOVO,Caco-2)and normal colorectal cells(NCM460)in vitro,and detect the expression of LINC00626 and KHSRP in colorectal cancer tissue and cell lines using qRT-PCR.Screening out cell lines infected with lentivirus,SW620 and HCT116 cell lines were transfected with knockdown lentivirus and its control,while HT29 and DLD-1 cell lines were transfected with overexpressing lentivirus and its control,respectively.Select stable transfected cell lines for cell function experiments to detect proliferation,migration,and invasion abilities.Detection of the effect of LINC00626 on the growth and migration of colorectal cancer tumors in live mouse experiments.The expression level of KHSRP protein in stable labeled cells was determined using a western blot analysis.Rescue experimental research on the regulatory relationship between LINC00626 and KHSRP.Results qRT-PCR showed low expression of LINC00626 and high expression of KHSRP in colorectal cancer tissues and cell lines.Cell function experiments showed that compared with the sh-NC group,the sh-LINC00626 group promoted cell proliferation,migration,and invasion in SW620 and HCT116 cells,while the overexpression group showed the opposite.Cell rescue experiments showed that,LINC00626+KHSRP significantly reversed the promotion effects of knocking down LINC00626 on cell proliferation,migration,and invasion.In the nude mouse experiment,com-pared with the sh-NC group,the sh-LINC00626 group showed a significant increase in tumor volume and weight,cell proliferation rate,and the number of lung metastases from colorectal cancer in the nude mice;Overexpression results in the opposite.The signal pathway experiment revealed that relative to the sh-NC group,the expression levels of JAK1 and STAT3 mRNA in the sh-LINC00626 group were significantly increased,whereas the results in the overexpression group were the opposite.Conclusion LINC00626 suppression the malignant progression of colorec-tal cancer metastasis through the JAK1/STAT3/KHSRP signaling axis.
8.Correlation analysis of functional constipation and its related factors with acute appendicitis in children
Na FAN ; Anding ZHANG ; Chunhui WANG ; Lingchao ZENG ; Yuanxia LI ; Yan LIN ; Xia YU ; Yalong ZHANG ; Yaxing HUI ; Yang DAI ; Xun JIANG
Chinese Pediatric Emergency Medicine 2024;31(8):597-601
Objective:To explore the correlation between functional constipation (FC)and its related factors with acute appendicitis(AA)in children,so as to provide a reference for the prevention and clinical diagnosis and treatment of children with AA. Methods:A case-control study was conducted on 170 children diagnosed with AA in the Department of Pediatrics,the Second Affiliated Hospital of Air Force Military Medical University,from August 2022 to March 2023,and 170 non-AA children during the same period were selected as control objects.The clinical data,incidence of FC,symptoms related to FC,Bristol stool classification,past constipation history and other information were compared between two groups.Results:The incidence of FC in 170 children with AA was 22.9%(39/170),which was significantly higher than 10.6%(18/170)in the non-AA group( P<0.01);For children under four years old,the proportion of faecal retention in AA group was higher than that in non-AA group(25.6% vs. 9.3%, P<0.05);For children ≥ 4 years old,the proportion of faecal retention and dyschezia in AA group were higher than those in non-AA group(28.2% vs. 6.9%,29.0% vs. 16.4%,respectively,all P<0.05).The proportion of past constipation history in AA group was higher than that in non-AA group(29.4% vs.14.1%).The duration of constipation in AA group was longer than that in non-AA group [0.00(0.00,1.25)month vs. 0.00(0.00,0.00)month,all P<0.01].The proportion of children with low Bristol stool classification in AA group was higher than that in non-AA group( P<0.01).Multivariate Logistic regression analysis showed that faecal retention[ OR=6.186(95% CI 2.336~16.380)] and long constipation time [ OR=1.310(95% CI 1.095~1.567)]were independent risk factors for AA in children(all P<0.05). Conclusion:The incidence of faecal retention in children with AA is higher than that in children without AA,and the median duration of constipation is longer than that in children without AA.Fecal retention and long-term constipation are independent risk factors for AA in children.
9.Risk factors for bronchopulmonary dysplasia in twin preterm infants:a multicenter study
Yu-Wei FAN ; Yi-Jia ZHANG ; He-Mei WEN ; Hong YAN ; Wei SHEN ; Yue-Qin DING ; Yun-Feng LONG ; Zhi-Gang ZHANG ; Gui-Fang LI ; Hong JIANG ; Hong-Ping RAO ; Jian-Wu QIU ; Xian WEI ; Ya-Yu ZHANG ; Ji-Bin ZENG ; Chang-Liang ZHAO ; Wei-Peng XU ; Fan WANG ; Li YUAN ; Xiu-Fang YANG ; Wei LI ; Ni-Yang LIN ; Qian CHEN ; Chang-Shun XIA ; Xin-Qi ZHONG ; Qi-Liang CUI
Chinese Journal of Contemporary Pediatrics 2024;26(6):611-618
Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.
10.Prognostic Value of IGF2BP3 Gene Expression Levels in Patients with Acute Myeloid Leukemia
Ning LE ; Jing-Jing YANG ; Yu-Chen LIU ; Xia-Wei ZHANG ; Hao WANG ; Ya-Nan WEN ; Yi-Fan JIAO ; Li-Li WANG ; Li-Ping DOU
Journal of Experimental Hematology 2024;32(2):355-364
Objective:To investigate the relationship between IGF2BP3 gene expression and prognosis in patients with acute myeloid leukemia(AML).Methods:High throughput transcriptome sequencing was performed on bone marrow primary leukemia cells from 27 patients with AML in our center,the relationship between IGF2BP3 expression levels and clinical characteristics were analyzed and verify the samples from patients with newly treated AML and refractory AML.The expression level of IGF2BP3 gene were analyzed in 20 healthy subjects and 26 patients with AML.The expression of IGF2BP3 in two anthracycline-resistant cell lines(HL60/ADR,K562/ADR)was detected by RT-qPCR and Western blot,and the expression difference of IGF2BP3 was compared with that in sensitive cells(HL60,K562).The relationship between the expression level of IGF2BP3 in patients with AML and prognostic were analyzed through data analysis of 746 patients with AML,and the prognostic value of IGF2BP3 in AML was analyzed by multivariate Cox regression analysis.Results:In the bone marrow primary leukemia cells of 27 AML patients in our center,the expression level of IGF2BP3 in patients with refractory AML was significantly higher than that in chemotherapy sensitive patients(P=0.0343).The expression of IGF2BP3 in leukemia patients with extramedullary infiltration(EMI)was significantly higher than that in AML patients without extramedullary infiltration(P=0.0049).Compared with healthy subjects(n=20),IGF2BP3 expression in AML patients(n=26)was higher(P=0.0009).The expression of IGF2BP3 mRNA in the anthracycline resistant cell lines(HL60/ADR,K562/ADR)was significantly higher than that in the sensitive cell lines(K562/ADR vs K562,P=0.0430;HL60/ADR vs HL60,P=0.7369).Western blot results showed that the expression of IGF2BP3 protein in mycin resistant cells was significantly higher than that in sensitive cells(P<0.001).qPCR results showed that the expression level of IGF2BP3 mRNA in refractory AML patients was significantly higher than that in patients with chemotherapy sensitive(P=0.002).High expression of IGF2BP3 was associated with poor prognosis in AML(P<0.05)in 3 large sample cohorts of AML patients.Univariate and multivariate prognostic analyses demonstrated that high expression of IGF2BP3 was significantly associated with shorter event-free survival(EFS,HR=1.887,P=0.024)and overall survival(OS,HR=1.619,P=0.016).Conclusion:The high expression of IGF2BP3 gene may be an important factor in the poor prognosis of AML,suggesting that IGF2BP3 gene may be a new molecular marker for the clinical prognosis evaluation and treatment strategy of AML.

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