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28 July 2024, Volume 44 Issue 7 Previous Issue   
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Innovative research team achievement column
Topics on advances in translational medicine frontiers
Basic research
Clinical research
Public health
Review


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Innovative research team achievement column

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Expression of cancer-testis antigen SPANXB and its mechanism in affecting hepatocellular carcinoma progress XUE Yu, ZHANG Hailong, LEI Ming 2024, 44 (7):  801-813.  doi: 10.3969/j.issn.1674-8115.2024.07.001 Abstract ( 169 )   HTML ( 24 )   PDF (9250KB) ( 98 )   Objective ·To analyze the expression of cancer-testis antigen (CTA) family member SPANXB (sperm protein associated with the nucleus on the X chromosome B) in liver cancer and its correlation with the prognosis of liver cancer patients, and to explore the impact of SPANXB on liver cancer cell proliferation and its potential mechanism. Methods ·By using liver cancer sample data from the cancer genome atlas (TCGA) database, the expression of SPANXB in liver cancer tissue and its correlation with patient survival were analyzed. By constructing stable knockdown of SPANXB and stable overexpression of SPANXB in liver cancer cell lines, the effects of SPANXB on liver cancer cell proliferation were evaluated with live cell imaging experiments, EdU cell proliferation experiments and plate clone formation experiments. The regulatory pathways of SPANXB in liver cancer cell proliferation were explored through RNA-sequence (RNA-seq), and the effect of SPANXB on liver cancer cell cycle was validated through cell cycle experiments. Immunoprecipitation-mass spectrometry (IP-MS) was used to explore the proteins that interacted with SPANXB, and co-immunoprecipitation (Co-IP) was used to verify their interaction. Results ·The expression of SPANXB mRNA in liver cancer tissues was higher than that in normal tissues (P=0.003), and was negatively correlated with the survival of liver cancer patients. Stable knockdown of SPANXB could reduce the proliferation and clone formation ability of liver cancer cells, while stable overexpression of SPANXB could promote these processes. The analysis results of RNA-seq showed that knockdown of SPANXB could lead to downregulation of DNA replication and G1/S cell cycle transition-related pathways. The results of cell cycle experiments showed that knockdown of SPANXB could result in changes in the liver cancer cell cycle. The results of IP-MS and Co-IP showed that SPAXNB interacted with cell cycle-related proteins such as mitotic arrest defect 2-like protein 1 (MAD2L1) and WD repeat domain 5 (WDR5). Conclusion ·The high expression of SPANXB is negatively correlated with the prognosis of liver cancer. SPANXB may regulate the cell cycle and enhance the proliferation activity of liver cancer cells by interacting with MAD2L1 and WDR5. Figures and Tables | References | Related Articles | Metrics

Topics on advances in translational medicine frontiers

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Progress in translational research on immunotherapy for osteosarcoma HU Fei, CAI Xiaohan, CHENG Rui, JI Shiyu, MIAO Jiaxin, ZHU Yan, FAN Guangjian 2024, 44 (7):  814-821.  doi: 10.3969/j.issn.1674-8115.2024.07.002 Abstract ( 264 )   HTML ( 22 )   PDF (1336KB) ( 567 )   Osteosarcoma is a common primary malignant bone tumor in adolescents and children, characterized by a high recurrence rate and metastasis, making its treatment extremely challenging. Traditional treatment modalities, including surgery, radiation therapy, and chemotherapy, can alleviate symptoms to some extent, but improving long-term survival rates remains a pressing issue. With the continuous development of immunotherapy, breakthroughs have been made in the research of tumor immune microenvironment and the application of immunotherapy in recent years, providing new perspectives and strategies for osteosarcoma treatment. Currently, immunotherapy strategies include tumor vaccines, targeted cytokines, immune checkpoint inhibition, adoptive cell therapy, combination therapy, etc., significantly enhancing patient immune responses from the aspects of boosting immunity, overcoming immune tolerance, and preventing immune evasion, thereby effectively improving the patients′ survival rates and prognosis. This review aims to systematically introduce the immune microenvironment of osteosarcoma and discuss the latest advances in immunotherapy in clinical translational research of osteosarcoma. By deeply understanding the immune characteristics of osteosarcoma and corresponding treatment methods, it is hopeful to provide more effective strategies for personalized treatment, contributing to the improvement of the patients′ survival rates and prognosis. References | Related Articles | Metrics

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Advances in drug therapy of diabetic retinopathy CHEN Minghao, LIU Peiyu, WANG Xuan, WU Yixiang, JIANG Yujin, ZHANG Chaoyang, ZHANG Jingfa 2024, 44 (7):  822-829.  doi: 10.3969/j.issn.1674-8115.2024.07.003 Abstract ( 355 )   HTML ( 25 )   PDF (1330KB) ( 520 )   Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes and has become one of the leading causes of blindness and visual impairment in diabetes patients. The pathogenesis of DR is multifaceted, involving inflammation, oxidative stress, neurovascular abnormalities, and other factors that present potential targets for disease management interventions. Currently, anti-vascular endothelial growth factor (VEGF) drugs serve as the primary treatment for advanced stages of DR when irreversible neurovascular damage and visual impairment have occurred. Additionally, some patients show poor or no response to anti-VEGF treatment. There is a lack of early intervention options for the initial phases of the disease. Therefore, there is an urgent need to develop novel local or systemic therapies based on the underlying mechanisms of DR to enable early prevention and treatment with the aim of preserving patients′ vision. Medications targeting various pathways including anti-inflammatory agents (corticosteroids and nonsteroidal anti-inflammatory drugs), neurotrophic and neuroprotective drugs, drugs modulating biochemical pathways, antioxidant phytochemicals, and gene therapy can complement each other in terms of therapeutic effects to benefit a larger number of individuals affected by DR. This article reviews previous research reports on the pathogenesis, drug treatment methods, and potential therapeutic targets associated with DR in order to provide guidance for clinical practice. References | Related Articles | Metrics

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Research progress in immune cells regulating drug resistance of tumor cells in tumor microenvironment ZHANG Yesheng, YANG Yijing, HUANG Yiwen, SHI Longyu, WANG Manyuan, CHEN Sisi 2024, 44 (7):  830-838.  doi: 10.3969/j.issn.1674-8115.2024.07.004 Abstract ( 556 )   HTML ( 26 )   PDF (1687KB) ( 599 )   Tumor microenvironment (TME) is a complex cellular environment where tumor cells reside, along with various types of cells and extracellular components surrounding the tumor cells. Immune cells are key components of TME, including tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), lymphocytes, regulatory T cells (Tregs), natural killer cells (NK cells), dendritic cells (DCs), and many others. It is worth noting that drug resistance is currently a major factor limiting the efficacy of cancer treatment methods such as chemotherapy, radiotherapy, targeted therapy, and immunotherapy, and a leading cause of treatment failure. Research has found that the development of drug resistance in tumor cells is the result of interactions between tumor cells and TME. Consequently, overcoming drug resistance in tumors caused by TME is considered a significant challenge in cancer treatment. In recent years, with in-depth research into immune cells within TME, significant progress has been made in understanding the specific mechanisms by which immune cells regulate drug resistance in tumor cells. Furthermore, therapeutic strategies that target these immune cells, signaling pathways, or cytokines have been shown to effectively combat tumor drug resistance and enhance the therapeutic outcomes of cancer treatment. This article reviews the research advancements regarding the roles of TAMs, MDSCs, Tregs, and NK cells in tumor drug resistance within TME and discusses the development of targeting strategies to overcome this resistance. Additionally, we explore the relationship of tumor-associated neutrophils (TANs) and B regulatory cells (Bregs) with tumor drug resistance. It is hoped that this review will offer insights and serve as reference for reducing tumor drug resistance and improving the efficacy of anti-tumor therapies. Figures and Tables | References | Related Articles | Metrics

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Research progress of the role of intestinal microbiota-mediated bile acids in inflammatory bowel disease XIA Xixi, DING Keke, ZHANG Huiheng, PENG Xufei, SUN Yimin, TANG Yajun, TANG Xiaofang 2024, 44 (7):  839-846.  doi: 10.3969/j.issn.1674-8115.2024.07.005 Abstract ( 235 )   HTML ( 22 )   PDF (1788KB) ( 301 )   It is estimated that approximately seven million people worldwide are affected by inflammatory bowel disease (IBD), causing a huge burden on healthcare systems and society. In the occurrence, progression, and treatment of IBD, the intestinal microbiota and its key metabolic product, bile acids, play a crucial role. The intestinal microbiota not only participates in the biotransformation of bile acids, enriching the diversity of bile acids, but also regulates their synthesis and transport through the farnesoid X receptor (FXR). Meanwhile, bile acids contribute to regulating the structure and function of the intestinal microbiota by supporting microbial diversity, exerting direct toxicity, participating in indirect antimicrobial pathways, and influencing microbial metabolic capabilities. Furthermore, under normal physiological conditions, intestinal microbiota-derived bile acids facilitate the repair process of the intestinal epithelial barrier. They also promote the balance of the immune system by modulating the functions of various immune cells including helper T (Th) cells 17, regulatory T (Treg) cells, CD8+ T cells and natural killer T(NKT) cells, thereby slowing down the development of IBD. This article focuses on exploring the role of intestinal microbiota and bile acids in the onset and progression of IBD, and investigating new effective treatment strategies by targeting intestinal microbiota and bile acids, such as bile acid receptor modulators, probiotics, prebiotics, fecal microbiota transplantation (FMT), and phage therapy. Figures and Tables | References | Related Articles | Metrics

Basic research

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Correlation analysis of COMP and autophagy in diabetic nephropathy and its functional verification WEI Yunxin, JIANG Xushun, CAI Mengyao, WEN Ruizhi, DU Xiaogang 2024, 44 (7):  847-858.  doi: 10.3969/j.issn.1674-8115.2024.07.006 Abstract ( 126 )   HTML ( 20 )   PDF (15327KB) ( 106 )   Objective ·To further clarify the mechanism of podocyte damage by studying the expression of cartilage oligomeric matrix protein (COMP) in glomerular podocytes and its relationship with podocyte autophagy under high glucose environment. Methods ·The gene expression dataset GSE104948 was downloaded from the GENE EXPRESSION OMNIBUS (GEO) database, and differentially expressed genes (DEGs) were obtained via GEO2R. The molecular functions and signaling pathways related to differential genes were summarized. The most correlated key genes (hub genes) were acquired by Weighted Gene Co-Expression Network Analysis (WGCNA) and the protein-protein interaction network (PPI) of DEGs was constructed with STRING database. The enrichment analysis was performed again. Conditionally immortalized mouse podocyte cells were cultured in vitro. After being fully differentiated, they were stimulated with high glucose, and the expressions of COMP, mammalian target of rapamycin (mTOR), microtubule-associated protein 1 light chain3 (LC3) and other proteins in podocytes were detected by Western blotting. The shRNA constructed by lentiviral vector was further used to infect podocytes to inhibit the expression of COMP, and the stable cell strains were screened by puromycin. The expression of COMP, mTOR, and LC3 of stable strains were detected by Western blotting, in order to observe the effect of COMP on autophagy. Results ·A total of 362 DEGs were filtered for subsequent analysis. Among these DEGs, 284 genes were up-regulated and 78 genes were down-regulated. The results of Gene Onotology (GO) term analysis showed that DEGs in diabetic nephropathy (DN) were mainly enriched in cell surface receptor signaling pathway, receptor binding, etc. The main enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways included phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/AKT) signaling pathway, extracellular matrix (ECM)-receptor interaction, etc. Sixty-four hub genes were refined through the intersection of WGCNA and PPI hub genes, and the hub genes with significantly increased or decreased expression were sifted. The hub genes were annotated with KEGG again, and it was found that most of the hub genes were enriched in "ECM-receptor interaction" and "PI3K/AKT signaling pathway". The PI3K/AKT/mTOR signaling pathway is a classic autophagy pathway, and COMP was absolutely overexpressed (logFC>2) in the 64 hub genes, suggesting that it may affect autophagy through this pathway. Western blotting showed that compared with the mannitol control group and the low glucose group, the expression of COMP in podocytes was significantly increased under high glucose stimulation. Compared with the control group, the expression of LC3-II in the high glucose group was significantly decreased, indicating that the autophagy initiation of podocytes was inhibited under the high glucose environment. Compared with the negative control, the expression of LC3-II in renal podocytes of mice with knockdown of COMP was significantly increased, and the mTOR decreased with the decrease of the expression of COMP, indicating that inhibiting COMP contributed to the recovery of autophagy in podocytes. Conclusion ·COMP is highly expressed in DN patients and highly enriched in ECM receptor and PI3K/AKT signaling pathway. Autophagy in mouse renal podocytes is inhibited under high glucose conditions, and the high expression of COMP induced by high glucose may be a key factor in autophagy inhibition. Inhibiting COMP helps to restore autophagy in mouse renal podocytes. Figures and Tables | References | Related Articles | Metrics

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Trend analysis of differentially expressed genes in retinoic acid-induced neural tube defects in mouse model CAO Rui, WEI Kaixin, ZHANG Xiaona, LIU Yurong, ZHANG Li 2024, 44 (7):  859-870.  doi: 10.3969/j.issn.1674-8115.2024.07.007 Abstract ( 165 )   HTML ( 17 )   PDF (7523KB) ( 112 )   Objective ·To explore the molecular regulatory mechanism of neural tube defect (NTD) induced by retinoic acid (RA) in mouse embryos, and reveal the gene expression regularity of neural tube closure in mice. Methods ·Based on the high-quality brain vesicle transcriptome data of mouse embryo during the critical period of neural tube closure [embryonic day 8.5 (E8.5), E9.5 and E10.5], the gene expression trend data of the NTD group and the control group were obtained by using Short Time-series Expression Miner (STEM) software. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed for genes with different expression trends between the NTD group and the control group. Some candidate genes were screened for validation. Pregnant mice were divided into the NTD group and control group, with 9 mice in each group. Pregnant mice in the NTD group were treated with RA and those in the control group were treated with sesame oil by gavage at E7.5. Foetal rat brain vesicle tissues were collected at E8.5, E9.5 and E10.5 for experiments. Based on the above animal tissues, the screened candidate genes were validated by quantitative real-time PCR (RT-PCR). Results ·A total of 18 255 genes were detected in the transcriptome data of the control group, and the expression patterns of these genes could be summarized into 7 significant profiles. A total of 19 037 gene expression data were detected in the transcriptome data of the NTD group, and gene expression patterns could be summarized into 6 profiles with significant significance. A total of 46 genes in the control group showed an upward trend but a downward trend in the NTD group. They were enriched in the positive and negative regulation of organ development, neuronal apoptosis, oligodendrocyte proliferation, and fibroblast growth factor signaling pathway at the biological process level. At the cellular component level, they were mainly involved in the basic structure of cells and neurons; At the molecular functional level, they were mainly related to the binding of fibroblast growth factor receptor. A total of 61 genes showed a downward trend in the control group but an upward trend in the NTD group. These genes were enriched in functions such as cell lysis and amino acid/ion transport at the biological process level. At the cellular component level, they were enriched in intracellular molecules, particles, extracellular region, intercellular space, etc. At the molecular function level, they were related to the activity of a series of enzymes and transporters. The results of RT-qPCR showed that the transcriptome sequencing data were authentic and reliable. Conclusion ·RA intervention causes abnormal cellular activities and stress responses during mouse embryo development, leading to abnormal embryo development, activation of signalling pathways related to organismal self-protection, and suppression of genes that maintain normal embryo development. Figures and Tables | References | Related Articles | Metrics

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Study on the developmental function of CT14 using the model organism Caenorhabditis elegans YANG Shuwen, CHEN Juan, YANG Qin, LEI Ming, HUANG Chenhui 2024, 44 (7):  871-882.  doi: 10.3969/j.issn.1674-8115.2024.07.008 Abstract ( 165 )   HTML ( 16 )   PDF (5768KB) ( 123 )   Objective ·To investigate the effects of the cancer-testis antigen 14 (CT14) on embryonic and larval development in nematodes by using the model organism Caenorhabditis elegans (C. elegans), aiming to uncover its potential functions and mechanisms during development. Methods ·Transgenic C. elegans strains were constructed by using microinjection for the inducible expression of human CT14 (HsCT14), a truncated mutant of CT14 (HsCT14?CIR) lacking CT14-specific intermediate region (CIR), and a green fluorescent protein (GFP) control. The impacts of full-length and truncated mutant CT14 on nematode embryonic and larval development were analyzed and compared. Additionally, transgenic C. elegans strains with inducible expression of CT14 from various primates, including the crab-eating macaque (Macaca fascicularis) and mouse lemur (Microcebus murinus), were also constructed to assess the effects on egg hatching and larval-to-adult transformation rates. The differential gene expression in nematode embryos induced by CT14 was analyzed by Smart-seq transcriptome sequencing, with further insights gained through KEGG (Kyoto Encyclopedia of Genes and Genomes) and GSEA (Gene Set Enrichment Analysis), to explore the involved biological processes and pathways. Results ·The induced expression of HsCT14 and its truncated mutant HsCT14?CIR significantly reduced the hatching rate of nematode eggs, with a more pronounced effect observed in HsCT14-expressing strains. Differential interference contrast (DIC) microscopy imaging revealed significant morphological abnormalities in embryos expressing HsCT14 during the comma stage. Nematodes expressing HsCT14 or HsCT14?CIR exhibited developmental arrest in larvae and substantially lower larval-to-adult transformation rates compared to the GFP control. The impact was more pronounced in nematodes expressing HsCT14 than those with HsCT14?CIR. The expression of Macaca fascicularis CT14 (MfCT14) exhibited significant effects on the hatching rate and adult transformation rate, similar to that of HsCT14, while the expression of Microcebus murinus CT14 (MmCT14) displayed significantly reduced impact compared to HsCT14 and MfCT14. Smart-seq results indicated that CT14 expression affected various biological processes in nematode embryos, related to ATP-dependent chromatin remodeling and DNA replication. Conclusion ·Ectopic expression of the cancer-testis antigen CT14 significantly disrupts both embryonic and larval developments in C. elegans, with the CIR sequence substantially enhancing this effect. It suggests that CT14 may play an important regulatory role in biological development by affecting gene expression in multiple pathways, including chromatin remodeling. Figures and Tables | References | Related Articles | Metrics

Clinical research

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Observation on the effect of hydrogel probiotics colonized in inflammatory sites in the treatment of inflammatory bowel disease XU Wei, LI Meng, WANG Haoze, CUI Kai, XIAO Zeyu 2024, 44 (7):  883-890.  doi: 10.3969/j.issn.1674-8115.2024.07.009 Abstract ( 198 )   HTML ( 10 )   PDF (3672KB) ( 98 )   Objective ·To construct a probiotic ( Escherichia coli Nissle1917,EcN) system (EcN@PVA-ALG) loaded on polyvinyl alcohol (PVA) / alginate (ALG) hydrogel (PVA-ALG) rich in negative hydroxyl groups, and to explore its colonization in the inflammatory site of colon and its therapeutic effect on dextran sulfate sodium salt (DSS)-induced inflammatory bowel disease (IBD). Methods ·EcN suspension was added to the PVA-ALG hydrogel, and then EcN@PVA-ALG hydrogel probiotic complex was obtained after screening and centrifugation. The synthesis of PVA-ALG hydrogel was verified by rheometer. The surface charge of EcN@PVA-ALG was detected by potentiometer and the load of EcN on PVA-ALG was observed by fluorescence microscope. The absorbance of EcN@PVA-ALG at 600 nm was detected by enzyme labeling instrument. Meanwhile, the bacterial plate count of EcN@PVA-ALG complex suspension was taken to study the growth activity of EcN in EcN@PVA-ALG. The CCK-8 kit was used to assess the inhibitory ability of EcN@PVA-ALG on HEK cell proliferation. In vivo imaging system (IVIS) was used to firstly analyze the enrichment of PVA-ALG on inflammatory colon to study its inflammatory targeting property; then EcN was loaded on PVA-ALG, and IVIS was used to observe the enrichment of EcN@PVA-ALG on inflammatory colon to study its ability to colonize the inflammatory site. To establish the model of IBD mice induced by DSS, EcN@PVA-ALG group ( n=5) was given 1×10 8CFU EcN@PVA-ALG every day for 5 d, and PVA-ALG group, EcN group, PBS group and healthy control group with 5 mice were set up. During the treatment, the body mass of the mice was recorded every day. After treatment, the colonic tissue was taken, and the length of colon was measured. The disease activity index (DAI) score was graded. The levels of inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-10 and transforming growth factor-β (TGF-β) were detected, and the pathological evaluation of colonic tissue was made by H-E staining. Results ·Both PVA-ALG and EcN@PVA-ALG were negatively charged. EcN was successfully loaded onto PVA-ALG and PVA-ALG did not affect the growth viability of EcN, which contributed to the subsequent colonization of inflammatory colons. PVA-ALG had a favorable safety profile on normal cells. Compared with healthy controls, PVA-ALG had more than 2-fold enrichment effect on inflammatory colon tissue. In vitro and in vivo experiments revealed that EcN@PVA-ALG complex loaded with EcN had 8 times higher enrichment effect on inflammatory tissue than EcN without any modification. After EcN@PVA-ALG treatment, the body weight of mice recovered rapidly. The increase of DAI was significantly inhibited. The length of colon was similar to that of healthy mice. The levels of TNF- α and IL-6 decreased, while the levels of IL-10 and TGF- β increased. The crypt structure of colon tissue recovered. Conclusion ·Compared to unmodified EcN, EcN@PVA-ALG promotes the colonization of EcN at inflammatory sites of colon and allows it to exert better efficacy on treating DSS-induced IBD. Figures and Tables | References | Related Articles | Metrics

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Effect of early postoperative administration of zoledronic acid on the prognosis of osteoporotic femoral intertrochanteric fracture in patients with advanced ages WANG Beichen, YANG Yaoqi, BAO Qiyuan, WEN Junxiang, ZHANG Weibin, WAN Rong 2024, 44 (7):  891-898.  doi: 10.3969/j.issn.1674-8115.2024.07.010 Abstract ( 146 )   HTML ( 14 )   PDF (1374KB) ( 108 )   Objective ·To investigate the effect of early postoperative administration of zoledronic acid on fracture healing and functional recovery in elderly patients with osteoporotic femoral intertrochanteric fracture treated with proximal femoral nail antirotation (PFNA) surgery, and explore other potential prognostic factors. Methods ·A total of 174 patients with femoral intertrochanteric fractures of 80 years old or above who underwent PFNA treatment in Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from January, 2016 to February, 2022, were divided into experimental group (n=26) and control group (n=148) according to whether they received zoledronic acid early after surgery. All patients were followed up twice at 6 weeks and 12 weeks after surgery. The patients in the experimental group were matched with the control group by propensity score matching (PSM) at a ratio of 1:3 (the matching factors included age, gender, fracture type, and body mass index). General characteristics, as well as fracture healing and functional recovery at the two follow-up visits were compared between the two groups after matching. Subsequently, Logistic regression was used to explore the potential prognostic factors on fracture healing at 12 weeks after surgery. Results ·PSM resulted in 25 patients in the experimental group and 65 patients in the control group, and there were no statistically significant differences in baseline characteristics between the two groups. The fracture healing rates at 6 weeks and 12 weeks after surgery in the experimental group (16.0% and 96.0%, respectively) were higher than those in the control group (1.5% and 73.8%), and the differences were statistically significant (P<0.05). Harris hip function score in the experimental group at 12 weeks was significantly higher than that of the control group (P=0.019). The results of Logistic regression analysis showed that good surgical reduction (OR=12.52, 95%CI 2.67?58.74, P=0.001), early postoperative administration of zoledronic acid (OR=10.14, 95%CI 1.01?102.09, P=0.049), and higher serum albumin level (OR=1.15, 95%CI 1.02?1.29, P=0.025) were the favorable factors of early fracture healing, while unstable fracture (OR=0.10, 95%CI 0.03?0.31, P=0.000) was the unfavorable factor. Conclusion ·For elderly patients with osteoporotic intertrochanteric femoral fractures treated with PFNA surgery, early postoperative administration of zoledronic acid can promote fracture healing and lead to better functional recovery; in addition, good surgical reduction and higher serum albumin levels are favorable factors for fracture healing, whereas unstable fracture presents as a hindrance to the healing process. Figures and Tables | References | Related Articles | Metrics

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Clinical predictive value of 20-minute residual rate of diuretic renal scintigraphy in the timing of pyeloplasty JI Xueli, GOU Jinyu, CHEN Suyun, FU Hongliang, ZOU Renjian, WANG Hui 2024, 44 (7):  899-906.  doi: 10.3969/j.issn.1674-8115.2024.07.011 Abstract ( 121 )   HTML ( 10 )   PDF (2436KB) ( 106 )   Objective ·To explore the predictive value of diuretic renal scintigraphy parameters such as 20-minute residual rate (R20) for pyeloplasty in children with congenital unilateral ureteropelvic junction obstruction (UPJO). Methods ·The clinical data and diuretic renal scintigraphy results of 110 children with congenital unilateral UPJO who were first treated at the Department of Nuclear Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine from August 2018 to August 2023 were retrospectively analyzed. The imaging results and the progress of hydronephrosis were followed up after the first diuretic renal scintigraphy. According to the outcome event of pyeloplasty due to the progression of hydronephrosis, the children were divided into operation group and non-operation group. Age, gender, side of hydronephrosis, and baseline diuretic renal scintigraphy parameters including blood perfusion rate (BPR), differential renal function (DRF), time to peak (Tmax), time to half (T1/2) and R20 were compared between the two groups. Logistic regression was used to analyze the effect of various parameters on the progression of hydronephrosis. The receiver operating characteristic (ROC) curve was used to analyze the predictive value of diuretic renal scintigraphy parameters for surgical intervention. Wilcoxon test was used to compare the examination parameters of two diuretic renal dynamic imaging. Results ·During the follow-up, 60 children underwent pyeloplasty after progression, and the other 50 children did not progress. The differences in DRF, Tmax, T1/2 and R20 between the two groups of children at baseline were statistically significant (all P<0.05). Univariate and multivariate Logistic regression analysis showed that only R20 was an independent predictor of pyeloplasty (OR=4.730, 95%CI 1.009-1.178, P=0.030). R20 predicted pyeloplasty with a sensitivity of 88.3%, specificity of 56%, the area under the ROC curve of 0.758 (95% CI 0.667-0.850, P=0.000), and the cut-off value of 90.08%. During the follow-up, 38 children underwent the second diuretic renal scintigraphy, and the DRF was lower than before. The difference between the two DRFs was statistically significant (Z=-2.589, P=0.010), especially in children with R20≥90.08% (Z=-2.166, P=0.030). R20 in the non-operation group decreased significantly compared with the baseline (Z=-2.062, P=0.039). However, R20 in the operation group was higher than baseline, but the difference was not statistically significant (P>0.05). Conclusion ·R20 plays an important role in the prediction of pyeloplasty in children with congenital unilateral UPJO. For children with R20≥90.08%, pyeloplasty should be performed as soon as possible to prevent further deterioration of renal function. Figures and Tables | References | Related Articles | Metrics

Public health

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Effect of hypertension and dyslipidemia on cognition of urban elderly residents ZHANG Yiyi, NI Changyu, JIN Ying, HE Yaping, FENG Nannan 2024, 44 (7):  907-914.  doi: 10.3969/j.issn.1674-8115.2024.07.012 Abstract ( 124 )   HTML ( 11 )   PDF (1618KB) ( 86 )   Objective ·To explore the effects of hypertension and dyslipidemia on cognitive function in the elderly. Methods ·A dynamic population cohort was established by using prospective cohort study methods. In 2019, a complete cohort was selected from residents aged 65 and above who voluntarily participated in a free physical examination program in a community in Shanghai, serving as the baseline cohort. In 2022, 512 community-dwelling elderly aged 67 to 93 were randomly selected from the same community as the follow-up cohort for the study. The collected date included residents′ health records, various physical examination measurements, and Mini-mental State Examination (MMSE) scale scores. Results ·Of the 512 cases that were followed up, the valid sample size was reduced to 495 after data cleaning. According to the baseline and follow-up cognitive assessments and changes, the cases were categorized into three cognitive groups: the improvement group, the normal group, and the decline group. The prevalence of hypertension in the decline group was 43.14% higher than that in the improvement group and 24.39% higher than that in the normal group (66.67% in the decline group vs 23.53% in the improvement group, P=0.011; 66.67% in the decline group vs 42.28% in the normal group, P=0.040). Total cholesterol (TC) in the improvement group was lower than that in the normal group [improvement group (4.38±1.04) mmol/L vs normal group (5.11±1.12) mmol/L, P=0.009]. Additionally, TC in the decline group in 2022 was higher than that in 2019 [paired difference (0.46±0.87) mmol/L, 95% CI 0.08?0.84, P=0.021]. LDL-Ch in the improvement group was lower than that in the normal group [improved group (2.51±0.92) mmol/L vs normal group (3.07±1.00) mmol/L, P=0.024], and their HDL-Ch in 2022 was higher than that in 2019 [paired difference (0.16±0.20) mmol/L, 95% CI 0.06?0.26, P=0.005]. The results of multinomial Logistic regression showed: TC in the improved group was lower than that in the normal group [β=4.12, OR=61.64, 95% CI 1.52?2494.07, P=0.029] and the decline group [β=5.88, OR=357.35, 95% CI 4.54?28149.75, P=0.008]; the TAG [β=1.85, OR=6.34, 95% CI 1.05?38.43, P=0.045], LDL-Ch [β=5.61, OR=274.06, 95% CI 3.65?20567.57, P=0.011], and hypertension [β=1.90, OR=6.69, 95% CI 1.53?29.16, P=0.011] in the decline group were higher than those in the improvement group; the age of the decline group was greater than that of the normal group [β=0.08, OR=1.08, 95% CI 1.00?1.16, P=0.041], and the education level was lower than that of the normal group [β=1.22, OR=3.39, 95% CI 1.28?8.94, P=0.014]. Conclusion ·Low TC and LDL-Ch and high HDL-Ch are beneficial to cognitive improvement. Conversely, hypertension, high TC, high TAG, high LDL-Ch, low education level, and advanced ages are risk factors for cognitive decline. Figures and Tables | References | Related Articles | Metrics

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Advances in molecular mechanisms of iodine-131 therapy resistance in thyroid carcinoma LIU Shiqi, WANG Hui, FENG Fang 2024, 44 (7):  915-921.  doi: 10.3969/j.issn.1674-8115.2024.07.013 Abstract ( 210 )   HTML ( 17 )   PDF (1296KB) ( 502 )   Thyroid cancer is the most common malignant tumor of the endocrine system, with differentiated thyroid carcinoma (DTC) accounting for over 90%. Most DTC patients have a good prognosis after systematic treatment, but a few develop dedifferentiation of primary tumor site or metastases, progressing to radioiodine-refractory DTC (RAIR-DTC), leading to significantly worse prognosis, which is a major cause of thyroid carcinoma-related mortality. Dysregulation of sodium iodide symporter (NIS) expression and function is the main reason for iodine-131 therapy resistance in thyroid carcinoma, influenced by genetic changes, epigenetic changes, tumor microenvironment, autophagy, and other factors. Genetic alterations such as the BRAFV600E mutation and RET/PTC chromosomal rearrangements activate oncogenic signaling pathways, directly or indirectly affecting NIS expression and its normal localization on the cell membrane. Epigenetic regulation modulates specific gene expression patterns, regulating NIS gene expression levels, thereby affecting the radioiodine uptake function of thyroid cells. Components in the tumor microenvironment, including immune cells, cytokines, and extracellular matrix, may also disrupt iodine uptake by reducing the expression levels of NIS and/or disrupting its normal function on the cell membrane. Additionally, autophagy, as an intracellular metabolic regulatory mechanism, can also modulate NIS expression and its intracellular distribution, thus impacting the radioiodine uptake and the sensitivity to iodine-131 therapy. Reviewing the roles of these factors in thyroid carcinoma dedifferentiation comprehensively can provide a more thorough understanding of the occurrence and progression of RAIR-DTC, aiding in the exploration of new therapeutic targets, improving prognosis, and providing more effective personalized treatment strategies for patients. References | Related Articles | Metrics

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Review of sublobar resection for lung adenocarcinoma with ground-glass presence ZHU Mingyang, XU Yuanyuan, REN Jianghao, HUANG Jiazheng, LI Ruonan, TAN Qiang 2024, 44 (7):  922-927.  doi: 10.3969/j.issn.1674-8115.2024.07.014 Abstract ( 145 )   HTML ( 14 )   PDF (1223KB) ( 228 )   Surgery is the mainstay of lung cancer treatment options. Traditionally, lobectomy has held its place as the gold standard for treating localized lung cancer, while sublobar resection, including wedge resection and segmentectomy, was primarily considered as an alternative, often reserved for patient ineligible to sustain a radical intervention. However, with the widespread application of computed tomography (CT) to clinical practice, the increasing detection rate of pulmonary ground glass nodules (GGNs) has reshaped this landscape. Ground glass opacity (GGO) in persistent lung nodules is an indicative factor of a favorable prognosis, typically corresponding to pathological changes such as atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), or adenocarcinomas predominantly featuring a lepidic growth pattern. A large number of retrospective studies have shown that sublobar resection can achieve satisfactory therapeutic outcomes for such lesions. A series of prospective studies from Japan have confirmed that for early-stage lung cancers dominated by GGOs, sublobar resection is also a viable curative surgical option. The follow-up data showed that there was no statistical difference in the survival status of these patients compared with that of pulmonary lobectomy. This article aims to delve into the role of limited lung resection in the context of lung adenocarcinoma presenting with GGO features. References | Related Articles | Metrics

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Research progress in systemic complications induced by autonomic dysfunction after acute ischemic stroke ZHONG Jiaqi, CAO Wenfei, ZHOU Huizhong, YANG Jiajun 2024, 44 (7):  928-934.  doi: 10.3969/j.issn.1674-8115.2024.07.015 Abstract ( 156 )   HTML ( 16 )   PDF (1371KB) ( 241 )   Cerebrovascular diseases pose a serious threat to human health. According to the latest epidemiological data, stroke is one of the leading causes of death and disability among adults worldwide. Acute ischemic stroke (AIS), which is caused by local circulatory disorders in the brain, accounts for over 80% of all strokes and is the most common type of stroke. Due to extensive damage to the cerebral cortex or direct involvement of the autonomic nerve centers and pathways caused by AIS, the balance between the sympathetic and parasympathetic nervous systems is disturbed (with a predominance of sympathetic activation). Therefore, the organs targeted by the downstream pathways of the sympathetic and parasympathetic nervous systems are affected by the neurotransmitters they secrete, resulting in a range of systemic complications (such as cardiac complications, stroke-related infections, gastrointestinal complications, acute kidney injury, metabolic changes, and sexual dysfunction). These systemic pathological changes, in turn, affect the progression of AIS, thereby exacerbating brain damage or directly leading to patient death. Treatments targeting imbalances in the autonomic nervous system may play a role in reducing complications and improving the prognosis of AIS. This article reviews the systemic effects of autonomic dysfunction following AIS and its mechanisms, providing insights for the treatment of AIS and intervention of systemic complications. References | Related Articles | Metrics