1.Advances in the diagnosis and treatment of hepatocellular carcinoma with bile duct tumor thrombus
Yuxiang GUO ; Maosen WANG ; Zhongyuan LIU ; Xudong ZHANG ; Pengfei MA ; Xiangkun WANG ; Renfeng LI
Journal of Clinical Hepatology 2025;41(2):359-364
Hepatocellular carcinoma (HCC) with biliary duct tumor thrombus (BDTT) is currently not common in clinical practice and is easily misdiagnosed, and previously, it was often considered an advanced stage of the disease with a poor prognosis, making its treatment challenging. However, in-depth studies in recent years have gradually deepened our understanding of this disease, leading to significant changes in diagnostic and treatment concepts. Currently, comprehensive treatment, mainly surgery, is used for treatment, but there is still controversy over the selection of clinical treatment strategies. This article provides a detailed discussion on surgical methods and prognosis, in order to provide a reference for clinical treatment options.
2.Mechanism by which KRT18 interacts with mRNA and long non-coding RNA to regulate intervertebral disc nucleus pulposus cell injury
Zhongyuan LIU ; Yang LI ; Zhiwen ZHANG
Chinese Journal of Tissue Engineering Research 2025;29(2):312-321
BACKGROUND:Differentially expressed RNA-binding proteins in the intervertebral disc plays a key role in intervertebral disc degeneration,and decreased levels of the RNA-binding protein KRT18 are associated with degenerative disc disease,but its specific role in the nucleus pulposus cells has not yet been fully determined. OBJECTIVE:To investigate the interaction of KRT18 with mRNA and long non-coding RNA on nucleus pulposus cells of the intervertebral disc and its mechanism. METHODS:Normal and degenerated nucleus pulposus cells were obtained from nucleus pulposus samples of patients undergoing interbody fusion for lumbar fracture or intervertebral disc degeneration.iRIP-seq,functional enrichment analysis,and DNA microarray analysis were performed to identify the mRNA and long non-coding RNA binding with KRT18.Subsequently,KRT18 was knocked down in nucleus pulposus cells based on the analysis results,and the expression levels of related genes were detected at the protein and RNA levels through protein immunoblotting and qRT-PCR,respectively. RESULTS AND CONCLUSION:Through iRIP-seq analysis,we identified abundant KRT18 binding sites within the GUAAUC and AGCCUC sequences,indicating that KRT18 may be involved in regulating RNA transcription,translation,stability or play a role in cell signaling pathways.It can stably bind to mature mRNA,among which highly expressed genes include CRLF1,IGFBP4,etc.At the same time,the peak genes of long non-coding RNA binding with it include SNHG25,SNHG12,NEAT1,USP32,EIF4A2 and CDH4.Most of these genes are involved in various biological processes such as apoptosis and inflammation,and can mediate related pathways of extracellular matrix metabolism.KRT18 can regulate their stability,transport,translation,splicing and other functions,thus affecting gene expression and cell function.We further verified through experiments the knockdown of KRT18 in nucleus pulposus cells,and found that the level of extracellular matrix metabolism was inhibited and unbalanced,resulting in intervertebral disc degeneration in vitro.This study investigated the regulatory mechanism of KRT18 from the perspective of its binding with mRNA and long non-coding RNA for the first time,and speculated the potential function of KRT18 in the pathogenesis of intervertebral disc degeneration,laying a foundation for future research on the key functions of KRT18.
3.Research progress on the clinical treatment methods and mechanisms of traditional Chinese medicine for pediatric allergic rhinitis
Zhongyuan ZHANG ; Shuo ZENG ; Zhenyao YANG ; Keyan CHEN ; Shaowei LIU ; Shan ZHU
China Pharmacy 2025;36(22):2879-2884
Allergic rhinitis (AR) is one of the most common chronic non-infectious inflammatory diseases in children. Traditional Chinese medicine (TCM) employs a comprehensive therapeutic system integrating treatment by stages and syndrome differentiation and treatment, demonstrating significant advantages in the management of pediatric AR. This article systematically reviews the clinical treatment methods and underlying mechanisms of TCM for pediatric AR in recent years. It is found that internal therapies (such as herbal formulas or Chinese patent medicines like Xiaoqinglong decoction, Yiqi tuomin decoction), external therapies (including intradermal needles, acupoint application, tuina, and herbal nasal therapy), as well as combined internal and external approaches (oral herbs combined with acupoint application), have demonstrated significant effects in alleviating clinical symptoms, improving immune indicators, and reducing recurrence rates in children with AR. The underlying mechanisms are primarily associated with the regulation of signaling pathways such as Toll-like receptor/nuclear factor-kappa B and mitogen-activated protein kinase, thereby modulating immune balance, suppressing inflammatory responses, inhibiting pyroptosis, reducing mucus secretion, and promoting nasal mucosal repair.
4.Ablation of macrophage transcriptional factor FoxO1 protects against ischemia-reperfusion injury-induced acute kidney injury.
Yao HE ; Xue YANG ; Chenyu ZHANG ; Min DENG ; Bin TU ; Qian LIU ; Jiaying CAI ; Ying ZHANG ; Li SU ; Zhiwen YANG ; Hongfeng XU ; Zhongyuan ZHENG ; Qun MA ; Xi WANG ; Xuejun LI ; Linlin LI ; Long ZHANG ; Yongzhuo HUANG ; Lu TIE
Acta Pharmaceutica Sinica B 2025;15(6):3107-3124
Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.
5.Recombinant expression of Sphingobium yanoikuyae esterase SyEst870 capable of degrading carbamate pesticides.
Xiaoqian XIE ; Yin FENG ; Yuanyuan ZHOU ; Xin YAN ; Xiaoqin YUAN ; Wuxia QIU ; Xinfang MAO ; Zhongyuan LIU
Chinese Journal of Biotechnology 2025;41(4):1605-1620
Carbamate pesticides, a new type of broad-spectrum pesticides for controlling pests, mites, and weeds, are developed to address the shortcomings of organochlorine and organophosphorus pesticides. Their widespread use and slow degradation have led to environmental pollution, causing damage to ecosystems and human health. Managing pesticide residues is a pressing issue in the current environmental protection. This study aims to investigate the expression of SyEst870, a member of the SGNH/GDSL hydrolase family in Sphingobium yanoikuyae, in a prokaryotic system and evaluate the ability of the recombinant protein to degrade carbamate pesticides. The prokaryotic expression vector pET-32a-SyEst870 was constructed and transformed into the Escherichia coli BL21 for heterologous expression. The purified protein was studied in terms of enzyme activity and effects of temperature, pH, and metal ions on the enzyme activity, with p-nitrophenol acetate as the substrate and based on the standard curve of p-nitrophenol. LC-MS (liquid chromatography-mass spectrometry) was employed to examine the degradation effects of SyEst870 on carbaryl, metolcarb, and isoprocarb. GC-MS (gas chromatography-mass spectrometry) was employed to detect the degradation products of SyEst870 for the three pesticides. The soluble protein SyEst870 was successfully obtained through the heterologous expression in Escherichia coli, which yielded an enzyme with the activity of 677.5 U after affinity chromatography. SyEst870 exhibited degradation rates of 82.34%, 84.43%, and 92.87% for carbaryl, metolcarb, and isoprocarb, respectively, at an initial concentration of 100 mg/L within 24 h at 30 ℃ and pH 7.0. The primary degradation products of carbaryl were identified as α-naphthol and methyl isocyanate. Metolcarb was mainly degraded into m-cresol and methyl isocyanate, and isoprocarb was mainly degraded into 2-isopropylphenol and methyl isocyanate. Compared with the half-life of carbamate pesticides in the natural environment, which ranges from a few days to several weeks, the recombinant protein SyEst870 can rapidly eliminate the residues of carbamate pesticides. This study lays a foundation for addressing pesticide residues in the environment and in fruits and vegetables.
Escherichia coli/metabolism*
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Sphingomonadaceae/genetics*
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Recombinant Proteins/metabolism*
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Biodegradation, Environmental
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Esterases/metabolism*
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Pesticides/isolation & purification*
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Carbamates/isolation & purification*
6.Treatment of Cardiovascular Diseases in Diabetes Mellitus with Traditional Chinese Medicine: A Review
Yu ZHANG ; Yu LI ; Zhongyuan ZHENG ; Yan LIANG ; Chengcheng LIU ; Yue DAI ; Luqi WANG ; Tuo LIU ; Lina CHEN ; Yujie LI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(23):327-337
The complex pathophysiological mechanisms between diabetes mellitus and cardiovascular diseases have not yet been fully elucidated, becoming one of the challenges in clinical care. Glucagon-like peptide-1 receptor agonist (GLP1-RA) and sodium glucose cotransporter-2 inhibitors (SGLT2) are clinically used to reduce the cardiovascular risk of patients with diabetes mellitus. Traditional Chinese medicine has diverse biological activities and unique advantages in the treatment of chronic complex diseases due to its multi-component and multi-target effects. Based on recent reports, this paper reviewed the common risk factors of diabetes mellitus and cardiovascular diseases (e.g., hyperglycemia, insulin resistance, and inflammation), related targets such as apolipoprotein C-Ⅲ (APOC3), S100 calcium-binding protein A8/A9 (S100A8/A9), growth/differentiation factor-15 (GDF-15), and NACHT, LRR, and PYD domains-containing protein 3 (NLRP3), advanced glycation end products, insulin resistance, endothelial dysfunction, endoplasmic reticulum stress, mitochondrial dysfunction, and intestinal flora disorder. In addition, this paper summarized the research progress in the treatment of cardiovascular diseases in diabetes mellitus with the active ingredients (e.g., baicalein, puerarin, curcumin, notoginsenoside, and tanshinone ⅡA), single herbal medicines (e.g., Astragali Radix, Ginseng Radix et Rhizoma, Sophorae Flavescentis Radix, Cinnamomi Cortex, and Corni Fructus), and compound formulas (e.g., Buzang Tongluo Fang, Yiqi Yangyin Huoxue Fang, Shenqi Fang, Huangqisan, Danggui Buxue Tang, and Liuwei Dihuang Wan) of traditional Chinese medicine. Traditional Chinese medicine mainly treats cardiovascular diseases in diabetes mellitus by reducing inflammation and oxidative stress, ameliorating dyslipidemia and insulin resistance, protecting islet β cell function, repairing endothelial damage, inhibiting smooth muscle cell proliferation, foam cell formation, macrophage polarization, and cardiac hypertrophy and fibrosis, and regulating intestinal flora disorder. These processes involve insulin receptor substrate/ phosphatidylinositol 3-kinase/protein kinase B (IRS/PI3K/Akt), peroxisome proliferator-activated receptor α/γ (PPAR α/γ), nuclear factor-kappa B (NF-κB), adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK), hypoxia-inducible factor-1-BCH domain-containing protein (HIF-1-BNIP), vascular endothelial growth factor/hypoxia-inducible factor-1α (VEGF/HIF-1α) and other signaling pathways. This review is expected to provide a theoretical basis and reference for the treatment of cardiovascular diseases in diabetes mellitus with traditional Chinese medicine.
7.Preventive and therapeutic effects of Yiyang Pill in treating cardiovascular adverse reactions post-surgery in patients with differentiated thyroid cancer and qi and yin deficiency syndrome
Yuyuan LU ; Jiajun QIAO ; Xinyi LIU ; Aijing CHU ; Shouyao LIU ; Zhongyuan XIA
Journal of Beijing University of Traditional Chinese Medicine 2024;47(6):753-759
Objective To evaluate the effectiveness and safety of Yiyang Pill in preventing and treating cardiovascular adverse reactions in patients with traditional Chinese medicine(TCM)syndrome with qi and yin deficiency and thyroid stimulating hormone(TSH)inhibition after differentiated thyroid cancer(DTC)resection.Methods A randomized,double-blind,placebo-controlled clinical trial was conducted,and 120 patients with TSH inhibition after DTC surgery were enrolled and randomized into two groups in a 1∶1 ratio using SAS 9.4 software generated random tables.The control group received a placebo and TSH suppression therapy,whereas the treatment group received the Yiyang Pill and TSH suppression therapy.The treatment period was 3 months.The incidence of cardiovascular adverse reactions,blood pressure,blood lipids,thyroid function,the dosage of levothyroxine,the efficacy of TCM syndrome,and safety indicators were compared between the two groups.Multivariate Logistic regression was used to analyze the influencing factors of cardiovascular adverse reactions.Results The incidence of cardiovascular adverse reactions in the treatment group was lower than that in the control group(P<0.05),and the efficacy of TCM syndrome treatment was significantly higher than in the control group(P<0.05).The free tetraiodothyronine level in the treatment group was higher than that before treatment(P<0.05),and the systolic and diastolic blood pressure in the control group increased compared to those before treatment(P<0.05).No severe adverse events were observed in either group.Compared with the control group,the cardiovascular incidence in the treatment group was lower,and the cardiovascular incidence in the<100 μg/d group was lower than that in the group with≥100 μg/d before treatment.Conclusion The Yiyang Pill can reduce the incidence of cardiovascular adverse reactions in patients after DTC surgery,effectively improve TCM syndromes,and be safe to use.Yiyang Pill treatment is a protective factor for cardiovascular adverse reactions,and the dosage of levothyroxine≥100 μg/d was a risk factor.
8.Comparison of the efficacy of different surgical strategies in the treatment of patients with initially resectable gastric cancer liver metastases
Li LI ; Yunhe GAO ; Lu ZANG ; Kan XUE ; Bin KE ; Liang SHANG ; Zhaoqing TANG ; Jiang YU ; Yanrui LIANG ; Zirui HE ; Hualong ZHENG ; Hua HUANG ; Jianping XIONG ; Zhongyuan HE ; Jiyang LI ; Tingting LU ; Qiying SONG ; Shihe LIU ; Yawen CHEN ; Yun TANG ; Han LIANG ; Zhi QIAO ; Lin CHEN
Chinese Journal of Surgery 2024;62(5):370-378
Objective:To examine the impact of varied surgical treatment strategies on the prognosis of patients with initial resectable gastric cancer liver metastases (IR-GCLM).Methods:This is a retrospective cohort study. Employing a retrospective cohort design, the study selected clinicopathological data from the national multi-center retrospective cohort study database, focusing on 282 patients with IR-GCLM who underwent surgical intervention between January 2010 and December 2019. There were 231 males and 51 males, aging ( M(IQR)) 61 (14) years (range: 27 to 80 years). These patients were stratified into radical and palliative treatment groups based on treatment decisions. Survival curves were generated using the Kaplan-Meier method and distinctions in survival rates were assessed using the Log-rank test. The Cox risk regression model evaluated HR for various factors, controlling for confounders through multivariate analysis to comprehensively evaluate the influence of surgery on the prognosis of IR-GCLM patients. A restricted cubic spline Cox proportional hazard model assessed and delineated intricate associations between measured variables and prognosis. At the same time, the X-tile served as an auxiliary tool to identify critical thresholds in the survival analysis for IR-GCLM patients. Subgroup analysis was then conducted to identify potential beneficiary populations in different surgical treatments. Results:(1) The radical group comprised 118 patients, all undergoing R0 resection or local physical therapy of primary and metastatic lesions. The palliative group comprised 164 patients, with 52 cases undergoing palliative resections for gastric primary tumors and liver metastases, 56 cases undergoing radical resections for gastric primary tumors only, 45 cases undergoing palliative resections for gastric primary tumors, and 11 cases receiving palliative treatments for liver metastases. A statistically significant distinction was observed between the groups regarding the site and the number of liver metastases (both P<0.05). (2) The median overall survival (OS) of the 282 patients was 22.7 months (95% CI: 17.8 to 27.6 months), with 1-year and 3-year OS rates were 65.4% and 35.6%, respectively. The 1-year OS rates for patients in the radical surgical group and palliative surgical group were 68.3% and 63.1%, while the corresponding 3-year OS rates were 42.2% and 29.9%, respectively. A comparison of OS between the two groups showed no statistically significant difference ( P=0.254). Further analysis indicated that patients undergoing palliative gastric cancer resection alone had a significantly worse prognosis compared to other surgical options ( HR=1.98, 95% CI: 1.21 to 3.24, P=0.006). (3) The size of the primary gastric tumor significantly influenced the patients′ prognosis ( HR=2.01, 95% CI: 1.45 to 2.79, P<0.01), with HR showing a progressively increasing trend as tumor size increased. (4) Subgroup analysis indicates that radical treatment may be more effective compared to palliative treatment in the following specific cases: well/moderately differentiated tumors ( HR=2.84, 95% CI 1.49 to 5.41, P=0.001), and patients with liver metastases located in the left lobe of the liver ( HR=2.06, 95% CI 1.19 to 3.57, P=0.010). Conclusions:In patients with IR-GCLM, radical surgery did not produce a significant improvement in the overall prognosis compared to palliative surgery. However, within specific patient subgroups (well/moderately differentiated tumors, and patients with liver metastases located in the left lobe of the liver), radical treatment can significantly improve prognosis compared to palliative approaches.
9.Percutaneous vertebroplasty combined with radiofrequency ablation for spinal metastases:a meta-analysis of clinical efficacy and safety
Zhongyuan LIU ; Chuanfu WEI ; Nianhu LI
Journal of Interventional Radiology 2024;33(10):1088-1094
Objective To investigate the clinical efficacy and safety of percutaneous vertebroplasty(PVP)combined with radiofrequency ablation(RFA)for spinal metastases.Methods A computerized retrieval of academic papers concerning the case-control studies(CCS)and randomized controlled trials(RCT)of PVP combined with RFA for spinal metastases from the databases of CNKI,Wanfang,Chinese Biomedical Literature Database(CBM),PubMed,Cochrane Library,Web of science and other databases was conducted.A control group(receiving PVP treatment alone)and a test group(receiving PVP combined with RFA treatment)were established.Newcastle-Ottawa scale(NOS)score was used to evaluate case-controlled trial literature,and the Cochrane risk bias assessment tool was used to evaluate the RCT literature.Results A total of 12 articles(10 CCS articles and 2 RCT articles)including 1 051 patients were included in this analysis.Meta-analysis showed that the recurrence rate of spinal metastases(OR=0.17,95%CI=0.08-0.34,P<0.001),incidence of complications(OR=0.29,95%CI=0.21-0.41,P<0.001)and pain visual analog scale(VAS)score(WMD=-1.21,95%CI=-1.64--0.78,P<0.001)in the test group were significantly lower than those in the control group.The Karnofsky functional status(KPS)score(WMD=14.69,95%CI=-12.25-17.14,P<0.001)in the test group was remarkably higher than that in the control group,but the long-term efficacy in the test group(OR=1.55,95%CI=0.90-2.68,P=0.12)was not obviously better than that in the control group.Conclusion For the treatment of spinal metastases,PVP combined with RFA has significant clinical short-term efficacy and safety,although its long-term efficacy is not obvious.Due to the limited quantity and quality of the included literature,larger-scale and higher-quality clinical trial studies need to be done before the above conclusions can be further clarified.
10.Comparison of the efficacy of different surgical strategies in the treatment of patients with initially resectable gastric cancer liver metastases
Li LI ; Yunhe GAO ; Lu ZANG ; Kan XUE ; Bin KE ; Liang SHANG ; Zhaoqing TANG ; Jiang YU ; Yanrui LIANG ; Zirui HE ; Hualong ZHENG ; Hua HUANG ; Jianping XIONG ; Zhongyuan HE ; Jiyang LI ; Tingting LU ; Qiying SONG ; Shihe LIU ; Yawen CHEN ; Yun TANG ; Han LIANG ; Zhi QIAO ; Lin CHEN
Chinese Journal of Surgery 2024;62(5):370-378
Objective:To examine the impact of varied surgical treatment strategies on the prognosis of patients with initial resectable gastric cancer liver metastases (IR-GCLM).Methods:This is a retrospective cohort study. Employing a retrospective cohort design, the study selected clinicopathological data from the national multi-center retrospective cohort study database, focusing on 282 patients with IR-GCLM who underwent surgical intervention between January 2010 and December 2019. There were 231 males and 51 males, aging ( M(IQR)) 61 (14) years (range: 27 to 80 years). These patients were stratified into radical and palliative treatment groups based on treatment decisions. Survival curves were generated using the Kaplan-Meier method and distinctions in survival rates were assessed using the Log-rank test. The Cox risk regression model evaluated HR for various factors, controlling for confounders through multivariate analysis to comprehensively evaluate the influence of surgery on the prognosis of IR-GCLM patients. A restricted cubic spline Cox proportional hazard model assessed and delineated intricate associations between measured variables and prognosis. At the same time, the X-tile served as an auxiliary tool to identify critical thresholds in the survival analysis for IR-GCLM patients. Subgroup analysis was then conducted to identify potential beneficiary populations in different surgical treatments. Results:(1) The radical group comprised 118 patients, all undergoing R0 resection or local physical therapy of primary and metastatic lesions. The palliative group comprised 164 patients, with 52 cases undergoing palliative resections for gastric primary tumors and liver metastases, 56 cases undergoing radical resections for gastric primary tumors only, 45 cases undergoing palliative resections for gastric primary tumors, and 11 cases receiving palliative treatments for liver metastases. A statistically significant distinction was observed between the groups regarding the site and the number of liver metastases (both P<0.05). (2) The median overall survival (OS) of the 282 patients was 22.7 months (95% CI: 17.8 to 27.6 months), with 1-year and 3-year OS rates were 65.4% and 35.6%, respectively. The 1-year OS rates for patients in the radical surgical group and palliative surgical group were 68.3% and 63.1%, while the corresponding 3-year OS rates were 42.2% and 29.9%, respectively. A comparison of OS between the two groups showed no statistically significant difference ( P=0.254). Further analysis indicated that patients undergoing palliative gastric cancer resection alone had a significantly worse prognosis compared to other surgical options ( HR=1.98, 95% CI: 1.21 to 3.24, P=0.006). (3) The size of the primary gastric tumor significantly influenced the patients′ prognosis ( HR=2.01, 95% CI: 1.45 to 2.79, P<0.01), with HR showing a progressively increasing trend as tumor size increased. (4) Subgroup analysis indicates that radical treatment may be more effective compared to palliative treatment in the following specific cases: well/moderately differentiated tumors ( HR=2.84, 95% CI 1.49 to 5.41, P=0.001), and patients with liver metastases located in the left lobe of the liver ( HR=2.06, 95% CI 1.19 to 3.57, P=0.010). Conclusions:In patients with IR-GCLM, radical surgery did not produce a significant improvement in the overall prognosis compared to palliative surgery. However, within specific patient subgroups (well/moderately differentiated tumors, and patients with liver metastases located in the left lobe of the liver), radical treatment can significantly improve prognosis compared to palliative approaches.

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