1.Value of serum Aldo-keto reductase family 1 member B10 (AKR1B10) in diagnosis of hepatocellular carcinoma
Yunling DU ; Changjiang SHI ; Fangyuan GAO ; Mengna ZHANG ; Lingling WANG ; Zhuqing ZHANG ; Ying MING ; Shoujun XIE
Journal of Clinical Hepatology 2025;41(4):684-689
ObjectiveTo investigate the expression of serum Aldo-keto reductase family 1 member B10 (AKR1B10) in patients with hepatocellular carcinoma (HCC) in northern China, and to provide a new and valuable biomarker for the clinical diagnosis of HCC. MethodsThis study was conducted among 102 patients with HCC, 119 patients with benign liver disease, and 132 patients with other malignant tumors who attended The Affiliated Hospital of Chengde Medical University and 148 healthy individuals who underwent physical examination from May 2020 to May 2024. ELISA and chemiluminescence were used to measure the serum levels of AKR1B10 and alpha-fetoprotein (AFP). The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, and the Kruskal-Wallis H test was used for comparison between three groups and further comparison between two groups; the chi-square test was used for comparison of categorical data between groups. The area under the ROC curve (AUC) was used to assess diagnostic efficiency. ResultsThe expression level of AKR1B10 was 3 053.79 (1 475.67 — 4 605.86) pg/mL in the HCC group, 1 324.42 (659.68 — 2 023.88) pg/mL in the benign liver disease group, 660.68 (377.56 — 2 087.77) pg/mL in the other malignant tumor group, and 318.30 (82.73 — 478.82) pg/mL in the healthy group, with a significant difference between the four groups (H=240.86, P<0.001), and further comparison between two groups showed that the HCC group had a significantly higher level than the other three groups (all P<0.001). The ROC curve analysis of the HCC group and the other three groups showed that serum AKR1B10 had an optimal cut-off value of 1 584.97 pg/mL in the diagnosis of HCC, with an AUC of 0.86 (95% confidence interval [CI]: 0.82 — 0.90), a sensitivity of 74.3%, and a specificity of 85.2%. Compared with each indicator alone, a combination of AKR1B10 and AFP could improve the sensitivity (81.8%) and specificity (91.4%) of HCC diagnosis. AKR1B10 had an AUC of 0.84 (95%CI: 0.78 — 0.90) in the diagnosis of patients with early- or middle-stage HCC, with a sensitivity of 76.2% and a specificity of 81.2%. AKR1B10 had an AUC of 0.85 (95%CI: 0.77 — 0.92) in the diagnosis of patients with AFP-negative HCC, with a sensitivity of 81.6% and a specificity of 79.9%. ConclusionAKR1B10 is a promising serological marker for the diagnosis of HCC, and a combination of AKR1B10 and AFP can improve the detection rate of HCC patients in northern China, especially those with early- or middle-stage HCC and AFP-negative HCC.
2.Characteristics and advantages of integrated traditional Chinese and Western medicine therapy in whole-course management of acute-on-chronic liver failure
Fangyuan GAO ; Ying FENG ; Xianbo WANG
Journal of Clinical Hepatology 2025;41(6):1001-1007
Acute-on-chronic liver failure (ACLF) is a complex clinical syndrome characterized by acute deterioration of liver function caused by different factors on the basis of chronic liver disease, accompanied by liver failure and/or extrahepatic organ failure, and it often has a high short-term mortality rate. With the increasing evidence of evidence-based medicine, multiple guidelines and consensus statements have been released, such as Guidelines for clinical diagnosis and treatment of acute-on-chronic liver failure in traditional Chinese medicine, Expert consensus on the diagnosis and treatment of acute-on-chronic liver failure with integrated traditional Chinese and Western medicine, and Guidelines for the integrated traditional Chinese and Western medicine diagnosis and treatment of acute-on-chronic liver failure, and integrated traditional Chinese and Western medicine therapies for ACLF have been constantly standardized and perfected. This article explores the characteristics and advantages of integrated traditional Chinese and Western medicine therapy in the whole-course management of ACLF from the aspects of early warning and prevention, treatment in the acute stage, management of complications, and rehabilitation care, in order to enhance the understanding of traditional Chinese and Western medicine treatment strategies among clinicians.
3.Expression and clinical significance of Ciz1 in colorectal cancer
Jin CAO ; Fangyuan GAO ; Shengbo SUN ; Huanhu ZHANG ; Chuanji HAN ; Qing GONG ; Gangxing LI
China Modern Doctor 2024;62(23):78-80,86
Objective To observe the expression of ciz1 in human colorectal cancer tissues and analyse the relationship between their expression and clinicopathologic features.Methods We detected the expression of Ciz1 and Ciz1 mRNA by immunohistochemistry and Western blotting.The relationship between the expression of ciz1 and clinicopathologic features was analied.Results According to immunohistochemical results,Ciz1 showed significant high expression in the primary lesion of colorectal cancer tissue,compared to normal adjacent tissues(66.7%vs.35.0%,P=0.001).Through Western blot analysis,it was found that the relative expression level in colorectal cancer tissue was 0.32±0.03,while in normal colorectal mucosal tissue it was 0.11±0.01.In addition,the relative expression level of Ciz1 in colorectal cancer tissue was significantly higher than that in normal intestinal mucosal tissue(P<0.05).The study found that the overexpression of Ciz1 in colorectal cancer tissue is significantly correlated with the T stage(P=0.018),lymph node metastasis(P=0.022),and AJCC stage(P=0.017)of the cancer.The age,gender,tumor location,degree of differentiation,and the presence of distant metastasis of patients were not correlated with this(P>0.05).The expression level of Ciz1 in colorectal cancer tissue is significantly increased,which is closely related to the T stage(P=0.018),lymph node metastasis(P=0.022),and American Joint Committee on Cancer stage(P=0.017)of colorectal cancer.Conclusion This association suggests that Ciz1 may play an important role in tumor staging,participating in the development and spread of tumors.Therefore,it can be foreseen that Ciz1 is expected to become a new biomarker for evaluating the prognosis of colorectal cancer patients.
4.The effects of fast walking on persons with sarcopenia
Haiying HUANG ; Ping LIN ; Qin WANG ; Qian REN ; Kanglu GAO ; Chengcheng KONG ; Fangyuan WANG
Chinese Journal of Physical Medicine and Rehabilitation 2023;45(8):715-719
Objective:To observe any effect of fast walking on walking speed, 6-minute walking test (6MWT) time, and on serum levels of growth differentiation factor-8 (GDF-8) and insulin-like growth factor-1 (IGF-1) in patients with sarcopenia.Methods:A total of 61 sarcopenia patients were randomly divided into an observation group ( n=31) and a control group ( n=30). Both groups were given conventional drug therapy. In addition, the observation group underwent 30-minutes of walking at 100-120 steps/min (about 60% of maximum heart rate) three times a week for 12 weeks. The control group also walked, but at 70-90 steps/min (less than 50% of maximum heart rate). Grip strength, walking speed, 6MWT time, skeletal muscle index (ASMI) and serum GDF-8 and IGF-1 were compared before and after the intervention. Results:There were no significant differences in grip strength or ASMI between observation group and control group (comparing males with males and females with females) before the experiment. Afterward, grip strength and ASMI in the observation group had increased significantly on average. Both were then significantly higher than the control groups′ averages, which had not changed significantly. Average walking speed, 6MWT time and serum IGF-1 levels had improved significantly in both groups, but the observation group′s average improvement was significantly greater. A significant decrease the average serum GDF-8 level was observed in the observation group, but not in the control group.Conclusion:Fast walking can improve the walking of persons with sarcopenia, raise serum IGF-1 levels, and significantly reduce serum GDF-8.
5.Safety of interferon β-1a for treatment of COVID-19: a real-world study based on FAERS database
Rongqing YANG ; Yongqing GAO ; Fangyuan HU ; Yinghong ZHAI ; Kuiling WANG ; Chang LU ; Jia HE ; Haiying ZHANG
Shanghai Journal of Preventive Medicine 2023;35(6):549-554
ObjectiveTo systematically evaluate the safety of interferon β-1a for treatment of corona virus disease 2019 (COVID-19), and to provide references for interferon β-1a's clinical application. MethodsThis study was conducted with the database from US Food and Drug Administration adverse event reporting system (FAERS) from January 1, 2015 to March 31, 2021. Information component (IC) and reporting odds ratio (ROR) methods were applied for signal mining. ResultsA total of 463 700 records of COVID-19 were selected for analysis, and 45 positive drug adverse event signals were detected. Headache (IC025=1.09, ROR025=2.28), pyrexia (IC025=0.51, ROR025=1.51) and multiple sclerosis relapse (IC025=3.67, ROR025=14.71) were positive adverse events with higher frequency. Autoimmune disorder (IC025=4.42, ROR025=24.03), streptococcal infection (IC025=4.12, ROR025=19.82), and multiple sclerosis relapse (IC025=3.67, ROR025=14.71) were positive adverse events. Acute lung injury, cardio-respiratory arrest and metabolic acidosis were associated with a higher proportion and frequency of death. ConclusionThere are certain safety issues with interferon β-1a in the treatment of COVID-19, and some adverse events with high frequency and high death rate deserve further attention by medical staffs.
6.Research progress in detection method for bisphenol A in food packaging materials
Yuqing MA ; Wanli DUAN ; Lei PENG ; Bingjie GENG ; Lingxuan TANG ; Haoneng WANG ; Fangyuan GAO
Shanghai Journal of Preventive Medicine 2023;35(6):604-612
As an industrial chemical, bisphenol A is widely used in various food packaging materials. However, it is an endocrine disrupting chemical, which has estrogen activity and can cause certain damage to humans. So far, there are few studies on the detection of bisphenol A in self-heating food packaging materials, and there remains a lack of relevant standard. Therefore, it is necessary to establish a simple, sensitive and efficient method for the detection of bisphenol A in self-heating food. This study briefly introduces the pretreatment methods of bisphenol A, such as ultrasonic extraction, solid phase extraction, accelerated solvent extraction, and detection methods, such as gas chromatography-mass spectrometry, high performance liquid chromatography, fluorescent detection, and electrochemical detection.
7.Cytochrome P450s in algae: Bioactive natural product biosynthesis and light-driven bioproduction.
Shanmin ZHENG ; Jiawei GUO ; Fangyuan CHENG ; Zhengquan GAO ; Lei DU ; Chunxiao MENG ; Shengying LI ; Xingwang ZHANG
Acta Pharmaceutica Sinica B 2022;12(6):2832-2844
Algae are a large group of photosynthetic organisms responsible for approximately half of the earth's total photosynthesis. In addition to their fundamental ecological roles as oxygen producers and as the food base for almost all aquatic life, algae are also a rich source of bioactive natural products, including several clinical drugs. Cytochrome P450 enzymes (P450s) are a superfamily of biocatalysts that are extensively involved in natural product biosynthesis by mediating various types of reactions. In the post-genome era, a growing number of P450 genes have been discovered from algae, indicating their important roles in algal life-cycle. However, the functional studies of algal P450s remain limited. Benefitting from the recent technical advances in algae cultivation and genetic manipulation, the researches on P450s in algal natural product biosynthesis have been approaching to a new stage. Moreover, some photoautotrophic algae have been developed into "photo-bioreactors" for heterologous P450s to produce high-value added pharmaceuticals and chemicals in a carbon-neutral or carbon-negative manner. Here, we comprehensively review these advances of P450 studies in algae from 2000 to 2021.
8.Gold nanoparticle-directed autophagy intervention for antitumor immunotherapy via inhibiting tumor-associated macrophage M2 polarization.
Siyue ZHANG ; Fangyuan XIE ; Kaichun LI ; He ZHANG ; You YIN ; Yuan YU ; Guangzhao LU ; Shihao ZHANG ; Yan WEI ; Ke XU ; Yan WU ; Hong JIN ; Lan XIAO ; Leilei BAO ; Can XU ; Yulin LI ; Ying LU ; Jie GAO
Acta Pharmaceutica Sinica B 2022;12(7):3124-3138
Tumor-associated macrophages (TAMs), one of the dominating constituents of tumor microenvironment, are important contributors to cancer progression and treatment resistance. Therefore, regulation of TAMs polarization from M2 phenotype towards M1 phenotype has emerged as a new strategy for tumor immunotherapy. Herein, we successfully initiated antitumor immunotherapy by inhibiting TAMs M2 polarization via autophagy intervention with polyethylene glycol-conjugated gold nanoparticles (PEG-AuNPs). PEG-AuNPs suppressed TAMs M2 polarization in both in vitro and in vivo models, elicited antitumor immunotherapy and inhibited subcutaneous tumor growth in mice. As demonstrated by the mRFP-GFP-LC3 assay and analyzing the autophagy-related proteins (LC3, beclin1 and P62), PEG-AuNPs induced autophagic flux inhibition in TAMs, which is attributed to the PEG-AuNPs induced lysosome alkalization and membrane permeabilization. Besides, TAMs were prone to polarize towards M2 phenotype following autophagy activation, whereas inhibition of autophagic flux could reduce the M2 polarization of TAMs. Our results revealed a mechanism underlying PEG-AuNPs induced antitumor immunotherapy, where PEG-AuNPs reduce TAMs M2 polarization via induction of lysosome dysfunction and autophagic flux inhibition. This study elucidated the biological effects of nanomaterials on TAMs polarization and provided insight into harnessing the intrinsic immunomodulation capacity of nanomaterials for effective cancer treatment.
9.Influencing factors for chronic kidney disease in patients with hepatitis B cirrhosis
Li YANG ; Ke SHI ; Fangyuan GAO ; Chongping RAN ; Jie HOU ; Xianbo WANG
Journal of Clinical Hepatology 2021;37(8):1817-1821.
ObjectiveTo investigate the influencing factors for chronic kidney disease (CKD) in patients with hepatitis B cirrhosis within 3 years. MethodsA total of 376 patients with hepatitis B cirrhosis who attended Beijing Ditan Hospital, Capital Medical University, from January 2014 to July 2017 were enrolled and followed up for 3 years, and according to the presence or absence of CKD, they were divided into CKD group with 23 patients and non-CKD group with 353 patients. Related general information and laboratory markers were collected. The t-test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups; a stepwise forward Cox regression analysis was used to screen out the independent influencing factors for CKD within 3 years in patients with hepatitis B cirrhosis. The area under the receiver operating characteristic curve (AUC) was used to investigate the value of the influencing factors in predicting CKD in patients with hepatitis B cirrhosis; the Kaplan-Meier method was used for survival analysis, and the log-rank test was used for comparison of the cumulative incidence rate of CKD between the patients with different risks. ResultsThe multivariate Cox regression analysis showed that age (hazard ratio [HR]=1.078, 95% confidence interval [CI]: 1.007-1.114, P=0.026), albumin (Alb) (HR=0.923, 95% CI: 0.860-0.989, P=0.024), and estimated glomerular filtration rate (eGFR) (HR=0.977, 95% CI: 0.955-0.999, P=0.037) were independent influencing factors for CKD within 3 years in patients with hepatitis B cirrhosis. Age, Alb, and eGFR had a relatively good value in predicting CKD, with AUCs of 0.701, 0.710, and 0.706, respectively. The Kaplan-Meier survival curve showed that the patients with baseline age ≥55 years, Alb <32 g/L, and eGFR ≥60 ml·min-1·1.73 m-2 and <76 ml·min-1·1.73 m-2 had a higher risk of CKD (χ2=9647, 13621, and 30.940, all P<0.05). ConclusionRenal function should be closely monitored for patients with old age and low Alb and eGFR levels.
10.Prediction of acute-on-chronic liver failure and integrated traditional Chinese and Western medicine therapy
Xianbo WANG ; Qun ZHANG ; Fangyuan GAO
Journal of Clinical Hepatology 2020;36(1):19-25
Acute-on-chronic liver failure (ACLF) is a reversible and complex clinical syndrome caused by various factors in patients with pre-existing chronic liver diseases, with the clinical features of acute liver function decompensation and high short-term mortality rate. ACLF has a complex pathogenesis, rapid progression, and a dangerous prognosis, and early and accurate prediction of prognosis is of vital importance. At present, there is still no ideal therapy for ACLF, and in recent years, integrated traditional Chinese and Western medicine therapy has achieved a certain effect in the treatment of this disease. This article reviews the advances in prognostic evaluation and integrated traditional Chinese and Western medicine therapy for ACLF, in order to provide guidance to prognostic evaluation of ACLF and selection of the regimens of integrated traditional Chinese and Western medicine therapy.

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