1.Changes in renal function in chronic hepatitis B patients treated initially with entecavir versus tenofovir alafenamide fumarate and related influencing factors
Shipeng MA ; Yanqing YU ; Xiaoping WU ; Liang WANG ; Liping LIU ; Yuliang ZHANG ; Xin WAN ; Shanfei GE
Journal of Clinical Hepatology 2025;41(1):44-51
ObjectiveTo investigate the influence of entecavir (ETV) versus tenofovir alafenamide fumarate (TAF) on renal function in previously untreated patients with chronic hepatitis B (CHB). MethodsA retrospective analysis was performed for the clinical data of 167 previously untreated CHB patients who received ETV or TAF treatment for at least 48 weeks at the outpatient service of Department of Infectious Diseases in The First Affiliated Hospital of Nanchang University from September 2019 to November 2023, and according to the antiviral drug used, they were divided into ETV group with 117 patients and TAF group with 50 patients. In order to balance baseline clinical data, propensity score matching (PSM) was used for matching and analysis at a ratio of 2∶1, and the two groups were compared in terms of estimated glomerular filtration rate (eGFR) and the incidence rate of abnormal renal function at week 48. According to eGFR at week 48, the patients were divided into normal renal function group and abnormal renal function group. The independent-samples 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. The multivariate Logistic regression analysis was used to investigate the influencing factors for abnormal renal function, and the receiver operating characteristic (ROC) curve was used to assess the performance of each indicator in predicting abnormal renal function. The Kaplan-Meier method was used to analyze the cumulative incidence rate of abnormal renal function, and the log-rank test was used for comparison. The analysis of variance with repeated measures was used to compare the dynamic changes of eGFR during antiviral therapy in CHB patients. ResultsAfter PSM matching, there were 100 patients in the ETV group and 50 patients in the TAF group. There were no significant differences in baseline clinical data between the ETV group and the TAF group (all P>0.05), with an eGFR level of 112.29±9.92 mL/min/1.73 m2 in the ETV group and 114.72±12.15 mL/min/1.73 m2 in the TAF group. There was a reduction in eGFR from baseline to week 48 in both groups, and compared with the TAF group at week 48, the ETV group had a significantly lower eGFR (106.42±14.12 mL/min/1.73 m2 vs 112.25±13.44 mL/min/1.73 m2, t=-2.422, P=0.017) and a significantly higher incidence rate of abnormal renal function (17.00% vs 4.00%, χ2=5.092, P=0.024). After the patients were divided into normal renal function group with 131 patients and abnormal renal function group with 19 patients, the univariate analysis showed that there were significant differences between the two groups in age (Z=-2.039, P=0.041), treatment drug (ETV/TAF) (χ2=5.092, P=0.024), and baseline eGFR level (t=4.023, P<0.001), and the multivariate Logistic regression analysis showed that baseline eGFR (odds ratio [OR]=0.896, 95% confidence interval [CI]: 0.841 — 0.955, P<0.001) and treatment drug (OR=5.589, 95%CI: 1.136 — 27.492, P=0.034) were independent influencing factors for abnormal renal function. Baseline eGFR had an area under the ROC curve of 0.781 in predicting abnormal renal function in CHB patients, with a cut-off value of 105.24 mL/min/1.73 m2, a sensitivity of 73.68%, and a specificity of 82.44%. The Kaplan-Meier curve analysis showed that the patients with baseline eGFR≤105.24 mL/min/1.73 m2 had a significantly higher cumulative incidence rate of abnormal renal function than those with baseline eGFR>105.24 mL/min/1.73 m2 (χ2=22.330, P<0.001), and the ETV group had a significantly higher cumulative incidence rate of abnormal renal function than the TAF group (χ2=4.961, P=0.026). With the initiation of antiviral therapy, both the ETV group and the TAF group had a significant reduction in eGFR (F=5.259, P<0.001), but the ETV group only had a significant lower level of eGFR than the TAF group at week 48 (t=-2.422, P=0.017); both the baseline eGFR≤105.24 mL/min/1.73 m2 group and the baseline eGFR>105.24 mL/min/1.73 m2 group had a significant reduction in eGFR (F=5.712, P<0.001), and there was a significant difference in eGFR between the two groups at baseline and weeks 12, 24, 36, and 48 (t=-13.927, -9.780, -8.835, -9.489, and -8.953, all P<0.001). ConclusionFor CHB patients initially treated with ETV or TAF, ETV antiviral therapy has a higher risk of renal injury than TAF therapy at week 48.
2.Improvement of neutral protease activity of Bacillus amyloliquefaciens LX-6 by combined ribosome engineering and medium optimization and its application in soybean meal fermentation.
Yifan ZHU ; Xinyi HUANG ; Tao HAN ; Jiteng WANG ; Xiaoping YU ; Zheng MA
Journal of Zhejiang University. Science. B 2025;26(8):805-812
Soybean meal (SBM) prepared by soybean crushing is the most popular protein source in the poultry and livestock industries (Cai et al., 2015) due to its economic manufacture, high protein content, and good nutritional value. Despite these benefits, SBM contains various antigen proteins such as glycinin and β-conglycinin, which account for approximately 70% of the total proteins of the SBM and reduce digestibility and damage intestinal function (Peng et al., 2018). Treating SBM with proteases (neutrase, alcalase, and trypsin) or fermentation can eliminate these antigen proteins (Contesini et al., 2018). Because of its safety and rapid growth cycle, Bacillus strains are considered ideal for the fermentation industry (Yao et al., 2021). SBM fermented by Bacillus yields products with high nutritional value and low levels of antinutritional factors (ANFs), stimulating research in this area (Yuan et al., 2017). Kumari et al. (2023) demonstrated that fermentation with Bacillus species effectively degrades antigen proteins and increases crude protein content. The degradation of antigen proteins relies on protease hydrolysis. Low protease production is the major obstacle hindering the widespread use of microbial fermentation techniques.
Bacillus amyloliquefaciens/metabolism*
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Fermentation
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Glycine max/metabolism*
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Soybean Proteins/metabolism*
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Peptide Hydrolases/metabolism*
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Ribosomes/metabolism*
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Globulins
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Antigens, Plant
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Seed Storage Proteins
3.Databases, knowledge bases, and large models for biomanufacturing.
Zhitao MAO ; Xiaoping LIAO ; Hongwu MA
Chinese Journal of Biotechnology 2025;41(3):901-916
Biomanufacturing is an advanced manufacturing method that integrates biology, chemistry, and engineering. It utilizes renewable biomass and biological organisms as production media to scale up the production of target products through fermentation. Compared with petrochemical routes, biomanufacturing offers significant advantages in reducing CO2 emissions, lowering energy consumption, and cutting costs. With the development of systems biology and synthetic biology and the accumulation of bioinformatics data, the integration of information technologies such as artificial intelligence, large models, and high-performance computing with biotechnology is propelling biomanufacturing into a data-driven era. This paper reviews the latest research progress on databases, knowledge bases, and large language models for biomanufacturing. It explores the development directions, challenges, and emerging technical methods in this field, aiming to provide guidance and inspiration for scientific research in related areas.
Biotechnology/methods*
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Knowledge Bases
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Synthetic Biology
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Databases, Factual
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Artificial Intelligence
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Systems Biology
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Computational Biology
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Fermentation
4.Intelligent mining, engineering, and de novo design of proteins.
Cui LIU ; Zhenkun SHI ; Hongwu MA ; Xiaoping LIAO
Chinese Journal of Biotechnology 2025;41(3):993-1010
Natural components serve the survival instincts of cells that are obtained through long-term evolution, while they often fail to meet the demands of engineered cells for efficiently performing biological functions in special industrial environments. Enzymes, as biological catalysts, play a key role in biosynthetic pathways, significantly enhancing the rate and selectivity of biochemical reactions. However, the catalytic efficiency, stability, substrate specificity, and tolerance of natural enzymes often fall short of industrial production requirements. Therefore, exploring and modifying enzymes to suit specific biomanufacturing processes has become crucial. In recent years, artificial intelligence (AI) has played an increasingly important role in the discovery, evaluation, engineering, and de novo design of proteins. AI can accelerate the discovery and optimization of proteins by analyzing large amounts of bioinformatics data and predicting protein functions and characteristics by machine learning and deep learning algorithms. Moreover, AI can assist researchers in designing new protein structures by simulating and predicting their performance under different conditions, providing guidance for protein design. This paper reviews the latest research advances in protein discovery, evaluation, engineering, and de novo design for biomanufacturing and explores the hot topics, challenges, and emerging technical methods in this field, aiming to provide guidance and inspiration for researchers in related fields.
Protein Engineering/methods*
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Artificial Intelligence
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Proteins/genetics*
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Computational Biology
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Machine Learning
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Data Mining
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Algorithms
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Deep Learning
5.Application value of 100 kVp low tube voltage combined with ASIR-V in Adamkiewicz artery imaging of spinal cord
Jiantao DENG ; Ting MA ; Gaowu YAN ; Jing YAN ; Siyi WU ; Xiaoping FAN ; Yong LI
Journal of Practical Radiology 2024;40(3):464-467,498
Objective To investigate the effect of 100 kVp low tube voltage combined with adaptive statistical iterative reconstruc-tion-Veo(ASIR-V)on the imaging display,image quality and radiation dose of Adamkiewicz artery(AKA).Methods Ninety patients with computed tomography angiography(CTA)of aorta were randomly divided into two groups.In group A,the tube voltage was 100 kVp,and ASIR-V was 80%reconstructed.The tube voltage in group B was 120 kVp,and adaptive statistical iterative recon-struction(ASIR)was 40%reconstructed.The CT value and the standard deviation(SD)value of descending aorta were measured at the 12th thoracic vertebra level,and the CT value and the SD value of the spinal cord were measured at the same level to calculate the signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)of AKA.According to the continuity between AKA and intercostal artery or lumbar artery,the visualization of AKA was evaluated by two doctors with a double-blinded method and a five-point method,and the radiation doses of group A and group B were compared.Results Compared with group B,the CT value of aorta in group A was sig-nificantly increased by about 22.83%(P<0.001).The background noise of AKA in group A was significantly lower than that in group B(P<0.001),and the SNR and CNR were significantly higher than those in group B(P<0.001).The visualization score of AKA in group A was higher than that in group B(P<0.05).The effective dose(ED)in group A was significantly lower than that in group B by about 41.28%(P<0.001).Conclusion 100 kVp combined with ASIR-V technique for spinal cord AKA imaging can obtain better image quality,improve the sensitivity of AKA display and reduce the radiation dose.
6.Effect of Shuanglu Tongnao Formula on Neuronal Ferroptosis in Ischemic Stroke Rats by Regulating the SIRT1/Nrf2/GPx4 Signaling Pathway
Guangshan ZHENG ; Yang ZHAI ; Kaihua WANG ; Wei MA ; Xiaoping MEI ; Ying CHEN ; Min ZOU ; Yan PANG ; Peng YANG ; Yan LYU
Herald of Medicine 2024;43(4):526-534
Objective To explore the effect of Shuanglu Tongnao Formula on neuronal ferroptosis in ischemic stroke rats and its regulatory mechanism on the silent information regulator 2 homolog 1(SIRT1)/nuclear factor erythroid 2-related fac-tor 2(Nrf2)/glutathione peroxidase 4(GPx4)signaling pathways.Methods Twenty rats were selected as sham operation group by the random number table method,and the remaining seventy rats were made ischemic stroke rat models by the middle cerebral artery occlusion method.The rats that had been successfully modeled were randomly divided into the model control group,Shuanglu Tongnao formula group,Shuanglu Tongnao formula+SIRT1 inhibitor group(Shuanglu Tongnao formula+EX527 group),with 20 rats in each group.After 14 days,the rats were scored for neurological injury;TTC staining was applied to detect the area of cerebral infarction in rats;HE staining was applied to detect pathological changes in rat brain tissue;Nissl staining was applied to detect the number of neurons in rat brain tissue;the kit was applied to detect the levels of ferri ion(Fe2+),superoxide dismutase(SOD),glutathione(GSH),and malonaldehyde(MDA)in rat brain tissue;immunohistochemistry was applied to de-tect the positive expression of acyl-CoA synthetase long-chain family member 4(ACSL4),transferrin receptor(TFR),and ferritin heavy polypeptide 1(FTH1)proteins in rat brain tissue;Western blotting method was applied to detect the expression of SIRT1,Nrf2,GPx4,and cystine/glutamate antiporter solute carrier family 7 member 11(SLC7A11)proteins in rat brain tissue.Results Compared with the sham operation group,the neurological deficit score,cerebral infarction area,the contents of Fe2+and MDA,and the protein expressions of ACSL4 and TFR in model control group were increased(P<0.05);the number of neurons,the con-tents of SOD and GSH,the protein expression of FTH1,SIRT1,Nrf2,GPx4,and SLC7A11 were all reduced(P<0.05).Compared with the model control group,the neurological deficit score,cerebral infarction area,the contents of Fe2+and MDA,and the protein expression of ACSL4 and TFR in the Shuanglu Tongnao formula group were reduced(P<0.05),and the number of neurons,the contents of SOD and GSH,the protein expressions of FTH1,SIRT1,Nrf2,GPx4,and SLC7A11 are all increased(P<0.05).The results of the SIRT1 inhibitor supplementation experiment showed that the SIRT1 inhibitor reversed the inhibitory effect of Shuan-glu Tongnao formula on neuronal ferroptosis,while also inhibited the expression of Nrf2 and GPx4(P<0.05).Conclusion The Shuanglu Tongnao formula may inhibit neuronal ferroptosis in ischemic stroke rats by activating the SIRT1/Nrf2/GPx4 signa-ling pathway.
7.MSCT post-processing technologies for diagnosing otosclerosis
Rong GUAN ; Hong ZHANG ; Xiaoping WU ; Jing YANG ; Xiangchun YANG ; Zengzeng ZHANG ; Mingyue MA
Chinese Journal of Interventional Imaging and Therapy 2024;21(1):28-32
Objective To observe the value of multi-slice spiral CT(MSCT)post-processing technologies for diagnosing otosclerosis.Methods Clinical data and original axial plain MSCT of 47 patients with otosclerosis(92 ears)and 65 patients with non-otosclerosis hearing impairment(79 ears)were retrospectively enrolled.MSCT post-processing images,including multi-planar reformation(MPR)of stapes and cochleas and curved planar reformation(CPR)of ossicular chains were obtained.The diagnostic value of original MSCT images alone and raw data of MSCT combing with post-processing images for diagnosing otosclerosis were compared.Results Otosclerosis was correctly diagnosed in 66 ears according to original MSCT images alone,but in 89 ears combined with MSCT post-processing images.The sensitivity of original MSCT images alone and combined with MSCT post-processing images was 71.74%and 96.74%,respectively,and the diagnostic accuracy was 81.29%and 96.49%,respectively,those of the latter were both higher than of the former(both P<0.05),which had specificities being not significantly different(92.41%vs.96.20%,P>0.05).Conclusion Combining with post-processing technologies could increase the sensitivity and accuracy of MSCT for diagnosing otosclerosis.
8.PET/MR attenuation correction method based on transmission scan
Shengnan FAN ; Xingzhao GUO ; Weidong MA ; Jun DENG ; Lei DENG ; Xiaoping LIU
Chinese Journal of Radiological Health 2024;33(5):499-504
Objective To propose a method for correcting the attenuation of positron emission tomography (PET) data in PET/magnetic resonance (MR) based on transmission scan, and to improve image quality, diagnostic accuracy, and lesion location accuracy. Methods In this study, the head phantom in the national standard GB/T 18988.1—2013 was used as the experimental model. The head phantom contained three 50 mm diameter cylindrical inserts filled with air, water, and solid teflon. The attenuation correction coefficients were calculated and analyzed based on transmission scan. Results With slice = 33 and theta = 0, the attenuation correction coefficient was the largest (about 7.5) when the coincidence line passed through the axis of the phantom. The spatial distribution of the attenuation correction coefficients clearly showed the positions of air insert and teflon insert, indicating that the attenuation correction coefficients calculated from transmission scan data were accurate. In the clinical verification experiment, the attenuation correction method based on transmission scan significantly improved the image quality and showed efficient attenuation correction. Conclusion This paper studied the attenuation correction method for PET data in PET/MR based on transmission scan. This method can improve the image quality. In the future work, the attenuation correction method of PET/MR will be further studied and optimized to facilitate clinical applications.
9.PET/MR attenuation correction method based on transmission scan
Shengnan FAN ; Xingzhao GUO ; Weidong MA ; Jun DENG ; Lei DENG ; Xiaoping LIU
Chinese Journal of Radiological Health 2024;33(5):499-504
Objective To propose a method for correcting the attenuation of positron emission tomography (PET) data in PET/magnetic resonance (MR) based on transmission scan, and to improve image quality, diagnostic accuracy, and lesion location accuracy. Methods In this study, the head phantom in the national standard GB/T 18988.1—2013 was used as the experimental model. The head phantom contained three 50 mm diameter cylindrical inserts filled with air, water, and solid teflon. The attenuation correction coefficients were calculated and analyzed based on transmission scan. Results With slice = 33 and theta = 0, the attenuation correction coefficient was the largest (about 7.5) when the coincidence line passed through the axis of the phantom. The spatial distribution of the attenuation correction coefficients clearly showed the positions of air insert and teflon insert, indicating that the attenuation correction coefficients calculated from transmission scan data were accurate. In the clinical verification experiment, the attenuation correction method based on transmission scan significantly improved the image quality and showed efficient attenuation correction. Conclusion This paper studied the attenuation correction method for PET data in PET/MR based on transmission scan. This method can improve the image quality. In the future work, the attenuation correction method of PET/MR will be further studied and optimized to facilitate clinical applications.
10.Advances in therapeutic drug monitoring methods based on liquid chromatography-tandem mass spectrometry
Ziying LI ; Jie XIE ; Ziyu QU ; You JIANG ; Di ZHANG ; Songlin YU ; Xiaoli MA ; Ling QIU ; Xinhua DAI ; Xiang FANG ; Xiaoping YU
Chinese Journal of Laboratory Medicine 2024;47(3):332-340
Liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology has the characteristics of high specificity and high throughput, making it rapidly applied and developed in the field of clinical testing. Its application in the monitoring of therapeutic drugs can effectively improve the quantitative accuracy and sensitivity, and formulate a personalized and optimal dosing plan for patients. However, this technology still faces some challenges, and automation, quality control, and quantitative traceability will be the future development direction.

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