1.Predictive model for severe adverse reaction associated with bevacizumab based on the global trigger tool and machine learning
Yongfei FU ; Xin LONG ; Hongzhen XU ; Jian TANG ; Xiangqing LI ; Yucheng LONG ; Dong QIN
China Pharmacy 2026;37(4):497-503
OBJECTIVE To confirm trigger items for adverse drug reaction (ADR) induced by bevacizumab, to identify and analyze the occurrence of related ADR, and to establish a predictive model for severe adverse reaction (SAR) caused by this drug. METHODS Based on the global trigger tool (GTT) theory, and referencing the GTT White Paper, drug package inserts and relevant literature, trigger items for bevacizumab-related ADR were confirmed using a single-round Delphi method. Utilizing these established items, electronic medical records of relevant patients at Guilin People’s Hospital from January 2020 to September 2024 were actively screened via the China Hospital Pharmacovigilance System. Pharmacists then identified and tallied the occurrence of bevacizumab-induced ADR. Data from patients with any positive trigger item served as the study subjects (divided into training and test sets at a ratio of 7∶3), candidate feature variables were selected from 39 related variables using the Boruta algorithm, and the multivariable Logistic regression analysis was performed with the occurrence of SAR as the dependent variable. Based on these candidate features, Logistic Regression, Extreme Gradient Boosting, Light Gradient Boosting Machine, Random Forest, and Categorical Boosting models were constructed. Model performance was evaluated using metrics including the area under the curve (AUC) of receiver operating characteristic curve and recall rate. The Shapley Additive exPlanations (SHAP) method was applied to analyze and interpret the contribution of each variable. A nomogram was constructed based on the optimal model. RESULTS A total of 38 trigger items for active monitoring of bevacizumab-related ADR were determined, comprising 17 laboratory indicators, 13 clinical manifestations, and 8 intervention measures. In total, 483 patients with positive trigger items were included, and 318 patients with bevacizumab-induced ADR were identified, including 83 SARs. The positive predictive values for the trigger items and cases were 43.57% (708/1 625) and 63.84% (318/483), respectively. Bevacizumab-induced ADR involved 7 systems/organs, with the hematological system being the most frequently involved (64.15%). The Boruta algorithm selected 7 vari ables: serum potassium, hematocrit, albumin-to-globulin ratio, prealbumin, hypertension history, age and red blood cell count. Multivariable Logistic regression showed that elevated serum potassium levels were associated with a decreased risk of bevacizumab-induced SAR (OR=0.234, P =0.002), while a history of hypertension (OR=2.642, P =0.006) and increased age (OR=1.040, P =0.025) were associated with an increased risk. The Logistic Regression model demonstrated superior performance with higher AUC, F1 score and recall rate (0.761, 0.447, 0.607), compared to other models. SHAP evaluation results indicated that variables such as serum potassium, hematocrit, and age ranked highest in importance. CONCLUSIONS Totally 38 trigger entries have been successfully identified for active screening of bevacizumab-related ADR. Elevated serum potassium levels are a protective factor against bevacizumab-induced SAR, whereas the hypertension history and increased age are risk factors. The Logistic Regression model is the optimal predictive model.
2.Applications of Optical Technology in Non-invasive Hemoglobin Detection
Yao PENG ; Xian-Long WANG ; Bi-Tie LAN ; Jian-Hai YU
Progress in Biochemistry and Biophysics 2026;53(6):1561-1580
Hemoglobin (Hb) concentration is a key clinical biomarker for diagnosing and managing anemia, ischemic stroke, perioperative blood loss, and chronic diseases such as renal failure. Traditional venous blood sampling remains the gold standard due to its high accuracy, but its invasive nature limits frequent testing, real time monitoring, and large scale screening. This has driven growing interest in non-invasive Hb detection technologies over the past decade. Among these, optical methods are the most promising because of their safety, potential for continuous monitoring, and compatibility with portable or wearable devices. This paper systematically reviews major advances in optical non invasive Hb detection from the last ten years. We focus on near-infrared spectroscopy branches—photoplethysmography (PPG) and dynamic spectrum (DS)—and also cover color analysis/RGB imaging, Raman spectroscopy, and photoacoustic spectroscopy. For each technology, we explain its detection principles, analyze advantages and limitations, and summarize optimization strategies reported in recent literature. PPG, based on pulsatile blood volume changes, underpins many commercial continuous monitors. However, its accuracy is constrained by motion artifacts, individual physiological variations (e.g., skin tone, tissue thickness), and low AC signal to noise ratio. In contrast, DS—an advanced derivative of PPG—uses a differential principle to extract absorbance changes between systolic and diastolic peaks. This theoretically eliminates interference from static tissues (skin, bone, venous blood) and common mode noise (e.g., ambient light), positioning DS as a more robust framework for high precision Hb quantification. Beyond spectral methods, color analysis/RGB imaging offers a hardware minimalist approach. By analyzing images of vascular rich, thin tissues (e.g., conjunctiva, nail beds, palms), it enables Hb estimation using smartphone cameras. Recent advances have shifted from manual RGB feature extraction to deep learning models and spectral super resolution that reconstruct hyperspectral data from RGB inputs, significantly improving screening accuracy. Our academic perspective emphasizes critical and integrative analysis. We highlight persistent challenges that hinder clinical translation: profound individual biological variability (skin optics, microvascular architecture), sensitivity to measurement conditions (pressure, ambient light), and a lack of standardized validation protocols and multi center trials. A central thesis is that no single optical method is universally superior; each involves trade offs between accuracy, complexity, cost, and practicality. Looking forward, we posit that the next performance leap will come from multimodal information fusion—combining PPG, electrocardiogram (ECG), bioimpedance, or different optical modalities to compensate for individual differences and environmental noise. AI and deep learning are essential not only for image analysis but also for automated, end to end feature extraction from complex waveforms like PPG sequences. Advancing hardware (tunable lasers, quantum dot LEDs, novel sensor designs) is crucial to improve signal fidelity and portability. Finally, we advocate for clinical scenario specific optimization and rigorous standardized evaluation frameworks to gain regulatory approval (e.g., FDA, NMPA) and achieve widespread clinical acceptance. In conclusion, this review synthesizes a decade of progress. Optical non-invasive Hb detection has evolved from proof of concept studies to emerging products and validated screening tools, but the journey toward reliable, clinic ready quantitative devices continues. The convergence of smarter algorithms, fused sensing modalities, and focused clinical validation offers the most promising path to transform this potential into routine medical practice, ultimately enabling personalized, continuous, and accessible hematological management.
3.Microstructural mapping of time-dependent diffusion MRI for the discrimination of clinically significant prostate cancer
Yanling CHEN ; Wenxin CAO ; Jinhua LIN ; Jian LING ; Zhihua WEN ; Long QIAN ; Yan GUO ; Huanjun WANG
Chinese Journal of Radiology 2025;59(7):777-783
Objective:To investigate the diagnostic efficacy of time-dependent diffusion MRI (t d-dMRI)-derived microstructural parameters for clinically significant prostate cancer (csPCa) and their associations with the pathological grade of prostate cancer(PCa) based on the International Society of Urological Pathology (ISUP) grades. Methods:This cross-sectional study prospectively enrolled 196 patients suspected of PCa from March 2023 to March 2024 at the First Affiliated Hospital, Sun Yat-Sen University. All patients underwent multiparametric MRI and t d-dMRI to obtain microstructural parameters, including cell diameter (d), intracellular volume fraction (f in), extracellular diffusion coefficient (D ex), cellularity, and apparent diffusion coefficient (ADC) value at oscillation frequencies of 33 Hz, 17 Hz, 0 Hz (ADC 33, ADC 17, and ADC 0). Pathologically, 95 cases were classified as csPCa (ISUP 2-5), and the rest 101 cases were classified as non-csPCa (benign or ISUP 1). Comparison of these microstructural metrics was made between csPCa and non-csPCa groups by independent t-tests or Mann-Whitney U tests, and multivariable logistic regression was used to identify independent predictors. A combined diagnostic model was then constructed based on the independent predictors. The receiver operating characteristic curve analysis was used to evaluate the diagnostic performance. Finally, in PCa, the correlation between microstructural parameters and ISUP grades was investigated by Spearman correlation. Results:The t d-dMRI measurements, including d, f in, cellularity, ADC 33,ADC 17 and ADC 0, were significantly different between csPCa and non-csPCa groups (All P<0.05). But D ex was not significantly different between the two groups ( Z=-1.27, P=0.204). The area under the receiver operating characteristic curve (AUC) for diagnosing csPCa were 0.701 (95% CI 0.628-0.775) for d, 0.869 (95% CI 0.819-0.920) for f in, 0.884 (95% CI 0.835-0.932) for cellularity, 0.777 (95% CI 0.712-0.842) for ADC 33, 0.852 (95% CI 0.799-0.905) for ADC 17, and 0.840 (95% CI 0.786-0.894) for ADC 0. Cellularity ( OR=6.142, 95% CI 2.920-12.929, P<0.001) and ADC 17 ( OR=0.108, 95% CI 0.027-0.429, P=0.002) were identified as the independent predictors, and their combined model achieved an AUC of 0.896 (95% CI 0.852-0.941). In PCa f in and cellularity were positively correlated with ISUP grades ( r=0.490 and 0.397, P<0.001), while ADC 33, ADC 17, and ADC 0 were negatively correlated with ISUP grades ( r=-0.198, -0.345, -0.360; P=0.041,<0.001,<0.001). d and D ex were not correlated with ISUP grades ( P>0.05). Conclusion:t d-dMRI based microstructural mapping correlates with ISUP grades of PCa and may be useful for the differential diagnosis of csPCa.
4.Chemical constituents from Tylophora ovata and their antibacterial activities
Xi-yue HE ; Xiao-jiang HAO ; Qi-long LIANG ; Jun-you JIAN ; Lie-jun HUANG
Chinese Traditional Patent Medicine 2025;47(4):1172-1181
AIM To study the chemical constituents from Tylophora ovata(Lindl.)Hook.ex Steud.and their antibacterial activities.METHODS Ethanol extract was isolated and purified by MCI,silica gel,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by spectral data.The inhibitory activities of each compound against Phomopsis sp.were determined by mycelial growth rate method.RESULTS Twenty-six compounds were identified as paeonol(1),stigmast-4-en-3-one(2),ergosta-4,6,8(14),22-tetraen-3-one(3),2,4-methoxyphenol(4),1,2,4-trimethoxybenzene(5),3-methoxyphenol(6),3,4-dimethoxyacetophenone(7),5α,8α-epidioxy-ergosta-6,22(E)-diene-3β-ol(8),kaempferol 3-O-β-D-galactopyranoside(9),glaucogenind C(10),glaucoge-nin A 3-O-β-D-cymaropyranoside(11),dibutyl phthalate(12),cynatratoside A(13),hirundigoside C(14),sublanceoside B2(15),cynanoside A(16),dipentyl phthalate(17),5-hydroxymethyl-2-furancarboxaldehyde(18),bis-(2-ethyl)hexylphthalate(19),p-hydroxybenzoic acid(20),syringic acid(21),β-hydroxypropiovanillone(22),3-hydroxy-l-(4-hydroxy-3,5-dimethoxyphenyl)-1-propanone(23),(+)-syringare sinol(24),(-)-syringare sinol(25),(+)-medioresinol(26).IC50 value of compound 12 was 37.27 μg/mL.CONCLUSION Compounds 1-26 are isolated from this plant for the first time.Compound 12 has inhibitory activity against Phomopsis sp.
5.Pharmacological effects of linarin on Aβ deposition and neuroinflammation in APP/PS1 mice
Pei-zhi MAO ; Ying-yan YAN ; Zeng-ze YAN ; Jian-hua QI ; Long-hu WANG ; Qi-jun CHEN
Chinese Pharmacological Bulletin 2025;41(4):661-667
Aim To investigate the effect of linarin on improving cognitive behavior of APP/PS1 mice,and to explore the therapeutic effect of linarin on A β deposi-tion and neuroinflammation and its correlation.Meth-ods APP/PS1 transgenic mice were randomly divid-ed into the model group,high-dose group,medium-dose group,low-dose group and positive control group.C57BL/6J mice were set as the normal group.Morris water maze was used to evaluate the learning and mem-ory abilities of mice.TUNEL staining was used to de-tect the apoptosis of neurons in the CA1 region of mice.IHC was used to detect the expression levels of Aβ42 and GFAP.Western blot was used to detect the expression levels of BACE1 and PS-1.Results Com-pared with the normal group,mice of the model group showed lower NCP,shorter target quadrant travel,less target quadrant residence time percentage(all P<0.01),higher apoptosis rate of neurons in the CA1 re-gion(P<0.01),significantly higher protein expres-sion levels of A β42 and GFAP(all P<0.01),and significantly higher protein expression levels of BACE1 and PS-1(all P<0.01).Compared with the model group,the medium-dose group,high-dose group and positive control group showed higher NCP,longer tar-get quadrant travel,more target quadrant residence time percentage(all P<0.05),lower apoptosis rate of neurons in the CA1 region(P<0.01),significantly lower protein expression levels of A β42 and GFAP(all P<0.01),and significantly lower protein expression levels of BACE1 and PS-1(all P<0.01).Conclu-sions Linarin can inhibit two key enzymes to reduce the decomposition of APP and the generation of A β42,thereby inhibiting the activation of astrocytes,allevia-ting neuroinflammation,improving the core pathologi-cal features of AD,and thus significantly improving learning and memory impairment in APP/PS1 mice.
6.Evaluation of antimicrobial activity of milk exosomes loaded with rifamycin S derivative
Zhanqun YANG ; Xiang LI ; Chenghua LIU ; Mengzhu ZHENG ; Shiyong FAN ; Yuchao DONG ; Zihao WANG ; Jian LIN ; Guang YANG ; Long CHEN
Chinese Journal of Pharmacology and Toxicology 2025;39(3):208-215
OBJECTIVE To design and synthesize rifamycin S derivatives and load them into milk exosomes to evaluate their in vitro antimicrobial activity.METHODS Rifamycin S derivatives were synthe-sized and characterized by mass spectrometry and NMR.Using the dilution assay method,the inhibitory activity of each rifamycin S derivatives molecule against Staphylococcus aureus and Pseudomonas aerugi-nosa was determined,and the IC50 was calculated.Derivatives molecules with excellent antimicrobial activity were selected and loaded into milk exosomes using the ultrasonication method,resulting in the preparation of milk exosome-loaded rifamycin S derivatives.The antimicrobial activity against Staphylo-coccus aureus was determined using the dilution assay method.The inhibitory effect of the exosome-loaded rifamycin S derivatives on Staphylococcus aureus residing within macrophages was detected using the plate colony counting method.RESULTS Three rifamycin S derivatives were successfully designed and synthesized,which demonstrated superior antimicrobial activity against Staphylococcus aureus(the parent compound's antimicrobial activity is merely from 1/20 to 1/80 of that of the three rifamycin S derivatives)and Pseudomonas aeruginosa(the parent compound's antimicrobial activity is only 1/14 and 1/9 of that of compound 1 and compound 3)compared to the parent compound.The loading of milk exosomes with the rifamycin S derivatives compound 3 was successfully achieved,with a loading efficiency of 10.9%.The antimicrobial activity of the compound after exosome loading was significantly enhanced against Staphylococcus aureus in vitro and against Staphylococcus aureus residing within macrophages(P<0.01).CONCLUSION The designed and synthesized derivatives of rifamycin S possess stronger anti-microbial activity,and their antibacterial efficacy against both extracellular and intracellular bacteria can be further enhanced after loading into exosomes.
7.Evaluation of antimicrobial activity of milk exosomes loaded with rifamycin S derivative
Zhanqun YANG ; Xiang LI ; Chenghua LIU ; Mengzhu ZHENG ; Shiyong FAN ; Yuchao DONG ; Zihao WANG ; Jian LIN ; Guang YANG ; Long CHEN
Chinese Journal of Pharmacology and Toxicology 2025;39(3):208-215
OBJECTIVE To design and synthesize rifamycin S derivatives and load them into milk exosomes to evaluate their in vitro antimicrobial activity.METHODS Rifamycin S derivatives were synthe-sized and characterized by mass spectrometry and NMR.Using the dilution assay method,the inhibitory activity of each rifamycin S derivatives molecule against Staphylococcus aureus and Pseudomonas aerugi-nosa was determined,and the IC50 was calculated.Derivatives molecules with excellent antimicrobial activity were selected and loaded into milk exosomes using the ultrasonication method,resulting in the preparation of milk exosome-loaded rifamycin S derivatives.The antimicrobial activity against Staphylo-coccus aureus was determined using the dilution assay method.The inhibitory effect of the exosome-loaded rifamycin S derivatives on Staphylococcus aureus residing within macrophages was detected using the plate colony counting method.RESULTS Three rifamycin S derivatives were successfully designed and synthesized,which demonstrated superior antimicrobial activity against Staphylococcus aureus(the parent compound's antimicrobial activity is merely from 1/20 to 1/80 of that of the three rifamycin S derivatives)and Pseudomonas aeruginosa(the parent compound's antimicrobial activity is only 1/14 and 1/9 of that of compound 1 and compound 3)compared to the parent compound.The loading of milk exosomes with the rifamycin S derivatives compound 3 was successfully achieved,with a loading efficiency of 10.9%.The antimicrobial activity of the compound after exosome loading was significantly enhanced against Staphylococcus aureus in vitro and against Staphylococcus aureus residing within macrophages(P<0.01).CONCLUSION The designed and synthesized derivatives of rifamycin S possess stronger anti-microbial activity,and their antibacterial efficacy against both extracellular and intracellular bacteria can be further enhanced after loading into exosomes.
8.Risk Assessment of Radiation Prevention and Treatment Drugs
Ran ZHANG ; Chang LU ; Huan LONG ; Keer XUAN ; Wanlong ZHANG ; Yuxian ZHANG ; Hongzhu LIU ; Dong CHAI ; Jian GONG
Herald of Medicine 2025;44(10):1648-1654
Radiation prevention and treatment drugs are a rapidly developing field.Radiation prevention and treatment drugs can be roughly divided into four categories:chemical synthetic drugs,biological products,natural plant extracts and traditional Chinese medicine compounds,which are widely used in medical,scientific research and other fields.This paper reviews the classification of radiation prevention and treatment drugs,which can be roughly divided into four categories:chemical synthetic drugs,biological products,natural plant extracts and traditional Chinese medicine compounds.At the same time,its mechanism of action and clinical application are elaborated in detail,and the risk assessment is carried out from the aspects of effectiveness,safety and drug interaction.Finally,the risk reduction strategies are summarized from the aspects of clinical medication specification and monitoring,continuous drug safety research,improvement of emergency reserve and support capacity and construction of full-cycle regulatory system,so as to provide reference for the rational application and further research of radiation prevention and treatment drugs.
9.Pharmacological effects of linarin on Aβ deposition and neuroinflammation in APP/PS1 mice
Pei-zhi MAO ; Ying-yan YAN ; Zeng-ze YAN ; Jian-hua QI ; Long-hu WANG ; Qi-jun CHEN
Chinese Pharmacological Bulletin 2025;41(4):661-667
Aim To investigate the effect of linarin on improving cognitive behavior of APP/PS1 mice,and to explore the therapeutic effect of linarin on A β deposi-tion and neuroinflammation and its correlation.Meth-ods APP/PS1 transgenic mice were randomly divid-ed into the model group,high-dose group,medium-dose group,low-dose group and positive control group.C57BL/6J mice were set as the normal group.Morris water maze was used to evaluate the learning and mem-ory abilities of mice.TUNEL staining was used to de-tect the apoptosis of neurons in the CA1 region of mice.IHC was used to detect the expression levels of Aβ42 and GFAP.Western blot was used to detect the expression levels of BACE1 and PS-1.Results Com-pared with the normal group,mice of the model group showed lower NCP,shorter target quadrant travel,less target quadrant residence time percentage(all P<0.01),higher apoptosis rate of neurons in the CA1 re-gion(P<0.01),significantly higher protein expres-sion levels of A β42 and GFAP(all P<0.01),and significantly higher protein expression levels of BACE1 and PS-1(all P<0.01).Compared with the model group,the medium-dose group,high-dose group and positive control group showed higher NCP,longer tar-get quadrant travel,more target quadrant residence time percentage(all P<0.05),lower apoptosis rate of neurons in the CA1 region(P<0.01),significantly lower protein expression levels of A β42 and GFAP(all P<0.01),and significantly lower protein expression levels of BACE1 and PS-1(all P<0.01).Conclu-sions Linarin can inhibit two key enzymes to reduce the decomposition of APP and the generation of A β42,thereby inhibiting the activation of astrocytes,allevia-ting neuroinflammation,improving the core pathologi-cal features of AD,and thus significantly improving learning and memory impairment in APP/PS1 mice.
10.Investigation of tumor-suppressive mechanism of Guiqi Yiyuan Extract combined with cisplatin in Lewis lung cancer mice via TXNIP/NLRP3/Caspase-1/GSDMD pathway
Qiong-qiong GUO ; Wen-jie LI ; Jin-tian LI ; Jian-qing LIANG ; Ping TIAN ; Rong HU ; Xu-chao DONG ; Mei-hao XUE ; Long-xin XU
Chinese Traditional Patent Medicine 2025;47(9):2894-2901
AIM To investigate the tumor-suppressive mechanism of Guiqi Yiyuan Extract combined with cisplatin in Lewis lung cancer mice.METHODS Ten intact C57BL/6J mice were assigned to the blank group.Sixty additional mice were developed into Lewis lung cancer models bearing transplanted tumor and subsequently allocated into the model group,the cisplatin group(5 mg/kg),the high-dose Guiqi Yiyuan Extract group(6.6 g/kg),and the low-dose,medium-dose and high-dose Guiqi Yiyuan Extract combined with cisplatin group(1.6,3.3,6.6 g/kg+5 mg/kg),with 10 mice in each group.Mice in the blank and model groups received saline via daily gavage,while treatment groups were administered Guiqi Yiyuan Extract orally(once daily),and cisplatin injection intraperitoneally(once every other day).After 14 days of drug administration,mice were euthanized for endpoint analysis.The following assessments were conducted:general health status and body weight changes monitored throughout the study period;tumor excision and weighing for inhibition rate calculation;histopathological examination of tumors via hematoxylin-eosin(HE)staining;serum quantification of IL-1 β,IL-18 and HMGB1 by ELISA;ultrastructural analysis of tumor cell death using transmission electron microscopy(TEM);spatial localization of TXNIP and GSDMD-N in tumor sections via immunofluorescence(IF);and Western blot detection of TXNIP,NLRP3,Caspase-1,cleaved Caspase-1,GSDMD,GSDMD-N protein expressions in tumor tissues.RESULTS Compared to the model group,the cisplatin group and all combination therapy groups exhibited significant reduction in tumor weight(P<0.05)and increased tumor suppression rate;enhanced tumor tissue necrosis with characteristic pyroptotic morphology;elevated serum levels of IL-1β,IL-18 and HMGB1(P<0.05);and upregulated expressions of pyroptosis-associated proteins TXNIP,NLRP3,Caspase-1,cleaved Caspase-1,GSDMD and GSDMD-N(P<0.05).The high dose combination group demonstrated optimal therapeutic efficacy(P<0.05).CONCLUSION Guiqi Yiyuan Extract enhances cisplatin sensitivity,demonstrating synergistic anti-tumor effects in Lewis lung carcinoma-bearing mice.This combinatorial therapeutic effect likely involves modulation of the TXNIP/NLRP3/Caspase-1/GSDMD pathway.

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