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.

A method for simultaneous determination of 21 kinds of Aconitum alkaloids(ATS)in biological specimens and infused liquor using ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)was developed.The biological samples were pretreated with methanol-acetonitrile(1∶2,V/V)for protein precipitation,while infused liquors were diluted 100-fold with acetonitrile,followed by centrifugation,and filtration by a 0.22-μm membrane.Chromatographic separation was carried out on an EC-C18 column using gradient elution with the mixture of 10 mmol/L ammonium acetate and 0.2%formic acid as mobile phase A and acetonitrile as mobile phase B.With this method,all the analytes were separated within 9.5 min.The samples were detected in positive ESI mode with dynamic multiple reaction monitoring(MRM)and quantified via external standard calibration.The results showed that the concentrations of the analytes in the range of 2-1000 ng/mL had excellent linearity(R2>0.9992)with the peak area.The developed method was successfully used for detection of 21 kinds of aconitum alkaloids,with limits of detection of 0.5-2 ng/mL,quantification limits of 2-6 ng/mL,intra/inter-day precision≤6.0%,spiked recoveries of 89.4%-100.9%,extraction recoveries of 74.2%-104.4%,and matrix effects ranging from-11.1%to 9.2%in blood/urine.The method was applied to detection of 12 samples from 4 fatal aconite poisoning cases,and all 21 kinds of ATS with total alkaloid concentrations of 0.04-4.18 μg/mL in blood and 154.96-422.83 μg/mL in medicinal liquors were detected.Tissue distribution revealed that the order of concentrations from highest to lowest is as follows:urine(157.22 μg/mL)>gastric contents(51.37 μg/mL)>kidney(21.6 μg/g)>whole blood(4.18 μg/mL)>liver(0.03 μg/g).This method showed many advantages such as simple pretreatment,low detection limits,accurate quantification,broad analyte coverage,and superior anti-interference capability in complex matrices,proving ideal for forensic and toxicological analysis of aconitum alkaloids.

Objective To construct a prognostic model of future asthma exacerbation risk in adults by com-bining novel biomarkers of serum chitinase-3-like protein 1(YKL-40),dipeptidyl peptidase-4(DPP4)and conventional predictors.Methods Patients with asthma in the non-acute exacerbation phase were recruited from the People's Hospital of Yubei District of Chongqing,from March 2022 to May 2023.Baseline clinical da-ta collected included medical history,forced expiratory volume in the first second(FEV1)/forced vital capacity(FVC),percentage of predicted forced expiratory volume in the first second(FEV1％pred),blood eosinophil count(EOS),blood neutrophil count(NEU),fractional exhaled nitric oxide(FeNO),serum YKL-40,and ser-um DPP4,etc.The patients were followed for one year to gather data on asthma acute exacerbations and their timings as defined in this study.A COX proportional hazards regression model was used to construct a prog-nostic model for future asthma exacerbations,with internal validation and results presentation.Results A to-tal of 224 patients with asthma completed the study.During the one-year follow-up period,102 patients experi-enced acute exacerbations as defined in this study.Based on univariate COX regression,stepwise regression for variable selection,clinical significance,and model simplicity,asthma control test(ACT)score group,number of asthma exacerbations in the past year group,log10(YKL-40),log10(FeNO),log10(EOS),and FEV1％pred were the following predictors were included in the final model.The overall C-statistic of the model was 0.795(95％CI:0.754-0.836),the area under the curve at the 52-week follow-up was 0.879(95％CI:0.834-0.924),and the Brier score at the 52-week follow-up was 0.142(95％CI:0.117-0.168).The calibration curve was close to a slope of 1,and bootstrap validation suggested good stability of the prediction model.The model was presented using a Nomogram and a dynamic scoring table in a web APP,which can be used to predict the risk of asthma exacerbations within 52 weeks for individual patients.Conclusion The prediction model based on serum YKL-40,EOS,FeNO,the number of asthma exacerbation in the past year group,FEV1％pred and ACT scores group can accurately predict the probability of acute attacks in 52 weeks of asthma patients.

Objective To observe the effect of emodin on lung injury in rats with stroke associated pneumonia(SAP)through regulating Janus kinase 2(JAK2)/signal transducer and activators of transcription 3(STAT3)signaling pathway.Methods The SAP rat model was established by modified thread embolization method combined with intratracheal injection of Pseudomonas aeruginosa method.The successfully modeled rats were randomly divided into model group,emodin low-and high-dose groups and emodin high-dose+coumermycin(JAK2 activator)group,with 12 rats in each group,and another 12 SD rats were selected as the sham-operated group.After the intervention,the partial pressure of arterial blood gas indexes such as carbon dioxide(PaCO2)and partial pressure of oxygen(PaO2)were measured,the ratio of lung wet/dry mass(W/D)was determined,the inflammatory cell count in the bronchoalveolar lavage fluid(BALF)was detected,the histopathological feature in the lung tissues was observed by hematoxylin-eosin(HE)staining and the pathological injury was scored,enzyme-linked immunosorbent assay(ELISA)was used to detect myeloperoxidase(MPO)activity in the lung tissues and interleukin 6(IL-6)and cyclooxygenase 2(COX-2)levels in BALF and serum,and Western Blot was used to detect the expression of JAK2/STAT3 pathway key proteins in lung tissues.Results Compared with the sham-operated group,the model group rats showed that more obvious pathological injury in lung tissues was seen,and PaCO2 value,ratio of lung W/D,white blood cell count and eosinophils count in BALF,pathological injury score,MPO activity in lung tissues,IL-6 and COX-2 levels in BALF and serum,and ratios of p-JAK2/JAK2 and p-STAT3/STAT3 in lung tissues were significantly increased,and PaO2 value was significantly decreased,the differences being statistically significant(P<0.05);compared with the model group,the emodin low-and high-dose groups rats showed that the pathological injury in lung tissues was reduced,PaCO2 value,ratio of lung W/D,white blood cell count and eosinophils count in BALF,pathological injury score,MPO activity in lung tissues,IL-6 and COX-2 levels in BALF and serum,and ratios of p-JAK2/JAK2 and p-STAT3/STAT3 in lung tissues were all decreased,and PaO2 value was increased,the differences being statistically significant(P<0.05),and the improvement effect was more stronger in high-dose emodin group;coumermycin attenuated the improvement effect of emodin on the above various indexes in the model rats.Conclusion Emodin can reduce the inflammation levels in SAP rats through inhibiting the activation of JAK2/STAT3 signaling pathway,thus reducing the lung tissue damage and improving the lung function of rats.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

The accumulation of uremic toxins such as urea nitrogen, blood creatinine, and uric acid of patients with renal failure in vivo would lead to aggravated kidney damage. In this study, coated aldehyde oxy-starch (CAO) was used as an adsorbent to investigate its in vitro adsorption performance on renal failure indexes for urea, indoxyl sulfate (INS), monomethylamine (MMA), dimethylamine (DMA), uric acid (UA), and creatinine (Cr). The effects of variables such as pH, temperature, concentration, dosage, and time on the adsorption capacity of CAO were systematically investigated, employing analytical techniques of high-performance liquid chromatography (HPLC) and gas chromatography (GC). The results revealed that CAO exhibited a strong adsorption capacity for urea, INS, and MMA, alongside a moderate adsorption capacity for DMA, UA, and Cr. The adsorption kinetics and thermodynamic studies indicated that the adsorption of urea and UA by CAO were fitted in pseudo-first-order kinetics, and the adsorption isotherm aligned with the Freundlich adsorption model. The enthalpy change ΔH of urea in adsorption was in the range of 40 to 60 kJ·mol^-1, which demonstrated the presence of strong adsorption force due to the interactions of coordinating groups. The ΔH of UA was greater than 80 kJ·mol^-1, indicating the generation of chemical bonds during the adsorption. Both of them, Gibbs free energy ΔG was less than 0, within the range of -20 to 0 kJ·mol^-1, suggested that the adsorption of urea and UA by CAO occurred spontaneously as physical adsorption process. The adsorption entropy ΔS of urea and UA was > 0, which indicated an increase in entropy throughout the adsorption. The infrared spectroscopygram showed the formation of a chemical bond, specifically the imine bond, following the adsorption of urea by CAO, thereby indicating a chemical reaction during the adsorption. This study elucidates the adsorption mechanism of CAO on various indexes of renal failure, providing a scientific basis for its clinical usage.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

A chemical investigation of secondary metabolites (SMs) from Aspergillus nidulans resulted in the identification of five novel dioxopiperazine (DKP)-diphenyl ether hybrids, designated as diphenylemestrins A-E (1-5). These compounds 1-5 represent the first known dimers combining DKP and diphenyl ether structures, with compound 4 featuring an uncommon dibenzofuran as the diphenyl ether component. The structural elucidation and determination of absolute stereochemistry were accomplished through spectroscopic analysis and electronic circular dichroism (ECD) calculations. Notably, diphenylemestrin C (3) exhibited moderate cytostatic activity against NB4 cells, with a half maximal inhibitory concentration (IC₅₀) value of 21.99 μmol·L^-1, and induced apoptosis at higher concentrations.
Aspergillus nidulans/metabolism* ; Diketopiperazines/pharmacology* ; Molecular Structure ; Phenyl Ethers/pharmacology* ; Humans ; Apoptosis/drug effects* ; Cell Line, Tumor