ObjectiveTo investigate the effect and mechanism of simvastatin pretreatment on kidney ischemia reperfusion injury （IRI） in mice. MethodsFifteen male C57BL/6 mice aged 6-8 weeks were divided into three groups： Sham operation group （Sham group）， kidney IRI group （IR group）， and simvastatin pretreatment+kidney IRI group （SIM group）. Hematoxylin-eosin （HE） staining of kidney tissue and detection of serum creatinine （SCr） and lactate dehydrogenase （LDH） were used to evaluate kidney injury. The levels of superoxide dismutase （SOD）， reduced glutathione （GSH）， malondialdehyde （MDA） and reactive oxygen species （ROS） were detected to evaluate oxidative stress. The contents of ferrous iron （Fe²⁺） and ferric iron （Fe³⁺） in kidney tissue were detected， and the morphological changes of mitochondria were observed by transmission electron microscope. The relative expression levels of Kruppel-like factor 2 （KLF2）， glutathione peroxidase 4 （GPX4）， solute carrier family 7 member 11 （SLC7A11）， and acyl-coa synthetase long chain family member 4 （ACSL4） protein in kidney tissue were detected. ResultsCompared with the IR group， the SIM group had significantly reduced renal tubular injury and decreased contents of Scr and LDH in serum （P < 0.001）. It also showed increased expression of SOD and GSH and decreased expression of MDA and ROS （P < 0.01）. Simvastatin pretreatment reduced the contents of Fe²⁺ and Fe³⁺ in the tissues （P < 0.01） and alleviated mitochondrial damage. It also promoted the expression of KLF2 （P < 0.01）， up-regulated the expression of ferroptosis-related protective proteins GPX4 and SLC7A11， and down-regulated the expression of ferroptosis-related damage protein ACSL4 （P < 0.05）. ConclusionSimvastatin pretreatment may inhibit kidney ferroptosis by promoting the expression of KLF2 to alleviate kidney IRI.

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.

AIM:To investigate the effect of ranibizumab on blood flow density in different regions of the macula in patients with macular edema(ME)secondary to ischemic and non-ischemic branch retinal vein occlusion(BRVO).METHODS:This retrospective study enrolled patients with BRVO-ME who were treated at the hospital from September 2019 to March 2021. Patients were divided into ischemic and non-ischemic groups based on fundus findings. All patients received intravitreal injections of ranibizumab once monthly for three consecutive months. Best corrected visual acuity(BCVA), central macular thickness(CMT), and macular blood flow density were measured before treatment and at 1 d, 1 wk, 1 and 3 mo after treatment.RESULTS: A total of 46 patients(46 eyes)with BRVO-ME were included, comprising 21 eyes in the ischemic group(7 males, 14 females; mean age 55.81±10.36 y)and 25 eyes in the non-ischemic group(11 males, 14 females; mean age 54.84±9.81 y). At 3 mo after treatment, BCVA(LogMAR)in the non-ischemic group was superior to that in the ischemic group(0.19±0.19 vs 0.38±0.27, P=0.009). Analysis of CMT changes showed that the reduction amplitude in the ischemic group was significantly greater than that in the non-ischemic group at both 1 and 3 mo after treatment(all P<0.05). Blood flow densities in the whole, parafoveal, and perifoveal regions of the superficial capillary plexus(SCP), as well as in the whole and perifoveal regions of the deep capillary plexus(DCP), were significantly lower in ischemic patients than in non-ischemic patients, while blood flow density in the foveal region of DCP was significantly higher in the ischemic group(all P<0.05).CONCLUSION: Ranibizumab is effective for both types of patients. Non-ischemic patients have a better long-term visual prognosis, and the advantage may be related to better blood flow perfusion patterns in specific areas 3 mo after treatment. Monitoring changes in blood flow density in these areas can help provide personalized treatment for patients.

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 explore the efficacy of Qingjin Huatan Decoction combined with conventional Western medicine for the treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) with phlegm-heat obstructing lung syndrome.Methods:A randomized controlled trial was conducted. Totally 90 hospitalized patients with AECOPD phlegm-heat obstructing lung syndrome in the respiratory department of Shunyi Hospital, Beijing Traditional Chinese Medicine Hospital from January 2023 to June 2024 were selected as the observation subjects. According to the simplified randomization method (single-double number method), the patients were divided into two groups, with 45 cases in each group. The conventional Western medicine group was given conventional Western medicine treatment, and the combined Chinese materia medica group was given Qingjin Huatan Decoction on the basis of the conventional Western medicine group. The treatment for both groups lasted for 7 d. TCM symptoms were scored before and after treatment; FEV 1 and FVC were detected by pulmonary function analyzer, PaO 2, PaCO 2, PaO 2/FiO 2 were detected by blood gas biochemical analyzer, CRP and PCT were detected by ELISA, and white blood cell count (WBC) was detected by automatic blood cell analyzer. Adverse reactions were recorded, and the clinical efficacy was evaluated. Results:The total effective rate was 93.33% (42/45) in the combined Chinese materia medica group and 77.78% (35/45) in the conventional Western medicine group, with statistical significance ( χ2=4.41, P=0.036). After treatment, the scores of cough, wheezing, chest tightness and shortness of breath and fever and the total score in the combined Chinese materia medica group were lower than those in the conventional Western medicine group ( t=4.83, 2.26, 5.36, 10.43, 5.27,respectively, P<0.01 or P<0.05); the levels of FEV 1 and FVC in the combined Chinese materia medica group were higher than those in the conventional Western medicine group ( t=3.03, 2.64, respectively, P<0.01); the levels of PaO 2 and PaO 2/FiO 2 in the combined Chinese materia medica group were higher than those in the conventional Western medicine group ( t=4.83, 5.36, P<0.01), while the level of PaCO 2 in the combined Chinese materia medica group was lower than that in the conventional Western medicine group ( t=2.26, P<0.05); the levels of CRP, PCT and WBC in the combined Chinese materia medica group were lower than those in the conventional western medicine group ( t=10.53, 11.29 and 2.59, respectively, P<0.01 or P<0.05). During the treatment, the incidence of adverse reactions was 6.67% (3/45) in the combined Chinese materia medica and 8.89% (4/45) in the conventional Western medicine group, without statistical significance ( χ2=0.16, P=0.694). Conclusion:Qingjin Huatan Decoction can effectively improve the lung function and blood gas indicators of AECOPD with phlegm-heat obstructing lung syndrome, and relieve the inflammation, with safety and effectiveness.

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 three-dimensional (3D) printed bone tissue repair guide scaffold is considered a promising method for treating bone defect repair. In this experiment, chitosan (CS), sodium alginate (SA), and mineralized collagen (MC) were combined and 3D printed to form scaffolds. The experimental results showed that the printability of the scaffold was improved with the increase of chitosan concentration. Infrared spectroscopy analysis confirmed that the scaffold formed a cross-linked network through electrostatic interaction between chitosan and sodium alginate under acidic conditions, and X-ray diffraction results showed the presence of characteristic peaks of hydroxyapatite, indicating the incorporation of mineralized collagen into the scaffold system. In the in vitro collagen release experiments, a weakly alkaline environment was found to accelerate the release rate of collagen, and the release amount increased significantly with a lower concentration of chitosan. Cell experiments showed that scaffolds loaded with mineralized collagen could significantly promote cell proliferation activity and alkaline phosphatase expression. The subcutaneous implantation experiment further verified the biocompatibility of the material, and the implantation of printed scaffolds did not cause significant inflammatory reactions. Histological analysis showed no abnormal pathological changes in the surrounding tissues. Therefore, incorporating mineralized collagen into sodium alginate/chitosan scaffolds is believed to be a new tissue engineering and regeneration strategy for achieving enhanced osteogenic differentiation through the slow release of collagen.
Chitosan/chemistry* ; Alginates/chemistry* ; Tissue Scaffolds/chemistry* ; Printing, Three-Dimensional ; Osteogenesis ; Collagen/chemistry* ; Cell Differentiation ; Animals ; Tissue Engineering/methods* ; Cell Proliferation ; Biocompatible Materials ; Glucuronic Acid/chemistry* ; Hexuronic Acids/chemistry*

OBJECTIVE To analyze chemical components of Yao ethnic medicine Pittosporum pauciflorum， establish its fingerprint and investigate the spectrum-effect relationship of its anti-inflammatory effect. METHODS UHPLC-Q-Orbitrap-MS technology was used to analyze the chemical components of P. pauciflorum （batch S6）. The fingerprints for 10 batches of P. pauciflorum from different producing areas in Guangxi Province （batches S1-S10） were established by HPLC， and similarity assessment and chemometric pattern recognition analysis were conducted. RAW264.7 inflammatory cell model was induced by lipopolysaccharide， and the anti-inflammatory activity of P. pauciflorum was investigated. Using inhibition rates of nitric oxide （NO）， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-1β as efficacy indicators， grey relational analysis and partial least squares regression analysis were adopted to evaluate the spectrum-effect relationship of the anti-inflammatory effect of P. pauciflorum. RESULTS There were 60 chemical components， including flavonoids， phenolic acids， lipids， etc.， identified in P. pauciflorum. The fingerprints for 10 batches of P. pauciflorum showed 14 common peaks，with similarity values ranging from 0.883 to 0.991. Three common peaks were assigned neochlorogenic acid （peak 5）， chlorogenic acid （peak 7）， and syringaldehyde （peak 10）. The classification results of the systematic clustering analysis and the principal component analysis were basically consistent. Batches S1 to S10 of P. pauciflorum significantly reduced the levels of NO， TNF-α， IL-6 （except for batch S5） and IL-1β in the cell supernatant （P＜0.05 or P＜0.01）. Inhibition rates of above inflammatory indexes were 10.26%-39.96%， 14.96%-31.36%， 1.38%-21.27%， 18.54%-28.00%， respectively. The contents of neochlorogenic acid， syringaldehyde， as well as the components corresponding to peaks 1， 3， 9， 12 and 14，exhibited a strong correlation with the anti-inflammatory effects of P. pauciflorum. CONCLUSIONS The present study has analyzed the chemical components of P. pauciflorum and established HPLC fingerprints for 10 batches of P. pauciflorum. Each batch of medicinal herbs demonstrates certain anti- inflammatory activities， among which neochlorogenic acid， syringaldehyde， and the components corresponding to peaks 1， 3， 9， 12 and 14 are likely to be the active anti-inflammatory components.