Accurate prediction of drug-induced adverse drug reactions(ADRs)is crucial for drug safety evaluation,as it directly impacts public health and safety.While various models have shown promising results in predicting ADRs,their accuracy still needs improvement.Additionally,many existing models often lack interpretability when linking molecular structures to specific ADRs and frequently rely on manually selected molecular fingerprints,which can introduce bias.To address these challenges,we propose ToxBERT,an efficient transformer encoder model that leverages attention and masking mechanisms for simplified molecular input line entry system(SMILES)representations.Our results demonstrate that ToxBERT achieved area under the receiver operating characteristic curve(AUROC)scores of 0.839,0.759,and 0.664 for predicting drug-induced QT prolongation(DIQT),rhabdomyolysis,and liver injury,respectively,outperforming previous studies.Furthermore,ToxBERT can identify drug substructures that are closely associated with specific ADRs.These findings indicate that ToxBERT is not only a valuable tool for understanding the mechanisms underlying specific drug-induced ADRs but also for mitigating potential ADRs in the drug discovery pipeline.

Accurate prediction of drug-induced adverse drug reactions (ADRs) is crucial for drug safety evaluation, as it directly impacts public health and safety. While various models have shown promising results in predicting ADRs, their accuracy still needs improvement. Additionally, many existing models often lack interpretability when linking molecular structures to specific ADRs and frequently rely on manually selected molecular fingerprints, which can introduce bias. To address these challenges, we propose ToxBERT, an efficient transformer encoder model that leverages attention and masking mechanisms for simplified molecular input line entry system (SMILES) representations. Our results demonstrate that ToxBERT achieved area under the receiver operating characteristic curve (AUROC) scores of 0.839, 0.759, and 0.664 for predicting drug-induced QT prolongation (DIQT), rhabdomyolysis, and liver injury, respectively, outperforming previous studies. Furthermore, ToxBERT can identify drug substructures that are closely associated with specific ADRs. These findings indicate that ToxBERT is not only a valuable tool for understanding the mechanisms underlying specific drug-induced ADRs but also for mitigating potential ADRs in the drug discovery pipeline.

[Objective]To clearly identify the difference between rescue injuries and agonal injuries and to avoid duplicate identifications and misidentifications.[Methods]Based on the forensic pathological data of 5 923 cases of death cause identification from 2013 to 2022 in Sun Yat-sen University Forensic Identification Center and Guangzhou Tianhe District Branch of Guangzhou Public Security Bureau,this study retrospectively studied the characteristics of rescue injuries and agonal injuries seen in cause of death identification and their influence on cause of death identification.[Results]Among all the 5 923 cases,640 cases were found to have rescue injuries or agonal injuries,and 624 cases received treatment,of which 609 cases were found to have rescue injuries(97.60%),44 cases were found to have agonal injuries,and 13 cases were found to have both types of injuries.Among the 640 cases,441 were male and 199 were female.The age of death was discontinuously distributed from 0 to 95 years old.The leading cause of death was disease,followed by mechanical injury and asphyxia.The main manifestations of rescue injuries were rib and sternum fractures,soft tissue injuries in the prechest area or face,and pericardial rupture.The most common injuries in agonal stage were falling after unconsciousness,inhalation of foreign body in respiratory tract or multiple violent injuries.Among the 640 cases,19 cases were repeatedly identified,including 15 cases of rescue injuries,6 cases of agonal injuries,and 2 cases of both types of injuries.Compared with the cases where neither type of injuries was detected,the repeated identification rate of treatment injuries and agonal injuries was significantly increased(χ2=4.04,P=0.044;χ2=43.49,P<0.001).Among the 640 cases,11 cases(1.72%)were misidentified as the initial injuries in the first identification,and 13 cases had combined rescue injuries or agonal injuries that were involved in death.[Conclusions]By elucidating the epidemiological characteristics of the two types of injuries,this study proved that the two types of injuries were associated with higher rates of repeated identification and misidentification,which provided a reference for reducing repeated identification and misidentification and improving the accuracy of cause of death identification.

Purpose To investigate the diagnostic significance of modified lung ultrasound score(MPUS)for pediatric bacterial and viral pneumonia.Materials and Methods A total of 93 eligible children with suspected community-acquired pneumonia in Quanzhou Maternal and Child Care Hospital(Quanzhou Children’s Hospital)from December 2022 to June 2023 were elected as the study subjects.All these children received lung ultrasound and the MLUS was recorded according to the ultrasound manifestations of A line,B line and lung consolidation.According to the etiological results,the children were divided into a bacterial pneumonia group and a viral pneumonia group.According to disease severity,the children were divided into the mild group and the severe group.The MLUS was used to analyze the diagnostic significance of pediatric bacterial and viral pneumonia.Results The MLUS in the mild pneumonia group was 7(4,13)points and the MLUS in the severe pneumonia group was 20(14,30)points,and MLUS scores of pneumonia in the two groups were different(Z=-5.205,P<0.05).By drawing receiver operating characteristic curve,MLUS score of 14.5 was used as the cut-off point,the sensitivity for diagnosing severe pneumonia was 75.9%,the specificity was 82.8%.Area under the curve was 0.838.There was no significant differences in MLUS of 8.00(4.00,16.00)between the bacterial pneumonia group and 13.00(7.00,21.75)between the viral pneumonia group(Z=-1.981,P>0.05).The MLUS of 10.00(5.25,17.75)in the mild bacterial pneumonia group and 5.00(4.00,9.50)in the mild viral pneumonia group were significantly different(Z=-3.403,P<0.05).There was no significant differences in MLUS between the severe bacterial pneumonia group and the severe viral pneumonia group(t=0.017,P>0.05).In mild pneumonia,the cut-off value for the modified lung ultrasound score of 10.5 predicted moderate diagnostic efficacy of mild bacterial pneumonia,the area under the curve was 0.747,sensitivity was 50%and specificity was 87.5%.Large-area lung consolidation was more common in the bacterial pneumonia group than in the viral pneumonia group(χ2=8.360,P<0.05).Conclusion The modified lung ultrasound score can effectively evaluate the severity of pediatric bacterial pneumonia and viral pneumonia.For the identification of the two,MLUS may be a certain guiding significance.

Purpose To investigate the diagnostic significance of modified lung ultrasound score(MPUS)for pediatric bacterial and viral pneumonia.Materials and Methods A total of 93 eligible children with suspected community-acquired pneumonia in Quanzhou Maternal and Child Care Hospital(Quanzhou Children’s Hospital)from December 2022 to June 2023 were elected as the study subjects.All these children received lung ultrasound and the MLUS was recorded according to the ultrasound manifestations of A line,B line and lung consolidation.According to the etiological results,the children were divided into a bacterial pneumonia group and a viral pneumonia group.According to disease severity,the children were divided into the mild group and the severe group.The MLUS was used to analyze the diagnostic significance of pediatric bacterial and viral pneumonia.Results The MLUS in the mild pneumonia group was 7(4,13)points and the MLUS in the severe pneumonia group was 20(14,30)points,and MLUS scores of pneumonia in the two groups were different(Z=-5.205,P<0.05).By drawing receiver operating characteristic curve,MLUS score of 14.5 was used as the cut-off point,the sensitivity for diagnosing severe pneumonia was 75.9%,the specificity was 82.8%.Area under the curve was 0.838.There was no significant differences in MLUS of 8.00(4.00,16.00)between the bacterial pneumonia group and 13.00(7.00,21.75)between the viral pneumonia group(Z=-1.981,P>0.05).The MLUS of 10.00(5.25,17.75)in the mild bacterial pneumonia group and 5.00(4.00,9.50)in the mild viral pneumonia group were significantly different(Z=-3.403,P<0.05).There was no significant differences in MLUS between the severe bacterial pneumonia group and the severe viral pneumonia group(t=0.017,P>0.05).In mild pneumonia,the cut-off value for the modified lung ultrasound score of 10.5 predicted moderate diagnostic efficacy of mild bacterial pneumonia,the area under the curve was 0.747,sensitivity was 50%and specificity was 87.5%.Large-area lung consolidation was more common in the bacterial pneumonia group than in the viral pneumonia group(χ2=8.360,P<0.05).Conclusion The modified lung ultrasound score can effectively evaluate the severity of pediatric bacterial pneumonia and viral pneumonia.For the identification of the two,MLUS may be a certain guiding significance.

With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth＞3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.

Objective: Patients with late life depression sometimes refuse to receive electroconvulsive therapy (ECT) owing to its adverse reactions. To alleviate patient’s resistance, a novel ECT stimulation strategy named mixed-strategy ECT (msECT) was designed in which patients are administered conventional ECT during the first three sessions, followed by low energy stimulation during the subsequent sessions. However, whether low energy electrical stimulation in the subsequent stage of therapy affect its efficacy and reduce adverse reactions in patients with late life depression remains unknown. To explore differences between msECT and regular ECT(RECT) with respect to clinical efficacy and side effects Methods: This randomized, controlled trial was conducted from 2019 to 2021 on 60 patients with late life depression who were randomly assigned to two groups: RECT or msECT. A generalized estimating equation (GEE) was used to compare the two stimulation strategies regarding their efficacy and side effects on cognition. Chi-squared test was used to compare side effects in the two strategies. Results: In the intent-to-treat group, the GEE model suggested no differences between-group difference in Hamilton Depression Rating Scale-17 score over time (Wald χ2=7.275, p=0.064), whereas the comparison of side effects in the two strategies favored msECT (Wald χ2=8.463, p=0.015) as fewer patients had adverse events during the second phase of treatment with msECT (χ2 =13.467, p=0.004). Conclusion msECT presents its similar efficacy to RECT. msECT may have milder side effects on cognition.

Activation of nuclear factor erythroid 2-related factor 2(Nrf2)by Kelch-like ECH-associated protein 1(Keap1)alkylation plays a central role in anti-inflammatory therapy.However,activators of Nrf2 through alkylation of Keap1-Kelch domain have not been identified.Deoxynyboquinone(DNQ)is a natural small molecule discovered from marine actinomycetes.The current study was designed to investigate the anti-inflammatory effects and molecular mechanisms of DNQ via alkylation of Keap1.DNQ exhibited signif-icant anti-inflammatory properties both in vitro and in vivo.The pharmacophore responsible for the anti-inflammatory properties of DNQ was determined to be the α,β-unsaturated amides moieties by a chemical reaction between DNQ and N-acetylcysteine.DNQ exerted anti-inflammatory effects through activation of Nrf2/ARE pathway.Keap1 was demonstrated to be the direct target of DNQ and bound with DNQ through conjugate addition reaction involving alkylation.The specific alkylation site of DNQ on Keap1 for Nrf2 activation was elucidated with a synthesized probe in conjunction with liquid chromatography-tandem mass spectrometry.DNQ triggered the ubiquitination and subsequent degra-dation of Keap1 by alkylation of the cysteine residue 489(Cys489)on Keap1-Kelch domain,ultimately enabling the activation of Nrf2.Our findings revealed that DNQ exhibited potent anti-inflammatory capacity through α,β-unsaturated amides moieties active group which specifically activated Nrf2 signal pathway via alkylation/ubiquitination of Keap1-Kelch domain,suggesting the potential values of targeting Cys489 on Keap1-Kelch domain by DNQ-like small molecules in inflammatory therapies.

The comparison between traditional Chinese medicine Jinzhen oral liquid (JZOL) and Western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or ambroxol hydrochloride and clenbuterol hydrochloride oral solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1, and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and the immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels were the key mechanism of action.