Artificial intelligence (AI) researchers and cheminformatics specialists strive to identify effective drug precursors while optimizing costs and accelerating development processes. Digital molecular representation plays a crucial role in achieving this objective by making molecules machine-readable, thereby enhancing the accuracy of molecular prediction tasks and facilitating evidence-based decision making. This study presents a comprehensive review of small molecular representations and AI-driven drug discovery downstream tasks utilizing these representations. The research methodology begins with the compilation of small molecule databases, followed by an analysis of fundamental molecular representations and the models that learn these representations from initial forms, capturing patterns and salient features across extensive chemical spaces. The study then examines various drug discovery downstream tasks, including drug-target interaction (DTI) prediction, drug-target affinity (DTA) prediction, drug property (DP) prediction, and drug generation, all based on learned representations. The analysis concludes by highlighting challenges and opportunities associated with machine learning (ML) methods for molecular representation and improving downstream task performance. Additionally, the representation of small molecules and AI-based downstream tasks demonstrates significant potential in identifying traditional Chinese medicine (TCM) medicinal substances and facilitating TCM target discovery.
Artificial Intelligence ; Drug Discovery/methods* ; Humans ; Machine Learning ; Medicine, Chinese Traditional ; Small Molecule Libraries/chemistry*

Metabolic dysfunction-associated steatotic liver disease (MASLD), the most prevalent chronic liver condition globally, lacks adequate and effective therapeutic remedies in clinical practice. Recent studies have increasingly highlighted the close connection between the ubiquitin-proteasome system (UPS) and the progression of MASLD. This relationship is crucial for understanding the disease's underlying mechanism. As a sophisticated process, the UPS govern protein stability and function, maintaining protein homeostasis, thus influencing a multitude of elements and biological events of eukaryotic cells. It comprises four enzyme families, namely, ubiquitin-activating enzymes (E1), ubiquitin-conjugating enzymes (E2), ubiquitin-protein ligases (E3), and deubiquitinating enzymes (DUBs). This review aims to delve into the array of pathways and therapeutic targets implicated in the ubiquitination within the pathogenesis of MASLD. Therefore, this review unveils the role of ubiquitination in MASLD while spotlighting potential therapeutic targets within the context of this disease.

Acute liver injury (ALI) serves as a critical precursor and major etiological factor in the progression and ultimate manifestation of various hepatic disorders. The prevention and treatment of ALI is still a serious global challenge. Given the limited therapeutic options for ALI, exploring novel targeted therapeutic agents becomes imperative. The potential therapeutic efficacy of inhibiting RIPK2 is highlighted, as it may provide significant benefits by attenuating the MAPK pathway and NF-κB signaling. Herein, we propose a CMD-OPT model, a two-stage molecular optimization tool for the rapid discovery of RIPK2 inhibitors with optimal properties. Compound RP20, which targets the ATP binding site, demonstrated excellent kinase specificity, ideal oral pharmacokinetics, and superior therapeutic effects in a model of APAP-induced ALI, positioning RP20 as a promising preclinical candidate. This marks the first application of RIPK2 inhibitors in ALI treatment, opening a novel therapeutic pathway for clinical applications. These results highlight the efficacy of the CMD-OPT model in producing lead compounds from known active molecules, showcasing its significant potential in drug discovery.

Objective:To investigate the expression of the proinflammatory factor IL-18-mediated NOD-like receptor thermal protein domain associated protein 3/nuclear factor κB(NLRP3/NF-κB)signaling pathway in penile tissues of rats with high-fat diet-in-duced erectile dysfunction(ED),and to explore the intervention effect of sildenafil.Methods:Fifty-five sexually normal male SD rats were randomly divided into 10 cases as the normal control group,and the rest of the rats were fed with high-fat chow to establish the ED rat model,and the successfully screened ED rats were randomly divided into the ED group,the Sil group,the IL-18 group,and the IL-18+Sil group,with 8 rats in each group.Following 14 days of nonstop treatment,the morphological alterations in the penile tis-sue were observed by HE staining.Using immunohistochemistry,the amount and distribution of NF-κB p65 and Adropin in penile tis-sues were found.RT-qPCR was used to identify the expression of NLRP3 and NF-κB p65 mRNA in penile tissues.Western blot exami-nation showed the expression of the proteins NLRP3,pro-IL-18,p-NF-κB p65,NF-κB p65,and Adropin in penile tissues.Results:The ED group showed altered penis tissue morphology,destroyed muscle fibers,enlarged sinus cavity,increased mRNA and protein expressions of NLRP3,p-NF-κB p65/NF-κB p65,and pro-IL-18(all P<0.05),and decreased Adropin protein expression(P<0.05).While the protein expression of Adropin was increased(P<0.05),the mRNA and protein expressions of NLRP3,p-NF-κB p65/NF-κB p65,and pro-IL-18 in the penis tissues were decreased(all P<0.05)when compared to the ED group.The muscle fibers and sinus cav-ities of the penis were recovered to varying degrees in the Sil group.The IL-18 group experienced the destruction of muscle fibers,an enlargement of the sinus cavity,an increase in the mRNA and protein expressions of NLRP3,p-NF-κB p65/NF-κB p65,and pro-IL-18 in the penile tissues(all P<0.05),as well as a decrease in the protein expression of Adropin(P<0.05).The rat penile tissues in the IL-18+Sil group showed variable degrees of recovery in the muscle fibers and sinus cavities when compared to the IL-18 group.Ad-ditionally,there was a drop(all P<0.05)in the expressions of NLRP3,pro-IL-18 m RNA and protein,p-NF-κB p65/NF-κB p65,and p-NF-κB p65 in the penile tissues.The expression of the Adropin protein was elevated(P<0.05).Conclusion:Significant changes have been observed in the NLRP3/NF-κB signaling pathway,which is regulated by IL-18,in the hyperlipidemia ED rat model.In ED rats,sildenafil can increase erectile function by promoting the production of Adropin and blocking the activation of this pathway.

Objective To investigate the efficacy of extracorporeal shock wave therapy(ESWT)combined with ultrasound-guided corticosteroid injection(CSI)for the treatment of primary frozen shoulder(PFS).Methods Ninety-nine patients with PFS who visited the pain department of the Affiliated Hospital of Xuzhou Medical University between April 2024 and July 2024 were enrolled and randomly divided into three groups according to the randomized number table method:ESWT group(T group),CSI group(I group),and combined treatment group(TI group),with 33 patients in each group.Visual analogue scale(VAS)scores,shoulder range of motion(SROM),and Constant-Murley shoulder scores(CMS)were recorded before treatment and at 1,4,8,and 12 weeks post-treatment.Additionally,the patients'Ascens Insomnia Scale(AIS)scores were recorded before treatment and 1 month after treatment.The occurrence of adverse effects and the use of remedial medications during the treatment period were also documented.Results Compared with pre-treatment,VAS scores decreased,and SROM and CM scores improved at all time points after treatment in all three groups(P<0.05).AIS scores also decreased in all three groups at 1 month post-treatment(all P<0.05).Intergroup comparisons revealed that the TI group exhibited signifi-cantly lower VAS pain scores,greater SROM(forward flexion and backward extension),and higher CM scores at 4,8,and 12 weeks post-treatment compared to the T and I groups(Bonferroni-corrected P<0.05).No statistically significant differences were observed between the T and I groups for these measures(Bonferroni-corrected P>0.05).Additionally,there were no statistically significant differences in AIS scores or adverse effects occurrence among the three groups at 1 month post-treatment(P>0.05).Conclusion The combined treatment demonstrated greater efficacy compared to trigger point extracorporeal shock wave therapy alone and periapical steroid injection alone,resulting in significant improvement in the patient's clinical symptoms and quality of life.

Objective To construct an evidence-based discharge preparation service plan for patients after receiving percutaneous transhepatic biliary drainage(PTBD)so as to provide a theoretical reference basis for improving the quality of discharge nursing service.Methods A computerized retrieval of academic papers concerning the discharge preparation service plan for patients after receiving PTBD was conducted.The quality of the included literature was evaluated and the evidences were summarized.According to the clinical actual requirements,the first draft of discharge preparation service for patients after receiving PTBD was formed.Using Delphi method,two rounds of letter inquiries were conducted in 17 experts to determine the final version.Results In the first round of expert consultation,17 questionnaires were distributed and 15 questionnaires were recovered;and in the second round of expert consultation,15 questionnaires were distributed and 15 questionnaires were recovered.In the first round of expert correspondence,11 experts made suggestions for modification,and in the second round of expert correspondence,4 experts made suggestions,indicating that the experts were more motivated to participate in the research.The coefficient of expert consultation judgment(Ca)was 0.90,the degree of familiarity(Cs)was 0.91,the coefficient of authority(Cr)was 0.91,and the Kendall's w for round 1 and round 2 were 0.363 and 0.368 respectively.The final discharge preparation service scheme consisted of 13 items at six different time points from patient admission to after discharge.Conclusion The established discharge preparation service plan for patients after receiving PTBD is scientific and reliable,which can provide theoretical basis for patients'discharge service.

Objective Based on the best evidences to establish the practice plan of discharge preparation service for patients after receiving percutaneous transhepatic biliary drainage(PTBD),and to assess its clinical application value.Methods According to the PIPOST principle the clinical questions were proposed,the best evidences of discharge preparation service for patients after receiving PTBD were retrieved and summarized.The review indicators and review methods were formulated.The baseline review was carried out,the facilitators and barrier factors were analyzed,the change strategies were developed,the clinical transforms were implemented,and the patient outcomes were evaluated.Results After application of the evidences,the implementation of the review indicators of discharge preparation services after PTBD was improved.After discharge,the incidence of catheter complications(including catheter falling-off and puncture site skin infection)was decreased,and the difference was statistically significant(P＜0.05).There were no statistically significant differences in the incidences of tube obstruction and fluid extravasation.Conclusion The evidence-based practice of discharge preparation service for patients after receiving PTBD is helpful for improving the self-care ability of patients after discharge,reducing the incidence of tubular complications and improving the clinical outcome of patients.

Objective To investigate the efficacy of extracorporeal shock wave therapy(ESWT)combined with ultrasound-guided corticosteroid injection(CSI)for the treatment of primary frozen shoulder(PFS).Methods Ninety-nine patients with PFS who visited the pain department of the Affiliated Hospital of Xuzhou Medical University between April 2024 and July 2024 were enrolled and randomly divided into three groups according to the randomized number table method:ESWT group(T group),CSI group(I group),and combined treatment group(TI group),with 33 patients in each group.Visual analogue scale(VAS)scores,shoulder range of motion(SROM),and Constant-Murley shoulder scores(CMS)were recorded before treatment and at 1,4,8,and 12 weeks post-treatment.Additionally,the patients'Ascens Insomnia Scale(AIS)scores were recorded before treatment and 1 month after treatment.The occurrence of adverse effects and the use of remedial medications during the treatment period were also documented.Results Compared with pre-treatment,VAS scores decreased,and SROM and CM scores improved at all time points after treatment in all three groups(P<0.05).AIS scores also decreased in all three groups at 1 month post-treatment(all P<0.05).Intergroup comparisons revealed that the TI group exhibited signifi-cantly lower VAS pain scores,greater SROM(forward flexion and backward extension),and higher CM scores at 4,8,and 12 weeks post-treatment compared to the T and I groups(Bonferroni-corrected P<0.05).No statistically significant differences were observed between the T and I groups for these measures(Bonferroni-corrected P>0.05).Additionally,there were no statistically significant differences in AIS scores or adverse effects occurrence among the three groups at 1 month post-treatment(P>0.05).Conclusion The combined treatment demonstrated greater efficacy compared to trigger point extracorporeal shock wave therapy alone and periapical steroid injection alone,resulting in significant improvement in the patient's clinical symptoms and quality of life.

Objective To explore the clinical value of high frequency ultrasound combined with dermoscopy in preoperative evaluation of cutaneous malignant tumors.Methods A total of 323 patients with suspected cutaneous malignant tumors were selected from Jinhua Municipal Central Hospital from January 2022 to December 2023.The clinical value of high frequency ultrasound,dermoscopy and their combined examination in preoperative diagnosis of cutaneous malignant tumors were analyzed and compared.Results A total of 323 patients with suspected cutaneous malignant tumors,223 patients with confirmed cutaneous malignant tumors by skin pathology,234 skin lesions,and 100 patients with benign skin tumors were included.141 skin lesions were detected by dermoscopy,195 skin lesions by high frequency ultrasound,and 213 skin lesions by the combination of dermoscopy and high frequency ultrasound.The sensitivity,specificity and accuracy of high frequency ultrasound combined with dermoscopy in diagnosis of cutaneous malignant tumors were 87.6％,92.0％and 88.9％,respectively,which was higher than that of single high frequency ultrasound and single dermoscopy.The diagnosis results of dermoscopy combined with high frequency ultrasound were in good agreement with the pathological results(kappa=0.75).Conclusion Dermoscopy and high frequency ultrasound are convenient,non-invasive and sensitive imaging methods for skin detection.They can balance resolution and depth of detection,reveal morphological information of tumors,and predict the risk of tumor recurrence.

Objective:To investigate the expression of the proinflammatory factor IL-18-mediated NOD-like receptor thermal protein domain associated protein 3/nuclear factor κB(NLRP3/NF-κB)signaling pathway in penile tissues of rats with high-fat diet-in-duced erectile dysfunction(ED),and to explore the intervention effect of sildenafil.Methods:Fifty-five sexually normal male SD rats were randomly divided into 10 cases as the normal control group,and the rest of the rats were fed with high-fat chow to establish the ED rat model,and the successfully screened ED rats were randomly divided into the ED group,the Sil group,the IL-18 group,and the IL-18+Sil group,with 8 rats in each group.Following 14 days of nonstop treatment,the morphological alterations in the penile tis-sue were observed by HE staining.Using immunohistochemistry,the amount and distribution of NF-κB p65 and Adropin in penile tis-sues were found.RT-qPCR was used to identify the expression of NLRP3 and NF-κB p65 mRNA in penile tissues.Western blot exami-nation showed the expression of the proteins NLRP3,pro-IL-18,p-NF-κB p65,NF-κB p65,and Adropin in penile tissues.Results:The ED group showed altered penis tissue morphology,destroyed muscle fibers,enlarged sinus cavity,increased mRNA and protein expressions of NLRP3,p-NF-κB p65/NF-κB p65,and pro-IL-18(all P<0.05),and decreased Adropin protein expression(P<0.05).While the protein expression of Adropin was increased(P<0.05),the mRNA and protein expressions of NLRP3,p-NF-κB p65/NF-κB p65,and pro-IL-18 in the penis tissues were decreased(all P<0.05)when compared to the ED group.The muscle fibers and sinus cav-ities of the penis were recovered to varying degrees in the Sil group.The IL-18 group experienced the destruction of muscle fibers,an enlargement of the sinus cavity,an increase in the mRNA and protein expressions of NLRP3,p-NF-κB p65/NF-κB p65,and pro-IL-18 in the penile tissues(all P<0.05),as well as a decrease in the protein expression of Adropin(P<0.05).The rat penile tissues in the IL-18+Sil group showed variable degrees of recovery in the muscle fibers and sinus cavities when compared to the IL-18 group.Ad-ditionally,there was a drop(all P<0.05)in the expressions of NLRP3,pro-IL-18 m RNA and protein,p-NF-κB p65/NF-κB p65,and p-NF-κB p65 in the penile tissues.The expression of the Adropin protein was elevated(P<0.05).Conclusion:Significant changes have been observed in the NLRP3/NF-κB signaling pathway,which is regulated by IL-18,in the hyperlipidemia ED rat model.In ED rats,sildenafil can increase erectile function by promoting the production of Adropin and blocking the activation of this pathway.