Advancements in artificial intelligence (AI) and emerging technologies are rapidly expanding the exploration of chemical space, facilitating innovative drug discovery. However, the transformation of novel compounds into safe and effective drugs remains a lengthy, high-risk, and costly process. Comprehensive early-stage evaluation is essential for reducing costs and improving the success rate of drug development. Despite this need, no comprehensive tool currently supports systematic evaluation and efficient screening. Here, we present druglikeFilter, a deep learning-based framework designed to assess drug-likeness across four critical dimensions: 1) physicochemical rule evaluated by systematic determination, 2) toxicity alert investigated from multiple perspectives, 3) binding affinity measured by dual-path analysis, and 4) compound synthesizability assessed by retro-route prediction. By enabling automated, multidimensional filtering of compound libraries, druglikeFilter not only streamlines the drug development process but also plays a crucial role in advancing research efforts towards viable drug candidates, which can be freely accessed at https://idrblab.org/drugfilter/.

Aim To explore the potential mechanism of metformin on ATP-binding cassette transport A1(ABCA1)expression.Methods J774A.1 macrophages were treated with metformin and cycloheximide,and ABCA1 expression was determined by Western blot.His-tagged ABCA1 and HA-tagged Ub plasmids were co-transferred into HEK293 cells and stimulated with metformin.Co-immunoprecipitation(Co-IP)was used to test the binding ability of ABCA1 and ubiquitin.Candidate E3 ubiquitin-protein ligases(CE3)of ABCA1 were identified through Co-IP-based pro-teomics.The MIB1 plasmid was constructed and transferred into HEK293 cells,and Western blot was used to determine the effect of metformin and MIB1 on ABCA1 expression.Results Metformin increased the expression of ABCA1 in J774A.1 cells(P<0.01),and inhibited ABCA1 degradation(P<0.05).Metformin disrupted the binding of ABCA1 to ubiquitin(P<0.05).The proteins regulated by metformin in ABCA1 expression were primarily enriched in pathways re-lated to cell development,inflammation and immune defense.Metformin may upregulate ABCA1 protein expression via MIB1(P<0.05).Conclusion Metformin inhibits the degradation of ABCA1 by blocking the ubiquitin-proteasome system(UPS),and MIB1 might act as a candidate E3 ubiquitin-protein ligase(CE3)for ABCA1.

Advancements in artificial intelligence(AI)and emerging technologies are rapidly expanding the exploration of chemical space,facilitating innovative drug discovery.However,the transformation of novel compounds into safe and effective drugs remains a lengthy,high-risk,and costly process.Comprehensive early-stage evaluation is essential for reducing costs and improving the success rate of drug development.Despite this need,no comprehensive tool currently supports systematic evaluation and efficient screening.Here,we present druglikeFilter,a deep learning-based framework designed to assess drug-likeness across four critical dimensions:1)physicochemical rule evaluated by systematic determination,2)toxicity alert investigated from multiple perspectives,3)binding affinity measured by dual-path analysis,and 4)compound synthesizability assessed by retro-route prediction.By enabling automated,multidimensional filtering of compound libraries,druglikeFilter not only streamlines the drug development process but also plays a crucial role in advancing research efforts towards viable drug candidates,which can be freely accessed at https://idrblab.org/drugfilter/.

Objective:To analyze the registration status of clinical trials related to contraceptives based on the data of World Health Organization International Clinical Trials Registry Platform (ICTRP), so as to understand the situation of contraceptives development, and provide reference for improving the quality of clinical trials.Methods:All records in the database of ICTRP before January 1, 2025 was researched to screen out contraceptives clinical trials, and the registration time, registration platform, regional distribution, trial design and research content were analyzed.Results:A total of 206 clinical trials related to contraceptives were included. The projects were mainly carried out in the United States, Germany, and India. About 95.63% (197/206) of the study subjects were women of reproductive age. The　main　type　of　study　was　intervention [89.32% (184/206)], among which random trials accounted for 53.26% (98/184), and parallel group trials were the most common [82.65% (81/98)]. Over 64.56% (133/206) of the trials were indicated with open-label. Most of the clinical trials were in phase Ⅲ [47.57% (98/206)] and phase Ⅳ [16.50% (34/206)]. The interventions in female studies were mainly in three aspects: oral contraceptive [42.64% (84/197)], intrauterine delivery [15.23% (30/197)], and vaginal delivery [15.23% (30/197)], and the primary outcome included pregnancy rate [54.82% (108/197)], adverse drug reactions [13.20% (26/197)], ovulation inhibition [8.63% (17/197)], and vaginal infection [4.06% (8/197)].Conclusion:The　clinical　trials　of contraceptives were unevenly distributed, the research types were mainly randomized interventional trials, the included participants were mainly women of reproductive age, the intervention measures were mostly oral contraceptive, intrauterine delivery and vaginal delivery.

Objective To explore the effects of subanesthetic dose esketamine in endoscopic thyroidectomy through the chest and breast approach.Methods 68 female patients who underwent complete endoscopic thyroidectomy through the chest and breast approach from August 2023 to February 2024 were selected as the study subjects and divided into a control group(34 cases)and esketamine group(34 cases)by random number table method.In the esketamine group,sufentanil 0.2 μg/kg plus esketamine 0.2 mg/kg.In the control group,sufentanil 0.4 μg/kg intravenous infusion was given.Observe the systolic blood pressure(SBP),mean arterial pressure(MAP),and heart rate(HR)of the patients at each time point post-sedated(T0),immediately after induction(T1),immediately before intubation(T2),3 min after intubation(T3),5 min after intubation(T4),10 min after intubation(T5),immediately after skin incision(T6),5 min after incision skin(T7),and electroencephalogram bispectral index(BIS)of electroencephalogram at time points T1,T2,T3,T4,T5,T6 and T7 time points;The peroperative blood,anesthesia-related conditions[recovery time,PACU stay time and intraoperative utilization rate of vasoactive drugs],the incidence of adverse reactions(choking cough during recovery,incidence of hypotension after induction,tachycardia during induction,postoperative nausea,vomiting)and the degree of postoperative pain were compared between the two groups of patients.Results Compared to the control group,the esketamine group showed significantly higher SBP and MAP at T2,T4,and T5,the differences were statistically significant(P<0.05);There were 3 cases of tachycardia in the control group and 2 cases in the esketamine group.However,there was no statistically significant difference in HR at each time point between the two group(P>0.05).The BIS at T2 time point in the esketamine group was higher than that of the control groups,the difference was statistically significant(P<0.05),there was no statistically significant difference at the other time points(P>0.05).The use of vasoactive drugs of norepinephrine in the esketamine group was significantly lower than that of the control group(P<0.05).There was no statistically significant difference in the recovery time and PACU stay time between the two groups of patients(P>0.05).The esketamine group exhibited fewer cough reflexes during recovery,lower incidence of hypotension at T2 and T5 time points,lower incidences of nausea and vomiting at 12 and 24 h postoperatively,the differences were statistically significant(P<0.05).There were no statistically significant difference in the peroperative blood and incidence of tachycardia during induction between the two groups of patients(P>0.05).There was no statistically significant difference in the visual analogue scale(VAS)score of the two groups of patients 2 h after surgery(P>0.05).The VAS score of the esketamine group at 12 and 24 h after surgery were significantly lower than those of the control group,and the differences were statistically significant(P<0.05).Conclusion The subanesthetic dose of esketamine used in endoscopic thyroidectomy through the chest and breast approach can maintain hemodynamic stability in patients,reduce the incidence of hypotension after induction,decrease postoperative nausea,vomiting and choking cough,and provide long-lasting analgesia.It is worthy of clinical promotion and application.

Objective:To analyze the registration status of clinical trials related to contraceptives based on the data of World Health Organization International Clinical Trials Registry Platform (ICTRP), so as to understand the situation of contraceptives development, and provide reference for improving the quality of clinical trials.Methods:All records in the database of ICTRP before January 1, 2025 was researched to screen out contraceptives clinical trials, and the registration time, registration platform, regional distribution, trial design and research content were analyzed.Results:A total of 206 clinical trials related to contraceptives were included. The projects were mainly carried out in the United States, Germany, and India. About 95.63% (197/206) of the study subjects were women of reproductive age. The　main　type　of　study　was　intervention [89.32% (184/206)], among which random trials accounted for 53.26% (98/184), and parallel group trials were the most common [82.65% (81/98)]. Over 64.56% (133/206) of the trials were indicated with open-label. Most of the clinical trials were in phase Ⅲ [47.57% (98/206)] and phase Ⅳ [16.50% (34/206)]. The interventions in female studies were mainly in three aspects: oral contraceptive [42.64% (84/197)], intrauterine delivery [15.23% (30/197)], and vaginal delivery [15.23% (30/197)], and the primary outcome included pregnancy rate [54.82% (108/197)], adverse drug reactions [13.20% (26/197)], ovulation inhibition [8.63% (17/197)], and vaginal infection [4.06% (8/197)].Conclusion:The　clinical　trials　of contraceptives were unevenly distributed, the research types were mainly randomized interventional trials, the included participants were mainly women of reproductive age, the intervention measures were mostly oral contraceptive, intrauterine delivery and vaginal delivery.

Aim To explore the potential mechanism of metformin on ATP-binding cassette transport A1(ABCA1)expression.Methods J774A.1 macrophages were treated with metformin and cycloheximide,and ABCA1 expression was determined by Western blot.His-tagged ABCA1 and HA-tagged Ub plasmids were co-transferred into HEK293 cells and stimulated with metformin.Co-immunoprecipitation(Co-IP)was used to test the binding ability of ABCA1 and ubiquitin.Candidate E3 ubiquitin-protein ligases(CE3)of ABCA1 were identified through Co-IP-based pro-teomics.The MIB1 plasmid was constructed and transferred into HEK293 cells,and Western blot was used to determine the effect of metformin and MIB1 on ABCA1 expression.Results Metformin increased the expression of ABCA1 in J774A.1 cells(P<0.01),and inhibited ABCA1 degradation(P<0.05).Metformin disrupted the binding of ABCA1 to ubiquitin(P<0.05).The proteins regulated by metformin in ABCA1 expression were primarily enriched in pathways re-lated to cell development,inflammation and immune defense.Metformin may upregulate ABCA1 protein expression via MIB1(P<0.05).Conclusion Metformin inhibits the degradation of ABCA1 by blocking the ubiquitin-proteasome system(UPS),and MIB1 might act as a candidate E3 ubiquitin-protein ligase(CE3)for ABCA1.

Objective To explore the effects of subanesthetic dose esketamine in endoscopic thyroidectomy through the chest and breast approach.Methods 68 female patients who underwent complete endoscopic thyroidectomy through the chest and breast approach from August 2023 to February 2024 were selected as the study subjects and divided into a control group(34 cases)and esketamine group(34 cases)by random number table method.In the esketamine group,sufentanil 0.2 μg/kg plus esketamine 0.2 mg/kg.In the control group,sufentanil 0.4 μg/kg intravenous infusion was given.Observe the systolic blood pressure(SBP),mean arterial pressure(MAP),and heart rate(HR)of the patients at each time point post-sedated(T0),immediately after induction(T1),immediately before intubation(T2),3 min after intubation(T3),5 min after intubation(T4),10 min after intubation(T5),immediately after skin incision(T6),5 min after incision skin(T7),and electroencephalogram bispectral index(BIS)of electroencephalogram at time points T1,T2,T3,T4,T5,T6 and T7 time points;The peroperative blood,anesthesia-related conditions[recovery time,PACU stay time and intraoperative utilization rate of vasoactive drugs],the incidence of adverse reactions(choking cough during recovery,incidence of hypotension after induction,tachycardia during induction,postoperative nausea,vomiting)and the degree of postoperative pain were compared between the two groups of patients.Results Compared to the control group,the esketamine group showed significantly higher SBP and MAP at T2,T4,and T5,the differences were statistically significant(P<0.05);There were 3 cases of tachycardia in the control group and 2 cases in the esketamine group.However,there was no statistically significant difference in HR at each time point between the two group(P>0.05).The BIS at T2 time point in the esketamine group was higher than that of the control groups,the difference was statistically significant(P<0.05),there was no statistically significant difference at the other time points(P>0.05).The use of vasoactive drugs of norepinephrine in the esketamine group was significantly lower than that of the control group(P<0.05).There was no statistically significant difference in the recovery time and PACU stay time between the two groups of patients(P>0.05).The esketamine group exhibited fewer cough reflexes during recovery,lower incidence of hypotension at T2 and T5 time points,lower incidences of nausea and vomiting at 12 and 24 h postoperatively,the differences were statistically significant(P<0.05).There were no statistically significant difference in the peroperative blood and incidence of tachycardia during induction between the two groups of patients(P>0.05).There was no statistically significant difference in the visual analogue scale(VAS)score of the two groups of patients 2 h after surgery(P>0.05).The VAS score of the esketamine group at 12 and 24 h after surgery were significantly lower than those of the control group,and the differences were statistically significant(P<0.05).Conclusion The subanesthetic dose of esketamine used in endoscopic thyroidectomy through the chest and breast approach can maintain hemodynamic stability in patients,reduce the incidence of hypotension after induction,decrease postoperative nausea,vomiting and choking cough,and provide long-lasting analgesia.It is worthy of clinical promotion and application.

Recently, small nucleolar RNAs (snoRNAs) have transcended the genomic "noise" to emerge as pivotal molecular markers due to their essential roles in tumor progression. Substantial evidence indicates a strong association between snoRNAs and critical clinical features such as tumor pathology and drug resistance. Historically, snoRNA research has concentrated on two classical mechanisms: 2'-O-ribose methylation and pseudouridylation. This review specifically summarizes the novel regulatory mechanisms and functional patterns of snoRNAs in tumors, encompassing transcriptional, post-transcriptional, and post-translational regulation. We further discuss the synergistic effect between snoRNA host genes (SNHGs) and snoRNAs in tumor progression. More importantly, snoRNAs extensively contribute to the development of tumor cell resistance as oncogenes or tumor suppressor genes. Accordingly, we provide a comprehensive review of the clinical diagnosis and treatment associated with snoRNAs and explore their significant potential as novel drug targets.

Objective:To investigate the surgical situations and perioperative outcome of pancreaticoduodenectomy in Jiangsu Province and the influencing factors for postoperative 90-day mortality.Methods:The retrospective case-control study was conducted. The clinicopathological data of 2 886 patients who underwent pancreaticoduodenectomy in 21 large tertiary hospitals of Jiangsu Quality Control Center for Pancreatic Diseases, including The First Affiliated Hospital of Nanjing Medical University, from March 2021 to December 2022 were collected. There were 1 732 males and 1 154 females, aged 65(57,71)years. Under the framework of the Jiangsu Provincial Pancreatic Disease Quality Control Project, the Jiangsu Quality Control Center for Pancreatic Diseases adopted a multi-center registration research method to establish a provincial electronic database for pancrea-ticoduodenectomy. Observation indicators: (1) clinical characteristics; (2) intraoperative and post-operative conditions; (3) influencing factors for 90-day mortality after pancreaticoduodenectomy. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(IQR), and comparison between groups was conducted using the Mann-Whitney U test. Count data were expressed as absolute numbers or constituent ratio, and comparison between groups was conducted using the chi-square test, continuity correction chi-square test and Fisher exact probability. Maximal Youden index method was used to determine the cutoff value of continuous variables. Univariate analysis was performed using the corresponding statistical methods based on data types. Multivariate analysis was performed using the Logistic multiple regression model. Results:(1) Clinical characteristics. Of the 2 886 patients who underwent pancreaticoduodenectomy, there were 1 175 and 1 711 cases in 2021 and 2022, respectively. Of the 21 hospitals, 8 hospitals had an average annual surgical volume of <36 cases for pancreaticoduodenectomy, 10 hospitals had an average annual surgical volume of 36-119 cases, and 3 hospitals had an average annual surgical volume of ≥120 cases. There were 2 584 cases performed pancreaticoduodenectomy in thirteen hospitals with an average annual surgical volume of ≥36 cases, accounting for 89.536%(2 584/2 886)of the total cases. There were 1 357 cases performed pancrea-ticoduodenectomy in three hospitals with an average annual surgical volume of ≥120 cases, accounting for 47.020%(1 357/2 886) of the total cases. (2) Intraoperative and postoperative conditions. Of the 2 886 patients, the surgical approach was open surgery in 2 397 cases, minimally invasive surgery in 488 cases, and it is unknown in 1 case. The pylorus was preserved in 871 cases, not preserved in 1 952 cases, and it is unknown in 63 cases. Combined organ resection was performed in 305 cases (including vascular resection in 209 cases), not combined organ resection in 2 579 cases, and it is unknown in 2 cases. The operation time of 2 885 patients was 290(115)minutes, the volume of intra-operative blood loss of 2 882 patients was 240(250)mL, and the intraoperative blood transfusion rate of 2 880 patients was 27.153%(782/2 880). Of the 2 886 patients, the invasive treatment rate was 11.342%(327/2 883), the unplanned Intensive Care Unit (ICU) treatment rate was 3.087%(89/2 883), the reoperation rate was 1.590%(45/2 830), the duration of postoperative hospital stay was 17(11)days, the hospitalization mortality rate was 0.798%(23/2 882), and the failure rate of rescue data in 2 083 cases with severe complications was 6.529%(19/291). There were 2 477 patients receiving postoperative 90-day follow-up, with the 90-day mortality of 2.705%(67/2477). The total incidence rate of complication in 2 886 patients was 58.997%(1 423/2 412). The incidence rate of severe complication was 13.970%(291/2 083). The comprehensive complication index was 8.7(22.6) in 2 078 patients. (3) Influencing factors for 90-day mortality after pancreaticoduodenectomy. Results of multivariate analysis showed that age ≥ 70 years, postoperative invasive treatment, and unplanned ICU treatment were independent risk factors for 90-day mortality after pancreaticoduodenectomy ( odds ratio=2.403, 2.609, 16.141, 95% confidence interval as 1.281-4.510, 1.298-5.244, 7.119-36.596, P<0.05). Average annual surgical volume ≥36 cases in the hospital was an independent protective factor for 90-day mortality after pancreaticoduodenectomy ( odds ratio=0.368, 95% confidence interval as 0.168-0.808, P<0.05). Conclusions:Pancreaticoduodenectomy in Jiangsu Province is highly con-centrated in some hospitals, with a high incidence of postoperative complications, and the risk of postoperative 90-day mortality is significant higher than that of hospitallization mortality. Age ≥ 70 years, postoperative invasive treatment, and unplanned ICU treatment are independent risk factors for 90-day motality after pancreaticoduodenectomy, and average annual surgical volume ≥36 cases in the hospital is an independent protective factor.