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/.

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.

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.

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 investigate the effect of multi-sided foramen ultrafine drainage tube with metal support on the formation of thoracic residual cavity after uniportal video-assisted thoracoscopic (VATS) upper lobectomy. Methods The clinical data of the patients who underwent uniportal VATS upper lobectomy for lung cancer in the Department of Thoracic Surgery of the First Hospital of Lanzhou University from January 2021 to April 2022 were retrospectively analyzed. According to the type of ultrafine drainage tube used in the surgery, the patients were divided into a test group (using metal-supported multi-sided foramen ultrafine drainage tube) and a control group (using ordinary 12F ultrafine drainage tube). The incidence of postoperative thoracic residual cavity and operation-related data were compared between the two groups. Results A total of 200 patients were enrolled, including 126 males and 74 females, with a mean age of 57.52 years. There were 90 patients in the test group, and 110 patients in the control group. The incidence of postoperative thoracic residual cavity in the test group was lower than that in the control group (P=0.045). The differences in the postoperative bedtime, postoperative visual analogue scale, postoperative analgesic pump using time, postoperative hospitalization time, times of postoperative thoracentration and drainage, postoperative drainage time and hospitalization cost between the two groups were statistically significant (P<0.05). The incidences of postoperative lung infection, pleural effusion and atelectasis complications were lower in the test group than those in the control group (P<0.05). The differences in the preoperative anesthesia time, operation time, intraoperative bleeding and postoperative lung leakage were not statistically significant (P>0.05). Conclusion The use of multi-sided foramen ultrafine drainage tube with metal support can reduce the incidence of thoracic residual cavity after uniportal VATS upper lobectomy, and can reduce pain and economical burdens and the incidence of operation-related complications, accelerating the recovery of patients after surgery. The application of multi-sided foramen ultrafine drainage tube with metal support in uniportal VATS upper lobectomy can be widely used in the clinic.

Objective To investigate the clinical effect of metal supported multi-sided versus ordinary ultra-fine drainage tube in the uniportal video-assisted thoracic surgery (VATS) lower pulmonary lobectomy. Methods From January 2021 to June 2022, the clinical data of patients who underwent uniportal VATS lower lobectomy in our hospital were retrospectively analyzed. According to the different types of ultra-fine drainage tubes used in the surgery, the patients were divided into an experimental group (using multi-sided hole 10F ultra-fine drainage tubes with metal support) and a control group (using ordinary 12F ultra-fine drainage tubes). The clinical data of the two groups were compared. Results A total of 190 patients were enrolled, including 108 males and 82 females. There were 90 patients in the experimental group aged 56.60±10.14 years; and 100 patients in the control group aged 57.07±11.04 years. The incidences of postoperative lung infection and pleural effusion in the experimental group were lower than those in the control group, with statistically significant differences (P<0.05). The postoperative visual analogue scale score, the need to adjust the chest drainage tube after the surgery, the need for chest puncture after the surgery, the time of postoperative chest tube removal, and the hospitalization cost were statistically different (P<0.05). There was no statistical difference in the length of postoperative hospital stay or the incidences of postoperative lung leakage, arrhythmia, and atelectasis complications (P>0.05). Conclusion Compared with the ordinary ultra-fine drainage tubes, multi-sided hole ultra-fine drainage tubes with metal support can reduce the incidences of lung infection and pleural effusion complications after the uniportal VATS lower lobectomy, reduce the pain and economic burden, which can be applied in the uniportal VATS lower lobectomy.