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 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.

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/.

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 develop and evaluate a fine-tuned large language model(LLM)for traditional Chinese medicine(TCM)prescription recommendation named TCMLLM-PR.Methods First,we constructed an instruction-tuning dataset containing 68 654 samples(ap-proximately 10 million tokens)by integrating data from eight sources,including four TCM textbooks,Pharmacopoeia of the People's Republic of China 2020(CHP),Chinese Medicine Clinical Cases(CMCC),and hospital clinical records covering lung disease,liver disease,stroke,diabetes,and splenic-stomach disease.Then,we trained TCMLLM-PR using Chat-GLM-6B with P-Tuning v2 technology.The evaluation consisted of three aspects:(i)compari-son with traditional prescription recommendation models(PTM,TCMPR,and PresRecST);(ii)comparison with TCM-specific LLMs(ShenNong,Huatuo,and HuatuoGPT)and general-domain ChatGPT;(iii)assessment of model migration capability across different disease datasets.We employed precision,recall,and F1 score as evaluation metrics.Results The experiments showed that TCMLLM-PR significantly outperformed baseline models on TCM textbooks and CHP datasets,with F1@10 improvements of 31.80%and 59.48%,respectively.In cross-dataset validation,the model performed best when migrating from TCM textbooks to liver disease dataset,achieving an F1@10 of 0.155 1.Analysis of real-world cases demonstrated that TCMLLM-PR's prescription recommendations most closely matched actual doctors'prescriptions.Conclusion This study integrated LLMs into TCM prescription recommendations,leverag-ing a tailored instruction-tuning dataset and developing TCMLLM-PR.This study will pub-licly release the best model parameters of TCMLLM-PR to promote the development of the decision-making process in TCM practices(https://github.com/2020MEAI/TCMLLM).

Objective To compare the safety and efficacy of the da Vinci robot and thoracoscopic subxiphoid approach for the treatment of anterior mediastinal tumors. Methods The clinical data of patients who underwent anterior mediastinal tumor resection through the subxiphoid approach admitted to the same medical group in the Department of Thoracic Surgery of the First Hospital of Lanzhou University between June 2020 and April 2022 were retrospectively analyzed. According to the surgery approach, the patients were divided into a robot-assisted thoracoscopic surgery (RATS) group and a video-assisted thoracoscopic surgery (VATS) group. The perioperative data and the incidence of postoperative complications were compared between the two groups. Results A total of 79 patients were enrolled. There were 41 patients in the RATS group, including 13 males and 28 females, with an average age of 45.61±14.99 years. There were 38 patients in the VATS group, including 14 males and 24 females, with an average age of 47.84±15.05 years. All patients completed the surgery successfully. Hospitalization cost and operative time were higher or longer in the RATS group than those in the VATS group, and the difference was statistically significant (P<0.05). Intraoperative bleeding, postoperative hospital stay, postoperative water and food intake time, postoperative off-bed activity time, white blood cell count, neutrophil percentage and visual analogue scale (VAS) score on the first postoperative day, white blood cell count and neutrophil percentage on the third postoperative day, duration of analgesic pump use, the number of voluntary compressions of the analgesic pump, and mediastinal drainage volume were all superior to those in the VATS group (P<0.05). The differences in VAS scores on the third postoperative day, duration of drainage tube retention and postoperative complication rates were not statistically different between the two groups (P>0.05). Conclusion RATS subxiphoid anterior mediastinum tumor resection is a safe and feasible surgical method with less injury and higher safety, which is conducive to rapid postoperative recovery and has wide clinical application prospects.