Transformer models have emerged as pivotal tools within the realm of drug discovery, distinguished by their unique architectural features and exceptional performance in managing intricate data landscapes. Leveraging the innate capabilities of transformer architectures to comprehend intricate hierarchical dependencies inherent in sequential data, these models showcase remarkable efficacy across various tasks, including new drug design and drug target identification. The adaptability of pre-trained transformer-based models renders them indispensable assets for driving data-centric advancements in drug discovery, chemistry, and biology, furnishing a robust framework that expedites innovation and discovery within these domains. Beyond their technical prowess, the success of transformer-based models in drug discovery, chemistry, and biology extends to their interdisciplinary potential, seamlessly combining biological, physical, chemical, and pharmacological insights to bridge gaps across diverse disciplines. This integrative approach not only enhances the depth and breadth of research endeavors but also fosters synergistic collaborations and exchange of ideas among disparate fields. In our review, we elucidate the myriad applications of transformers in drug discovery, as well as chemistry and biology, spanning from protein design and protein engineering, to molecular dynamics (MD), drug target identification, transformer-enabled drug virtual screening (VS), drug lead optimization, drug addiction, small data set challenges, chemical and biological image analysis, chemical language understanding, and single cell data. Finally, we conclude the survey by deliberating on promising trends in transformer models within the context of drug discovery and other sciences.

Objective:To evaluate the effectiveness of a mobile extracorporeal cardiopulmonary resuscitation (ECPR) team in treating cardiac arrest (CA) in the mountainous regions of southwest Zhejiang Province, and to provide clinical insights for ECPR in patients with prolonged low blood flow time in such areas.Methods:A retrospective analysis was conducted on 55 CA patients treated with ECPR at Lishui People's Hospital from June 2020 to June 2024. These patients were compared with 55 CA patients treated with ECPR in urban areas during the same period. The mobile team from our center established ECMO support at county-level hospitals before transferring patients to our hospital's ECMO treatment center for further care. General patient data and blood gas analysis results before and 2 hours after ECPR were collected. Clinical data differences between the two groups were compared, and factors influencing patient prognosis were analyzed using univariate and multivariate Cox regression analyses.Results:The average age of the patients was (52.45 ± 15.66) years, with an average low blood flow time of 151.42 ± 49.31 minutes. The 30-day survival rate was 23.64%, and the rate of good neurological recovery was 18.18%. Although the survival rate and good neurological function rate were lower than those of ECPR patients in urban areas, the differences were not statistically significant ( P > 0.05). Univariate Cox analysis revealed that defibrillation rhythm, low blood flow time, pH before and after ECMO, blood lactate levels before and after ECMO, and hemoglobin significantly influenced the prognosis of ECPR patients ( P < 0.05). Multivariate Cox analysis identified post-ECMO pH ( HR = 0.037) and post-ECMO blood lactate levels ( HR = 1.078) as independent prognostic factors for ECPR patients ( P < 0.05). Conclusions:Despite the longer low blood flow time in CA patients from mountainous areas, the mobile ECPR team can effectively enhance the treatment success rate of these patients through ECPR.

Objective To explore the application value of stage rehabilitation intervention under the Health action process approach(HAPA)model(SRI-HAPAM)combined with tranexamic acid(TXA)in elderly patients with femoral neck fracture(FNF)undergoing total hip arthroplasty(THA).Methods Elderly FNF patients with unilateral THA in the First Affiliated Hospital of Wenzhou Medical University from December 2022 to June 2023 were enrolled.According to the random number table method,the patients were divided into routine nursing(RN)group and TXA+SRI-HAPAM group.The RN group received conventional treatment after surgery,and the TXA+SRI-HAPAM group received TXA combined with SRI-HAPAM after surgery.The bleeding indexes[hidden blood loss(HBL),explicit blood loss(EBL)and blood transfusion volume(BTV)],and the levels of hemoglobin(Hb),C-reactive protein(CRP)and D-dimer(DD)were compared between the two groups at 24 h after surgery.The hip function[joint deformity(JD),joint function(JF),joint pain(JP),joint motion(JM)and total hip function(THF)],anxiety and depression[self-rating anxiety scale and self-rating depression scale],satisfaction with care,and complications were compared between the two groups at 3 months after surgery.Results A total of 100 elderly patients with unilateral THA due to FNF were included in the study,including 54 in the TXA+SRI-HAPAM group and 46 in the RN group.Before operation,there was no significant difference in Hb,CRP,DD,JD,JF,JP,JM,THF and SAS between the two groups(P>0.05).At 24 hours after operation,Hb decreased in the two groups,while CRP and DD increased(P<0.05),and the decrease in Hb and the increase in CRP and DD,as well as HBL,EBL and BTV in the TXA+SRI-HAPAM group,were lower than those in the RN group(P<0.05).At 3 months after operation,JD,JF,JP,JM and THF in both groups increased compared with those before operation,while SAS and SDS decreased compared with those before operation(P<0.05),and the functional scores of JD,JF,JP,JM and THF in the TXA+SRI-HAPAM group were significantly higher than those in the RN group,and the scores of SAS and SDS were lower than those in the RN group(P<0.05).3 months after surgery,the nursing satisfaction of the TXA+SRI-HAPAM group was significantly higher than that of the RN group,and the total complication rate was lower than that of the RN group(P<0.05).Conclusion Compared the Routine nursing,TXA combined with SRI-HAPAM more effectively promotes postoperative recovery in patients with THA.

Objective:To explore the role of tripartite motif-containing protein 21(TRIM21)in chronic apical periodontitis(CAP)and its potential mechanism.Methods:Human CAP tissue and normal periodontal tissue were collected.The expression of inflamma-tory factors(IL-1 β,IL-6,TNF-a,TGF-β1),osteoclast related genes(TRAP,RANKL,CTSK),macrophage polarization related genes(CD86,iNOS,CD206,Arg1)and TRIM21 were detected by RT-qPCR.TRIM21 protein was detected by immunohistochemical staining,and the osteoclasts was detected by tartrate resistant acid phosphatase(TRAP)staining.The inflammation cell model was es-tablished by stimulating Raw264.7 cells with lipoteichoic acid(LTA)or lipopolysaccharide(LPS),and the expression of the above factors was detected.The bone marrow-derived macrophages(BMDMs)extracted from wild-type and TRIM21-/-mice stimulated by LPS were used to verify the expression of the above factors by RT-qPCR,the osteoclasts were detected by TRAP staining,and the po-larization of macrophages was detected by immunofluorescence staining.Results:In CAP tissue the expression of inflammatory factors,osteoclast related genes,CD86,iNOS and TRIM21 increased,while CD206 and Arg1 decreased,and osteoclasts were more than that in normal tissue.The stimulation of LTA/LPS promoted the proliferation of Raw264.7 cells,and the expression of these factors in cells was consistent with that in tissues.After LPS stimulation,BMDMs of TRIM21-/-mice had lighter inflammation,lower expression of os-teoclast specific genes,fewer osteoclasts and lower M1 polarization than those of wild type mice.Conclusion:TRIM21 might promote the progress of CAP by promoting M1 polarization of macrophages.

Objective:To summarize the anesthesia management of living small bowel transplantation.Methods:Severn patients undergoing living and allogeneic small bowel transplantation for the first time were selected.The intraoperative hemodynamics, indexes of blood gas analysis, body temperature and blood transfusion and volume of liquid infused were analyzed.Postoperative outcomes were tracked.Results:Six cases survived and were successfully discharged from hospital successfully, and one patient died.In the operation room, 71% patients were successfully extubated after surgery.Compared with the values during anatomical separation period, Hb during vascular anastomosis and intestinal reconstruction periods and concentration of Ca 2+ during intestinal reconstruction period were significantly decreased, and the blood glucose concentration during vascular anastomosis period were increased ( P<0.05 or 0.01). Compared with the values during vascular anastomosis period, the blood glucose concentration was increased significantly during intestinal reconstruction period ( P<0.05). Crystalloid solution (57±30) ml/kg and colloid solution which mainly containing 20% albumin (15±13) ml/kg were infused mainly during anatomical separation and vascular anastomosis periods in all the patients. Conclusion:The condition of successful living small bowel transplantation is fully evaluation and preparation before surgery.Intravenous-inhalational anesthesia combined with transverses abdominis plane block and rational infusion of colloid solution with vasoactive drugs to maintain hemodynamics stability and monitor blood gas, body temperature, active adjustment of electrolytes and internal environment and stable body temperature can be helpful in maintaining perioperative stable vital signs during the perioperative period, removing the tracheal tube early at the end of surgery, and reducing the development of postoperative complications in patients undergoing living small bowel transplantation.

Since the coronavirus disease 2019 (COVID-19) affects the cardio-pulmonary function of pregnant women, the anesthetic management and protection of medical staff in the cesarean section is significantly different from that in ordinary surgical operation. This paper reports a case of cesarean section for a woman with COVID-19, which was successfully performed in the First Affiliated Hospital of Zhejiang University School of Medicine on February 8, 2020. Anesthetic management, protection of medical staff and psychological intervention for the pregnant woman during the operation were discussed. Importance has been attached to the preoperative evaluation of pregnant women with COVID-19 and the implementation of anesthesia plan. For moderate patients, intraspinal anesthesia is preferred in cesarean section, and try to reduce its influence in respiration and circulation in both maternal and infant; general anesthesia with endotracheal intubation should be adopted for severe or critically ill patients. Ensure the safety of medical environment, and anesthetists should carry out level-Ⅲ standard protection. Special attention and support should be paid to maternal psychology: fully explanation before operation to reduce anxiety; relieve the discomfort during operation, so as to reduce tension; avoid the bad mood due to pain after operation.
Anesthesia ; Betacoronavirus ; isolation & purification ; Cesarean Section ; methods ; Coronavirus Infections ; complications ; Female ; Humans ; Infant ; Injections, Spinal ; Pandemics ; Pneumonia, Viral ; complications ; Pregnancy

Since the corona virus disease 2019 (COVID-19) affects the cardio-pulmonary function of pregnant women, the anesthetic management in the cesarean section for the patients, as well as the protection for medical staff is significantly different from that in ordinary surgical operation. This paper reports a pregnant woman with COVID-19, for whom a cesarean section was successfully performed in our hospital on February 8, 2020. Anesthetic management, protection of medical staff and psychological intervention for the patients during the operation are discussed. Importance should be attached to the preoperative evaluation of pregnant women with COVID-19 and the implementation of anesthesia plan. For ordinary COVID-19 patients intraspinal anesthesia is preferred in cesarean section, and the influence on respiration and circulation in both maternal and infant should be reduced; while for severe or critically ill patients general anesthesia with endotracheal intubation should be adopted. The safety of medical environment should be ensured, and level-Ⅲ standard protection should be taken for anesthetists. Special attention and support should be given to maternal psychology. It is important to give full explanation before operation to reduce anxiety; to relieve the discomfort during operation to reduce tension; to avoid the bad mood of patients due to pain after operation.
Anesthesia ; Betacoronavirus ; Cesarean Section ; Coronavirus Infections ; complications ; surgery ; Female ; Humans ; Infant ; Injections, Spinal ; Pneumonia, Viral ; complications ; diagnosis ; surgery ; Pregnancy ; Pregnancy Complications, Infectious ; surgery ; Pregnancy Outcome ; Preoperative Care

Aim To investigate the proliferative effect and the apoptosis of rat epididymal epithelial cells induced by podophyllotoxin and its underlying mechanisms.Methods Primary epididymal epithelial cells were cultured in vitro.CCK-8 assay was used to analyze proliferation of epididymal epithelial cells induced by podophyllotoxin on 24, 48 and 72 h.The ultra structural changes of the epididymal epithelial cells were observed by transmission electron microscope.AnnexinV-FITC/PI staining was used to quantify the percentages of apoptosis in the total cell population.The TdTmediated dUTP nick end labeling(TUNEL) technique was applied to observe the morphological changes of apoptotic cells.The expression of tumor necrosis factor alpha(TNF-α) mRNA was investigated by real-time RT-PCR.The level of TNF-α in cell culture supernatant was measured by enzyme-linked immunosorbent assay(ELISA) technology.Western blot was per-formed to determine the protein expression of cytochrome C, caspase-3, caspase-8, caspase-9.Results Podophyllotoxin significantly inhibited the activity of proliferation and induced apoptosis of epididymal epithelial cells in a dose-and time-dependent manner(P<0.05), with a 50％ inhibitory concentration(IC50) value and corresponding 95％ confidence intervals(CI) of 59.36(15.50～227.41), 0.37(0.080～1.70), 0.077(0.017～0.35) μmol·L-1 at 24, 48 and 72 h, respectively.Podophyllotoxin induced cell volume turned round and cell nuclear fragmentation and mitochondrial vacuolation.RT-PCR and ELISA results showed that podophyllotoxin improved the expression of TNF-α mRNA and protein.Western blot results demonstrated that podophyllotoxin activated the protein expression of cytochrome C, caspase-3, caspase-8 and caspase-9.Conclusion Podophyllotoxin can induce rat epididymal epithelial cell apoptosis through both the mitochondria-regulated intrinsic pathway and the TNF receptor-mediated extrinsic pathway.

Objective:To compare the clinical utility of mammography with automated breast ultrasound system (ABUS) for detecting breast lesions. Methods:Data of 142 patients with 149 breast lesions who underwent both mammography and ABUS in Tianjin Medi-cal University Cancer Institute and Hospital were collected from Jnly 2016 to September 2016. The detection rates of the two methods were then determined. Results:The overall detection rate using ABUS was significantly higher than that of mammography (mammog-raphy: 87.2% vs. ABUS: 98.0%, P<0.05). However, no significant difference was observed in breast cancer detection rates between mammography and ABUS (mammography:91.1%vs. ABUS:97.0%, P<0.05). Moreover, the benign lesion detection rate was significant-ly higher in ABUS than in mammography (mammography:79.2%, vs. ABUS:100%, P<0.05). In dense breasts, the detection rates of overall lesions, breast cancers, and benign lesions for ABUS were 97.7%, 96.5%, and 100.0%, respectively;whereas those for mammog-raphy were 86.0%, 90.6%, and 77.3%, respectively (P<0.05). Owing to overlapping dense breast tissue and deep anatomic location, sev-eral lesions were missed on mammography. Conversely, most lesions missed on ABUS presented as calcifications. Conclusion:Com-pared with mammography, ABUS can detect more lesions especially in dense breasts. However, ABUS failed to detect calcifications, whereas mammography had distinct advantages in this regard. Overall, the two methods had potential supplementary value for breast cancer screening.