Increasing evidence showed that histone deacetylase 6 (HDAC6) dysfunction is directly associated with the onset and progression of various diseases, especially cancers, making the development of HDAC6-targeted anti-tumor agents a research hotspot. In this study, artificial intelligence (AI) technology and molecular simulation strategies were fully integrated to construct an efficient and precise drug screening pipeline, which combined Voting strategy based on compound-protein interaction (CPI) prediction models, cascade molecular docking, and molecular dynamic (MD) simulations. The biological potential of the screened compounds was further evaluated through enzymatic and cellular activity assays. Among the identified compounds, Cmpd.18 exhibited more potent HDAC6 enzyme inhibitory activity (IC₅₀ = 5.41 nM) than that of tubastatin A (TubA) (IC₅₀ = 15.11 nM), along with a favorable subtype selectivity profile (selectivity index ≈ 117.23 for HDAC1), which was further verified by the Western blot analysis. Additionally, Cmpd.18 induced G2/M phase arrest and promoted apoptosis in HCT-116 cells, exerting desirable antiproliferative activity (IC₅₀ = 2.59 μM). Furthermore, based on long-term MD simulation trajectory, the key residues facilitating Cmpd.18's binding were identified by decomposition free energy analysis, thereby elucidating its binding mechanism. Moreover, the representative conformation analysis also indicated that Cmpd.18 could stably bind to the active pocket in an effective conformation, thus demonstrating the potential for in-depth research of the 2-(2-phenoxyethyl)pyridazin-3(2H)-one scaffold.

Objective To explore the influencing factors of cognitive impairment in non-dialysis patients with chronic kidney disease(CKD).Methods A total of 60 hospitalized non-dialysis patients with CKD in the Department of Nephrology of Northern Jiangsu People's Hospital Affiliated to Yangzhou University from September 2022 to September 2023 were enrolled as research objects.According to the estimated glomerular filtration rate(eGFR),they were divided into stage 1 to 2 of CKD group[eGFR ≥60 mL/(min·1.73 m2)]with 23 cases,the stage 3 of CKD group[eGFR 30～＜60 mL/(min·1.73 m2)]with 20 cases,and stage 4 to 5 of CKD group[eGFR＜30 mL/(min·1.73 m2)]with 17 cases.The Montreal Cognitive Assessment Scale(MoCA)was used to evaluate the cognitive function of the patients.Basic data and common clinical laboratory in-dicators on hospital admission were collected to analyze the differences in cognitive function levels under different renal function statuses and to explore the influencing factors of cognitive impairment.Results The incidence rates of cognitive impairment in the stage 1 to 2 of CKD group,stage 3 of CKD group,and stage 4 to 5 of CKD group were 47.8％,85.0％,and 94.1％respectively,the median MoCA scored 26,24 and 20 respectively,with statistically significant between-group differ-ences(P＜0.05).Cognitive function was significantly negatively correlated with age(r=-0.634,P＜0.001),blood urea nitrogen(BUN)(r=-0.574,P＜0.001),serum creatinine(Cr)(r=-0.417,P＜0.001),cystatin C(Cys-C)(r=-0.327,P=0.011),serum β2-microglobulin(β2-MG)(r=-0.259,P=0.046),and N-terminal pro-brain natriuretic peptide(NT-proBNP)(r=-0.474,P＜0.001),and was significantly positively correlated with hemoglobin(HB)(r=0.401,P=0.001)and eGFR(r=0.485,P＜0.001).Multivariate Logistic regression analysis showed that age(P=0.006)and NT-proBNP(P=0.041)were influencing factors of cognitive im-pairment in non-dialysis patients with CKD.Receiver operating characteristic(ROC)curve analysis showed that the area under the curve(AUC),sensitivity,and specificity of age for prediction were 0.860,0.864 and 0.812 respectively,the AUC,sensitivity,and specificity of NT-proBNP for pre-diction were 0.808,0.795 and 0.875 respectively,and the combined prediction of age and NT-proBNP had an AUC,sensitivity,and specificity of 0.893,0.955,and 0.750,respectively.Conclusion As renal function deteriorates,the incidence rate and severity of cognitive impairment in non-dialysis patients with CKD tend to increase.Advanced age,renal function deterioration,high NT-proBNP level,and anemia are associated with the occurrence of cognitive impairment in non-di-alysis patients with CKD,among which age and NT-proBNP are influencing factors for cognitive im-pairment.

Exosomes are extracellular vesicles that regulate various signaling pathways in the body by mediating the release of proteins, nucleic acids and lipids, thus playing an important role in pathophysiological processes such as inflammation, tumor, immunity and nervous system. More and more studies have shown that exosomal non-coding RNA (ncRNA) plays a crucial role in pancreatic diseases. This article reviews the role of exosome ncRNA in the occurrence, diagnosis and treatment of pancreatic diseases such as acute pancreatitis and pancreatic cancer, in order to provide a reference for clinical practice.

Leonurine(SCM-198)was discovered as one of the active constituents of the Herba Leonuri(HL).Now it can be artificially synthesized.Several recent researches has proven that it exhibits anti-inflammatory effect in several systems in animal models and cell culture in vitro.The key mechanism involves downgrading the activity of nuclear transcription factor-κB(NF-κB),thereby inhibiting the phosphorylation of several signal pathways such as PI3K/Akt,MAPK,ERK,and JNK,or upregulating the activity of Nrf2 related pathways,resulting in downregulated expression of inflammatory cytokines such as tumor necrosis factor-α(TNF-α),IL-1β,IL-2,IL-6,IL-8,inducible nitric oxide synthase(iNOS),cyclooxygenase-2(COX-2),chemokines,adhesion molecules,etc.Owing to the advantages of high safety and efficiency,the ease of administration,as well as its effectiveness in many organs and systems,leonurine has a widely prospect for future research and clinical applications.This article reviews the progress in the fundamental research of leonurine in multiple inflammation-related disease,and it could be expect to offer new possibilities for the treatment of these disease.

Objective To explore the dynamic changes and mechanisms of neurological and cognitive functions in mice with traumatic brain injury (TBI). Methods Totally 60 12⁃month⁃old Balb/ c mice were divided into control group (10 in group) and TBI group (50 in group). TBT model mice were divided into 5 subgroups according to the time of model construction, including model 1 day, model 1 day, model 3 day, model 7 day, model 14 days and model 28 days group with 10 in each group. At the 29th day of the experiment, neurological scores and step down tests were carried out. After the test, the mice were sacrificed for brains which were detected by immunohistochemistry staining, inflammatory cytokine tests and Western blotting. Results Compared with the control group, the neurological scores of mice in TBI group increased, and then decreased after the 7th day when the scores reached the peak. However, the latency of step down errors was lower than control group, and the number of step down errors was higher than control group which had no changes. Compared with the control group, the expression of lonized calcium⁃binding adapter molecule 1(IBA1), chemokine C⁃X3⁃C⁃motif ligand1 (CX3CL1), C⁃X3⁃C chemokine receptor 1(CX3CR1), NOD⁃like receptor thermal protein domain associated protein 3 (NLRP3), and phosphorylation nuclear factor(p⁃NF)⁃κB in TBI group increased and reached to the peak at the 7th day, and then started to decrease. At the same time, the levels of inflammatory cytokines interleukin⁃6(IL⁃6) and tumor necrosis factor⁃α(TNF⁃α) first increased to the peak, and then began to decrease. However, compared with the control group, the expression of amyloid β(Aβ) protein and p⁃Tau protein in the model group continued to increase at all time. Conclusion The TBI model caused continuous activation of microglia along with inflammatory response, which first increased and then decreased, resultsing in neurological scores changes. In addition, the inflammatory response may act as a promoter of Aβ protein deposition and Tau protein phosphorylation, leading to cognitive impairment in mice.

Objective:To evaluate the effect of low-dose recombinant interleukin-2(rIL-2)therapy on immunocyte subsets and its side effects in children with solid tumor.Methods:A total of 22 children(11 males and 11 females)with solid tumor in our department from December 2012 to November 2017 were selected,with a median age of 9(3-16)years old when starting IL-2 therapy.ALL surgeries and chemotherapy of children had been completed before low-dose rIL-2 therapy,and 17 cases achieved complete remission(CR)and 5 cases achieved partial remission(PR).A low-dose rIL-2 therapy was given 1 month after chemotherapy for 1 year:4 × 105 IU/(m2·d),s.c.for every other day,3 times per week.The immunocyte subsets were detected every 3 months until the end of treatment,meanwhile,disease condition and therapy-related side effects were followed up.Results:After low-dose rIL-2 therapy in 22 children,the absolute values of CD3+T cells,CD3-CD56+natural killer cells,CD3+CD4+helper T cells(Th)and CD3+CD8+cytotoxic T cells were up-regulated remarkably,as well as Th/suppressor T cells(all P＜0.05).While,there were no significant differences in absolute value and proportion of CD4+CD25+CD127-Treg cells during therapy.Among the 17 children who achieved CR before rIL-2 therapy,14 cases continued to maintain CR after therapy,while 3 cases relapsed,and with 2 died after treatment abandonment.The 5 children who achieved PR before low-dose rIL-2 therapy were evaluated CR by PET/CT scan after treatment.In the early stage of low-dose rIL-2 therapy,1 child developed skin rashes at the injection sites,and 2 children ran a slight to mild transient fever.Their symptoms disappeared without any organ damage after symptomatic treatment.Conclusion:Low-dose rIL-2 therapy has good drug tolerance,and changes the distribution of anti-tumor immune-cell subgroup in peripheral blood of children with solid tumor remarkably without up-regulation of absolute value and ratio of Treg cells.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

OBJECTIVE: To observe the clinical effect of acupuncture for delayed sleep-wake phase disorder (DSWPD). METHODS: A total of 84 patients with DSWPD were randomized into an observation group (42 cases, 2 cases dropped off) and a control group (42 cases, 3 cases dropped off). On the basis of sleep hygiene education, acupuncture was applied at Shenmai (BL 62), Zhaohai (KI 6), Hegu (LI 4), Taichong (LR 3), Zusanli (ST 36) and Sanyinjiao (SP 6) in the observation group, while placebo acupuncture was applied at the same acupoints in the control group. The treatment lasted for 8 weeks, once every other day, 3 times a week in the 1st to 4th weeks; once every 3 days, 2 times a week in the 5th to 8th weeks. Before and after treatment, the actigraphy (ACT) indexes of objective sleep (total time of stay in bed, total sleep time, sleep efficiency, the number of awakenings and the wake time after falling asleep) and plasma cortisol (CORT) level were observed; before and after treatment and in follow-up of 1, 3 months after treatment, the scores of morningness-eveningness questionnaire (MEQ), insomnia severity index (ISI), fatigue severity scale (FSS) and Epworth sleepiness scale (ESS) were observed in the two groups. RESULTS: Compared before treatment, the total sleep time was prolonged, the sleep efficiency was improved, the number of awakenings was reduced, and the wake time after falling asleep was shortened after treatment in the observation group (P<0.01, P<0.05), and those in the observation group after treatment were superior to the control group (P<0.01, P<0.05). Compared before treatment, the MEQ scores after treatment in both groups and in the follow-up of 1, 3 months after treatment in the observation group were increased (P<0.01), and the MEQ score of each time point after treatment in the observation group was higher than the control group (P<0.01). The scores of ISI, FSS and ESS after treatment, and the scores of ISI、ESS in follow-up of 1, 3 months after treatment in the observation group were decreased compared with those before treatment (P<0.01, P<0.05), and in the observation group, the scores of ISI, FSS and ESS of each time point after treatment were lower than those in the control group (P<0.01, P<0.05). After treatment, the plasma CORT level in the observation group was decreased compared with that before treatment and that in the control group (P<0.01, P<0.05). CONCLUSION Acupuncture can improve the sleep and wake phase of patients with DSWPD, improve sleep quality and daytime function, and its mechanism may be related to the down-regulation of plasma CORT level.
Humans ; Acupuncture Therapy ; Sleep ; Acupuncture Points ; Down-Regulation ; Sleep Duration

Because the classification system of radical surgery for rectal cancer has not been established, it is impossible to select the appropriate surgical method according to the clinical stage of the tumor. In this paper, we explained the theory of " four fasciae and three spaces " of pelvic membrane anatomy and then combined this theory with the membrane anatomical basis of Querleu-Morrow classification for radical cervical cancer resection. Based on this theory and the membrane anatomy of Querleu-Morrow classification of radical cervical cancer resection, we proposed a new classification system of radical rectal cancer surgery based on membrane anatomy according to the lateral lymph node dissection range of the rectum. This system classifies the surgery into four types (ABCD) and defines corresponding subtypes based on whether the autonomic nerve was preserved. Among them, type A surgery is total mesorectal excision (TME) with urogenital fascia preservation, type B surgery is classical TME, type C surgery is extended TME, and type D surgery is lateral extended resection. This classification system unifies the anatomical terminology of the pelvic membrane, validates the feasibility of using the " four fasciae and three fascial spaces " theory to classify rectal cancer surgery, and lays the theoretical foundation for the future development of a unified and standardized classification of radical pelvic tumor surgery.
Female ; Humans ; Uterine Cervical Neoplasms ; Rectal Neoplasms/pathology* ; Rectum/anatomy & histology* ; Pelvis/innervation* ; Proctectomy

OBJECTIVE: To compare the clinical effect of three types of Kirschner wire tension band for olecranon fracture. METHODS: The clinical data of 64 patients with olecranon fracture treated by Kirschner wire tension band fixation from March 2016 to May 2020 were retrospectively analyzed. Among them, 19 patients were treated with intramedullary K-wires fixation(group A) including 8 males and 11 females with an average of (48.2±18.3) years old, 3 patients were typeⅠ, and 16 patients were typeⅡ according to Mayo classification;20 patients were treated with transcortical K-wires fixation (group B) including 13 males and 7 females with an average of (43.5±20.4) years old, 3 patients were typeⅠand 17 patients were typeⅡ according to Mayo classification;25 patients were treated with perforated Kirschner wire(group C) including 15 males and 10 females with an average of (55.2±17.5) years old, 4 patients were typeⅠand 21 patients were typeⅡ according to Mayo classification. The operative time, intraoperative blood loss, times of Intraoperative fluoroscopy, fracture healing time and complications of 3 groups were compared. At the final follow-up, elbow function was assessed using the Mayo Elbow Function Scale. RESULTS: There were differences in operative time, intraoperative fluoroscopy times, postoperative VAS and soft tissue irritation among the three groups(P<0.05). The operative time, intraoperative fluoroscopy times in group A and C was better than that in group B. The postoperative VAS score, skin irritability in group C was better than that of group B. The difference was statistically significant on Mayo elbow function score at the final follow-up among three groups(P<0.05), the scores of group A and C were higher than that of group B. CONCLUSION Compared with transcortical K-wires screw fixation, both intramedullary K-wires screw fixation and perforated Kirschner wire fixation, which can significantly reduce the occurrence of soft tissue irritation, reduce surgical complications and shorten the operation time.
Male ; Female ; Humans ; Adult ; Middle Aged ; Aged ; Young Adult ; Bone Wires ; Retrospective Studies ; Fracture Fixation, Internal ; Ulna Fractures/surgery* ; Olecranon Process/surgery* ; Inflammation ; Treatment Outcome