Aim To explore the underlying molecular mechanism of Alisol A 24-acetate(24A)in improving oxygen-glucose deprivation/reoxygenation(OGD/R)injury in brain microvascular endothelial cells(BMECs)and its correlation with miR-98-5p/transi-ent receptor potential melastatin-2(TRPM2).Meth-ods The ischemia-reperfusion injury in brain micro-vascular endothelial cells(BMECs)was established u-sing bEnd.3 cells subjected to 8 h of oxygen-glucose deprivation followed by 16 h of re-oxygenation.The cells were intervened by miR-98-5p mimics and/or 18.77 μmol·L-1 24A for 24 h and divided into the control group,OGD/R group,OGD/R+24A group,OGD/R+24A+miR-98-5p mimics group and OGD/R+miR-98-5p mimics group.The mRNA levels of miR-98-5p and TRPM2 were detected by qPCR.IL-1 β and TNF-α levels were detected by ELISA.The expression levels of TRPM2,p-AKT,p-GSK3 β,AKT,GSK3 β,Bcl-2,Bax,ZO-1,Occludin,Claudin-5 were detected by Western blot.Apoptosis and reactive oxygen species(ROS)levels were detected by flow cytometry.The targeting relationship between miR-98-5p and TRPM2 was verified using dual luciferase assay.Results Compared with the control group,the apoptosis of OGD/R group was obvious,Bcl-2/Bax decreased,ZO-1,Occludin,Claudin-5 decreased,IL-1 β,TNF-α and ROS increased,miR-98-5p,p-AKT/AKT,p-GSK3β/GSK3β decreased but TRPM2 increased.But com-pared with the OGD/R group,except the control group,the other three groups showed the opposite trend in the above aspects;compared with the OGD/R+24A group,OGD/R+24A+miR-98-5p mimics group showed decreased apoptosis,decreased degradation of ZO-1,Occludin and Claudin-5,and decreased inflam-mation and ROS.miR-98-5p,p-AKT/AKT,p-GSK3β/GSK3β increased and TRPM2 decreased.However,compared with the OGD/R+24A+miR-98-5p mimics group,the OGD/R+miR-98-5p mimics group reversed this trend.Dual luciferase confirmed that miR-98-5p targeted regulation of TRPM2.Conclusion 24A in-hibits the expression of TRPM2 in BMECs through miR-98-5p,regulates AKT/GSK3β signal pathway,re-duces OGD/R inflammation and oxidative stress-medi-ated apoptosis,prevents the degradation of ZO-1,Oc-cludin and Claudin-5,and improves BBB permeability.

OBJECTIVE: To investigate the molecular mechanism and explore blood transfusion strategies for a proband exhibiting the JK (a-b-) phenotype and anti-JK³ high frequency antigen antibody and her eight family members. METHODS: The Kidd blood phenotype and irregular antibodies in a family were identified by serologic tests. Exon 4-11 and intron region of SLC14A1 gene were sequenced by Sanger method. RESULTS: The combination of the gene JK*B (c.499A>G,c.512G>A,c.588A>G) and gene JK*B (c.342-1G>A,588A>G) in this family were considered to result in the JK (a-b-) phenotype in two members. The members carrying gene JK*A(c.130G>A,588A>G) all present serological JK^a+W. Members carrying gene JK*B (c.499A>G,c.588A>G) all present serological JK^b+W, which has not been previously reported to cause antigenic weakening. The proband with JK (a-b-) phenotype produced anti-JK³ antibodies, the hospital formulated a number of blood preparation strategies for the patient and she was discharged after recovery. CONCLUSION In this study, the molecular mechanism of JK (a-b-) in this family was identified, the transfusion strategy of rare blood group was established in our institution preliminary, and the necessity of establishing a rare blood group bank was revealed in this region. It is suggested that JK*B (c.499A>G,c.588A>G) may be a new genetic pattern leading to the weakening of Kidd antigenicity, which lays a foundation for the study of population genetics.
Humans ; Blood Transfusion ; Female ; Kidd Blood-Group System/genetics* ; Phenotype ; Pedigree

Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Objective To investigate the effect and safety of esketamine combined with general anesthesia and ultrasound-guided cervical plexus block in axillary endoscopic thyroidectomy.Methods The subjects of this study,112 female patients who underwent axillary endoscopic thyroidectomy in our hospital from January 2022 to October 2024,were randomly divided into an observation group and a control group,each with 56 cases.All patients were administered with ultrasound-guided cervical plexus block followed by general anesthesia.The observation group was injected with 0.1 mg/kg of esketamine prior to anesthesia induction and continuously pumped with esketamine at a rate of 0.1 mg/(kg·h)during the operation until sutures were completed,while the control group was administered with an equal volume of normal saline following the same procedure.The vital sign indicators[mean arterial pressure(MAP),heart rate(HR)and percutaneous arterial oxygen saturation(SpO2)]immediately after establishing electrocardiogram monitoring(T0),immediately before tracheal intubation(T1),immediately after tracheal intubation(T2),immediately after skin incision(T3)and immediately after the operation(T4)were compared between the two groups.Surgical related indicators such as propofol dosage,remifentanil dosage,and extubation time were also compared between them.Pain visual analogue scale(VAS)scores were performed on patients from the two groups at 1,6,12,and 24 h postoperatively.The 40-item quality of recovery score(QoR-40)was used before the surgeries and 1 d after surgeries to assess the patients.Adverse reactions were also compared.Results The difference was significant in terms of MAP,HR time effect in the two groups(F=24.63,F=20.11,P<0.05)and inter-group MAP,HR values(F=13.54,F=11.49,P<0.05).There were statistically significant differences in the interaction effects of MAP and HR between the two groups(F=4.10,F=3.46,P<0.05).The difference was not statistically significant in time,inter group,and interaction effects of SpO2(P>0.05).The dosage of propofol,remifentanil,and postoperative 1 d drainage in the observation group were less than those in the control group,the differences were statistically significant(P<0.05).The differences were not statistically signiciant in extubation time and awakening time between the two groups(P>0.05).The VAS scores at 1,6,12,and 24 h after operation in the observation groups were lower than those in the control group,the differences were statistically significant(P<0.05).Physical comfort,pain dimension ratings,and total score of the QoR-40 scale:1)those 1 d after operation were lower than those before operation in both groups(P<0.05);2)1 d after operation:those in the control group were lower than those in the observation group(P<0.05).The control group witnessed a remarkable decrease in QoR-40 emotional state rating 1 d after operation than it did before operation(P<0.05),while no significant change was seen by the observation group in this regard(P>0.05).The incidence of coughing after extubation in the observation group was lower than that in the control group(14.29%and 37.50%),the difference was statistically significant(P<0.05).The differences were not statistically signiciant in the incidence of other adverse reactions such as nausea,vomiting,dizziness,headache,respiratory depression,awakening restlessness and awakening delirium between the two groups(P>0.05).The total incidence of adverse reactions in the observation group was significantly lower than that in the control group(25.00%and 66.07%,P<0.05).Conclusion The application of esketamine combined with general anesthesia and ultrasound-guided cervical plexus block in axillary endoscopic thyroidectomy can significantly stabilize hemodynamics in patients,reduce postoperative pain,and promote postoperative recovery.It is worthy clinical application.

Aim To investigate the anti-acute lung injury(ALI)effect of Sterculiae Lychnophorae Semen(SLS)and its mechanism.Methods The main ac-tive components of SLS and their core targets and path-ways of action against ALI were obtained by network pharmacology methods.Subsequently,molecular doc-king technology and in vitro cellular experiments were applied for validation.Results A total of 19 core tar-gets were obtained,including HSP90AA1,CASP3,TNF,MAPK8 and MAPK14.The mechanisms may in-volve signaling pathways such as cancer,PI3K/Akt and MAPK.Molecular docking confirmed that the key targets of SLS formed a better binding activity with the relevant active ingredients.The in vitro results showed that SLS was able to protect the PM2.5-contaminated BEAS-2B cells,inhibit their NO,IL-1β and TNF-αlevels,and reduce the expression of p-p38 MAPK and p-JNK proteins.Conclusions The study successfully predicts the active ingredients,targets and signaling pathways of SLS against ALI,and in vitro experiments demonstrate that SLS might protect BEAS-2B cells from PM2.5 stimulus-induced inflammation and apoptosis by inhibiting the over-activation of p38 MAPK and JNK signaling pathways.

The paper explores the etiology and pathogenesis of chronic fatigue syndrome (CFS), and its diagnosis and treatment with acupuncture and moxibustion based on "body-qi-mind trinity life view". It is believed that CFS refers to the comorbidity of body, qi and mind. In the disease, spleen deficiency in transportation and transformation is the root, resulting in malnutrition of muscles; liver qi stagnation is the pivot, causing dysfunction of three jiao; and disharmony between heart and kidney is crucial, leading to dysfunction of mind. The strategy of treatment with acupuncture and moxibustion is proposed, "relieving general pain of the body as the top priority, regulating qi is the pivot, and housing the mind is the foundation". For relieving general pain of the body, acupuncture is applied to Sanyinjiao (SP6) and Zusanli (ST36) that is the essential prescription to relieve muscular pain. For regulating qi, Waiguan (TE5) and Gongsun (SP4) are selected to promote the pivot of shaoyang and regulate qi movement of three jiao. For housing the mind, acupuncture is delivered at Shenmen (HT7) and moxibustion is applied to Yongquan (KI1), Gaohuang (BL43) and Baihui (GV20) to harmonize the heart and kidney and tranquilize the mind. This intervention mode, i.e. harmonizing among body, qi and mind, and promoting the circulation of qi and blood, is conductive to restoring the body, qi and mind. It provides a new idea to clinical diagnosis and treatment of CFS with acupuncture and moxibustion.
Humans ; Moxibustion ; Fatigue Syndrome, Chronic/physiopathology* ; Acupuncture Therapy ; Qi ; Acupuncture Points ; Male ; Female

Prostate cancer (PCa) ranks as the second most prevalent malignancy among men worldwide. Early diagnosis, personalized treatment, and prognosis prediction of PCa play a crucial role in improving patients' survival rates. The advancement of artificial intelligence (AI), particularly the utilization of deep learning (DL) algorithms, has brought about substantial progress in assisting the diagnosis, treatment, and prognosis prediction of PCa. The introduction of the foundation model has revolutionized the application of AI in medical treatment and facilitated its integration into clinical practice. This review emphasizes the clinical application of AI in PCa by discussing recent advancements from both pathological and imaging perspectives. Furthermore, it explores the current challenges faced by AI in clinical applications while also considering future developments, aiming to provide a valuable point of reference for the integration of AI and clinical applications.
Humans ; Prostatic Neoplasms/diagnosis* ; Male ; Artificial Intelligence ; Deep Learning ; Prognosis

OBJECTIVE: To explore the accuracy of human-computer interaction software in identifying and locating type C1 distal radius fractures. METHODS: Based on relevant inclusion and exclusion criteria, 14 cases of type C1 distal radius fractures between September 2023 and March 2024 were retrospectively analyzed, comprising 3 males and 11 females(aged from 27 to 82 years). The data were assigned randomized identifiers. A senior orthopedic physician reviewed the films and measured the ulnar deviation angle, radial height, palmar inclination angle, intra-articular step, and intra-articular gap for each case on the hospital's imaging system. Based on the reduction standard for distal radius fractures, cases were divided into reduction group and non-reduction group. Then, the data were sequentially imported into a human-computer interaction intelligent software, where a junior orthopedic physician analyzed the same radiological parameters, categorized cases, and measured fracture details. The categorization results from the software were consistent with manual classifications (6 reduction cases and 8 non-reduction cases). For non-reduction cases, the software performed further analyses, including bone segmentation and fracture recognition, generating 8 diagnostic reports containing fracture recognition information. For the 6 reduction cases, the senior and junior orthopedic physicians independently analyzed the data on the hospital's imaging system and the AI software, respectively. Bone segments requiring reduction were identified, verified by two senior physicians, and measured for displacement and rotation along the X (inward and outward), Z (front and back), and Y (up and down) axes. The AI software generated comprehensive diagnostic reports for these cases, which included all measurements and fracture recognition details. RESULTS: Both the manual and AI software methods consistently categorized the 14 cases into 6 reduction and 8 non-reduction groups, with identical data distributions. A paired sample t-test revealed no statistically significant differences (P>0.05) between the manual and software-based measurements for ulnar deviation angle, radial ulnar bone height, palmar inclination angle, intra-articular step, and joint space. In fracture recognition, the AI software correctly identified 10 C-type fractures and 4 B-type fractures. For the 6 reduction cases, a total of 24 bone fragments were analyzed across both methods. After verification, it was found that the bone fragments identified by the two methods were consistent. A paired sample t-tests revealed that the identified bone fragments and measured displacement and rotation angles along the X, Y, and Z axes were consistent between the two methods. No statistically significant differences(P>0.05) were found between manual and software measurements for these parameters. CONCLUSION Human-computer interaction software employing AI technology demonstrated comparable accuracy to manual measurement in identifying and locating type C1 distal radius fractures on CT imaging.
Humans ; Male ; Female ; Radius Fractures/surgery* ; Middle Aged ; Adult ; Aged ; Aged, 80 and over ; Tomography, X-Ray Computed/methods* ; Retrospective Studies ; Software ; Wrist Fractures

Objective To investigate the effect and safety of esketamine combined with general anesthesia and ultrasound-guided cervical plexus block in axillary endoscopic thyroidectomy.Methods The subjects of this study,112 female patients who underwent axillary endoscopic thyroidectomy in our hospital from January 2022 to October 2024,were randomly divided into an observation group and a control group,each with 56 cases.All patients were administered with ultrasound-guided cervical plexus block followed by general anesthesia.The observation group was injected with 0.1 mg/kg of esketamine prior to anesthesia induction and continuously pumped with esketamine at a rate of 0.1 mg/(kg·h)during the operation until sutures were completed,while the control group was administered with an equal volume of normal saline following the same procedure.The vital sign indicators[mean arterial pressure(MAP),heart rate(HR)and percutaneous arterial oxygen saturation(SpO2)]immediately after establishing electrocardiogram monitoring(T0),immediately before tracheal intubation(T1),immediately after tracheal intubation(T2),immediately after skin incision(T3)and immediately after the operation(T4)were compared between the two groups.Surgical related indicators such as propofol dosage,remifentanil dosage,and extubation time were also compared between them.Pain visual analogue scale(VAS)scores were performed on patients from the two groups at 1,6,12,and 24 h postoperatively.The 40-item quality of recovery score(QoR-40)was used before the surgeries and 1 d after surgeries to assess the patients.Adverse reactions were also compared.Results The difference was significant in terms of MAP,HR time effect in the two groups(F=24.63,F=20.11,P<0.05)and inter-group MAP,HR values(F=13.54,F=11.49,P<0.05).There were statistically significant differences in the interaction effects of MAP and HR between the two groups(F=4.10,F=3.46,P<0.05).The difference was not statistically significant in time,inter group,and interaction effects of SpO2(P>0.05).The dosage of propofol,remifentanil,and postoperative 1 d drainage in the observation group were less than those in the control group,the differences were statistically significant(P<0.05).The differences were not statistically signiciant in extubation time and awakening time between the two groups(P>0.05).The VAS scores at 1,6,12,and 24 h after operation in the observation groups were lower than those in the control group,the differences were statistically significant(P<0.05).Physical comfort,pain dimension ratings,and total score of the QoR-40 scale:1)those 1 d after operation were lower than those before operation in both groups(P<0.05);2)1 d after operation:those in the control group were lower than those in the observation group(P<0.05).The control group witnessed a remarkable decrease in QoR-40 emotional state rating 1 d after operation than it did before operation(P<0.05),while no significant change was seen by the observation group in this regard(P>0.05).The incidence of coughing after extubation in the observation group was lower than that in the control group(14.29%and 37.50%),the difference was statistically significant(P<0.05).The differences were not statistically signiciant in the incidence of other adverse reactions such as nausea,vomiting,dizziness,headache,respiratory depression,awakening restlessness and awakening delirium between the two groups(P>0.05).The total incidence of adverse reactions in the observation group was significantly lower than that in the control group(25.00%and 66.07%,P<0.05).Conclusion The application of esketamine combined with general anesthesia and ultrasound-guided cervical plexus block in axillary endoscopic thyroidectomy can significantly stabilize hemodynamics in patients,reduce postoperative pain,and promote postoperative recovery.It is worthy clinical application.

Aim To investigate the protective effect of liraglutide(LIRA)on acetaminophen(APAP)-in-duced hepatotoxicity at the in vivo level and to reveal the underlying mechanism.Methods Forty SPF grade male C57BL/6J mice were randomly divided into the Control,LIRA(200 μg·kg-1),APAP(500 mg·kg-1),LIRA+APAP,LIRA+APAP+3-methylade-nine(3-MA,30 mg·kg-1)groups,with eight mice in each group.The mice were administered for three con-secutive days,and the materials were taken after 24 h.The general condition and body weight of mice in each group were recorded,and liver morphology was ob-served.Serum ALT and AST levels,as well as SOD ac-tivity,MDA,and GSH content in liver homogenates,were measured using biochemical assay kits.The levels of inflammatory cytokines IL-6,TNF-α,and IL-1β in serum were detected by ELISA.Liver pathological changes were assessed by HE staining,while mitochon-drial and autophagosome structures in liver tissues were observed using transmission electron microscopy.The number of PCNA-positive cells in liver tissues was e-valuated using immunohistochemical staining.The pro-tein expression levels of LC3Ⅱ,p62,Bax,Bcl-2,PC-NA,and CyclinD1 in liver tissues were determined by Western blot.Results LIRA pretreatment can im-prove the general condition of mice with acetamino-phen-induced liver injury(AILI),reduce serum ALT and AST levels,and effectively ameliorate the appear-ance and morphology of the liver as well as the patho-logical damage to liver tissue.Simultaneously,the lev-els of inflammatory cytokines IL-6,TNF-α,and IL-1βare significantly decreased;SOD activity and GSH con-tent are significantly increased,while MDA content is significantly reduced.Transmission electron microsco-py observations reveal the presence of numerous auto-phagosomes in the cytoplasm of liver tissue.Immuno-histochemical staining results indicate a significant in-crease in the number of PCNA-positive cells.Further-more,the expression of LC3Ⅱ,Bcl-2,PCNA,and Cy-clinD1 proteins in liver tissue is significantly upregulat-ed,while the expression of p62 and Bax proteins is significantly downregulated.However,after interven-tion with the autophagy inhibitor 3-MA,the aforemen-tioned protective effects of LIRA are significantly.Conclusions LIRA pretreatment can significantly im-prove liver injury in AILI mice.Its protective mecha-nism may be related to enhancing autophagy in hepato-cytes,thereby reducing oxidative stress,inflammatory response and apoptosis in liver of AILI mice.